FEDERAL COURT OF AUSTRALIA

Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634

THE COURT ORDERS THAT:

1.    The parties are to bring in draft orders giving effect to these reasons by 4.00 pm on 13 July 2015.

2.    If the parties are unable to agree on the question of costs, they are to provide short written submissions (not exceeding three pages) on that question, together with a draft of the order that is sought.

Note:    Entry of orders is dealt with in Rule 39.32 of the Federal Court Rules 2011.

REASONS FOR JUDGMENT

Introduction

1    The first applicant, Otsuka Pharmaceutical Co., Ltd (Otsuka), is the patentee of Patent No. 2005201772, titled “Substituted carbostyril derivatives as 5-HT1A receptor subtype agonists” (the 772 patent).

2    The 772 patent claims the use of a carbostyril compound (relevantly, aripiprazole) for the production of a medicament having certain features and a method for treating a patient involving, relevantly, the use of aripiprazole.

3    The complete application for the 772 patent was a divisional application of the complete application for Patent No. 2002226752, also titled “Substituted carbostyril derivatives as 5-HT1A receptor subtype agonists” (the 752 patent).

4    The second applicant, Bristol-Myers Squibb Company (BMS), is a licensee of the 772 patent and the 752 patent. It says that it is the “exclusive licensee” of each patent for the purposes of the Patents Act 1990 (Cth) (the Act).

5    The respondent is a pharmaceutical company that supplies generic pharmaceuticals and other products. It has obtained registration of a number of aripiprazole products on the Australian Register of Therapeutic Goods (the ARTG). These products are registered under either the ARIPIPRAZOLE GENERICHEALTH label or the ARIPIPRAZOLE GH label (respectively, the GENERICHEALTH products and the GH products).

6    The GENERICHEALTH products are registered for:

    the treatment of schizophrenia including maintenance of clinical improvement during continuation therapy;

    the acute treatment of manic or mixed episodes associated with Bipolar I Disorder in adults in monotherapy and in combination with lithium or valproate; and

    maintenance treatment of manic or mixed episodes in Bipolar I Disorder in adults as monotherapy.

7    The GH products are registered for:

    the treatment of schizophrenia including maintenance of clinical improvement during continuation therapy.

8    The applicants have alleged that, by engaging or threatening to engage in certain acts in respect of the GENERICHEALTH products and the GH products, the respondent has infringed or threatened to infringe claims 1 and 7 of the 772 patent. The respondent has denied these allegations. It has also challenged the validity of these claims.

9    The applicants have also alleged that, by engaging or threatening to engage in certain acts in respect of the GENERICHEALTH products and the GH products, the respondent has infringed or threatened to infringe claims 1, 2 and 3, and claims 8, 9 and 10, of the 752 patent. The respondent has denied these allegations. It has also challenged the validity of these claims.

10     At the outset, it is necessary to refer to two events that have changed the landscape of the case that falls for decision.

11    The first is that, when opening its case, the respondent gave certain undertakings to the Court, without admissions of liability: see Exhibit 3. As a consequence, the applicants did not pursue their case in respect of the GENERICHEALTH products or their case on infringement of the 752 patent in relation to the GH products. That left the applicants’ case on infringement of the 772 patent in respect of the GH products. I will return to discuss more fully the effect of those undertakings when considering that case.

12    The second is that, shortly before the commencement of closing submissions, the respondent advised the applicants that it no longer pursued its case for revocation of the relevant claims of the 752 patent.

13    Thus, by the time of closing submissions, the issues for determination were limited to the applicants’ case on infringement of claims 1 and 7 of the 772 patent, to the extent that that case concerned acts done or threatened to be done in respect of the GH products, and the respondent’s case on the invalidity of those claims.

14    For the reasons that follow, I am of the view that claims 1 and 7 of the 772 patent are invalid and should be revoked. But for that finding, I would have found that the applicants’ final case in respect of the threatened infringement of claims 1 and 7 had been established. However, only Otsuka has standing to sue for infringement. BMS is not an exclusive licensee of the patent.

The witnesses

15    The applicants read affidavits made by the following expert witnesses:

    Bruce Sugriv Singh (19 January 2012, 29 October 2012, 8 March 2013 and 13 June 2013);

    Jonathan Phillips (13 June 2013); and

    Trevor Ronald Norman (2 November 2012; 5 March 2013 and 13 June 2013)

16    These witnesses were cross-examined.

17    Professor Singh is a consultant psychiatrist in private practice at The Melbourne Clinic and a senior consultant psychiatrist at the Royal Melbourne Hospital. He was Deputy Dean of the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne, where he has been a Professor of Psychiatry since 1991. He has been a Fellow of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) since 1979.

18    Associate Professor Phillips is a consultant psychiatrist in private practice. He is an Associate Professor at the University of New South Wales, the University of Adelaide and James Cook University. He is a Fellow of the RANZCP and was President from 1998 to 2000.

19    Associate Professor Norman is an Associate Professor in the Department of Psychiatry at the University of Melbourne. He was an Adjunct Professor in the School of Behavioural Sciences at La Trobe University and President of the International Society for the Investigation of Stress from 2002 to 2004.

20    The applicants read affidavits made by the following lay witnesses:

    Phillip John Kerr (8 February 2012); and

    Robert Dwyer McQuade (16 April 2013).

21    The respondent read affidavits made by the following expert witnesses:

    Patrick Dennistoun McGorry (2 November 2012, 2 March 2013, 12 June 2013 and 10 September 2013);

    Jeremy Francis O’Dea (17 October 2012, 31 October 2012, 2 November 2012, 5 March 2013, 12 June 2013 and 11 September 2013); and

    Iain Stewart McGregor (4 April 2013).

22    These witnesses were cross-examined.

23    Professor McGorry is a consultant psychiatrist and Professor of Youth Mental Health at the University of Melbourne. He is an Executive Director of the Orygen Youth Health Research Centre (Orygen) and has been a Fellow of the RANZCP since 1986.

24    Dr O’Dea is a consultant psychiatrist in public and private practice and a Conjoint Lecturer in the School of Psychiatry at the University of New South Wales. He has been a been a Fellow of the RANZCP since 1991.

25    Professor McGregor is Professor of Pharmacology at the University of Sydney. He is a Professorial Fellow of the Australian Research Council.

26    The respondent read affidavits made by the following lay witnesses:

    Elmo De Alwis (22 February 2012 and 5 March 2012); and

    Timothy Cameron Francis (22 February 2012).

Background

27    The parties provided an agreed primer of the medical and scientific background relevant to this case: Administrative Exhibit 1. The primer was prepared from the affidavit evidence given by the expert witnesses. The following summary is based substantially on the primer.

Schizophrenia and its symptoms

28    Schizophrenia is a serious mental disorder affecting 1% of the population worldwide. It generally comes on in early adulthood. Its main features are disturbances in the ability to experience reality, a lack of capacity to engage with others in the outside world, and disturbances in thinking, behaviour and emotional responses. The disorder may run a number of courses, but standard definitions of schizophrenia state that the symptoms must last for at least six months for the diagnosis to be made. In the majority of cases, the condition is chronic. The cause of schizophrenia is not known, but both genetic factors and environmental stressors operating prenatally and in childhood may play a part.

29    The symptoms of schizophrenia can be classified according to separate dimensions. Positive symptoms and negative symptoms are two of those dimensions. The positive symptoms include hallucinations (the perception of a sensory experience in the absence of a source), delusions (fixed false beliefs not shared by others), and disorganised speech. Negative symptoms include blunting of emotional response, apathy, amotivation and poverty of thought.

30    The Positive and Negative Syndrome Scale (PANSS) is an internationally recognised medical scale used for measuring symptom severity in schizophrenia patients. The PANSS Positive Subscale is used for measuring the positive symptom dimensions of schizophrenia. The PANSS Negative Subscale is used for measuring the negative symptom dimensions of schizophrenia. A reference to, for example, a “PANSS-Negative score” is a reference to a score on the PANSS Negative Subscale.

31    There appears to be universal recognition that the range of symptoms associated with schizophrenia can be categorized around positive symptoms and negative symptoms. This certainly seems to have been the case historically. However, since the 1990s, some have classified the symptoms of schizophrenia by reference to two additional dimensions, namely cognitive symptoms and mood symptoms (including, anxiety and depression). Others have continued to treat cognitive impairment as co-related to the negative symptoms of schizophrenia: cognitive impairment tends to occur together with a patient’s negative symptoms.

32    The diagnosis of schizophrenia is made on the basis of the criteria set out in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV). The diagnosis is made by conducting clinical interviews with the patient, with the aim of eliciting the recognised signs and symptoms of the disorder. The diagnosis may also take into consideration information from collateral sources, such as information from the patient’s relatives and friends, police, and other health care professionals. There are no independent diagnostic tests that would confirm a diagnosis of schizophrenia. However, when a patient presents and is first diagnosed with the disorder, the patient is, by the current definition set out in DSM IV, inevitably suffering positive symptoms.

Cognitive impairment and schizophrenia

33    Cognitive impairment is a term referable to a range of impaired higher cognitive functions. These functions include problems with attention, long-term memory, and abstraction and planning. These impairments are also referred to as cognitive defects and cognitive symptoms.

34    Cognitive impairment also occurs in other serious psychiatric disorders, such as severe mood disorders. It is not, therefore, diagnostically specific to schizophrenia. However, compared to other psychiatric disorders, the pattern of cognitive impairment in some schizophrenia patients may be somewhat different.

35    The main manifestations of cognitive symptoms of schizophrenia are disturbances in attention, memory and executive function (such as the ability to generate and implement plans). A patient suffering from cognitive impairment will generally exhibit difficulty in thinking and in articulating thoughts. These problems include slow speech and thinking, memory problems, problem-solving, rationalising, being able to handle different mental activities at once, poverty of thought, poverty of content of thought, and problems relating to others. The term can also be used to cover problems with general thinking.

36    There is disagreement between the expert witnesses as to whether psychiatrists are able to measure and assess the response of cognitive impairment in schizophrenia to medication, and whether specific neuropsychological tests are used by psychiatrists in clinical practice to assess cognitive impairment in schizophrenia.

37    For example, Professor Singh gave evidence that the disturbances that manifest cognitive impairment in schizophrenia patients can be demonstrated by a range of neuropsychological tests, such as:

    the Wechsler Memory Scale (a standard test of visual and verbal memory);

    the Wisconsin Card Sorting Test (in which the subject is expected to follow instructions as to how a series of cards are to be sorted); and

    a full scale IQ test.

38    On the other hand, Dr O’Dea, for example, gave evidence, based on his experience, that formal neuropsychological tests are not routinely used by clinical psychiatrists to assess the response of a schizophrenia patient’s cognitive impairment symptoms and signs to antipsychotic drugs. He said, for example, that, although the Wechsler Memory Scale is a well-respected, detailed psychometric test, it is usually administered by psychologists and not used by psychiatrists clinically to assess cognitive impairment in schizophrenia. Indeed, he said that he was not aware of any psychiatrist who employs the Wechsler Memory Scale, the Wisconsin Card Sorting Test, or Standard IQ tests to assess cognition in schizophrenia.

39    The current view, as reflected in the literature, is that the majority of all patients with schizophrenia suffer from some degree of cognitive impairment. In some cases, this impairment is identifiable when the patient first presents with the illness. That said, in the early stages of the illness, cognitive impairment may be masked by the more florid positive symptoms of schizophrenia and become more evident and pronounced as the illness progresses and as the more florid positive symptoms and signs subside. Cognitive impairment can fluctuate and present at any time through the course of the illness.

The course of the illness

40    The course of schizophrenia can be very variable. Generally speaking, a broad distinction is usually made between “acute” schizophrenia and “chronic” schizophrenia. In addition, chronic schizophrenia includes a particularly severe form of schizophrenia known as “treatment-resistant” schizophrenia. Professor McGorry gave evidence that chronic and treatment-resistant schizophrenia are descriptions of the duration and responsiveness to treatment of the same disorder, namely schizophrenia. Chronic and treatment-resistant schizophrenia are terms that simply describe people with schizophrenia who have not made a full recovery.

41    Acute schizophrenia is schizophrenia that lasts for more than six months and then remits (meaning that the patient recovers). Approximately 25% to 35% of patients who suffer from one or more episodes of schizophrenia will recover. If acute schizophrenia is remitted, it may relapse from time to time. Where a patient periodically recovers and relapses, that patient would not be seen as “deteriorating” but rather as experiencing intermittent episodes of acute schizophrenia. Such a patient would be described as suffering from “recurring acute” schizophrenia or “intermittent” schizophrenia. Recovery from such a condition may occur even after a number of years.

42    Chronic schizophrenia is schizophrenia which lasts significantly longer than six months and usually for many years. A patient suffering from chronic schizophrenia may have his or her positive symptoms under control, but the negative symptoms persist, and the illness has not been eliminated. Generally speaking, the symptoms of chronic schizophrenia are the negative symptoms and cognitive impairment, but there may also be a relapse in positive symptoms from time to time. The nature and extent of the residual symptoms and/or signs of schizophrenia vary widely between patients. Chronic schizophrenia is the outcome for the majority of those who suffer from the illness.

43    Treatment-resistant schizophrenia (sometimes referred to as treatment-refractory schizophrenia) is a particular form of chronic schizophrenia. Treatment-resistant schizophrenia is schizophrenia in which the patient’s positive symptoms, in addition to negative and cognitive symptoms, are unresponsive to antipsychotic medication. Of all patients suffering from schizophrenia, 20% are partially unresponsive and 5% are totally unresponsive to antipsychotic medication so far as their positive symptoms are concerned. The key to a diagnosis of treatment-resistant schizophrenia is the non-remission of positive symptoms.

44    Treatment-resistant schizophrenia is defined in the RANZCP Clinical Practice Guidelines (the RANZCP guidelines) as schizophrenia in which there have been two six to eight week trials of two separate antipsychotics, where the patient’s positive symptoms do not respond with full remission to those drugs.

How is schizophrenia treated?

45    Schizophrenia is treated with antipsychotic medications described as being either “typical” (also known as “first generation”) antipsychotics, and “atypical” (also known as “second generation”) antipsychotics.

46    Typical antipsychotics were developed in the 1950s and 1960s. They include: chlorpromazine; haloperidol; sulpiride; fluphenazine; perphenazine; thiroidazine; pimozide; and, zotepine. However, sulpiride, perphenazine, thiroidazine, pimozide and zotepine were never available in Australia or, if originally available, are no longer available for prescription or no longer prescribed in practice.

47    Atypical antipsychotics block serotonin as well as dopamine receptors. They are also known as “SDAs” (serotonin dopamine antagonists). Atypical antipsychotics include: risperidone; olanzapine; quetiapine; and, amisulpride.

48    Atypical antipsychotics have fewer side effects than typical antipsychotics, particularly in terms of causing movement disorders in the form of unwanted and uncontrolled movements of arms, legs and facial muscles (such as twitching, restlessness and grimacing). Agents, known as anticholinergics, are often used with typical antipsychotics in order to control these movement disorders.

49    Currently, in Australia, atypical antipsychotics are more widely used than typical antipsychotics. The most widely used atypical antipsychotics are: olanzapine; risperidone; and, quetiapine. It would now be very rare for a new patient presenting with schizophrenia to be commenced on a typical antipsychotic. This has been the case since the mid to late 1990s.

50    The treatment of schizophrenia with antipsychotic medications is complemented by:

    case management (active involvement of mental health staff with individual patients);

    assertive community treatment (assertively following up patients in the community by visiting them);

    cognitive behavioural therapy, cognitive remediation and various other psychotherapies (which teach patients psychological techniques to manage their symptoms);

    rehabilitation social skills therapies (retraining people in social skills);

    vocational rehabilitation (retraining people for work); and

    supportive psychotherapy.

51    Certain patients may not respond well to a particular medication that is first prescribed. They may also experience unacceptable side effects (such as movement side effects). It is common, in clinical practice, to then try prescribing a different medication for those patients. This change to a different medication is known as “switching”.

52    Switching antipsychotics is done in an effort to optimise response. It can lead to a worsening, as well as an improvement, of symptoms due to non-response or delayed response to the new drug. Other problems can occur with the adverse effects of the medication being enhanced.

53    The patient’s response rate diminishes with the more drugs that are tried. Thus, the chance of responding to the second or third antipsychotic drug is much less than responding to the first drug.

54    Practising psychiatrists tend to distinguish between two types of treatment for schizophrenia. The first is “acute” treatment, in which the emphasis is placed on getting the patient’s positive symptoms under control. The second is longer-term treatment, in which the aims are to maintain control of the positive symptoms and to try to counter the negative symptoms and cognitive impairment.

55    Acute treatment involves low dose atypical antipsychotic medication and psychosocial interventions. The psychosocial interventions (interventions involving social or psychological interventions or blends of these) become more central as the patient recovers from the acute phase of the illness.

56    The RANZCP guidelines state that switching is advised for patients “in whom there are persistent positive or negative symptoms, or who are experiencing distressing side-effects.” The guidelines emphasise that there is a need to try clozapine early in the treatment-resistant stage, where there has been “the failure of full remission of positive symptoms or the lack of satisfactory clinical improvement despite sequential use of recommended doses of two or more antipsychotic medications for 6-8 weeks.” In other words, there is recommendation in the guidelines to use clozapine when third line treatment is required (ie when two previous drug treatments have been used).

The position at the priority date (29 January 2001)

57    The prescription of antipsychotic medications was the cornerstone of the treatment of schizophrenia. An antipsychotic was used to begin the treatment of a patient presenting in the acute phase of schizophrenia, and was used to maintain control of the positive symptoms of schizophrenia during the period of recovery (known as “continuation therapy”). The use of antipsychotic medicines in this way had been in practice since the 1950s. Antipsychotic medications were prescribed in the hope that they might treat a whole range of symptoms—positive, negative and cognitive.

58    Switching to try different antipsychotics, where the response of the patient’s positive symptoms to his or her current medication was not satisfactory, was common. Switching to improve the patient’s cognitive symptoms associated with schizophrenia was also practised. If the patient’s cognitive impairment improved but there were other factors at play (such as extrapyramidal or metabolic issues, or weight gain), there could be a reason to switch from one antipsychotic to another.

59    The atypical antipsychotic medications available in Australia (and the time at which they became available) were: risperidone (1993); clozapine (1994); olanzapine (1996); quetiapine (2000); and amisulpride (2000). Depot preparations of risperidone and olanzapine, and further atypical antipsychotics (aripiprazole, ziprasidone and asenapine), became available in Australia after that time.

60    There were no blood tests or other tests that could identify which antipsychotic would be the most effective to treat a particular patient with schizophrenia. It was therefore a process of trial and error to discover the most effective antipsychotic to use to treat the individual schizophrenia patient.

61    By the mid to late 1990s and early 2000s, there was an increased recognition among researchers and clinicians, as well as in the academic literature, that cognitive impairment, at least in established schizophrenia, was a key correlate of vocational and functional impairment. From about the late 1990s/early 2000s, there was an emphasis in the research community to find drug and psychosocial treatments to assist with remediation of cognitive impairment. A program—called “Measurement and Treatment Research to Improve Cognition in Schizophrenia” (MATRICS)—was commenced in 2003. It was initiated by the National Institute of Mental Health (NIMH) in the United States of America in order to identify and remedy barriers to the development and evaluation of drugs targeting the treatment of cognitive impairment in schizophrenia. A contract was awarded to the University of California, Los Angeles and a number of other centres to develop the MATRICS battery (ie a collection of tests) and to conduct research in neurocognition and interventions to ameliorate cognitive deficits.

62    At the priority date, there was no clear consensus among psychiatrists as to:

    how to best conceptualise and measure cognitive impairment in schizophrenia; and

    whether cognitive impairment could be effectively treated with the presently available antipsychotic medications.

63    Further, at the priority date, there was significant overlap between the negative and cognitive symptoms of schizophrenia. They were not treated as two distinctly different domains in clinical practice.

Neurotransmitters and receptors

64    In humans and other species, the transmission of nerve impulses in the brain and peripheral nervous system takes place by means of specific chemical agents called neurotransmitters. Transmission within the peripheral nervous system is important not only for everyday processes without which an organism cannot survive (such as breathing, heartbeat, movement and so on), but also for functions such as thinking (cognition) and feeling (emotion).

65    Neurotransmission is the process by which neurotransmitters transmit signals (electrical impulses) from one neuron to the next. This takes place at a synapse, where two neurons are in close proximity to, but do not touch, one another. Neurotransmission usually occurs when an electrical impulse is initiated in a neuron—the pre-synaptic neuron. The impulse arrives at the nerve terminal and causes the release of neurotransmitters. The neurotransmitters bind with receptors on a post-synaptic neuron. This may cause changes to the electrical charge contained by the post-synaptic neuron or may activate certain complex second messenger systems. Neurotransmission takes place only in one direction: from the pre-synaptic cell to the post-synaptic cell.

66    A receptor is a protein molecule consisting of chains of amino acids. Typically, these chains comprise 500 to 700 amino acids connected in a specific order to make unique molecules. Such receptors are located partially within neuronal cell membranes and generally consist of three parts.

67    The first part is an extra-cellular portion which protrudes above the cell membrane, such that it may receive signals from nearby cells.

68    The second part is a transmembrane-spanning domain located within the cell membrane, arranged as a series of helical shapes which give the receptor its shape. For some receptors, a neurotransmitter will act as a ligand at this part of the receptor. The term “ligand” refers to a molecule that will bind to a receptor to induce a conformational change (ie a change in shape) and bring about an alteration in the function of the receptor. Neurotransmitters and hormones are endogenous ligands (ie they are present in the body). Drugs are exogenous ligands (ie they are introduced to the body).

69    The third part is an intracellular domain which interacts with intracellular elements to produce changes in second messenger systems.

70    Several receptor types may be found within a cell. Each type will be coupled to a particular biochemical pathway. The various receptors recognise and only bind with certain ligands. The binding of a selective ligand to its receptor either activates or inhibits a specific biochemical pathway.

71    An agonist is a drug that mimics the effects of an endogenous neurotransmitter by bringing about a similar conformational change—and thus a similar biological response—in the receptor as that brought about by the endogenous ligand.

72    An antagonist is a drug that binds to the receptor but does not bring about a biological response. Its effect is to block the action of the endogenous ligand (neurotransmitter).

73    The differences in efficacy of agonists and antagonists at the receptor (ie the nature of their biological effect elicited by binding) is independent of their affinity for the receptor (ie their binding strength) and their potency for the receptor (ie the amount of a drug required to produce an effect of a given intensity).

74    A drug may be a partial agonist. Such drugs bind to and activate a given receptor but have only partial efficacy at the receptor in that they elicit less than the maximal response from the receptor. Partial agonists may exert both agonist and antagonist effects under certain conditions. At high doses, a partial agonist may antagonise the effects of a full agonist if its affinity for the receptor is greater than that of the full agonist. This is sometimes referred to as mixed agonist-antagonist actions.

75    Serotonin (5-hydroxytryptamine or “5-HT”) is a neurotransmitter intimately connected to neuropharmacology because of certain chemical structural resemblances to that of the hallucinogenic compound LSD. Serotonin is found throughout the body, including in many cells that are not neurons. Only a small percentage of total body serotonin is synthesised in serotonergic neurons of the central nervous system. Indeed, 90% of serotonin is made in the gut.

76    The serotonin system in the brain is perhaps one of the most complex due to the multiplicity of receptors with which serotonin can interact. To date, at least 14 unique receptor subtypes have been identified which use serotonin as their neurotransmitter. These are denoted by the numeral and letters “5-HT”. The function of all these receptors is not certain because drugs which act specifically at the various subtypes have not been synthesised. Nevertheless, the roles of some subtypes in various physiological processes have, to some extent, been delineated.

77    5-HT1A receptors are the best characterised of the 5-HT1 family of receptors. They have high affinity for serotonin. Studies in several species, including humans, show the presence of these receptors in significant levels in almost all parts of the brain. 5-HT1A receptors function as both pre-synaptic auto-receptors (ie they control their own firing rate and, therefore, the release of serotonin) and as post-synaptic receptors (ie they receive the neurotransmitter released and, as a consequence of the changes in receptor conformation, they alter biochemical processes within the post-synaptic neuron). The major electrical effect brought about by interaction with 5-HT1A receptors on neurons involves attenuation of the firing of neurons, thus resulting in decreased release of neurotransmitters from the synaptic ends of the neurons. Thus, 5-HT1A receptors have an inhibitory effect on neurotransmission when an agonist binds to them.

The 772 patent

78    The complete specification of the 772 patent (more specifically identified as AU 2005201772 C1) (the 772 specification) is organised in a conventional way. It makes a number of disclosures, in this case supported by extensive citations, by way of background before proceeding to summarise and then describe the invention more fully. It is necessary to refer to the background section of the 772 specification in some detail.

Background

79    The 772 specification describes the invention as relating to a method of treating a patient suffering from a disorder of the central nervous system associated with the 5-HT1A receptor subtype.

80    The 772 specification identifies US Patent No. 5,006,528 (US 528), European Patent No. 367,141 (EP 141) and another patent, as related art containing “the same chemical structural formula as the carbostyril derivatives in the present invention”. In this proceeding, it has been accepted that the disclosures of US 528 and EP 141 are materially the same. I will return to consider these patents in more detail when dealing with the respondent’s challenge to the validity of claims 1 and 7 of the 772 patent. For present purposes, it is important to note that the 772 specification states that these carbostyril derivatives have pharmacological properties that are beneficial drug treatments for schizophrenia. Claim 27 of EP 141 and claim 17 of US 528 claim a pharmaceutical composition for treating schizophrenia in which aripiprazole or its salt is the active ingredient. Unlike US 528, EP 141 specifically claims the use of aripiprazole for the preparation of a drug useful in the treatment of schizophrenia. This claim is a Swiss type claim.

81    Otsuka does not hold an Australian patent for the compound aripiprazole or for its use in treating schizophrenia generally.

82    The 772 specification records that it has been reported that aripiprazole binds with high affinity to D2 receptors and with moderate affinity to D3 and 5-HT7 receptors. The notation “D” refers to dopamine. Further, the 772 specification records that it has been reported that aripiprazole possesses:

    presynaptic dopaminergic autoreceptor agonistic activity;

    postsynaptic D2 receptor antagonistic activity; and

    D2 receptor partial agonistic activity.

83    However, the 772 specification notes that it has not been reported that “compounds in the present invention”, which include aripiprazole, have agonistic activity at the 5-HT1A receptor subtype.

84    The 772 specification then records that the following matters concerning the 5-HT1A receptor subtype have been reported (citations omitted):

    Therapeutic interventions using 5-HT1A receptor ligands may be useful drug treatments for alcohol abuse.

    5-HT1A agonist drugs may be useful for the treatment and/or prophylaxis of disorders associated with neuronal degeneration resulting from ischemic events in mammals.

    5-HT1A receptor hypersensitivity could be the biological basis for the increased frequency of migraine attack “in stressful and anxious conditions”.

    A particular 5-HT1A receptor agonist has neuroprotective, anxiolytic and anti-depressant-like effects in animal models.

    5-HT1A receptor agonists appear to be broad spectrum antiemetic agents.

    Serotonin plays a role in several neurological and psychiatric disorders, including Alzheimer’s disease, depression, nausea and vomiting, eating disorders, and migraine.

    Buspirone, a 5-HT1A receptor agonist, is efficacious in treating a variety of symptoms associated with attention deficit hyperactivity disorder (ADHD), and that combined use of a D2 receptor agonist and 5-HT1A agonist provides effective treatments for ADHD and Parkinson’s disease.

    5-HT1A agonists are effective in the treatment of cognitive impairment in Alzheimer’s disease, Parkinson’s disease or senile dementia.

    Ipsapirone, a 5-HT1A agonist, is effective in treating Alzheimer’s disease by improving memory.

    Buspirone is useful for improving short-term memory in patients “in need of treatment.”

    Use of 5-HT1A partial agonists have been used for the treatment or prevention of cognitive disorders associated with Alzheimer’s disease, Parkinson’s disease or senile dementia.

    5-HT1A agonists are effective in the treatment of depression.

    Gepirone, a 5-HT1A receptor partial agonist, is useful in alleviating certain primary depressive disorders, such as severe depression, endogenous depression, major depression with melancholia, and atypical depression.

    The combined use of gepirone with an antidepressant can effectively treat depression.

    Buspirone alleviates motor disorders such as neuroleptic-induced Parkinsonism and extrapyramidal symptoms.

    5-HT1A agonists reverse neuroleptic-induced catalepsy in rodents, which mimic movement impairments observed in Parkinson’s disease.

    Aripiprazole can be used to manage psychosis in geriatric patients, Alzheimer’s disease, Parkinson’s disease or senile dementia, because it possesses potent, partial agonistic activities at D2 and 5-HT1A receptors. These patients might not experience extrapyramidal symptoms due to this property of aripiprazole.

85    The 772 specification turns to consider the treatment of schizophrenia. It makes the following disclosures in that regard (citations omitted):

    Heretofore, schizophrenia has been understood to be caused by hyperactivity in the brain dopaminergic system. For this reason, some drugs were developed with strong dopaminergic receptor blocking activity. These typical antipsychotic drugs are effective in treatments for the positive symptoms of schizophrenia.

    A variety of atypical anti-psychotic drugs have been developed, which include clozapine, risperidone, olanzapine and quetiapine. These drugs have less extrapyramidal side effects and have other activities in addition to their dopaminergic receptor blocking activity.

    In contrast to typical antipsychotic drugs, such as chlorpromazine and haloperidol, it is reported that atypical antipsychotic drugs are more effective against “the negative symptoms and cognitive impairments associated with schizophrenia than typical antipsychotic drugs”, and atypical antipsychotic drugs have less extrapyramidal side effects.

    Certain patients are resistant to the therapy provided by atypical antipsychotic drugs. These patients may either not respond to the therapy or may become refractory (that is, “may feel more anxious, depressed or [suffer from] cognitive dysfunction”) in response to that therapy. These treatment-resistant patients pose a problem for how a physician may provide an appropriate therapy.

    A number of treatment-resistant and treatment-refractory schizophrenic patients display symptoms that do not respond adequately to a variety of known effective classes and doses of typical or atypical antipsychotic drugs. Further, these patients may also be “inveterate” schizophrenics or chronic schizophrenics, who are often repeatedly admitted to and discharged from hospitals.

    The symptoms of patients corresponding to treatment-resistant and treatment-refractory schizophrenics involve not only the positive symptoms, but also the negative symptoms and emotional disorders, as well as cognitive impairments.

    Cognitive impairment exists separately from the psychic symptoms in a schizophrenic individual. Medical treatment is quite important because cognitive impairment may disturb the socially adaptable behaviour of these individuals.

86    The 772 specification gives particular attention to the role of clozapine, an atypical antipsychotic drug, in the treatment of schizophrenia, and the role played by the 5-HT1A receptor subtype in the therapeutic efficacy of clozapine and other drugs (citations omitted):

    Clozapine is effective against treatment-resistant schizophrenia. It has been reported to be “effective against cognitive impairments in treatment-resistant schizophrenics”.

    It is reported that clozapine “improves cognitive impairments in attention, response time, fluent-speech, etc.” in treatment-resistant schizophrenics.

    It has also been reported that clozapine provides “effective improvements in cognitive impairments in an objective evaluation scale of the Wechsler Adult Intelligence Scale-Revised Full Scale”.

    The 5-HT1A receptor has been demonstrated to play a role in the therapeutic efficacy of clozapine against “treatment-resistant schizophrenia and cognitive impairments.” This relationship was revealed by a binding experiment using human 5-HT1A receptors.

    It is clearly understood that 5-HT1A receptor agonistic activity or 5-HT1A receptor partial agonistic activity plays an important role in treatment-resistant schizophrenia and cognitive impairments.

    It has been reported that the number of 5-HT1A receptors is increased in the prefrontal cortex of chronic schizophrenics classified as treatment-resistant. This observation was explained as a compensatory process mediated by hypofunctional 5-HT1A receptors. Therefore, a lowering in neuronal transmission mediated through 5-HT1A receptors is expected in treatment-resistant schizophrenics.

    The clinical efficacy of clozapine may be related to its partial agonist efficacy at 5-HT1A receptors. This hypothesis is supported by a positron emission tomography study in primates which showed that clozapine interacts with brain 5-HT1A receptors at a therapeutically effective dose.

    Tandospirone, which is a known selective 5-HT1A receptor agonist, improved cognitive impairments in chronic schizophrenic patients.

    In animal tests, the reports do not always suggest that 5-HT1A receptor agonist activity may be related to cognitive impairment. However, a known selective 5-HT1A receptor agonist (8-OH-DPAT), improves learning and memory impairments induced by scopolamine, known as a muscarinic receptor antagonist. This suggests a relationship between 5-HT1A receptor agonistic activity and improvements in cognitive impairments.

87    The 772 specification also records that it has been reported that later atypical antipsychotic drugs, such as risperidone and olanzapine, improve treatment-resistant schizophrenia or cognitive impairments in treatment-resistant schizophrenics. However, these drugs were not shown to be consistently superior to typical antipsychotic drugs in their effectiveness against treatment-resistant schizophrenia. The 772 specification discloses that risperidone and olanzapine bind with lower affinity to human 5-HT1A receptors and thus “cannot clearly perform activities through human 5-HT1A receptors at clinical effective doses.”

88    The 772 specification also discloses that, while it is understood that clozapine is effective against treatment-resistant schizophrenia, its use is limited due to its severe side- effect of producing agranulocytosis.

89    The 772 specification reasons that, under these circumstances, the development of a safe antipsychotic drug with potent, full or partial agonist activity at 5-HT1A receptors is “earnestly desired.”

90    The 772 specification continues:

The carbostyril compound in the present invention binds with high affinity and displays a potent, partial agonist activity at the 5-HT1A receptors and it has higher intrinsic activity (about 68%) as compared with that of clozapine. Therefore, the compound in the present invention has a 5-HT1A receptor agonistic activity that is more potent than the agonistic activity of clozapine. Thus, the present carbostyril compound may represent a more potent and highly safe drug for curing treatment-resistant schizophrenia, cognitive impairments caused by treatment-resistant schizophrenia, inveterate schizophrenia, cognitive impairments caused by inveterate schizophrenia, chronic schizophrenia, cognitive impairments caused by chronic schizophrenia and the like, as compared with other currently available pharmacotherapeutic treatments. That is, the compound in the present invention may prove to be a potent and safer drug therapy for treatment-resistant schizophrenia, cognitive impairments caused by treatment-resistant schizophrenia, inveterate schizophrenia, cognitive impairments caused by inveterate schizophrenia, chronic schizophrenia, or cognitive impairments caused by chronic schizophrenia, etc., which fail to respond adequately to currently available antipsychotic drugs such as chlorpromazine, haloperidol, sulpiride, fluphenazine, perphenazine, thioridazine, pimozide, zotepine, risperidone, olanzapine, quetiapine, amisulpride, etc.

(Emphasis added.)

91    This passage of the 772 specification speaks of the carbostyril compound providing an alternative drug therapy for the identified disorders where patients have failed to respond or to respond adequately to other available antipsychotic drugs. The 772 specification exemplifies the use of the invention as drug therapy “against treatment-resistant schizophrenia, cognitive impairments caused by treatment-resistant schizophrenia, inveterate schizophrenia, cognitive impairments caused by inveterate schizophrenia, chronic schizophrenia or cognitive impairments caused by chronic schizophrenia” which fail to respond adequately to:

    “both of 1 to 3 typical antipsychotic drugs selected from the group consisting of chlorpromazine, haloperidol and perphenazine, and one atypical antipsychotic drug selected from the group consisting of risperidone, olanzapine, quetiapine and amisulpride”;

    “both of 2 typical antipsychotic drugs selected from the group consisting of chlorpromazine, haloperidol and perphenazine, and one atypical antipsychotic drug selected from the group consisting of risperidone, olanzapine, quetiapine and amisulpride”;

    “both of 1 to 2 typical antipsychotic drugs selected from the group consisting of chlorpromazine and haloperidol, and one atypical drug selected from the group consisting of risperidone, olanzapine, quetiapine and amisulpride”; and

    “both of 2 typical antipsychotic drugs selected from the group consisting of chlorpromazine and haloperidol, and one atypical antipsychotic drug selected from the group consisting of risperidone, olanzapine, quetiapine and amisulpride”.

92    It can be seen that these four examples teach the use of, relevantly, aripiprazole in relation to these conditions where the patient has failed to respond adequately to the previous administration of at least two of the specified antipsychotic drugs. In short, these particular examples are directed, unequivocally, to the use of, relevantly, aripiprazole as third line or later line treatment. That said, the 772 specification does not teach that aripiprazole can only be used as third line or later line treatment.

The invention as summarised and described

93    After setting out the extensive background to the invention that I have summarised above, the 772 specification summarises the invention by reference to two consistory statements, which find later expression in claims 1 and 7 of the 772 specification: see below.

94    The 772 specification makes clear that the compounds of the invention may be suitably prepared into pharmaceutically acceptable formulations, with reference to, amongst other things, US 528 and EP 141.

95    The 772 specification describes the utility of the invention as follows:

The potent, partial 5-HT1A receptor agonist in the present invention is useful for various disorders of the central nervous system associated with the 5-HT1A receptor subtype that induces bipolar disorders, such as bipolar I disorder with most recent hypomanic, manic, mixed, depressed or unspecified episode; bipolar II disorder with recurrent major depressive episodes with hypomanic episodes, and cyclothymic disorder; depression, such as endogenous depression, major depression, melancholia, and treatment-resistant depression; panic disorder; obsessive compulsive disorder (OCD); sleep disorders; sexual dysfunction; alcohol abuse and drug addiction; cognitive impairment; neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and the like, cognitive impairments caused by neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and related disorders; emesis; motion sickness; obesity; migraine; autism; Down’s syndrome; attention-deficit hyperactivity disorder (ADHD); treatment-resistant, inveterate or chronic schizophrenia, (which fail to respond adequately to currently available antipsychotic drugs); cognitive impairments caused by treatment-resistant schizophrenia, inveterate schizophrenia or chronic schizophrenia and the like.

(Emphasis added.)

Relevant claims

96    Claim 1 of the 772 specification is:

Use of a carbostyril compound of [a given structural formula] … or a pharmaceutically acceptable salt or solvate thereof, for the production of a medicament, effective in the treatment of disorders of the central nervous system associated with [the] 5-HT1A receptor subtype, which disorder

(i)    is selected from cognitive impairment caused by treatment-resistant schizophrenia, cognitive impairment caused by inveterate schizophrenia, or cognitive impairment caused by chronic schizophrenia, and

(ii)    fails to [respond] to antipsychotic drugs selected from chlorpromazine, haloperidol, sulpiride, fluphenazine, perphenazine, thioridazine, pimozide, zotepine, risperidone, olanzapine, quetiapine, or amisulpride.

97    This is a Swiss type claim.

98    Claim 7 of the 772 specification is:

A method for treating a patient suffering from disorders of the central nervous system associated with [the] 5-HT1A receptor sub-type, which disorder

(i)    [is] selected from cognitive impairment caused by treatment-resistant schizophrenia, cognitive impairment caused by inveterate schizophrenia, or cognitive impairment caused by chronic schizophrenia, and

(ii)    fails to [respond] to antipsychotic drugs selected from chlorpromazine, haloperidol, sulpiride, fluphenazine, perphenazine, thioridazine, pimozide, zotepine, risperidone, olanzapine, quetiapine, or amisulpride,

comprising administering to said patient a therapeutically effective amount of a carbostyril compound of [the given structural formula] … or a pharmaceutically acceptable salt or solvate thereof.

99    It is not in dispute that, in one form, the carbostyril compound, referred to in each claim, is aripiprazole.

Swiss type claims

100    It is convenient at this point to deal with a question of characterisation concerning claim 1 of the 772 patent. As I have noted, this is a Swiss type claim. Such claims are also referred to in the cases and in the literature as, variously, “Swiss form” or “Swiss style” or, simply, “Swiss” claims. I will use the expression Swiss type claim in deference to the use of that expression by Crennan and Kiefel JJ in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Limited (2013) 304 ALR 1.

101    The generalised form of such a claim is “the use of compound X in the manufacture of a medicament for a specified (and new) therapeutic use”: Bristol-Myers Squibb v Baker Norton Pharmaceuticals Inc [1999] RPC 253 at [44]; Actavis UK Ltd v Merck & Co Inc [2009] 1 WLR 1186 at [7]; see also Apotex 304 ALR 1 at [248]. In the discussion that follows, my reference to Swiss type claims is to claims which, as a matter of substance, accord with this generalised form.

102    The appellation “Swiss” derives from a statement of legal advice from the Swiss Federal Intellectual Property Office dated 30 May 1984, which was published in [1984] OJ EPO 581. The headnote to that statement is as follows:

A claim for the “use of compound X to treat … (indication) …” is inadmissible under Swiss Law. Limited claims directed to the “use of a compound … to produce agents against …” are admissible even where they relate to a second (or subsequent) medical use of a known medicament. Details concerning the formulation of a medicament (e.g. labelling, packaging or dosage) may be included in a patent application’s description.

103    The validity of such claims under the Convention on the Grant of European Patents, opened for signature 5 October 1973, 1065 UNTS 199 (entered into force 7 October 1977) (the EPC) was considered and accepted by the Enlarged Board of Appeal of the European Patent Office (the Enlarged Board and the EPO, respectively) in EISAI/Second Medical Indication (G05/83) [1979-85] EPOR B241 (Eisai). The Enlarged Board was there considering the EPC before revisions introduced in 2000: see the Act revising the Convention on the Grant of European Patents of 29 November 2000 (entered into force on 13 December 2007).

104    It is important to understand the particular legal setting in which Eisai was decided. The first particular matter to note is that, under (then) Art 52(4) of the EPC, methods for, amongst other things, treatment of the human body by surgery or therapy were not patentable as European patents, on the fiction that such methods were not susceptible of industrial application, as understood by Art 57—one of the requirements for patentability of an alleged invention. Article 53(c) of the EPC now provides for the same exclusion from patentability but removes the rationale of non-industrial application. Importantly, the exclusion from patentability of such methods of treatment did not (and, at the present time, does not) include products for use in those methods.

105    The second particular matter to note is that, when dealing with the requirement for novelty, (then) Art 54(5) provided that any substance or composition comprised in the state of the art (and hence not itself new) for use in a (then) Art 52(4) method was not denied patentability for lack of novelty, provided that the use of the substance or composition for “any method” referred to in (then) Art 52(4) was not comprised in the state of the art. As interpreted, the proviso meant that a product claim directed to the substance or composition for a first medical indication—in other words, a purpose-limited product claim—was allowable under the EPC. However, a claim directed to the substance or composition for a second or later medical indication was not allowable: see Sopharma SA’s Application [1983] RPC 195 at 197-198.

106    Eisai was one of seven cases which came before the Enlarged Board to determine whether, by means of a Swiss type claim, patent protection could be obtained for an invention where the substance or composition was to be used for a second medical indication.

107    The Enlarged Board held that it was “legitimate in principle” to allow Swiss type claims where the medicament was for a specified new and inventive therapeutic application, even where the process of manufacture did not differ from known processes using the same active ingredient.

108    The Enlarged Board’s conclusion was based on the following reasoning:

    Claims directed to substances or compositions for use in any method for treatment of the human body are directed to inventions that are susceptible of industrial application.

    Even though a substance or composition is known, an inventor can obtain a purpose-limited product claim for that substance or composition in respect of a first medical indication. The requirement for novelty is derived from the new pharmaceutical use.

    Claims directed to the use of a substance or composition for the preparation of a pharmaceutical product (ie, Swiss type claims) are equally directed to inventions that are susceptible of industrial application.

    The required novelty for the process which forms the subject matter of such claims is also derived from the new therapeutic use of the medicament. This is so, irrespective of whether any pharmaceutical use of the medicament is already known.

    The special provision of (then) Art 54(5) is directed to a purpose-limited product claim. It did not exclude second (and further) medical indications from patent protection other than by a purpose-limited product claim.

109    To summarise: Prior to Eisai, it was possible under the EPC to obtain patent protection for a known substance or composition for a medical use by means of a purpose-limited product claim, provided no medical use of the substance or composition was previously known. It was not possible, by means of a purpose-limited product claim, to obtain patent protection for the known substance or composition for a second or later medical use; after Eisai, it was possible, by employing the Swiss type claim, to obtain patent protection in respect of the known substance or composition for a second or later medical use, even though such protection could not be obtained by a purpose-limited product claim.

110    It is apparent, therefore, that the Swiss type claim derives from the need to accommodate and satisfy the particular requirements for patentability that, at the time of Eisai, existed under the EPC. In Baker Norton at [44], Jacob J explained the rationale for Swiss type claims as the need to steer clear of two obstacles to patentability—the requirement of novelty (by which Jacob J must have meant the particular requirement of novelty in respect of substances and compositions for therapeutic use under (then) Art 54(5)) and the ban on methods of treatment of the human body by therapy.

111    Dealing with the requirement for novelty, Jacob J explained that such claims are unnecessary when the substance or composition (used in the manufacture of the medicament) is new, because the substance or composition itself can be patented. However, when the substance or composition is old, the Swiss type claim is accepted as satisfying the requirement for novelty because the specified therapeutic use of the medicament, as opposed to the specified therapeutic use of the substance or composition (used in the manufacture of the medicament), is new. As Jacob J put it, “the manufacture of an old pill for use in a new treatment” is considered to be novel. In a later case (Takeda Chemical Industries Ltd’s SPC Applications (No.3) [2004] RPC 3 at [3]), Jacob J described the Swiss type claim as “intellectually questionable”.

112    Nevertheless, it can readily be seen how the Swiss type claim avoids the prohibition under the EPC on patents for methods for treatment of the human body. The manufacture of a medicament for use in particular treatment is not itself use of the medicament for that treatment: see Actavis [2009] 1 WLR 1186 at [21]. Swiss type claims are directed to the manufacturer of the medicament, not the physician who prescribes the medicament for use by a patient.

113    I should add that the revisions to the EPC in 2000 included a provision that now specifically allows purpose-limited product claims that are directed to substances or compositions for second (or later) medical uses, removing at least the novelty justification for permitting Swiss type claims: see (current) Art 54(5). Following those revisions, the Enlarged Board in ABBOTT RESPIRATORY/Dosage Regime (G02/08) [2010] EPOR 26 declared that, as this reason for Swiss type claims had ceased, applications for such claims should also cease. Now, Swiss type claims are no longer permitted for European patents. This is also the position in the United Kingdom for patents granted under the Patents Act 1977 (UK).

114     The rationale for Swiss type claims, as explained by Jacob J in Baker Norton, is not one that applies to Australian patents. The legal position in Australia is different. Methods for treating the human body with pharmaceutical products are patentable: Apotex 304 ALR 1 at [50], [286] and [314]. In Australia, such methods are accommodated by the general principles outlined in National Research Development Corporation v Commissioner of Patents (1959) 102 CLR 252. The particular impediment presented by the EPC in respect of methods for treatment does not exist for the applicant for an Australian patent.

115    Nevertheless, under Australian law, an invention which is a method for treating the human body with a pharmaceutical product must still satisfy the other requirements for a patentable invention specified in s 18 of the Act, including the requirement for novelty. But, unlike the requirements of the EPC considered in Eisai, no special novelty requirements exist under Australian law in relation to inventions involving substances or compositions for medical uses.

116    It is convenient to note here that, in its written submissions, the respondent stated that it “put in issue” whether Swiss type claims are “a valid form of claiming”. This submission seems to have been advanced merely formally. The respondent did not develop that fundamental question. Rather, it directed its submissions to a subsidiary question, with specific reference to the facts of the present case. In that connection, the respondent relied on the (then) generally-stated proposition in European patent law that novelty of purpose for use will confer novelty that is sufficient to support a Swiss type claim. In so doing, the respondent must be taken as having accepted, for the purposes of its submission, the general proposition that a new therapeutic use for a known medicament can provide the element of novelty required to support an invention claimed in the form of a Swiss type claim. However, the respondent submitted that no “new use” is in fact disclosed in claim 1 of the 772 patent because aripiprazole, as a product, was claimed for all uses in the treatment of schizophrenia in EP 141/US 528, and the selection of a sub-set from those uses in claim 1 does not involve a “new use”. It developed that submission in the context of certain grounds of invalidity referable to s 18(1) of the Act. I leave for later consideration in these reasons the question of whether claim 1 of the 772 patent, as a Swiss type claim, satisfies the requirement of “a patentable invention”, having regard to the particular arguments raised by the respondent in its case on invalidity. I will not address the fundamental question raised by the respondent because the respondent has not itself addressed that question.

117    The question for consideration in this section of my reasons is, as I have stated, one of characterisation. Should an invention defined by a Swiss type claim be characterised as a product or as a method or process? Are these characterisations apt for a Swiss type claim? The importance of determining the proper characterisation of the invention lies in determining how the question of infringement of claim 1 of the 772 patent is to be approached.

118    The applicants submitted that Swiss type claims are process claims. The respondent submitted that they are neither method or process claims, nor product claims.

119    The Enlarged Board in Eisai plainly considered (at [21] and [23]) Swiss type claims to be directed to a process of manufacture. In John Wyeth & Brother Ltd’s Application; Schering AG’s Application [1985] RPC 545, Whitford and Falconer JJ, siting in banc in two appeals to the Patents Court, held that Swiss type claims are claims directed to a method of manufacture. Whitford and Falconer JJ reasoned that a claim in the form of “[t]he use of substance A in the manufacture of a medicament to treat disease B” is, in reality, a claim to the method of manufacture of such a medicament by using substance A in its manufacture: see at 563. The New Zealand Court of Appeal in Pharmaceutical Management Agency Ltd v Commissioner of Patents [2000] 2 NZLR 529 reached a similar conclusion. Their Honours said that Swiss type claims are not product claims. They reasoned that such claims are akin to method claims: see at [47] and [60].

120    In my view, an invention defined by a Swiss type claim is appropriately characterised as method or process. For the purpose of this analysis, no useful distinction exists between the words “method” and “process”. In the Act, the words “method” and “process” are not defined. In my view, neither word has a meaning that is different from its ordinary English signification. My conclusion reflects, therefore, what I consider to be an apt use of the words “method” and “process” when applied as ordinary English words to describe the content and subject matter of the generalised form of the claim to which I have referred.

121    My conclusion on the question of characterisation also accords with the cases noted above which, whilst not binding, stand as persuasive authorities on the question. I propose to follow them.

Issues of construction

122    The parties are at issue in relation to a number of questions of construction that are common to both claims 1 and 7 of the 772 specification.

The person skilled in the art

123    It is trite law that, whilst construction is ultimately a question for the court, a patent specification, and relevant prior art documents, are to be construed through the eyes of the hypothetical person skilled in the art. The words are to be given the meaning which the person skilled in the art would attach to them in light of the common general knowledge and what is disclosed in the document itself: see, for example, Decor Corporation Pty Ltd v Dart Industries Inc (1988) 13 IPR 385 at 391; Root Quality Pty Ltd v Root Control Technologies Pty Ltd (2000) 177 ALR 231 at [49]; Flexible Steel Lacing Company v Beltreco Ltd (2000) 49 IPR 331 at [81]; Kinabalu Investments Pty Ltd v Barron & Rawson Pty Ltd [2008] FCAFC 178 at [45].

124    It is also trite law that the person skilled in the art may be taken, in an appropriate case, as having the composite skills of a team of persons. In General Tire & Rubber Company v Firestone Tyre & Rubber Company Ltd [1972] RPC 457, Sachs LJ, who delivered the judgment of the Court of Appeal, said (at 485):

The earlier publication and the patentee’s claim must each be construed as they would be at the respective relevant dates by a reader skilled in the art to which they relate having regard to the state of knowledge in such art at the relevant date. The construction of these documents is a function of the court, being a matter of law, but, since documents of this nature are almost certain to contain technical material, the court must, by evidence, be put in the position of a person of the kind to whom the document is addressed, that is to say, a person skilled in the relevant art at the relevant date. If the art is one having a highly developed technology, the notional skilled reader to whom the document is addressed may not be a single person but a team, whose combined skill would normally be employed in that art in interpreting and carrying into effect instructions such as those which are contained in the document to be construed.

125    The applicants submitted that, in Root Quality, Finkelstein J (at [70]-[72] and [94]) proceeded on the basis that the person skilled in the art, considered as a notional “team”, might be differently constituted depending on whether the task for that person is the construction of documents or on whether the task is, for example, considering whether an invention as claimed is obvious. The applicants then submitted that, in the present case, the person skilled in the art, for the purpose of construing the claims, is a team comprised of a psychiatrist in clinical practice and a psychopharmacologist. However, for the purpose of considering whether the invention as claimed involves an inventive step, the applicants submitted that the person skilled in the art is a team comprised of a psychiatrist in clinical practice, a pharmacologist (which I take to mean a psychopharmacologist) and a medicinal chemist.

126    The respondent expressed no substantial disagreement with this approach or, indeed, the characteristics of those who make up these respective teams. This may have been because the applicants’ approach made no difference to the respondent’s case on construction or its case on invalidity.

127    I do not accept that, in Root Quality, Finkelstein J was saying that, in relation to a given patent, it is permissible to treat the person skilled in the art as constituted by different teams depending on the patent question involved. Rather, his Honour was stating that, depending on the question involved, it may be necessary to focus on particular characteristics of the person skilled in the art considered as a team. In that case, the invention was a container suitable for growing plants that are later to be transplanted. When considering the question of whether it would have been obvious that certain variants did not have a material effect on the way the invention worked, his Honour remarked (at [72]) that the relevant member of the team, if there need be a team, was the person who intends to use the invention.

128    Thus, I do not accept the applicants’ differential approach to identifying the characteristics of the person skilled in the art when considered as a team. However, given the absence of substantial disagreement by the respondent, I will treat the person skilled in the art as a team comprised of a psychiatrist in clinical practice, a psychopharmacologist and a medicinal chemist. I will not treat the team as differently constituted depending on the patent question involved.

129    In written submissions, the applicants referred to this team as “the notional research group”. Although advocating the inclusion of a medicinal chemist as part of the team, the applicants adduced no evidence from a medicinal chemist on any issue arising in the proceeding.

Disorders associated with the 5-HT1A receptor subtype

130    The claims require the medicament to be effective in the treatment of “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype …”

131    The applicants submitted that this is a “broad requirement” and means no more than that the 5-HT1A receptor is implicated in, or plays a role in, the claimed disorders. The applicants submitted:

The necessary relationship will be found to exist even if the 5-HT1A receptor is not faulty or defective in a patient suffering from the claimed disorder. There will also be the necessary relationship notwithstanding the 5-HT1A receptor is not solely responsible for the claimed disorder. Moreover, the necessary relationship will be satisfied notwithstanding the 5-HT1A receptor is not directly responsible for the claimed disorder.

(Original emphasis.)

132    The applicants developed a number of submissions, and referred to an extensive body of evidence, under the following headings:

    the anatomical location of 5-HT1A receptors and serotonin;

    alterations in 5-HT1A receptor function in people suffering from schizophrenia;

    preclinical evidence of drugs which act at the 5-HT1A receptor; and

    clinical evidence of the efficacy of partial agonists at the 5-HT1A receptor.

133    The applicants submitted that this evidence supports the conclusion that the 5-HT1A receptor is “relevantly associated” with cognitive impairment in chronic and treatment-resistant schizophrenia. For reasons which will soon become apparent, I do not propose to detail the evidence to which reference was made in this regard.

134    The respondent submitted that the applicants’ construction of the word “associated” in this context took on a “chameleon character” that is inconsistent with the ordinary English meaning of the word. The respondent submitted that “associated”, as used in the claims, required “a significant and consistent connection”. It submitted that the evidence does not demonstrate that connection.

135    The respondent argued:

What appears from the evidence is that a vast number of receptors may affect cognitive impairment, of which the 5-HT1A is just one possible receptor. Further, some 5-HT1A agonists appear to have an effect on cognition but others do not. Those which do also affect other receptors, so that one cannot say which is the site of the relevant activity, and some drugs which appear to have an effect on cognition do not have activity at the 5-HT1A receptor at all.

136    In a similar vein, the respondent argued that:

… not all drugs which work on the 5-HT1A receptor do have an effect on cognitive impairment in schizophrenia and not all drugs which have an effect on cognitive impairment in schizophrenia work on the 5-HT1A receptor and even when drugs which work on the 5-HT1A receptor do have an effect on cognitive impairment in schizophrenia they may have that effect because of their work on other receptors. The respondent respectfully submits that it is not apt to describe the disorder as “associated with the 5-HT1A receptor”.

(Original emphasis.)

137    Like the applicants, the respondent developed these submissions by reference to an extensive body of evidence.

138    The body of evidence to which the parties referred included some 90 scientific papers. The papers included reports on clinical and laboratory studies, extracts from textbooks, and review articles. A number of the papers were referenced in the 772 specification.

139    A good deal of the hearing was devoted to cross-examination of the expert witnesses on a large number of these papers. The purpose of the cross-examination was either to demonstrate or, from the respondent’s perspective, to call into question, by reference to the literature, the involvement, in some way, of the 5-HT1A receptor in cognition, the extent of any such involvement, the action of certain antipsychotic drugs on the 5-HT1A receptor and other receptors, and the effect that such drugs have or might have in improving impaired cognition.

140    Without descending to details, it is sufficient for me to record that this evidence led to a significant debate between the experts on what could and should be taken from the literature. As one would expect, all the experts gave their evidence in a very open, careful and helpful manner. In the course of doing so, they provided insights—albeit personal insights—into how the literature should be read and how the reported results, and scientific and clinical observations, should be treated. The parties’ submissions were replete with references to this evidence. They provided tables summarising the literature and providing comments thereon, including references to the affidavit and oral evidence.

141    The parties treated the described association as one that required scientific proof. They said that this association was, in and of itself, an essential feature of the invention, as claimed. Each party had its own forensic reasons for adopting this approach. Based on the submissions made, I would suggest that: for the respondent, such an approach would make it more difficult for the applicants to prove their case on infringement; for the applicants, such an approach would make it more difficult for the respondent to prove its case on invalidity. Where they differed was, essentially, on what needed to be proved in that regard. The applicants contended that it is only necessary to show that the 5-HT1A receptor is implicated in, or plays a role in, the disorders. The respondent said that it is necessary to show a significant and consistent connection between the 5-HT1A receptor and the claimed disorders. The respondent submitted, further, that there is no such connection and hence there are no such disorders “associated” with the 5-HT1A receptor. To resolve that difference, the Court was invited, in effect, to decide a scientific controversy based on the literature in evidence, and the witnesses’ opinions on that literature.

142    That is not an invitation I propose to accept because, apart from anything else, I do not accept the position advanced by the applicants or the respondent. In my view, there is no need to debate the scientific questions thrown up in this part of the case, let alone decide, on the balance of probabilities, scientific facts. The specification teaches that “it is clearly-understood that 5-HT1A receptor agonistic activity or 5-HT1A receptor partial agonistic activity plays an important role in treatment-resistant schizophrenia and cognitive impairments”. The specification acknowledges that, while reports on animal testing do not always suggest that 5-HT1A receptor agonistic activity may be related to cognitive impairment, certain reports do suggest a relationship between that activity and improvements in cognitive impairment. The specification proceeds on the basis that “5-HT1A receptor agonistic activity is important for improving treatment-resistant schizophrenia or cognitive impairment caused by treatment-resistant schizophrenia.” I have summarised the relevant disclosures at [86]-[87].

143    Therefore, regardless of any debate about these matters, when the claims refer to “the treatment of disorders of the central nervous system associated with [the] 5-HT1A receptor subtype”, they are reflecting no more than a statement of the specification’s teaching.

144    Further, and importantly, the reference in the claims to the association between the disorders and the 5-HT1A receptor is immediately followed by, and qualified by, the words “which disorder is selected from …”. The claims then list specific disorders, namely certain nominated forms of cognitive impairment. The focus of each claim then becomes the treatment of these forms of cognitive impairment. It does not matter, therefore, that different medical or scientific views might be held about the involvement of the 5-HT1A receptor in the identified forms of cognitive impairment or their treatment. The claims take those forms of cognitive impairment as being “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype”.

145    In this way, it can be seen that, as used in the claims, the words “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype …” are but part of the description of an essential feature—the disorders to be treated. The other part of the description is the identification of the forms of cognitive impairment to be treated. Both parts of the description—defining the one essential feature—must be read together, not treated as separate integers.

146    Therefore, contrary to the parties’ submissions, I do not accept that the words “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype …” define a free-standing essential feature of the invention that adds, meaningfully, to the identification of the specific forms of cognitive impairment already referred to. The specification does not suggest, for example, that the identified forms of cognitive impairment can be further divided into disorders of the central nervous system that are associated with the 5-HT1A receptor, and those that are not. The claims treat the nominated forms of cognitive impairment as disorders that are associated with the 5-HT1A receptor. It follows that, for the purposes of the claims, and importantly for the question of infringement, use of the compound to produce a medicament for (claim 1), or use of the compound as a method of treating (claim 7), one of those forms of cognitive impairment is use of the medicament or the method to treat a disorder of the central nervous system that is associated with the 5-HT1A receptor.

147    The respondent advanced an additional argument under this heading. It submitted that, not only had the applicants failed to establish that the claim disorders are not associated with the 5-HT1A receptor, they had also not proved the effectiveness of aripiprazole in treating those disorders. The respondent advanced the same submission in the context of addressing the infringement of claim 7 arising under s 117(2)(b) of the Act. In this connection, the respondent placed particular significance on the ARTG Product Information for Abilify which, at 23 September 2011 and 26 November 2013, stated that trials had not been conducted in patients with first episode schizophrenia or treatment-resistant schizophrenia, with the consequence that the efficacy of aripiprazole in these groups had not been determined at those times.

148    This additional argument must be rejected. It is a disguised challenge to the utility of the invention. As I will later explain (at [481]-[483]), the respondent’s challenge to the validity of claims 1 and 7 of the 772 patent on the ground of inutility was a very limited one. In any event, the evidence of Professor Singh and Associate Professor Phillips (discussed at [211]-[225]) satisfies me that aripiprazole can be effective in treating cognitive impairment in schizophrenia, including for patients in the chronic phase of the illness who have failed to adequately respond to previous medication.

Cognitive impairment as a disorder caused by schizophrenia

149    The claims describe the cognitive impairment to be treated as “caused by” treatment-resistant schizophrenia, inveterate schizophrenia or chronic schizophrenia. With some justification, the respondent submitted that no such disorders exist.

150    There was no disagreement between the experts: cognitive impairment can be a symptom of schizophrenia. However, properly described, it is not a disorder caused by schizophrenia.

151    The respondents’ position appears to be that the claims should be construed strictly literally, with the consequence that, as there is no disorder of cognitive impairment caused by one of the three types of schizophrenia, there can be no infringement of the claims.

152    I do not accept that submission. The specification and claims must be given a sensible interpretation. In British Thomson-Houston Company Ltd v Corona Lamp Works Ltd (1921) 39 RPC 49, Lord Shaw said (at 89):

I think there is no rule, whether of benevolent or malevolent construction, which should apply to patent specifications. A specification must take its rank among all ordinary documents which are submitted to a reader for his guidance or instruction, and a reader ordinarily intelligent and versed in the subject-matter. Such a reader must be supposed to bring his stock of intelligence and knowledge to bear upon the document, not unduly to struggle with it, but anyhow to make the best of it; if, as the result, he understands what the invention is, can produce the object and achieve the manufacture by the help of the written and drawn page, then the subject-matter of the invention cannot fail on the head of vagueness.

153    The cases are not lacking in observations to similar effect. It is not necessary to cite them.

154    How would the notional person skilled in the art interpret and understand this part of the claims? I do not accept that the person skilled in the art would persist with a literal construction that he or she regarded to be nonsensical. The person skilled in the art would strive to give the claim what he or she regarded to be its intended meaning. He or she would know, as a matter of common general knowledge, that there is no disorder of cognitive impairment caused by schizophrenia. But, equally, he or she would know, as a matter of common general knowledge, that cognitive impairment can be a symptom of schizophrenia. The person skilled in the art would therefore understand the claims to be referring to cognitive impairment as a symptom of schizophrenia and would not be diverted by the claims’ use of medically incorrect language. The person skilled in the art would know that there is no other reasonably alternative construction of this part of the claims.

155    In this connection, the claims must be construed in the context of the specification as a whole. It is true that the body of the specification, in several places, uses the same language employed in the claims. In other parts of the specification, different language is used. For example, when turning to discuss the treatment of schizophrenia, the specification refers to the fact that it has been reported that atypical antipsychotic drugs are “more effective against the negative symptoms and cognitive impairments associated with schizophrenia” than typical antipsychotic drugs. The specification refers to treatment-resistant and treatment-refractory schizophrenics suffering from not only the positive symptoms of schizophrenia, but also from the negative symptoms, emotional disorders and cognitive impairments. It discloses that clozapine has been reported to be “ineffective against cognitive impairments in treatment-resistant schizophrenics”.

156    Thus, the specification itself makes tolerably clear that it is speaking of cognitive impairment as a symptom of schizophrenia, despite the awkwardness of other language used in the description. The claims should be understood accordingly. In these reasons, I will refer to cognitive impairment in schizophrenia or cognitive impairment associated with schizophrenia, with the same intended meaning.

Failure to respond to antipsychotic drugs

157    The claims require that the medicament or method of treatment be for one of the nominated forms of cognitive impairment where the patient has failed to respond to antipsychotic drugs selected from a group comprising certain typical and atypical antipsychotics. The parties are at issue as to whether this requirement means that there has been a failure to respond to one or more such drugs (second line or later line treatment) or two or more such drugs (third line or later line treatment). The applicants submitted that the former construction is correct; the respondent, the latter.

158    In my view, the respondent’s submission is correct. The claims characterise this feature by the words “fails to [respond] to antipsychotic drugs selected from” the identified drugs. The use of the plural form “antipsychotic drugs” plainly denotes two or more of the identified drugs. There is no justification for reading into the claims the words “one or more” so that the integer reads “one or more antipsychotic drugs”.

159    The use of the plural form is no slip of the pen. This part of the claims is in complete accord with the description of the invention in the body of the specification, and the examples given. I refer, in that regard, to the passages of the specification quoted and discussed at [91]-[92].

160    That said, the specification does not provide any reason for limiting claims 1 and 7 to third line or any other line of treatment. There is a general statement that “the compound in the present invention may prove to be a potent and safer drug therapy for [the described disorders], which fail to respond adequately to currently available antipsychotic drugs …” I am satisfied that, here, the person skilled in the art would understand the specification to be disclosing that “the compound of the present invention” may prove to be a useful addition to the physician’s armamentarium and thus a useful alternative to other known medications in the treatment of schizophrenia, particularly where, speaking at the priority date, the previously known antipsychotic drugs may not have been effective in treating a patient’s schizophrenia. But the specification does not teach that aripiprazole will only be effective where other drug treatments have failed.

161    The specification goes on to give various combinations of typical and atypical drugs to which a patient’s symptoms might not be responsive. No explanation is given for providing these particular combinations or, indeed, for the nomination of the other known drugs referred to in those combinations. Having regard to the practice at the priority date of switching medications in the treatment of schizophrenia where the patient’s response to his or her medication was not satisfactory (for whatever reason), I am satisfied that the person skilled in the art would simply read these combinations as nothing more than illustrations or examples of the general statement in the specification—that is to say, as illustrations or examples of when “the compound in the present invention” might be a useful alternative. Thus, read in the context of the specification as a whole, this limitation in claims 1 and 7, whilst standing as an essential feature of the invention as claimed, appears to be nothing more than one that has been arbitrarily imposed. The specification does not teach against the use of the compound as, for example, first line or second line treatment and there would be no reason for the person skilled in the art to think, on reading the specification, that the compound would not be equally efficacious in the treatment of a patient’s cognitive impairment if used as first line or second line treatment. None of the expert witnesses gave evidence that, on his reading of the specification, aripiprazole would only have utility in the treatment of cognitive impairment associated with schizophrenia if used as third line or later line treatment after the patient’s symptoms had failed to respond to the drugs listed in claims 1 and 7. Indeed, such an understanding would have been at odds with the prescribing practices of a number of the experts in relation to aripiprazole.

162    As I will come to explain, the conclusion that this feature is an arbitrary limitation is significant when considering the respondent’s case on invalidity.

Infringement

Claim 1

163    The applicants submitted that the respondent’s intention to market and supply the GH products in Australia constitutes a threatened infringement of claim 1, based on the meaning of “exploit” as used in the Act. The applicants submitted that it does not matter that the method or process claimed in claim 1 is performed outside the patent area. It is enough that the product resulting from the claimed method or process is exploited in the patent area.

164    A patentee has the exclusive right to exploit the invention in the patent area: s 13(1) of the Act. The definition of “exploit” (Schedule 1 of the Act) is as follows:

exploit, in relation to an invention, includes:

(a)    where the invention is a product—make, hire, sell or otherwise dispose of the product, offer to make, sell, hire or otherwise dispose of it, use or import it, or keep it for the purpose of doing any of those things; or

(b)    where the invention is a method or process—use the method or process or do any act mentioned in paragraph (a) in respect of a product resulting from such use.

165    In Alphapharm Pty Ltd v H Lundbeck A/S (2008) 76 IPR 618, the applicant (the alleged infringer) argued that, in order for there to be an exploitation of an invention that is a method or process, para (b) of this definition requires the method or process to be used in the patent area. This argument was rejected by Lindgren J, who found (at [693]-[694]):

693    A consequence of the construction supported by Alphapharm is that in the case of an invention which is a method or process, importation is not a form of exploitation unless the product imported had resulted from the use of the method or process in Australia. However, as the Lundbecks submit, where the product results from the use of the method or process in Australia, the very making of the product, having occurred in Australia, would itself be a contravention of the patented method or process (para (a) of the definition of “exploit”). Accordingly, the effect of Alphapharm's submission would be that in the case of an invention of a method or process, the reference to importing is superfluous.

694    I do not think that the construction supported by Alphapharm is correct. There is no suggestion in the express terms of the definition of “exploit” that importation, with nothing more, is not to be a form of exploitation in the case of a patented method or process. The territorial connection with Australia is one that is implied, and the proper construction of the definition of “exploit” has the territorial connection attaching twice, but not three times. The notion of “in Australia” does not follow the expression “from such use” at the end of para (b). The correct construction is, in my view, as follows:

exploit, in relation to an invention includes:

(a)    where the invention is a product—[in Australia, or more accurately, in the patent area] make, hire, sell or otherwise dispose of the product, offer to make, sell, hire or otherwise dispose of it, use or import it, or keep it for the purpose of doing any of those things; or

(b)    where the invention is a method or process—[in Australia, or more accurately, in the patent area] use the method or process or do any act mentioned in paragraph (a) in respect of a product resulting from [the use, anywhere, of the method or process].

166    The respondent did not contest this construction of “exploit”. Nevertheless, it submitted that the applicants’ case is “misconceived”. As I have recorded (at [118]), the respondent submitted that, whatever place Swiss type claims have in the Australian patent system, they are neither method or process claims, nor product claims.

167    Further, the respondent submitted that, if the applicants’ case is correct, the importation and sale of a drug containing aripiprazole would infringe claim 1, “even if the intended use, reasonable use, suspected use and actual use did not fall within the method of claim 7 because … the medicament would be ‘effective’ for the treatment of cognitive impairment in schizophrenia even if not used therefor.” The respondent submitted that this would leave s 117 of the Act (see [179]) “with no work to do at all”.

168    I do not accept the respondent’s submission. First, as I have already found (at [120]), the invention claimed in claim 1 is properly characterised as a “method or process” for the purposes of the definition of “exploit” in the Act. Secondly, s 117 has no relevant application to claim 1. In the context of claim 1, the product that is being used is the carbostyril compound (relevantly, aripiprazole) to make the medicament. Although the intended therapeutic use of the medicament is defined in claim 1, the manufacture of the medicament itself does not stand as use of the medicament for the defined purpose. In the present case, the application of s 117 of the Act to the therapeutic use of the medicament so made, falls to claim 7, not to claim 1.

169    This is not to say that the therapeutic use defined in claim 1 can be ignored when considering whether that claim has been, or is threatened to be, infringed. The therapeutic use defined in the claim qualifies, and thus confines, the scope of the monopoly that is claimed. For prescription medicines, such as the GH products, the therapeutic use of the medicament will be manifest from the marketing approval and registration that has been granted for it.

170    As I have noted (at [7]), the respondent has sought and obtained marketing approval and, consequently, registration of the GH products for the treatment of schizophrenia, including maintenance of clinical improvement during continuation therapy. There are in fact a number of separate approvals and registrations, covering the various dosage forms in which the GH products are presented. The approvals and registrations are in terms which comprehend the treatment of all the symptoms and domains of schizophrenia. This plainly includes the treatment of cognitive impairment associated with schizophrenia in all its forms, such as treatment-resistant schizophrenia and chronic schizophrenia. The approvals and registrations are also in terms which comprehend treatment using the GH products regardless of whether they are used with, or in substitution for, other drugs or other therapies. The use of the GH products, whether as first line, second line or later line therapy is plainly within the approvals that the respondent has sought and obtained. Therefore, there is no doubt that the therapeutic use of the GH products, as revealed by the approvals and registrations held by the respondent, includes the therapeutic use defined in claim 1 of the 772 patent.

171    The respondent has proffered an undertaking to the Court that, notwithstanding the approvals and registrations it has obtained, it will not advertise or otherwise promote the GH products specifically for use in the treatment of cognitive impairment in persons suffering from treatment-resistant schizophrenia, inveterate schizophrenia, or chronic schizophrenia, in circumstances where the cognitive impairment has failed to respond to at least two of the following drugs: chlorpromazine; haloperidol; sulpiride; fluphenazine; perphenazine; thioridazine; pimozide; zotepine; risperidone; olanzapine; quetiapine; or, amisulpride: Exhibit 3. In other words, the respondent has proffered an undertaking not to advertise or promote the GH products specifically for the therapeutic use defined in claim 1 or the method claimed in claim 7.

172    For the purpose of determining infringement of a Swiss type claim, does it matter that the alleged infringer does not actually advertise or promote the medicament specifically for the therapeutic use defined in the claim? I do not think it necessarily does. The question is whether, objectively ascertained, the medicament that results from the claimed method or process is one that has the therapeutic use defined in the claim. The question is not really about how the alleged infringer markets its product, although, plainly, its conduct in that regard may well assist in determining, objectively, whether the accused product has the claimed therapeutic use.

173    In the present case, I am not persuaded that an absence of advertising or promotion by the respondent of the GH products for the therapeutic use defined in claim 1 would change the objective characterisation of those products as ones that are, nevertheless, “effective in the treatment” defined in claim 1.

174    For these reasons, I am satisfied that the respondent’s intention to import, market and supply the GH products, whose scope of therapeutic use, as registered, plainly includes the therapeutic use defined in claim 1, is a threatened exploitation of the invention and would have been a threatened infringement of the claim, had it been valid.

175    Before leaving this question, I should record that the applicants advanced their case on infringement of claim 1 on an alternative basis. They submitted that the operation of the so-called Saccharin doctrine means that, even though the GH products are manufactured outside Australia, the respondent’s importation of them would be an infringement of claim 1.

176    The Saccharin doctrine derives its name from Saccharin Corporation Ltd v Anglo-Continental Works Ltd (1900) 17 RPC 307, although its origins can be seen in much earlier cases which in fact establish the common law principle for which the applicants contend: Elmslie v Boursier (1869) LR 9 Eq 217; Wright v Hitchcock (1870) LR 5 Ex 37; Von Heyden v Neustadt (1880) 14 Ch D 230. The Saccharin doctrine is a development of the earlier principle. In Saccharin the claimed invention was for a process of manufacturing ortho-toluene-sulpho-chloride. The process was used abroad to manufacture this substance as an intermediate. The intermediate was then subjected to further processes to produce saccharin. The saccharin was imported for sale in England. The plaintiffs argued that the importation and sale of saccharin, so produced, was an infringement of the patent. The defendants argued that, as the patented process was for the manufacture of ortho-toluene-sulpho-chloride, and as the product it imported was saccharin, the importation and sale of saccharin could not be an infringement of the patent.

177    After referring to Elmslie and Von Heyden, and noting that neither case covered the case for decision, Buckley J said (at 319):

    If the patented process were the last stage in the production of the article sold, the importation and sale of the product would, in my opinion, plainly be an infringement. Does it make it any the less an infringement that the article produced and sold is manufactured by the use of the patented process which is subjected to certain other processes? In my opinion it does not. By the sale of saccharin, in the course of the production of which the patented process is used, the Patentee is deprived of some part of the whole profit and advantage of the invention, and the importer is indirectly making use of the invention. In my judgment, therefore, this contention fails.

178    It does not seem to me that the applicants’ reliance on the Saccharin doctrine is entirely apposite. The present case is not one concerning the manufacture abroad of an intermediate substance by a patented method or process which is then further processed to yield a product that is then imported and sold in Australia. Insofar as the applicants rely on the decision in Saccharin to illustrate the earlier common law principle to which I have referred, then the decision adds nothing to the applicants’ case framed in terms of the definition of “exploit” used in the Act. It is not necessary for me to decide the question of whether the common law principle, or indeed the Saccharin doctrine itself, is part of Australian patent law under the Act.

Claim 7

179    The applicants’ case on infringement of claim 7 is based on s 117 of the Act, which provides:

117    Infringement by supply of products

(1)     If the use of a product by a person would infringe a patent, the supply of that product by one person to another is an infringement of the patent by the supplier unless the supplier is the patentee or licensee of the patent.

(2)    A reference in subsection (1) to the use of a product by a person is a reference to:

(a)    if the product is capable of only one reasonable use, having regard to its nature or design—that use; or

(b)     if the product is not a staple commercial product—any use of the product, if the supplier had reason to believe that the person would put it to that use; or

(c)     in any case—the use of the product in accordance with any instructions for the use of the product, or any inducement to use the product, given to the person by the supplier or contained in an advertisement published by or with the authority of the supplier.

180    The applicants place reliance on the use referred to in s 117(2)(b). This requires the applicants to establish that the GH products are “not … staple commercial product[s]” and that the respondent has reason to believe that the GH products would be used in a way that infringes claim 7. The applicants submitted that both requirements have been established in this case.

181    The respondent submitted that the GH products are “staple commercial products”, with the consequence that s 117(2)(b) has no application to its supply of the GH products. Further, the respondent submitted that the applicants have not established that there is reason to believe that the GH products would be used in a way that infringes claim 7.

Are the GH products staple commercial products?

182    The respondent submitted that the GH products are “staple commercial products" because “they have significant non-infringing uses”.

183    In that connection, the respondent submitted:

Claim 7 requires the administration of a medicament containing aripiprazole as its active pharmaceutical ingredient in order for the method of treatment to be undertaken. A medicament containing aripiprazole has a variety of uses. It can be used in treatments which will not infringe claim 7. The evidence was that aripiprazole is a second generation antipsychotic drug which is used as a first line treatment, as a second line treatment, or at any stage in the course of schizophrenia. It is used to treat different phases and episodes of schizophrenia, and may be prescribed when a patient is ‘switched’ from a previous antipsychotic drug. Its use is not limited to use in the circumstances described in claim 7, which requires that aripiprazole be used for the treatment of cognitive impairment caused by one of three identified sub-forms of schizophrenia which has not responded to previous treatment by at least two named antipsychotic drugs.

184    The respondent also pointed to the fact that the applicants’ pharmaceutical product containing aripiprazole—Abilify—is approved for a number of indications.

185    In this connection, it pointed to the approval to use Abilify for:

    the treatment of schizophrenia including maintenance of clinical improvement during continuation therapy;

    the acute treatment of manic or mixed episodes associated with Bipolar I Disorder in adults as monotherapy and in combination with lithium and valproate; and

    the maintenance treatment of manic or mixed episodes in Bipolar I Disorder in adults as monotherapy.

186    The respondent submitted that this shows that a medicament containing aripiprazole as its active pharmaceutical ingredient has “a wide variety of applications” and is, thus, a staple commercial product.

187    I do not accept that the GH products are “staple commercial products”.

188    First, the reference in s 117(1) of the Act to the “product” is to the allegedly infringing product (here, the GH products), not to (here) aripiprazole as such: cf Sanofi-Aventis Australia Pty Ltd v Apotex Pty Ltd (No 3) (2011) 196 FCR 1 at [267]. The GH products are registered for, and only approved for, the treatment of schizophrenia including maintenance of clinical improvement during continuation therapy. The GH products do not have "a wide variety of applications".

189    Secondly, even if aripiprazole were to be taken as the “product” for the purposes of s 117(1), it, similarly, does not have “a wide variety of applications”. It is, in Australia, an antipsychotic agent whose only use is to treat, by prescription, the symptoms of certain types of mental illness. It is true that, within that limited field of use, aripiprazole can be used for both infringing and non-infringing purposes. However, as the Full Court pointed out in AstraZeneca AB v Apotex Pty Ltd (2014) 226 FCR 324 at [431], that fact is not conclusive.

190    In Northern Territory v Collins (2008) 235 CLR 619, Crennan J said (at [145]) that the phrase “staple commercial product”, as used in s 117(2)(b) of the Act, means “a product supplied commercially for various uses”. However, as the plurality in the Full Court in AstraZeneca 226 FCR 324 pointed out at [429], her Honour's statement must be read in its proper context, including the factual setting in which it came to be made. That setting was the supply of a species of timber which Crennan J acknowledged (at [143]-[144]) to be a “basic product commonly used for various purposes”. Aripiprazole is simply not of the same commercial character as the species of timber considered in Collins.

191    I am satisfied, therefore, that the GH products are not staple commercial products and that, accordingly, the threshold requirement of s 117(2)(b) of the Act is met in the present case. I would be of the same view even if aripiprazole, as an active pharmaceutical ingredient, were to be taken as the “product” for the purposes of s 117(1) of the Act.

Reason to believe

192    The “reason to believe” requirement in s 117(2)(b) of the Act is determined objectively.

193    When considering that requirement in the context of whether leave to appeal should be granted from my earlier judgment in this matter (in which I held that interim injunctive relief should be granted against the respondent: Otsuka Pharmaceutical Co Ltd v Generic Health Pty Ltd (2012) 291 ALR 763), Emmett J in the Full Court (Generic Health Pty Ltd v Otsuka Pharmaceutical Co Ltd (2013) 296 ALR 50) said (at [35]):

35    The question is whether there were factual matters known to Generic Health that would lead a reasonable person to believe that the GH Products would be put to an infringing use. It is not to the point that Generic Health, through its relevant officers, did not actually have such a belief. The question is whether there was material before the primary judge that could support a finding that a reasonable person in the position of Generic Health would have reason to hold such a belief.

194    This approach is also reflected in the reasons for judgment of Greenwood J (at [221]-[230]), where his Honour considered whether there was evidence to support a prima facie case that, objectively viewed, the respondent had reason to believe that the GH products “would be put to a claim 7 infringing use”.

195    In the same case, Bennett J put the matter somewhat differently. Her Honour said (at [103]):

103    The question that arises in this application is the meaning to be attributed to the phrase “reason to believe that the person would put it to that use”. The reason to believe is that of the supplier and may be subjective: an actual belief, or objective: that there are reasonable grounds to believe. In each case, the belief is determined on the balance of probabilities.

196    Later, her Honour said (at [106]):

106    The proper construction of s 117(b) must be that there is a reasonable belief of a significant likelihood that a person will put a product to that use. This construction is assisted by the use of the words “reasonable belief”, rather than “knowledge”. A person may have a reasonable belief that an event will or would happen without having knowledge that the event will or would necessarily happen. A reasonable belief that an event would happen arises from a belief in the likelihood of that event. That likelihood must be significant. A belief that an event is of a low likelihood would amount to a reasonable belief that the event may happen. The word used by s 117(b) is that that a person would put the product to that use.

(Original emphasis.)

197    The objective determination of whether there is “reason to believe” in the context of s 117(2)(b) of the Act was earlier discussed by French J (when in this Court) in Collins v Northern Territory (2007) 161 FCR 549, where his Honour said (at [64]-[66]):

64    The words “reason to believe” in s 117(2)(b) have long standing statutory antecedents. They and similar formulae frequently condition the exercise of statutory powers and require at least, an objective basis for the relevant belief and, according to context, require actual belief: WA Pines Pty Ltd v Bannerman (1980) 41 FLR 175 at 185-186; 30 ALR 559 at 571 and authorities there cited. On the other hand the formula may be taken, according to its statutory context, to convey a requirement for an objective basis for belief without the necessity of actual belief: eg George v Rockett (1990) 170 CLR 104 at 112.

65    Where the words “reason to believe” condition a power they are used to ensure that the exercise of the power is justified by reference to objective facts and is not to be exercised simply upon unsupported belief. The same term in s 117(2)(b) defines a necessary condition of liability for contributory infringement in relation to the supply of non-staple commercial products. It could be construed as purely objective in the sense that there were factual matters known to the supplier which would lead a reasonable person to believe that the product would be put to an infringing use. An alternative construction would additionally require the supplier to actually believe that the person supplied would put the product to such a use. The analogous provision in § 271(c) of the Patents Act 1952 (US) is satisfied by actual knowledge without requiring reasonable grounds for the knowledge. Section 60(2) of the Patents Act 1977 (UK) would also be satisfied by actual knowledge without reasonable grounds. But it provides an alternative basis for liability, namely that “ … it is obvious to a reasonable person in the circumstances that those means are suitable for putting, and are intended to put, the invention into effect in the United Kingdom”.

66    To construe s 117(2)(b) as requiring actual knowledge supported by reasonable grounds would render the scope of liability for contributory infringement under Australian law narrower than that under United States or United Kingdom law. Unlike those jurisdictions, it would require both subjective belief and the objective basis for it to be proven. The better construction, consistent with the harmonisation purpose of the legislation, would appear to be objective. In the present case his Honour's finding as to the Northern Territory's reason to believe that ACOC would use the timber from the trees for the purpose of producing cypress oil appears to have been supported by reference to purely objective criteria. His finding in that respect is not in issue in this appeal. The preceding observations about the proper construction of the “reason to believe” requirement are therefore strictly obiter.

198    In light of the need to show that, objectively, the respondent had “reason to believe” that the GH products would be used in a way that would infringe claim 7, the applicants traversed the evidence—much of it undisputed—about the nature of schizophrenia, the course of the illness, and the manner of its treatment.

199    The applicants referred to the fact that the majority of patients suffering from schizophrenia have some degree of cognitive impairment and that chronic schizophrenia is the outcome for the majority of those who suffer from the illness. They referred to the clinical practice of switching antipsychotics in an effort to optimise the patient’s response.

200    In this connection, Professor Singh gave the following evidence:

    It is possible that certain patients may not respond well to a particular medication that is first prescribed or will experience unacceptable side effects, such as … movement side effects ... In fact, about a quarter of all patients suffering from Schizophrenia who are prescribed antipsychotic medication will not respond to, or will not tolerate, their medication. It is common to then try prescribing a different medication for those patients. I would therefore estimate that about 25% of all patients suffering from Schizophrenia would be switched from one atypical antipsychotic to another. The majority of patients suffering from chronic Schizophrenia will need to switch medications at some stage, and this may be because the positive symptoms have not been brought under control or, if the positive symptoms have been addressed, negative or cognitive symptoms persist. It is also not uncommon for patients to fail to respond to the second medication which they are prescribed, and for such patients to then be switched to a third medication in order to bring their symptoms under control.

    (Original emphasis.)

201    Professor Singh’s evidence concerning switching medication to treat the negative or cognitive symptoms of schizophrenia was the subject of debate in the evidence. I will return to that debate below. But I do not think that there was any real dispute in the evidence about the need, for many patients, to switch medication for the treatment of their schizophrenia. Some of the witnesses emphasised the risks of switching medication; others emphasised the exercise of clinical judgment in assessing the risks associated with switching medication. Notwithstanding these differences in emphasis, none of the witnesses doubted the fact that switching antipsychotic medication may well be needed to attempt to bring a patient’s symptoms of schizophrenia under control. Similarly, none of the witnesses doubted the fact that switching medication in the treatment of schizophrenia will involve risks that must be evaluated as part of the responsible exercise of clinical judgment.

202    The respondent’s pleaded case on common general knowledge supports the fact that, at least at the priority date, switching a patient’s medication for schizophrenia, where the patient had failed to respond to two or more existing antipsychotics, was common general knowledge. In its amended particulars of invalidity filed on 4 February 2014, the respondent provided the following particulars of common general knowledge in relation to claims 1 and 7 of the 772 patent:

… (iii)    switching of patients suffering from schizophrenia from treatment with one antipsychotic drug to another antipsychotic drug;

(iv)    switching of patients suffering from chronic schizophrenia from treatment with one antipsychotic drug to treatment with another antipsychotic drug;

(v)    switching of patients suffering from treatment-resistant schizophrenia from treatment with one antipsychotic drug to treatment with another antipsychotic drug;

(vi)    switching of patients undergoing treatment with typical antipsychotic drugs to atypical antipsychotic drugs;

(vii)    switching of patients undergoing treatment with atypical antipsychotic drugs to other atypical antipsychotic drugs;

(viii)    switching of patients undergoing treatment with antipsychotic drugs known to be effective in the treatment of schizophrenia to other antipsychotic drugs known to be effective in the treatment of schizophrenia;

(ix)    switching the medication of a patient with chronic, treatment-resistant (or inveterate) schizophrenia, where that patient’s symptoms and signs of schizophrenia had failed to respond to 2 or more existing antipsychotics; …

203    The applicants also pointed to the evidence that the treatment of schizophrenia comprehends the treatment of all its symptoms, whether those symptoms be positive symptoms, negative symptoms, cognitive impairment or mood disorders.

204    In this connection, there was general agreement amongst the experts that, once a patient’s positive symptoms are under control, long-term treatment (or continuation therapy) involves maintaining control of the patient’s positive symptoms with a view also to countering the other symptoms of the illness. However, different views were expressed about how this might be done. These different views are illustrated by the following evidence.

205    Professor McGorry said that, in his experience, switching was commonly done to improve a patient’s positive symptoms but rarely, if ever, done to improve cognitive impairment. Professor McGorry said that there is little evidence or clinical experience of cognitive impairment in schizophrenia being specifically responsive to medication independently of a response in positive symptoms. Professor McGorry’s view was that the use of antipsychotics in continuation therapy is a key part of the patient’s treatment to maintain response or remission from positive symptoms. He said that, if this treatment resulted in any other benefit in the effect on negative symptoms and the other domains of schizophrenia, which was not uncommonly the case, then the benefit was viewed by him as a “bonus”.

206    Dr O’Dea expressed a broadly similar opinion in relation to the course of treatment. Speaking as at the priority date, he said, when treating a patient with schizophrenia in an acute hospital setting or clinic, he often used olanzapine as a first line antipsychotic medication. He considered olanzapine to be more effective than other atypical antipsychotics (other than clozapine) for such patients, where efficacy for positive symptoms is the overriding concern. He said, however, that, for patients in the community, the level of sedation associated with medication, such as olanzapine, was difficult to manage with ongoing employment, home duties and/or study commitments. He said that, in these cases, he prescribed less sedating alternatives, including risperidone. Indeed, he said that, although the focus of his treatment of patients with schizophrenia are the patient’s positive symptoms, he might review the patient’s medication to address negative or cognitive symptoms via reducing the level of sedation.

207    However, he also said that, at the priority date, and at the present time, a number of patients with schizophrenia that he treated had significant residual positive, negative and cognitive symptoms, and signs of severe chronic treatment-resistant schizophrenia. Frequently, he would switch these patients to clozapine which he considered to be the best clinical practice, both at the priority date and now.

208    Dr O’Dea expressed the view that most antipsychotics are equally ineffective in treating negative and cognitive symptoms. He said that when he prescribes clozapine over other antipsychotics, it is usually in the context of addressing positive symptoms that are treatment-resistant. He said:

I do not switch patients with treatment-resistant schizophrenia to another antipsychotic on the basis that I consider the alternative antipsychotic medication more effective for treating cognitive impairment or negative symptoms. I may change a patient to a less sedating antipsychotic medication in order to ameliorate the potential effects of sedation on cognitive functioning, but that is a different consideration. I might also change a patient’s medication because the alternative medication might have a more tolerable side effects profile.

209    In this connection, Dr O’Dea said that he would be “very reluctant to switch to treat cognitive or negative symptoms”.

210    Dr O’Dea also said:

Patients with treatment-resistant schizophrenia whom I switch to clozapine invariably have residual positive symptoms of schizophrenia that I am endeavouring to better treat by switching. If a patient’s positive symptoms are well controlled on an atypical antipsychotic other than clozapine, my usual clinical practice is to continue with this medication rather than switch to clozapine. I then focus more on psychosocial interventions to address any ongoing cognitive or negative symptoms and signs. When I switch a patient to clozapine, I usually do so because I consider it more effective than other antipsychotics in treating positive symptoms and signs, but not necessarily negative and cognitive symptoms and signs of schizophrenia.

211    On the other hand, Professor Singh placed emphasis on the role of drug therapy to address, specifically, the patient’s negative or cognitive symptoms: see, for example, the quote at [200]. He disagreed with Professor McGorry’s view that switching is rarely, if ever, done to improve cognitive impairment. He said that while switching medications to improve the negative and cognitive symptoms of schizophrenia may not be done “commonly”, it is a practice that was undertaken at the priority date and at the present time. He also said:

Different patients have different needs and therefore value their response to certain drugs more highly, so certain drugs may bring about a better response with certain patient types than with other patient types. For instance, some patients with chronic schizophrenia may be “high functioning” (meaning that they are engaged in occupations which require a high level of cognitive function, such as lawyers or engineers) and these patients would have different needs to other patients with chronic schizophrenia.

212    In cross-examination, Professor Singh gave the following evidence:

I teach that whenever you see a patient with a psychosis, a chronic psychosis you review the full symptom spectrum, you review the medication that they’re on and … if the person has continuing negative or cognitive symptoms, you attempt to treat them. They’re not a bonus.

213    Professor Singh drew attention to MATRICS. This was a major program undertaken by the NIMH which recognised, amongst other things, the importance of seeking new drug treatment to improve cognition in patients with schizophrenia.

214    Professor Singh also drew a distinction between the treatment of patients in the public system (which, he said, tends to deal “with the more severe cases, the more damaged cases, people who have less capacity for rehabilitation”) and the treatment of patients in the private system, thereby suggesting that, in the private system, there is more opportunity to optimise the patient’s treatment to address, by medication, the adverse effects of a patient’s cognitive impairment or mood disorders associated with schizophrenia.

215    Professor Singh gave evidence that, since about 2008 or 2009, he has switched medication for four patients with schizophrenia and four patients with Bipolar I Disorder for reasons to do with their need for full cognitive function in their occupations. He said that in four of the eight cases, “it has made a significant difference”.

216    Associate Professor Phillips gave similar evidence concerning the role of drug therapy to address the patient’s cognitive impairment and mood disorders associated with schizophrenia. He said:

If a patient presents with only cognitive symptoms and mood symptoms (that is the positive and negative symptoms are under control), modern antipsychotic agents can improve cognition. I usually prescribe Abilify [aripiprazole] or Seroquel (quetiapine) because in my experience both agents have a useful capacity to stabilise mood, and also to improve cognition … I accept that improvement in cognition may be an indirect result of reduced thought disorder and elimination of depression. However, there are many views on this in the profession and I believe that there is no conclusive answer yet, other than that at a neuroscience level, as to why Abilify and Seroquel appear to improve mood and cognition.

217    Associate Professor Phillips also said:

Although many of my patients suffer from severe illness, I have a small number of high-performing patients who are successful in their professions. The typical treatment plan for these individuals will generally involve medication combined with a talking therapy [cognitive behavioural therapy]. I recall a small number of high functioning patients who presented with cognitive problems, usually in the context of depressive symptoms, who overcame their cognition difficulties when medicated with Abilify.

218    In cross-examination, Professor Singh and Associate Professor Phillips illustrated their views with specific case examples.

219    Professor Singh gave the example of a young man who was an architect who had been sent to him for review (a second opinion). The young man had suffered an episode of schizophrenia approximately 9 months earlier and had been treated with olanzapine. The patient found olanzapine to be very sedative. He also put on weight. His then treating psychiatrist switched him to risperidone. However, even though the patient’s positive symptoms were well under control, his negative symptoms and neurocognitive symptoms remained a problem for him. These symptoms were affecting his work. He was unable to complete tasks. He was in danger of losing his job. Professor Singh reviewed the patient’s symptoms and switched the patient gradually from risperidone to aripiprazole. Professor Singh said that the patient made an excellent recovery using aripiprazole. His thinking was clearer. He was able to do his job better. His positive symptoms were also kept under control.

220    Associate Professor Phillips gave the example of a young medical student who, in the 1980s, commenced to develop symptoms of schizophrenia. By the time he came under Associate Professor Phillips’ care, the patient was unable to continue with his university course. Associate Professor Phillips initially treated him with trifluoperazine (a typical antipsychotic). The patient’s positive symptoms diminished, but he had major problems with cognition, as well as mood problems. Associate Professor Phillips described the patient as someone who “probably would have become a very good doctor, to a person who was coping marginally in the community and receiving social benefits”.

221    At a later time, Associate Professor Phillips switched the patient from trifluoperazine to olanzapine. However, the patient’s cognitive symptoms and mood problems did not alter. The patient experienced rapid weight gain. Sedation was also a problem. Associate Professor Phillips altered the patient’s dosage of olanzapine in an endeavour to address these problems. There was no significant improvement. Associate Professor Phillips suggested the use of clozapine but, because of its significant side effects, the patient did not wish to have that treatment. Associate Professor Phillips then started the patient on quetiapine. However, even switching to quetiapine did not lead to a material improvement in what Associate Professor Phillips described as the patient’s “two residual problems”—the patient’s cognitive problems and mood problems.

222    Subsequently, Associate Professor Phillips introduced the patient to aripiprazole. Associate Professor Phillips said that, over a period of six months on aripiprazole, the patient demonstrated “very significant movement forward.” The patient was able to undertake an educational program resulting in him obtaining a diploma in horticulture at a tertiary institution and, through Darwin University, obtaining a position as a tutor in Aboriginal communities. Associate Professor Phillips described this as “an enormous step from where he was”. Associate Professor Phillips said that the patient “became a functional human being again after years and years of being immobilised by his illness.”

223    The following exchange took place in the course of this account:

Professor, a situation where you have a patient with positive symptoms under control and you switch that patient to a different anti-psychotic in order simply to improve cognitive difficulties would be an extremely rare one, would it not, in your practice?---I don’t think so. I mean I think it’s a matter of what weight you give to cognitive and mood symptoms and I think that for many people with schizophrenia and schizophrenia-like illnesses, the issues of cognition and mood become ultimately as important as the awfulness of the hallucinations and delusions that they had at an earlier time. So I would not – in my practice I would keep working to try and minimise all four domains of the illness, not just the first domain which is the positive symptoms which seems to get an awful lot of airplay.

224    Associate Professor Phillips gave evidence that, over the last five years, he would have switched an existing antipsychotic medication to aripiprazole (Abilify) in two to three cases each year, in order to treat the patient’s “cognitive difficulties”.

225    Professor Singh’s case example and Associate Professor Phillips’ case example relate to the use of aripiprazole as third line treatment and fourth line treatment, respectively, directed to the alleviation of the patient’s cognitive impairment associated with schizophrenia in its chronic phase, where the patient failed to respond to two of the medications referred to in claim 7 of the 772 patent.

226    In light of Professor Singh’s evidence and Associate Professor Phillips’ evidence, the respondent submitted that the “cross-section of the patient universe”, likely to be treated in the way claimed in claim 7, is “tiny” or “extremely small”. Further, based on Professor McGorry’s evidence and Dr O’Dea’s evidence, the respondent submitted that practitioners might not switch, but pursue “non-pharmaceutical” treatment for cognitive impairment in schizophrenia.

227    In this connection, the respondent contrasted the size of the patient groups with whom Professor McGorry is involved with the patient groups with whom Professor Singh and Associate Professor Phillips are involved. As noted above, Professor McGorry is the Executive Director of Orygen. He said that the clinical program at Orygen treats 200 first episode patients every year. This program obviously involves a number of clinicians apart from Professor McGorry. Professor McGorry said that he knows “what the general trends are amongst [his] colleagues.” Professor Singh gave evidence that, since about 2008/2009, he had seen about 100 patients suffering from schizophrenia. At the time of giving evidence, Associate Professor Phillips said that he had 106 patients in active treatment, two thirds of whom “would predominantly have a mood disturbance or mood disorder”. Of this group, Associate Professor Phillips said that about 30 of those patients have a psychotic disorder, “most of them schizophrenia”. The evident purpose of comparing the respective sizes of patient groups was to downplay the significance of Professor Singh’s and Associate Professor Phillips’ evidence in terms of the likely numbers of patients to whom aripiprazole might be administered in accordance with the method of treatment claimed in claim 7 of the 772 patent.

228    More generally, the respondent pointed to the RANZCP guidelines, which recommends the early introduction of clozapine in treatment-resistant schizophrenia where, despite sequential use of recommended doses of two or more antipsychotic medications, there has not been a full remission of the patient’s positive symptoms or there has been a lack of satisfactory clinical improvement. The guidelines also include aripiprazole as an oral atypical medication that should be prescribed as first line and second line treatment in first episode psychosis.

229    Whilst the RANZCP guidelines certainly concern the switching of medication in the treatment of schizophrenia and the choices to be made in that regard, they are not directed, specifically, to the treatment of cognitive impairment in schizophrenia, although, as I explain below, the treatment of cognitive impairment is discussed.

230    I should also record that the “guidelines” are, of course, no more than that. This is not to diminish their significance. But Dr O’Dea, for example, gave evidence that, although clozapine is the main antipsychotic medication used to treat treatment-resistant schizophrenia, he has prescribed other antipsychotics for that purpose. This is because the patient might not have complied with the clozapine treatment regime, or the patient might have had physical conditions (such as heart and blood problems) that may have rendered him or her unsuitable for treatment with clozapine.

231    The respondent pointed to references in the RANZCP guidelines concerning the use of cognitive interventions in the treatment of schizophrenia. Reference is made, for example, to the use of cognitive remediation (also called cognitive rehabilitation) which aims to address cognitive impairments, such as distractibility, memory problems, lack of vigilance, attentional deficits, and limitations in planning and decision-making. In this connection, the guidelines state:

Since these deficits correlate more closely with functioning than do symptom levels, addressing them may enable the patients to be able to engage in and benefit from other interventions, and consequently function better in social and other domains. So far results in controlled trials of cognitive remediation have been equivocal.

232    However, whilst discussing the role of non-pharmacological interventions in the treatment of schizophrenia, and whilst emphasising that, as at the date of their acceptance for publication (26 August 2004), it is now accepted that the treatment of schizophrenia cannot be a one-dimensional “biological” approach, the RANZCP guidelines nevertheless make clear that pharmacological treatments are the “cornerstone” or “mainstay” treatments for both acute and maintenance therapy for schizophrenia.

233    In support of its submission that the patient group who might be switched to aripiprazole to treat cognitive impairment is “tiny” or “extremely small”, the respondent pointed to the product information for Abilify. I have briefly referred to this information when dealing with the respondent’s submissions on construction: see [147]. The product information refers to the suitability of Abilify for treating the positive symptoms of schizophrenia. The product information also states that no trials of Abilify have been conducted in patients with treatment-resistant schizophrenia. The product information refers to the fact that Abilify, like other antipsychotics, may have the potential to impair judgment, thinking, or motor skills. The product information says that patients should be cautioned about operating hazardous machinery, including automobiles, until reasonably certain that therapy with Abilify does not affect them adversely. I should, however, note here that there is evidence that aripiprazole (in the form of Abilify) is considered to be less sedating than other atypical antipsychotics. I shall return to discuss that evidence. Nevertheless, the respondent submitted that the applicants have not put forward evidence showing the efficacy of aripiprazole in the treatment of the claim disorders.

234    The respondent also called in aid the information about aripiprazole published by National Prescribing Services Limited in RADAR (Rational Assessment of Drugs and Research). This publication provides health professionals with information on, amongst other things, new drugs and listings on the Pharmaceutical Benefits Scheme. This review states that there is presently no evidence to suggest that aripiprazole is more effective than other antipsychotics in the treatment of schizophrenia, although “it offers prescribers another treatment option for this illness.” It also states that aripiprazole’s efficacy in treatment-resistant schizophrenia has not been established and that, for these patients, clozapine is generally considered to be the drug of choice. The respondent’s reference to this publication was, presumably, to suggest that there is no particular reason to believe that aripiprazole would be prescribed for the claim disorders as opposed to being prescribed for the other symptoms or signs of schizophrenia.

235    The respondent also relied on the CATIE trial (Clinical Antipsychotic Trials of Intervention Effectiveness) for the same purpose. This trial was conducted to compare the neurocognitive effects of several atypical antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a typical antipsychotic (perphenazine) in patients with chronic schizophrenia. The researchers’ hypothesis was that neurocognitive response would be significantly different between these treatments.

236    The researchers found that after two months of antipsychotic treatment, all patient groups had a small but significant improvement in neurocognition. There were no differences between any pair of agents, including the typical antipsychotic, perphenazine. Associate Professor Norman said that this result suggests that the small cognitive enhancement that was observed was most likely a “class effect” of all antipsychotic drugs, unrelated to the 5-HT1A receptors.

237    Although aripiprazole is not among the drugs tested in CATIE, Professor McGorry gave evidence that, on the literature he had reviewed for the purpose of this proceeding, there appeared to be no advantage in using aripiprazole over other atypical antipsychotics in treating cognitive impairment in schizophrenia. Nevertheless, Professor McGorry concluded that “there may be the capacity for improvement in neurocognition with Aripiprazole”, although this would not “compel [him] to switch a chronic or treatment resistant schizophrenic patient suffering from cognitive impairment to Aripiprazole, to treat that cognitive impairment”. This is because, according to Professor McGorry, the patient would, more likely than not, already be using an atypical antipsychotic and the “modest effects on neurocognition represented in the [papers he reviewed] provide no clinical support for such a switch.”

238    There is, however, a considerable body of evidence that, compared to some atypical antipsychotics, aripiprazole is less sedating.

239    In this connection, Professor McGorry said that he would consider prescribing Abilify because it is less sedating than olanzapine and quetiapine, and because it has low anticholinergic properties, meaning that the drug would not impair the patient’s cognition as much as more anticholinergic agents. He said, however, that these are the only reasons he would consider prescribing Abilify. Indeed, Professor McGorry said that, from his experience, Abilify was not commonly used to treat acute episodes of schizophrenia because “it is not especially sedative”. He gave this evidence:

In my experience, compared to certain other SGAs, [Abilify] has a lower impact on weight gain and it is less sedating. These characteristics provide an advantage when treatment is initiated in more stable outpatients either for the first time or through switching, because avoiding sedation is a major advantage here and the lesser impact on weight gain in most patients is desirable.

240    Professor McGorry was asked in cross-examination about switching a patient from quetiapine to aripiprazole (Abilify). The following exchange took place:

Is that because it would have the consequence that the sedating effect of quetiapine to some extent impairs the aspects of cognition that we spoke about before?---It could be – or just, even just functioning. I mean, some of these drugs like quetiapine might be useful in the acute phases. You can imagine, with a person very agitated and you might want – the situation might change, then, when they’re out of hospital, or they’re back at – they’re trying to study or work, and you might want a change of drug, just so the person functions better. And obviously if people are sedated, their cognitive performance is going to be impaired in a general sort of way.

So their judgment would be impaired?---Possibly. More things like attention and concentration I would have thought.

241    I have already referred to Dr O’Dea’s evidence that he might review a patient’s medication to address negative or cognitive symptoms via reducing the level of the patient’s sedation: see [208].

242    The applicants submitted that Professor McGorry’s evidence and Dr O’Dea’s evidence that they would not switch a patient’s medication to treat cognitive impairment in schizophrenia should be evaluated in the context that each would consider switching in an appropriate case to lessen the effects of sedation, and thereby improve the patient’s cognitive symptoms. The applicants submitted that this supports a finding that Professor McGorry and Dr O’Dea do, and will in future, prescribe aripiprazole for the purposes of improving cognitive impairment in schizophrenic patients.

243    I do not think that Professor McGorry’s evidence or Dr O’Dea’s evidence should be treated in this way. However, I do accept that their evidence, in this regard, shows that, in certain cases arising in practice, it may be appropriate to switch the patient’s medication to a less sedating alternative. I also accept that aripiprazole is such an alternative. Further, I accept that, from the clinician’s point of view, the use of a less sedating antipsychotic may assist in improving a patient’s cognitive impairment associated with schizophrenia.

244    Notwithstanding the differences in treatment strategies reflected in Professor McGorry’s and Dr O’Dea’s evidence, on the one hand, and Professor Singh’s and Associate Professor Phillips’ evidence, on the other, I am satisfied that, at least for some clinicians, switching (including, importantly, switching to aripiprazole even as third line or later line treatment) is, and would be, a realistic and legitimate option to treat the patient’s cognitive impairment associated with schizophrenia, where those problems persist, even though the patient’s positive symptoms are otherwise satisfactorily under control using other antipsychotic medication(s). I accept the applicants’ submission that there is nothing in the evidence to suggest that Professor Singh’s and Associate Professor Phillips’ practices in this regard, are idiosyncratic. I accept that the evidence of their practice in switching medications to treat cognitive impairment associated with schizophrenia can be taken as representative of the practice of a not insignificant number of other clinicians in Australia. Moreover, I am satisfied that such treatment would extend, realistically, to the method of treatment claimed in claim 7, even though, in practice, such treatment might only be required for a relatively small proportion of patients being treated for schizophrenia. Professor Singh and Associate Professor Phillips were able to point to real world examples of such treatment. Plainly, in each case, the method of treatment, if carried out using aripiprazole in the form of the GH products, would fall within the scope of the respondent’s registrations for those products.

245    Equally, I take the evidence of Professor McGorry and Dr O’Dea in relation to their treatment strategies in this regard as representative of the practice of a not insignificant number of other clinicians in Australia. However, it does not follow from Professor McGorry’s evidence and Dr O’Dea’s evidence that, on an objective assessment, the respondent would not have reason to believe that the GH products would be used in the method of treatment claimed in claim 7.

246    Once it is accepted that a not insignificant number of clinicians in Australia would use the GH products as a realistic and legitimate option to treat a patient’s cognitive impairment associated with schizophrenia, including for the method of treatment claimed in claim 7, it is really beside the point that other clinicians might adopt different treatment strategies in like cases. Indeed, it does not even matter that the treatment regimens of other clinicians represents a “majority view”—although I make no specific finding that Professor McGorry’s evidence and Dr O’Dea’s evidence, in this particular regard, represents such a view. The evidence only allows me to confidently conclude that, amongst clinicians, there are two broad views regarding the switching of antipsychotic medication to treat cognitive impairment associated with schizophrenia—the view represented by Professor McGorry and Dr O’Dea and the view represented by Professor Singh and Associate Professor Phillips.

247    Having considered all the evidence, I am satisfied that the applicants have discharged the onus of establishing that the respondent has reason to believe that, if supplied in Australia, the GH products would be put to a use that would infringe claim 7 of the 772 patent. That is enough to establish infringement under s 117(1) of the Act. Infringement under that provision cannot be avoided by establishing that the product will also be put to non-infringing uses, although this may influence, for example, the scope of injunctive relief that might be granted: AstraZeneca 226 FCR 324 at [444]. I am satisfied, therefore, that the case on infringement of claim 7 would have been established, had the claim been valid.

248    Finally, I should refer again to the respondent’s proffered undertaking not to advertise or promote the GH products for the method claimed in claim 7. The respondent submitted that such an undertaking has a role to play in determining whether, in the face of such a restriction on its exploitation of the GH products, it could be said that it would have reason to believe that the products would be put to a use that would infringe claim 7.

249    I accept that such an undertaking is relevant to my consideration of this question. However, it does not alter the conclusion to which I have come. The respondent has not sought to limit the regulatory approvals it has for the GH products. The GH products can be used for the method of treatment claimed in claim 7 of the 772 patent. In that context, I do not accept that the prescribing practices of clinicians, represented by Professor Singh and Associate Professor Phillips, would be changed or modified simply because the GH products are not specifically advertised or promoted for the method of treatment claimed in claim 7.

Validity

Introduction

250    As I have noted, the respondent now only challenges the validity of claims 1 and 7 of the 772 patent. Its challenge to the validity of the 752 patent is no longer made.

251    The respondent’s challenge to the validity of claims 1 and 7 of the 772 patent focused on three grounds, namely that the invention as claimed was not novel, was not a manner of new manufacture and was obvious. The respondent raised other grounds of invalidity, but, as I will come to explain, these were, at best, subsidiary attacks that were put somewhat fleetingly at the time of closing submissions.

The prior art

EP 141/US 528

252    As I have also noted (at [80]), the parties are in agreement that the disclosures in EP 141 are materially the same as in US 528.

253    US 528 describes the field of the invention as follows:

The present invention relates to novel carbostyril derivatives. More particularly, the invention relates to novel carbostyril derivatives and salts thereof, processes for preparing said carbostyril derivatives and salts thereof, as well as pharmaceutical compositions for treating schizophrenia containing, as the active ingredient, said carbostyril derivative or salt thereof.

254    When dealing with the background to the invention, US 528 discloses that schizophrenia is the most common type of psychosis caused by excessive neurotransmission activity of the dopaminergic nervous system in the central nervous system.

255    US 528 states:

Heretofore, a number of drugs, having the activity for blocking the neurotransmission of dopaminergic receptor in the central nervous system, have been developed, the example for said drugs are phenothiazine-type compounds such as Chlorpromazine; butyrophenone-type compounds such as Haloperidol; and benzamide-type compounds such as Sulpiride. These known drugs are now used widely for the purpose of improving so-called positive symptoms in the acute period of schizophrenia such as hallucinations, delusions and excitations and the like.

256    When referring to known drugs in this passage, US 528 is talking about typical antipsychotic drugs.

257    US 528 continues:

However, many of these drugs are considered as not effective for improving so-called the negative symptoms which are observed in the chronic period of schizophrenia such as apathy, emotional depression, hypo-psychosis and the like. In addition to the above, these drugs give important side-effects such as akathisia, dystonia, Parkinsonism dyskinesia and late dyskinesia and the like, which are caused by blocking the neurotransmission of dopaminergic receptor in the striate body. Furthermore, other side-effects such as hyperprolactinemia and the like given by these drugs are become [sic] other problems.

258    In this passage, US 528 is talking about the treatment of the negative symptoms of schizophrenia with typical antipsychotic drugs.

259    US 528 states that, under these circumstances, the development of drugs for treating schizophrenia having safety and clinical efficacy have been “eagerly expected”.

260    US 528 continues:

The present inventors have made an extensive study for the purpose of developing drugs for treating schizophrenia, which would be not only effective for improving the negative symptoms, but also effective for improving the positive symptoms of schizophrenia, furthermore such drugs would have less side-effects as compared with those shown by drugs known in prior art. As the result, the present inventors have successfully found carbostyril derivatives having strong activity for blocking neurotransmission of dopaminergic receptor. As to the side-effects given by known drugs for treating schizophrenia are for example, in the case of phenothiazine-type drugs, the orthostatic hypotension and hypersedation on the basis of strong a-blocking activity; and in the case of drugs having strong activity for blocking neurotransmission of dopaminergic receptor, the side-effects are so-called extrapyramidal tract syndromes such as catalepsy, akathisia, dystonia and the like caused by the blocking neurotransmission of dopaminergic receptor in the atriate body.

(Errors in original.)

261    US 528 states that the objects of invention are to provide:

    novel carbostyril derivatives and salts;

    processes for preparing those carbostyril derivatives and salts, and

    a pharmaceutical composition for treating schizophrenia.

262    Claim 16 of US 528 is as follows:

A pharmaceutical composition for treating schizophrenia containing, as the active ingredient, a carbostyril compound or pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier.

263    Claim 17 is as follows:

The pharmaceutical composition of claim 16, wherein the carbostyril compound or salt thereof is 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4- dihydrocarbostyril.

264     Aripiprazole is the compound claimed in claim 17.

265    Relevantly, EP 141 contains a similar claim. As I have noted (at [80]), it also contains, in claim 32, a Swiss type claim directed to the use of aripiprazole for the preparation of a drug useful in the treatment of schizophrenia.

Serper

266    It is not in dispute that the article titled Novel Neuroleptics Improve Attentional Functioning in Schizophrenic Patients: Ziprasidone and Aripiprazole by Serper et al was published in CNS Spectrums 2(8) (1997) before the priority date (Serper).

267    In a section headed “Overview”, the authors state:

Attentional dysfunction has long been recognized as a core feature of schizophrenia (SZ) illness. It has been consistently found that SZ patients manifest significant deficits in their ability to sustain their attention over time, as well as their ability to focus their attention on target stimuli when distractors are present. SZ attentional deficits are found across all developmental periods and clinical states including in children at high risk for the disorder, acutely ill patients, and remitted outpatients. These cognitive deficits, however, have been shown to improve over the course of neuroleptic treatment.

Numerous studies have confirmed that SZ performance, particularly on the digit span distraction task (a measure of selective attention) and the Continuous Performance Test (CPT: a measure of sustained attention), is highly responsive to classical neuroleptic treatment. For example, Oltmanns et al found that neuroleptic-withdrawn SZ patients showed a significant decline in their selective attention performance on digit span distraction task from their stabilized medication baseline. Additionally, SZ patients’ digit span attentional performance has been found to be associated with higher serum neuroleptic levels in patients who were receiving neuroleptic treatment.

(Citations omitted.)

268    Later in this section, the authors state:

The finding that antipsychotic drugs improve attentional processes has led researchers to hypothesize, in much the same way they did for psychotic symptoms, that dopamine (DA) dysfunction underlies SZ attentional deficits. A recent model, for example, postulated that SZ attentional impairment is attributable to hypodopaminergic functioning in the prefrontal regions of the cortex.

Novel neuroleptics hold great promise in achieving further significant improvement in SZ attentional functioning because they preferentially increase prefrontal DA activation. Few studies to date have examined SZ attentional functioning during the course of novel neuroleptic treatment. Therefore, we compared attentional functioning of SZ patients receiving either typical or novel neuroleptics (ie, aripiprazole or ziprasidone) at both medication-free baseline and 30 days after receiving novel or classical neuroleptic treatment. We hypothesized that SZ patients receiving novel neuroleptics would demonstrate significant improvement in attentional functioning compared with patients receiving typical neuroleptic treatment.

(Citations omitted.)

269    The reference to “neuroleptic treatment” in these passages is to treatment with antipsychotic drugs. The reference to “classical” neuroleptics is to typical antipsychotic drugs, and the reference to “novel neuroleptics” is to atypical antipsychotic drugs.

270    Serper concerns a study involving the treatment of 21 patients who presented with an acute episode of schizophrenia. Five patients received aripiprazole, and four patients received ziprasidone. The remaining 12 patients received an unidentified typical antipsychotic drug. A table of demographic information in relation to the two patient groups (those receiving typical antipsychotic medication, and those receiving aripiprazole or ziprasidone) contains data on the number of previous hospitalisations. Professor Singh and Associate Professor Norman each agreed that this data showed that the patients in both groups suffered chronic schizophrenia.

271    In a section headed “Discussion”, the authors state:

Consistent with the study hypothesis, the present results found that SZ patients receiving novel neuroleptic treatment showed superior performance in CPT reaction time and in digit span immediate recall compared with SZ patients receiving traditional neuroleptic therapy. The present study also found that all patients receiving classical or novel neuroleptic therapy showed significant improvement in selective and sustained attentional functioning. These results are consistent with past investigations examining SZ attentional improvement following typical neuroleptic treatment and further support the notion that SZ attentional impairment, like many SZ symptoms, is mediated by mesostriatal DA pathways.

(Citations omitted.)

272    The authors conclude:

Overall, the present results suggest that enhanced attentional performance obtained while on novel neuroleptic medication may enable SZ patients to further advance their functioning in important life domains.

Saha

273    The article titled Safety and Efficacy Profile of Aripiprazole, A Novel Antipsychotic by Saha et al was published in (1999) Schizophrenia Research 36(1-3) before the priority date (Saha).

274    Saha reports that aripiprazole is a novel antipsychotic undergoing Phase 3 development. It states that a unique feature of aripiprazole is its agonistic effect at presynaptic dopamine receptors with a post synaptic D2 antagonistic effect.

275    Saha reports on a completed double-blind, four-week, placebo-and-haloperidol-controlled Phase 2 study conducted in relation to 307 acutely relapsing hospitalised schizophrenic patients. The report includes the following:

In this study aripiprazole fixed doses of 2 mg, 10 mg, and 30 mg per day were administered. Based on the last observation carried forward (LOCF) analysis, aripiprazole was superior to placebo in improving the Positive and Negative Syndrome Scale (PANSS)‒total for each dose group, and the 30-mg dose showed significant effect also for PANSS-negative score. The related items of PANSS were clustered and were analysed (LOCF) to determine the effect of aripiprazole on the following dimensions: excitement, depression, and cognitive function. On each of these dimensions the aripiprazole doses showed improvement over baseline, starting from week 1 to the last visit. In addition, at last visit, improvement for excitement and depression was statistically significant compared to placebo for each aripiprazole dose group; and for cognition, the aripiprazole 30-mg dose also showed statistically significant improvement over placebo.

276    By way of further explanation (see generally [30]), PANSS is used to evaluate the severity of the symptoms of schizophrenia in patients, and the efficacy of medications used to treat schizophrenia. The scale includes a list of positive symptoms (of which there are seven), negative symptoms (of which there are also seven) and general psychopathology symptoms (of which there are 16). Professor Singh gave evidence that, within the General Psychopathology Scale, “disorientation”, “poor attention” and “lack of judgment and insight” are cognitive functions. He also said that, within the negative scale, “difficulty in abstract thinking” is possibly related to cognition because it is about whether a patient’s thinking is logical or concrete. Nevertheless, Professor Singh said that “difficulty in abstract thinking” is not the same as cognition.

277    Dr O’Dea gave evidence that the following PANSS symptoms and signs of schizophrenia are generally considered in the field of psychiatry to overlap with the symptoms and signs of cognitive impairment in schizophrenia: “difficulty in abstract thinking”, “lack of spontaneity and flow of conversation”, “stereotyped thinking”, “disorientation”, “poor attention”, “lack of judgment and insight”, and “preoccupation”. Dr O’Dea said that the first three symptoms or signs are grouped in the PANSS Negative Subscale, but they can also be conceptualised as forms of cognitive impairment.

278    In response to Dr O’Dea’s evidence, Professor Singh reiterated his acceptance that “difficulty in abstract thinking” may be related to cognition. He disagreed, however, that “lack of spontaneity and flow of conversation” and “stereotyped thinking” can be conceptualised as elements of cognitive impairment. Associate Professor Norman was of the same opinion as Professor Singh on this matter. He gave evidence that “difficulty in abstract thinking” would involve cognition “to some extent”. However, he disagreed with Dr O’Dea that “lack of spontaneity and flow of conversation” and “stereotyped thinking” could be conceptualised as forms of cognitive impairment.

279    Saha concludes:

An impressive effectiveness and a favourable safety profile indicate that aripiprazole should be a substantial addition to the new generation antipsychotics.

Petrie 1997

280    The article titled Aripiprazole, A New Typical Antipsychotic: Phase 2 Clinical Trial Result by Petrie et al was published in European Neuropsychopharmacology Volume 7, Supplement 2, September 1997 before the priority date (Petrie 1997). Petrie 1997 reports that aripiprazole is a new atypical antipsychotic starting worldwide Phase 3 development. It states that aripiprazole is a postsynaptic dopamine receptor antagonist as well as a presynaptic autoreceptor agonist. Petrie 1997 says that this latter action distinguishes aripiprazole from other (then) currently available antipsychotic drugs. It also reports that aripiprazole had demonstrated affinity for the 5-HT2 receptor.

281    Petrie 1997 reports on two completed double-blind Phase II studies conducted in a total of 410 acutely relapsing hospitalised schizophrenic patients. In the first study, aripiprazole was titrated up from 5 to 30 mg in 13 days. In the second study, fixed doses of 2, 10, and 30 mg per day were administered. Both studies were of four weeks duration and haloperidol was used as the control.

282    Petrie 1997 includes the following:

Based on the last observation carried forward (LOCF) analysis, in both studies aripiprazole was superior to placebo in improving the BPRS-total, BPRS-score, CGI-severity, and PANSS-total. Results of the fixed-dose study of 31-94-202 showed that all three aripiprazole doses (2, 10, and 30 mg/day) showed clinical effect in improving the symptoms of acute psychiatric exacerbation of schizophrenia and the 30 mg dose was consistently more effective than the lower two doses. The 30 mg dose demonstrated a unique early onset of efficacy from week 1 on all efficacy variables including PANSS-negative score.

283    The acronym BPRS refers to the Brief Psychiatric Rating Scale (BPRS), which is used to measure the symptoms and signs of schizophrenia. The acronym CGI refers to the Clinical Global Impression scale.

284    Petrie 1997 concludes:

A favourable safety profile combined with data supporting efficacy in the treatment of the positive and negative symptoms of schizophrenia, suggests that aripiprazole may represent an important advance in the management of psychotic disorders.

Petrie 1998

285    The article titled Acute and Long-Term Efficacy and Safety of Aripiprazole: A New Atypical Antipsychotic by Petrie et al was published in (1998) Schizophrenia Research 29(1-2) before the priority date (Petrie 1998).

286    Petrie 1998 reports on the same Phase II trials reported in Petrie 1997 (although it designates them as Phase 2 trials). It also refers to aripiprazole having agonist effect at pre-synaptic dopamine autoreceptors and a post-synaptic antagonist effect at D2 and 5-HT2 receptors. Petrie 1998 says that this profile may be responsible for “the impressive clinical effectiveness and tolerability seen thus far.”

287    Petrie 1998 includes the following:

The fixed-dose study showed that 30 mg could be given without titration. The 30-mg dose showed significant effect on all assessments (including PANSS-Negative score) starting at week-1 evaluations. The 10-mg and 2-mg doses showed effect on many assessments, but not on all (and not on PANSS-Negative), starting at week 2 or week 3.

Keefe

288    The article titled The Effects of Atypical Antipsychotic Drugs on Neurocognitive Impairment in Schizophrenia: A Review and Meta-analysis by Keefe et al, was published in Schizophrenia Bulletin, Volume 25, No 2 (1999) before the priority date (Keefe).

289    The abstract to Keefe states:

Cognitive deficits are a fundamental feature of the psychopathology of schizophrenia. Yet the effect of treatment on this dimension of the illness has been unclear. Atypical antipsychotic medications have been reported to reduce the neurocognitive impairment associated with schizophrenia. However, studies of the pattern and degree of cognitive improvement with these compounds have been methodologically limited and have produced variable results, and few findings have been replicated. To clarify our understanding of the effects of atypical antipsychotic drugs on neurocognitive deficits in patients with schizophrenia, we have (1) reported on newly established standards for research design in studies of treatment effects on cognitive function in schizophrenia, (2) reviewed the literature on this topic and determined the extent to which 15 studies on the effect of atypical antipsychotics met these standards, (3) performed a meta-analysis of the 15 studies, which suggested general cognitive enhancement with atypical antipsychotics, and (4) described the pharmacological profile of these agents and considered the pharmacological basis for their effects on neurocognition. Finally, we suggest directions for the development of new therapeutic strategies.

290    Keefe contains a discussion on the possible relationship between cognitive improvement and drugs that bind to serotonin receptors which “may facilitate or impair certain cognitive functions, depending on the location and sub-type of the affected receptors”.

291    Keefe states that 15 studies were included in the meta-analysis undertaken by the authors. These studies were listed in Table 1. Serper is one of the studies listed and summarised in the table. It is also referenced. In a section headed “Meta-analysis and Review of Study Results”, Serper is specifically mentioned and described as a study in which the patients on atypical antipsychotics and a portion of the patients on haloperidol were assessed under double-blind conditions. In a section headed “Meta-analysis”, Keefe reports that none of the 15 studies that were reviewed met all of the recently developed standards for the assessment of cognitive change in schizophrenia. It notes that, most importantly, only three of the 15 studies used double-blind methodology. I am satisfied that the person skilled in the art would understand that Serper was one of the three studies referred to in that regard, given the author’s specific citation of Serper. It should be noted, however, that Table 1 indicates that the double-blind condition was not met by Serper. This seems to be because, as the text states, the patients on atypical antipsychotics were assessed under double-blind conditions, but only some of the patients on haloperidol were assessed under those conditions.

292    In discussing the authors’ conclusions from the meta-analysis and their review of the studies, Keefe states:

Despite a conservative statistical approach, correcting the results of each study for the number of statistical comparisons made, the meta-analysis conducted in this study suggests that atypical antipsychotics, when compared with conventional antipsychotics, improve cognitive functions in patients with schizophrenia. Verbal fluency, digit-symbol substitution, fine motor functions, and executive functions were the strongest responders to novel antipsychotics. Attention subprocesses were also responsive; learning and memory functions were the least responsive.

novelty

Introduction

293    The respondent’s challenge on the ground that the invention, as claimed, is not novel, was based on the test of “information made publicly available in a single document”. The respondent’s challenge was not based on information made publicly available by a prior act or prior acts.

294    In this connection, the respondent relied on the disclosures made by each of the following documents: EP 141/US 528 (each document accepted as containing materially the same disclosures), Serper and Saha.

295    In this case, therefore, the statutory question is whether the invention as claimed is not novel in light of the prior art information made publicly available by each of these documents, considered separately: see s 7(1) of the Act.

296    In advancing its case on lack of novelty, the respondent relied on Aickin J’s observation in Meyers Taylor Pty Limited v Vicarr Industries Limited (1977) 137 CLR 228 at 235 that the basic test for anticipation or want of novelty is the same as that for infringement. His Honour continued:

… generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement.

297    This statement of general principle was recently discussed by the plurality in the Full Court in AstraZeneca 226 FCR 324 at [299]-[302]. There, the plurality pointed out that the reverse infringement test is not applied by simply asking whether something within the prior art document would, if carried out after the grant of the patent, infringe the invention as claimed. The plurality referred to certain observations by Parker J in Flower Oxidizing Company Ltd v Carr & Company Ltd (1908) 25 RPC 428 at 457 and by Black CJ and Lehane J in Bristol-Myers Squibb Company v FH Faulding & Company Ltd (2000) 97 FCR 524 at [67], which stress the need for a clear description of, or a clear direction, recommendation or suggestion to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent, in order for the prior art document to be anticipatory. The plurality said (at [302]):

302     Sufficiency of disclosure is a cardinal anterior requirement in the analysis of whether a prior art document anticipates a claimed invention. It is only after the stage of assessing the sufficiency of disclosure — which involves a determination about whether a prior document has “planted the flag” as opposed to having provided merely “a signpost, however clear, upon the road” or, perhaps, something less — that the notion of reverse infringement comes into play as the final and resolving step of the required analysis. It is not the first step of the required analysis; nor is it the only step.

298    Relatedly, the respondent also relied on the well-known passage in General Tire at 485-486 concerning anticipation arising from the “inevitable result” of following the directions in a prior publication, where the Court of Appeal said that:

… if carrying out the directions contained in the prior inventor’s publication will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.

299    The significance of this reliance was that, in the respondent’s submission, using aripiprazole for the treatment of schizophrenia, as taught in the relevant prior art documents, would have resulted, inevitably, in the treatment of a patient’s cognitive impairment associated with schizophrenia, including in the circumstances referred to in claim 7 of the 772 patent. Further, according to the teaching of the 772 patent, this would have involved the 5-HT1A receptor subtype. Thus, the respondent argued, it is not necessary, in those circumstances, for any of the relevant prior art documents to make reference to an association between the 5-HT1A receptor subtype and the treatment of cognitive impairment in schizophrenia in order for the prior art document to constitute an anticipation.

300    In Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd (No 2) (2012) 204 FCR 494, Bennett and Yates JJ (at [165]) questioned whether, under the present Act, the unyielding logic of the “inevitable result” cases can be applied uncritically in every case of alleged anticipation, particularly where the invention in suit is claimed as a new method of medical treatment involving the administration of a known compound for a hitherto unknown and unexpected, but nevertheless useful, therapeutic use: see also the reference to these observations in AstraZeneca 226 FCR 324 at [296].

301    The same strand of thought was raised by Floyd J in Actavis UK Ltd v Janssen Pharmaceutica NV [2008] FSR 35. In that case, Floyd J discussed the influence of the decision of the Enlarged Board in MOBIL/Friction Reducing Additive (G02/88) [1990] EPOR 73 (Mobil) on the question of anticipatory disclosure in United Kingdom patent jurisprudence. Mobil stands for the general proposition, in European patent law, that if a technical feature has not been previously made available to the public, then the claimed invention is novel, even though the technical effect may have inherently taken place in the course of carrying out what has previously been made available to the public.

302    Mobil concerned the patentability of an additive for oil that was known for rust prevention in engines. The patentee was allowed to claim the use of the known additive for a new purpose, namely friction reduction. This new purpose, coupled with the fact of an undisclosed technical effect (friction reduction), was enough to confer novelty on the invention as claimed.

303    In Actavis [2008] FSR 35, Floyd J said (at [90]):

90    If MOBIL is correctly decided, then unadvertised technical effects which underlie new uses of known materials are an exception to the rule about inevitable results. The technical feature of the claim (actually achieving friction reduction) was inherent in the old use and an inevitable result of pouring the additive into the engine. Yet this technical feature was held not to have been made available to the public. Mr Alexander says this is no different from the new medical treatment cases. No doubt when an old medicine (known for disease X) is found to treat a new disease, Y, it could be said that it is inevitable that some of the patients treated to date with this medicine for X may have had disease Y, and inherently been treated for it. Yet the novelty of purpose, using it for making a medicine for Y is enough. That principle is now definitely part of our law: see EISAI/Second Medical Indication (G05/83) [1985] OJ EPO 64; [1979–85] E.P.O.R. B241 and Wyeth (John) & Brother Ltd’s Application, Schering AG’s Application [1985] R.P.C. 545

304    However, Floyd J went on to discuss the limitations of the principle in Mobil and the recognition by other EPO cases of a distinction between “true new cases” and cases of “mere more information about old uses”: DOW/Sequestering Agent (T958/90) [1994] EPOR 1 (Dow) and AMERICAN CYANAMID/Melamine Derivatives (T279/93) [1999] EPOR 88 (American Cyanamid). On the basis of those cases, Floyd J noted that patents for alleged inventions falling within the latter category have not been accepted as satisfying the requirement of novelty.

305    Floyd J also considered Jacob J’s decision in Baker Norton, where the claim in suit was for the use of the pharmaceutical compound taxol (and other, sufficient medications to prevent severe anaphylactic reactions) for manufacturing a medicament for administration (within a specified range) over a period of about three hours or less as a means for treating cancer and simultaneously reducing neutropenia. The invention, as claimed, was challenged on the grounds of lack of novelty and obviousness. Both challenges were based on a lecture (the Winograd lecture) which published the use of taxol with premedication for a three hour infusion to treat cancer. The only feature of the claimed invention that was not published by the Winograd lecture was the fact that, so administered, taxol would lead to reduced neutropenia. The patentee sought to support the claim, relying on Mobil. It submitted that the feature of reduced neutropenia, although “inherent” in the prior art, was, nonetheless, a “hidden” feature and thus not made available to the public. Jacob J rejected the patentee’s reliance on Mobil, finding (at [59]) that:

[59]    [T]his is not a case of second medical use at all. The use is the same. All you have new in the patent is more information about that use. I think that is right. As Laddie J. said in Evans Medical Ltd’s Patent [1998] R.P.C. 517 at 576.

“First, one must identify what the alleged invention is, that is to say what is covered by the claims of the patent, and then one must decide whether or not that invention, or any part of it, would be made inevitably by following the instruction in the prior art. If it would be, then it does not matter whether the skilled reader of the prior art would realise that he was working within the area claimed in the subsequent patent.”

It is implicit in what Laddie J. said, I think, that Mobil has its limits. It should be remembered that Mobil was treated as a case where the new use was different from the old. Perhaps a clearer example is BASF/Triazole derivatives (T231/85) [1989] O.J. EPO 74 of the discovery that a particular compound (previously used for influencing plant growth) also controlled fungi. One can imagine cases where it was used for one purpose or the other. The purposes do not necessarily overlap. That is simply not the case here. All you have is more information about the old use. In due course no doubt more information about the exact mode of action of taxol will emerge. No-one could obtain a patent for its use simply by adding “for” at the end of the claim and then adding the newly discovered details of the exact mode of action.

306    After considering Jacob J’s judgment in Baker Norton, and the EPO decisions in Dow and American Cyanamid, Floyd J, in Actavis [2008] FSR 35, said (at [99]):

99    In my judgement, merely explaining the mechanism which underlies a use already described in the prior art cannot, without more, give rise to novelty. In MOBIL, the technical effects which underlay the new and old uses were different and distinct. So also in [the] example about disease X and disease Y. It is not the case that every discovery about the mode of action of a drug can be translated into a new purpose and claimed as such.

307    The influence of European patent law in the reasoning applied in the United Kingdom cases must be recognised: see, for example, the observations of Whitford and Falconer JJ in John Wyeth at 565. The same influence is not present in Australian patent law. Nevertheless, in my respectful view, the United Kingdom cases do provide valuable insights in analysis which assist in considering closely similar questions arising under Australian patent law.

EP 141/US 528

308    The respondent placed primary reliance on the prior art information made publicly available by EP 141/US 528. Put simply, the respondent submitted that each document discloses that aripiprazole is useful for treating schizophrenia. The respondent submitted that this can only be understood as treating “any kind of schizophrenia and all its symptoms by any line of attack, including the method as claimed and construed by the [a]pplicants”. The respondent submitted that there was no reason to read down the disclosure so as to exclude, in effect, the treatment of chronic or treatment-resistant schizophrenia, any symptom thereof, or prior attempts at treatment with other drugs. Thus, EP 141/US 528 rendered the invention claimed in claim 7 of the 772 patent not novel.

309    The respondent also submitted that the invention claimed in claim 1 could stand in no better position and was not novel. If the respondent is correct on its principal argument then I accept this conclusion must follow, given that claim 1 is directed to, relevantly, the use of aripiprazole in the production of a medicament for the same therapeutic use.

310    The applicants submitted that EP 141/US 528 do not anticipate the invention claimed in claims 1 and 7 because neither document discloses that:

    aripiprazole is a partial agonist at the 5-HT1A receptor;

    aripiprazole (whether due to its partial 5-HT1A agonism or otherwise) is useful in the treatment of cognitive impairment in schizophrenia patients; and

    aripiprazole has been or could be used to effectively treat patients who have failed to respond to previous treatment with any other antipsychotic medication.

311    It may be accepted that EP 141/US 528 do not disclose that aripiprazole is a partial agonist at the 5-HT1A receptor. Indeed, no reference is made to 5-HT1A receptors or the action of aripiprazole on 5-HT1A receptors or the serotonergic system more generally. It may also be accepted that EP 141/US 528 do not make express reference to switching or, in the context of claims 1 and 7, the use of aripiprazole as third line treatment where the patient’s cognitive impairment has failed to respond to other identified antipsychotics. That said, EP 141/US 528 do teach that the carbostyril derivatives they describe, including aripiprazole, are alternatives to a range of drugs including chlorpromazine, haloperidol and sulpiride (amongst other drugs), each of which is identified in claims 1 and 7 as a drug used in the treatment of cognitive impairment “caused by” treatment-resistant, inveterate or chronic schizophrenia.

312    The applicants’ contention that EP 141/US 528 do not disclose that aripiprazole is useful in the treatment of cognitive impairment in schizophrenia patients is also problematic because EP 141/US 528 do disclose that aripiprazole and the other carbostyril derivatives are useful for improving both the positive and negative symptoms of schizophrenia. Each application was filed in October 1989. EP 141 was published in May 1990. No date of publication is given for US 528, although the patent is dated 9 April 1991 and it can be taken that its date of publication was at some time around this date. EP 141/US 528 should be interpreted as at their respective dates of publication, having regard to the surrounding circumstances that then existed, without regard to subsequent events: General Tire at 485. By reference to EP 141 alone, it can be seen that the relevant date for interpreting its disclosures was more than 10 years before the priority date.

313    It is accepted by the parties that, at the priority date, the person skilled in the art would have understood that there was a significant overlap between the negative and cognitive symptoms of schizophrenia. They were not treated as distinctly different domains in clinical practice: see [63].

314    Dr O’Dea gave evidence that, at the priority date, clinical psychiatrists did not generally draw a clear distinction between cognitive signs and symptoms and negative signs and symptoms. He said that, even today, some psychiatrists consider that most negative symptoms and signs overlap with cognitive symptoms.

315    Professor McGorry said that there are mixed views in the professional community as to whether cognitive impairment is an additional symptom or falls within the category of negative symptoms of schizophrenia. Nevertheless, he said that, given his knowledge of schizophrenia in 1988 and 1989, he would read the expression “negative symptoms” in US 528 as including cognitive impairment. He said that he would read US 528 as recommending use of aripiprazole as a method of treatment to address both the positive and negative symptoms of schizophrenia, which include cognitive impairment. Professor McGorry appeared to qualify this evidence in cross-examination. He accepted that apathy, emotional depression and “hypopsychosis” (all referred to in EP 141/US 528 as examples of negative symptoms) are not symptoms of cognitive impairment, although he was unsure of what was meant by “hypopsychosis”. But Professor McGorry’s acceptance must be seen in the context that EP 141/US 528 refer to negative symptoms generally. I think it is clear from Professor McGorry’s evidence, considered as a whole, that he did not understand the reference to “negative symptoms” in EP 141/US 528 to be confined by the three examples given. Thus, I do not understand Professor McGorry to have resiled from the evidence he gave in chief on this question.

316    Similarly, Professor Singh accepted, specifically with respect to US 528, that its reference to the negative symptoms which are observed in the chronic period of schizophrenia includes some of the symptoms which are now regarded as cognitive symptoms.

317    In my view, a fair reading of EP 141/US 528, taken as at May 1990, and even at the priority date, shows that each is talking about all the symptoms of schizophrenia which, for the purposes of each document, have been classified into two broad classes—positive symptoms and negative symptoms. I am satisfied that, at the priority date, the person skilled in the art, interpreting each document at the time of its publication, would have understood the “negative symptoms” referred to in each as including those symptoms which, at a later time, and by further classification, have come to be seen as symptoms of cognitive impairment.

318    For these reasons, I am satisfied that EP 141/US 528 disclose the use of aripiprazole, amongst other carbostyril derivatives, as a drug for the treatment of schizophrenia generally, which is a useful alternative to earlier generation drugs such as, for example, chlorpromazine, haloperidol and sulpiride, including in the chronic period of the illness. I am also satisfied that, at the priority date, the person skilled in the art would have understood that when EP 141/US 528 refer to aripiprazole’s utility in treating negative symptoms, those symptoms included at least some of the symptoms which claims 1 and 7 of the 772 patent categorise as cognitive impairment.

319    The following question arises: When the invention claimed in each of claims 1 and 7 of the 772 patent is compared with the prior art information in EP 141/US 528, is the invention, as so claimed, novel because no disclosure is made with respect to the action of aripiprazole on 5-HT1A receptors (whether due to its partial agonism or otherwise) or the use of aripiprazole specifically as third line treatment where the patient has failed to respond to two or more of the identified prior art drugs? If the present case were to be decided by reference to the reasoning in the United Kingdom cases such as Actavis [2009] 1 WLR 1186 and Baker Norton, the answer to that question, it seems to me, would be “no”. For one thing, the invention, as clamed in each claim, would not be directed to a new use of the known substance. Is that reasoning, or similar reasoning, applicable in the Australian legal context? In my respectful view, it is.

320    The test provided by s 7(1) of the Act is directed to whether an invention, as claimed, is novel. This raises a question of substance, not one of mere claim form. Once the claim is properly construed, the question of substance is whether the invention, as so defined, is novel in the sense of providing an invention (here, a method of treating schizophrenia) that is new. Properly understood, claim 7 of the 772 patent is directed to the use of aripiprazole to treat a subset of the symptoms of schizophrenia in certain patients on certain occasions, when it is already known that aripiprazole can be used to treat schizophrenia generally. Claim 7 merely partitions something that is old under the guise that the part it takes and claims as an invention is new. However, such an “invention” is not new. Claim 7 is not directed to a new therapeutic use, but an old one. The forms of cognitive impairment referred to in claim 7 were, at the priority date, but some of the known symptoms of schizophrenia. If, at that time, aripiprazole had been used in a therapeutically effective amount to treat schizophrenia, it would inevitably have treated cognitive impairment of the kind referred to in claim 7, including if used as third line or later line treatment in those patients whose symptoms had failed to respond to two or more of the antipsychotic drugs identified in the claim. In substance, claim 7 claims a then known substance, aripiprazole, for its then known therapeutic purpose, the treatment of schizophrenia, only that some of the symptoms of schizophrenia and only some occasions of use are referred to in the claim. The same is true of the invention claimed in claim 1, being the use of aripiprazole in the production of a medicament for treating patients in respect of the same symptoms in the same circumstances.

321    Novelty of invention is not provided merely because information given as part of the definition of the invention in a claim is new information. With specific reference to claims 1 and 7, new information is provided by the feature that aripiprazole can be used to treat a patient suffering from disorders of the central nervous system associated with the 5-HT1A receptor. However, the disorders referred to were part of the known symptoms of schizophrenia. The provision of information that certain of the then known symptoms of schizophrenia are also associated with the 5-HT1A receptor is really no more than an elucidation of the action of the known carbostyril compounds, including aripiprazole, in treating schizophrenia, and a contribution to knowledge of the possible aetiology of those particular symptoms. These accretions to knowledge, without more, do not provide novelty of invention. They are simply aspects of knowledge, albeit new information, about the then known therapeutic use (the treatment of schizophrenia) of a then known compound.

322    Moreover, as I have explained, I do not accept, in any event, that the reference in claims 1 and 7 to this knowledge defines a free-standing, essential feature of the invention which is to be considered as meaningfully adding to the identification of the specific forms of cognitive impairment referred to: see [146]. Thus, the further description in claims 1 and 7 of the disorders as “disorders of the central nervous system associated with [the] 5-HT1A receptor subtype …” cannot confer novelty. It is merely supplementary information about the symptoms of cognitive impairment associated with schizophrenia generally and, more specifically, the particular forms of schizophrenia identified in the claims.

323    Further, the feature in the claims that specifically limits the use of aripiprazole to third line or later line treatment where the patient’s cognitive impairment has not been responsive to the identified drugs, cannot provide novelty over the disclosures in EP 141/US 528 because neither document limits the therapeutic use of the carbostyril compounds, including aripiprazole, to a particular line or phase of treatment. As I have noted, EP 141/US 528 disclose that the carbostyril compounds, including aripiprazole, are useful alternatives to a number of prior art drugs in the treatment of schizophrenia. Further, as the evidence makes clear, switching to different antipsychotics, when the response of the patient to his or her symptoms of schizophrenia, including cognitive impairment, was not satisfactory, was a feature of clinical practice at the priority date. Thus, the evidence does not disclose any reason why, in those circumstances, the person skilled in the art, at the priority date, would have read down EP 141/US 528 in a way that would be inconsistent with the then accepted clinical practice involving the administration of antipsychotic drugs to treat schizophrenia.

324    This conclusion is not arrived at by adding common general knowledge to the disclosures of a prior art document: cf AstraZeneca 226 FCR 324 at [352]. Rather, it simply acknowledges that the prior art must be construed through the eyes of the person skilled in the art in light of the common general knowledge. There is simply no reason or cause for the person skilled in the art to have selectively read down EP 141/US 528 to exclude their teachings from covering the administration of the carbostyril compounds, including aripiprazole, from any particular line of treatment, including third line or later line treatment, where the patient fails to respond to two or more of the identified antipsychotic drugs.

325    Thus, the arbitrary limitation of claims 1 and 7 to third line or later line treatment, in the face of the disclosures of EP 141/US 528 that the carbostyril compounds, including aripiprazole, are alternatives to various other prior art drugs, cannot confer novelty. A contrary conclusion would be a triumph of mere claim form over substance, simply because the prior art document does not descend to describe every possible circumstance and detail of when and how aripiprazole might possibly be used to treat schizophrenia, even though all such circumstances and details are necessarily included in the general teaching that aripiprazole can be used to treat schizophrenia. EP 141/US 528 impose no limitations on the patients to whom aripiprazole can be administered to treat schizophrenia, the symptoms of schizophrenia for which aripiprazole is useful, or the circumstances in which it can be used.

326    Is this conclusion consistent with the principle that, in order to be anticipatory, a prior art document must contain a clear description of, or a clear direction, recommendation or suggestion to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent? In my view it is. EP 141/US 528 each contain a clear direction, recommendation or suggestion to use the relevant carbostyril compounds, including aripiprazole, in the treatment of schizophrenia, including in relation to negative symptoms (which, at the priority date, would have been understood by the person skilled in the art as comprehending at least some of the symptoms of cognitive impairment referred to in claims 1 and 7) in the chronic period of schizophrenia as an alternative to prior art drugs (including at least three of those identified in claims 1 and 7), regardless of whether, as alternatives, the carbostyril compounds, including aripiprazole, are used as first, second, third or later line treatment relative to the earlier drugs. If, before the priority date, and following the direction, recommendation or suggestion of EP 141/US 528, aripiprazole had been used to treat a particular patient suffering from schizophrenia, whose symptoms of cognitive impairment associated with the forms of schizophrenia described in the claims had failed to respond to two or more of the drugs identified in the claims, then that method of treatment inevitably would have infringed claim 7 of the 772 patent, assuming the patent to have then been granted.

327    Similarly, the direction, recommendation or suggestion of EP 141/US 528 to use aripiprazole in the production of a medicament to treat schizophrenia (see, in particular, the express disclosure in claim 32 of EP 141) was one that was for the use of aripiprazole on all occasions in the treatment of the illness. If, before the priority date, that direction, recommendation or suggestion had been followed, the medicament so produced would also have met the description of the medicament of claim 1, such that that use would also have inevitably infringed claim 1, assuming the patent to have then been granted.

328    For these reasons, I do not accept that the invention claimed in claims 1 and 7 of the 772 patent is novel in light of the information made publicly available by EP 141/US 528.

329    Given my conclusion that the invention claimed in claims 1 and 7 of the 772 patent is not novel in light of the prior art information in EP 141/US 528, it is not necessary for me to consider whether Serper and Saha are also novelty-destroying publications. Nevertheless, for completeness, I will briefly state my views on this aspect of the case.

Serper

330    I am satisfied that, at the priority date, the person skilled in the art would have understood Serper as disclosing that aripiprazole is a drug that is used to treat schizophrenia, including in patients suffering from cognitive impairment associated with chronic schizophrenia. I am also satisfied that the person skilled in the art would have understood Serper as disclosing that, on the basis of the study on which it reports, patients taking aripiprazole showed a greater improvement in their cognitive performance compared to patients taking typical antipsychotic medication. Necessarily, the person skilled in the art would also have understood that aripiprazole had been used to produce a medicament for use in the study to which it refers.

331    The applicants submitted that Serper does not anticipate the invention as claimed in claims 1 and 7 because it does not disclose that:

    aripiprazole is a partial agonist at the 5-HT1A receptor;

    the 5-HT1A partial agonism of aripiprazole is useful in the treatment of cognitive impairment in schizophrenic patients;

    aripiprazole has been or could be used to effectively treat patients who have failed to respond to previous treatment with other antipsychotic medication, in particular the failure of the patients in the study to respond to previous treatment with any identified antipsychotic medication.

332    This defence of the invention claimed in claims 1 and 7 proceeds along similar lines to that advanced by the applicants with respect to EP 141/US 528. The conclusions to which I have come in that regard lead to similar conclusions in relation to Serper as anticipating claims 1 and 7. Thus, whilst I accept that Serper does not disclose that aripiprazole is a partial agonist at the 5-HT1A receptor or that aripiprazole’s 5-HT1A partial agonism is useful in the treatment of cognitive impairment in schizophrenic patients, this does not persuade me that the invention as claimed in each of claims 1 and 7 is novel in light of the information which Serper does make publicly available. I repeat, in this context, my reasons at [321]-[322].