FEDERAL COURT OF AUSTRALIA

InterPharma Pty Ltd v Hospira, Inc (No 5) [2019] FCA 960

ORDERS

THE COURT ORDERS THAT:

1.    Pursuant to s 136 of the Evidence Act 1995 (Cth) the use of the following documents be limited to the use stated below:

(a)    The document entitled “Abbott-85499 Dexmedetomidine Clinical Study Report: A Phase III, Multicenter, Double-Blind, Randomized, Comparative Study Evaluating The Effect of Two Doses of Dexmedetomidine Versus Placebo In Adult Patients Undergoing Elective Coronary Artery Bypass Graft(s) Surgery”, be admitted and used solely as evidence of the previous representations that the study identified as DEX-95-004:

(i)    was a Phase III, Multicenter, Double-Blind, Randomized, Comparative Study Evaluating The Effect of Two Doses of Dexmedetomidine Versus Placebo In Adult Patients Undergoing Elective Coronary Artery Bypass Graft(s) Surgery;

(ii)    (ii)    was initiated on 2 January 1996 and completed on 7 December 1997;     and

(iii)    was conducted in compliance with Good Clinical Practice (GCP) guidelines.

(b)    The document entitled “Abbott-85499 Dexmedetomidine Clinical Study Report: A Phase II, Single-Center, Two-Part Study Evaluating the Safety, Efficacy, and Dose Titratability of Dexmedetomidine in ICU Sedation” be admitted and used solely as evidence of the previous representations that the study identified as W97-249:

(i)    was a Phase II, Single-Center, Two-Part Study Evaluating the Safety, Efficacy, and Dose Titratability of Dexmedetomidine in ICU Sedation;

(ii)    was initiated on 14 January 1998 and completed on 12 March 1998; and

(iii)    was conducted in compliance with GCP guidelines.

(a)    The document entitled “Duke University Medical Center Institutional Review Board (IRB)” and an attached document entitled “Duke University Medical Center – Informed Consent for a Research Project: A Phase III, Multicenter, Double-Blind, Randomized, Comparative Study Evaluating The Effect of Two Doses of Dexmedetomidine Versus Placebo In Adult Patients Undergoing Elective Coronary Artery Bypass Graft(s) Surgery: DEX-95-004, Version 2” (Duke Form) be admitted and used solely as evidence of the previous representations that:

(i)    the patient informed consent form that was approved by the IRB for use in the DEX-95-004 study at the Duke Medical Center was the Duke Form;

(ii)    the DEX-95-004 study was a Phase III, Multicenter, Double-Blind, Randomized, Comparative Study Evaluating the Effect of Two Doses of Dexmedetomidine Versus Placebo In Adult Patients Undergoing Elective Coronary Artery Bypass Graft(s) Surgery; and

(iii)    the approval was given for a period of one year terminating on 11 October 1996.

(b)    The document entitled “Information for Patients: A phase II, single-center, two part study evaluating the safety, efficacy and dose titratability of Dexmedetomidine in ICU sedation”, having the protocol “W97-249”, version 5 (part 1) dated 14 January 1998 (249 Form) and correspondence dated 19 January 1998 on behalf of the Board of Directors of the Academic Hospital Utrecht be admitted and used solely as evidence of the previous representations that:

(i)    the patient informed consent form that was approved for use in part 1 of the W97-249 study was the 249 Form; and

(ii)    the W97-249 study was a Phase II, Single-Center, Two-Part Study Evaluating the Safety, Efficacy and Dose Titratability of Dexmedetomidine in ICU Sedation.

2.    Leave be granted to amend the Third Further Amended Particulars of Invalidity in accordance with these reasons (delivered on 20 June 2019) (these reasons).

3.    The Proposed Fourth Further Amended Particulars of Invalidity stand as the Fourth Further Amended Particulars of Invalidity to the extent leave is granted in Order 2 above.

4.    By 4:00 pm on 4 July 2019, each party file and serve proposed minutes of orders reflecting the conclusions in these reasons and short submissions (limited to 3 pages) addressing:

(a)    the form of the proposed orders; and

(b)    costs (other than with respect to the interlocutory application filed on 12 January 2018).

5.    By 2:00 pm on 21 June 2019, each party inform the other parties and the associate to Justice Kenny whether it has any confidentiality issue with these reasons.

6.    Until 2:00 pm on 21 June 2019 or further order, these reasons not be made available to or published to any person other than the parties and their legal advisors.

7.    The question of costs be determined on the papers unless a party wishes to be heard on that question orally.

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

REASONS FOR JUDGMENT

KENNY J:

Introduction

1    This proceeding involves the construction, validity and, if valid, alleged infringement of a patent entitled “Use of dexmedetomidine for ICU sedation” (Patent). Hospira, Inc and Pfizer Australia Pty Ltd (together referred to as Pfizer) are respectively the registered proprietor and exclusive licensee of the Patent. The Patent is Australian Patent No 754484. Pfizer sells pharmaceutical products under the name “Precedex®”, the sole active ingredient of which is dexmedetomidine hydrochloride (a pharmaceutically acceptable salt of dexmedetomidine). These products are registered on the Australian Register of Therapeutic Goods (ARTG), with Pfizer as sponsor.

2    InterPharma Pty Ltd (InterPharma), which carries on the business of importing and distributing pharmaceutical products for sale in Australia, is the sponsor of a listing on the ARTG for a family of products, which contain dexmedetomidine hydrochloride as their sole active ingredient (Generic Products). The Generic Products are listed on the ARTG under the brand name “Dexmedetomidine Ever Pharma” and are registered “for sedation of initially intubated patients during treatment in an intensive care setting” (ICU sedation indication) and “for sedation of non-intubated patients prior to and/or during surgical and other procedures” (procedural sedation indication). These indications are the same as for Precedex®.

3    InterPharma, which initially commenced the proceeding to revoke the claims of the Patent, relied on a number of grounds of invalidity. The grounds relied on were that the invention as claimed: (a) was not a “manner of new manufacture”; (b) was not novel; (c) lacked an inventive step; (d) was not fairly based on the matter described in the specification; and (e) did not comply with s 40 of the Patents Act 1990 (Cth) (Patents Act) in that the claims were not clear and succinct.

4    In a cross-claim, Pfizer contended that InterPharma threatened to infringe each claim of the Patent by, amongst other things, offering to supply and supplying the Generic Products. InterPharma admitted that, subject to the question of validity, its proposed conduct threatened to directly infringe claim 1 and indirectly infringe claims 13, 15 and 26 of the Patent. InterPharma also admitted threatened infringement of claims 2, 14 and 27 of the Patent on the basis of a particular construction of those claims (which, for the reasons given below, I accept).

5    There was a substantive hearing of the claim and cross-claim on 3, 4, 7, 21 and 22 May 2018. On 6 August 2018, InterPharma filed an application to re-open the hearing. The hearing was resumed, by consent, on 15 November 2018, when further expert evidence was adduced.

6    InterPharma was, until the Patent expired on 31 March 2019, subject to interlocutory orders restraining it from apprehended infringement of the Patent. The focus at this stage of the proceeding was on Pfizer’s entitlement to final relief. For the reasons stated below, I have found that InterPharma threatened to infringe the Patent during its term and that InterPharma’s challenge to the validity of the Patent should be rejected.

Abbreviated references

7    In these reasons, the following abbreviations are used:

Belleville means the article by Belleville J, Ward D, Bloor B, and Maze M, “Effects of intravenous dexmedetomidine in humans: I. Sedation, ventilation, and metabolic rate”, Anesthesiology 1992, 77: 1125-1133.

Bloor means the article by Bloor B, Ward D, Belleville J, and Maze M, “Effects of intravenous dexmedetomidine in humans: II. Hemodynamic changes”, Anesthesiology 1992, 77: 1134-1142.

Belleville/Bloor means Belleville and Bloor together.

Böhrer 1990 means the article by Böhrer H, Bach A, Layer M and Werning P, “Clonidine as a sedative adjunct in intensive care”, Intensive Care Medicine 1990, 16: 265-266.

GCP Guidelines means the Guideline for Good Clinical Practice E6(R1), Current Step 4 version dated 10 June 1996, developed by the appropriate Expert Working Group of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

Hall 2010 means the article by Hall J, “Creating the animated intensive care unit”, Critical Care Medicine 2010, 38(10): S668-S675.

Jalonen 1997 means the article by Jalonen J, Hynynen M, Kuitunen A, Heikkila H, Perttila J, Salmenpera M, Valtonen M, Aantaa R, and Kallio A, “Dexmedetomidine as an anaesthetic adjunct in coronary artery bypass grafting”, Anesthesiology 1997, 86: 331-345.

Kress 1996 means the article by Kress J, O’Connor M, Pohlman A, Olson D, Lavoie A, Toledano A, and Hall J, “Sedation of critically ill patients during mechanical ventilation”, American Journal of Respiratory and Critical Care Medicine 1996, 153: 1012-1018.

Kress 2000 means the article by Kress J, Pohlman A, O’Connor M, and Hall J, “Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation”, New England Journal of Medicine 2000, 342(20): 1471-1477.

Petty editorial means the editorial by Petty T, “Suspended life or extending death?”, Chest 1998, 114(2): 360-361.

Pohlman 1994 means the article by Pohlman A, Simpson K, and Hall J, “Continuous intravenous infusions of lorazepam versus midazolam for sedation during mechanical ventilator support: a prospective, randomized study”, Critical Care Medicine 1994, 22(8): 1241-1247.

Talke means the article by Talke P, Li J, Jain U, Leung J, Drasner K, Hollenberg M, and Mangano D, “Effects of perioperative dexmedetomidine infusion in patients undergoing vascular surgery”, Anesthesiology 1995, 82: 620-633.

Tuxen 1998 means the article by Tuxen D, “Sedation and paralysis in mechanical ventilation”, Clinical Pulmonary Medicine 1998, 5(5): 314-328.

1997 Review Article means the article by French C and Bellomo R, “The role of [alpha]-receptor manipulation in the prevention of renal dysfunction”, Current Opinion in Critical Care 1997, 3: 408-413.

Overview of the patent

8    The Patent claimed an earliest priority date of 1 April 1998 (priority date). The priority date is uncontested. The Patent expired on 31 March 2019 (Patent expiry date).

9    The application for the Patent was made on 31 March 1999. Issues of infringement and validity are therefore to be determined under the Patents Act, in the form in which it existed prior to, among other Acts, the Patents Amendment (Innovation Patents) Act 2000 (Cth), the Patents Amendment Act 2001 (Cth), and the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth).

The background to the invention

10    The invention the subject of the Patent relates to the use of dexmedetomidine or a pharmaceutically acceptable salt thereof (referred to in these reasons as dexmedetomidine unless specified otherwise) in intensive care unit (ICU) sedation; a method of sedating a patient in the ICU by administering dexmedetomidine; and the use of that compound in the manufacture of a medicament for ICU sedation.

11    The specification explains:

In addition to the actual sedation of a patient in the ICU, the word sedation in the ICU context also includes the treatment of conditions that affect patient comfort, such as pain and anxiety. Also, the word intensive care unit includes any setting that provides intensive care.

…

The aim of ICU sedation is to ensure that the patient is comfortable, relaxed, and tolerates uncomfortable procedures such as placement of iv-lines or other catheters, but is still arousable.

12    According to the specification:

Particularly, the present invention relates to a method of sedating a patient while in the ICU by administering dexmedetomidine … wherein dexmedetomidine is essentially the sole active agent or the sole active agent administered for this purpose.

13    The specification explains that ICU patients often receive a variety of drugs concurrently. It states:

The agents used most commonly are given to achieve patient comfort. Various drugs are administered to produce anxiolysis (benzodiazepines), amnesia (benzodiazepines), analgesia (opioids), antidepression (antidepressants/benzodiazepines), muscle relaxation, sleep (barbiturates, benzodiazepines, propofol) and anaesthesia (propofol, barbiturates, volatile anaesthetics) for unpleasant procedures. These agents are cumulatively called sedatives in the context of ICU sedation, though sedation also includes the treatment of conditions that affect patient comfort, such as pain and anxiety, and many of the drugs mentioned above are not considered sedatives outside the context of ICU sedation.

14    The specification describes the side effects associated with ICU sedatives as follows:

The presently available sedative agents are associated with such adverse effects as prolonged sedation or oversedation (propofol and especially poor metabolizers of midazolam), prolonged weaning (midazolam), respiratory depression (benzodiazepines, propofol, and opioids), hypotension (propofol bolus dosing), bradycardia, ileus or decreased gastrointestinal motility (opioids), immunosuppression (volatile anaesthetics and nitrous oxide), renal function impairment, hepatotoxicity (barbiturates), tolerance (midazolam, propofol), hyperlipidemia (propofol), increased infections (propofol), lack of orientation and cooperation (midazolam, opioids, and propofol), and potential abuse (midazolam, opioids, and propofol).

15    The specification further states that the combination of ICU sedatives (referred to as polypharmacy) “may cause adverse effects”:

For example, the agents may act synergistically, which is not predictable; the toxicity of the agents may be additive; and the pharmacokinetics of each agent may be altered in an unpredictable fashion.

16    According to the specification, “[t]he preferred level of sedation for critically ill patients has changed considerably in recent years”. It explains:

Today, most intensive care doctors in the ICU prefer their patients to be asleep but easily arousable, and the level of sedation is now tailored towards the patient’s individual requirements.

17    The specification identifies the known problems with α2-adrenoceptor agonists, particularly clonidine. It states that:

According to Tryba et al., clonidine has its limitations in sedating critically ill patients mainly because of its unpredictable hemodynamic effects, i.e., bradycardia and hypotension, so that it must be titrated for each individual patient. Long term treatment of critically ill patients with clonidine has been reported to be associated with such rebound effects as tachycardia and hypertension.

18    The specification states that “α2-agonists are not presently used by themselves in ICU sedation”. It continues as follows:

Further, α2-agonists are not generally used in ICU sedation even in conjunction with other sedative agents. Only clonidine has been evaluated for use in ICU sedation, and then only in conjunction with opioids, benzodiazepines, ketamine, and neuroleptics. Further, administration of clonidine as essentially the sole active agent or the sole active agent to a patient in the ICU to achieve sedation has not been disclosed to the best of the applicants’ knowledge.

19    Some of the characteristics of an “ideal sedative agent for a critically ill patient” are identified. According to the specification:

An ideal sedative agent for a critically ill patient should provide sedation at easily determined doses with ready arousability together with hemodynamic stabilizing effects. Further, it should be an anxiolytic and an analgesic, and should prevent nausea, vomiting, and shivering. It should not cause respiratory depression. Preferably, an ideal sedative agent should be used by itself in ICU sedation to avoid the dangers of polypharmacy.

20    The specification depicts the chemical structure of dexmedetomidine as follows:

21    The specification states that dexmedetomidine has been described in US Patent 4910214 (US 214) as “an α2-receptor agonist for general sedation/analgesia and the treatment of hypertension or anxiety”.

The invention as described in the specification

22    Under the heading, “Summary of the invention”, the specification states that it had been “unexpectedly found that dexmedetomidine … is an ideal sedative agent to be administered to a patient in the ICU to achieve patient comfort”. Regarding the invention as a method of sedating a patient in the ICU by administering dexmedetomidine, wherein that compound is essentially the sole active agent or the sole active agent, the specification states:

The method is premised on the discovery that essentially only dexmedetomidine … need[s] to be administered to a patient in the ICU to achieve sedation and patient comfort. No additional sedative agents are required.

23    The Ramsay Scale (an assessment of the level of sedation in experimental subjects) is described under the heading, “Brief description of the drawings”. The specification states that, in the Ramsay Scale, the level of wakefulness is scored on a scale of 1 to 6 (Ramsay Sedation Score) based on progressive loss of responsiveness to stimuli ranging from auditory to deep painful stimuli. Figure 2 (set out below) shows the Ramsay Sedation Score of a patient in the dexmedetomidine study described in example 3.

24    The dotted line signifies fluctuations in the Ramsay Sedation Score in response to dose adjustments.

25    Under the heading, “Detailed description of the invention”, the specification further explains the particular method of sedating a patient in the ICU by administering dexmedetomidine as essentially the sole active agent or the sole active agent for this purpose. It states:

Particularly, it has been found that dexmedetomidine … can be essentially the sole active agent or the sole active agent administered to a patient in the ICU in order to sedate the patient.

26    The specification goes on to describe the unique quality of the sedation in the ICU achieved by administering dexmedetomidine. It states, in particular:

Patients sedated by dexmedetomidine … are arousable and oriented, which makes the treatment of the patient easier. The patients can be awakened and they are able to respond to questions. They are aware, but not anxious, and tolerate an endotracheal tube well. Should a deeper level of sedation or more sedation be required or desired, an increase in dexmedetomidine dose smoothly transits the patient into a deeper level of sedation.

27    It is further said that:

Dexmedetomidine does not have adverse effects associated with other sedative agents, such as, respiratory depression, nausea, prolonged sedation, ileus or decreased gastrointestinal motility, or immunosuppression.

28    The specification explains that the precise amount of dexmedetomidine to be administered to achieve the desired outcome depends on a number of factors. It further states that:

The dose range of dexmedetomidine can be described as target plasma concentrations. The plasma concentration range anticipated to provide sedation in the patient population in the ICU varies between 0.1-2 ng/ml depending on the desired level of sedation and the general condition of the patient. These plasma concentrations can be achieved by intravenous administration by using a bolus dose and continuing it by a steady maintenance infusion. For example, the dose range for the bolus to achieve the forementioned plasma concentration range in a human is about 0.2-2 µg/kg, preferably about 0.5-2 µg/kg, more preferably 1.0 µg/kg, to be administered in about 10 minutes or slower, followed by a maintenance dose of about 0.1-2.0 µg/kg/h, preferably about 0.2-0.7 µg/kg/h, more preferably about 0.4-0.7 µg/kg/h.

29    The specification provides 3 examples, which exemplify the invention.

The claims

30    The independent claims of the Patent are:

Claim 1:    “Use of dexmedetomidine … in the manufacture of a medicament for use in intensive care unit sedation”.

Claim 13:    “A method of sedating a patient in an intensive care unit, wherein said method comprises administering dexmedetomidine … to a patient in need thereof”.

Claim 15:    “A method of sedating an intensive care unit patient, comprising administering a pharmaceutical composition to the patient, wherein the pharmaceutical composition comprises an active agent and an inactive agent, wherein the active agent consists of dexmedetomidine”.

Claim 26:    “Use of dexmedetomidine … in the intensive care unit sedation”.

Claim 1, dependent claims 2 to 12 and omnibus claim 38

31    The use according to claim 1 is the use of dexmedetomidine in the manufacture of a medicament for use in ICU sedation. Claim 1 is therefore a “Swiss-style” or “Swiss-type” claim in the form of “the use of [known] compound X in the manufacture of a medicament for a specified (and new) therapeutic use”: see Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50; 253 CLR 284 (Apotex v Sanofi-Aventis HCA) at [248].

32    In Otsuka Pharmaceutical Co Ltd v Generic Health Pty Ltd (No 4) [2015] FCA 634; 113 IPR 191 (Otsuka Pharmaceutical v Generic Health (No 4)) at [120], Yates J explained that a claim of this kind should be characterised as a method (or process) claim. Although the Swiss-style claim in that case (as here) was to a method of manufacture of a medicament, it was accepted that the novelty of the claim might arise from the new therapeutic use to which the medicament was applied: Otsuka Pharmaceutical v Generic Health (No 4) at [116]; see also Actavis UK Ltd v Merck & Co Inc [2008] EWCA Civ 444; [2009] 1 All ER 196 (Actavis UK v Merck) at [31], [49].

33    As will be seen, claims 2 to 12 are dependent Swiss-style claims, dependent on claim 1. Each of claims 2 to 12 further qualifies what is said to be the hitherto undiscovered therapeutic use of the medicament by reference to its particular administration (see [189]-[199] below). Claim 38, which is to a “use according to claim 1 substantially as hereinbefore described”, is an omnibus claim to claim 1. As stated below, I reject InterPharma’s submission that the use claimed in claims 2 to 12 and 38 can be understood as “directed to the clinician administering the product that results from the manufacture of the medicament”.

34    It is convenient to note at this point that claim 3 relates to the use of dexmedetomidine in the manufacture of a medicament for use in ICU sedation (as described in claim 1 or 2), “wherein the dexmedetomidine … is administered in an amount to achieve a plasma concentration of 0.1-2 ng/ml”; and that InterPharma made submissions about the plasma concentration integer, which are considered below.

Claims 13, 15 and 26, dependent claims 14, 16 to 25, 27 to 37 and omnibus claim 39

35    Claims 13, 15 and 26 are method (of treatment) claims. Claim 13 is for a method of sedating a patient in an ICU, wherein the method comprises administering dexmedetomidine to a patient in need of that drug. Claim 14 is a dependent claim, dependent on claim 13.

36    Claim 15 is for a method of sedating an ICU patient, comprising administering a pharmaceutical composition to the patient, amongst other things, “wherein the active agent consists of dexmedetomidine”.

37    Claim 16 is a dependent claim, dependent on claims 13, 14 or 15, wherein dexmedetomidine is administered “in an amount to achieve a plasma concentration of 0.1-2 ng/ml”. Again, I note that the significance of this latter integer is considered below.

38    Claims 17 to 25 are all dependent claims (dependent on claims 16, 17, 18, 19, 20, 21, 23 or 24). Relevant aspects of these claims are discussed below.

39    Claim 26 is an independent claim for the “[u]se of dexmedetomidine … in the intensive care unit sedation”.

40    Claim 27 is a dependent claim (dependent on claim 26), wherein dexmedetomidine is “essentially the sole active agent or the sole active agent”. Claims 28 to 37 are also dependent claims (dependent on claims 26, 27, 28, 29, 30, 31, 32, 33, 35 or 36), relevant aspects of which are further discussed below.

41    Claim 39 is a second omnibus claim, for a method according to claim 13 or 15 “substantially as hereinbefore described”.

Overview of witness evidence

Intensive care specialists

42    Three specialists in intensive care medicine gave evidence at trial. They were: Professor Russell Booth Hall; Professor Rinaldo Bellomo; and Associate Professor (Assoc Professor) Craig John French.

43    Professors Hall and Bellomo and Assoc Professor French met together on 2 May 2018, and created their Joint Expert Report (Joint Report). The Joint Report was in evidence.

44    InterPharma called Professor Hall. Since 1981, Professor Hall has been an Attending Physician, Critical Care Services, at the University Of Chicago Pritzker School Of Medicine. Amongst other things, he holds a certification in Critical Care Medicine from the American Board of Internal Medicine and is a Member of the Society for Critical Care Medicine. He is an author or co-author of very many articles published in leading medical journals.

45    Professor Hall had a specific interest in ICU sedation as at the priority date (April 1998). It may be accepted that his interest and knowledge about ICU sedation would have been significantly greater than that of the average ICU specialist at that time.

46    Professor Hall’s research interest is particularly relevant to the invention of the Patent. He was a co-author of Kress 2000, a highly influential paper leading intensive care specialists to question the previously accepted practice of deep sedation (see [537], [549] below). He was also a co-author of Kress 1996 and Pohlman 1994 (see [550] below).

47    Professor Hall is an experienced witness, who, on his own account, gives evidence in 15 to 20 cases a year, and has given evidence in United States (US) courts in two cases concerning the US equivalent of the Patent in suit.

48    Pfizer called Professor Bellomo, who has been delivering intensive care medicine to patients in Australia for well over 25 years. Professor Bellomo is the Director of Intensive Care Research at the Austin Hospital and has worked and continues to work as an intensive care specialist at that hospital and other hospitals, including the Royal Melbourne Hospital (RMH) ICU. Since 2002 he has been a Professor in the Faculty of Medicine at the University of Melbourne and since 2016 he has been a Board Member of the Australian and New Zealand College of Intensive Care Medicine.

49    Professor Bellomo came to intensive care medicine from a general physician’s background. Throughout his career, he has been engaged in clinical research in intensive care medicine, with a particular interest in the kidneys. He has an extensive list of publications, and has held editorial and reviewer positions for leading international medical journals, including US journals.

50    Pfizer also called Assoc Professor French, who has been practising in both anaesthesia and intensive care medicine in Australia since 1995. Assoc Professor French was undergoing training in both anaesthesia and intensive care medicine between 1992 and 1997. He was working as an anaesthetics registrar during 1995 and, from midway through that year, as an intensive care registrar. In 1998, he was admitted to the Fellowship of the Faculty of Intensive Care of the Australian and New Zealand College of Anaesthetists.

51    From January 1998 to 2001, Assoc Professor French worked as a consultant intensive care specialist and anaesthetist at the Western Hospital in Melbourne. In 2002, he was appointed Director of Intensive Care at the Sunshine Hospital, also in Melbourne. Since 2003, he has been the Director of Intensive Care at Western Health, a health services body that manages multiple hospitals in Melbourne. Among other things, he has been a Clinical Associate Professor at the University of Melbourne since 2011.

52    At the priority date, in April 1998, Assoc Professor French was a recently qualified specialist intensivist and anaesthetist. He considered his breadth of knowledge in intensive care and anaesthesia as at that date to be at its greatest level in his career. In subsequent years he maintained his overall general knowledge of intensive care and anaesthesia, although he gravitated towards his particular interests. Also as at the priority date, he had been involved in clinical trials for the development of new drugs within the ICU. Since 2015, he has been the chair of the Australian and New Zealand Intensive Care Society Clinical Trials Group.

53    Assoc Professor French has a particular interest in transfusion medicine in the ICU and the role of erythropoietin in clinical illness, although he had an early interest in mechanical ventilation and volatile anaesthetics. He published two papers prior to April 1998, and subsequently a large number of papers, many of them in the intensive care field. He co-authored numerous papers with Professor Bellomo. He has held editorial and reviewer roles for international, including US, medical journals.

54    As noted, Professors Hall and Bellomo and Assoc Professor French were each involved in research, including clinical trials, in intensive care medicine before April 1998. Both Professor Bellomo and Assoc Professor French specifically attested to their familiarity with the GCP Guidelines, the principles required to be followed in clinical trials, and with the investigator brochure supplied by drug companies to those designing and carrying out clinical trials. They both gave evidence about the training that was required to become an intensive care specialist in Australia. For example, Assoc Professor French had obtained an undergraduate medical degree in 1988, completed his residency in 1991, was an anaesthetic registrar from 1992 to 1995, and qualified as an intensive care specialist in 1998. Their evidence was, and it may be accepted, that the training to become an intensive care specialist called for extensive knowledge and the standard for the examinations was high. Those practising in intensive care medicine in Australia at the priority date also had another specialist qualification in medicine. Assoc Professor French and Professor Bellomo both affirmed that all intensive care specialists, regardless of their background or their additional practice, were equally skilled and equipped to administer intensive care medicine.

55    In addition to giving evidence at the trial, Professors Hall and Bellomo and Assoc Professor French each subsequently gave further evidence at the resumed hearing in November 2018.

Other witnesses

56    There were five other witnesses whose affidavits were tendered without objection and without cross-examination.

57    InterPharma adduced the affidavit evidence of Ms Carolyn Stewart. Ms Stewart is the Business and Operations Manager of the Melbourne Children’s Trials Centre at the Murdoch Children’s Research Institute. She has a Masters of Medical Science (Drug Development) from the University of New South Wales and, since the late 1980s, she has acquired extensive experience in respect of the conduct of local and international clinical trials.

58    While working for Amgen Australia Pty Ltd and its US parent company (Amgen) between 1992 and 2004, Ms Stewart was involved in drug research and development, and in clinical trials in Australia and overseas. Her responsibilities during those years included clinical trial management and conduct, writing protocols, designing and preparing participant information sheets and consent forms, and preparing study reports and publications.

59    Since working for Amgen, Ms Stewart has provided consultancy services to third parties regarding clinical trial site management and third party vendor management of clinical trials. She has also worked for the Nucleus Network Centre for Clinical Studies, where she was engaged in similar work. Ms Stewart gave evidence about the applicable legal and ethical requirements for the management and conduct of clinical drug trials and about good clinical practice.

60    InterPharma also adduced the affidavit evidence of Mr Bob van Der Kamp. Mr van Der Kamp is an Attorney at Law in the Netherlands. His evidence was confined to confirming: (1) the implementation into Dutch law of European Union (EU) Directive 91/507/EEC concerning good clinical practice for clinical trials, by a Decree on Manufacturing and Delivery of Pharmaceutical Products (Decree); and (2) that the Decree was part of Dutch law in 1998. His evidence was that the Decree became effective on 1 August 1994 and was in force until 1 July 2007. As will be seen, his evidence was relevant because one of the clinical trials on which InterPharma’s lack of novelty case relied was carried out in the Netherlands at the relevant time (see [400] below).

61    Pfizer relied on the affidavit evidence of Mr Rodney Ian Lindsay Cruise. Mr Cruise is a Patent Attorney with more than 28 years’ experience in conducting intellectual property research in the areas of patents, trademarks and designs. He was familiar with the conduct of searches on different databases of medical scientific literature and gave evidence about conducting searches of the medical literature as at the priority date. The evidence of Mr Cruise was that the most common medical scientific literature search database used as at 1 April 1998 was Medline, and that the two platforms most commonly used at that time for searching that database were PubMed and STN. His evidence was relevant to Pfizer’s response to InterPharma’s case on lack of inventive step (see [593] below).

62    At the start of the trial, Pfizer also relied on the affidavit evidence of Ms Melissa Jane Ankravs. Ms Ankravs is the Senior ICU Pharmacist and Team Leader at the RMH and is based in the ICU at the RMH. Ms Ankravs gave evidence about the role of the RMH Pharmacy and the means by which medicines were made available by the RMH Pharmacy for administration to patients in the RMH. She stated that she was involved in maintaining the stock levels in the ICU imprest at the RMH. She gave evidence about the numbers of vials of dexmedetomidine 200microg/50mL distributed to the ICU imprest and to the operating theatre imprests (located at other hospital locations outside the ICU). Her evidence was relevant to an issue that arose concerning the use of dexmedetomidine for procedural sedation, an aspect of the way InterPharma initially put its case. As this aspect of InterPharma’s case was subsequently abandoned, her evidence was not relied on in the parties’ final submissions.

63    Lastly, Pfizer relied on the affidavit evidence of Mr Michael Joseph Ryan. Mr Ryan had been the Director of Pharmacy at a number of hospitals in Melbourne between 1977 and 1994. He subsequently held the following positions: Manager of Health Information and Technology Services at the Victorian Healthcare Association (1997 to 1999); National Pharmacy Services Manager for Hospital Supplies of Australia (HSA) (1999 to 2001); and National Business Manager – Pharmacy at HSA (2001 to 2004). By 2018, he was an independent hospital and medicines management consultant, who ran his own business, PharmConsult Pty Ltd. He was also a Fellow of the Society of Hospital Pharmacists of Australia, having completed his Fellowship between 1979 and 1983.

64    It may be accepted that Mr Ryan had substantial knowledge and experience in the provision of pharmacy services within public and private hospitals, the procurement and supply of pharmaceutical products in the public health system, and in prescribing practices in hospitals. He gave evidence about the way in which medicines were dispensed to public and private hospital patients. He described tendering processes and outcomes. He gave evidence about the anticipated effect of the Generic Products entering the market, in terms of lessening restrictions related to cost-minimisation on the formulary in public hospitals. Pfizer relied on his evidence in support of an aspect of its case on infringement concerning the “essentially the sole active agent or the sole active agent” integer in claims 2, 14 and 27. It was unnecessary to refer to this aspect of Mr Ryan’s evidence in these reasons in light of InterPharma’s admission of infringement of these claims on the basis of a construction which, as will be seen, I accept. His evidence was also referred to in opening submissions in the context of the procedural sedation issue that was not ultimately pursued by InterPharma (see [62] above).

Principles of patent construction

65    In Jupiters Ltd v Neurizon Pty Ltd [2005] FCAFC 90; 65 IPR 86; 222 ALR 155 (Jupiters) at [67], a Full Court of this Court summarised the principles for the construction of patents as follows:

(i)    the proper construction of a specification is a matter of law: Décor Corporation Pty Ltd v Dart Industries Inc (1988) 13 IPR 385 at 400;

(ii)    a patent specification should be given a purposive, not a purely literal, construction: Flexible Steel Lacing Co v Beltreco Ltd (2000) 49 IPR 331; [2000] FCA 890 at [81] … ; and it is not to be read in the abstract but is to be construed in the light of the common general knowledge and the art before the priority date: Kimberley-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1; 177 ALR 460; 50 IPR 513; [2001] HCA 8 at [24];

(iii)    the words used in a specification are to be given the meaning which the normal person skilled in the art would attach to them, having regard to his or her own general knowledge and to what is disclosed in the body of the specification: Décor Corporation Pty Ltd at 391;

(iv)    while the claims are to be construed in the context of the specification as a whole, it is not legitimate to narrow or expand the boundaries of monopoly as fixed by the words of a claim by adding to those words glosses drawn from other parts of the specification, although terms in the claim which are unclear may be defined by reference to the body of the specification: Kimberley-Clark v Arico at [15]; Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588 at 610; Interlego AG v Toltoys Pty Ltd (1973) 130 CLR 461 at 478; the body of a specification cannot be used to change a clear claim for one subject matter into a claim for another and different subject matter: Electric & Musical Industries Ltd v Lissen Ltd [1938] 4 All ER 221 at 224–5; (1938) 56 RPC 23 at 39;

(v)    experts can give evidence on the meaning which those skilled in the art would give to technical or scientific terms and phrases and on unusual or special meanings to be given by skilled addressees to words which might otherwise bear their ordinary meaning: Sartas No 1 Pty Ltd v Koukourou & Partners Pty Ltd (1994) 30 IPR 479 at 485–6 … ; the court is to place itself in the position of some person acquainted with the surrounding circumstances as to the state of the art and manufacture at the time (Kimberley-Clark v Arico at [24]); and

(vi)    it is for the court, not for any witness however expert, to construe the specification; Sartas No 1 Pty Ltd, at 485–6.

66    The need to read a patent specification as a whole and in light of the common general knowledge in the art before the priority date continues to be emphasised. So too is the need to read a patent specification in a practical way and to give it a purposive construction.

This approach to construction requires the court to read the specification through the eyes of the skilled addressee with practical knowledge and experience in the field of work in which the invention was intended to be used and a proper understanding of the purpose of the invention.

See GlaxoSmithKline Consumer Healthcare Investments (Ireland) (No 2) Ltd v Generic Partners Pty Ltd [2018] FCAFC 71; 131 IPR 384 (Generic Partners) at [106].

67    As Lord Hoffmann explained in Kirin-Amgen Inc v Hoechst Marion Roussel Ltd [2004] UKHL 46; 64 IPR 444; [2005] 1 All ER 667 at [34]:

“Purposive construction” does not mean that one is extending or going beyond the definition of the technical matter for which the patentee seeks protection in the claims. The question is always what the person skilled in the art would have understood the patentee to be using the language of the claim to mean. And for this purpose, the language he has chosen is usually of critical importance. … There will be occasions upon which it will be obvious to the skilled man that the patentee must in some respect have departed from conventional use of language or included in his description of the invention some element which he did not mean to be essential. But one would not expect that to happen very often.

68    With respect to this passage, the Full Court in Generic Partners at [109]-[110] added:

It is important to note that Lord Hoffman[n] was referring here to the meaning conveyed to the skilled addressee by the language used and was not directing himself to a situation in which the skilled addressee deduced that the language of the claim, although conveying to him or her a particular meaning, could never have been intended to mean what it conveyed.

… These are situations in which the court endeavours to give effect to the skilled addressee’s understanding of the claim language in preference to a purely literal or grammatical construction, not because the skilled addressee understands that the claim contains a mistake that requires correction, but because, when read in the context of the document as a whole and the common general knowledge, the words used would convey that meaning to the skilled addressee.

Regarding the claims

69    With respect to the claims in a patent specification, as Lord Russel explained in Electric and Musical Industries, Ltd v Lissen, Ltd [1938] 4 All ER 221 at 224; (1939) 56 RPC 23 at 39:

The function of the claims is to define clearly and with precision the monopoly claimed, so that others may know the exact boundaries of the area within which they will be trespassers. Their primary object is to limit, and not to extend, the monopoly. What is not claimed is disclaimed. The claims must undoubtedly be read as part of the entire document, and not as a separate document. Nevertheless, the forbidden field must be found in the language of the claims, and not elsewhere.

See also Otsuka Pharmaceutical Co Ltd v Generic Health Pty Ltd (No 2) [2016] FCAFC 111; 120 IPR 431 (Otsuka FCAFC) at [94] (Besanko and Nicholas JJ).

70    Section 40(3) of the Patents Act requires that the claims of a patent be clear and succinct. It is an objection to the validity of a patent that “the scope of any claim of the complete specification is not sufficiently and clearly defined”: see Blanco White, Patents for inventions and the protection of industrial design (5th ed, 1983) (Blanco White) at 4-701, p 143. The need for clarity arises because, as Dixon CJ said in Martin v Scribal Pty Ltd (1954) 92 CLR 17 (Martin v Scribal) at 59, “the principles governing the definition of a monopoly operating over the public at large require a description which is not reasonably capable of misunderstanding”.

71    A court may refer to the body of the specification to identify the background of the claims and the meaning of technical terms, and also to resolve ambiguities in, or other doubts about, the claims’ construction: Austal Ships Sales Pty Ltd v Stena Rederi Aktiebolag [2008] FCAFC 121; 77 IPR 229 (Austal Ships) at [13], citing Flexible Steel Lacing Co v Beltreco Ltd [2000] FCA 890; 49 IPR 331 (Flexible Steel) at [71]-[78]; Nesbit Evans Group Australia Pty Ltd v Impro Ltd [1997] FCA 1092; 39 IPR 56 (Nesbit Evans) at 94-95. A claim is not invalid merely because it might have been better drafted nor because it is difficult to construe, “provided it can be properly and fairly construed”: Britax Childcare Pty Ltd v Infa-Secure Pty Ltd (No 4) [2015] FCA 651; 113 IPR 280 at [583] (emphasis in original); see also Flexible Steel at [80]-[81], quoting Blanco White at 4-701, and cited with approval by the Full Court in Austal Ships at [14].

72    In Martin v Scribal at 97, Taylor J observed:

The claims also must be construed without an eye on the alleged infringer’s acts. … On the other hand, it is right to construe a claim with an eye benevolent to the inventor and with a view to making the invention work — this is an application of the old doctrine ut res magis valeat quam pereat … ; and, where the language of a claim is obscure or doubtful, the doubt may sometimes be resolved by referring to words in the body of the document to explain it. This is known as the dictionary principle. …

This remains a correct approach: see Otsuka FCAFC at [95] (Besanko and Nicholas JJ).

73    In Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 (Minnesota Mining) at 274, Aickin J said that the principle with respect to clarity is that “[l]ack of precise definition in claims is not fatal to their validity so long as they provide a workable standard suitable to the intended use”. Stephen J had applied this principle in Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59 (Monsanto), in holding at 61 that the use of the word “substantial” was clear in the phrase “in an amount to have any substantial effect as a cooling medium” in a claim in the patent in suit. Stephen J said, at 60, that:

The lack of clarity which is complained of results, it is said, solely from the use of the adjective “substantial” in the phrase “any substantial effect as a cooling medium”. It is said that its use makes it impossible to determine the limits of the claim to monopoly, that the specification contains no criteria of substantiality of effect and that its meaning cannot be determined by simple experiment.

… Of course what is substantial is a question of degree and is, in that sense, imprecise but in its present context it does not, I think, give rise to any ambiguity.

…

It will in each case be a question of fact and degree whether or not an injected admixture has a substantial effect as a cooling medium and this is the very sort of question which not only do courts have to answer daily, but which I believe that those skilled in the art would have little difficulty in resolving. When only small quantities of admixed fluids are involved, as will be the case when modifiers or solvents are in question, the evidence discloses that they will have no “substantial” effect as cooling media. …

There will, I think, in the present case be no difficulty in a third party ascertaining whether or not what he proposes to do falls within the ambit of the claim … .

74    The principle stated by Aickin J in Minnesota Mining has since been regularly applied in Australian courts: see, for example, Freeman v TJ and FL Pohlner Pty Ltd (1994) 30 IPR 377 at 381-382; Nesbit Evans at 94-95; Austal Ships at [14], quoting Flexible Steel at [81]. In Nesbit Evans at 95, Lindgren J, with whom Hill J agreed, said that:

… it is not unusual for a claim to define an invention partly by the use of a relative expression which necessitates exercise of judgment … and so long as the claims provide a workable standard suitable to the intended use, they will be valid … . The expressions in question must be understood in a practical, common sense manner.

75    In Flexible Steel at [81], Hely J said that:

It is permissible for an invention to be described in a way which involves matters of degree.  Lack of precise definition in claims is not fatal to their validity, so long as they provide a workable standard suitable to the intended use. The consideration is whether, on any reasonable view, the claim has meaning. In determining this, the expressions in question must be understood in a practical, commonsense manner.  Absurd constructions should be avoided and mere technicalities should not defeat the grant of protection.

(Citations omitted)

76    Whether or not a degree of imprecision is fatal to the validity of a claim depends on whether the claim provides a workable standard for those skilled in the art in the circumstances of the intended use. Where there is no workable standard, imprecision in a claim spells invalidity for lack of clarity, as Albany Molecular Research Inc v Alphapharm Pty Ltd [2011] FCA 120; 90 IPR 457 (Albany Molecular) illustrates. In that case, Jessup J held at [174]-[175] that the expression “substantially pure” when used in the claims in the patent in suit failed to satisfy s 40(3) of the Patents Act, because it left “the definition of the boundaries of the invention uncertain or variable”. (The lack of clarity in that case was cured by a subsequent amendment to the specification, which indicated that the claim to substantial purity was limited to compounds of at least 98% purity: Albany Molecular at [182], [186].)

Regarding the skilled addressee

77    The construction of a patent specification is the responsibility of the Court, since it is a matter of law. To construe a specification, however, the Court must place itself in the positon of the skilled addressee in Australia to whom the specification is addressed: see W R Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) 25 IPR 481 (Grace v Asahi) at 496. The words of the specification are to be given the meaning that that skilled addressee would give them in light of the common general knowledge immediately prior to the priority date and what is disclosed in the specification itself.

[S]ince 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.

General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd [1972] RPC 457 (General Tire) at 485.

78    The “skilled addressee” is essentially a hypothetical construct equivalent to a person “acquainted with the surrounding circumstances as to the state of [the] art and manufacture at the time”: Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8; 207 CLR 1 at [24], citing with approval British Dynamite Co v Krebs (1879) 13 RPC 190 at 192. Such a person is “likely to have a practical interest in the subject matter of the invention”: Catnic Components Ltd v Hill & Smith Ltd [1982] RPC 183 at 242. The skilled addressee is taken to be a person of ordinary skill in the field to which the invention relates, rather than a leading expert in the field: see Streetworx Pty Ltd v Artcraft Urban Group Pty Ltd [2014] FCA 1366; 110 IPR 82 at [67] (Beach J). As the Full Court in Jupiters at [67] said, “the words used in a specification are to be given the meaning which the normal person skilled in the art would attach to them, having regard to his or her own general knowledge and to what is disclosed in the body of the specification”.

79    The Patent relates to the field of intensive care medicine and concerns the sedation of patients in intensive care using dexmedetomidine. The skilled addressee to whom the Patent is addressed is an intensive care specialist engaged in clinical practice and in some research in the field of intensive care medicine in Australia immediately prior to the priority date. Such a person would have the requisite knowledge of the state of the “art and manufacture” at the relevant time and a practical interest in the subject matter of the invention.

80    Intensive care specialists (or intensivists) in Australia at the priority date were the specialist doctors who were responsible for the clinical care of patients in an intensive care setting in a hospital. Such specialists were typically physicians or anaesthetists with specialist intensive care training. The clinical practice of intensive care specialists in Australia at the priority date would have included sedating intensive care patients in the ICU.

81    Professor Bellomo’s evidence was (and I accept) that immediately before the priority date, intensivists in Australia generally focussed their research on “issues related to major organs of the body rather than on areas such as sedation”. Assoc Professor French gave evidence to the same effect. Assoc Professor French explained (and again I accept) that, at the priority date, sedation was thought to be “a fairly benign procedure” in that “the practice of ICU sedation was not thought to generally impact patient outcomes adversely”.

82    Although the Patent concerns the sedation of patients in the ICU using dexmedetomidine, I do not accept, as InterPharma contended, that the relevant skilled addressee was an intensive care specialist with a particular interest in research in the field of intensive care sedation. To qualify the skilled addressee in this way is to select a sub-set of intensivists, with a particular level of interest, knowledge and skill in an aspect of intensive care medicine. This is not to identify the person of ordinary skill who works in the field of the invention (intensive care medicine) in Australia, and therefore not to identify the skilled addressee. Whilst highly skilled individuals, the ordinary intensive care specialist in Australia at the priority date did not have a specific interest, let alone research interest, in the sedation of patients in intensive care.

83    It may be accepted that the skilled addressee is not a manifestation of or “avatar” for the expert witness whose testimony is accepted by the court: AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30; 257 CLR 356 (AstraZeneca HCA) at [23]. The skilled addressee is a tool of analysis that is given form and content by the testimony of those witnesses. In this context, I accept that Professor Bellomo in particular was able to, and did, give relevant evidence as to how the skilled addressee would have understood the teaching, terms and expressions in the Patent and the relevant prior art. His evidence also assisted in ascertaining the knowledge that the skilled addressee would have had immediately before the priority date, including what the skilled addressee would have done as a matter of routine when faced with the problem that the invention of the Patent was intended to address.

84    The evidence of Assoc Professor French was able to, and did, assist from time to time with respect to particular matters, often in explaining or augmenting Professor Bellomo’s evidence. It is necessary to bear in mind, however, that although he had been working in the field of intensive care medicine as a registrar for some years before April 1998, Assoc Professor French did not complete his qualification as an intensive care specialist until early 1998. It will be recalled that he said, and I accept, that he had a greater breadth of knowledge of matters relevant to intensive care medicine at the time he completed his examinations for Fellowship of the Faculty of Intensive Care in 1998 than thereafter. It may be inferred from this that, as at and immediately before the priority date, his knowledge of some matters relevant to intensive care medicine would have been greater than that of the ordinary intensivist at that time. It may also be relevant to bear in mind that although Assoc Professor French had been engaged in clinical trials for the development of new drugs and had published two papers, as at April 1998, his research interest was to develop much more in the ensuing years.

85    Care also needs to be taken as regards Professor Hall’s evidence, bearing in mind that his medical training and clinical experience are in the US, including his training and experience in critical care medicine (as intensive care medicine is called in the US). For this reason, the testimony of Professor Bellomo and, subject to the qualifications already mentioned, the testimony of Assoc Professor French are likely to be of more assistance in enabling the Court to place itself in the positon of the skilled addressee in Australia than the evidence of Professor Hall. This does not mean that Professor Hall’s testimony can or should be entirely disregarded, since the evidence showed that the relevant “art and manufacture” had some important international dimensions. Rather, the fact that Professor Hall gave testimony based on knowledge and experience gained outside Australia has to be borne in mind in considering issues of evidentiary relevance, cogency and weight. It has also to be borne in mind that, in contrast to the ordinary intensive care specialist in Australia at the priority date, Professor Hall had at that date a particular research interest in sedation in critical care medicine and, in consequence, his knowledge of sedation in this field would have been more extensive than that of the ordinary intensive care specialist. It is also the case that his field of research was relevant to the invention of the Patent.

Are the claims in the Patent clear?

86    It is convenient to address the parties’ submissions on clarity at this point, since they also involve issues concerning the construction of the claims of the Patent in suit.

87    Before doing so, however, it is necessary to address InterPharma’s application for leave to amend its particulars of invalidity as regards its clarity ground in accordance with its Proposed Fourth Further Amended Particulars of Invalidity.

Leave to amend particulars of invalidity — clarity

88    When the hearing began on 3 May 2018, InterPharma was relying on its “Further Further [sic] Amended Particulars of Invalidity” filed on 12 April 2018. InterPharma subsequently prepared another document entitled “Third Further Amended Particulars of Invalidity”, which it filed on 11 May 2018. This document was created following a discussion in court on 7 May 2018, in the course of which senior counsel for Pfizer noted that InterPharma’s case on invalidity appeared to have “slimmed down somewhat” and requested that InterPharma file amended particulars of invalidity and an amended defence to cross-claim (the effect of which need not be addressed here) to reflect the case that it sought to make. The Court granted leave to InterPharma that day to amend its pleadings and particulars to this end.

89    In its closing submissions filed on 18 May 2018, however, Pfizer took issue with the form of the particulars filed by InterPharma on 11 May 2018. The matter was taken up at the commencement of the hearing of closing submissions on 21 May 2018. In response to the discussion that day, InterPharma filed another document on 24 May 2018, also entitled “Third Further Amended Particulars of Invalidity”. A Proposed Fourth Further Amended Particulars of Invalidity was filed on 25 May 2018 (incorporating the amendments made by the Third Further Amended Particulars of Invalidity filed on 24 May 2018). This document also indicated the proposed amendments for which leave was still required. Pfizer opposed a substantial part of these amendments, including InterPharma’s proposed amendments with respect to its clarity objection.

90    As indicated, when the trial began, InterPharma was relying on its Further Further Amended Particulars of Invalidity, according to which it alleged (in para 7A) that all the claims were invalid on the basis that they did not comply with s 40(3) of the Patents Act, because the limitation “for use in intensive care unit sedation” in claims 1 to 12 and 38, the limitation “a patient in an intensive care unit” in claims 13 to 25 and 39, and the limitation “in the intensive care unit sedation” in claims 26 to 37 were not clear to the skilled reader. This was said to be because it was not clear to the skilled reader:

... whether “intensive care unit sedation” referred to in claims 1 to 12, and claims 26 to 38, inclusive comprises sedation of all patients who are in an intensive care unit or only comprises sedation of a sub-set of critically ill patients who are in an intensive care unit and if so how that sub-set is defined[; and]

… whether a “patient in an intensive care unit” referred to in claims 13 to 25 inclusive includes any patient who is in an intensive care unit or only includes a sub-set of critically ill patients who are in an intensive care unit and if so how that sub-set is defined.

InterPharma retained these particulars in its Proposed Fourth Further Amended Particulars of Invalidity.

91    In opening written submissions filed before trial, InterPharma submitted as to lack of clarity that:

20.    While the Patent states that an ICU encompasses “any setting that provides     intensive care”, it does not further describe or elucidate the features of such a     setting.

21.    The Patent also states that in the ICU context, sedation includes the actual     sedation of a patient and “the treatment of conditions that affect patient     comfort, such as pain and anxiety”. Thus, analgesic agents such as opioids are     “called sedatives in the context of ICU sedation …”.

…

23.    InterPharma will contend that the claims of the Patent lack clarity because the     concept of an ICU, which is a limiting feature of all of the claims of the Patent,     lacked a sufficiently clear meaning before April 1998 to define a precise     boundary of Pfizer’s patent monopoly. …

24.    [T]he claims of the Patent are not directed to the particular qualities of the     patients to whom dexmedetomidine is administered but rather the setting of     that administration. The Patent covers any use of dexmedetomidine in an     intensive care setting suitable to achieve sedation of a patient (or, as that term     is defined in the Patent, to treat their pain or anxiety).

…

26.    While intensivists agree that there are areas within hospitals that are designated     as ICUs, and that these areas have certain features such as constant monitoring     and availability of life support, there is no delineation between the level of care     relevantly given to patients in other hospitals settings such as the operating     theatre, a high care post-operative unit, high dependency unit or recovery     room. …

27.    The lack of clarity of what is an ICU cannot be resolved by defining a certain     class of ICU patients. … Pfizer’s attempt to do so depends on excluding certain     ICU patients (e.g. those not intubated) from the class for the reason that     sedatives are less important for those ICU patients.

(Citations omitted)

92    In her oral opening, senior counsel for InterPharma also submitted, in relation to these limitations, that “the boundaries are not clear and it includes, on our case, the … relatively healthy compared to the critically ill who are being monitored in the ICU”.

93    Pfizer contended that InterPharma did not pursue the sub-set argument foreshadowed in its Further Further Amended Particulars of Invalidity. I reject this submission. It seems to me that InterPharma retained this argument throughout, although it also mounted other arguments (foreshadowed above) to support its fundamental contention that the limitations “for use in intensive care unit sedation”, “a patient in an intensive care unit”, and “in the intensive care unit sedation” are so unclear as to invalidate the claims in which they appear, essentially because the concept of an ICU is itself unclear.

94    InterPharma’s case in closing was not substantially different from its case in opening. In closing written submissions, InterPharma submitted:

86.    The concept of an ICU lacked a sufficiently clear meaning before April 1998     to define a precise boundary of Pfizer’s patent monopoly.

87.    While the Patent states that an ICU encompasses “any setting that provides     intensive care”, it does not further describe or elucidate the features of such a     setting.

88.    As appears from the discussion earlier, the experts agreed that there were units     designated as ICUs and that these were intensive care settings that shared     certain features. However, intensive care could also be given outside a unit     designated as an ICU. The independent claims lack clarity as there is no clear     boundary to be drawn between, for example, the level of monitoring and care     provided to patients in an ICU who are not on life support, and that which they     received in other post-operative care units. A sensible boundary cannot be     drawn by reference to the person overseeing the care: it was clear that not every     intensive care setting was overseen by an ICM specialist.

89.    The concept of an ICU patient cannot clarify or confine the meaning of an ICU.     While the specification refers for example to “critically ill patients” and those     who are “mechanically ventilated”, and provides examples of post-surgical     patients who were sedated in an ICU (such as those who underwent coronary     artery bypass surgery, or aortic valve replacement), there is no definition of an     ICU patient in the Patent. An ICU patient is any patient who is in an intensive     care setting, and the experts agree that such patients are a heterogeneous group.     Further, whether a given patient is in an ICU … depends on clinical judgment,     the availability of ICU beds and other care options.

90.    In any event, the claims are not drawn by reference to the patients who are     treated with dexmedetomidine but rather the setting of its administration. It     would be impermissible to put a gloss on the claims by limiting their scope to     a specific population of ICU patients described in the Patent.

91.    Nor can the concept of ICU sedation itself clarify or confine the meaning of     ICU. It is clear that ICU sedation could be given to any patient who is in an     intensive care setting and is to be broadly construed, including the “actual     sedation of a patient” and “the treatment of conditions that affect patient     comfort, such as pain and anxiety”. ...

95    The sub-set argument is included at [89] of InterPharma’s closing submissions, although these submissions evidently include other arguments, foreshadowed in opening, in support of the proposition that the relevant limitations are so unclear as to invalidate the claims.

96    At a general level, this is the position that is sought to be reflected in InterPharma’s Proposed Fourth Further Amended Particulars of Invalidity. By this document, InterPharma indicates that it seeks leave to incorporate paras (f) and (g) into the particulars to para 7A. These proposed particulars allege that it is not clear to the skilled reader:

(f)    … whether a patient outside a unit designated as an intensive care unit does or does not constitute a “patient in an intensive care unit”/“intensive care unit patient” referred to in claims 13 to 25 and 39 of the Patent and if so in what circumstances[; and]

(g)    … whether sedation of patients outside a unit designated as an intensive care unit does or does not constitute “intensive care unit sedation” referred to in claims 1 to 12, and claims 26 to 38, and if so in what circumstances.

97    In submissions filed, with leave, on 29 May 2018, Pfizer opposed the grant of leave to permit the incorporation of paras (f) and (g), on the basis that they alleged a new basis for invalidity and that the evidence at trial had been completed. Pfizer submitted that, had these amendments been made at trial, it might have questioned witnesses and cross-examined Professor Hall on relevant matters and that it had now lost the opportunity to do so. Pfizer also submitted that the proposed amendments were unclear and ambiguous.

98    Pfizer argued that the proposed paras (f) and (g) to the particulars to para 7A would give rise to new factual issues not in issue at trial, including as to whether a patient outside a unit designated as an “ICU” did or did not constitute an “ICU patient” and whether sedation outside a unit designated as an “ICU” did or did not constitute “intensive care unit sedation”.

99    Noting that amendments to the same or similar effect had been proposed in the earlier Third Further Amended Particulars of Invalidity filed on 11 May 2018, Pfizer also emphasised that InterPharma had added, without explanation, a reference to claim 39 in para (f) of the particulars to para 7A.

100    In any event, so Pfizer contended, it was apparent from the expert evidence that the skilled addressee would have no difficulty reading and understanding each of the claims in the context of the Patent and that invalidity did not arise by virtue of failure to comply with s 40(3) of the Patents Act on the basis that the expressions “patient in an intensive care unit”, “intensive care unit patient”, “intensive care unit sedation”, and “intensive care unit” lacked clarity.

101    Save for two matters, I am not persuaded that, if leave were granted, Pfizer would have missed a relevant opportunity to meet the case delineated by paras (f) and (g) to the particulars to para 7A of InterPharma’s Proposed Fourth Further Amended Particulars of Invalidity. It should be inferred from InterPharma’s written and oral submissions in opening that, in substance, InterPharma’s clarity case at the commencement of the trial was that the use in the claims of the relevant limitations deprived the claims of the requisite clarity because the concept of an ICU was not sufficiently clear before the priority date, and intensive care could be given both within and outside a designated ICU, the concept of ICU sedation was very broad, and the lack of clarity could not be resolved by reference to a defined class of ICU patients. InterPharma’s written opening submissions made it clear that its attack on clarity included the proposition that there was no clear boundary between the level of care in an ICU and the level of care in other hospital settings, and that, in this context, it was unclear whether “intensive care unit sedation” included the sedation of patients who were not in a designated ICU. These arguments were filled out at [88] and [91] of InterPharma’s closing written submissions, but they remained the same arguments. Doubtless, the addition of paras (f) and (g) to the particulars to para 7A of the Fourth Further Amended Particulars of Invalidity will elaborate on what was earlier set out in para 7A of the Further Further Amended Particulars of Invalidity. Save in two respects, this elaboration will merely express the case that InterPharma opened and ran at trial. Pfizer was put on notice of InterPharma’s case before the commencement of the trial, when InterPharma filed its opening written submissions. It is not the case that these proposed new particulars raise factual issues that were not raised at the commencement of, or during, the trial. This is, so it seems to me, confirmed by certain of the questions addressed to the medical experts, the answers to which were included in the Joint Report, by the course of some of the concurrent evidence, and by other evidence adduced by Pfizer in chief and in cross-examination.

102    It does not seem to me, however, that leave should be given to include the words “and if so in what circumstances” in either para (f) or (g) of the particulars to para 7A. The inclusion of these words would, in my view (and substantially for the reason identified by Pfizer in connection with the proposed amendment to the particulars to para 7B), enlarge the case beyond that made at the trial, after the close of evidence and to Pfizer’s prejudice since it has lost the opportunity to adduce evidence or cross-examine Professor Hall on relevant matters. In any event, the intended significance of these words is unclear.

103    Secondly, in the absence of any explanation by InterPharma as to the late incorporation of claim 39 into para (f) of the particulars to para 7A, leave to include a reference to claim 39 should be granted only on the basis that, as it is an omnibus claim, then if InterPharma were successful in this aspect of its invalidity case, any such success should flow through to claim 39 on the same basis and no other basis.

104    Accordingly, subject to these qualifications, leave is granted to InterPharma to amend its particulars to include paras (f) and (g) to the particulars to para 7A in its Proposed Fourth Further Amended Particulars of Invalidity (hereafter referred to as the Fourth Further Amended Particulars of Invalidity).

105    There was a second basis for the alleged invalidity of the Patent’s claims on the basis of lack of clarity, as set out in para 7B of InterPharma’s Further Further Amended Particulars of Invalidity. This referred to the limitation introduced by the expression “essentially the sole active agent or the sole active agent” in claims 2 to 12, 14 to 25, 27 to 37 and 39 (although claim 15 did not include this specific limitation but an analogous limitation “an active and an inactive agent”). The particulars to para 7B of InterPharma’s Further Further Amended Particulars of Invalidity relevantly alleged that it is not clear to the skilled reader:

(c)    … whether the administration of dexmedetomidine … with an anaesthetic, analgesic, anti-psychotic or a non-sedative agent in an intensive care unit constitutes its use as “essentially the sole active agent” for sedation and/or for sedating a patient.

106    By its Fourth Further Amended Particulars of Invalidity, InterPharma sought to add the words “or in what circumstances”, so that proposed para (c) of the particulars to para 7B alleged that:

(c)    It is not clear to the skilled reader whether or in what circumstances the administration of dexmedetomidine … with an anaesthetic, analgesic, anti-psychotic or non-sedative agent in an intensive care unit constitutes its use as “essentially the sole active agent” for sedation and/or for sedating a patient.

(Emphasis added)

107    InterPharma also sought to delete para (b) of the particulars to para 7B of its Further Further Amended Particulars of Invalidity.

108    In its 29 May 2018 submissions Pfizer opposed the grant of leave to add the words “or in what circumstances” to para (c) of the particulars to para 7B. As Pfizer noted, InterPharma has not provided any explanation as to why it seeks to add the words “in what circumstances”. It may be that the proposed amendment is intended to align the particulars to this paragraph more closely to InterPharma’s opening written submissions, which stated:

The word “essentially” indicates that dexmedetomidine may be co-administered with another agent. If the other agent is a drug with analgesic or anxiolytic qualities then, given that the Patent defines ICU sedation to include actual sedation and the treatment of pain or anxiety, it is not clear in what circumstances involving the administration of a second agent with analgesic or anxiolytic qualities, such as an opioid or benzodiazepine, the use of dexmedetomidine would fall within these claims.

(Emphasis added)

109    Viewed in this way, it may be that the proposed amendment to para (c) of the particulars to para 7B is not intended to expand InterPharma’s case beyond its submissions in opening. The precise import of the proposed amendment is, however, uncertain. On another reading, the amendment would, as Pfizer contended, substantially expand InterPharma’s case in relation to the clarity of the “essentially the sole active agent” limitation, by advancing an alternative case to that which InterPharma ran at trial. That is, the proposed addition of “or in what circumstances” might be thought to raise the possibility that:

if contrary to InterPharma’s pleaded case, it is clear to the skilled addressee that the administration of dexmedetomidine with an anaesthetic, analgesic, anti-psychotic or a non-sedative agent in an intensive care setting does or does not constitute use of dexmedetomidine as “essentially the sole active agent” for ICU sedation, … [then] it is not clear “in what circumstances” the administration of dexmedetomidine with such an agent constitutes use of dexmedetomidine as “essentially the sole active agent” for ICU sedation.

110    This question was not put in issue in the Further Further Amended Particulars of Invalidity or in any subsequent version of InterPharma’s Particulars of Invalidity. It was not raised at trial. The proposed amendment to para (c) would in this case prejudice Pfizer since it has lost the opportunity to adduce evidence or cross-examine Professor Hall about this issue. In any event, as before, the intended significance of the proposed additional words is unclear.

111    In these circumstances, I would not grant leave to amend para (c) of the particulars to para 7B. In any event, it does not seem to me that the amendment is necessary. InterPharma will not be prevented from advancing the case it has already run with respect to this limitation at trial.

112    Pfizer did not oppose the proposed deletion of para (b) of the particulars to para 7B of InterPharma’s Further Further Amended Particulars of Invalidity. Leave will be granted to make this amendment.

113    There was a third basis for the alleged invalidity of the claims for reason of lack of clarity set out in para 8 of InterPharma’s Further Further Amended Particulars of Invalidity. Paragraph 8 asserted that claims 3 to 12 and 38 do not comply with s 40(3) because “[i]t is unclear which ‘use’ in claim 1 is the intended ‘use’ in claims 3 to 12 and 38”. Further, it was asserted that to the extent that the “use” is:

… use of dexmedetomidine to make a medicament of claim 1 it is not clear to the skilled reader how this could be construed to include a method of administering the medicament of claim 1 to a patient as part of the process for making the medicament [; and]

… the “for use” defining the purpose of the medicament in claim 1 it is not clear to the skilled reader how the method or process of manufacturing the medicament of claim 1 could be construed to include a method of administering the medicament.

114    InterPharma sought to amend para 8 by substituting a reference to “claims 2 to 12” for the references to “claims 3 to 12”. Pfizer did not oppose a grant of leave to make this amendment. Leave will be granted to make this amendment.

115    There was a fourth basis for alleged invalidity on the basis of lack of clarity set out in para 9 of the Further Further Amended Particulars of Invalidity, which was said to relate to claims 23, 24 and 25 “on the grounds that [these] claims do not comply with the requirements of section 40(3) of the Patents Act in that the claims are not clear and succinct”. By its Fourth Further Amended Particulars of Invalidity, InterPharma sought to delete para 9. Pfizer did not oppose a grant of leave to make this amendment. Leave will be granted to make this amendment.

Overview of InterPharma’s submissions as to lack of clarity

116    InterPharma submitted in closing that:

(a)    none of the claims comply with s 40(3) of the Patents Act as it is not sufficiently clear from the claims when post-operative care outside a designated ICU constitutes a setting of intensive care within the meaning of those claims;

(b)    claims 2, 14 and 27 (and their dependent claims and claim 39) do not comply with s 40(3) as it is not sufficiently clear from the claims what is meant by the expression “essentially the sole active agent”; and

(c)    claims 2 to 12 and 38 do not comply with s 40(3) as it is not sufficiently clear from the claims how the purported Swiss-style dependent claims are intended to be construed.

117    In closing submissions InterPharma also contended that claims 3, 16, and 28 (and dependent claims 4 to 12, 17 to 25 and 29 to 36) do not comply with s 40(3) as it is not sufficiently clear from the claims what is meant by the expression administration of dexmedetomidine “in an amount to achieve a plasma concentration of 0.1-2 ng.ml”. This allegation is not to be found in the relevant Particulars of Invalidity. Pfizer did not make any submission about this omission, and I shall address it in these reasons in the manner it was argued (see [201]-[208] below). InterPharma made no submission in this regard about claim 37.

All claims: lack of clarity from use of the expressions “for use in intensive care unit sedation”; “a patient in an intensive care unit”; “an intensive care unit patient”; and “in the intensive care unit sedation”?

118    The Patent relates to the sedation of ICU patients. As already noted, InterPharma contended that all of the claims of the Patent lack clarity because the concept of an ICU, which was a limiting feature of all claims, lacked a sufficiently clear meaning before April 1998 to define the monopoly precisely.

119    Noting that the Patent states that “the word intensive care unit includes any setting that provides intensive care”, InterPharma contended that the lack of clarity arose because the Patent did not further describe the features of such a setting. Referring to the experts’ evidence that intensive care could be given outside a designated ICU, InterPharma submitted that there was no clear boundary between what was, and was not, an ICU setting. No such boundary existed, so InterPharma submitted: (a) between the level of monitoring and care for patients not on life-support in an ICU and the level of monitoring and care that such patients received in a high care post-operative unit or a high dependency unit; or (b) by reference to the overseeing specialist since not every intensive care setting was overseen by such a specialist. Although the experts were in broad agreement about the characteristics of an ICU, InterPharma submitted that “the fact that there are these other non-ICU units complicates where the edge is” and the experts were not agreed on “where the border of where they understood it to be an ICU … is”.

120    InterPharma further submitted that the concept of an “ICU patient” could not clarify the meaning of an ICU, because there was no definition of an ICU patient in the Patent, and patients in an intensive care setting were, so the experts agreed, a heterogeneous group and even more so in hospitals in regional centres than in cities. In any event, InterPharma emphasised that whether or not a given patient was in an ICU depended on clinical judgment, the availability of ICU beds and other care options.

121    InterPharma also submitted that the concept of ICU sedation could not clarify the meaning of an ICU, because: (1) ICU sedation could be administered to any patient in an intensive care setting; and (2) ICU sedation was to be broadly construed to include not only “actual sedation” but also “the treatment of conditions that affect patient comfort, such as pain and anxiety”. InterPharma noted that the Patent states that many drugs were only considered sedatives in the context of ICU sedation and that the concept of ICU sedation under the Patent extended to administering any agent to a patient who is in any ICU setting, where the agent helped to keep the patient calm and allowed them to tolerate their treatment. InterPharma further noted that the Patent claimed levels of sedation on the Ramsay Scale from 2 to 6.

122    Pfizer contended that the skilled addressee would have no difficulty in identifying “an intensive care unit”, as that expression was used in the claims and that the claims were not made doubtful or unclear by the use of the expressions “for use in intensive care unit sedation”, “a patient in an intensive care unit”, “an intensive care unit patient”, or “in the intensive care unit sedation”. I accept Pfizer’s submission in this regard, for the reasons I am about to give.

123    It may be accepted that the expression “intensive care unit” and its cognate expressions, “for use in intensive care unit sedation”, “a patient in an intensive care unit”, “an intensive care unit patient”, and “in intensive care unit sedation”, are limitations, in one or other form, of all the claims of the Patent.

“Intensive care unit”

124    As used in the Patent, the expression “intensive care unit” and its acronym “ICU” can refer to any setting that provides intensive care. The specification specifically explains that “the word intensive care unit includes any setting that provides intensive care”.

125    Professors Hall and Bellomo and Assoc Professor French had no difficulty in identifying “a setting that provides intensive care”. This is apparent from their Joint Report, where, in answer to the question, “[w]hat is a setting that provides intensive care?”, they replied that:

The ICU is a defined area within a hospital. It contains specially trained medical and nursing staff at high staff patient ratio and contains continuous patient monitoring and life support equipment.

126    Nor did the medical experts have any difficulty identifying an ICU patient. In answer to the question, “[w]ho is an ICU patient?”, their agreed response in their Joint Report was that:

Intensive care patients are those who require specialised treatments or a level of monitoring that is not able to be provided in a general hospital environment.

127    The three medical experts agreed upon the identifying characteristics of an intensive care setting, by reference to the type of patients, the type of care, the type of monitoring, the ratio of nurses or doctors to patients and the direct supervision of an exclusively rostered specialist. Their evidence was that, prior to April 1998 (and now) there were (and remain) areas within hospitals designated as ICUs, which have certain characteristics, such as specially trained medical and nursing staff at a high staff-patient ratio, continuous patient monitoring, and life support equipment.

128    Professor Bellomo’s evidence was that the term “intensive care unit” or “ICU” refers to an area in a hospital dedicated to the care of the sickest patients in the hospital; and that, in Australia, in 1998, an ICU typically had:

(a)    one to one nurse to patient ratio at all times;

(b)    senior doctors (including intensive care specialists) available 24 hours a day;

(c)    advanced trainee doctors and residents available 24 hours a day; and

(d)    continuous monitoring.

129    Professor Hall stated in evidence that he agreed with Professor Bellomo’s account of the typical characteristics of an ICU, but would add reference to the availability in an ICU of continuous intravenous infusion. Professor Bellomo and Assoc Professor French later stated their substantial agreement with Professor Hall and that continuous infusion of sedatives was unlikely to be found outside the operating theatre or the ICU. Similarly a bolus administration was almost exclusively given in an ICU. This is also consonant with the Joint Report.

130    Professor Bellomo’s evidence was that, immediately before April 1998 (and now), intensive care medicine (involving the assessment, stabilisation and ongoing care of patients who required advanced life support and/or advanced monitoring as a result of life-threatening illnesses, conditions, injuries or complications) was typically conducted in an ICU. His evidence was that an intensive care specialist was required to assess and repeatedly reassess vital functions, including breathing rate, oxygen and carbon dioxide levels, concentrations of key elements in the blood, blood pressure, heart rate, brain function, liver function and kidney function. This occurred in an ICU.

131    All three medical experts agreed that the ICU environment (or setting) can be distinguished from other hospital settings where nurse to patient ratios are lower, moment to moment patient care is not required and certain life supports, such as mechanical ventilation, are not available. In the opinions of Professor Bellomo and Assoc Professor French, immediately before the priority date (as now) a high care post-operative unit, a high care dependency unit, a coronary care unit and a step-down unit were (and are) relevantly distinguishable from an ICU because of the differences in type of patients, type of care and type of monitoring within them. Professor Hall agreed that, in his North American experience, the differences between these units was “more than language and [the] name on the door”.

132    For example, Professor Bellomo said in evidence:

My view is that the high-care post-operative area, or the high-dependency unit, as we often refer to in Australia, is a separate entity, and it is so named because it is a separate entity even though it has some features of monitoring and treatment that resemble those of the ICU.

…

The location of a high-dependency unit, geographically, may be within the structure, or the room or the floor of the ICU, or may be actually entirely physically separate, depending on hospitals, but the type of patients, and the type of care, and the type of monitoring and the ratio of nurses to – or doctors to patient is different from that of the ICU, hence a different name for it.

133    Assoc Professor French also gave evidence that:

[I]t’s not just the type of patient and the level of monitoring and the level of nursing staff, but another feature of an Intensive Care Unit in Australian practice is that it’s under the direct supervision of an exclusively rostered intensive care specialist. And, in general, the majority of stand-alone high-dependency units, coronary care units and step-down units don’t have that same overarching medical structure and leadership. So at least in the Australian context, an Intensive Care Unit is all those things that Professor Bellomo described, plus having that overarching medical leadership from an appropriately trained intensive care specialist.

134    Assoc Professor French acknowledged that hospital arrangements in regional centres may differ a little from arrangements in the cities in that, for example, in regional centres an ICU might not be under the direct supervision of an intensive care specialist, but would usually be under the direct supervision of an exclusively rostered doctor in a related discipline, such as anaesthesia. Such a doctor would, for example, “be working as a consultant anaesthetist but would also be, at times, exclusively rostered to the Intensive Care Unit”.

135    Both Professor Bellomo and Assoc Professor French agreed that, in Australia, variations in patient demand and the availability of resources at any one time might determine patient placement in some cases. Professor Bellomo’s evidence was that “the logistics, the resources, the needs, the financial burden and the patient type of operations” may result in different patient placements. He said that “[s]ometimes we have to triage. The demand on the ICU beds is greater than the availability and we have to make decisions about how best to manage the resources available”.

136    Professor Bellomo’s evidence concerning ICUs and the existence of comparable areas within a hospital, the practice of intensive care medicine, and the effect of patient demand and resource constraints was compelling. As already noted, he had well over 25 years’ experience in the practice of intensive care medicine in hospitals in Australia. This was apparent in the evidence he gave. His evidence was, moreover, supported by that of Assoc Professor French and in some material respects (as indicated above and allowing for differences in Australian and US hospital arrangements) by that of Professor Hall.

137    In substance, the evidence of the medical experts established that ICUs and intensive care settings in Australia were readily identifiable immediately prior to April 1998 by reference to their typical features, which were a one to one nurse to patient ratio, constant availability of senior doctors and advanced trainee doctors and residents, continuous monitoring, and the availability of continuous intravenous infusion. Put another way, the evidence established that as at April 1998 the ICU environment (or setting) could be readily distinguished from other hospital settings because of the differences in the type of patients, the type of care, the type of monitoring, the ratio of nurses to patients, the availability of doctors and supervision by an exclusively rostered specialist.

138    It is true, as InterPharma noted, that Assoc Professor French’s evidence was that the ICUs in hospitals in regional centres might not be under the direct supervision of an intensive care specialist, although they would be under the direct supervision of an exclusively rostered doctor in a related discipline. It does not seem to me that this diminished his evidence that an ICU was different from other areas of a hospital. Rather, this evidence showed that the same kind of arrangements were made for ICUs in regional centres and city hospitals, necessarily adjusted to take account of a difference in the availability of medical specialist staff. For like reasons, it does not seem to me that the fact that the availability of resources and patient demand at any one time might determine patient placement in or out of the ICU militated against the fact that the skilled addressee would well understand the concept of an ICU, including a setting that provides intensive care. This kind of triage reflected a different consideration, namely, how best to manage finite resources.

139    Each of Pfizer and InterPharma sought to call in aid the definition of “Intensive Care Unit” in item T1.7 of the Medicare Benefits Schedule Book (operating from 1 November 1997) (Medicare Benefits Schedule). InterPharma submitted that the definition was different from a description given by Assoc Professor French. Pfizer submitted that the definition was broadly consistent with the evidence of the medical experts. It does not seem to me that much turned on the differences between the medical experts’ evidence as to the typical identifying characteristics of an ICU and the definition in the Medicare Benefits Schedule, bearing in mind the nature and function of the Medicare Benefits Schedule. At most, the Medicare Benefits Schedule highlighted that, at the level of payment to individuals to meet hospital and medical expenses, the concept of an ICU was well-recognised.

140    Further, it does not appear to me that the experts’ disagreement about the study in Talke (discussed below) militates against the conclusion that the skilled addressee would have readily understood the concept of an “intensive care unit” or ICU immediately before the priority date in Australia.

141    The expression “intensive care unit” and its acronym “ICU” as used in the Patent would have been well-understood and its meaning would be clear to a skilled addressee immediately before the priority date in Australia. The skilled addressee in Australia as at that date would have been readily able to identify an ICU and any setting that provided intensive care.

“Patient in an intensive care unit”; “intensive care unit patient”

142    The parties did not suggest that there was any relevant difference between the expressions “patient in an intensive care unit” and “intensive care unit patient”. As noted above, the experts agreed about who were “intensive care unit patients”, being, in the words of their Joint Report, “those who require specialised treatments or a level of monitoring that is not able to be provided in a general hospital environment”. The experts agreed, moreover, that in the context of the Patent “patient in an intensive care unit” meant “[a]ny patient in an environment that provides intensive care”.

143    It may be recalled from the earlier discussion of InterPharma’s lack of clarity submissions that InterPharma contended that the concept of an ICU patient cannot clarify or confine the meaning of an ICU; there is no definition of an ICU patient in the Patent; and whether a patient became an ICU patient depended on clinical judgment and other extraneous matters. In so far as these submissions alleged a relevant lack of clarity in the expressions “patient in an intensive care unit” and “intensive care unit patient”, I would reject them for the following reasons.

144    The evidence established that in order to become an ICU patient, a patient must be admitted to an ICU in accordance with the applicable admissions policy. The evidence of Professor Bellomo and Assoc Professor French was, and I accept, that the intensive care specialist on duty would first determine whether intensive care would benefit the patient. Professor Bellomo agreed with Assoc Professor French’s evidence that the duty intensivist would:

… make an overall assessment whether the treatments that we can offer in the ICU are of benefit to the patient and those benefits outweigh the risks, or they make an assessment whether the patient’s level of disease is such they could be managed in a general ward environment.

145    When asked by the Court what united patients in the ICU environment, Professor Bellomo agreed that it was either that they had a life-threatening condition or that they were at risk of a life-threatening condition if things went wrong. This was consistent with Professor Bellomo’s evidence that immediately before the priority date ICU patients were a unique class of hospital patients, united by their need for advanced life support and/or advanced monitoring. He said that between 50% and 80% of ICU patients required intubation in order to allow for mechanical ventilation.

146    Professor Bellomo also said in evidence that the individual characteristics of ICU patients were very variable, and that such patients might arrive from various places, including emergency departments, operating theatres and other specialties within hospitals. Notwithstanding this variability, he emphasised that the care of ICU patients was complex, bearing in mind that most had unstable vital functions; required multiple medications administered in various ways; were under excessive physiological and psychological stress; and were subject to complex interacting conditions. Assoc Professor French gave evidence to similar effect. I accept their evidence in that regard. I also accept Professor Bellomo’s evidence that, while patients in an ICU might be described as heterogeneous because their individual characteristics were variable, the ICU patients at the priority date were critically ill patients, whose care was complex. All the medical experts agreed that the most severely ill patients often had multiple organ failures, while other critically ill patients might not be experiencing organ failure but be assessed to be at risk of complications or deterioration, for example, after major surgery or because of a medical condition.

147    The expressions “patient in an intensive care unit” and “intensive care unit patient” as used in the Patent would have been well-understood and their meaning would have been clear to a skilled addressee immediately before the priority date in Australia. A skilled addressee in Australia as at that date would have been readily able to identify a “patient in an intensive care unit” or an “intensive care unit patient”; and I would reject InterPharma’s submissions to the contrary.

“Intensive care unit sedation”

148    It may also be recalled from the earlier discussion of InterPharma’s lack of clarity submissions that InterPharma contended that the concept of ICU sedation could not confine the meaning of an ICU; that ICU sedation could be administered to any patient who is in an intensive care setting; and that the concept is to be broadly construed, including the “actual sedation of a patient” and “the treatment of conditions that affect patient comfort, such as pain and anxiety”. In so far as these submissions alleged a relevant lack of clarity in the expression “intensive care unit sedation”, I would reject them for the following reasons.

149    In their Joint Report, in answer to the further question, “[w]hat is ‘ICU sedation’?”, the three medical experts agreed that:

ICU sedation is the administration of medication to ICU patients in circumstances where it is necessary so that the patient can tolerate and accept intensive care treatments and environment, for example, the presence of an endotracheal tube to enable mechanical ventilation.

150    It should be observed that this statement about ICU sedation focussed on inducing patient tolerance and acceptance of intensive care treatments and environment by administering medication. The experts agreed that this was what “ICU sedation” meant in the Patent.

151    The medical experts emphasised that the concept of sedation was different to sleep. They agreed that what was meant by “sedation” differed, depending on the medical context, and that the concept of sedation in an ICU was relevantly different from the concept of sedation in other contexts.

152    Professor Hall’s evidence, which I accept, was that sedation involved bringing an ICU patient into a calmer state, along a spectrum from agitated to tranquil, tranquil to asleep. His evidence also was that a patient was brought into a calmer state, in order that the patient could accept intensive care treatment. He observed that calming a patient for this purpose did not always involve medication and might, for example, involve repositioning a mechanical device if that was making the patient uncomfortable, talking with patients and involving their family to allay the patient’s fears, and even medicating to address a “pure source of pain”. Professor Hall added that “we would go to medication that would calm them” only after going through such a checklist.

153    In order to appreciate Professor Hall’s evidence about the purpose of sedation, it is useful also to refer to his evidence that:

Within an ICU, patients have varying sedation needs. In an ICU a patient is very likely to have one or more devices in them, such as peripheral intravenous catheters (IVs), larger catheters going into a major vessel of the body to deliver medications or for monitoring (for example, arterial catheters, where the device is put in and left in the artery of the wrist or the groin) and, in the majority of cases, endotracheal tubes that pass over the tongue and into the airways to allow mechanical ventilation (or “machine breathing”).

…

[M]ost ICU patients are in a state somewhere between mild discomfort and severe pain and are anxious or agitated.

154    I interpolate here that the medical experts agreed that, as at April 1998 (and today), sedatives were (and are) normally administered in an ICU by continuous infusion, although a bolus might first be used if the rapid onset of sedation were desired. Professor Hall stated, and it was not disputed, that the amount of sedatives administered per patient is much higher in an ICU than in a general ward and that a patient being continuously infused with a sedative needs to be continuously monitored, as his or her dosage may need to be titrated.

155    Professor Hall’s evidence about the purpose of sedating an ICU patient was consistent with the evidence of Professor Bellomo and Assoc Professor French. The evidence of Professor Bellomo and Assoc Professor French was that immediately before the priority date (and today) the concept of ICU sedation involved affecting an ICU patient’s awareness or alertness to some degree to induce calm and allow the patient to accept treatment. In Professor Bellomo’s words:

“ICU sedation” … refers to the administration of a drug or drugs to an ICU patient that affect the patient’s awareness to some degree to induce calm and allow the patient to tolerate their circumstances, including necessary medical interventions such as mechanical ventilation and procedures.

Assoc Professor French deposed that:

[S]edation in an ICU or, “ICU sedation”, is the administration of medication to ICU patients in circumstances where it is necessary so that the patient can tolerate and accept intensive care, for example, the presence of an endotracheal tube to enable mechanical ventilation. ICU sedation generally affects the ICU patient’s level of alertness to some degree.

156    The three medical experts agreed that, immediately before April 1998, there was “a variable spectrum on the appropriate level of sedation depending on the patient’s circumstances and response to the drugs”. Professors Hall and Bellomo, in particular, explained this idea in similar terms. They agreed that the target level of sedation for an ICU patient would be likely to vary in the course of treatment. Professor Bellomo’s evidence was that the target for sedation was “dynamic, … related to the patient’s condition, to [the] therapeutic intent, to what you’re intending to do [to] the patient”, for example:

… whether you’re going to put lines or do interventions that would be upsetting the patient[,] whether the patient’s wakefulness might mean that the patient interacts with a breathing machine in a way that is dissynchronous … [a]nd, of course, whether the illness has begun to resolve or has resolved, therefore, justifying the step in the direction of awakening the patient with the intent to remove the ventilator.

157    Depending on the particular needs of the patient, Professor Bellomo’s evidence was that:

ICU sedation may involve drug induced calmness and tolerance, without drowsiness, or it may involve drug induced calmness and tolerance together with some level of drowsiness ranging from light drowsiness to deep “sleep”.

Assoc Professor French made it clear that this remained the case today. His evidence was that the level of sedation would vary, depending on the patient’s needs, from moderate to deep sedation, “to no sedation, and just analgesia”.

158    It is in this context that the Patent specification’s description of levels of sedation equivalent to a Ramsay Sedation Score of 2 (patient co-operative, oriented and tranquil) to 6 (asleep, no response) is to be understood. None of the claims contain a limitation as to the level of sedation.

159    The experts also understood that there was a distinction between administering a medication to address pain and/or anxiety and medicating for sedation. Professor Hall made this point in the evidence to which I have already referred in which he said that intensivists would resort to medicating to calm an ICU patient so as to accept intensive care treatment only after they had endeavoured to allay the patient’s fears through talking and family support and by administering an analgesic for pain-relief. In particular, Professor Hall said:

I think by elimination, … [if] a patient remains agitated despite those things being gone through on a checklist or addressed and then we would go to a medication that would calm them, yes.

160    The same understanding is reflected in Assoc Professor French’s observation that the level of sedation would vary, depending on the patient’s needs, from moderate to deep sedation, “to no sedation, and just analgesia”.

161    InterPharma submitted in closing submissions that:

ICU sedation under the Patent plainly extends to administering any agent to a patient who is in any ICU setting, where the agent helps to keep the patient calm and allow them to tolerate their treatment. ICU sedation must include, for example, administering an analgesic such as opioid as well as anxiolytic and anaesthetic agents such as benzodiazepines, propofol, and barbiturates.

162    This submission involves a level of confusion that was not evident in the evidence of the experts. Their evidence established that, immediately before the priority date, a drug administered for the purpose of sedating a patient in an ICU was a drug administered for the purpose of inducing calmness in the patient so as to facilitate the patient’s acceptance of intensive care treatment. Where a drug was administered in order to treat pain or anxiety without inducing such calmness and acceptance, that drug was not acting as a sedative agent. Where, for example, an analgesic drug does not have any sedative properties at the dose being administered to an ICU patient, then it is acting as an analgesic but it is not acting as a sedative agent as understood in an ICU.

163    In support of its contention that ICU sedation in the context of the Patent includes sedation or treatment of pain and anxiety, InterPharma relied on the Patent specification at p 2, lines 2-3, which states that “sedation also includes the treatment of conditions that affect patient comfort, such as pain and anxiety”.

164    As the medical experts explained, opioids such as morphine may be seen as an analgesic or a sedative, depending on the dose that is administered. The same or a similar difference, depending on dose, is manifest in other classes of drugs.

165    In answer to my question, “[i]f you were administering morphine … you wouldn’t regard that as a sedative, though, would you?”, Professor Bellomo said:

It depends on the dose that you give of morphine. So, for example, if somebody gave me maybe by continuous infusion 0.5 of a milligram, it would be unlikely that [I] would be sedated but if they gave me 10 milligrams, I would be profoundly sedated. So it’s a dose relationship.

If a high sedating dose is administered, then the morphine is being used as a sedative, whilst at a lower dose the morphine will be used as an analgesic. Professor Bellomo’s evidence was that morphine had been administered at a high sedating dose in ICUs in the 1990s and was regarded as an ICU sedative when used in this way.

166    Against this background, I accept Professor Bellomo’s evidence that the passage at p 2 of the Patent identifies that, in addition to a sedative effect, “sedation also includes treatment of conditions that affect patient comfort, such as pain and anxiety and so on” and that this passage was consistent with the experts’ agreed understanding of the meaning of “ICU sedation”, as stated in their Joint Report. Professor Bellomo’s evidence in this regard is also consistent with the subsequent statement in the specification (at p 3, lines 23-25) that “[a]n ideal sedative agent for a critically ill patient should provide sedation … . Further, it should be an anxiolytic and an analgesic … ”. Professor Bellomo was clear, however, that, in the context of the Patent, the administration of morphine for pain alone was not to be understood as the use of morphine as an ICU sedative. Having regard to the way the drug worked when administered to patients in an ICU, whether or not morphine was used as an analgesic or sedative was, to use his own words, “very much dependent on the dose”.

167    For the reasons stated, a skilled addressee in Australia immediately before the priority date would have had no difficulty understanding the expression “in the intensive care unit sedation” as used in the Patent and would have been readily able to identify whether or not a drug was administered “in the intensive care unit sedation”. I would reject InterPharma’s submissions to the contrary.

168    For the reasons stated, I reject InterPharma’s submissions that the claims lacked clarity by reason of the use of the expressions “for use in intensive care unit sedation”; “a patient in an intensive care unit”; “an intensive care unit patient”; and “in the intensive care unit sedation”. Further, it would have been clear to a skilled addressee that none of these concepts was limited by reference to any particular sub-set of patients in the ICU and that such a limitation was not required in the interests of clarity.

Claims 2, 14, 27 (and their dependent claims): lack of clarity from use of the expression “essentially the sole active agent or the sole active agent”?

169    Each of claims 2, 14 and 27 relate to the use of dexmedetomidine in ICU sedation, wherein the dexmedetomidine is “essentially the sole active agent or the sole active agent”. There are numerous dependent claims. As to claim 15, see [187] below.

170    In opening written submissions filed before trial, InterPharma’s submissions as to lack of clarity included that the meaning of “essentially the sole active agent” was not sufficiently clear before April 1998 to define the precise boundary of Pfizer’s monopoly. It was said that:

The word “essentially” indicates that dexmedetomidine may be co-administered with another agent. If the other agent is a drug with analgesic or anxiolytic qualities then, given that the Patent defines ICU sedation to include actual sedation and the treatment of pain or anxiety, it is not clear in what circumstances involving the administration of a second agent with analgesic or anxiolytic qualities, such as an opioid or benzodiazepine, the use of dexmedetomidine would fall within these claims.

171    As noted earlier, InterPharma alleged in para 7B of its Further Further Amended Particulars of Invalidity that it is not clear whether the administration of dexmedetomidine with an anaesthetic, analgesic, anti-psychotic or a non-sedative agent in an ICU constitutes its use as “essentially the sole active agent” for the purpose of ICU sedation.

172    In closing submissions, InterPharma drew attention to the fact that in their Joint Report, the medical experts agreed that the term “essentially the sole active agent” was “a difficult term to understand”, and submitted that their agreed interpretation could not assist in determining the circumstances in which the use of dexmedetomidine with another sedative or analgesic agent would be considered as the use of dexmedetomidine as “essentially the sole active agent” in the claimed method. In this context, InterPharma relied on Professor Hall’s evidence that he would have “no ability to draw any line” between a case in which the drug was used as “essentially the sole active agent” and another case where the drug was administered not as “essentially the sole active agent”, and with an anaesthetic or non-sedative agent. InterPharma also referred to the difficulty that each of Professor Bellomo and Assoc Professor French said that they had in drawing this line, and the fact that none of the experts could say where that line lay. InterPharma contended that there was no clear boundary defined by the expression “essentially the sole active agent” that could be drawn by the person skilled in the art, and that the lay understanding of “essentially” did not have any clinical significance. Senior counsel for InterPharma submitted that:

[I]n the context … where this Patent defines sedatives in an ICU far more broadly than they are understood outside the ICU ... we say this claim really has no boundary that any of the experts were able to articulate.

173    InterPharma contended in the alternative that, if the term “essentially” had a sufficiently clear meaning, then the effect of the term is that the sole agent claims permit the co-administration of dexmedetomidine with a second agent, provided that the second agent is not administered for sedation but for a different purpose such as analgesia. It submitted that this construction was consistent with the evidence from the experts that an analgesic agent is not ordinarily understood by those in the field as a “sedative agent”. For the reasons outlined below, I accept this alternative construction (see [181]-[186]).

174    I accept that, as Pfizer submitted (and contrary to the assertion in para 7B of InterPharma’s Further Further Amended Particulars of Invalidity: see [171]), none of the experts considered that the administration of dexmedetomidine with an anaesthetic or other agent administered for the purpose of ICU sedation consisted the use of dexmedetomidine as “essentially the sole active agent or the sole active agent”. This was, as Pfizer submitted, an absurd construction, which was to be avoided.

175    As will also be apparent by now, much of InterPharma’s clarity case at this point in fact depended on the alleged lack of clarity introduced by the word “essentially”. Whilst InterPharma’s Further Further Amended Particulars of Invalidity were themselves far from clear in this regard, it seems to me that this was the case that it ran at trial.

176    Pfizer submitted, and I accept, that the expression “essentially the sole active agent or the sole active agent” described the administration of dexmedetomidine by itself or “essentially” by itself for the purpose of ICU sedation. Pfizer submitted that although the use of the word “essentially” involved some imprecision, it did not involve any lack of clarity. For the reasons stated below, I agree that the expression does not lack clarity in the relevant sense.

177    Reference to the Patent confirms that this is what is intended by the expression. In discussing the background to the invention, the specification identifies that patients in an ICU may receive a variety of drugs concurrently. It further identifies that the most commonly used drugs are given for patient comfort; that such drugs are “cumulatively called sedatives in the context of ICU sedation”; and that many are not considered sedatives in any other context. The specification further states that “the combination of these agents (polypharmacy) may cause adverse effects”, and that “[p]referably, an ideal sedative agent should be used by itself in ICU sedation to avoid the dangers of polypharmacy”.

178    The Patent states that the invention relates to a method of sedating a patient in the ICU by administering dexmedetomidine. One aspect of the invention is identified as follows:

Particularly, the present invention relates to a method of sedating a patient while in the ICU by administering dexmedetomidine … wherein dexmedetomidine is essentially the sole active agent or the sole active agent administered for this purpose.

(Emphasis added)

179    There is a further description in the specification of this method of sedating a patient in an ICU by administering dexmedetomidine, wherein dexmedetomidine is essentially the sole active agent or the sole active agent, where it is said that:

The method is premised on the discovery that essentially only dexmedetomidine … need[s] to be administered to a patient in the ICU to achieve sedation and patient comfort. No additional sedative agents are required.

The specification makes it clear that this method looks to the totality of the drugs administered to an ICU patient for the purpose of ICU sedation.

180    The medical experts had no difficulty in interpreting the words “sole active agent”. In their Joint Report they agreed that “[s]ole active agent means only one agent being used”. This was confirmed in their concurrent evidence, where they agreed that “sole active agent” meant “a single agent … is being administered to calm th[e] patient”. Further, and consistently with this, Assoc Professor French said that, in his opinion, dexmedetomidine would be the “sole active agent” where it is the only agent administered to the patient for the purpose of ICU sedation. This aligned with Professor Hall’s evidence that he understood this limitation to mean that “in what is being infused, the only thing that could account for any sedative effect, whatever its quality, is dexmedetomidine”.

181    In their Joint Report, the medical experts also agreed that the words “essentially the sole active agent” mean “that the agent is being administered with another agent that has either sedative and/or analgesic properties”. Professor Bellomo’s evidence was that he understood “essentially sole active agent or sole active agent” to refer to a situation where dexmedetomidine was “essentially the only agent or the only agent administered to the patient for the purpose of achieving ICU sedation”.

182    In the course of concurrent evidence, Professor Bellomo said that whilst he agreed with Professor Hall that the expression “essentially the sole active agent” is “different and difficult because it is difficult to perceive a specific dose that would be limited in significance and impact on the sedation”. He added:

Nonetheless, I took the view that, in common conversation and lay conversation, essentially would mean that somewhere in the perception of the assessor, that about 90 per cent of the perceived sedation was thought to or believed to come from dexmedetomidine, and a little bit extra was thought to be coming from the morphine or the fentanyl. I took it to mean in a lay sense. I understand the difficulty in drawing the line, but I … assumed it to be indicative that a small amount of another drug which was doing just a little bit of assistance was the scenario [that was] referred to in the Patent.

Assoc Professor French agreed with this interpretation.

183    Professor Bellomo’s evidence was that the “line” to which Professor Hall referred was “very much dependent on the dose”:

… because even if … one mentioned a specific dose in milligrams, a specific dose would have a completely different effect in a 130-kilo man and an 82 year old 50-kilogram lady. … That’s why we said we had trouble with that argument. And that’s why we ended up describing a commonsensical understanding of that word, but not a specific or a medical understanding of that word … .

184    By way of example, Professor Bellomo explained that, in his view, dexmedetomidine would be “essentially the sole active agent” if administered to a patient for the purpose of achieving ICU sedation when administered at a maintenance dose of around 1-1.5 µg/kg/h in conjunction with a low dose of morphine, for example, at around 1-2 mg/hr. Professor Bellomo further explained that:

If you’re using two drugs like we use with morphine and midazolam, the way we used them in the 90s, very much equivalent contribution, I would not regard that as essentially the sole [active agent]. There was very much a partnership of equal. I would regard it as a sole [active agent] when one of the additional drugs would be seen to make a minimal contribution to the entire therapeutic endeavour.

185    Assoc Professor French gave evidence that, in his opinion, dexmedetomidine would be “essentially the sole active agent” when dexmedetomidine was administered as the dominant agent for the purpose of ICU sedation, where more than one drug was administered, for example, where a patient was given a low dose of morphine for pain relief along with dexmedetomidine for ICU sedation. He added that in that situation, in his view, dexmedetomidine was essentially the sole active sedative agent, acknowledging that morphine at a low dose has mild sedative effects.

186    This practical, common-sense construction, which I accept, provides a workable standard suitable to the intended use. InterPharma, supported by Professor Hall, said in effect that the use of the word “essentially” in the expression “essentially the sole active agent or the sole active agent” made it impossible to determine the boundary of the claim to monopoly. I reject this proposition. Plainly enough, as Professor Bellomo’s examples illustrate, what is “essentially” the sole active agent is a question of degree and, to that extent, a matter for judgment, but it does not seem to me to give rise to any ambiguity or other lack of clarity. Its meaning is clear, although in each case it will be a question of fact and degree as to whether dexmedetomidine is administered to a patient in an ICU as “essentially the sole active agent or the sole active agent” for the purpose of ICU sedation. Having regard to the evidence of Professor Bellomo and Assoc Professor French, understood in this practical, common sense way, it seems to me that a person skilled in the art would have little difficulty in practice in resolving the question, and in ascertaining whether what was proposed to be done fell within the ambit of the claims.

187    In this context, it may be observed that InterPharma included claim 15 in para 7B of its Further Further Amended Particulars of Invalidity, even though claim 15 included a different though verbally similar integer — “administering a pharmaceutical composition … [which] comprises an active agent and an inactive agent, wherein the active agent consists of dexmedetomidine”. In closing written submissions, InterPharma submitted that the inclusion of that integer required that dexmedetomidine be the only active agent of the pharmaceutical composition that is administered. For present purposes, this may be accepted. InterPharma also submitted that “[i]t may be noted that nothing in claim 15 precludes the administration of a further pharmaceutical composition with the claimed pharmaceutical composition. It is unclear precisely what InterPharma intended by this latter statement, and, in any event, the parties did not address it. To the extent that InterPharma challenged the validity of this claim on the basis of lack of clarity, that challenge should be rejected. It put forward nothing more to advance such a case.

188    It follows, for the reasons stated, that I reject InterPharma’s submission that there was a lack of clarity in claims 2 to 12, 14 to 25, 27 to 37 and 39 by virtue of the integer, “essentially the sole active agent or the sole active agent” (or the analogous integer in claim 15), such that the relevant claims were invalid.

Claims 2 to 12 and 38: lack of clarity as to how purported Swiss-style dependent claims are to be construed?

189    As indicated above, para 8 of InterPharma’s Fourth Further Amended Particulars of Invalidity alleged that claims 2 to 12 and 38 do not comply with the requirements of s 40(3) of the Patents Act in that the claims are not clear. In Particulars to para 8 InterPharma claimed:

(a)    Claim 1 is a Swiss style claim, properly characterised as a method or process of making the claimed medicament.

(b)    Claims 2 to 12 and 38 are ultimately dependent on claim 1 and claim “the use according to claim 1”.

(c)    It is unclear which “use” in claim 1 is the intended “use” in claims 2 to 12 and 38.

(d)    To the extent that the “use” is use of dexmedetomidine to make the medicament of claim 1 it is not clear to the skilled reader how this could be construed to include a method of administering the medicament of claim 1 to a patient as part of the process for making the medicament.

(e)    To the extent that the “use” is the “for use” defining the purpose of the medicament in claim 1 it is not clear to the skilled reader how the method or process of manufacturing the medicament of claim 1 could be construed to include a method of administering the medicament.

190    In opening address at trial, senior counsel for InterPharma elaborated on this argument in the following terms:

Claim 2 can be read as a Swiss-claim in that there’s the making of the medicament and, in that medicament, [dexmedetomidine] is the sole – or essentially the sole active agent in that medicament. The difficulty is when one applies Pfizer’s construction … we have the Swiss-claim, which is a method for manufacture, but it has now turned into a method of administration addressed to the doctor.

…

… It could be construed as to the medicament and whether dexmedetomodine is in the medicament with something else, and that would be our construction on claim 2, but claim 3 doesn’t work, in that it is a direction to the manufacturer making the medicament, as well as the clinician who is administering it. … So we say that that claim is a bit unclear, because it’s a Swiss-claim tangled up with a method of administration addressed to two different people.

191    In closing written submissions, InterPharma reiterated its opening submissions, submitting that the balance of claims 4 to 12 and 38 suffered from the same default.

192    In opening address at the hearing, senior counsel for Pfizer responded that:

There seems to be some dispute between us as to how [the Swiss-style claims are] properly to be interpreted, in particular, from claims 2 onwards – or 3. InterPharma says that these are not Swiss-style claims because they are directed to a new method of administration, not use of dexmedetomidine in the manufacture of a medicament. We don’t see that … . For our purposes, first of all, we have the use in claim 1 of dexmedetomidine in the manufacture of a medicament for use in intensive care sedation. Then you have the use according to claim 1, wherein the [dexmedetomidine] or the pharmaceutically acceptable salt is essentially a sole active agent. Well … we say that’s talking about the method there.

Then the use according to 1 or 2, wherein the dexmedetomidine or pharmaceutical salt is administered in an amount to achieve a plasma concentration – we will say that’s to the method of treatment. It would be odd to try and say that that should somehow relate to the use of dexmedetomidine to make the product and it’s not the right use.

193    Senior counsel for Pfizer subsequently added that:

Ultimately, a Swiss claim is said to gain its novelty from the method of treatment and so here, when you look at the dependent claims, it’s not unusual, we would say, to ask yourself, “Well, what is that as to the method of treatment?” So, here, the first thing is – the method of treatment is sedation in the ICU. The next thing is that a method involves essentially a sole – dexmedetomidine – essentially, a sole or sole active agent. Then to achieve plasma concentrations, then – it’s all looking to the method of treatment, those additional claims, and we don’t … see why – if all of those just appeared in the first claim, why that wouldn’t still be a Swiss claim.

Pfizer reiterated this position in closing submissions.

194    I accept that, as Pfizer submitted, each of claims 2 to 12 is a dependent “Swiss-style” claim, ultimately dependent on claim 1. The dispute between the parties arose from the fact that, since claim 1 is a Swiss-style claim, it mentions of two “uses”. When claim 2 refers to the “use according to claim 1”, one might therefore ask, to which use is the claim referring. This is only a matter of semantics, however. When considered fairly, there is no real lack of clarity here.

195    The specification identifies that “an ideal sedative agent should be used by itself in ICU sedation to avoid the dangers of polypharmacy”. As senior counsel for Pfizer put it in closing submissions:

No doubt the problem arises because it’s a Swiss claim because there’s two uses identified. Your Honour then has to construe which use … we are talking about in a sensible way. And we say … to do that, you read the patent. What is the patent worried about? The patent is not worried about having two sedatives in the one medicament. That’s not what it describes as the problem. It describes the problem as people being treated with two sedatives.

196    In this context, having regard to claim 2 and each of the following dependent claims, it is clear that the relevant use is what is said to be the hitherto undiscovered therapeutic use. This is consistent with the fact that, because claim 1 is a Swiss-style claim, novelty will arise from the claimed new therapeutic use, and not from the manufacture of the medicament. It is clear that each of claims 2 to 12 further qualifies what is said to be the hitherto undiscovered therapeutic use of the medicament.

197    Senior counsel for Pfizer submitted in closing that:

It’s … said that [in] claim 2 the relevant use, if I can put it that way, wherein the dexmedetomidine or pharmaceutical salt thereof as essentially sole active agent or sole active agent, means that it’s in the making of the medicament rather than in the use for intensive care unit sedation. And we say, your Honour, when one reads not only that claim but each of the following claims, it’s plain that the limitation in each of the claims, that is, limiting claim 1, is to how the drug is administered, that is, the method of treatment, not the making of the drug itself. And that’s what is intended by these claims.

198    I accept this submission. It is equally clear, so it seems to me, that the subsequent dependent Swiss-style claims should be read in the same way. For example, I accept that, as Pfizer submitted, claim 5 is to be read as a claim for “use of dexmedetomidine in the manufacture of a medicament for use in ICU sedation”, “wherein a loading dose and a maintenance dose of dexmedetomidine are administered”. InterPharma’s submission that the “use according to claim 1” relates to the use of dexmedetomidine to make the product is contrived.

199    It follows, for the reasons stated, that I reject InterPharma’s submission that there was a lack of clarity in claims 2 to 12 and 38 by virtue of being dependent on the Swiss-style claim in claim 1, such that the relevant claims were invalid.

InterPharma’s other allegations as to lack of clarity

200    As noted earlier, InterPharma originally alleged that there was a lack of clarity in claims 23, 24 and 25. As discussed above, leave is granted to delete the relevant allegation from InterPharma’s Fourth Further Amended Particulars of Invalidity. Since the allegation is no longer pressed, it is unnecessary to consider it.

201    It should also be noted that in its written opening submissions, InterPharma submitted that claims 3, 16 and 28 (plasma concentration claims) and dependent claims 4 to 12, 17 to 25 and 29 to 36 were invalid because the words “administered in an amount to achieve a plasma concentration of 0.1-2 ng/ml” lacked clarity. InterPharma submitted:

This is because it is not clear from this expression whether it refers to an administration of dexmedetomidine in order to achieve the claimed range of plasma concentration or an administration of dexmedetomidine which inevitably achieves that range.

202    At the time these submissions were filed, however, InterPharma’s Further Further Amended Particulars of Invalidity did not include an allegation of lack of clarity on this basis.

203    InterPharma sought to add a lack of clarity allegation by inserting para 9A into its Third Further Amended Particulars of Invalidity filed on 11 May 2018 (before the parties made their written and oral closing submissions to the Court). Proposed para 9A alleged that there was a lack of clarity in claims 3 to 12, 16 to 25 and 28 to 37 on the basis that each of those claims requires that dexmedetomidine be “administered in an amount to achieve a plasma concentration of 0.1-2 ng/ml”, and it is not clear to the skilled reader:

(b)    … whether this expression requires that the administration of dexmedetomidine be directed to achieving a plasma concentration in the range claimed or whether the claim requires that dexmedetomidine be administered in any amount which achieves a plasma concentration in the range claimed[; and]

(c)     … when the plasma concentration is required to be achieved.

204    In written closing submissions, InterPharma made submissions in relation to the “construction” of the plasma concentration claims (see [238]-[241] below), and then stated that “[i]f InterPharma’s construction is not accepted then it is submitted that the words [of the plasma concentration claims] are inherently ambiguous and capable of bearing multiple meanings, thus do not have a sufficiently clear meaning to define a patent monopoly” (emphasis added).

205    In written closing submissions, Pfizer opposed the inclusion of proposed para 9A on the basis that it was a new argument that had not been run at trial and that Pfizer would have led evidence or cross-examined differently had the point been taken earlier.

206    Subsequently, during oral closing submissions on 21 May 2018, shortly after Pfizer took issue with the form of InterPharma’s Third Further Amended Particulars of Invalidity filed on 11 May 2018, senior counsel for InterPharma, Ms Rofe QC, confirmed that InterPharma’s point with respect to the plasma concentration claims was not one of lack of clarity, but one of construction relevant to its answer to Pfizer’s infringement case. This is apparent from the following exchange between the Court and senior counsel:

THE COURT:     It’s not a lack of clarity complaint though, is it? It’s a clear enough integer. It’s a clear enough – it’s saying something which is measurable. It can be measured and everyone knows it can.

MS ROFE:        Yes.

THE COURT:         So what’s the problem with it?

MS ROFE:     Well, it’s probably more of the infringement that it’s not done in order to achieve. Well, we say it has a meaning and it is to achieve a plasma concentration. The person administering it is administering it in order to achieve that plasma concentration and we say … that it’s not.

            …

THE COURT:     If I were not to accept that, is there any other difficulty with the integer?

MS ROFE:     No. I think, your Honour, it is the direction to achieve the plasma concentration, which, on the evidence, is not what is done. ...

THE COURT:     … I just want to understand it a little bit better. Is that a clarity point or is that something else?

MS ROFE:     Your Honour, I think it’s more just a construction point relevant to infringement, although our friends are saying that it has a different construction, which we say is not clear.

(Emphasis added)

207    Consistently with that exchange, when, on 24 May 2018, InterPharma subsequently filed another document, also entitled “Third Further Amended Particulars of Invalidity” to reflect various amendments discussed during closing submissions, the previously proposed para 9A had been removed. Moreover, InterPharma’s Fourth Further Amended Particulars of Invalidity filed on 25 May 2018 did not seek leave to include para 9A or any other allegation of lack of clarity in respect of the plasma concentration claims.

208    The outcome of the discussion between the Court and senior counsel for InterPharma in the course of InterPharma’s closing submissions identified that InterPharma’s point with respect to this integer was not one of lack of clarity but one in answer to Pfizer’s infringement case. Consistently with this, InterPharma no longer included this lack of clarity allegation in the Particulars of Invalidity that it has since filed or in relation to which it seeks leave to amend. It must be inferred from this that InterPharma no longer seeks to allege lack of clarity specifically in respect of the plasma concentration claims. In any event, it seems to me that this would in substance have been a new clarity point. It is therefore unnecessary to address either this particular lack of clarity allegation or Pfizer’s opposition to raising it. Further, as will be seen, there is, in my opinion, no lack of clarity associated with the plasma concentration claims on the construction advanced by Pfizer, and which I accept.

Infringement

209    It was common ground at trial that InterPharma intended, unless enjoined, to supply the Generic Products in Australia with a product information (PI) document containing an indication for “ICU sedation”, that is, “[f]or sedation of initially intubated patients during treatment in an intensive care setting”. When the trial began on 3 May 2018, Pfizer alleged that InterPharma’s proposed conduct in respect of the Generic Products constituted a threatened infringement of each of the claims of the Patent. InterPharma denied any threatened infringement, primarily on the basis that all the claims of the Patent were invalid. For the reasons set out below, I have rejected InterPharma’s submissions with respect to invalidity.

210    Broadly speaking, as set out below, Pfizer made out its case of threatened infringement.

InterPharma’s Infringement Analysis

211    Before considering the substantive issues relevant to infringement, it is necessary to deal with an issue raised by Pfizer after the hearing in relation to a document entitled “InterPharma’s Infringement Analysis Australian Patent No. 754484” (Infringement Analysis). The Infringement Analysis was presented to the Court by senior counsel for InterPharma during closing submissions as a summary of InterPharma’s position. At its request, Pfizer was granted leave to file short submissions after the hearing concerning the Infringement Analysis. Pfizer filed written submissions dated 28 May 2018 contending, relevantly, that the Infringement Analysis “is replete with bare assertions unsupported by evidence”. Pfizer did not expressly submit, however, that the Court should disregard the Infringement Analysis.

212    InterPharma submitted, and I accept, that the Infringement Analysis was a means to direct the Court to relevant parts of InterPharma’s written closing submissions and summarised InterPharma’s position with respect to each of the claims. I accept that, as InterPharma submitted, the document was not intended to have any greater significance than InterPharma’s submissions. I have had regard to InterPharma’s Infringement Analysis on this basis only, subject to one matter.

213    It seems to me that the Infringement Analysis incorrectly stated InterPharma’s position in relation to claim 27. In written closing submissions, InterPharma admitted infringement of claim 27 (along with claims 2 and 14), if the Court took the view that the claims were sufficiently clear and were “construed to allow the co-administration of dexmedetomidine with an agent administered for analgesia (albeit it also has a sedative effect) rather than for sedation”. This is not reflected in the Infringement Analysis, which states instead that InterPharma denies infringement. There is an admission of infringement in relation to claim 28, however, which was not part of InterPharma’s closing written submissions. It appears to me, therefore, that there has been a typographical mistake in the Infringement Analysis, with the result that the relevant admission mistakenly appears in relation to claim 28, instead of claim 27. In any event, I have read the Infringement Analysis in this way, which is consistent with InterPharma’s closing written submissions and the way it ran its case at trial.

General principles and relevant matters

214    An infringement proceeding is designed to enforce the exclusive rights granted to the patentee under s 13 of the Patents Act to exploit an invention, as that term is defined in Sch 1, for the term of the patent. Pfizer instituted its cross-claim alleging threatened infringement as part of its response to InterPharma’s Patent invalidity claims. (With respect to any permanent injunctive relief that the Court might have granted, InterPharma initially sought to “carve out” the ICU sedation indication so that the Generic Products could continue to be supplied with the procedural sedation indication. It did not ultimately press this contention.)

215    The term of the Patent ended on 31 March 2019, while judgment was reserved. For this reason, the interlocutory injunction, which was the subject of Order 1 of orders made on 18 December 2017, restraining InterPharma from marketing, selling and supplying the Generic Products for use in ICU sedation, also came to an end on that date. The infringement proceeding, even if successful, would no longer support the grant of a permanent injunction. The outcome of that proceeding is, however, relevant to other issues, including costs. It therefore remains necessary to decide whether by its proposed conduct InterPharma threatened to infringe Pfizer’s rights under the Patent prior to its expiry.

216    There is no dispute about the basic test for infringement. A patent is infringed if, on a proper construction of the claim, a product possesses all the integers of that claim, without the patentee’s authorisation: see recently Davies v Lazer Safe Pty Ltd [2018] FCA 702; 132 IPR 202 at [240] (appeal dismissed: Davies v Lazer Safe Pty Ltd [2019] FCAFC 65), citing Rodi & Wienenberger AG v Henry Showell Ltd [1969] RPC 367 at 369 (Lord Upjohn); Olin Corporation v Super Cartridge Co Pty Ltd (1977) 180 CLR 236 at 246 (Gibbs J); Fresenius Medical Care Australia Pty Limited v Gambro Pty Limited [2005] FCAFC 220; 67 IPR 230; 224 ALR 168 at [49] (Wilcox, Branson and Bennett JJ).

217    As already indicated, claim 1 is a Swiss-style claim, claims 2 to 12 are dependent Swiss-style claims and claim 38 is an omnibus claim to claim 1. The parties accepted that Swiss-style claims may only be infringed directly and cannot be infringed indirectly by operation of s 117 of the Patents Act: see Otsuka Pharmaceutical v Generic Health (No 4) at [168] (Yates J). Accordingly, these claims may only be infringed directly, including by the importation, supply and offer to supply in Australia of the medicament resulting from the claimed manufacture overseas: Warner-Lambert Co LLC v Apotex Pty Ltd (No 2) [2018] FCAFC 26; 129 IPR 205 at [156]-[168] (Jagot, Yates and Burley JJ). As Yates J also said in Otsuka Pharmaceutical v Generic Health (No 4) at [169] and [172]:

This is not to say that the therapeutic use defined in [a claim] 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 the purpose of determining infringement of a Swiss type claim … [t]he 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.

218    In Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2019] FCA 28; 138 IPR 402 (Mylan), Nicholas J gave further consideration to the infringement of Swiss-style claims, finding that infringement of the Swiss-style claims in the Patent in suit in that case was not established because the manufacturer’s intention in making the medicament was not established: see Mylan at [92]-[106]. His Honour held at [102]:

The crucial question is whether the manufacturer has made (or will make) the relevant medicament with the intention that it be used in the treatment of the designated condition. In my view, the answer to that question is to be ascertained objectively in light of all the relevant facts and circumstances including, in particular, the PI for the product, any product labelling, and the nature, size and other pertinent characteristics of the market into which the product is to be sold.

219    While judgment was reserved, the parties drew my attention to Mylan and his Honour’s discussion about novelty. No party relied on his Honour’s statements with respect to infringement of a Swiss-style claim. The reason for this is clear enough: in this case his Honour’s analysis, especially in [102], would have made no difference. This is because, in this case, the product information for the Generic Products unequivocally indicated a use “for sedation” of patients in “an intensive care setting”. The relevant product information is discussed further below.

220    Claims 13 to 37 and 39 (the second omnibus claim) are method claims. Pfizer’s case regarding infringement of the method claims was based on s 117 of the Patents Act. That section sets out the conditions under which a supply of a product will constitute an infringement of an indirect kind. Section 117 relevantly provided:

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:

    …

(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.

There was no dispute between the parties that the Generic Products are not “staple commercial products” for the purposes of s 117(2)(b) of the Patents Act.

221    Method claims may be infringed indirectly pursuant to s 117(1) by the importation, supply and offer to supply in Australia of products the use of which infringes a claim of the Patent. For Pfizer to establish indirect infringement of the method claims under s 117(1) of the Patents Act, it needed to show that InterPharma:

    had “reason to believe” that a person to whom the Generic Products were supplied “would” put the Generic Products to use in accordance with a relevant method claim: see s 117(2)(b); or

    provided instructions or inducements to use the Generic Products in accordance with a relevant method claim: see 117(2)(c).

222    Since 13 July 2017, InterPharma has been recorded as the sponsor of a listing on the ARTG for the Generic Products. InterPharma has a product information document approved by the TGA (Generic Products PI). The provision of product information is regulated by the Therapeutic Goods Act 1989 (Cth) (Therapeutic Goods Act).

223    As at 20 June 2017, s 23(2)(ba) of the Therapeutic Goods Act provided that an application for registration or listing of therapeutic goods on the ARTG, in the case of a restricted medicine (such as dexmedetomidine), must be accompanied by product information in the form approved under s 7D. Section 3(1) of the Therapeutic Goods Act specified that product information, in relation to therapeutic goods, “means information relating to the safe and effective use of the goods, including information regarding the usefulness and limitations of the goods”. (Section 23 has been amended subsequently, but none of these amendments concern the present discussion.)

224    Also in evidence in the proceedings were the Australian Regulatory Guidelines for Prescription Medicines, Guidance 8: Product Information, published by the TGA. They provided:

The PI is a document associated with a medicine that contains technical information relating to its safe and effective use, including:

•    the characteristics of the active ingredient

•    indications, contraindications and precautions

•    adverse reactions that may occur

•    relevant clinical trials

•    dosage and storage.

The PI:

•    includes scientific and technical information about the risks and benefits of the medicine to support its use for the indications for which it is approved.

•    informs medical practitioners, pharmacists and other health professionals about the safe and appropriate prescribing and dispensing of the medicine.

•    assists healthcare professionals to provide patient education about the medicine to support high-quality and safe clinical care.

225    The Generic Products PI refers to two “indications” for the Generic Products as follows:

INDICATIONS

ICU Sedation

For sedation of initially intubated patients during treatment in an intensive care setting. The use of DEXMEDETOMIDINE EVER PHARMA by continuous infusion in these patients should not exceed 24 hours.

Procedural Sedation

For sedation of non-intubated patients prior to and/or during surgical and other procedures.

226    Under the heading, “Dosage and administration”, the Generic Products PI further relevantly states:

NOTE: Dexmedetomidine should be administered only by persons skilled in anaesthetics or in the management of patients in the intensive care setting. Due to the known pharmacological effects, patients should be continuously monitored.

Clinically significant events of bradycardia and sinus arrest have been associated with dexmedetomidine hydrochloride administration in young, healthy volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration of dexmedetomidine hydrochloride.

Adults: Dexmedetomidine should be individualised and titrated to the desired clinical effect.

ICU Sedation

Initiation

For adult patients, DEXMEDETOMIDINE EVER PHARMA is generally initiated with a loading infusion of 1 (one) microgram/kg over 10 to 20 minutes, if needed. The use of DEXMEDETOMIDINE EVER PHARMA by continuous infusion in these patients should not exceed 24 hours.

For patients being converted from alternate sedative therapy a loading dose may not be required.

Maintenance of ICU sedation

Adult patients will generally require a maintenance infusion of 0.2 to 1 microgram/kg/h*. The rate of the maintenance infusion should be adjusted to achieve the desired level of sedation. As a guide, it is recommended that 0.4 microgram/kg/h should be the initial maintenance infusion. If after approximately 5 minutes sedation is not adequate, the rate of infusion can be increased in increments of 0.1 microgram/kg/h or higher. Dosages as low as 0.05 microgram/kg/h have been used in clinical studies. Patients receiving dexmedetomidine hydrochloride have been observed to be rousable and alert when stimulated. This is an expected component of dexmedetomidine sedation and should not be considered a lack of efficacy in the absence of other clinical signs and symptoms.

A dose reduction for both the loading and maintenance infusions should be considered in patients with impaired hepatic function and in patients over 65 years of age.

Dexmedetomidine hydrochloride has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. It is not necessary to discontinue DEXMEDETOMIDINE EVER PHARMA prior to extubation.

227    The Therapeutic Goods Act and the marketing approval granted for the Generic Products, together with the Generic Products PI, were relevant to the infringement claims. In its closing written submissions, InterPharma accepted that the Generic Products PI supplied with the Generic Products relevantly instructs, with respect to the ICU sedation indication, that:

(a)    dexmedetomidine should only be administered by persons skilled in anaesthetics or in the management of patients in an intensive care setting and, due to the known pharmacological effects, patients should be continuously monitored;

(b)    for adults, dexmedetomidine should be individualised and titrated to the desired clinical effect;

(c)    for adult patients, dexmedetomidine “is generally initiated with a loading infusion of 1 (one) microgram/kg over 10 to 20 minutes, if needed”;

(d)    the use of dexmedetomidine by continuous infusion in these patients should not exceed 24 hours; and

(e)    a maintenance dose is generally required for ICU sedation.

228    InterPharma disputed, however, that the Generic Products PI “contains instructions for the use of the [Generic Products], to assist healthcare professionals in prescribing, dispensing and administering” the Generic Products. I accept that, as Pfizer contended, this assertion “is wholly without merit” in the context of the regulatory regime established by the Therapeutic Goods Act.

229    It may be accepted that specific indications in a PI for a pharmaceutical product listed on the ARTG constitute instructions to do what is indicated: see Apotex v Sanofi-Aventis HCA at [303] (Crennan and Kiefel JJ). Citing Apotex v Sanofi-Aventis HCA at [303], Pfizer submitted that the Generic Products PI was an “emphatic instruction” to recipients of Generic Products to use the Generic Products for ICU sedation in accordance with the dosage and administration stated in that PI and that s 117(2)(c) of the Patents Act was thereby engaged. I accept that submission. I further accept that, as Pfizer submitted, it can reasonably be inferred that InterPharma had “reason to believe” that a person to whom Generic Products were supplied would use the Generic Products in that manner, thereby engaging s 117(2)(b) of the Patents Act. It may, however, also be accepted that, as InterPharma submitted, whether other information in a PI constitutes a relevant instruction or inducement depends on a close consideration of the PI.

InterPharma’s admitted infringement of claims

230    At trial Pfizer submitted that InterPharma’s proposed conduct in respect of its Generic Products would infringe each of the claims of the Patent. InterPharma accepted that, to the extent that the claims were valid, its proposed conduct would infringe claims 1, 13 and 26 (the independent claims), and claims 2, 14 and 27 (the sole active agent claims) if the claims were construed as I have done. It also conceded that its conduct in respect of its Generic Products would infringe claim 15 provided the claim was valid and did not preclude administration of the Generic Products with another pharmaceutical composition.

231    In other words, it was not in dispute that, if claims 1, 13 and 26 were valid (and I have found they were: see below):

•    any supply of the Generic Products by InterPharma prior to the Patent expiry date would have directly infringed claim 1, because each of the Generic Products “is a product resulting from the use of a pharmaceutically acceptable salt of dexmedetomidine in the manufacture of a medicament for use in intensive care sedation”: see Further Amended Defence to Cross-Claim filed 11 May 2018; Amended Defence to Cross-Claim filed 5 February 2018; Defence to Cross-Claim filed 20 September 2017; see also InterPharma’s closing written submissions at [134](a); and

•    any supply of the Generic Products prior to the Patent expiry date would have indirectly infringed claims 13 and 26 by reason of s 117(1), together with s 117(2)(b) or s 117(2)(c) of the Patents Act, because the Generic Products PI instructs, and InterPharma has reason to believe, that a person or persons to whom it would supply the Generic Products would use the Generic Products in a method that falls within claims 13 and 26: see Further Amended Defence to Cross-Claim filed 11 May 2018; Amended Defence to Cross-Claim filed 5 February 2018; Defence to Cross-Claim filed 20 September 2017; see also InterPharma’s closing written submissions at [134](b).

232    As stated above, I have rejected InterPharma’s clarity challenge to the validity of claim 15 and, as appears below, I have rejected InterPharma’s other validity challenges. I can discern no relevant distinction as regards infringement of claim 15 and infringement of claims 13 and 26, notwithstanding the qualified nature of InterPharma’s concession with respect to claim 15.

233    As will be seen, InterPharma denied any further threatened infringement (even if the claims were valid) on the basis of its arguments about claim construction.

234    I also note at this point that, after the trial had concluded and while judgment was reserved, InterPharma applied (on 6 August 2018) for the proceeding to be re-opened on the basis that Pfizer had amended its Precedex® PI prior to trial in a manner which, so InterPharma said, was material to Pfizer’s infringement case at trial. Pfizer consented to InterPharma’s application to re-open in written submissions filed on 1 November 2018. The resumed hearing took place on 15 November 2018. The evidence and submissions referable to the resumed hearing are discussed below in relation to the parties’ submissions about the infringement of the loading dose claims.

Claims 2, 14 and 27 (essentially the sole active agent or the sole active agent)

235    InterPharma accepted in written closing submissions that, if claims 2, 14 and 27 were “sufficiently clear and are construed to allow the co-administration of dexmedetomidine with an agent administered for analgesia (albeit it also has a sedative effect) rather than for sedation”, then the supply of the Generic Products would directly infringe claim 2 (on Pfizer’s construction) and indirectly infringe claims 14 and 27. The reference to “Pfizer’s construction” of claim 2 above is a reference to Pfizer’s contention (which I have accepted) that claim 2 is properly characterised as a dependent Swiss-style claim. As stated above, I have rejected InterPharma’s clarity challenge to claims 2, 14 and 27. Further, I accepted that, on their proper construction, these claims would be satisfied where dexmedetomidine was administered to a patient for the purpose of achieving ICU sedation (at a dose to achieve that purpose) with another agent administered for a purpose other than sedation (such as analgesia) albeit there might be some sedative effect. It therefore follows from InterPharma’s admission regarding the infringement of claims 2, 14 and 27 that:

    claim 2 would have been directly infringed by the exploitation of the Generic Products in Australia prior to the Patent expiry date; and

    prior to the Patent expiry date, claims 14 and 27 would have been indirectly infringed by the supply of the Generic Products, by reason of s 117(1), together with s 117(2)(b) or s 117(2)(c) of the Patents Act.

Claims 3, 16 and 28 (plasma concentration)

236    Amongst other things, claims 3, 16 and 28 require that dexmedetomidine is “administered in an amount to achieve a plasma concentration of 0.1-2 ng/ml”.

237    InterPharma denied that the supply of the Generic Products would infringe claims 3, 16 and 28 on the basis that, in practice, the Generic Products would not be “administered in an amount to achieve” any particular plasma concentration as required by these claims. This proposition depended on InterPharma’s construction of these claims.

238    InterPharma contended that the plain meaning of the plasma concentration claims is that an amount of dexmedetomidine is administered to achieve (ie to target) a specific plasma concentration within the claimed range that the clinician anticipates will be suitable given the desired level of sedation and the general condition of the patient. InterPharma argued that this construction was supported by the specification of the Patent, which relevantly stated:

The dose range of dexmedetomidine can be described as target plasma concentrations. The plasma concentration range anticipated to provide sedation in the patient population in the ICU varies between 0.1-2 ng/ml depending on the desired level of sedation and the general condition of the patient. …

239    InterPharma submitted that to construe the plasma concentration claims as covering the administration of dexmedetomidine in any dose that is likely to achieve a plasma concentration anywhere in the claimed range would denude the words “to achieve” and the concept of a “target” of any meaning and would give the claims no substantial work to do. InterPharma relied on the evidence of Professor Hall that he and other clinicians “do not titrate the dose of dexmedetomidine … to achieve any particular serum level (i.e. plasma concentration)”, but instead “to achieve the … desired level of sedation”. InterPharma also referred to the evidence of Assoc Professor French and Professor Bellomo, who said that they did not routinely measure the plasma concentration in their patients and there was no standard laboratory test to do so. Professor Bellomo added that the reason for this was because clinicians titrate the dose of dexmedetomidine “to the patient’s condition … not to a particular blood level”. The evidence of Assoc Professor French and Professor Bellomo was that, even if they were told to target a certain plasma level, they would not know what infusion rate they would need to use, and would need to further investigate and test each patient. In this regard, Professor Bellomo observed that:

You would have to measure literally with high-performance liquid chromatography because there is so much variability in the disposal of the drug in the critically ill that even if you had information in normal human volunteers that if you gave a particular dose, you will get a particular level, you could not draw robust inferences about what would happen in a critically ill patient.

… You would have to measure it, which is not what we do.

240    Professor Bellomo accepted that a patient’s plasma level would be affected by their metabolism and that would differ depending on the health of the patient, including “[o]rgan dysfunction, kidney dysfunction, liver dysfunction, the severity of the illness, … other drugs that might interfere with the breakdown and metabolism and the volume of distribution of a given drug”. In closing senior counsel for InterPharma submitted that his evidence in this regard indicated that, because these factors affected the plasma concentration, there was “no correlation between the dose and the plasma concentration”. I reject this characterisation of Professor Bellomo’s evidence. As will be seen, Professor Bellomo accepted that, based on the information in the Patent, it was “highly likely” the administration of the Generic Products in the amount identified in the Generic Products PI would achieve the target plasma concentration. I would infer from this that he in fact accepted that there is a correlation between dose and plasma concentration.

241    InterPharma further submitted that it followed from the experts’ evidence that, while a dose that achieves a sedative effect in a patient (other than in a patient at the extremes) might ordinarily be expected to fall within what is the extremely wide plasma concentration range set out in the Patent, those patients would not have been administered dexmedetomidine by a clinician “in an amount to achieve” a plasma level within that range, but instead to achieve a desired level of sedation. I reject this construction of the claims for the reasons I am about to state.

242    Pfizer submitted that the plasma concentration claims relate to the dose of dexmedetomidine administered to a patient that achieves a plasma concentration within the specified range (that being the range anticipated to provide sedation in the patient population in the ICU). I accept that this is the proper construction of the plasma concentration claims.

243    This construction is, in my view, supported by both the specification of the Patent and the structure of the claims. The specification states that the dose range of dexmedetomidine “can be described as target plasma concentrations”. The specification goes on to state that “[t]hese plasma concentrations can be achieved by intravenous administration by using a bolus dose and continuing it by a steady maintenance infusion”. It also identifies the dose range (by reference to the loading dose and the maintenance dose) to achieve the plasma concentration range anticipated to provide sedation in the patient population in the ICU of between 0.1 and 2 ng/ml depending on the desired level of sedation.

244    The link between dose and plasma concentration was also reflected in the structure of the claims of the Patent. Most particularly, while claim 3 is to the administration of dexmedetomidine “in an amount to achieve a plasma concentration of 0.1-2 ng/ml”, the subsidiary claims limit the plasma concentration by reference to specific dose ranges and regimes for administering dexmedetomidine. Furthermore, the experts also agreed in the Joint Report that the expression “administered in an amount to achieve a plasma concentration of 0.1-2 ng/ml” in the context of claim 3 of the Patent meant “the amount of drug administered to a patient to achieve a plasma concentration of 0.1-2 ng/ml” (emphasis added).

245    Senior counsel for Pfizer submitted, and I accept, that a common-sense construction of the plasma concentration claims requires having regard to the fact that the claims relate to the treatment of patients by clinicians; and they are not concerned with clinical scientific research conducted in a laboratory environment. Understood in this context, it is not to the point that the skilled addressee would not, in practice, measure the plasma concentration levels of their patients nor administer dexmedetomidine with the object of achieving a particular plasma concentration. The plasma concentration claims are not claims to administration of dexmedetomidine “for the purpose of” or with the “objective” of achieving the claimed target plasma concentration. Rather, the claims relate to the amount (ie the dosage range) of dexmedetomidine administered to a patient that achieves the target plasma concentrations.

246    As discussed at [204]-[207], InterPharma indicated in passing in closing written and oral submissions that if its construction of the plasma concentration claims was not accepted, then it would allege that the claims lacked clarity. For the reasons already stated, however, InterPharma did not particularise its case in this way and it must be inferred that it did not ultimately seek to allege lack of clarity in respect of the plasma concentration claims. This is reflected in InterPharma’s Infringement Analysis, which does not refer to any lack of clarity allegation in relation to these claims (unlike other claims). In any event, I accept that the plasma concentration claims, as construed above, are sufficiently clear. Amongst other things, it is evident that the experts were able to identify the amount of dexmedetomidine administered to a patient to achieve a plasma concentration in the specified range in the context of the Generic Products PI.

247    Based on its construction of the plasma concentration claims (which I have rejected), InterPharma contended that although its Generic Products PI contains general dosage and administration instructions and information about pharmacokinetic parameters, this information does not constitute instructions to administer the Generic Products, nor did InterPharma have reason to believe the Generic Products would be administered, “in an amount to achieve a plasma concentration” within the claimed range. Accordingly, InterPharma denied that its proposed conduct would infringe the plasma concentration claims.

248    Since I do not accept InterPharma’s construction of the plasma concentration claims, this defence to Pfizer’s infringement claim falls away. The critical question, as senior counsel for Pfizer submitted, is whether or not the relevant dosage range in the Generic Products PI in fact achieves the plasma concentrations identified in the claims. The evidence indicated that it did. Professor Bellomo gave evidence that he examined the Generic Products PI and observed that, although “some variations are noted for particular circumstances”, the general dosage and administration instructions in the Generic Products PI were as follows:

(a)    loading infusion of 1 µg/kg over 10 to 20 minutes; and

(b)    maintenance infusion of 0.2 to 1 µg/kg/h.

His evidence was that, based on the information in the Patent, he considered it was highly likely that the administration of the Generic Products in the amount specified in the Generic Products PI would achieve a plasma concentration of 0.1-2 ng/mL in patients in the ICU. Allowing for patients “at the extremes and not represented by previously published pharmacokinetic data”, Professor Hall gave evidence substantially to the same effect. Professors Bellomo and Hall agreed that the Generic Products PI instructs clinicians to administer the Generic Products in an amount within the dosage range that would achieve a plasma concentration of 0.1-2 ng/ml in most cases. I would therefore conclude that the Generic Products PI instructs clinicians to administer the Generic Products in an amount within the dosage range that would achieve a plasma concentration of 0.1-2 ng/ml in most cases. There was no evidence to the contrary. I would infer from the experts’ evidence that InterPharma had reason to believe that the Generic Products would be used in this way.

249    For these reasons, I find that claim 3 would have been directly infringed by the exploitation of the Generic Products in Australia prior to the Patent expiry date; and that prior to the Patent expiry date, claims 16 and 28 would have been indirectly infringed by the supply of the Generic Products, by reason of s 117(1), together with s 117(2)(b) or s 117(2)(c) of the Patents Act.

Claims 4, 17 and 29 (intravenous administration)

250    Claims 4, 17 and 29 are each claims relating to the intravenous administration of dexmedetomidine. There is no dispute that the Generic Products PI instructs, and InterPharma has reason to believe, that the Generic Products are to be administered to patients intravenously. InterPharma submitted, however, that its proposed conduct would not infringe claims 4, 17 and 29 because each of these claims depend on one of the plasma concentration claims. For the reasons set out above, I have rejected InterPharma’s argument as to the plasma concentration claims. Accordingly, I find that claim 4 would have been directly infringed by the exploitation of the Generic Products in Australia prior to the Patent expiry date; and that prior to the Patent expiry date, claims 17 and 29 would have been indirectly infringed by the supply of the Generic Products, by reason of s 117(1), together with s 117(2)(b) or s 117(2)(c) of the Patents Act.

Claims 5 to 12, 18 to 25 and 30 to 37 (loading dose and maintenance dose)

251    Claims 5 to 12, 18 to 25 and 30 to 37 each relate to use for ICU sedation wherein a loading dose and maintenance dose of dexmedetomidine are administered. The focus of the dispute between the parties with respect to these claims was on the loading dose integer. This was also the focus of the re-opened trial on 15 November 2018. (The experts accepted that a reference in the evidence to “rapid intravenous or bolus administration” was a reference to a loading dose. Professor Bellomo explained that a maintenance infusion or dose is “a steady administration of the drug over a long period of time in order to maintain a certain effect”.)

252    There was no dispute that, except for the issues relating to the loading dose integer, claims 5 to 12 of the Patent would have been infringed directly by the exploitation of the Generic Products in Australia prior to the Patent expiry date; and claims 18 to 25 and 30 to 37 would have been indirectly infringed by the supply of the Generic Products by reason of s 117(1), together with s 117(2)(b) or s 117(2)(c) of the Patents Act.

253    Further to this conclusion, a matter relating to the maintenance dose integer should be noted. The Generic Products PI stated that adult patients “will generally require” a maintenance infusion (or dose) of 0.2-1 µg/kg/hr and recommended the initial maintenance infusion of 0.4 μg/kg/hr, with increments of 0.1 μg/kg/hr if sedation is not adequate at that dose. Professor Bellomo’s evidence was (and I accept) that the Generic Products PI instructs the administration of a maintenance dose within the range claimed in claims 10 to 12, 23 to 25 and 35 to 37. This was not contradicted by any other expert evidence.

The focus of the case as re-opened and heard on 15 November 2018

254    Leave was granted, by consent, to re-open the trial in this proceeding for consideration of two matters, namely:

(a)    Whether or not the Product Information approved by the Therapeutic Goods Administration for the [Generic Products] Products dated 9 July 2018 (the Amended [Generic Products] PI) provides instructions to administer a loading dose of dexmedetomidine hydrochloride as claimed in claims 5-12, 18-25 and 30-39 of Australian Patent No. 754484 (the Patent); and

(b)    Whether or not, in light of the Amended [Generic Products] PI, InterPharma would have reason to believe that, upon the introduction of a generic version of dexmedetomidine hydrochloride, there would be any (or alternatively any significant) use of a loading dose as claimed in claims 5-12, 18-25 and 30-39 of the Patent.

255    At the conclusion of the hearing on 22 May 2018, InterPharma’s position in relation to claims 5 to 12, 18 to 25 and 30 to 37 was that although the Generic Products PI instructed the administration of a loading dose, it had no reason to believe that the Generic Products would be used in the manner claimed in the loading dose claims. InterPharma’s submission about indirect as opposed to direct infringement of claims 5 to 12 apparently reflected its view that claims 5 to 12 were not Swiss-style claims (a view I have rejected). InterPharma’s position was apparently that (subject to its other arguments) it had infringed claims 5 to 12, 18 to 25 and 30 to 37 by reason of s 117(1) read with s 117(2)(c) of the Patents Act, but had not infringed by reason of s 117(1) read with s 117(2)(b).

256    As already stated, InterPharma filed its application to re-open on 6 August 2018, together with affidavits asserting that, without its knowledge, Pfizer had amended the Precedex® PI on 6 March 2018 (prior to trial) with the consequence that InterPharma had conducted its case under a misapprehension of fact. InterPharma asserted that it would have conducted its infringement defence differently had it known of Pfizer’s amendment to its Precedex® PI. InterPharma explained that it made its application in August 2018, since its legal representatives had only became aware in July 2018 that Pfizer had amended its Precedex® PI.

257    At the resumed hearing, InterPharma relied on the affidavit of Professor Hall affirmed on 6 September 2018, and Pfizer relied on the affidavit of Professor Bellomo affirmed on 13 November 2018 and the affidavit of Assoc Professor French affirmed on 8 November 2018. The three affidavits were tendered without objection. The experts each gave evidence in a resumed concurrent session. InterPharma also relied on written submissions filed on 19 October 2018, and Pfizer relied on written submissions dated 1 November 2018. The parties made further submissions at the resumed hearing.

258    There was no dispute that, as a practical matter, InterPharma was required to update the Generic Products PI to reflect the amendments that had been made to the Precedex® PI; and that InterPharma did in fact make corresponding amendments to its Generic Products PI. The TGA approved these amendments on 20 July 2018 (Amended Generic Products PI). Since InterPharma’s submissions depended in part on its Amended Generic Products PI, it may be useful to describe the amendments here.

259    The Amended Generic Products PI is substantially identical to the Generic Products PI, save for some formatting changes and two amendments to section 4.2 headed “Dose and method of administration”.

260    The relevant passages in the Generic Products PI originally stated:

For adult patients, DEXMEDETOMIDINE EVER PHARMA is generally initiated with a loading infusion of 1 (one) microgram/kg over 10 to 20 minutes, if needed. The use of DEXMEDETOMIDINE EVER PHARMA by continuous infusion in these patients should not exceed 24 hours.

For patients being converted from alternate sedative therapy a loading dose may not be required.

(Emphasis added)

261    The Amended Generic Products PI states:

For adult patients, DEXMEDETOMIDINE EVER PHARMA may be initiated with a loading infusion of 1 (one) microgram/kg over 10 to 20 minutes, if needed. The use of DEXMEDETOMIDINE EVER PHARMA by continuous infusion in these patients should not exceed 24 hours.

The use of loading dose of dexmedetomidine was associated with an increased rate of adverse event, including hypotension, hypertension and bradycardia, in clinical trials involving adult ICU patients.

For patients being converted from alternate sedative therapy a loading dose may not be required.

(Emphasis added)

It will be seen that the reference to dexmedetomidine being “generally” initiated with a loading dose, if needed, was removed and replaced with a statement that it “may be” initiated, if needed; and a new paragraph concerning the loading dose was incorporated into the Amended Generic Products PI.

262    In broad terms, InterPharma’s position was that, in light of the Amended Generic Products PI, it had a complete defence to alleged infringement of the loading dose claims, while Pfizer contended that the Amended Generic Products PI made no difference at all.

Instruction to administer a loading dose — s 117(2)(c)

263    As already indicated, before the re-opening, it was not in dispute that the Generic Products PI instructed the administration of a loading dose of the Generic Products. In the re-opened hearing, InterPharma contended that the Amended Generic Products PI “would not instruct the use of dexmedetomidine in accordance with any of those claims of the Patent that depend on the integer of administering a loading dose”. InterPharma contended that, having regard to the Amended Generic Products PI, there could be no infringement of the loading dose claims by reason of s 117(1) read with s 117(2)(c) of the Patents Act.

264    InterPharma submitted in written submissions that the “clear purpose” of the amendments to the Generic Products PI was to discourage the use of a loading dose and that the Amended Generic Products PI would be understood by the skilled addressee to caution against this practice. In closing submissions at the resumed hearing, counsel for InterPharma (Mr Thompson) contended that the Amended Generic Products PI:

… informs clinicians that a loading dose may be given to an ICU patient if needed and in a certain manner but does nothing to encourage such use, and, to the contrary, in referring to an increased rate of adverse events … it provides a prominent warning or caution against that use. Properly characterised, it is discouraging the use of a loading dose unless the clinician, exercising their own judgment, decides that it is necessary to do so.

…

What is submitted is that in the particular circumstances of this case, what is now contained [in the Amended Generic Products PI] falls short of constituting an instruction.

(Emphasis added)

265    InterPharma relied on the evidence of Professor Hall, who deposed that the words “is generally” in the Generic Products PI informed him and other clinicians that “as a matter of routine, dexmedetomidine should be administered by a loading dose or bolus for ICU sedation of a patient.” He stated that the replacement of “is generally” with the word “may” in the Amended Generic Products PI informed him and other clinicians “that the administration of dexmedetomidine using a loading dose or bolus is not a matter of routine”. His evidence was that the use of the words “may be” would cause him to “pause and think more about the risks of the drug versus the benefits”.

266    Professor Hall also gave evidence that the introduction of an additional paragraph regarding adverse events (the additional paragraph) in the Amended Generic Products PI “explicitly warns or cautions the clinician against the use of loading dose of dexmedetomidine” and that this instructs clinicians that “unless absolutely necessary, a loading dose or bolus should not be used”. Accordingly, his opinion was that the Amended Generic Products PI did not instruct a general recommended loading dose of dexmedetomidine for ICU sedation.

267    Pfizer submitted the Amended Generic Products PI was substantially identical to the original Generic Products PI and that it contained “instructions that a recipient may administer a loading dose of a Generic Product, if needed in a particular case”, such that s 117(2)(c) of the Patents Act was engaged. In closing submissions at the resumed hearing, senior counsel for Pfizer submitted that, for the purpose of s 117(2)(c) of the Patents Act, the Court should have regard to the Amended Generic Products PI “as it stands” and should not seek to read the Amended Generic Products PI by comparing it with the original PI. Senior counsel emphasised that the Amended Generic Products PI is not marked up with the changes made to the original Generic Products PI, and that there was no evidence before the Court that a clinician reading the Amended Generic Products PI would have in mind what was said in the previous version.

268    Having regard to the majority’s observations in AstraZeneca AB v Apotex Pty Ltd [2014] FCAFC 99; 107 IPR 177; 226 FCR 324 (AstraZeneca FCAFC) at [427] and to Jagot J’s analysis in Beadcrete Pty Ltd v Fei Yu (t/as Jewels 4 Pools) (No 2) [2013] FCA 187; 100 IPR 188 (Beadcrete) at [126], senior counsel for Pfizer submitted that it was sufficient that the Amended Generic Products PI indicated that dexmedetomidine can be administered in a loading dose to constitute an instruction for the purpose of s 117(2)(c). At the same time, senior counsel also emphasised that the Amended Generic Products PI “stretches well beyond just that, because there are so many indications that a loading dose is something that will be done, because it actually instructs you how to deal with the outcomes of [a] loading dose which might be adverse”. Pfizer relied on the evidence of Professor Bellomo and Assoc Professor French, both of whom gave significantly different evidence to Professor Hall concerning the effect of the amendments to the Generic Products PI.

269    Professor Bellomo and Assoc Professor French expressly disagreed with Professor Hall’s opinion that the Amended Generic Products PI instructs clinicians “that unless absolutely necessary, a loading dose or bolus should not be used”. Professor Bellomo deposed that the substitution of the words “may be” for “generally” instructed him that: