Federal Court of Australia

Boehringer Ingelheim Animal Health USA Inc v Zoetis Services LLC [2023] FCA 1119

ORDERS

THE COURT ORDERS THAT:

1.    If the parties agree on the appropriate orders to be made by the Court reflecting these reasons for judgment, the parties file a minute of proposed orders on or before 5 October 2023.

2.    If the parties are unable to agree on the orders which should be made, each of the parties file and serve on or before 5 October 2023:

(a)    A minute of the orders that the party proposes; and

(b)    Any outline of submissions in support of the proposed orders (limited to three pages).

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

REASONS FOR JUDGMENT

ROFE J:

INTRODUCTION

1    These proceedings are an appeal pursuant to s 60(4) of the Patents Act 1990 (Cth) (the Patents Act or Act) from a decision of a delegate of the Commissioner of Patents by the opponent, Boehringer Ingelheim Animal Health USA Inc, and a cross-appeal by the patent applicant, Zoetis Services LLC, to the grant of three related patent applications: Boehringer Ingelheim Animal Health USA Inc. v Zoetis Services LLC [2020] APO 40 (Delegate’s decision).

2    The three patent applications were each filed on 3 April 2013, and their claim of a priority date of 4 April 2012 was not challenged. The three Australian Patent applications are the:

(a)    535 Application, entitled “Mycoplasma hyopneumoniae vaccine”;

(b)    537 Application, entitled “PCV/Mycoplasma hyopneumoniae combination vaccine”; and

(c)    540 Application entitled “PCV/Mycoplasma hyopneumoniae/PRRS combination vaccine”.

3    The delegate found claims 1–2, 4–6, 9–10 and 12–18 of the 535 Application did not involve an inventive step. The oppositions to the 537 and 540 Applications were unsuccessful.

4    Boehringer filed a notice of appeal and notice of contention. Zoetis filed a notice of cross-appeal and a notice of contention.

5    Ultimately on appeal, the following grounds of opposition were pressed for each Application:

(1)    That the invention claimed is not supported by the matter disclosed in the specification within s 40(3) of the Act;

(2)    That the complete specification does not disclose the invention in a manner which is clear enough and complete enough for it to be performed by a person skilled in the relevant art within s 40(2)(a) of the Act;

(3)    That the complete specification does not disclose the best method known to Zoetis within the requirements of s 40(2)(aa) of the Act;

(4)    That the invention claimed does not involve an inventive step because it was obvious in light of the common general knowledge considered together with information in any one or more of the Okada papers (defined later); and

(5)    That the invention claimed in certain “kit” claims is not for a “manner of manufacture” within s 18(1)(a) of the Act.

6    Although styled as an appeal, the present proceeding is in the original jurisdiction of this Court and involves a hearing de novo on the grounds and evidence before the Court. As the opponent to the grant of a patent on each of the Applications, Boehringer bears the onus in relation to each ground of opposition raised.

7    Section 60(3A) of the Act, which was introduced with the passage of the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth) (RTB Act), provides that the Commissioner may refuse an application if satisfied, on the balance of probabilities, that a ground of opposition exists. That is the standard by which the present proceeding is to be judged.

8    The Patents Act that applies to the present dispute is in the form as amended by the introduction of the RTB Act.

9    For the reasons that follow, I have concluded that the opposition to the grant succeeds in respect of the following claims:

(a)    535 Application:

(i)    Claims 1, 3, 7–8, 11–12, 16–17

(b)    537 Application:

(i)    Claims 1 to 24

(c)    540 Application:

(i)    Claims 1 to 25

GLOSSARY/BACKGROUND

10    Before going further, I will set out a brief background to vaccines, taken principally from uncontroversial parts of the first affidavits of Professor Chase and Dr Nordgren and supplemented with extracts from Professor Browning’s affidavit.

Immune Response

11    A pathogen is an organism that can infect and cause disease to a host such as a pig or a human. There are four main types of pathogens:

(a)    bacteria;

(b)    viruses;

(c)    fungi; and

(d)    parasites, such as protozoa and helminths (eg nematodes or roundworms).

12    The immune system protects its host from infection by pathogens. The immune system is a complex system comprised of different types of cells, tissues and chemotypic messengers, each of which have specific roles, and which work together to protect and heal the host from damage caused by foreign invading pathogens.

13    There are three main types of immunity:

(a)    innate immunity (also known as the “innate immune system”, “innate immune response”, or “primary immune response”);

(b)    adaptive immunity (also known as the “adaptive immune system”, “adaptive immune response”, or “secondary immune response”); and

(c)    passive immunity (also known as the “passive immune system” or “passive immune response”).

14    Each pathogen has unique lifecycles and components, typically proteins or carbohydrates, which stimulate the immune response of a host. The components of pathogens which are capable of being recognised by the immune system and generating a response are known as “antigens”.

15    The innate immune response is the first line of defence against infection. Most components of innate immunity are present before the onset of infection and consist of a set of disease-resistant mechanisms that are not specific to a particular pathogen. These include physical barriers such as skin and the mucosal membranes, as well as phagocytic cells such as macrophages. The innate system is able to recognise a given class of molecules but does not change its response based on its previous exposure to the same pathogen.

16    Macrophages can engulf, or “phagocytize”, invading pathogens and foreign particles and expose them to other intracellular compounds involved in the innate immune response, such as lysozymes (enzymes which can cleave bacterial cell wall membranes). Macrophages, and other components of the innate immune response such as dendritic cells, also stimulate the adaptive immune response, by displaying antigens on their cell surface.

17    The adaptive immune response is typically triggered when there is a recognised antigenic challenge to a host organism. Adaptive immunity provides a second, specific and comprehensive line of defence that eliminates pathogens that evade the innate responses or persist in spite of them. An important consequence of adaptive immune response is memory. If the same pathogen infects the body a second time, memory cells provide the means for the adaptive immune system to make a rapid and often highly effective attack on the invading pathogen.

18    Two characteristics of the adaptive immune system that are crucial to a successful immune response are its antigenic specificity and its diversity. The antigenic specificity of the adaptive immune response enables it to recognise subtle differences among antigens, such as a difference of one amino acid in two otherwise identical proteins. The diversity of the adaptive immune response allows it to recognise billions of unique structures on foreign antigens.

19    The major agents of adaptive immunity are lymphocytes and the antibodies that they produce. Lymphocytes are a class of white blood cells that are produced in the bone marrow, and that produce and display antibodies. The two major types of lymphocytes are B lymphocytes (or B cells) and T lymphocytes (or T cells).

20    Antibodies, also known as immunoglobulins (or Ig), are proteins that mediate the humoral immune response by recognising and binding to antigens.

21    Antibodies bind to specific portions of an antigen. Each antibody-binding site of an antigen is called an “epitope”. The combined strength of the interactions between a single antigen-binding site on an antibody and a single epitope is referred to as the affinity of the antibody for that epitope.

22    There are five major antibody classes, or immunoglobulins: IgG, IgM, IgD, IgA and IgE, each of which plays a specific role in the immune response of a host.

23    Antibodies consist of “heavy” polypeptide chains and “light” polypeptide chains. Each chain comprises a “constant” region and a “variable” region. The constant region is common across all antibodies of a class, while the variable region of each antibody is specific to the antigen against which it was generated.

24    The most abundant immunoglobulin is immunoglobulin G (IgG), which is released by Plasma B cells. There are several sub-classes of IgG. IgG consists of two “heavy” polypeptide chains and two “light” polypeptide chains in a “Y” shape:

25    A vaccine is a preparation containing one or more antigens which is intended to trigger an adaptive immune response, but not cause disease, or at least not cause severe symptoms of disease, associated with that pathogen. The vaccine is intended to generate memory cells against a pathogen. This protects the host against the consequences of subsequent exposure to a pathogen bearing that antigen.

26    Vaccines involve presenting a killed or weakened version of a pathogen (or an antigen or antigens, or specific parts of an antigen or antigens of a pathogen) to the immune system, in a form suitable for the immune system to recognise the antigen or antigens and stimulate the body to produce antigen-specific antibodies and related memory cells in response. If the vaccinated individual is exposed to the pathogen again after vaccination, the immune system will be primed and able to rapidly produce antigen-specific antibodies in order to neutralize and prevent the pathogen from reproducing and the disease from developing.

27    Pathogens often have more than one antigen against which hosts will generate antibodies and memory cells that are capable of providing adaptive immunity. This means that, for a given pathogen, a number of different antigenic compositions may be able to confer acceptable levels of immunity.

THE PATENT APPLICATIONS

28    There are three patent applications in issue.

29    The Applications have substantially the same specification, save for different introductory statements as to the field of the invention and consistory statements, and different examples being included in the 537 and 540 Applications.

30    The 535 Application is entitled “Mycoplasma hyopneumoniae vaccine” and the invention is said to relate to Mycoplasma hyopneumoniae (M. hyo). More particularly, the invention relates to the soluble portion of an M. hyo whole cell preparation and its use in a vaccine for protecting pigs against enzootic pneumonia.

31    The 537 Application is entitled “PCV/Mycoplasma hyopneumoniae combination vaccine”, and the invention is said to relate to porcine circovirus and M. hyo. More particularly, the invention relates to a multivalent immunogenic composition including a soluble portion of an M. hyo whole cell preparation and a PCV-2 antigen and its use in a vaccine for protecting pigs against enzootic pneumonia and Post-weaning Multisystemic Wasting Syndrome (PMWS).

32    The 540 Application is entitled “PCV/Mycoplasma hyopneumoniae/PRRS combination vaccine” and the invention is said to relate to porcine circovirus, M. hyo and porcine reproductive and respiratory syndrome (PRRS) virus. More particularly, the invention relates to a trivalent immunogenic composition including a soluble portion of an M. hyo whole cell preparation, a PCV-2 antigen and a PRRS virus antigen and its use in a vaccine for protecting pigs against enzootic pneumonia and PMWS.

33    Relevant parts of the specification (of all three Applications), referred to throughout these reasons for judgment, include the following.

34    The background of the invention notes enzootic pneumonia in swine, also called mycoplasmal pneumonia, is caused by M. hyo. Whilst infected pigs show only mild cough and fever symptoms, the disease has significant economic impact due to reduced feed efficiency and reduced weight gain. The primary M. hyo infection may be followed by secondary infection by other mycoplasma species as well as other bacterial pathogens.

35    The specification describes M. hyo as a small, prokaryotic microbe capable of a free living existence, although it is often found in association with eukaryotic cells because it has absolute requirements for exogenous sterols and fatty acids. These requirements generally necessitate growth in serum-containing media. M. hyo is bounded by a cell membrane, but not a cell wall.

36    After describing in more detail the mechanism and effect of an M. hyo infection in a pig, and the characteristic lung lesions found in infected pigs, the specification observes (at page 1a, line 3) that there is a great need for effective preventative and treatment measures.

37    The specification continues (at page 2, lines 5–11):

Vaccines containing preparations of mycoplasmal organisms grown in serum-containing medium have been marketed, but raise concerns regarding adverse reactions induced by serum components (such as immunocomplexes or non-immunogenic specific proteins) present in the immunizing material. Other attempts to provide M. hyo vaccines have been successful, but the disease remains widespread.

38    The specification then explains that M. hyo and porcine circovirus type 2 (PCV-2) are the two most prevalent pathogens that are encountered in the pig industry. Swine infected with PCV-2 exhibit a syndrome commonly referred to as Post-weaning Multisystemic Wasting Syndrome (defined above as PMWS). In addition to PMWS, PCV-2 has been associated with several other infections, one of which is PRRS.

39    At page 2a, lines 1–2, the specification states that it is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. An example given is an improved vaccine against mycoplasma infection in swine.

40    The specification continues (at page 3, lines 1–4):

M. hyo vaccine will be compatible with other porcine antigens, such as PCV2 and PRRS virus, whether they are given concurrently as separate single vaccines or combined in a ready-to-use vaccine. It would be highly desirable to provide a ready-to-use, single-dose M. hyo/PCV2 combination vaccine.

41    Under the heading “summary of the invention”, the specification describes four aspects of the invention, the first aspect being (page 3, lines 7–11):

According to a first aspect, the present invention relates to an immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M.hyo) culture, wherein the supernatant of the M.hyo culture has been separated from insoluble cellular material by centrifugation, filtration, or precipitation and is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin.

42    The second aspect of the invention relates to a kit for use in carrying out the invention, the third aspect, a method for preparing an immunogenic composition, and the fourth, a method for immunising a pig against M. hyo.

43    At page 3a, lines 10–12, the specification states that in one aspect, the soluble portion of the M. hyo whole cell preparation has been treated with Protein A or Protein G prior to being added to the immunogenic composition.

44    The specification then describes some embodiments of the invention (at page 3a, line 14–page 5, line 13):

In one embodiment, the soluble portion of the M. hyo preparation includes at least one M. hyo protein antigen. In another embodiment, the soluble portion of the M. hyo preparation includes two or more M. hyo protein antigens.

In some embodiments, the immunogenic composition of the present invention further includes at least one additional antigen. In one embodiment, the at least one additional antigen is protective against a microorganism that can cause disease in pigs.

In one embodiment, the microorganism includes bacteria, viruses, or protozoans. In another embodiment, the microorganism is selected from, but is not limited to, the following: porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), Haemophilus parasuis, Pasteurella multocida, Streptococcum [sic] suis, Staphylococcus hyicus, Actinobacilllus [sic] pleuropneumoniae, Bordetella bronchiseptica, Salmonella choleraesuis, Salmonella enteritidis, Erysipelothrix rhusiopathiae, Mycoplama [sic] hyorhinis, Mycoplasma hyosynoviae, leptospira bacteria, Lawsonia intracellularis, swine influenza virus (SIV), Escherichia coli antigen, Brachyspira hyodysenteriae, porcine respiratory coronavirus, Porcine Epidemic Diarrhea (PED) virus, rotavirus, Torque teno virus (TTV), Porcine Cytomegalovirus, Porcine enteroviruses, Encephalomyocarditis virus, a pathogen causative of Aujesky's [sic] Disease, Classical Swine fever (CSF) and a pathogen causative of Swine Transmissable [sic] Gastroenteritis, or combinations thereof.

In certain embodiments, the at least one additional antigen is a porcine circovirus type 2 (PCV2) antigen, a PRRS virus antigen or a combination thereof. In one embodiment, the composition elicits a protective immune response in a pig against both M. hyo and PCV2. In another embodiment, the composition elicits a protective immune response in a pig against M. hyo, PCV2 and PRRS virus.

In one embodiment, the PCV2 antigen is in the form of a chimeric type-1-type 2 [sic] circovirus, the chimeric virus including an inactivated recombinant porcine circovirus type 1 expressing the porcine circovirus type 2 ORF2 protein. In another embodiment, the PCV2 antigen is in the form of a recombinant ORF2 protein. In still another embodiment, the recombinant ORF2 protein is expressed from a baculovirus vector.

In some embodiments, the composition of the present invention further includes an adjuvant. In one embodiment, the adjuvant is selected from, but is not limited to, the following: an oil-in-water adjuvant, a polymer and water adjuvant, a water-in-oil adjuvant, an aluminum hydroxide adjuvant, a vitamin E adjuvant and combinations thereof. In another embodiment, the composition of the present invention further includes a pharmaceutically acceptable carrier.

In certain embodiments, the composition of the present invention elicits a protective immune response against M. hyo when administered as a single dose administration. In further embodiments, the composition elicits a protective immune response against M. hyo and at least one additional microorganism that can cause disease in pigs when administered as a single dose administration. In still further embodiments, a composition of the present invention elicits a protective response against both M. hyo and at least one additional microorganism that causes disease in pigs when administered as a two dose administration.

The present invention also provides a method of immunizing a pig against M. hyo. This method includes administering to the pig an immunogenic composition including a soluble portion of an M. hyo whole cell preparation, wherein the soluble portion of the M. hyo preparation is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin. In one embodiment, the soluble portion of the M. hyo preparation of the administered composition includes at least one M. hyo protein antigen.

In one embodiment of the method of the present invention, the composition is administered intramuscularly, intradermally, transdermally, or subcutaneously. In another embodiment of the method of this invention, the composition is administered in a single dose. In yet another embodiment of the method of this invention, the composition is administered as two doses.

In a further embodiment of the method of the present invention, the composition is administered in conjunction with at least one additional antigen that is protective against a microorganism that can cause disease in pigs, such as one or more of the microorganisms described above. Such other antigens can be given concurrently with the M. hyo composition (i.e., as separate single vaccines) or combined in a ready-to-use vaccine.

45    There follows a brief description of the drawings and the sequences.

46    At page 8, lines 15–24, there is the following detailed description of the invention:

The present invention provides an immunogenic composition including a soluble portion of an M. hyo whole cell preparation, wherein the soluble portion of the M. hyo preparation is substantially free of both (i) IgG and (ii) antigen-bound immunocomplexes. Applicants have surprisingly discovered that the insoluble fraction of the M. hyo whole cell preparation is non-immunogenic. In contrast, the IgG-free M. hyo soluble preparation is immunogenic and can be effectively combined with antigens from other pathogens, such as PCV2, without analytical or immunological interference between the antigens. This makes the M. hyo soluble preparation of this invention an effective platform for multivalent vaccines, including one-bottle, ready-to-use formulations. Applicants have also surprisingly discovered that removing the immunoglobulin and the insoluble cell debris enhances the safety of the immunogenic composition.

47    The specification then includes (at page 8, line 26–page 13, line 4) a number of definitions of terms used in the specification, including “comprising” at page 8, lines 30–2:

As used herein, the term “comprising” is intended to mean that the compositions and methods include the recited elements, but do not exclude other elements.

48    At page 9, lines 1–9, the specification states that, as defined, a soluble portion of an M. hyo whole cell preparation refers to a soluble liquid fraction of an M. hyo whole cell preparation after separation of the insoluble material and substantial removal of IgG and antigen-bound immunocomplexes. The specification continues:

The M. hyo soluble portion may alternatively be referred to as the supernatant fraction, culture supernatant and the like. It includes M. hyo expressed soluble proteins (M. hyo protein antigens) that have been separated or isolated from insoluble proteins, whole bacteria, and other insoluble M. hyo cellular material by conventional means, such as centrifugation, filtration, or precipitation. In addition to including M. hyo-specific soluble proteins, the soluble portion of the M. hyo whole cell preparation also includes heterologous proteins, such as those contained in the culture medium used for M. hyo fermentation.

The term “antigen” as used in the specification refers to a compound, composition, or immunogenic substance that can stimulate the production of antibodies or a T-cell response, or both, in an animal, including compositions that are injected or absorbed into an animal. The immune response may be generated to the whole molecule, or to a portion of the molecule (e.g., an epitope or hapten).

49    The term an “immunogenic or immunological composition”, as used in the specification, refers to a composition of matter that comprises at least one antigen which elicits an immunological response in the host of a cellular and or antibody-mediated immune response to the composition or vaccine of interest.

50    At page 9, lines 20–30 the specification continues:

The term "immune response" as used in the specification refers to a response elicited in an animal. An immune response may refer to cellular immunity (CMI); humoral immunity or may involve both. The present invention also contemplates a response limited to a part of the immune system. Usually, an “immunological response” includes, but is not limited to, one or more of the following effects: the production or activation of antibodies, B cells, helper T cells, suppressor T cells, and/or cytotoxic T cells and/or yd T cells, directed specifically to an antigen or antigens included in the composition or vaccine of interest. Preferably, the host will display either a therapeutic or protective immunological response such that resistance to new infection will be enhanced and/or the clinical severity of the disease reduced. Such protection will be demonstrated by either a reduction or lack of symptoms normally displayed by an infected host, a quicker recovery time and/or a lowered viral titer in the infected host.

51    The term “adjuvant”, as used in the specification (at page 10, line 5), means:

[A] composition comprised of one or more substances that enhances the immune response to an antigen(s). The mechanism of how an adjuvant operates is not entirely known. Some adjuvants are believed to enhance the immune response by slowly releasing the antigen, while other adjuvants are strongly immunogenic in their own right and are believed to function synergistically.

52    The term “multivalent”, as used in the specification, means a vaccine containing more than one antigen whether from the same species (ie different isolates of Mycoplasma hyopneumoniae), from a different species (ie isolates from both Pasteurella hemolytica and Pasteurella multocida), or a vaccine containing a combination of antigens from different genera (eg a vaccine comprising antigens from Pasteurella multocida, Salmonella, Escherichia coli, Haemophilus somnus and Clostridium).

53    The term “vaccine composition”, as used in the specification, includes at least one antigen or immunogen in a pharmaceutically acceptable vehicle useful for inducing an immune response in a host.

54    At page 13, lines 5–9, the specification states:

All currently available M. hyo vaccines are made from killed whole cell mycoplasma preparations (bacterins). In contrast, the present invention employs a soluble portion of a Mycoplasma hyopneumoniae (M. hyo) whole cell preparation, wherein the soluble portion of the M. hyo preparation is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin.

55    The specification then discusses the growth media requirements specific to M. hyo at page 13, lines 11–23:

M. hyo has absolute requirements for exogenous sterols and fatty acids. These requirements generally necessitate growth of M. hyo in serum-containing media, such as porcine serum. Separation of the insoluble material from the soluble portion of the M. hyo whole cell preparation (e.g., by centrifugation, filtration, or precipitation) does not remove the porcine IgG or immune complexes. In one embodiment of the present invention, the M. hyo soluble portion is treated with protein-A or protein-G in order to substantially remove the IgG and immune complexes contained in the culture supernatant. In this embodiment, it is understood that protein A treatment occurs post- M. hyo fermentation. This is alternatively referred to herein as downstream protein A treatment. In another embodiment, upstream protein A treatment of the growth media (i.e., before M. hyo fermentation) can be employed. Protein A binds to the Fc portion of IgG. Protein G binds preferentially to the Fc portion of IgG, but can also bind to the Fab region. Methods for purifying/removing total IgG from crude protein mixtures, such as tissue culture supernatant, serum and ascites fluid are known in the art.

56    At page 13, lines 25–27, the specification notes that in some embodiments, the soluble portion of the M. hyo preparation includes at least one M. hyo protein antigen. In other embodiments, the soluble portion of the M. hyo preparation includes two or more M. hyo protein antigens.

57    The specification discusses (at page 13, line 29–page 14, line 25) at least one M. hyo antigen included in the M. hyo soluble portion. In one embodiment, the M. hyo supernatant fraction is said to include one or more of the following M. hyo protein specific antigens: M. hyo proteins of approximately 46kD (p46), 64kD (p64) and 97kD (p97); kD being molecular weight expressed in kilo Daltons. In another embodiment, the M. hyo culture supernatant may include further M. hyo specific antigens such as, but not limited to, proteins of approximately 41 kD (p41), 42kD (p42), 89kD (p89), and 65kD (p65). The specification cites Okada et al, “Protective effect of Vaccination with Culture Supernate of M. hyopneumoniae against Experimental Infection in Pigs” (2000) Journal of Veterinary Medicine, Series B 47(7) 527–533 (Okada 2000a) following the list of specific protein antigens.

58    At page 15, lines 18–22, the specification details another embodiment:

In one embodiment, M. hyo soluble p46 antigen is included in the compositions of the invention at a final concentration of about 1.5 µg/ml to about 10 µg/ml, preferably at about 2 µg/ml to about 6 µg/ml. It is noted that p46 is the protein used for the M. hyo potency test (see example section below). In another embodiment, the M. hyo antigen can be included in the compositions at a final amount of about 5.5% to about 35% of the M. hyo whole culture protein A-treated supernatant.

59    At page 15, lines 24–30, the specification states that the M. hyo soluble preparation of the present invention is both safe and efficacious against M. hyo and is suitable for single dose administration. In addition, it is said that it has been surprisingly discovered that the M. hyo soluble preparation can be effectively combined with antigens from other pathogens without immunological interference between the antigens. That is said to make the M. hyo soluble preparation of the invention an effective platform for multivalent vaccines. The additional antigens may be given concurrently with the M. hyo composition (ie as separate single vaccines) or combined in a ready-to-use vaccine.

60    At page 16, the specification provides details of other embodiments, including where:

(a)    The immunogenic composition includes at least one M. hyo soluble antigen and at least one additional antigen; or

(b)    The immunogenic composition includes the combination of at least one M. hyo soluble antigen (eg two or more) and a PCV-2 antigen.

61    See also page 19, lines 23–26, which describes further embodiments, including a combination of at least one M. hyo soluble antigen (eg two or more), a porcine circovirus type 2 (PCV-2) antigen and a PRRS virus antigen.

62    Page 19, lines 9–21, includes the following examples of absolute concentration:

In one embodiment, a chimeric PCV1-2 virus is included in the compositions of the invention at a level of at least 1.0 < RP< 5.0, wherein RP is the Relative Potency unit determined by ELISA antigen quantification (in vitro potency test) compared to a reference vaccine. In another embodiment, a chimeric PCV1-2 virus is included in the composition of the invention at a final concentration of about 0.5% to about 5% of 20-times (20X) concentrated bulk PCV1-2 antigen.

In another embodiment, the PCV2 ORF2 recombinant protein is included in the compositions of the invention at a level of at least 0.2 µg antigen/ml of the final immunogenic composition (µg/ml). In a further embodiment, the PCV2 ORF2 recombinant protein inclusion level is from about 0.2 to about 400 µg/ml. In yet another embodiment, the PCV2 ORF2 recombinant protein inclusion level is from about 0.3 to about 200 µg/ml. In a still further embodiment, the PCV2 ORF2 recombinant protein inclusion level is from about 0.35 to about 100 µg/ml. In still another embodiment, the PCV2 ORF2 recombinant protein inclusion level is from about 0.4 to about 50 µg/ml.

63    Examples of suitable adjuvants for use in the compositions of the invention are listed at page 24.

64    The specification notes at page 26, lines 24–27 the methods used to separate the M. hyo whole cell preparation from the insoluble cellular material. These conventional methods include filtration, centrifugation and precipitation across various embodiments.

65    The 535 Application has 13 examples. Example 1 provides a high level description of a method by which an M. hyo cell culture is fermented and inactivated for the purposes of producing a PCV-2 combinable M. hyo antigen. Example 2 provides a description of methods by which chimeric porcine circovirus (cPCV)1-2 can be produced. Examples 1 and 2 are replicated in the 537 and 540 Applications.

66    Example 3 (in each of the Applications) is entitled “Down Stream Processing of M. hyo antigens and Analytical Testing of these Processed Antigens”. This example describes how a number of M. hyo preparations prepared as described in example 1 were treated and then analysed for M. hyo specific p46 antigen. The processed M. hyo antigens were then employed in example 4 (in each of the Applications) to prepare M. hyo vaccine formulations. Formulations relevant to BI’s validity case, which are discussed later, include:

    T03: (10X UF (ultra filtration) concentrated) Concentrated by tangential flow filtration via a 100KDa molecular weight cut-off membrane (hollow fibre). Final volume reduction was equal to 10X.

    T04 and T05: (10X UF concentrated and centrifuged) Concentrated mycoplasma cells (from T03) were collected and washed one time with PBS via centrifugation at ~20,000xg (Sorvall model RCB).

    T06 and T07: (10X centrifuged) Inactivated fermentation fluid was centrifuged at ~20,000xg (Sorvall RC5B) and washed one time by resuspending the cells in PBS followed by additional centrifugation. Final volume reduction was equal to 10X.

    T08: (10X centrifuged and heated) Mycoplasma cells were concentrated and washed per T06 and heated to 65°C for 10 minutes.

    T09: (cell-free supernatant) Supernatant collected from the first centrifugation as described for T06 was filter sterilized through a 0.2 micron filter (Nalgene).

    T10: (cell-free-supernatant-Protein-A treated) Sterile supernatant (prepared per T09) was mixed with Protein A resin (Protein A Sepharose, Pharmacia Inc) at a 10:1 volume ratio for 4 hours. Resin was removed and sterile filtration and filtered fluid was stored at 2-8˚C. This process uses post-fermentation “downstream” Protein A treatment to remove antibodies and immunocomplexes.

67    The specification notes (at page 32) that, although the present invention does not preclude upstream Protein A treatment, the present inventors have found that, in the case of M. hyo, upstream processing of the growth media led to P46 results which were lower and inconsistent as compared to untreated media.

68    The specification continues at page 33, line 13:

Since it is known in the art that Protein A binds IgG, it is understood by those of ordinary skill in the art that not only PCV2 antibody, but other swine antibodies, including PRRS antibody, HPS antibody, and SIV antibody will be effectively removed by the Protein-A treatment. This makes the Cell-free Protein-A treated M. hyo supernatant of this invention compatible not only with PCV2 antigen, but also with other porcine antigens due to the lack of immunological interference between the antigens. Additionally, the removal of the non-protective cell debris and removal of the immunoglobulin and antigen/immunoglobulin complexes is reasonably expected to make a safer vaccine.

69    The differences between the three specifications as far as the examples are concerned can be summarised as follows:

(a)    Examples 12 and 13 of the 537 Application are not present in the 535 or 540 Applications. These examples describe two studies, the first designed to evaluate the efficacy of the PCV1-2 chimera, killed virus fraction of an experimental 1-bottle PCV-2/M. hyo combination vaccine, administered once to piglets, and the second to evaluate the efficacy of the M. hyo fraction of an experimental PCV1-2 chimera.

(b)    Examples 14 and 15 of the 537 Application are labelled example 12 and 13, respectively, in the 535 and 540 Applications.

(c)    The 540 Application contains three additional examples not present in the 535 or 537: examples 14 to 16. Examples 14 to 16 describe various further studies designed to evaluate the efficacy of the M. hyo, PCV-2 and PRRS components respectively of a trivalent vaccine of the invention.

70    The 535 Application’s specification ends with 18 claims. Claim 1 of the 535 Application claims:

An immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M. hyo) culture, wherein the supernatant of the M. hyo culture has been separated from insoluble cellular material by centrifugation, filtration, or precipitation and is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin.

71    Claim 2 of the 535 Application is dependent upon claim 1, and adds “wherein the soluble portion has been treated with Protein A or Protein G prior to being added to the immunogenic composition”.

72    Claim 3 of the 535 Application is dependent upon claims 1 or 2, and claims:

The composition of claim 1 or claim 2, wherein the composition further comprises at least one additional antigen which is protective against a microorganism selected from the group consisting of porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), Haemophilus parasuis, Pasteurella multocida, Streptococcum [sic] suis, Staphylococcus hyicus, Actinobacilllus [sic] pleuropneumoniae, Bordetella bronchiseptica, Salmonella choleraesuis, Salmonella enteritidis, Erysipelothrix rhusiopathiae, Mycoplama [sic] hyorhinis, Mycoplasma hyosynoviae, leptospira bacteria, Lawsonia intracellularis, swine influenza vims (SIV), Escherichia coli antigen, Brachyspira hyodysenteriae, porcine respiratory coronaviruses, Porcine Epidemic Diarrhea (PED) vims, rotavims, Torque teno virus (TTV), Porcine Cytomegalovirus, Porcine enterovimses, Encephalomyocarditis virus, a pathogen causative of Aujesky’s [sic] Disease, Classical Swine fever (CSF) and a pathogen causative of Swine Transmissable [sic] Gastroenteritis, or combinations thereof.

(Emphasis added.)

73    The bolded references above are to the “5 Pathogens” which were the subject of discussion by the experts and which are relevant to Boehringer’s validity case. Four of the 5 Pathogens are viruses, and one, Brachyspira hyodysenteriae, is a bacteria.

74    Claim 16 of the 535 Application is a “kit” claim, which claims:

A kit for use in carrying out the method of claim 9 comprising:

a bottle comprising an immunogenic composition including the supernatant of a Mycoplasma hyopneumoniae (M. hyo) culture, wherein the supernatant of the M. hyo culture has been separated from insoluble cellular material by centrifugation, filtration, or precipitation and is substantially free of both (i) IgG and (ii) antigen/immunoglobulin immunocomplexes.

75    The 537 Application contains 24 claims, the broadest of which is claim 1, which claims:

A multivalent immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M. hyo) culture; and a porcine circovirus type 2 (PCV2) antigen, wherein the supernatant of the M. hyo culture has been separated from insoluble cellular material by centrifugation, filtration, or precipitation and is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin.

(Emphasis added.)

76    Claim 2 of the 537 Application is dependent on claim 1 and claims where the soluble portion of the M. hyo preparation has been treated with Protein A or Protein G prior to being added to the immunogenic composition.

77    Claim 3 claims the composition of claim 1 or 2 wherein the composition is in the form of a ready-to-use liquid composition.

78    Dependent claim 8 of the 537 Application claims the composition of any one of claims 1 to 7, further comprising at least one additional antigen which is protective against a microorganism selected from the same group listed in claim 3 of the 535 Application with the exception of PRRSV which is in the list of antigens in claim 3 of the 535 Application but is not found in the list in claim 8 of the 537 Application.

79    The 540 Application contains 25 claims. Claim 1 of the 540 Application claims:

A trivalent immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M. hyo) culture; a porcine circovirus type 2 (PCV2) antigen; and a porcine reproductive and respiratory syndrome (PRRS) virus antigen, wherein the supernatant of the M. hyo culture has been separated from insoluble cellular material by centrifugation, filtration, or precipitation and is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin.

(Emphasis added.)

80    Claims 2 to 13 of the 540 Application are dependent claims that also define trivalent immunogenic compositions, adding various characteristics to claim 1. In particular, claim 3 defines a “ready-to-use” composition containing the M. hyo and PCV-2 antigens but not the PRRS virus antigen. Claims 24 and 25 are claims to methods of preparing an immunogenic composition comprising the M. hyo supernatant, and PCV-2 and PRRS antigens.

Summary of the disclosure

81    The invention described and claimed in the specification of each Application may be broadly summarised as the provision of an immunogenic composition being an M. hyo supernatant platform which may itself be used as a vaccine, or which can be combined with other vaccines to form a preferably single dose ready-to-use vaccine. Relevant to each application, the nature of the M. hyo supernatant platform is such that immunogenic interference when combined with other antigens is absent due to the removal of IgG and immunocomplexes comprised of antigen bound to immunoglobulin (immunocomplexes) in the production of the M. hyo supernatant.

82    The 535 Application claims an immunogenic composition being an M. hyo supernatant platform, which may itself be used as a vaccine, or which can be combined with other vaccines to form a preferably single dose ready-to-use vaccine.

83    The invention as claimed in the 537 Application is a multivalent immunogenic composition being an M. hyo supernatant platform combined with a PCV-2 antigen, which may be combined with other vaccines to form a preferably single dose ready-to-use vaccine.

84    The invention as claimed in the 540 Application is a trivalent immunogenic composition being an M. hyo supernatant platform combined with a PCV-2 antigen and a PRRS antigen.

STATUTORY PROVISIONS

85    The statutory provisions of particular relevance to this matter are as follows.

86    Section 7 of the Act states:

7 Novelty, inventive step and innovative step

Novelty

(1)      For the purposes of this Act, an invention is to be taken to be novel when compared with the prior art base unless it is not novel in the light of any one of the following kinds of information, each of which must be considered separately:

(a)      prior art information (other than that mentioned in paragraph (c)) made publicly available in a single document or through doing a single act;

(b)      prior art information (other than that mentioned in paragraph (c)) made publicly available in 2 or more related documents, or through doing 2 or more related acts, if the relationship between the documents or acts is such that a person skilled in the relevant art would treat them as a single source of that information;

(c)      prior art information contained in a single specification of the kind mentioned in subparagraph (b)(ii) of the definition of prior art base in Schedule 1.

Inventive step

(2)      For the purposes of this Act, an invention is to be taken to involve an inventive step when compared with the prior art base unless the invention would have been obvious to a person skilled in the relevant art in the light of the common general knowledge as it existed (whether in or out of the patent area) before the priority date of the relevant claim, whether that knowledge is considered separately or together with the information mentioned in subsection (3).

(3)      The information for the purposes of subsection (2) is:

(a)      any single piece of prior art information; or

(b)     a combination of any 2 or more pieces of prior art information that the skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have combined.

87    Section 40, which deals with sufficiency, support and best method, states:

40 Specifications

…

Requirements relating to complete specifications

(2)      A complete specification must:

(a)      disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art; and

(aa)      disclose the best method known to the applicant of performing the invention; and

(b)      where it relates to an application for a standard patent—end with a claim or claims defining the invention; and

(c)      where it relates to an application for an innovation patent—end with at least one and no more than 5 claims defining the invention.

(3)      The claim or claims must be clear and succinct and supported by matter disclosed in the specification.

(3A)      The claim or claims must not rely on references to descriptions, drawings, graphics or photographs unless absolutely necessary to define the invention.

(4)      The claim or claims must relate to one invention only.

OVERVIEW OF EVIDENCE

88    Four expert witnesses gave evidence at trial. Boehringer engaged Dr Nordgren and Professor Chase, and Zoetis engaged Professor McVey and Professor Browning.

89    Prior to the trial, the experts prepared a Joint Expert Report (JER). They were each cross-examined in the course of a joint session over 3 days. Dr Nordgren was also cross-examined in a separate session which followed the completion of the joint session.

Dr Nordgren

90    Dr Nordgren has more than 35 years of experience in vaccine development and formulation for animals and has been involved in the registration of over 80 animal health products. He has a Bachelor of Science, a Master of Science (Veterinary Parasitology) and a Doctorate of Philosophy in Veterinary Immunology.

91    Dr Nordgren has worked for leading animal healthcare companies, including Solvay Animal Health, Boehringer Ingelheim Vetmedica and Merial Ltd. Dr Nordgren has managed global teams which have been responsible for over 80 unique animal products, including vaccines. A significant number of the vaccines for which he was responsible were developed before 2012.

92    While working at BIV in approximately 1998, Dr Nordgren was involved in a vaccine development project which created a one-dose inactivated whole cell bacterin vaccine for M. hyo in pigs. During the joint expert session Dr Nordgren agreed with senior counsel for Zoetis, Mr Flynn, that bacterins were a state of the art product and the best available option by 1998.

93    While working at Merial from 1999, Dr Nordgren was responsible for reviewing patents, and on occasion gave evidence in patent proceedings for Merial. His role at Merial also required the surveillance of products entering the market and acquisition of innovative competitor products.

94    Zoetis strongly challenged Dr Nordgren’s independence and ability to give impartial and relevant expert evidence on four grounds which I consider at the end of the evidence section.

Professor Chase

95    Professor Chase has over 30 years of experience in veterinary immunology, including experience developing and researching vaccines for the treatment of diseases in swine. He is currently a Professor in the Department of Veterinary and Biomedical Science at South Dakota University. He holds a professional doctorate degree in Veterinary Medicine and a Master of Science and PhD.

96    During the period before the priority date, Professor Chase was involved in swine and ruminant disease diagnostics while teaching virology and immunology and undertaking research in infectious disease and immunology. Since 1 June 1998, Professor Chase has also held the position of President at his contract research company that undertakes, amongst other research, swine vaccine studies.

97    No challenge was made to Professor Chase’s independence. Professor Chase answered questions directly and engaged with the views expressed by his colleagues on technical matters. I consider that Professor Chase was a helpful witness who did his best to assist the Court throughout his evidence.

98    Zoetis made a hindsight challenge in relation to some of Professor Chase’s evidence. This challenge was based on the manner in which Professor Chase was briefed with the prior art and the questions put to him in the preparation of his evidence for the opposition proceeding. I deal with this challenge later where it is relevant to the issue of inventive step.

Professor McVey

99    Professor McVey has around 40 years’ experience in animal health and veterinary microbiology. He has worked with both academic institutions and pharmaceutical and animal health companies in the field of vaccine formulation and development. Professor McVey holds a Doctor of Veterinary Medicine degree and a PhD in Veterinary Microbiology. He also has experience in the field working as a veterinarian, including treating endemic diseases of commercial farm animals, and has been employed by Merial from 1995–1998, and Pfizer Animal Health from 1998–2006.

100    Professor McVey is currently a Professor and Director of the School and Veterinary Medicine and Biomedical Sciences at the University of Nebraska-Lincoln and the Associate Dean of the Nebraska/Iowa Program for Veterinary Medicine.

101    Professor McVey has particular expertise in the immunology of infectious diseases of livestock, including diseases associated with M. hyo, PCV-2 and PRRS, and associated control measures including vaccine development.

102    No challenge was made to Professor McVey’s independence as an expert witness and he gave helpful affidavit and oral evidence.

Professor Browning

103    Professor Browning is a Professor of Veterinary Microbiology in the Faculty of Veterinary and Agricultural Sciences at the University of Melbourne and has been since 2003. He has more than 35 years’ experience in veterinary microbiology, including the pathogenesis and epidemiology of infectious diseases and related animal vaccines.

104    Professor Browning’s research focuses on vaccines to control bacterial and viral respiratory diseases in swine and other livestock. He has particular expertise in relation to mycoplasmas including M. hyo.

105    Professor Browning has some industry experience, having collaborated on research projects on vaccine development and diagnostics with a range of industry partners including Pfizer, Bioproperties Pty Ltd, Grange Laboratories and BioBest Laboratories.

106    From 1998 to 2017, Professor Browning advised the Australian Pesticides and Veterinary Medicines Authority on the safety, efficacy, chemistry and manufacture of veterinary vaccines.

107    During oral evidence, Professor Browning described himself as “a bit pedantic”. This characteristic made him consider carefully all propositions put to him, or comments made by the other experts before accepting or rejecting them. Professor Browning was not afraid to depart from the comments of the other three expert witnesses where he felt it appropriate.

108    Boehringer pursued a line of questioning during the joint expert session which called Professor Browning’s independence into question. Professor Browning has worked on a number of projects that had received industry funding, including from Pfizer Animal Health (now Zoetis). As a result of these research projects, he is a named inventor on a number of patents co-owned by Zoetis and the University of Melbourne. The other named inventors on at least one of those patents are Zoetis employees. Professor Browning confirmed that he is entitled to a share of the royalties from this patent.

109    All of the research projects funded by Zoetis were declared in Professor Browning’s extensive CV, along with any patents on which he is a named inventor. I consider that Professor Browning was an independent, careful expert who gave considered and useful evidence.

Mr Eichmeyer

110    Mr Eichmeyer is Boehringer’s Director of International Project Management – Vaccines. He has been employed by Boehringer, and its predecessors, since 2001, and is responsible for leading teams involved in vaccine registration across the world. Mr Eichmeyer was the head of a research project undertaken by Boehringer to develop a ready-to-use bivalent M. hyo/PCV-2 vaccine combination product. This project did not lead to the development of a bivalent, ready-to-use vaccine that was superior to Boehringer’s monovalent offerings.

111    Mr Eichmeyer swore one affidavit in the proceeding but was not called by either party. Zoetis tendered part of his affidavit

Zoetis’ challenge to Dr Nordgren

112    Zoetis challenged Dr Nordgren’s independence and ability to give impartial and relevant expert evidence on four grounds.

113    First, as a result of his lengthy and ongoing consulting arrangements with Boehringer and its predecessors, Zoetis contends that Dr Nordgren cannot be considered to be an independent witness.

114    Second, Zoetis submits that Dr Nordgren took into account significant non-common general knowledge in forming his opinions. Dr Nordgren failed to disclose his involvement in highly relevant confidential in-house M. hyo research work during his time at Merial. This, combined with a failure in his evidence to differentiate his use of the knowledge derived from his involvement with in-house research work from information generally known to all in the field in the formation of his opinions, means that the Court cannot disentangle the confidential in-house information and the common general knowledge used to form the basis of his opinions.

115    Third, Zoetis submits that Dr Nordgren is not representative of the hypothetical non-inventive person skilled in the art. Zoetis contends that Dr Nordgren’s inventorship on relevant patents and patent applications, and his participation in inventive research work relevant to the subject matter of the Applications, before the priority date, means that he is particularly ill-equipped to opine on the knowledge or approach of an uninventive person of ordinary skill in the field of swine vaccine development.

116    Fourth, Zoetis submits that Dr Nordgren’s role at Merial and Boehringer was not limited to undertaking research and experiments in the development of animal vaccine products. His ongoing consultancy role at Boehringer and its predecessors required him to review, and be involved in (including by providing expert witness testimony), challenges to competitors’ patents and patent applications relating to vaccine products. Zoetis submits that, in giving evidence in this proceeding, Dr Nordgren was acting under an obligation to act in the best interests of Boehringer and was not acting as an independent expert.

117    Accordingly, Zoetis submits that the Court should be reluctant to rely on Dr Nordgren’s evidence other than where it has been corroborated by the other experts.

Ongoing consulting role with Boehringer

118    Zoetis submits that Dr Nordgren’s relationship with Boehringer, its predecessor companies, and related entities is unique by reason of its longevity and, in particular, having regard to the fact that the services provided by Dr Nordgren relate not only to technical matters, but also to patent reviews, strategy and providing expert evidence.

119    Over a 20-year period from 1996 to 2016, Dr Nordgren held senior positions in Boehringer’s predecessor companies, including Vice President, Global Biologics Research & Development at Boehringer Ingelheim Vetmedica (1996-1999), Executive Director, Global Biologics Research & Development at Merial Ltd (1999-2001), Head of Research & Technology Acquisition at Merial Ltd (2001-2006), Vice President & Global Head of Biologics Research & Development at Merial Ltd (2006-2013) and Vice President & Global Head of External Innovation at Merial Ltd (2013-2016).

120    In his first affidavit, Dr Nordgren stated in paragraph 3 that “[a]part from my role as an expert witness, I have no direct relationship with either the Boehringer Ingelheim or Zoetis groups of companies”.

121    Dr Nordgren’s third affidavit was filed the day before the trial commenced. In his third affidavit, Dr Nordgren was asked to “describe in greater detail any work that I undertake for the Boehringer Ingelheim group of companies, referred to in paragraph 3 of my First Affidavit”. Dr Nordgren clarified that his reference in his first affidavit to his role as an expert witness was intended to encompass his role as an expert witness in this proceeding and other cases, and stated:

I undertake consulting work for the Boehringer Ingelheim group of companies on matters including contract disputes and patent litigation. This work includes acting as an independent expert witness for the Boehringer Ingelheim group of companies. However, the work is broader than being an expert witness. This is because, from time to time, I review and provide comments to the Boehringer Ingelheim group of companies on patents and patent applications in matters where I am not also asked to act as an expert witness. I wish to correct paragraph 3 of my First Affidavit to the extent it suggested that I am always formally engaged by the Boehringer Ingelheim group of companies as an expert witness in matters where I provide consulting services.

(Emphasis added.)

122    As revealed in his third affidavit, after ceasing his employment with Merial in 2016, Dr Nordgren was engaged by Merial as a consultant pursuant to a confidential agreement. Sometime later, Dr Nordgren entered into a “very similar” agreement pursuant to which he provides consulting services for the Boehringer Ingelheim group of companies (which includes Boehringer). The consultancy services provided by Dr Nordgren under the terms of that agreement do not relate to vaccine development, but rather to “contract disputes and patent litigation”.

123    Dr Nordgren agreed that part of his Boehringer consultancy role required him to review, and be involved in (including by providing expert witness testimony) challenges to competitors’ patents and patent applications relating to vaccine products. Since November 2015, Dr Nordgren has been called by Merial and Boehringer as an expert witness in eight domestic animal vaccine related patent proceedings, including in the European Patent Office, the US Patent Office, this Court and the Australian Patent Office. Dr Nordgren did not recall being aware of, or exposed to, the Applications prior to being asked about them in the course of preparing his evidence in this proceeding.

124    The existence of Dr Nordgren’s consulting agreements with Merial and Boehringer was disclosed for the first time in his third affidavit. In cross-examination, Dr Nordgren confirmed that his work for the Boehringer group of companies and their predecessors under those agreements is “wider than acting as an independent expert witness”.

125    The first approach to Dr Nordgren to act as an expert in this proceeding was made by Boehringer, rather than Boehringer’s instructing solicitors in this proceeding.

126    In the course of cross-examination, the following exchange took place between Zoetis’ senior counsel and Dr Nordgren:

[Counsel]: And under that contract [i.e., the Boehringer Consultancy Agreement], although we don’t have it, you tell us in paragraph 5 [of your third affidavit], that under that contract, you undertake consulting work from BI group of companies on matters including contract dispute and patent litigation; correct?

DR NORDGREN: That’s correct.

[Counsel]: And under that contract, you’re required to act in the best interests of BI; correct?

DR NORDGREN: On those cases that I’m working on; yes.

[Counsel]: And there’s no requirement in that contract that you act independently of BI if you’re acting as an expert witness; do you agree?

DR NORDGREN: I would agree.

[Counsel]: And in these proceedings, you are engaged, pursuant to that contract with BI, aren’t you?

DR NORDGREN: Yes, sir.

127    Zoetis submits that Dr Nordgren’s answers in the exchange set out above make clear that, in giving evidence in this proceeding, Dr Nordgren understood himself, first, to be under an obligation to act in the best interests of Boehringer and, secondly, to be under no obligation to act independently, an approach which is inconsistent with the Court’s Expert Evidence Practice Note and the Harmonised Expert Witness Code of Conduct.

128    Boehringer sought to explain the reason for Dr Nordgren’s third affidavit as being to clarify that Dr Nordgren’s reference to his “role as an expert witness” was intended to encompass his role as an expert witness in other proceedings in addition to the present. Boehringer says that it became apparent at a hearing before the Registrar that Zoetis had interpreted the words as only referring to this proceeding. However, the third affidavit goes beyond clarifying Dr Nordgren’s role as an expert witness.

129    Dr Nordgren’s third affidavit makes plain that his role with Boehringer is broader than his being engaged as an expert witness. His statement in his first affidavit: “Aside from my role as an expert witness, I have no direct relationship with either Boehringer Ingelheim or Zoetis groups of companies” (emphasis added), was not correct when the first affidavit was made. If Dr Nordgren’s third affidavit had not been filed on the eve of the trial, the Court would not have been informed of Dr Nordgren’s ongoing consulting role with Boehringer.

Regard to confidential information not part of common general knowledge

130    In his first affidavit Dr Nordgren mentioned two instances of experience with M. hyo: he oversaw or supervised the development of “an industry-first, one-dose inactivated whole cell vaccine, also known as a bacterin for M. hyo in pigs”, and whilst at Merial, his involvement in “the development of a significant number of vaccine products, including for the following diseases of swine: (a) M. hyo; (b) PRRS; and (c) Porcine circovirus 2 (PCV-2), including the first PCV-2 vaccine, which was released first in Europe and subsequently in other countries”. No further details of his prior experience with M. hyo were provided.

131    It emerged in the course of the concurrent evidence session that, before the priority date, in approximately 2008 or 2009, Dr Nordgren had led a team of researchers at Merial engaged in experimental work aimed at combining a PCV-2 vaccine with, amongst others, an M. hyo vaccine.

132    Dr Nordgren’s experimental M. hyo and PCV-2 work included efforts aimed at addressing impediments the M. hyo formulation may present to combining it with a PCV-2 antigen. Strategies investigated by Dr Nordgren and his colleagues at Merial included attempting to source serum with a reduced likelihood of containing anti-PCV-2 antibodies, as well as attempting to clarify serum of anti-PCV-2 antibodies. The research work was done in an effort to develop a process that would eliminate to a substantial degree the antibodies from the serum to enable Merial to formulate a vaccine (the in-house Merial M. hyo research work).

133    According to Dr Nordgren, the M. hyo experimental work was regarded by Merial as being highly confidential and a trade secret that Merial was concerned to ensure that its competitors did not find out. The confidential information obtained by Dr Nordgren as a result of the Merial M. hyo experimental work was not publicly disclosed. The confidential in-house knowledge gained by Dr Nordgren in the course of the Merial M. hyo experimental work did not form part of the common general knowledge of the person skilled in the art.

134    Boehringer submitted that it was “unsurprising” that Dr Nordgren did not expressly mention his prior work at Merial on combination vaccines, even after reviewing the Applications. According to Boehringer, the Applications concern the use of an M. hyo supernatant, whereas Dr Nordgren’s work at Merial involved its existing bacterin product and seeing if they could be improved with a goal to potentially combining them with PVC-2.

135    Boehringer also submitted that Dr Nordgren’s first affidavit “does impliedly” refer to his in-house M. hyo/PCV-2 research work. Boehringer explained that part of that work involved looking for PCV-2 antibody free serum, and that Dr Nordgren discussed his experience in trying to source PCV-2 antibody free serum in his affidavit, but was not taken to that in cross-examination.

136    However, in Dr Nordgren’s first affidavit, he stated that in April 2012 there was a need for bivalent M. hyo/PCV-2 and trivalent M. hyo/PCV-2/PRRS combination vaccines. There was no requirement or limitation that the M. hyo be in the form of a supernatant.

137    Dr Nordgren conceded that he did not refer to the in-house Merial M. hyo research work in any of his affidavits filed in the proceeding, including his third affidavit filed on the eve of the trial.

138    Dr Nordgren agreed that it would have been “highly relevant” and “important” to disclose this work to the Court. In particular, Dr Nordgren agreed that the fact he had engaged in the in-house Merial M. hyo research work was material to assessing the difference between his own knowledge and the knowledge of others in the field.

139    Dr Nordgren agreed in cross-examination that he took information from the confidential in-house Merial M. hyo research work into account in reaching the views he expressed in his affidavits in these proceedings.

[Counsel]: And to the extent that you had held any view as at April 2012 about the potential preparations based on the supernatant of M. hyo vaccines, that view was based on matters including your particular knowledge regarding experimental vaccines. Correct?

DR NORDGREN: That’s correct.

140    Zoetis submits that Dr Nordgren’s failure to disclose his involvement in the in-house Merial M. hyo research work, or the fact that he took this work into account when preparing his affidavits, presents insurmountable difficulties for the evaluation of Dr Nordgren’s evidence. According to Zoetis, it is impossible to determine which of the opinions expressed by Dr Nordgren in his affidavits and the joint expert session are based upon material which formed part of the common general knowledge of those skilled in the art, and those which are infected with the confidential in-house Merial information.

141    Zoetis contends that the effect of Dr Nordgren’s failure to disclose his involvement in the in-house Merial M. hyo research work is compounded by the absence of any instruction to Dr Nordgren in the course of preparing his affidavits to differentiate between his own particular knowledge (such as that obtained from confidential in-house research projects) and matters he considered to be generally well known and accepted by those skilled in the area.

142    Dr Nordgren was aware in April 2012 of studies demonstrating that specific enrichments of different culture fractions can improve the effectiveness of a vaccine response. He provided no details of the studies but observed that the exact compositions of commercially available M. hyo vaccines were most often kept confidential, as a trade secret.

143    Before the priority date, Dr Nordgren had collaborated with Professor Ross (the author of the Ross 1984 paper referred to in the Okada papers discussed below in the inventive step section) to research an experimental subunit vaccine against M. hyo using the 97kD antigen. The 97kD antigen research program was not pursued further as the 97kD antigen on its own did not produce sufficient protection. The collaborative work with Professor Ross was not published. Dr Nordgren agreed that he knew from the Ross paper and his teams’ own experiments that the combination of different antigens in supernatant based M. hyo vaccines were immunogenic and provided an adaptive immune response.

144    In addition, Dr Nordgren was involved, before the priority date, in the development of a first-in-class one-dose inactivated whole-cell (bacterin) vaccine against M. hyo that was commercially released around 1998, the first commercially available vaccine against PRRS virus, and the first PCV-2 vaccine to be released.

145    Before the priority date, Dr Nordgren worked with and tested experimental M. hyo vaccine preparations made from M. hyo cell culture supernatant fractions in the course of his work at Solvay and in the course of supervising the work of his team at Boehringer. In both cases, the project did not result in the launch of a commercial product and the information concerning those M. hyo supernatant was never made public.

146    I consider that the in-house work done by Dr Nordgren on a bivalent M. hyo/PCV-2 combination vaccine, the choices made by his research team and the reasons for those choices, and the success or failure of that work may well have had a role in the formation of the opinions which Dr Nordgren was being asked to give when addressing the development of a new or improved bivalent M. hyo/PCV-2 vaccine.

Not representative of non-inventive person skilled in the art

147    During the concurrent session, Dr Nordgren agreed that he is “inventive” in relation to M. hyo/PCV-2 combinations, and that he “knew more than most” people who participate in project teams associated with vaccines.

148    Dr Nordgren is named as an inventor on a number of patents and patent applications. Several examples were tendered during the hearing. That Dr Nordgren is listed as an inventor on patents and patent applications is not apparent from his first affidavit (or subsequent affidavits) as he did not annexe a curriculum vitae (CV) listing the patents and patent applications on which he is listed as an inventor.

149    Boehringer submits that Dr Nordgren’s CV was omitted from his affidavits simply because the information in his CV was already summarised at paragraphs 6 to 20 of his first affidavit, and that no inference can be drawn from his failure to do so as the Expert Evidence Practice Note does not require an expert to annexe a CV. Whilst that may be correct, the inference is not sought to be drawn from the absence of a CV per se, rather from the absence of detailed information that would usually be found in a CV, such as inventorship on patents and published papers.

150    Being listed as an inventor on a patent itself is unsurprising in an expert witness in a patent case. However, it is relevant when assessing the evidence of an expert, for the purpose of determining by reference to the non-inventive person skilled in the art whether an invention as claimed involves an inventive step, to know whether the expert is listed as an inventor on one or multiple patents and patent applications. It will also be relevant if the invention claimed in the patent or patent application is in the same or a related field to the patent in suit.

151    At least one family of Dr Nordgren’s patents and patent applications were directed to subject matter bearing a relationship to the subject matter of the Applications, including the WO 462 application in the name of Merial Limited (WO 2005/009462), filed on 26 July 2004 (and the Australian patent granted on the WO 462 application: AU 2004259034). Dr Nordgren’s inventorship on the WO 462 application or its Australian progeny was not disclosed in any of his affidavits.

152    The WO 462 application is entitled “Vaccine formulations comprising an oil-in-water emulsion”. Claims 26 and 27 of the WO 462 application are directed to a novel M. hyo/PCV-2 combination vaccine, including a one-dose regimen. Although Dr Nordgren initially sought to suggest that the claims directed to M. hyo/PCV-2 combination vaccines were not adequately supported by experimental work and may have been dropped after the application was filed, he subsequently accepted that those claims were retained in an Australian patent granted on the WO 462 application.

153    Dr Nordgren agreed that it would be relevant for the Court to take the WO 462 application into account in determining the difference between his knowledge and the knowledge of those of ordinary skill in the art.

Conclusion on Dr Nordgren

154    Dr Nordgren’s first affidavit omitted relevant information including, in particular, his prior in-house experience with an M. hyo/PCV-2 vaccine and his ongoing consultancy with Boehringer. Details only emerged subsequently due to the tenacity of Zoetis’ legal team.

155    I do not consider that Dr Nordgren engaged in a deliberate practice to hide the extent of his prior knowledge of M. hyo by omitting his in-house Merial research experience from his affidavit. I consider that Dr Nordgren did his best to give independent evidence and answer the questions put to him by his instructors. However, the absence of a detailed description of that earlier confidential research work is unfortunate. That absence, combined with a lack of any explanation by Dr Nordgren as to how he was able to put any knowledge derived from that work aside in formulating his opinions, undermines the weight that would otherwise be given to his evidence as to what would be obvious to the non-inventive person skilled in the art, armed only with the common general knowledge and the Okada documents (separately or in combination) seeking to develop a new or improved M. hyo/PCV-2 vaccine, or trivalent M. hyo/PCV-2/PRRS vaccine.

156    Dr Nordgren agreed that he had used information that was not part of the common general knowledge in formulating his opinions. I am unable to disentangle the parts of Dr Nordgren’s evidence which are infected with information not generally known to others in the field of vaccine development from those that are based on solely common general knowledge. Where, particularly in matters relating to inventive step, Dr Nordgren’s evidence is not corroborated by the evidence of the other experts, particularly Professor Chase and Professor McVey, I will not accept that evidence. I note, however, that in large part, Dr Nordgren’s evidence was corroborated by the other experts.

157    Dr Nordgren’s evidence on the best method issue is in a different category. Dr Nordgren gives evidence as to what is disclosed in the examples of the Applications. This evidence was unchallenged, and I do not consider it to be undermined by his failure to disclose the information about his prior research and ongoing consultancy.

PERSON SKILLED IN THE ART

158    In Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1, Gleeson CJ, McHugh, Gummow, Hayne and Callinan JJ said at [24]:

It is well settled that the complete specification is not to be read in the abstract; here it is to be construed in the light of the common general knowledge and the art before 2 July 1984, the priority date; 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”.

159    For the purposes of the Joint Expert Report, the parties defined the relevant field as relating to animal vaccine development.

160    Zoetis submits that the technical field of the invention described and claimed in the Applications is animal vaccine development, in particular, vaccines for swine. According to Zoetis, the notional skilled team to which the Applications are directed would include microbiologists (including bacteriology and virology) together with individuals having expertise in the development and evaluation of vaccine candidates.

161    Boehringer contends that the skilled person to whom the Applications are directed is a team with experience in the field of animal health. That team consists of a vaccinologist, with expertise in vaccine development and formulation for animals, and an expert in the field of immunology and the development of vaccines for swine.

162    Where the parties differ is that Zoetis submits that the Applications are directed to a team with specific expertise in, and a deep understanding of, M. hyo (or mycoplasmas generally), and that depending on the combination of antigens in the immunogenic composition, the skilled team would collaborate with, or consult, scientists with a deep understanding of each target pathogen or disease (the list in claim 3 of the 535 Application and claim 8 of the 537 Application). Boehringer disagrees.

163    Each of the Applications disclose immunological compositions (including vaccines) being M. hyo platforms which may be combined with other antigens such as PCV-2 and those listed in claim 3 of the 535 Application and claim 8 of the 537 Application. Zoetis submits that the team should be differently constituted for each combination of antigens to be included in the immunogenic composition, and that the team would collaborate with academics or specialists with a deep understanding of each of the target pathogens and who had familiarity with the state of research and the literature published in relation to their particular pathogen.

164    Zoetis’ purported “skilling up” of the skilled addressee has particular relevance in the context of the assessment of the challenges for want of disclosure and support made in respect of the multiple antigen claims (for example, claim 3 of the 535 Application and claim 8 of the 537 Application).

165    Boehringer submits that defects in the support and disclosure requirements cannot be solved by adding specialists to the team such that the common general knowledge is expanded to include their specialised knowledge.

166    Boehringer submitted that a similar argument was considered and rejected by Jagot J in Gilead Sciences Pty Ltd v Idenix Pharmaceuticals LLC (2016) 117 IPR 252, in relation to the old (pre-RTB Act) test for sufficiency. Idenix contended that the relevant area of discourse may be characterised as the development of nucleoside analogues for use as antiviral drugs for Flaviviridae infections, including HCV. Gilead described that characterisation as so specific that it “is almost to require a person to have worked on the development of the invention in suit”. At [207], Jagot J observed:

Given the terms of the Idenix patent I do not consider Idenix’s characterisation unreasonable. This does not mean, however, that every expert must have expertise across the entire spectrum of the area of discourse in order to give evidence relevant to the common general knowledge. Nor does it mean that, insofar as the chemistry is concerned, the skilled addressee is a person with specialist, even unique (as in the case of Dr Borthwick), experience in the fluorination of a tertiary hydroxyl. As Idenix no doubt intended, to adopt this approach would pitch the debate at a level of specificity ensuring Professor Meier and Dr Borthwick alone could be representative of the skilled addressee. I do not accept this and I also do not accept that the evidence given by Professor Furneaux and Dr Lambert is immaterial to the common general knowledge of the skilled addressee.

167    Her Honour held at [209] that it was immaterial what label was placed on the notional skilled addressee, and continued:

The issue is the knowledge which the skilled addressee is taken to have, which is the common general knowledge of the skilled addressee of documents dealing with the development of nucleoside analogues for use as antiviral drugs for Flaviviridae infections, including HCV. As Gilead submitted, the need for inferences about the common general knowledge to be based on the evidence:

… cannot be avoided by artificially constructing a skilled team to include a person …with highly specific and unusual knowledge gained through literature searches or idiosyncratic experience not shared by others in the field. Nor can it be avoided by artificially excluding others who happen not to possess that knowledge. The common general knowledge is a general body of knowledge known and used by all those in the field.

168    The skilled addressee “is not an avatar for expert witnesses whose testimony is accepted by the court”, but a tool for analysis: AstraZeneca AB v Apotex Pty Ltd; AstraZeneca AB v Watson Pharma Pty Ltd; AstraZeneca AB v Ascent Pharma Pty Ltd (2015) 257 CLR 356 at [23] (AstraZeneca HCA). The issue is what common general knowledge is to be attributed to the skilled addressee for the purposes of assessing the grounds of invalidity alleged.

169    After reviewing the principles applicable to assessing the common general knowledge at [210] to [214], Jagot J concluded in Gilead at [219]:

In other words it is apparent from his evidence that Professor Meier had a particular expertise in the fluorination of nucleoside analogues by reason of work he had done in 1999 as part of which he had read and assimilated lots of papers about fluorination reactions. While some familiarity with fluorination reactions might be imputed to the skilled addressee of the 350 application and the Idenix patent it would be wrong to conceive of the skilled addressee as having specialist experience and expertise in that regard by reason of personal involvement in the fluorination of nucleosides (or, in the case of Dr Borthwick, carbocyclic nucleosides). Neither the 350 application nor the Idenix patent is directed towards such a narrow topic as the fluorination of nucleosides. I do not accept that the skilled addressee can be treated as having available as part of the common general knowledge all of the expertise and experience in the fluorination of nucleosides that Professor Meier and Dr Borthwick had by reason only of their involvement in particular projects for that purpose.

(Emphasis added.)

170    The field of the invention does not change. The characteristics attributed to the hypothetical person skilled in the art do not change according to the ground of invalidity which they are used to assess. In other words, the skilled addressee is not to be “skilled up” in relation to the support and disclosure requirements, and dumbed down for inventive step.

171    Neither side led evidence as to what additional matters might constitute the common general knowledge of specialists in the 5 Pathogens or those pathogens listed in claim 3 of the 535 Application. Boehringer, because it did not consider such specialist knowledge appropriate to the skilled addressee, and Zoetis, as it submitted that the onus was on Boehringer to establish the specialist knowledge of the skilled addressee.

172    Professor Browning, who came from a more academic than commercial background, had a greater understanding of mycoplasmas than the other experts. However, none of the experts were a specialist with a deep understanding of any of the 5 Pathogens relied on by Boehringer in relation to its disclosure and support grounds of challenge, which is considered later.

173    None of the Applications is directed towards the identification of the particular antigens protective against the range of potential microorganisms, which may be combined with the M. hyo supernatant platform. Rather, the 535 and 537 Applications claim the combination of the M. hyo supernatant platform combined with at least one additional antigen protective against a microorganism selected from the specified list, once that antigen or antigens have been identified.

174    I consider that persons skilled in the art, those with a practical interest in the subject matter of the invention, will include veterinary microbiologists (with expertise in bacteriology and virology) and immunologists with skill and expertise in the development and formulation of vaccines for animals, in particular swine. Each of the expert witnesses called in the present matter have experience in the development of animal vaccines against a range of pathogens, and are qualified to provide evidence in this proceeding.

CONSTRUCTION

175    There is one principal issue of construction in this case, Boehringer having abandoned its challenge to “substantially free”. That is, what was called by Zoetis, “the antigen issue”, which primarily arises from the use of the term “comprising” in claim 1 of the Applications. The resolution of this construction issue determines the extent of the invention required to be disclosed and supported for the purposes of s 40 of the Act.

176    Before addressing “the antigen issue”, it is necessary to construe the other integers in the claim to provide context. The construction of the remaining integers of the claim was not a matter of great dispute.

177    First, the principles of construction of patent claims are well settled and established. See Jupiters Ltd v Neurizon Pty Ltd (2005) 65 IPR 86 at [67] (per Hill, Finn and Gyles JJ).

178    I highlight the following principles which are of particular relevance to this case:

(a)    The Court is 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: GlaxoSmithKline Consumer Healthcare Investments (Ireland) (No 2) Ltd v Generic Partners Pty Ltd (2018) 2131 IPR 384 at [106] (per Middleton, Nicholas and Burley JJ).

(b)    In construing the claims, a generous measure of common sense should be used: Ranbaxy Laboratories Ltd v AstraZeneca AB (2013) 101 IPR 11 at [108] (per Middleton J); and Streetworx Pty Ltd v Artcraft Urban Group Pty Ltd (2014) 110 IPR 82 at [58]–[69] (per Beach J).

(c)    A construction that gives the claims a sensible and workable meaning is to be preferred: Asahi Kasei Kogyo Kabushiki Kaisha v WR Grace & Co (1991) 22 IPR 491 at 515 per Heerey (not disturbed on appeal: WR Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) 25 IPR 481 at 500–501 (per Northrop, Lockhart and Cooper JJ)). A construction that would lead to an absurd result is to be avoided: NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd (1993) 26 IPR 513 at 287 (per Northrop, Lockhart and Burchett JJ).

(d)    Although 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: Welch Perrin & Co Pty Ltd v Worrel (1961) 106 CLR 588 at 610 (per Menzies J).

(e)    Claims are to be construed by the Court through the eyes of the skilled addressee of the particular patent and without regard to the alleged infringing article: Fresenius Medical Care Australia Pty Ltd v Gambro Pty Ltd (2005) 67 IPR 230 at [95] (per Wilcox, Branson and Bennett JJ).

(f)    Claims should not be construed by applying “the kind of meticulous verbal analysis in which lawyers are too often tempted by their training to indulge”: Catnic Components Ltd v Hill & Smith Ltd [1982] RPC 183 at 243 per Lord Diplock, quoted with approval in Artcraft Urban Group Pty Ltd v Streetworx Pty Ltd (2016) 117 IPR 210 at [79] (per Greenwood J).

(g)    A patent may claim less than it teaches or enables: Kirin-Amgen v Hoechst Marion Roussel (2004) 64 IPR 444 at [33] (per Lord Hoffmann).

179    Claim 1 of the 535 Application claims an “immunogenic composition”, claim 1 of the 537 claims a “multivalent immunogenic composition”, and claim 1 of the 540 claims a “trivalent immunogenic composition”.

180    The term “immunogenic composition” is defined in the body of each specification to mean “a composition of matter that comprises at least one antigen which elicits an immunological response”. An “immunological response” is said in the specification to include, but not be limited to, effects such as the production or activation of antibodies, B cells and helper T cells, amongst others, directed specifically to an antigen or antigens included in the composition. As defined in the specification, an “immunogenic composition” is not required to elicit a protective immunological response which provides enhanced resistance to new infection, and/or reduction of the clinical severity of the disease caused by the antigen or antigens.

181    An immunological composition may or may not elicit a protective response. That the immunological response need not be protective for claim 1 of the Applications is confirmed by the existence of dependent claims which introduce such a requirement. For example, claim 7 in the 535 Application claims the composition of any of claims 1 to 6, “wherein the composition elicits a protective immune response against M. hyo”.

182    In the 537 and 540 Applications, the immunogenic composition claimed in claim 1 is a “multivalent” or “trivalent” immunogenic composition respectively. The term “multivalent” is defined in the specifications as meaning a vaccine (the term “composition” is not used in the definition) containing more than one antigen, whether from the same species or from different species, or a vaccine containing a combination of antigens from different genera. Again, the reference to an “immunogenic composition” does not require that each antigen provide any particular level of immunological response, such as a response which is protective in relation to a particular condition.

183    The 540 Application claims differ to those of the 535 and 537 Applications, in that claim 1 expressly claims (and is limited to) a trivalent composition. There is no dependent claim listing additional antigens as there is in both the 535 and 537 Applications. A trivalent composition does not admit the inclusion of more than three antigens, whether from the same species or from different species.

“Substantially free”

184    The experts agreed that “substantially free” means “close to pure of a specific component, but not absolutely or completely free” such that the supernatant may still contain trace amounts of IgG and/or immunocomplexes. They also accepted that the claim does not define or specify any quantitative threshold or require that any particular test be used, and that the assessment of whether a composition is free of the relevant components might depend on factors such as the technique used to detect them and the conditions under which the test is conducted.

185    In the context of Table 3 (of Example 3), Professor Browning suggested a numerical threshold S/P ratio (sample to positive ratio) of less than 0.099 as a reasonable threshold for what he considered would be “substantially free”. He agreed that the figure was not drawn from the specification, and that the S/P ratio was expressed to be relative to a positive control, which, in the case of Table 3, he agreed that he did not know how much antibody was in the positive control.

186    Professor Browning explained that the maximum possible optical density was two, so a ratio of below 0.099 was a significant reduction from the maximum value. Professor Browning agreed that his threshold ratio would allow for some anti-PCV-2 antibodies to be present and cause a degree of interference with the PCV-2 antigen.

187    The term “supernatant” is a technical term which the experts agreed meant the liquid component obtained from a whole bacterial culture that has been separated from substantially all of the bacterial cells and insoluble materials. The separation step would typically occur using centrifugation to separate the insoluble components from the soluble components in commercial vaccine processes, although filtration could also be used.

188    Claim 1 states that the supernatant has been “separated from insoluble cellular material”. The experts agreed that this expression means that the supernatant has been separated from the insoluble cellular fraction. During the expert evidence session, Professor McVey stated this does not require removal of absolutely all insoluble cellular material, some trace amounts may remain. Professor Browning did not consider the words of the specification to provide a threshold or indicate whether some trace amounts of insoluble cellular material could be present in the supernatant. The other experts agreed with this characterisation.

Antigen issue – “comprising”

189    Claim 1 of the 535 Application claims an “immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M hyo) culture”. Claim 1 of the 537 Application claims a “multivalent immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M hyo) culture; and a porcine circovirus type 2 (PCV-2) antigen”. Claim 1 of the 540 Application claims a “trivalent immunogenic composition comprising the supernatant of a Mycoplasma hyopneumoniae (M hyo) culture; and a porcine circovirus type 2 (PCV-2) antigen; and a porcine reproductive and respiratory syndrome (PRRS) virus antigen”.

190    Claim 3 of the 535 Application and claim 8 of the 537 Application, claims the composition of claim 1, further comprising at least one additional antigen which is protective against a microorganism selected from a specified list of microorganisms.

191    Each Application purports to provide a definition of the term “comprising” as used in the specification:

“[C]omprising” is intended to mean that the compositions and methods include the recited elements, but do not exclude other elements.

192    On Zoetis’ construction of the claims, antigens that are not expressly mentioned in a claim (either in terms or by reference to another claim) are not elements of the invention defined by that claim. Those additional elements are not expressly included in the claim, but neither are they excluded.

193    Zoetis refers to the definition of “comprising” in the specification and says that it means that the recited integers (the expressed elements of the claim) are included in the claim, but that the claim is neutral as to other elements that may be present (such as additional antigens, or adjuvants). They are not excluded from the composition, but neither are they required nor the subject of the claim. The claim does not define the invention by reference to the presence, or absence, of that (unidentified) integer.

194    Zoetis submits it is plain that a composition having additional integers not included in the claim can still infringe a claim. But that consequence does not mean that those additional integers must be regarded as part of the invention defined by the claim. Zoetis submits that the use of an immunogenic composition containing an additional antigen would infringe such a claim, but that such a composition did not need to be disclosed or supported by the description in the specification in order for the claim to be valid. This is illustrated by the example of a claim which claims a product comprising elements A+B+C, but which claim is infringed by a product which has elements A+B+C+D. Element D is not expressly claimed, but the product will infringe the claim because A, B and C are present. Element D does not need to be disclosed or supported in the specification for the claim to the product comprising A+B+C to be valid.

195    Similarly, Zoetis submits that the immunogenic composition of claim 1 so defined may be combined with other optional elements, such as a suitable adjuvant, or a pharmaceutically acceptable carrier. Those other elements are not integers of the composition defined by claim 1, but may still be present in the immunogenic composition. According to Zoetis, the person skilled in the art would understand that other elements of vaccines such as an adjuvant may be present in the product of the immunogenic composition claim for it to work, even if it is not expressly mentioned in the claim.

196    Zoetis refers to Lindgren J in General Clutch Corporation v Sbriggs Pty Ltd (1997) 38 IPR 359 at [376]–[377], in which his Honour stated that a construction that would result in non-compliance with s 40 of the Act should be avoided where possible, as a reason to prefer its construction.

197    Zoetis submits that its construction should be preferred as it is the construction that best accords with the language of the claims (considered in their context), gives coherence to the claim set, and is consistent with the nature of the invention as disclosed in the specification as a whole.

198    As it states in its closing submissions, Zoetis relies in particular on:

(a)    the absence in claim 1 of any reference to antigens other than “the supernatant of a Mycoplasma hyopneumoniae (M. hyo) culture, wherein the supernatant of the M. hyo culture has been separated from insoluble cellular material by centrifugation, filtration, or precipitation and is substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin” (M. hyo soluble preparation) (535 Application), the M. hyo soluble preparation and a PCV-2 antigen (537 Application) and the M. hyo soluble preparation, a PCV-2 antigen and a PRRS antigen (540 Application);

(b)    the use of the words “further comprises” or “in conjunction with” in all claims that identify additional antigens. It says that “further” would be otiose on Boehringer’s construction;

(c)    the use of the words “additional antigen” in claims identifying antigens other than M. hyo (535), M. hyo and PCV-2 (537), or M. hyo, PCV-2 and PRRS (540), again would be otiose on the Boehringer construction;

(d)    the dependencies of claims that refer to any “additional antigen” claim;

(e)    separately, and despite the extensive discussion about PCV-2 in the 535 specification, the deliberate absence of any reference to PCV-2 in the claims of the 535 Application;

(f)    similarly, the absence of any reference to PRRS in the claims of the 537 Application, despite it being discussed in the 535 specification; and

(g)    the invention as disclosed in the specification, which indicates that it is concerned with the ability to create particularly useful combinations of antigens, rather than combinations of any and all antigens.

199    In contrast, Boehringer propounded an inclusive construction of “comprising” and the claim, which it submits accords with Burley J’s construction of a closely analogous claim containing the term “comprising” in Merck Sharp & Dohme Corporation v Wyeth LLC (No 3) (2020) 155 IPR 1.

200    Given the disclosure in the body of the specification, Boehringer submits that the skilled person would understand that an immunogenic composition of the kind claimed in claim 1 may contain components other than those specifically identified in the claim, including additional antigens of the kind described in the specification (and claimed in claim 3), and other components such as adjuvants and pharmaceutically acceptable carriers (claim 6). It follows that the immunogenic composition is not limited to the features expressly referred to in the claim but may include additional antigens (such as those listed in claim 3 of the 535 Application) and other components.

201    On Boehringer’s proposed construction, by reason of the word “comprising” in claim 1 of the 535 and 537 Applications, Boehringer contends that:

(a)    every claim of the 535 and 537 Applications; and

(b)    claims 24 and 25 of the 540 Application;

“encompass” immunogenic compositions comprising antigens protective against microorganisms in addition to those specifically identified in the claim.

202    Boehringer submits that in accordance with orthodox claim construction, the claim set starts with a broad claim, the scope of which is then narrowed by the introduction of dependencies. Boehringer submits that its construction of claim 1 is confirmed by the features of the dependent claims of the 535 Application, which specify, by way of limitation, specific kinds of components that may be included in the immunogenic composition. These include additional antigens (claim 3), an adjuvant (claims 4 and 5) and a pharmaceutically acceptable carrier (claim 6). These claims, being dependent on claim 1, are narrower in scope by reason of the requirement to include the additional components. Their presence emphasises that claim 1 is broader, and encompasses compositions in which those components are present, as well as compositions in which they are not.

203    Boehringer submits that Zoetis’ approach to construction is wrong in principle and contrary to authority. The only relevant distinction on the question of construction is between something that is within the scope of a claim, on the one hand, and something that is outside its scope, on the other. There is no intermediate third position of the kind contended for by Zoetis.

204    Zoetis’ senior counsel, Mr Flynn, accepted that the Merck definition of “comprising” could not be distinguished from the definition in the Applications (see Merck at [179]–[180] (per Burley J)). Rather, he sought to distinguish Merck from the present case. First, on the basis that it was a different patent. Second, the Merck claim used “comprising” twice in the claim, and the only “further comprising” claims added the “further” integer of an adjuvant. Third, on the basis that the Court in Merck was plainly in error to the extent that it interpreted words similar to “does not exclude” to mean “includes”, and to the extent the Court in Merck apparently relied on an analysis which wrongly equated (at [549]):

(i)    all the elements of compositions which would infringe a claim (“fall within the monopoly of the claims”); with

(ii)    all the elements of a composition which are included in a claim for the purposes of identifying the invention defined by the claim within the meaning of s 40.

205    Zoetis submits that is wrong to speak of the “scope of the claim” in the context of construction. It points to the wording of s 40(2)(b) which requires the specification to end with a claim or claims defining the invention, and does not speak of the scope of the claim.

206    Zoetis submits that it is necessary and important to differentiate between the process of construction (which must occur without regard to an alleged infringing article) and the principles concerning infringement, including those concerning infringement of combination claims despite the addition of integers: see Nichia Corporation v Arrow Electronics Australia Pty Ltd [2019] FCAFC 2 at [45] (per Besanko, Jagot and Nicholas JJ). Zoetis submits that whilst claim 1 would be infringed by an immunogenic composition that might have additional antigens in addition to the M. hyo supernatant, those additional antigens are not elements of the composition claimed in claim 1.

207    As the specification describes, the immunogenic composition so defined may be combined with other optional elements, such as a suitable adjuvant, or a pharmaceutically acceptable carrier, or additional antigens. Those other elements are not integers of the composition defined by claim 1.

208    Zoetis submits that “comprising” in this instance should be understood as a practical means of drafting. If claim 1 defined an “immunogenic composition comprising of the M. hyo Soluble Portion and nothing else” then infringement could be avoided by adding any manner of additional things, for example, blue food colouring, or an M. hyo insoluble fraction, or water, or a preservative, and so on. Zoetis submits that its construction, which relates to the particular issue of “additional antigens” is not at odds with the “definition” of “comprising” set out in the specification.

209    Zoetis rejected Boehringer’s suggestion that claim 1 of the 535 Application could be rewritten as “monovalent” (or claim 2 of the 537 Application as “bivalent”). Zoetis submits that the claims of the 535 and 537 Applications include claims that do claim (“further comprise”) additional antigens protective against another pathogen, and which depend for their meaning on the terms of claim 1. Those claims would not make sense if the composition referred to in claim 1 was limited to a monovalent (or, for the 537 Application, bivalent) composition.

210    As Zoetis submitted, Boehringer’s attempt to rely on the inventor’s use of “trivalent” in claim 1 of the 540 Application to construe the claims of the 535 and 537 Applications, was not a legitimate approach to claim construction.

Merck and the meaning of “comprising”

211    In Merck, Burley J considered the meaning of “comprising” in a claim in a similar form to claim 1, involving an immunogenic composition, which used both “comprising” and “comprises” and claimed:

A multivalent immunogenic composition, comprising: 13 distinct polysaccharide-protein conjugates, together with a physiologically acceptable vehicle, wherein each of the conjugates comprises a capsular polysaccharide from a different serotype of Streptococcus pneumoniae conjugated to a carrier protein, and the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and wherein said carrier protein is CRM197.

(Emphasis added.)

212    Like the present case, the specification in Merck also included a definition of “comprising”, in the following terms:

Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

213    Like the present specifications, the specifications in Merck included dependent claims which used the phrase “further comprising”, albeit to claim an immunogenic composition of claim 1 “further comprising an adjuvant” (claim 2 of the 013 patent, claim 3 of the 844 patent), or which “further comprises one or more antigens for use against otitis media caused by infection with other bacteria” (claim 7 of the 844 patent): Merck at [155] and [157].

214    The relevant issue for determination in Merck was whether the asserted composition patent claims included within their scope one or more Streptococcus pneumoniae serotypes in addition to the 13 serotypes listed. This focussed attention on the meaning of the words “comprises” and “comprising” where they appeared in the asserted claims (“the comprising issue”).

215    In the context of the specification, the respondent, Wyeth, propounded an inclusive meaning for “comprising”, as opposed to an exhaustive meaning (“consisting of”), such that the claim included within its scope any immunogenic composition which had the integers of the claim. This included polysaccharide-protein conjugate which included each of the chosen 13 serotypes, notwithstanding such an immunogenic composition may also contain other integers, such as polysaccharide-protein conjugates of one or more Streptococcus pneumoniae serotypes in addition to the 13 chosen serotypes. Wyeth contended that any multivalent immunogenic composition that had the integers (2) to (5) within it, would infringe, even if additional components (such as additional Streptococcus pneumoniae serotypes) were included.

216    It is to be noted that the additional serotypes submitted by Wyeth to fall within the claim on the construction propounded by it were limited to Streptococcus pneumonia serotypes beyond the 13 listed (ie the 98 serotypes discovered by the time of the trial), and not serotypes at large unrelated to Streptococcus pneumoniae.

217    Merck argued that the claimed compositions were only to polysaccharide-protein conjugates of each of the chosen 13 serotypes and did not encompass immunogenic compositions which also have conjugates from any other Streptococcus pneumoniae serotypes. Merck submitted that the language of the claim made clear that it was limited to the 13 serotypes specified and that where one or more things in a class are expressly mentioned, other serotypes are excluded.

218    Merck submitted that its construction yielded a common sense and practical result. By the priority date, around 90 different serotypes had been described (and since then 98). On Wyeth’s construction, the claims would necessarily extend to an immunogenic composition of 90 or more serotypes and could cover millions of different combinations. Merck described such a construction as “untenable” and “absurd”.

219    Merck’s construction required the word “comprises” to be understood in an exhaustive sense, unlike “comprising” in the same claim.

220    At [178], Burley J held that there was no ambiguity in the use of the word “comprising” in the claim, given the clear definition in the specification. He observed that the question was to be resolved by, first, consideration of the language used in the claim. In this regard, there was no ambiguity. The words “comprising” and “comprises” were clearly defined in the specification in an inclusive sense, or in other words, “including” and “includes”. The only exception is whether the context required otherwise.

221    At [179], Burley J preferred Wyeth’s construction and found:

There can be no doubt that where in integer (1) the claim refers to “[a] multivalent immunogenic composition comprising…” the word “comprising” means “including”. If the definition of the term “comprising” in the body of the specification is not sufficient to establish this point, as much is confirmed as a matter of context, when one considers the claims dependent upon claim 1. For instance, in accordance with orthodox claim drafting, claim 9, which narrows the scope of claim 1, identifies amongst other things additional excipients to be included in the form of the excipients sodium chloride and sodium succinate buffer. If “comprising” was not inclusive, then claim 9 would make little sense.

(Emphasis in original.)

222    At [180], Burley J observed that the scope of claim 1 was apparently defined by reference to what the multivalent immunogenic composition under consideration for the purposes of infringement includes, not by reference to what it consists of. Thus, subject to some exceptions which he noted were not relevant to the case, Burley J held that an immunogenic composition that included all the elements of the integers of the claim would infringe, even if it also contained serotypes in addition to the 13 serotypes identified in the claim.

223    In answer to Merck’s contention that such a construction was “absurd”, Burley J observed at [185]:

In one such argument [Merck] contends that because all of the independent claims identify a specific number of polysaccharide-protein conjugates to be included, it would be “absurd” for the claim to be construed as applicable to a variable number of serotypes, extending potentially to 90 or more serotypes. However, the question at this point is what the claim under consideration means. If it is ambiguous, a construction that is not absurd might be chosen, but the first question is to identify ambiguity. This argument does not do so.

Further authorities on the meaning of “comprising”

224    In Abbott Laboratories v Corbridge Group Pty Ltd (2002) 57 IPR 432, Lee, Emmett and Hely JJ construed “comprising” in the sense of “consisting of”, contrary to the inserted inclusive definition of comprising. The Full Court stated at [31] that if it was construed in an inclusive sense, “then the scope of the claim might be enormous”.

225    The meaning and effect of “comprising” in a patent claim is to be determined having regard to the description of the invention in the whole of the specification: Abbott Laboratories at [34]. The term may bear different meanings in different parts of the specification depending upon the context, and “comprising” may be exhaustive of certain things without being exhaustive of others: Gambro Pty Ltd v Fresenius Medical Care South East Asia Pty Ltd (2004) 61 IPR 442 at [115]–[120] (per Allsop J, as his Honour then was) (not disturbed on appeal: Fresenius at [64] (per Wilcox, Branson and Bennett JJ)).

226    An indication in the specification that “comprises” is “not intended to exclude” other integers or steps may need to refer to the context (which includes the other claims and specification itself) in which the word “comprises” or “comprising” appears: see, for example, Actavis Pty Ltd v Orion Corporation [2016] FCAFC 121 at [168]–[181] (per Allsop CJ, Nicholas and Yates JJ); Apotex Pty Ltd v ICOS Corp (No 3) (2018) 135 IPR 13 at [563]–[578] (per Besanko J); ToolGen Incorporated v Fisher (No 2) [2023] FCA 794 at [159] (per Nicholas J).

227    In Actavis, the relevant claim, claim 17 claimed:

A method for preparing an oral solid composition comprising entacapone, levodopa, and carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, wherein the method comprises

a)     mixing pharmacologically effective amounts of entacapone and levodopa, or a pharmaceutically acceptable salt or hydrate thereof, with at least one pharmaceutically acceptable excipient and a disintegrant to obtain a first mixture;

b)     granulating the first mixture to obtain a granule batch;

c)     adding a pharmacologically effective amount of carbidopa, or a pharmaceutically acceptable salt or hydrate thereof, optionally a lubricant, and optionally one or more pharmaceutically acceptable excipients to the granule batch to obtain a second mixture;

d)    formulating the second mixture into a plurality of dosage forms.

228    The specification in Actavis also included the following explanation:

Throughout the description and claims of the specification the word “comprise” and variations of the word, such as “comprising” and “comprises”, is not intended to exclude other additives, components, integers or steps.

229    In Actavis, the appellants submitted that the primary judge’s construction of claim 17 was based on the word “comprises” having an inclusive meaning where used in the chapeau to the claim. The appellants submitted that, although the specification stated that the word “comprises” is “not intended to exclude other additives, components, integers or steps”, the word “comprises” cannot function to enable the addition of steps or features that are otherwise excluded by the claim itself. The appellants submitted that, if that were not the case, any words in the claim after the word “comprises” would not provide any limitation upon the claimed monopoly, and the claim would be unclear or fail for want of definition

230    The Full Court in Actavis (per Allsop CJ, Nicholas and Yates JJ) overrode the definition the primary judge had given “comprise”, stating at [178] and [179]:

178    Undoubtedly, this indication in the specification must be borne in mind when construing claim 17. It cannot, however, contort the claimed process into a substantively different process. Put another way, the indication cannot give the word “comprise” and its variants an unbridled operation, when the relevant description and claims themselves specify, with appropriate precision, the step or steps to be taken that will provide the promised advantage.

179    For this reason, the better reading of claim 17 is that the word “comprises” must yield to the direction that the intended pharmacologically effective amounts of each active agent must be added at the step in the process that is specified for that addition. In our respectful view, the primary judge erred in construing claim 17 otherwise.

231    The 946 Patent in ICOS included a definition of “comprising” as follows:

Throughout the specification, unless the context requires otherwise, the word “comprise” or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

232    In ICOS, a number of the relevant claims in the 946 Patent referred to a dosage form or method of treatment comprising identified elements. Justice Besanko observed at [563] that it is clear from the definition of the word “comprising” in the 946 Patent that the claims are not restricted to the identified elements. Apotex submitted that the relevant claims of the 946 Patent were not confined to monotherapy, the 946 Patent “contemplates” the co-administration of tadalafil and nitrates. It further submitted, by way of example, that claim 1 would include a composition containing both tadalafil and testosterone and, indeed, the claims would encompass any composition which included the relevant quantity of tadalafil.

233    At [577], Besanko J observed that to construe the 946 Patent as extending beyond monotherapy by reason of the definition of the word “comprising” would be to impermissibly change the nature of the invention. He noted that the Full Court in Actavis had considered a similar definition of “comprise” and rejected the suggestion that the definition was decisive: Besanko J in ICOS at [577] referring to Actavis at [178].

234    These authorities establish that a definition of “comprise” in a specification “cannot give the word ‘comprise’ and its variants an unbridled operation” to contort a claimed invention into a substantially different invention to that described in the specification: Actavis at [178] (per Allsop CJ, Nicholas and Yates JJ). Whether a definition of “comprise” may need to yield to the context of the description of the invention in the specification will be specific to the particular specification in each case.

Consideration

235    I consider that claim 1 of the 535 Application claims an immunogenic composition including at least one M. hyo antigen (one or more). Claim 1 is not limited to one M. hyo protein antigen, but it is limited to M. hyo antigens, ie those found in the M. hyo supernatant.

236    Embodiments of the immunogenic composition as being just the M. hyo supernatant (without the addition of other antigens) described in the specification support this construction. At page 3a, the specification describes embodiments where the soluble portion of the M. hyo preparation “includes at least one” or “two or more M. hyo protein antigens”. The specification explains at p13 that the M. hyo supernatant fraction includes one or more of the identified M. hyo specific protein antigens, such as P46. The description of embodiments at page 16 speak of “at least one M. hyo soluble antigen”.

237    I do not consider that the use of “comprising” extends the scope of claim 1 to include antigens to other diseases such as, but not limited to, those listed in claim 3, nor to a universe of antigens beyond those.

238    The 535 Application is entitled “Mycoplasma hyopneumoniae vaccine”, and the invention is said to relate to the soluble portion of an M. hyo whole cell preparation and its use in a vaccine for protecting pigs against enzootic pneumonia (also called mycoplasmal pneumonia) which is caused by M. hyo.

239    Claim 1 of the 535 is to an “immunogenic composition” comprising the supernatant of an M. hyo culture, wherein the supernatant has been separated from insoluble cellular material by one of three methods so as to be substantially free of both (i) IgG and (ii) immunocomplexes comprised of antigen bound to immunoglobulin. The specification defines an “immunogenic composition” as a composition of matter that comprises at least one antigen which elicits an immunological response.

240    Whilst an “immunogenic composition” may elicit an immunological response which is not sufficient to be considered protective, a composition which elicits a protective response is clearly an “immunogenic composition”. This is also supported by the claim structure where the protective response claims (claims 7 and 8) are dependent upon claim 1.

241    At page 13, the specification describes embodiments of the invention in which the soluble portion of the M. hyo preparation includes at least one M. hyo protein antigen or two or more M. hyo protein antigens. Example M. hyo protein antigens are described in the specification, including: p41, p42, p46, p64, p89, p97, p102 and p216.

242    The immunogenic composition including at least one M. hyo antigen from the soluble portion of the M. hyo preparation described in the specification and claimed in claim 1 is what Zoetis calls an “M. hyo platform”.

243    After a detailed description of the M. hyo immunological composition, the specification describes further embodiments in which the immunological composition of the invention includes at least one M. hyo soluble antigen and at least one additional antigen protective against a microorganism (bacteria, virus or protozoan) which can cause disease in pigs.

244    The person skilled in the art would not understand the invention defined by claim 1 to include a universe of antigens not mentioned in the specification, or even those listed in claim 3. The common sense result is a construction that the invention is limited by what is listed in the specification, and not the universe of other possible antigens that could be included with the M. hyo composition.

245    The composition in claim 3 states the invention “further comprises at least one additional antigen”. Such antigen or antigens is to be selected from a list of microorganisms that cause diseases in pigs.

246    The specifications of the three Applications are very similar. These later embodiments which include additional antigens (ie antigens other than M. hyo) protective against microorganisms that cause diseases in pigs are picked up as the subject of the claims in the 537 and 540 Applications. A specification may describe more than one invention — it does not need to claim everything described in the specification.

247    The immunological composition of claim 1 may also include inessential elements such as excipients and adjuvants. The definition of comprising ensures that the immunological composition of the invention is not limited to only the essential integers listed, but also includes elements which the skilled person would understand to be required for an immunological composition, but not to be an essential part of the invention.

248    Claim 1 of each Application does not expressly refer to an adjuvant being comprised in the immunogenic composition, although some of the dependent claims require one. Nonetheless, the experts explained that most vaccines (other than attenuated vaccines) require an adjuvant. In light of this fact, it is apparent that the skilled addressee would not consider that the immunogenic composition only consists of the supernatant of M. hyo (in the case of the 535 Application) or M. hyo and a PCV-2 antigen (in the case of the 537 Application). However, this same approach would not apply to other antigens not listed in the claims.

249    Claim 3 of the 535 Application claims the composition of claim 1 (or claim 2) wherein the composition further comprises at least one additional antigen which is protective against a microorganism selected from a list of microorganisms. Properly construed, the claim includes within its scope an immunogenic composition of claim 1 which includes one additional antigen selected from the list as well as one which includes many additional antigens selected from the list. No upper limit for the number of additional antigens is expressed in the claim. The language of “comprises at least one additional antigen” indicates that the claim covers the spectrum between these two possibilities. I do not consider that the claim extends to additional antigens beyond those listed in claim 3.

250    Claims 4 and 6 of the 535 Application define a combination of the composition of claim 1 with a further element (an adjuvant or a pharmaceutically acceptable carrier respectively).

251    Zoetis observes that PCV-2 is not included in the list of microorganisms in claim 3. A construction of claim 1 which included a universe of antigens beyond those listed in claim 3, gives the selection identified in claim 3 no work to do, and would be inconsistent with the patent applicant’s deliberate omission of PCV-2 from claim 3.

252    This construction is consistent with the steps of the method set out in claim 18 of the 535 Application.

253    Analogous reasoning applies to the claims of the 537 Application, save that the claims define a “multivalent” immunogenic composition that includes the M. hyo supernatant (including any number of M. hyo antigens) and a PCV-2 antigen in combination.

254    “Multivalent” is defined at page 10 of the specification as meaning a vaccine containing more than one antigen from the same species or a different species, or a vaccine containing a combination of antigens from different genera.

255    In the 537 Application, the list of microorganisms is found in claim 8. Again, the claim includes within its scope a multivalent immunogenic composition which includes the M. hyo supernatant, a PCV-2 antigen, and further comprising at least one additional antigen which is protective against a microorganism selected from the group listed, or many additional antigens selected from the group. In this case, the PRRS antigen is not included in those listed in claim 8.

256    Properly construed, claim 8 defines a multivalent immunogenic composition of claim 1 (or of any of claims 1–7) which includes one additional antigen selected from the list as well as one which includes many additional antigens selected from the list. No upper limit for the number of additional antigens is expressed in the claim. The language of “comprises at least one additional antigen” indicates that the claim covers the spectrum between these two possibilities. I do not consider that the claim extends to additional antigens beyond those listed in claim 8.

257    The claims of the 540 Application are different. Claim 1 claims a trivalent immunogenic composition and expressly refers to the M. hyo supernatant, a PCV-2 antigen and a PRRS antigen.

258    There is no claim in the 540 Application which features a “shopping list” of additional antigens in the 540 Application. Boehringer sought to suggest that the method claims 24 and 25 were broader than claim 1 because they did not specify that the composition is trivalent, and thus Boehringer contended that the claims encompassed immunogenic compositions with more than the three specified antigens. Claims 24 and 25 are to a method of preparing an immunogenic composition containing the M. hyo supernatant, a PCV-2 antigen and a PRRS virus antigen. I do not consider that claims 24 and 25 claim an invention which is broader than an immunogenic composition containing the antigens specified: the M. hyo supernatant, PCV-2 and PRRS.

OVERVIEW OF VALIDITY CHALLENGES

259    There is no challenge to the validity of any of the claims of the three Applications on the grounds of lack of novelty or inutility. Each claim of each of the Applications is thus taken to disclose a new and useful product or method: Sunbeam Corporation v Morphy Richards (Aust) Pty Limited (1961) 180 CLR 98 at 111 (per Windeyer J).

260    Boehringer challenges the validity of the Applications on the following grounds:

(a)    Lack of inventive step;

(b)    Lack of disclosure (s40(2)(a));

(c)    Lack of support (s40(3));

(d)    Lack of best method (s40(2)(aa); and

(e)    Lack of manner of manufacture.

COMMON GENERAL KNOWLEDGE

261    The content of common general knowledge was explained by Aickin J in Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd (1980) 144 CLR 253 (in the context of the Patents Act 1952 (Cth)) at 292, as:

[T]hat which is known or used by those in the relevant trade. It forms the background knowledge and experience which is available to all in the trade in considering the making of new products, or the making of improvements in old, and it must be treated as being used by an individual as a general body of knowledge.

262    In addition to the matters set out in the background section above, the following matters were widely and generally known by those in the field of animal vaccine development and formed part of the common general knowledge of the person skilled in the art as at the priority date.

Animal vaccination

263    Animal vaccination raises very different financial and economic considerations from human vaccination. Animal vaccine production (particularly, in the case of commercially farmed animals) must be cost-effective. In particular, because of the cost of production and because the profits per unit sold are often much lower than a human vaccine.

264    Most commercially reared pigs are only expected to live for approximately 6 months, and to be an economically viable product to the farmer, the pigs needed to reach market weight in that time period in a reasonably healthy condition without high medical overheads from, for example, vaccination costs.

265    Animal vaccination programs impose a significant cost, which varies depending on the method of vaccination. Certain important diseases are almost always present in swine herds, particularly in intensively raised herds, causing chronic economic losses.

266    Swine vaccines are usually administered through intramuscular administration to piglets from three weeks of age.

Types of commercially available vaccines

267    The main types of vaccines for animals that were commercially available before April 2012 included bacterins, inactivated viral vaccines, recombinant sub-unit vaccines and modified live vaccines.

268    Bacterins are inactivated or killed bacterial cells, typically prepared by a fermentation process. The pathogen may be inactivated by various methods including formaldehyde, binary ethanolamine or temperature. Bacterins can consist of inactivated whole cells including at least some of the culture medium in which they were grown (that is, culture supernatant).

269    Modified live vaccines are also known as live attenuated vaccines. Modified live vaccines contain whole pathogens such as viruses that have been attenuated (altered) so that they stimulate an adaptive immune response, but either do not cause disease or cause only a mild or attenuated version of the disease. Modified live virus vaccines suffer from stability issues. For this reason, as at the priority date, most modified live virus vaccines were freeze-dried, or “lyophilized”, to increase storage stability, and were sold in “pellets” of freeze-dried materials. Freeze-dried virus vaccines must be rediluted or resuspended immediately prior to administration using a pharmaceutically acceptable diluent.

270    Sub-unit vaccines are made from antigenic proteins or other suspended cellular components derived from the pathogenic organism of interest. Where the sub-unit of interest is a protein, for example a membrane lipoprotein, it (in some cases) can be recombinantly produced in vitro in a high volume.

271    Adjuvants are compositions containing certain substances that enhance the immune response to an antigen(s). There were many types of adjuvants available by the priority date, including oil or polymer-in-water, water-in-oil or aluminium hydroxide adjuvants. The type of adjuvant used was important in improving the immunogenic response to an antigen, and in improving the duration of immunity.

272    Most vaccines, except attenuated vaccines and some inactivated viral vaccines, (and mRNA vaccines, which were not commonly known or used at the priority date), require an adjuvant.

273    Autogenous vaccines are essentially personalized inactivated whole cell vaccines, which are developed from isolates of a pathogen taken from samples of infected animal(s), for use on the same farm as the animal(s) from which samples were taken.

274    Vaccines include monovalent vaccines, which are vaccines that contain antigen from a single species of microorganism, and multivalent or combination vaccines, which are vaccines that contain antigens from multiple species of microorganisms.

275    Supernatant vaccines were known, but not widely employed, at the priority date. Professor Browning gave evidence that he was aware of toxoid supernatant vaccines, which were directed to pathogens that secrete a toxin, such as Clostridium tetani and Clostridium perfringens. As the toxin is secreted into the culture medium during bacterial culture, toxoid vaccines can be prepared from the bacterial culture medium in which a culture of the bacteria is grown. The bacterial cells of the culture are separated from the culture medium containing the secreted toxin, for example, by centrifugation. The retained supernatant, which contains the toxins, is then treated to prepare the toxoid vaccine. This type of vaccine does not contain cells.

276    Professor Chase was aware of an E. coli supernatant vaccine in which the fimbriae (hair like appendages) of the E. coli cells are broken off and released into the liquid fraction of the cell culture. The cell culture is purified to remove cellular material and other unwanted proteins and impurities, leaving the liquid supernatant fraction.

Swine pathogens

277    The most damaging pathogens of concern to swine producers included M. hyo, PCV-2 and PRRS virus. These three pathogens were known to be the most important contributors to Porcine Respiratory Disease Complex (PRDC) which was of economic concern to swine producers.

278    M. hyo was known to be the primary pathogen responsible for enzootic pneumonia. It was known that M. hyo was highly prevalent worldwide, endemic in almost all commercial swine herds and an important factor in economic losses in the pig industry. Infections with M. hyo are highly prevalent in almost all swine producing areas, and they cause significant economic losses due to increased medication use and decreased performance of the pigs.

279    M. hyo infection enhances the susceptibility of infected pigs to other respiratory pathogens. In addition to causing a range of respiratory complications on its own, M. hyo infection exacerbates secondary infections that result in poor pig performance (eg a reduction in daily weight gain and inefficient feed conversion) and additional healthcare-related costs.

280    Mycoplasmas are single celled prokaryotes which lack a cell wall and only have a cytoplasmic membrane. They lack a nuclear membrane. Mycoplasmas are the smallest free-living self-replicating microorganisms. M. hyo is a relatively fragile organism that is prone to break into multiple membrane fragments during the processing steps involved in vaccine production.

281    PCV-2 is a small virus (a circovirus in the family circoviridae) endemic in swine herds that causes respiratory disease. Symptoms of PCV-2 infection include lung lesions, fever, wasting (ie weight loss), and related economic issues, such as requiring a greater amount of time to reach market weight.

282    The PCV-2 capsid protein “ORF-2” was known to be antigenic, and suitable for inducing immunity in vaccinated animals. As at the priority date, the ORF-2 protein was routinely produced using a modified baculovirus vector containing the gene encoding the PCV-2 ORF-2 protein. This virus was used to infect an insect cell line and cause it to produce the ORF-2 protein. The insect cells were then cultured to the required volume and the ORF-2 protein isolated and mixed with an adjuvant. This composition was then used for the final vaccine product.

283    PRRS virus is an arterivirus and is somewhat more complex than PCV-2. As at the priority date, the primary antigenic components of this virus were not definitively elucidated and understood. There were no successful purified sub-unit vaccines against PRRS virus available by that date. Instead, vaccines against PRRS virus were generally made from modified live PRRS viruses, which were lyophilized for stability, and reconstituted immediately prior to administration.

Culturing M. hyo

284    M. hyo is relatively fragile and prone to breaking into multiple membrane fragments during the processing steps involved in vaccine manufacture.

285    M. hyo has fastidious growth requirements. M. hyo has absolute requirements for exogenous sterols and fatty acids found in porcine serum in order to grow. These requirements generally necessitate growth of M. hyo in media containing animal serum, such as porcine serum. Few bacterial pathogens other than M. hyo require serum in their culture media.

286    Professor McVey described M. hyo as an extremely fastidious and slow growing organism, which must be grown in an expensive, highly enriched laboratory media which, by April 2012, usually included serum from the host animal and/or other tissue components. Culture of M. hyo for study or commercial use was therefore a long and onerous process requiring a specialized laboratory and specialized media. M. hyo growth medium typically includes 10–30% serum.

287    It was known in April 2012 that it was possible to grow M. hyo in synthetic media, but growth yields tended to be far lower and less consistent when working in this way.

288    Growth media containing animal serum could lead to adverse reactions in the vaccinated animal because of the presence of unaccounted for serum components (such as lipids, proteins, immunocomplexes or live microorganisms) in the immunising material.

289    Animal serum, and any other components used in the growth process that are derived from animals, are known as substances of animal origin, or SAO. SAO may include non-immunogenic proteins, lipids, immunocomplexes and sugars. SAO may also include antibodies against pathogens endemic to that animal, to which the animal is highly likely to have been exposed. These antibodies are known as serum-derived antibodies. For example, swine serum may contain serum-derived antibodies against PCV-2, ie antibodies that bind to PCV-2 or an antigen of PCV-2 (PCV-2 antibodies).

290    It was appreciated at the priority date that serum-derived antibodies and other components might reduce efficacy, affect uniformity of batches of vaccine because of analytical interference, and cause adverse reactions in vaccinated animals.

291    As at the priority, date, commercial supplies of PCV-2 antibody-free serum had become increasingly scarce, inconsistent and, for the purposes of commercial production, prohibitively expensive and difficult to source.

Maternal antibodies

292    As at the priority date, it was known that maternal antibodies (transmitted to the piglet via the colostrum) might interfere with a vaccine’s effectiveness in the piglet. PCV-2 antibodies strongly interfered whereas PRRS antibodies did not. Professor Browning explained that PCV-2 being a small, very regular virus induced a very high antibody response.

293    The maternal antibodies in piglets are relatively short lived (persisting in the piglet for around 3-4 weeks) so the timing of the piglet vaccination is a way to mitigate interference from maternal serum antibodies. The technique of timing vaccination to avoid maternal serum antibodies was also used for companion animals such as dogs, cats and horses.

Vaccines available for M. hyo

294    The experts agreed in the JER that, as at the priority date, there were many different antigens and processes examined experimentally for potential use in immunising swine against diseases associated with M. hyo, including: live attenuated vaccines, purified subunit vaccines, freeze-thaw saline solution extracts, supernatants of culture, whole cells, detergent extracts from cells, saline washed whole cells, adjuvants, and centrifuged clarified supernatant.

295    M. hyo vaccines were commercially available as at the priority date. In the JER, the experts noted that trade names vary and change by country and distributor, so they gave three examples of the types of M. hyo vaccine preparations commercially available at the priority date:

(a)    a monovalent M. hyo whole cell bacterin;

(b)    a “rough filtrate” vaccine known as “Mycobuster”; and

(c)    a live attenuated M. hyo vaccine delivered intrathoracically (in China).

296    In the joint session, the experts gave evidence that they knew of the following commercially available M. hyo vaccines at the priority date: Ingelvac CircoFLEX and MycoFLEX from Boehringer, RespiSure-ONE, and Suvaxyn MH1 from Fort Dodge/Zoetis.

297    The vast majority of the commercially available M. hyo vaccines were bacterins. The experts identified only two M. hyo vaccines commercially available at the priority date that were not bacterins: Mycobuster and a live attenuated vaccine administered intrathoracically that was available in China.

298    The M. hyo component of the commercially available monovalent and combination vaccines was based on a bacterin suspension of killed M. hyo cells. These were developed from killed M. hyo cultures, grown in media containing swine serum, and contained the whole cell bacterin in the medium in which it was grown.

299    Bacterins commonly include non-antigenic components. In addition to containing inactivated whole cells, bacterin vaccines may also include cell fragments, cellular membranes and cellular components from whole cells that have lysed as a consequence of the culturing, inactivating or processing steps used to create the vaccine (eg centrifugation and washing steps in the case of washed cell vaccines).

300    The bacterin was the state of the art for M. hyo vaccines in swine as at the priority date. Professor McVey confirmed that bacterins remained “the most suitable format because they were able to provide effective protection against M. hyo infection and were simple and economically efficient to produce”.

301    Professor Chase, Professor McVey and Dr Nordgren were aware of variability issues with the M. hyo bacterin vaccines on the market. Professor McVey described bacterins as “inherently crude compositions”.

302    As at the priority date several surface proteins of M. hyo had been characterised, including p65, p97, p46 and NrdF, and had been shown to induce an adaptive immune response to M. hyo. The fact that something elicits an adaptive immune response does not mean that it will provide protective efficacy, nor that it will provide adequate protection in the sense of being as good as, or better than, available vaccines. Lipoproteins were also suspected to induce an adaptive immune response, but their identity was not well defined.

303    No single characterised M. hyo protein antigen was known to provide adequate protection on its own. Membrane antigens were thought to provide protection. The experts agreed that p46 was characterised as a surface protein. The experts agreed that, during processing steps, membrane fragments including the p46, p65, p97 and NrdF antigenic proteins could break apart from the cells. Professor Chase, Professor McVey and Dr Nordgren considered that the antigen containing membrane fragments could be soluble, and that the antigen proteins themselves could be referred to as a membrane fragment of M. hyo. Professor Browning agreed with the other experts that p46 was a protein that might be contained in a membrane fragment.

304    The article by Simionatto et al, “Mycoplasma Hyopneumoniae: From Disease to Vaccine Development” (2013) 165 (No 3-4) Veterinary Microbiology 234 was published in in April 2013. The Simionatto article conducted a review of the literature on M. hyo vaccine development as at around the priority date. Although published shortly after the priority date, the published studies reviewed by the article were published prior to the priority date and provide a summary of the common general knowledge as to M. hyo vaccines at the priority date.

305    Simionatto confirmed that bacterins formed the basis of currently used commercial M. hyo vaccines and noted that bacterins had high production costs due to the difficulty of cultivating M. hyo in vitro, thus there was a need to develop more effective and lower cost vaccines. Simionatto summarised the investigative work into new vaccines to offer better protection against M. hyo as at just before the priority date. This investigative work included studies evaluating recombinant proteins of M. hyo in various forms of administration and formulations. Dr Nordgren agreed that Simionatto did not suggest that any viable alternative to commercial vaccines had actually been developed as at the date it was published.

Commercially available vaccines for swine pathogens

306    The M. hyo vaccine, “Mycobuster”, was available commercially in Japan as at the priority date. The experts agreed that the “rough filtrate” vaccine, Mycobuster, could also be described as a supernatant vaccine. Mycobuster was prepared by filter-separating the supernatant from some of the whole cells/insoluble material, and using the supernatant-containing filtrate.

307    The concentration of M. hyo is typically measured in colour changing units (CCU), which is a colorimetric test based on the change in pH in the medium resulting from acidic byproducts of growth that indicates the number of live M. hyo bacteria present. During M. hyo culturing, it is typically measured per mL of culture. CCU is a common method for measuring the amount of viable organisms that are in a sample (live bacteria). This method does not measure dead bacteria, insoluble proteins or fragments of membrane.

308    The Mycobuster product information sheet states that the amount of viable bacteria per filtration is 2.5 x 1010 CCU, which reduced to 2.5 x 107 CCU after the filtration step. Professor Chase observed that there had been a reduction of over 1000 fold in the number of viable bacteria in the preparation of the Mycobuster supernatant. The experts agreed that the final Mycobuster vaccine was a supernatant.

309    A one-dose bacterin was the state of the art vaccine for M. hyo. One-dose vaccination is preferable as it requires less labour and can be implemented more easily in routine management practices on the farm.

310    There were PCV-2 vaccines commercially available at the priority date. Examples included Merial’s Circoflex, Porcilis PCV-2 (Intervet/Schering Plough), Ingelvac Circoflex (Boehringer Ingelheim), and Suvaxyn PCV-2 (Fort Dodge/Zoetis). The majority of the PCV-2 vaccine doses sold were recombinant sub-unit vaccines.

311    There were several combination vaccines for protection against M. hyo and PCV-2 available at the priority date. An M. hyo bacterin was commonly included as the base or diluent for other swine vaccines, or was bundled together with other swine vaccines

312    One such product was Ingelvac’s FLEXCombo (from Boehringer Ingelheim). Ingelvac FLEXCombo consisted of two components: an M. hyo component (Ingelvac MycoFLEX) consisting of an inactivated M. hyo bacterin; and a PCV-2 component (Ingelvac CircoFLEX) consisting of inactivated baculovirus-expressed PCV-2 ORF2. This product required only one dose, but was not provided in a single “ready-to-use” pre-mixed vial. Instead, it was supplied in two separate bottles and required mixing of the two components from the separate bottles immediately before injection.