Merial Limited v Intervet International B.V
[2016] APO 39
•27 June 2016
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Merial Limited v Intervet International B.V. [2016] APO 39
Patent Application: 2006289102
Title:PCV-2 vaccine
Patent Applicant: Intervet International B.V.
Opponent: Merial Limited
Delegate: Dr B. Akhurst
Decision Date: 27 June 2016
Hearing Date: 6 April 2016
Catchwords: PATENTS – section 59 opposition to grant of a patent – manner of manufacture – a feature of the claims is not obvious of the face of the specification – manner of manufacture ground not established – novelty – the prior art documents relied on do not provide clear and unmistakable directions to the combination of features in the claims – lack of novelty not established – inventive step – the person skilled in the art would directly be led as a matter of course to try the Blanchard PCV-2 ORF-2 protein in doses encompassed by the opposed claims with a reasonable expectation that it might well solve the problem – the claims lack an inventive step – useful – lack of utility not established – fair basis – not established
Representation: Patent attorney for the applicant: David Myers of Spruson & Ferguson.
Counsel for the opponent: Jon Gottshall.
Patent attorney for the opponent: Jane Hutchison and Jenny Petering of FB Rice.
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2006289102
Title:PCV-2 vaccine
Patent Applicant: Intervet International B.V.
Date of Decision: 27 June 2016
DECISION
The opposition is successful. Claims 1-6 and 8-11 lack an inventive step.
Intervet International B.V. has 2 months from the date of this decision to propose amendments to the claims.
I make no award of costs.
REASONS FOR DECISION
Background
Intervet International B.V. (Intervet) filed patent application 2006289102 via the PCT on 8 September 2006, claiming priority from application EP 05108299.8 filed on 9 September 2005. Following examination, acceptance of the application was advertised on 15 December 2011.
Merial Limited (Merial) filed a notice of opposition on 15 March 2012 and a statement of grounds and particulars (SGP) on 15 June 2012. After extensions of time were granted at each stage, evidence in support was completed on 15 February 2013 and evidence in answer on 16 June 2014. Evidence in reply was completed on 15 September 2014. On 23 March 2015, Merial filed requests to amend the SGP and to file further evidence, accompanied by the evidence. The amendment request and the further evidence were allowed on 16 April 2015 and 9 June 2015, respectively. Intervet filed responding evidence on 10 August 2015.
The matter was heard on 6 April 2016 in Canberra.
The Evidence
Evidence in support consisted of declarations by:
- Christopher Chase dated 13 November 2012 (Chase#1) with exhibits CC-1 to CC-8
- Richard Bevan dated 13 February 2013 (Bevan#1) with exhibits RB-1 and RB-2
Evidence in answer consisted of a declaration by:
- Mark A. O’Dea (O’Dea#1) dated 16 June 2014 with exhibits MOD-1 to MOD-12
Evidence in reply consisted of declarations by:
- Christopher Chase dated 11 September 2014 (Chase#2) with exhibits CC-9 to CC-15
- Richard Bevan dated 10 September 2014 (Bevan#2) with exhibits RB-3 and RB-4 (Bevan#2)
Further evidence consisted of declarations by:
- Christopher Chase dated 18 March 2015 (Chase#3) with exhibits (i)-(iii).
- Jane Hutchison dated 20 March 2015 (Hutchison) with exhibits (i)-(vii).
Evidence in response to the further evidence consisted of a declaration by:
- Mark A. O’Dea dated 10 August 2015 (O’Dea#2) with exhibits MOD-13 to MOD-16.
Grounds of opposition
The grounds of opposition pressed by the opponent were manner of manufacture, novelty, inventive step, utility and fair basis.
Onus of Proof
The request for examination in relation to the patent application was filed on 8 January 2010. As a consequence, the substantive amendments of the Patents Act brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 do not apply to the present patent application. This includes the amendment to subsection 60(3A) that allows the Commissioner to refuse a patent application if satisfied on the balance of probabilities that a ground of opposition has been made out. Instead, the onus of proof in this opposition proceeding lies with the opponent, who must establish that it is clear that a valid patent cannot be granted (F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [29], [67]; 50 IPR 305; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18], [22]; 79 IPR 426).
The specification
In construing the specification I note what Middleton J said in Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214, 100 IPR 451 at [139]:
“It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense. The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent. From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date.”
The opposed specification is titled “PCV-2 vaccine”. On page, 1, it is stated that the invention relates to a vaccine against porcine circovirus type 2 (PCV-2) and the manufacture of such a vaccine for protecting piglets against PCV-2 infection (lines 3-4). The PCV-2 virus is a small non-enveloped virus containing a circular single-stranded DNA genome about 1768 bases long, and isolates originating in different regions in the world are closely related to each other (page 1, lines 19-23). The open reading frame 2 gene of the PCV-2 virus encodes the putative capsid protein ORF-2, which is 233 amino acids in length and has been found to be highly conserved between PCV-2 isolates (page 1, lines 23-27).
The specification discloses on page 1 that the PCV-2 virus is thought to be linked to post-weaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS) in young pigs (lines 6-7, 28-29), and a need is identified for a vaccine that protects piglets from such PCV-2-related diseases (lines 34-36). On page 2, since PMWS and PDNS caused by PCV-2 can be observed from about 4 weeks until about 15 weeks of age a vaccine would ideally have to protect piglets from weaning onwards. While a traditional strategy is to vaccinate with inactivated whole virus, matters are complicated for PCV-2 because it does not replicate well in cell culture (page 1). Thus, an alternative strategy is proposed based on recombinant PCV-2-derived antigens, which have previously been expressed in various expression systems (para bridging pages 1-2). An antigen is a substance that causes the host’s immune system to produce antibodies against it.
On page 2 of the specification piglets are likely to have maternally-derived antibodies against PCV-2 (PCV-2-specific MDAs or MDAs), which interfere with vaccination. Maternally-derived antibodies generally are antibodies raised in the mother as a result of exposure to antigen, either by infection with antigen-bearing material or intentional vaccination, which antibodies are then passed on to suckling offspring, and may provide protection (passive immunity) to the offspring from birth until they develop an effective immune system (O’Dea#1 at [23]). The specification states that while very high passive PCV-2-specific MDA titres (levels) may protect piglets against PCV-2 infection, lower titres will not be protective after weaning but may still be high enough to interfere with vaccination with, for example, a conventional inactivated PCV-2 antigen (page 2).
The invention is describes as providing a vaccine that can be used in a method to protect piglets, even PCV-2-specific MDA-positive piglets, against PCV-2 infection and associated diseases such as PMWS and PDNS (page 2, last para; page 3, para 1). On page 3 of the specification, the vaccine comprises at least a 20 microgram (mg) dose of the PCV-2 ORF-2 protein, which is capable of eliciting a protective immune response against PCV-2, even in the face of MDAs. A preferred vaccine dose contains 50 mg of the ORF-2 protein and most preferably 80 mg. However, vaccines containing up to 275 mg/dose can be prepared and do not elicit adverse reactions at the injection site (page 3, para 1).
The claims
The principles to be applied in construing the claims are well settled in law and were summarised by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70, 81 IPR 228 at [118]-[120]. Most relevantly, the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear. Words used in a specification, including the claims, are to be given the meaning which the person skilled in the art would attach to them, having regard to his or her own general knowledge and to what is disclosed in the body of the specification. While the claims define the monopoly claimed in the words of the patentee’s choosing, the specification should be read as a whole. It is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification. However, terms in the claims which are unclear may be defined or clarified by reference to the body of the specification. The construction of a specification, including the claims, is ultimately a question of law for the Court.
The patent application was accepted with 12 claims, reproduced below. Claims 1-4, 10 and 11 are independent.
1. Use of ORF-2 protein of Porcine Circovirus type 2 (PCV-2) for the manufacture of a vaccine that comprises at least 20 microgram/dose of said ORF-2, for the protection of Maternally Derived Antibody-positive (MDA-positive) piglets against PCV-2 infection.
2. Use of ORF-2 protein of PCV-2 for the manufacture of a vaccine that comprises at least 50 microgram/dose of said ORF-2, for the protection of MDA-positive piglets against PCV-2 infection.
3. Pharmaceutical composition comprising at least 20 microgram/dose of ORF-2 protein of PCV-2 and a pharmaceutically acceptable carrier, when used as a vaccine for the protection of MDA-positive piglets against PCV-2 infection.
4. Pharmaceutical composition comprising at least 50 microgram/dose of ORF-2 protein of PCV-2 and a pharmaceutically acceptable carrier, when used as a vaccine for the protection of MDA-positive piglets against PCV-2 infection.
5. Pharmaceutical composition according to claim 3 or 4, characterized in that said composition comprises a suitable adjuvant.
6. Pharmaceutical composition according to claim 5, characterized in that said adjuvant is an oil-in-water emulsion.
7. Pharmaceutical composition according to claim 5 or 6, characterized in that said adjuvant comprises vitamin E.
8. Use of ORF-2 protein of Porcine Circovirus type 2 according to claim 1 or 2, wherein that said ORF-2 protein has been produced by way of expression from a baculovirus expression vector in insect cells, and wherein the baculovirus expression vector comprises the PCV-2 ORF-2 gene sequence under the control of a suitable promoter.
9. Use of ORF-2 protein according to claim 8, wherein said promoter is the p10 promoter.
10. A method for the protection of MDA-positive piglets against PCV-2 infection, the method comprising administering a vaccine comprising at least 20 microgram/dose of ORF-2 protein of PCV-2 to an MDA-positive piglet.
11. A method for the protection of MDA-positive piglets against PCV-2 infection, the method comprising administering a vaccine comprising at least 50 microgram/dose of ORF-2 protein of PCV-2 to an MDA-positive piglet.
12. The use according to any one of claims 1, 2, 8 or 9, the composition according to any one of claims 3 to 7 or the method according to claim 10 or 11, substantially as herein before described with reference to any one of the examples.
Claims 3-4 and 10-11 are method claims involving the use of the PCV-2 ORF-2 protein as a vaccine for the protection of PCV-2-specific MDA-positive piglets against PCV-2 infection. Claims 1-2 are “Swiss-style” claims limited by the intended therapeutic use of the medicament - the protection of MDA-positive piglets against PCV-2 infection. The parties’ submissions revealed an ambiguity in the claims as to how this limitation should be construed - whether it requires sufficient protection to be achieved in the vaccinated piglet herd as a whole (Intervet’s position), or whether protective antibody production by the piglet’s immune system (seroconversion) in response to the vaccine is a necessary requirement in each and every individual MDA-positive piglet, regardless of the level of PCV-2-specific MDAs already present (Merial’s construction).
Resort to the description reveals that the invention provides a vaccine that can be used in a method to protect piglets, even MDA-positive piglets, against PCV-2 infection and PCV-related diseases (page 2, last para; page 3, para 1). The examples describe experiments in which pre-weaning piglets are categorised into three clusters having low, high, and very high blood serum titres of PCV-2-specific MDAs (specifically titres of ≤7, 8-12 or ≥13 in log2 units, in Clusters 1, 2 and 3, respectively). On page 7 it is stated that the Cluster 1 low titre piglets can usually be easily vaccinated, while Cluster 3 piglets with very high titres should be protected during the critical period of age (lines 5-11). However, since the majority of piglets fall within Cluster 2 with high PCV-2-specific MDAs, the specification concludes that it is important to protect these piglets to eliminate PMWS from a farm (page 7, lines 13-15). The specification refers to herd protection being obtained when 80% or more of the animals are protected (page 13, lines 11-14), either by seroconversion as a result of vaccination or by their already very high titre of passively acquired MDAs (page 12, line 19, to page 13, line 3).
In my view, the description of the invention supports a construction of the claims that the vaccine “for the protection of MDA-positive piglets against PCV-2 infection” must achieve seroconversion in a sufficient majority of the vulnerable MDA-positive piglets in the herd, rather than each and every individual MDA-positive piglet.
Manner of Manufacture
Section 18(1)(a) of the Act provides that an invention, so far as claimed in any claim, must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies. The threshold requirement for a patentable invention is that it must not be apparent on the face of the specification that the claimed invention lacks the necessary quality of inventiveness for it to be a proper subject of letters patent under the Statute of Monopolies (NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1995] HCA 15 at [9]; (1995) 183 CLR 655).
I accept Merial’s submissions to the effect that the specification admits on its face that the PCV-2 ORF-2 protein and its use in a vaccine against PCV-2 infection in piglets is known from the publication Blanchard, P. et al. (2003) Vaccine 21: 4565-4575 (Blanchard). This is apparent from page 2, para 1 of the opposed specification. However, to establish this ground of opposition, Merial also relied on information in Blanchard that not disclosed in the opposed specification, either directly or by an explicit incorporation by reference. Contrary to Merial’s submission, this approach is not supported by Merck & Co v Arrow Pharmaceuticals Limited (Merck & Arrow) [2006] FCAFC 91 at [75], in which the Full Court had regard to information in two prior art documents, the contents of which were explicitly incorporated into the patent specification by reference, to find that the specification on its face “discloses no new substance, no new characteristic of a known substance, no new use and no new method”.
The specification does not admit on its face that it was known to use the PCV-2 ORF-2 protein in doses of 20 mg or 50 mg or more to protect of MDA-positive piglets against PCV-2 infection. Merial’s submission that defining the minimum doses of ORF-2 protein to be included in a vaccine is a matter of mere routine and does not have the quality of inventiveness to satisfy the definition of “invention” is best addressed under the ground of inventive step.
Merial has not established that the claims do not define a manner of manufacture.
Novelty
Section 18(1)(b)(i) of the Act provides that an invention, so far as claimed in any claim, must be novel. It is well established that the general test for lack of novelty is the reverse infringement test. The classic formulation of this test is that given by Aicken J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20]; (1977) 137 CLR 228 at 235:
“The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement”
This test is satisfied if an alleged anticipation discloses all of the essential features of the invention as claimed (Nicaro Holdings Pty Ltd v Martin Engineering Co(Nicaro) [1990] FCA 40 at [19]; (1990) 91 ALR 513 at 517). In AstraZeneca AB v Apotex Pty Ltd (AstraZeneca) [2014] FCAFC 99 at [293], the majority of the Full Court identified the principles in General Tire [1972] RPC 457 at 486 as the criteria for determining anticipation by a prior publication. Most relevant to Merial’s submissions are those relating to inherency and inevitable outcome:
“When the prior inventor’s publication and the patentee’s claim have respectively been construed by the Court in the light of all properly admissible evidence ... the question whether the patentee’s claim is new ... falls to be decided as a question of fact. … if carrying out the directions contained in the prior inventor’s publications will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.
… To anticipate the patentee’s claim the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented ... a signpost, however clear, upon the road to the patentee’s invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee.”
Section 7(1) relevantly provides that an invention is to be taken to be novel when compared with the prior art base unless it is not novel in light of prior art information made publicly available in a single document. Merial relied on two documents to establish lack of novelty, as follows:
Blanchard, P. et al. (2003) Vaccine 21: 4565-4575 (Blanchard)
US 7223407 B2 (Jestin et al.) 29 May 2007 (US’407)
The 9 September 2005 priority date of the application was not in dispute - both documents form part of prior art base for novelty purposes.
Blanchard
Blanchard is in evidence as Exhibit CC-3. It is titled “Protection of swine against post-weaning multisystemic syndrome (PMWS) by porcine circovirus type 2 (PCV2) proteins”. The Blanchard Abstract states that PCV-2 is known to be associated with PMWS and that since no vaccine was available, the authors had developed a specific PCV-2 vaccine candidate. Blanchard describes experiments in which PCV-2 ORF-1 and/or ORF-2 protein subunits were delivered to specific-pathogen-free (SPF) piglets by way of DNA plasmids directing expression of the protein or as a baculovirus-expressed protein emulsion (the Blanchard Abstract, pages 4566-67 section 2.4 and Tables 1 and 2; consistent with Chase#1 at [24]-[25]; O’Dea#1 at [52]).
There was no dispute that Blanchard relevantly discloses the production of two DNA plasmids containing the coding sequences for PCV-2 ORF-1 or ORF-2 protein; the production of recombinant PCV-2 ORF-1 and ORF-2 proteins using a baculovirus expression system in insect cells; and the subsequent use of these components as DNA vaccines and protein subunit vaccines, respectively. Most relevantly, Intervet acknowledged that Blanchard teaches that DNA and protein vaccines based on ORF 2 were more antigenic and provided better protection than ORF-1 vaccines, and that the ORF-2 subunit vaccine was more effective than the DNA vaccine. This is consistent with the expert evidence (Chase#1 at [25]; Mr Bevan agreeing at [10]).
The opposed claims require the use of PCV-2 ORF-2 protein in a dose of at least 20 or 50 mg, for the protection of PCV-2-specific MDA-positive piglets against PCV-2 infection. A review of the expert evidence supports Intervet’s submission that Blanchard does not refer to MDAs in the context of the experiments it reports, nor does it provide the actual dose of ORF-2 administered or and whether it is sufficient to overcome MDAs to effectively immunise piglets against PCV-2 (O’Dea#1 at [52]; consistent with Chase#1 at [26]). Nevertheless, Merial submitted that these features were inherent in the Blanchard disclosure and would be arrived at the by skilled addressee as a matter of course.
Inherency in the dose administered
In Novozymes A/S v Danisco A/S (Novozymes) [2013] FCAFC 6 at [187], 99 IPR 417 at [187], Jessup J (with Greenwood and Yates JJ agreeing at [37] and [226], respectively) provided guidance on the application of the General Tire principles relating to inherency and inevitable outcome:
“..., the General Tire approach, if taken at all, may be taken only with respect to the whole of any claim asserted to have been anticipated. The “precise destination” at which the flag must have been planted is one which includes every integer of the claim. The approach cannot, in my view, be taken for some integers only, leaving others to be dealt with by reference to the understanding of the skilled addressee. In the present context, what this means is that, to the extent that [a party’s] case is based on General Tire, it is not sufficient that they be able to point to passages in the ... patent from which it would appear to the skilled addressee that [a feature of a claim] was contemplated or intended by the earlier inventors. It is necessary that they show that, if [the disclosure relied on] were worked as directed, it would inevitably, as a matter of hard fact, have involved [that feature].”
Regarding the dose, the evidence establishes that the Blanchard PCV-2 ORF-2 subunit vaccine was administered as a crude lysate of insect cells expressing ORF-2 protein, and the dose of the antigen was not known or reported (Chase#1 at [24]; Bevan agreeing at [10]; O’Dea#1 at [52]). Two of the experts reviewed the procedures used by Blanchard for preparing the ORF-2 vaccine, and while Dr O’Dea considers it unlikely that 20 mg ORF-2 protein was administered (#1 at [52]), Prof Chase “see[s] no reason why” the method employed would not have led to administration of at least 20 mg (#2 at [39]). Prof Chase relies on a report of the production of influenza antigens in baculovirus, to support his conclusion that the Blanchard lysate “could be expected to contain more than 20mg” of ORF-2 protein (#2 at [40]). Prof Chase’s ambivalent statements do not establish that the ORF-2 vaccine in Blanchard was inevitably, as a matter of fact, administered in a dose of at least 20 mg.
There was some discussion at the hearing as to whether the SPF piglets in Blanchard were likely to have PCV-2-specific MDAs, but in view of my finding with respect to the dose, it is not necessary for me to decide whether the treatment of MDA-positive piglets is inherent to the Blanchard disclosure.
I find the claims novel in light of Blanchard.
US’407
US’407 is in evidence as Exhibit CC-4.
Merial acknowledged at the hearing that this patent application by the Blanchard research team post-dates the priority date of the opposed application and that it had been relied on in error - the document the opponent intended to raise was US patent 6703023 (Jestin et al.) 9 March 2004 (US’023) from which US’407 is a later-filed “continuation-in-part”. Merial advised that the information it identified in US’407 for novelty purposes also appears in US’023 and it invited me to inform myself of US’023 under the provisions of reg 5.11 of the Patents Regulations 1991 as they stood immediately before 15 April 2013. Intervet did not object to this course of action.
Merial relied on Examples 5 and 8 and Figures 14-15 of US’407 for a disclosure of the production of PCV-2 ORF-2 protein using baculovirus in insect cells, and the vaccination of SPF and conventional piglets with recombinant PCV-2 ORF-2 protein and adjuvant. Merial submitted that Examples 5 and 8 relevantly teach administration of 5x106 baculovirus-infected insect cells expressing and containing an unspecified amount of PCV-2 ORF-2 protein, to provide clinical protection of piglets against PCV-2 infection.
Regarding the requirement in the opposed claims for a dose of at least 20 mg of PCV-2 ORF-2 protein, Merial drew my attention to the following statement in column 28 of US’407 (column 27 of US’023):
“… in the case of a vaccine according to the present invention comprising a polypeptide encoded by a nucleotide sequence of the genome of PCV, or a homologue or fragment thereof, the polypeptide will be administered one time or several times, spread out over time, directly or by means of a transformed cell capable of expressing the polypeptide, in an amount of about 0.1 to 10 mg per kilogram weight of the animal, preferably about 0.2 to about 5 mg/kg, more preferably about 0.5 to about 2 mg/kg for a dose.”
It was not in dispute that a piglet for vaccination would typically weigh around 6-8 kg, which is consistent with the evidence (Bevan#2 at [14]; O’Dea#1 at [54]). It follows that the doses in US’407 equate to 0.6-80 mg at its broadest, preferably 1.8-40 mg and most preferably 3-16 mg (Bevan#2 at [14]). Thus, US’407 discloses the use of PCV-2 ORF-2 protein in doses encompassed by Intervet’s claims, but also includes lower doses (consistent with O’Dea#1 at [53]; Bevan#2 at [14]).
Relevant to the MDA status of the piglets, noting that Table 5 of US’407 discloses vaccination of conventional pigs, Prof Chase states that in France, where the inventors were based, conventional herds were infected with PCV-2 (Chase#1 at [26]). However, with no serology data on the test pigs, he concludes that they could have been MDA-positive, but that you cannot be sure (Chase#1 at [26]). Dr O’Dea notes that US’407 does not mention MDAs or associated issues in vaccination (#1 at [53]).
Taken together, the evidence supports Intervet’s submission, that US’407 does not provide clear and unmistakable directions to vaccinate piglets with at least 20 mg of PCV-2 ORF-2 protein in order that a sufficient proportion of MDA-positive piglets would inevitably, as a matter of fact, be protected against PCV-2 infection. Consequently, I am not satisfied that the nature and significance of the same information in the earlier patent document US’023 is such that I should invoke reg 5.11 to bring this document into the hearing.
Novelty summary
Merial has not established that any claim lacks novelty.
Inventive Step
Section 18(1)(b)(ii) of the Act provides that an invention, so far as claimed in any claim, must involve an inventive step when compared with the prior art base. Under the provisions of subsections 7(2) and 7(3) of the Patents Act 1990, an invention is taken to involve an inventive step when compared with the prior art base unless it would have been obvious to a person skilled in the art. ‘Obvious’ means ‘very plain’ (Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) [2007] HCA 21 at [51]-[52], (2007) 72 IPR 447 at 461 [51]-[52]). The invention must be obvious in the light of the common general knowledge as it existed in the patent area before the priority date, either on its own or together with information in a document, or combination of documents, that the person skilled in the art could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood and regarded as relevant and, where necessary, combined.
The parties were in agreement that the relevant test is the reformulated Cripp’s question in this case, an approach approved by the High Court in Aktiebolaget Hässle v Alphapharm Pty Ltd [2002] HCA 59 at [51]-[53]; 212 CLR 411 at [51]-[53]. Thus, the question to be answered is:
Would the notional research group at the relevant date, in all the circumstances, directly be led as a matter of course to try the claimed combination of integers, in the expectation that it might well produce a useful or desired result.
The usual approach to determining inventive step is the problem-solution approach. Once the problem has been formulated and the common general knowledge and the prior art base has been determined, the question of whether the claimed solution is obvious must be addressed.
The person skilled in the art
The notional “person skilled in the art” is an artificial construct that is used as a tool of analysis “which guides the court in determining, by reference to expert and other evidence, whether an invention as claimed does not involve an inventive step” (AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30 at [18], [23], (2015) 89 ALJR 798 at [18], [23]). In general, the skilled person or addressee is the person who works in the art or science with which the invention is connected. He or she is a person, or team, likely to have a practical interest in the subject matter of the invention. While the skilled person may be assumed to be well-versed in the relevant art, such a person must be taken to be non-inventive. (Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [71] - [72], 49 IPR 225 at [71] - [72] referring to Catnic Components Ltd v Hill &Smith Ltd [1982] RPC 183 at 242 and General Tire [1972] RPC 457 at 485; Minnesota Mining [1980] HCA 9 at [115], 144 CLR 253 at 293).
The parties were in agreement that the person skilled in the art in this opposition is a person or team who, at the priority date, had a practical interest in PCV-2 and/or the development of veterinary vaccines including swine vaccines. In considering Intervet’s submission that Merial’s experts were not relevant persons skilled in the art, I have relied on each expert’s statements in this regard and their resume or curriculum vitae (CV) outlining their experience (Exhibits CC-1, MB-1 and MOD-1).
Christopher Chase describes himself as having “a thorough understanding of viral pathogens of livestock and the development of vaccines to viral pathogens of livestock in and around mid-2005” (#1 at [5]). He holds bachelor and doctorate degrees in veterinary medicine completed in 1990 (Exhibit CC-1). From 1990 until the priority date Prof Chase relevantly worked as a veterinarian and held positions as Assistant Professor in two universities in the USA (#1 at [3] and CC-1). Between 1992 and 2005, Prof Chase was associate/consulting swine veterinarian at a veterinary clinic (#1 at [3]).
Intervet questioned whether Prof Chase had a practical interest in PCV-2 at the priority date, noting that: only 7 publications among over 400 listed in his CV refer to PCV-2 in the title; these were published between 2006 and 2007; and in most cases Prof Chase is not the main author. However, in my view, being listed as an author on 7 publications in 2006-2007 relating to PCV-2 is not inconsistent with Prof Chase having had a practical interest in this field before the September 2005 priority date.
Intervet further submitted that Prof Chase was based in North America, and would not have been aware of the common general knowledge in the art in Australia before the priority date. In particular Intervet noted that Prof Chase is not an Australian scientist or resident and no evidence has been provided that he interacted with Australian experts before the priority date on PCV-2-related matters. These submissions by Intervet can only be based on a view that before the priority date the common general knowledge in Australia with respect to the PCV-2 virus and its clinical consequences (as distinct from the clinical situation in Australia regarding PCV-2 infection) was markedly different to that overseas. To refute this, Merial drew my attention to Exhibit CC-11, a one-page summary establishing that the 16th International Pig Veterinary Congress (IPVC) in September 2000, was held in Melbourne Australia, and was attended by over 1600 participants. The virology presentations involved circovirus (Exhibit CC-11) and one at least related specifically to PCV-2 and PMWS (Chase#2 at [16]). Prof Chase considers this IPVC meeting to be one example among many “showing the International nature of PCV2 veterinary research and that Australia was part of the International research community investigating PCV2” (Chase#2 at [16]). Further supporting a view that Australian scientists engaged with the rest of the world in the field of PCV-2 research, Dr O’Dea confirms that before the priority date he “was aware of most relevant information originating from Australia and overseas in relation to porcine viruses and, in particular, PCV-2” (O’Dea#2 at [9]). Taken together, it is reasonable to conclude that the common general knowledge in Australia in this field is not substantially different to that overseas. It follows that Prof Chase’s evidence is relevant to the opposition.
Richard Bevan graduated in 1970 with a B.Sc. in Agriculture specialising in microbiology. Between 1970-1997, Mr Bevan worked in the field of quality control of vaccine production in Australia, ultimately achieving the position of Associate Director Quality Assurance (Bevan#1 at [1]-[2]; Exhibit RB-1). During that time, Mr Bevan states that his work was focussed, most relevantly, on the production, testing and use of veterinary vaccines in a company that had, by 1997, an extensive range of vaccines for both large and small animals (#1 at [2] and Exhibit RB-1). Since 1997, Mr Bevan has worked as a pharmaceutical and veterinary vaccine consultant (#1 at [1] and Exhibit RB-1). It is apparent from his CV that Mr Bevan’s consultancy work before the priority date relevantly included preparing operating procedures, submitting and maintaining vaccine registrations, negotiating with regulatory authorities, auditing vaccine units to meet Australian regulatory standards and the introduction of vaccine technology to sites. There was no dispute that Mr Bevan has extensive experience in the production of veterinary vaccines in Australia, and in this regard his evidence is relevant to this opposition.
Intervet’s expert Mark O’Dea is a registered veterinary surgeon who, since 2004, has been employed by the Department of Agriculture and Food in Western Australia as a Veterinary Virologist. Dr O’Dea gained bachelor degrees in Veterinary Science and Veterinary Medicine and Surgery in 2000, and a doctorate in 2009. Leading up to the priority date, Dr O’Dea was researching the epidemiology and detection of PCV-2 in Australian pig herds, including assessing the expression and severity of conditions associated with PCV-2 infection. Thus, Dr O’Dea’s evidence is also relevant to this opposition.
In summary, before the priority date, each of the three experts was working in the art or science with which the invention is connected and as such is likely to have a practical interest in the subject matter of the opposed specification. For this reason their evidence is relevant to the skills and knowledge of the notional person skilled in the art in this opposition.
The common general knowledge in the art
A definition of common general knowledge was provided by Aitken J in Minnesota Mining and Manufacturing Company and Another v Beiersdorf (Australia) Limited [1980] HCA 9; 144 CLR 253 at 292:
“The notion of common general knowledge itself involves the use of that 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.”
The evidence establishes that the following matters were common general knowledge in the art before the priority date.
PCV-2 virus
Before the priority date, PCV-2 infection in pigs was well known and had been associated with PMWS overseas (Chase#1 at [9]; O’Dea#1 at [12]). There was no dispute that the PCV-2 virus was known to be present in Australian pig herds before the priority date, but PMWS had not been reported here (consistent with O’Dea#1 at [12]-[13]).
MDAs and vaccination
The parties were in agreement that despite a statement on page 2 of the specification that it was well known that the presence of MDAs will interfere with vaccination, it was not common general knowledge before the priority date that PCV-2-specific MDAs necessarily posed a problem for PCV-2 vaccination. Dr O’Dea states that “MDAs are potentially an issue in vaccination of young animals generally” (#1 at [23]), which is consistent with Prof Chase’s evidence that MDAs, particularly at high levels, “can have an effect on some vaccines but not others” (#1 at [16]). I conclude that it was common general knowledge in the art that MDAs generally were potentially an issue in vaccinating young animals.
Optimising the vaccine dose
On being asked how someone working in vaccine development in and around mid-2005 would determine an appropriate dose of antigen in a (protein) subunit vaccine to obtain a protective response, Prof Chase (#1 at [13]) answers:
“The appropriate dose of antigen to include in a vaccine would be determined by dose titration studies. These studies would usually be performed first in mice and would typically look at antibody responses to different dosages of antigen. Once an effective range of doses, for example four to six different doses, have been determined in mice, the dosages would be tested in the target animal in further titration studies. Once it is determined which dosages produce a desired immune response in the target animal, then a narrower range of two or three doses might be tested in a challenge trial in the target animal.
Prof Chase continues at [14] that the approach for determining the minimal effective dose of antigen to include in a vaccine was well known in and around mid-2005, such that it was codified in US law. Furthermore:
“… it is a requirement that a vaccine include the least amount of antigen you have to have to get a protective dose, although companies would actually use more antigen that that when they make the product due to shelf life and stability issues.” (#1 at [14])
Mr Bevan agrees with Prof Chase’s evidence in this regard (#1 at [9]), which is not disputed by Dr O’Dea. Thus, I am satisfied that it was common general knowledge in the art to optimise the dose of vaccine antigen by dose titration studies, ultimately in the target group of animals.
The problem
Intervet submitted that PCV-2 did not present a problem in Australia before the priority date. Relying on Dr O’Dea’s evidence (#1 at [22]), Intervet argued that since no PCV-2-related diseases had been identified in Australian pigs, there was no interest or motivation here to develop a vaccine against PCV-2, although methods for monitoring it were of interest. Merial disputed this, submitting that in view of the association with disease in piglets overseas, the PCV-2 virus was considered a potential problem in Australia. Merial identified the problem as the need to develop a dosage form of a vaccine against the PCV-2 virus.
In about 2000, in view of the outbreaks overseas, animal scientists in Australia started to pay attention to PMWS and PCV-2 (O’Dea#1 at [12]). However, PCV-2 had not been shown (i.e. proved) to be the sole causative agent for any specific disease (O’Dea#1 at [18], [47]-[48]) and given that PMWS had not been reported in Australia, despite the PCV-2 virus being “well and truly present” at the time, Dr O’Dea did not consider there to be any motivation to develop a vaccine here (O’Dea#1 at [22], [29]). In contrast, Prof Chase describes PCV-2 as an emerging pathogen of international significance, and he considers there would have been more interest in Australia than simply being able to correctly diagnose PCV-2 infection (#2 at [10]). Noting Dr O’Dea’s evidence (#1 at [20]) that there were several international publications relating to PCV-2 vaccines, Prof Chase considers these to be in direct response to the “serious problem of PCV-2 infection of pigs and the risks posed to the swine industry” (#2 at [12]). Noting that many countries including Australia produce or import pig meat, Prof Chase states that in 2005, PCV-2 infection in pigs was a “serious global problem being addressed by the international research community” (#2 at [12]). Prof Chase believes it improbable that funding by the Australian Biosecurity Cooperative Research Centre for Emerging Infectious Disease (AB-CRC), for Dr O’Dea’s post-graduate research at the Dept of Agriculture in WA into the epidemiology and detection of PCV-2 infection in pig herds, was not seen by both parties in the larger context of diagnosis, treatment or prophylaxis, including PCV-2 vaccines, should the need arise (Chase#2 at [7]-[8]). Consistent with this view, Mr Bevan finds it hard to believe that the AB-CRC was only interested in diagnosing PCV-2, since it was established to improve Australia’s capability to respond to emerging infectious diseases (#2 at [10]). On balance, since PCV-2 was associated with disease overseas, it is reasonable to expect that relevant groups in Australia, such as the AB-CRC and regulatory authorities, would have considered it desirable to prepare for the possibility that Australia may in the future be faced with an outbreak of PCV-2-associated disease.
Before the priority date work relating to pig vaccines generally was of commercial importance (Bevan #1 at [7]) and vaccine manufacturers in Australia were undertaking research into the development and production of such vaccines (Bevan#1 at [8]). Dr O’Dea does not dispute Prof Chase’s evidence that multiple factors are taken into account when deciding on countries to develop vaccines, which may or may not include the disease status in that country (Chase#2 at [9]). In this regard, prima facie, any PCV-2 vaccine manufactured in Australia would have a market in other countries affected by PCV-2-associated disease. Given the circumstances before the priority date, I consider it reasonable to conclude that the motivation would have existed in Australia, as overseas, to develop a vaccine against PCV-2. This is consistent with the need in the art identified on page 1 of the opposed specification for a vaccine that protects piglets against PCV-2 related diseases, which is not satisfied by commercially available vaccines, which Dr O’Dea believes is correct for Australia (O’Dea#1 at [32]). Thus, a reasonable formulation of the problem in this case is the need to develop a dosage form of a vaccine against the PCV-2 virus that can be used in a method to protect piglets against PCV-2 infection.
The prior art base
Merial submitted that the claimed invention does not involve an inventive step in light of each of the following documents:
Blanchard et al. (2003) Vaccine 21: 4565-4575 (Blanchard)
Fenaux et al. (2004) J. Virology 78(12): 6297-6303 (Fenaux)
Halbur, P. and Opressnig, T. (2004) Abstracts of the ISU Swine disease conference for Swine Practitioner (Halbur)
Ascertained, understood and regarded as relevant
“Ascertained” means found or discovered (Commissioner of Patents v Emperor Sports Pty Ltd [2006] FCAFC 26 at [29]-[30], (2006) 67 IPR 488). The person skilled in the art could be expected to have regarded a prior disclosure as relevant if it is directed to solving a particular problem or meeting a long-felt want or need as the patentee claims to have done (Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (No 2) [2007] HCA 21 at [152], (2007) 235 ALR 202). The question of what a person skilled in the relevant art would regard as relevant, when faced with the same problem as the patentee, is to be determined on the evidence (Lockwood (No 2) at [153]).
In commencing a project or conducting research the experts would all have used the search engine PubMed to find useful references (Chase#1 at [21]; Bevan#1 at [6], O’Dea#1 at [8]).
As indicated above, Blanchard was published in 2003 and relates to PCV-2 vaccine candidates and their use to protect piglets against PMWS caused by PCV-2. Fenaux is in evidence as Exhibit CC-7; it was published in 2004 and the title indicates that it relates to a recombinant chimeric porcine circovirus containing the PCV-2 orf-2 gene cloned into the PCV-1 genomic backbone, which induces protective immunity against PCV-2 infection in pigs. The Fenaux abstract concludes that when administered to piglets, “attenuated chimeric PCV1-2 live virus, as well as the chimeric PCV1-2 infectious clone, induces protective immunity against PCV-2 infection and could potentially serve as an effective vaccine.
Mr Bevan is confident he would have located Blanchard and Fenaux if he had been working on a vaccine project to protect pigs from PCV-2 infection around September 2005 (Bevan#1 at [6]). Using Prof Chase’s strategy of looking through the bibliographies to find useful articles (Chase#1 at [21]) it is reasonable to expect that he too would have ascertained both documents. Both are in English and in view of their subject matter, I am satisfied that they would have been understood and regarded as relevant. Supporting this conclusion, in describing the state of the art in the field of porcine viruses before the priority date, particularly PCV-2 in Australia, Dr O’Dea identified both documents as earlier reports of PCV-2 vaccines (O’Dea#1 at [4], [20]). In summary, I find that in seeking information with which to solve the problem before the priority date, the person skilled in the art could be reasonably expected to have ascertained and understood Blanchard and Fenaux, and considered them relevant to the problem identified above.
Halbur is in evidence as Exhibit CC-14. There are no clear citation details provided for this document. Halbur is cited on page 3 of the Merial’s amended SGP as “Abstracts of the ISU Swine disease conference for Swine Practitioner”. The SGP dates the document as 2004, which is consistent with the dates of the references it cites. Halbur is titled “Update on porcine circovirus Type 2 (PCV2)-associated diseases”. The introduction is short and ends with the statement “The final objective is to discuss current strategies for control of PCV2-associated diseases based on our research and field experiences”. There is very little evidence with respect to whether this document satisfied the requirements of s 7(3), nevertheless since nothing turns on it, I will accept for the purposes of this decision that the document would have been ascertained, understood and regarded as relevant.
Was the claimed invention obvious?
Blanchard
The opposed claims require the use of PCV-2 ORF-2 protein in a dose of at least 20 or 50 mg, for the protection of PCV-2-specific MDA-positive piglets against PCV-2 infection. The relevant question is therefore:
Would the notional research group at the relevant date, in all the circumstances, including knowledge of the problem (the need to develop a dosage form of a vaccine against the PCV-2 virus that can be used to protect piglets against PCV-2 infection) and the information in Blanchard, directly be led as a matter of course to try the PCV-2 ORF-2 protein described by Blanchard in a dose of at least 20 mg or 50 mg, in the expectation that it might well provide a useful or desired vaccine for the protection of piglets against PCV-2 infection.
The PCV-2 ORF-2 protein as the vaccine antigen
As indicated above under the novelty ground, there was no dispute that Blanchard discloses, among other things, the production of PCV-2 ORF-2 protein and its use to vaccinate piglets to protect them against PCV-2 infection. Intervet acknowledged that Blanchard discloses the ORF-2 protein subunit as the most effective antigen against PCV-2, which is consistent with the evidence (Chase#1 at [25]; Bevan#1 at [10]; O’Dea#1 at [52]). For this reason, Prof Chase and Mr Bevan and would have chosen to use the ORF-2 protein in a vaccine intended to induce a protective immune response to PCV-2 (Chase#1 at [25], [28]; Bevan#1 at [10]). Dr O’Dea does not comment on the potential of this Blanchard antigen in a vaccine against PCV-2. On this basis, I conclude that at the priority date, in light of the information in Blanchard, the person skilled in the art seeking to develop a dosage form of a PCV-2 vaccine to protect piglets against PCV-2 infection, would directly be led as a matter of course to try the PCV-2 ORF-2 protein as the vaccine antigen, with a reasonable expectation of success.
Determining the appropriate vaccine dose
Having identified the PCV-2 ORF-2 protein in Blanchard as the most effective antigen for vaccinating piglets, the evidence establishes that at the priority date, the person skilled in the art in Australia would have applied the common general knowledge and undertaken dose titration, ultimately in the target group of animals, to determine the appropriate dose of the PCV-2 ORF-2 protein for protecting piglets from PCV-2 infection (Chase#1 at [13], Bevan agreeing at #1[9] and not disputed by Dr O’Dea; Chase#2 at [26]).
The target group for dose titration
Regarding the target group for dose titration, I give little weight to Dr O’Dea’s evidence that in Sept 2005, had he thought that MDAs would be an issue in obtaining immunity against PCV-2, his first approach would be to vaccinate sows rather than their piglets (#1 at [27], [39]), since at #1[26] he states that he was unaware at that time whether MDAs were an issue. Prof Chase would have vaccinated piglets before weaning; he would not have vaccinated sows in order to protect piglets from PCV-2 because MDAs have a relatively short and variable half-life (#2 at [20]). On this basis, I conclude that the person skilled in the art in Australia would adopt the same approach and directly be led as a matter of course to undertake dose titration of the Blanchard ORF-2 protein in piglets rather than sows.
The PCV-2 virus was present in Australia before the priority date (O’Dea#1 at [12], [29]). As a consequence PCV-2-specific MDAs would have been present in the suckling piglets of infected females in Australian herds (O’Dea#1 at [23]; consistent with Chase#1 at [15], #2 at [33]). Intervet submitted that the herd chosen for dose titration may not be representative for MDA positivity in Australia. However, I have found above that it was common general knowledge that MDAs may potentially be an issue in vaccinating young animals. In this context, Prof Chase states that provision for MDAs would have been for him a routine part of real world PCV-2 vaccine research and development, since it was known that the virus was endemic in herds before the priority date and any vaccine had to operate in this environment (Chase#2 at [28]). Therefore, I agree with Merial that the knowledge that MDAs may potentially cause difficulties for vaccination would have informed the dose titration such that the person skilled in the art would include piglets with PCV-2-specific MDAs in the ultimate target group. The question at this point is whether faced with the problem and in light of Blanchard, the person skilled in the art would directly be led as a matter of course to try the doses of PCV-2 ORF-2 protein specified in the claims, with a reasonable expectation of success?
The dose
Prior to reading the opposed specification (Chase#1 at [8]), but having been advised that it generally relates to protecting pigs from PMWS caused by PCV-2 (Chase#1 at [6]), Prof Chase was invited to comment on the amount of protein antigen that would typically be included in a subunit vaccine, to which he responded:
“The amount of protein antigen in a given vaccine would routinely fall within the range of about 10 to 100s of micrograms, although in some cases milligram amounts may be necessary.” (Chase#1 at [12])
Intervet deemed this a “sweeping statement without any documentary or other support”, which could apply to any animal of any age or weight. However, since Prof Chase was clearly aware that the matter related to pig vaccines, it is reasonable to conclude his evidence was provided in this context. Given his qualifications and veterinary experience at the priority date, I am satisfied that Prof Chase was in a position to know the typical vaccine doses used in pigs at that time. Since the dosage range he identifies extends over at least two orders of magnitude, I accept that Prof Chase may well be providing a typical dose for pigs of any age and weight, but nothing turns on this. While Prof Chase does not corroborate his typical dose range with documentary evidence, neither has it been challenged by Dr O’Dea. Therefore, I am not prepared to disregard this evidence.
In commenting on the opposed specification, Prof Chase states at #1 [41]:
“Even if interference from maternally-derived antibodies was not a concern, you would typically start with a best guess dose of around 50 μg, for example, and bracket that down to 5 or 10 μg and up to a 100 μg dose. You would then perform further studies to narrow down the range to obtain the minimum effective dose.”
Although this last statement was provided with the benefit of hindsight, it is consistent with Prof Chase’s earlier evidence, that a dose of protein antigen in a vaccine would routinely be about 10 to 100s of micrograms. On this basis, I am satisfied that in seeking to solve the problem, and having read Blanchard, the person skilled in the art would directly be led as a matter of course to conduct dose titration studies in the target group identified above, trying the Blanchard PCV-2 ORF-2 protein in doses including 50 and 100 mg with a reasonable expectation that it might well provide a useful or desired vaccine for the protection of Australian piglets, including MDA-positive piglets, against PCV-2 infection.
Since the target piglet population includes PCV-2-specific MDA-positive piglets, and doses above 20 mg are in fact necessary to protect a sufficient proportion of MDA-positive piglets (as evidenced by the opposed specification) it is reasonable to conclude that the dose titration study would identify these higher doses as necessary to achieve seroconversion in a sufficient proportion of the target population as a whole, including the vulnerable MDA-positive piglets. It follows that the subject matter of claims 1-4, 10 and 11 lacks an inventive step in light of Blanchard.
Opposed claim 5 requires the addition of an adjuvant in the composition of claims 3-4, while claim 6 limits the adjuvant to an oil-in-water emulsion. Blanchard discloses the use of an oil and water adjuvant (page 4566, section 2.4). The evidence establishes that it was known that adjuvants in a vaccine can overcome MDAs (Chase#1 at [15], [18]; Bevan agreeing at #1 [9]) and Prof Chase would try this approach to make a subunit vaccine more effective if MDAs were a potential concern (#1 at [19]; Bevan agreeing at #1 [9]). In light of the explicit disclosure in Blanchard and this expert evidence, I am satisfied that the person skilled in the art seeking to solve the problem identified above, would directly be led as a matter of course to add the adjuvant specified in claims 5 and 6 with a reasonable expectation of success. Consequently, the additional features of claims 5 and 6 lack an inventive step.
Relevant to claim 8, Blanchard discloses the production of the ORF-2 protein by expression from a recombinant baculovirus expression vector in Sf9 insect cells (page 4566, section 2.3, confirmed by Prof Chase at #2 [39]). The evidence establishes that the baculovirus-expressed ORF-2 protein taught by Blanchard would easily be produced in large quantities (Chase#2 at [28]; Bevan#2 at [12]). Relevant to claim 9, while Blanchard does not explicitly identify the promoter that must necessarily be used to express the ORF-2 protein from the recombinant expression vector, the opposed specification identifies the p10 promoter as one of the two most commonly used promoters in the baculovirus expression system (page 3b, lines 5-7). In the absence of any evidence to the contrary on this point, it is reasonable to conclude that the use of the p10 promoter would also be a routine approach. I therefore conclude that in seeking to develop a dosage form of a vaccine against the PCV-2 virus to protect piglets against PCV-2 infection and in light of Blanchard, the person skilled in the art would directly be led as a matter of course to try the expression system and promoter in accordance with claims 8 and 9, in the expectation that it might well contribute to providing a useful or desired vaccine for the protection of those piglets against PCV-2 infection. I find claims 8 and 9 lack an inventive step.
In summary, claims 1-6 and 8-11 do not involve an inventive step in light of Blanchard.
Fenaux and Halbur
The Fenaux and Halbur documents are in evidence as Exhibits CC-7 and CC-14, respectively. Consistent with Dr O’Dea’s evidence that Fenaux describes vaccines based on live chimeric virus, not protein subunit vaccines (O’Dea#1 at [58]), Prof Chase summarises the Fenaux disclosure as follows:
“Fenaux et al. (2004) describe experiments in which piglets are vaccinated with a chimeric PCV1-2 virus. PCV-2 ORF-2 is the surface antigen on the chimeric virus and would have been seen first by the immune system. In this case, the production of ORF-2 protein relies on viral replication from DNA constructs or from a live virus, hence either very little or no recombinant protein is delivered to begin with.” (Chase #1 at [29)
Similarly, the section relied on by Merial on page 18 of Halbur is titled “Effect of PCV2 passive antibody levels on vaccination with chimeric PCV1-2 vaccine and challenge with wild-type PCV2” on page 18 of the document. The subsequent text describes vaccination with “live chimeric vaccine”.
Both Fenaux and Halbur disclose vaccination with live virus and/or replication-competent genetically-engineered virus, which once administered cause the ORF-2 protein to be produced in vivo. Neither discloses direct administration of ORF-2 protein. Prof Chase’s evidence that in Fenaux, very little or no protein is delivered in the vaccine, would apply equally to proteins encoded by the Halbur vaccine (page 17, para 3).
There is nothing in evidence to establish that the viral vaccines taught by Fenaux or Halbur contain an amount of ORF-2 protein required by the opposed claims, or that the person skilled in the art would directly be led as a matter of course add the requisite amount of ORF-2 protein to those viral vaccines, and administer the combination.
I find all claims involve an inventive step in light of each of Fenaux and Halbur.
Inventive step summary
Claims 1-6 and 8-11 do not involve an inventive step.
Utility
Section 18(1)(c) of the Act provides that an invention, so far as claimed in any claim, must be useful. The requirements for utility in a claimed invention were provided by the Full Court of the Federal Court as follows:
“If the claimed invention does what it is intended by the patentee to do and the end result obtained is itself useful, the invention is useful within the meaning of s 18(1)(c) … As to the first aspect, the invention as claimed must attain the result promised by the patentee” (Ranbaxy Australia Pty Ltd v Warner-Lambert Co LLC [2008] FCAFC 82 at [141], (2008) 77 IPR 449)
“A claim is bad if it covers means that will not produce the desired result, even if a skilled person would know which means to avoid. That is to say, everything that is within the scope of a claim must be useful, otherwise the claim will fail for inutility.” (H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [81], [217], 81 IPR 228)
There was no dispute that the promise of the invention is the protection of MDA-positive piglets against PCV-2 infection. Merial’s submissions to establish lack of utility can be summarised as:
(i) the data in the opposed specification shows that the claimed doses do not achieve protection against PCV-2 infection in piglets with the highest levels of MDAs;
(ii)Haake, M. et al. Veterinary Microbiology (2013), Epub (Haake) establishes that vaccination with PCV-2 ORF-2 antigen did not protect one week old piglets with high MDAs from challenge with the virus; and
(iii)a 2-shot vaccine regimen is necessary for successful vaccination.
I have addressed each of these submissions separately below.
Protection for piglets with the highest titres of PCV-2-specific MDAs
Merial submitted that the claimed invention does not achieve the promised benefit of providing protection against PCV-2 infection to all MDA-positive piglets. Merial further submitted that in order to achieve the promise of the invention, the lowest 20 mg dose of ORF-2 identified in the claims must adequately protect all piglets for the claimed invention to satisfy the requirement that it be useful.
I have construed the opposed claims as requiring the vaccine to achieve a protective response in a sufficient proportion of the MDA-positive piglets in a herd, rather than in each and every individual MDA-positive piglet. In my view, the promise of the invention disclosed in the specification is consistent with this construction - that after vaccination, a sufficient proportion of the piglet herd must have a protective titre of PCV-2-specific antibodies, either as a result of vaccination and/or as passively-acquired MDAs. Supporting this view, page 2 of the specification states that very high titres of passive MDAs may protect piglets against PCV-2 infection, while lower titres may not be protective and it is in this latter group of piglets that a vaccine according to the invention has been found to provide adequate protection (lines 25-37). Furthermore, the description states that herd protection against the consequences of PCV-2 infection only requires 80% of the animals to have a protective antibody titre (page 13, lines 11-14). Thus, I do not understand the promise of the invention to necessarily require all MDA-positive piglets to achieve a protective antibody response to the vaccine.
In any event, the specification identifies 80 mg as the most preferred dose of ORF-2 protein (page 3, lines 6-7), and refers to the potential use of higher doses, explicitly identifying 275 mg (page 3, para 1). The claims encompass the use of these higher doses of ORF-2 and Merial has not established that a protective immune response in piglets with the highest MDA titres would not be achieved with these doses of ORF-2 protein.
Haake – protection of one week old piglets with high MDAs
Haake is in evidence as Exhibit (iii) to Chase#3. It was published after the priority date but has been raised by Merial in order to establish as a factual matter that embodiments of the claimed invention lack utility. Haake is titled “Influence of age on the effectiveness of PCV2 vaccination in piglets with high levels of maternally derived antibodies”. There was no dispute, and evidence confirms, that the Porcilis® PCV vaccine used in Haake contains the PCV-2 ORF-2 protein (O’Dea#2 at [24], Exhibit MOD-15). Haake concludes that PCV-2 vaccination in the presence of high MDA levels, while efficacious in 3 week old piglets, is ineffective in 1 week old piglets (the Abstract, and conclusion on page 8 of the document).
Exhibited to Dr O’Dea’s second declaration as MOD-16 is a 2-page summary of findings in a thesis by Simon Eisele dated 17 July 2009 titled “Efficacy of an inactivated one-shot piglet vaccine at either one or three weeks of age with Porcilis® PCV against porcine circovirus type 2 (PCV2) at two farms in southern Germany” (Eisele). Eisele identifies the goal of the study as determining the efficacy of the vaccine administered at different times, and reports that vaccination of MDA-positive piglets with Porcilis® PCV at 1 and 3 weeks of age was “very effective” (O’Dea#2 at [27]).
Taken together, the information Haake and Eisele establishes that in some circumstances administration of the PCV-2 ORF-2 protein in a vaccine does not achieve a protective immune response in 1 week old MDA-positive piglets. Neither Haake nor Eisele identify the dose of vaccine administered. Although technical data sheets for two Porcilis® PCV vaccines are in evidence as Exhibit MOD-15 to O’Dea#2, they provide the dose in terms of the activity of the ORF-2 antigen, rather than the weight of protein administered. Therefore, no meaningful comparison can be made between the Haake and Eisele doses and those in Intervet’s claims. It follows that Merial has not established that when administered to 1 week old MDA-positive piglets in a dose encompassed by the opposed claims, the PCV-2 ORF-2 protein will not achieve the promised benefit of a protective immune response against PCV-2 infection.
a 2-shot vaccine regimen
Merial’s submissions on this basis were to the effect that the claims cover any number of administrations of a dose comprising at least 20 or 50 mg of PCV-2 ORF-2 protein, whereas the specification refers to and exemplifies a two-dose regimen, thus it is not possible to determine whether a single shot vaccine achieves the promise of the invention. However, Merial has not shown that a single shot vaccine in accordance with the claims will not achieve the promise of the invention, and both Haake and Eisele confirm that it can do so.
Utility Summary
Merial has not established that the claimed invention is not useful.
Fair basis
Subsection 40(3) requires that the claim or claims in a patent specification be fairly based on the matter described in the specification. As the test for fair basis, the High Court in Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (Lockwood) [2004] HCA 58 at [69]; (2004) 217 CLR 274 at 300 [69] approved the words of Gummow J in Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 at 95:
“... the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification.”
Merial submitted that the claims lack of fair basis insofar as they encompass:
(i)vaccine protection of piglets with MDA titres greater than 13 (log2);
(ii)a single dose of vaccine;
(iii)a whole inactivated PCV-2 form or other vaccines unrelated to the disclosure (eg. chimeric PCV-1/PCV-2 vaccines).
I will each of these submissions in turn.
piglets with MDA titres greater than 13 (log2)
Merial submission that the claims lack fair basis insofar as they encompass vaccine protection of piglets with MDA titres greater than 13 log2, which is inconsistent with the invention described in the specification, is based on the following statement on page 4 of the specification,
“It has been shown that a vaccine according to the invention can even provide adequate protection against PCV-2 infection to piglets that have MDA titres falling in “cluster 2” as defined in the Examples (Table 2). Piglets falling within this cluster have MDA titres between 8 and 12 log2 which is a high MDA titre.
A vaccine according to the invention can therefore even be used in a method for the protection of young piglets, which have an MDA titre against PCV-2 up to 10 log2, or even 12 log2 (as measured with a method as indicated in the Examples).”
Intervet submitted that the specification does not teach that piglets with the higher titres cannot be vaccinated, just that the may not benefit as much from the vaccination. Intervet argued that piglets with the highest MDA titres will already have sufficient protection against PCV-2 infection but, in a practical sense, it is easier to vaccinate all of the piglets in a herd rather than test them all beforehand, and vaccination of piglets with the highest MDA titres should not affect them adversely.
For the reasons that follow, I am not satisfied that the statement relied on by Merial should be understood to mean that piglets with higher PCV-2-specific MDA titres cannot be successfully vaccinated. On page 7, lines 20-21, the specification states that vaccination in the face of MDAs can be helped by an adjuvant and/or a high antigen content, but that it is not known which adjuvant or how much antigen is required to break through pathogen-specific MDA titres (page 7, lines 17-22). This is immediately followed by:
“Therefore, in the experiments described we sought to define the minimal amount of antigen that would be needed to protect the piglets in cluster 2 against a PCV-2 infection” (Emphasis added)
I understand from this that the subsequent experiments in the specification were aimed at successfully vaccinating predominantly the piglets in clusters 1 and 2. The results in Table 2 reflect this with successful vaccination of only one Cluster 3 piglet which, consistent with Merial’s submission, had an MDA titre of 13 log2 at the time of vaccination. In my view, the specification provides a real and reasonably clear disclosure of the principle that using an adjuvant and/or higher antigen doses may overcome the interference by high MDA titres (page 7). In Example 5, the specification demonstrates this principle using antigen doses of 20 and 80 mg to successfully vaccinate piglets with MDA titres up to 13 log2. The claims encompass the use of any higher doses of ORF-2 protein that may be required to successfully vaccinate a piglet, in addition to the use of adjuvant, and nothing in the specification is inconsistent with the application of these strategies to achieve seroconversion in piglets with MDA titres higher than 13 log2, should this be desired. For this reason, I find that the claims encompassing vaccine protection of piglets with MDA titres greater than 13 log2 are fairly based.
a single administration of the vaccine
Merial submitted that the claims lack fair basis insofar as they encompass a single administration of the vaccine, which it argued was inconsistent with the specification, which clearly contemplates a two-shot rather than a one-shot vaccine. Merial argued that the minimum doses in the claims are exemplified using two doses of antigen, and the more stringent requirements for effectiveness with a single dose are not consistent with the disclosure in the specification and are not fairly based.
In this regard, Merial relied on the following statement on page 2 of the specification:
“… to protect piglets with vaccination, the piglets will ideally have to be protected from weaning onwards since it is unpredictable when PCV-2 related diseases will manifest.
To achieve this with a two shot vaccination regime, the piglets need to obtain their priming vaccination already in the first week(s) of age so they can receive the booster vaccination round the time of weaning and have obtained full protection against PCV-2 infection just after weaning.”
In my view, that passage exemplifies the invention using a 2-shot vaccination protocol, rather than mandating this approach. Consistent with Intervet’s submission, on page 4, lines 40-41 of the description, a two shot vaccination is described as a preferred embodiment. The description contains consistory clauses mirroring the text of the independent claims (pages 3-3a), and the claims encompass any higher dose of antigen that may be required for a single shot vaccination regime. Consequently, the claims do not lack fair basis for this reason.
whole inactivated PCV-2 forms of the virus and other PCV-2 vaccines
Merial submitted that the claims encompass the use of whole inactivated PCV-2 virus which is distinguished in the specification, in addition to vaccines unrelated to the disclosure such whole inactivated forms of the virus and chimeric PCV-1/PCV-2 vaccines containing PCV-2 ORF-2. Responding, Intervet submitted that the body of the specification exemplifies the vaccine using recombinant ORF-2 protein, and does not state that the ORF-2 protein must be free of other PCV-2 or PCV-1 material.
Intervet’s claims require the vaccine to comprise at least 20 mg or 50 mg dose of the PCV-2 ORF-2 proteins. The examples in the specification provide a real and reasonably clear disclosure of the use of 20 or 80 mg doses of recombinant PCV-2 ORF-2 protein in vaccinating piglets, while higher doses are contemplated on page 3, para 1. Although a vaccine that “comprises” at least 20 or 50 mg of ORF-2 protein may contain other components, there is nothing in the specification that prohibits this. Thus, I am not satisfied that the claims lack fair basis for this reason.
Fair basis summary
Merial has not established that the claims lack fair basis.
Conclusion
The opposition is successful, claims 1-6 and 8-11 lack an inventive step.
It is usual in matters before the Commissioner that in the event that an opposition to grant is successful, the applicant is allowed the opportunity to propose amendments to the claims. I will allow Intervet a period of time to propose suitable amendments.
Costs
It is normal in matters before the Commissioner that costs should follow the event. However, Intervet submitted that it should be awarded costs in the opposition regardless of the outcome, due to Merial’s conduct in the opposition, in particular the filing of further evidence “of a doubtful nature” requiring Intervet to incur further expense and time delays. Merial made no submissions on costs.
Merial has been successful in this opposition. However, the additional material filed by Merial as further evidence did not contribute to establishing a ground of opposition, nor has it changed the outcome of the opposition. In these circumstances, I consider it reasonable to make no award of costs.
Barbara Akhurst
Delegate of the Commissioner of Patents
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