Oravax, Inc v CSL Limited - [2002] APO 20

OFFICIAL NOTICE
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 678195 in the name of Oravax, Inc

Title: Urease Vaccine Against Helicobacter Infection

Action: Opposition under section 59 of the Patents Act 1990 by CSL Limited

Decision: Issued 24 May 2002.
Abstract

The opposition was upheld on the grounds that:
1. Claims 1, 3 to 18 and 23 to 26 are not fairly based on the matter described in the specification insofar as they include within their scope active vaccines of the invention used in therapeutic treatment of mammals infected with Helicobacter.
2. Claims 1, 3 to 5, 7 to 18 and 23 to 27 lack novelty and an inventive step when compared with the prior art base, insofar as they relate to active vaccines used in the treatment of a mammal infected with Helicobacter.
It was found that, because the description fails to provide a "real and reasonably clear disclosure" of therapeutic use of an active vaccine for the treatment of mammals infected with Helicobacter, Claims 1, 4 to 18 and 23 to 26 in part and Claim 3 in full are not entitled to the claimed priority dates, but should take the priority date of the first disclosure of therapeutic vaccination as a result of amendment, viz. 17 February 1997.
Furthermore it was found that Claims 1, 2, 4, 8 to 18 and 22 to 24, 26 and 27 in part and Claims 5 to 7 and 25 in full, insofar as they are directed to polyaminoacid compositions comprising a single subunit of Helicobacter urease, are not fairly based on the disclosure in 07/970,996, but should take the priority date of 08/085938, viz. 6 July 1993.
The opposition failed on grounds of Manner of Manufacture in that the specification does not indicate prime facie that invention is obvious to a person skilled in the art.
Section 40 matters raised in the Statement of Grounds and Particulars were not pursued.
Costs were awarded against the applicant.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 678195 by Oravax, Inc and opposition under section 59 of the Patents Act 1990 by CSL Limited.

BACKGROUND

Patent application no. 678195 was filed under the Patent Cooperation Treaty on 2 November 1993 in the name of Fondation pour la recherche des maladies gastro-intestinales : Gastrofonds Mandataria Fiduciaire SA as International Application Number PCT/EP 93/3059. The application claimed priority from US Applications 07/970996 and 08/085938 dated 3 November 1992 and 6 July 1993 respectively. On 5 July 1994, the applicant changed its name to Oravax, Inc. The application entered the National Phase on 21 July 1994 and was advertised accepted on 22 July 1997. Notice of opposition was filed on 21 August 1997 by CSL Limited and the evidentiary stages completed by 17 August 1999.

The opposition was heard in Canberra on 29 November 2001. The applicant was represented by Ms Katrina Howard of counsel assisted by Dr Andrew Blattman, patent attorney of Spruson & Ferguson, Sydney. The opponent was represented by Mr David Yates, SC of counsel assisted by Mr John Slattery, patent attorney of Davies Collison Cave, Melbourne.
THE GROUNDS OF OPPOSITION
The grounds of opposition identified in the statement of grounds and particulars, are that the invention as claimed:
A.     is not novel in the light of published documents or acts done in Australia
B.     is obvious and does not involve an inventive step
C.     is not a manner of manufacture
D.     does not comply with the requirements of section 40 in respect of the provision of a full description of the invention and the fair basis, clarity and succinctness of the claims.
THE EVIDENCE
The evidence in support consists of statutory declarations by:
·    John Michael Slattery, patent attorney of Davies Collison Cave, Melbourne, dated 19 February 1998 and Exhibits JMS-A to JMS-G.
·    Graham F. Mitchell AO, principal of Foursight Associates Pty Ltd, dated 17 July 1998.
The evidence in answer consists of a statutory declaration by :
·    Harold Kleanthous, Director, Molecular Biology and Animal Studies, Oravax, Inc, dated 14 November 1998 and Exhibits Hk-1 to HK-9.
The evidence in reply consists of a statutory declaration by:
·    Christopher Vincent Doidge, dated 16 August 1999 and Exhibits CVD-1 to CVD-3.
FURTHER EVIDENCE
At the hearing, the applicant requested the admission of further evidence.
Regulation 5.10(4) governs the serving of further evidence:
"The Commissioner may:
           (a) on the application of a party; and
           (b) on such reasonable terms (if any) as the Commissioner specifies;
permit the party to serve further evidence on the other party."
Regulation 5.10(5) imposes further requirements that:
"The Commissioner must not give a direction under subregulation (1) or grant an application under subregulation (2) or (4) unless the Commissioner:
(a) if he or she proposes to grant an application by a party- is reasonably satisfied that the        other party has been notified of the application; and
           (b) if he or she proposes to act on his or her own motion- ensures that the parties are    notified of the proposed action; and
           (c) in either case:
  (i) gives the parties a reasonable opportunity to make representations concerning   the application or proposed action; and
  (ii) is reasonably satisfied that a direction, an extension of time or the serving of   further evidence is appropriate in all the circumstances.
The operation of Regulation 5.10(5) has been considered in Ferocem Pty Ltd v Commissioner of Patents (1994) 28 IPR 243, A Goninan & Co Ltd v Commissioner of Patents (1997) 38 IPR 213 and in National Starch & Chemical Company v Commissioner of Patents [2001] FCA 33. Although these decisions refer to this regulation as it relates to an extension of time to adduce evidence, they clearly relate to the same discretion. These decisions make it clear that reg. 5.10 confers a broad discretion that cannot be reduced to imperative compliance with particular requirements. It requires proper, genuine and realistic consideration of all the relevant aspects that pertain to the application including both the private interests of the parties concerned and the public interest to determine if, in all the relevant circumstances, the granting of the application is appropriate.
In the present case the further evidence is a copy of a statutory declaration by Dr Graham F. Mitchell, dated 13 October 1999. This declaration was originally filed by the opponent as part of the Evidence in Support of their opposition to Patent Application No. 694195. The applicant points to paragraphs 17 and 18 of this declaration as being in apparent conflict with the views expressed by Dr Mitchell in the declaration made by him in relation to the present case.
The interests of the applicant will be served by admission of this evidence as Dr Mitchell's comments clearly relate to the present case, while the opponent' interests would best be served by it not being admitted.
In terms of the content of this declaration, I find that this evidence is credible and likely to have an important influence on the outcome of the case.
In addition, it is in the public interest that a serious opposition should be dealt with on its merit rather than being shut out due to a failure in procedure. Thus, while some delay may result from its inclusion as evidence, I believe that the document's relevance outweighs this consideration. Having considered all these issues, I believe the serving of the further evidence is appropriate in all the circumstances and accept the further evidence.
I recognise, however that the opponent should not be unjustly disadvantaged as a result of the inclusion of this evidence. I therefore granted the opponent, at the hearing, until 3 January 2002 to file submissions in relation to it.
THE SPECIFICATION
The specification as accepted relates to the field of vaccines and broadly to the preparation of antigenic vaccines active against Helicobacter. It particularly refers to the use of Helicobacter urease antigen based vaccines against Helicobacter.
Throughout this decision, I will refer to antigenic therapeutic vaccines as "therapeutic vaccines".
There are two types of vaccines relevant to this decision:
1.Therapeutic vaccines, which are administered to a subject to cure, eradicate or suppress an existing infection, and
2.Protective vaccines, which are administered to a subject who is not currently infected to prevent infection or disease. This is also referred to as prophylactic vaccination.
The claims of the specification as filed were restricted to protective vaccines. This restriction was removed from the claims as a result of amendments filed 17 February 1997.
The specification as accepted ends with twenty-seven claims. The independent claims are as follows:
1.   A method of eliciting an immune response to Helicobacter in a mammal, said method comprising administering to a mucosal surface of said mammal a Helicobacter urease antigen presenting a sufficient number of epitopes of said Helicobacter urease antigen to elicit said immune response.
19. A method for preventing or treating Helicobacter infection in a mammal, said method comprising administering to a mucosal surface of said mammal an IgA antibody specific for Helicobacter antigen.
22. A method for assessing the immune response of a mammal infected by a Helicobacter said method comprising the steps of
(i)Administering a Helicobacter vaccine to a mucosal surface of said mammal; and
(ii)Detecting the presence of antibodies reactive with Helicobacter urease antigen in a sample from the gastrointestinal tract of said mammal.
23. A vaccine for inducing a mucosal immune response to Helicobacter in a mammal, said vaccine comprising a polypeptide presenting a sufficient number of epitopes of a Helicobacter urease antigen to induce said mucosal immune response, in a pharmaceutically acceptable carrier or diluent.
27. A method of eliciting an immune response to Helicobacter urease in a mammal substantially as hereinbefore described with reference to any one of the Examples.
Also noteworthy are dependant Claims 2 and 3:
2.   The method of Claim 1 wherein said mammal is at risk of developing, but does not have, Helicobacter infection.
3.   The method of claim 1, wherein said mammal is infected with Helicobacter.
Of these, Claims 1 and 23 and their appended claims include within their scope antigenic vaccines and their use in therapy of infected mammals.
DECISION
Priority Dates of the Claims
The key question in this opposition is whether the claims as accepted are entitled to priority dates based upon the claimed priority documents. I note that there was no dispute that the claims of the specification as filed were substantially disclosed in the priority documents. The entitlement of the accepted claims to these priority dates may therefore be assessed by determining if they were in substance disclosed in the specification as filed.
If, however, they were only introduced by amendment during examination they may have a later priority date as a result of Section 114 and reg. 3.14. These provisions are as follows:
Priority date of certain amended claims
114(1) Where a claim of a complete specification claims matter that was in substance disclosed as a result of amending the specification, the priority date of the claim must be determined under the regulations.
Priority dates: certain amended claims
3.14If subsection 114(1) of the Act ("priority date of certain amended claims") applies to a claim of a specification, the priority date of the claim is:
(a)in the case of an amendment to which subsection 89(4) or (5) of the Act ("modified application of Act") applies - the date on which the amendment is taken to have been made under that subsection; and
(b)in any other case - the date of filing of the statement of proposed amendments that resulted in the disclosure referred to in subsection 114(1) of the Act.
In determining whether matter is in substance disclosed in the specification as filed, the court in Merck & Co, Inc v Sankyo Co Ltd 23 IPR 415 indicated that the test for fair basis is applicable. Thus, for an amended claim to claim matter in substance disclosed in the specification as filed, then the claim must be fairly based on the specification as filed.
In the current case, the specification as filed did not explicitly refer to therapeutic vaccination and the opponent argued that there was thus no disclosure. The applicant argued, however, that there were parts of the specification directed to therapeutic use or treatment where clearly therapeutic vaccination was intended, and that, in any case, the broad disclosure would have been understood by the person skilled in the art to include therapeutic vaccination.
The applicant argued that the plain meaning of the word "treatment", which was used throughout the specification as filed, includes both protective and therapeutic vaccination. In support of this, the applicant referred me to several definitions of "treatment" in both general and technical dictionaries. All of these indicate that the word, in a medical context, refers to management of a disease or condition or to management in the application of medicaments or surgery. These definitions refer to the treatment of individuals and encompass both protective and therapeutic use.
In addition the term "treatment" is used in parts of the specification in combination with "prevention", i.e. prevention and treatment, suggesting that the term has to include treatment of a person suffering from the disease. (See, for example, page 1, lines 5-6).
The applicant then argued, on the basis of the "Mond Nickel Rules" for determining fair basis, posed by Lloyd-Jacob J. in Re Mond Nickel Company Ltd's Application (1956) RPC 189, that because the word treatment "broadly discloses" therapeutic vaccination, it provides sufficient support to the claims as accepted. I do not accept, however, that "broad disclosure" means any level or type of disclosure. I believe that there has to be a "real and reasonably clear disclosure" as enunciated in CCOM Pty Ltd v Jiejing Pty Ltd (1994) 51 FCR 260 at 278 and applied by the Full Court in determining whether matter was "in substance disclosed" in RGC Mineral Sands Pty Ltd v Wimmera Industrial Minerals Pty Ltd (1998) 42 IPR 353.
While I agree with the applicant's construction, the key issue is not how the term is construed, but what it disclosed to the person skilled in the art at the relevant date.
Both parties acknowledge that, at the filing date of the present case, antigenic therapeutic vaccination while mooted in the art, had not been successfully demonstrated. The question is whether the person skilled in the art, reading the specification in the light of this understanding in the art, would have interpreted the term "treatment" as a real and reasonably clear disclosure of therapeutic vaccination, despite it having not previously been achieved.
In the circumstances of the art at the relevant date, I believe that the person skilled in the art would have expected a disclosure of protective vaccination rather than therapeutic vaccination and would have interpreted general terms in this light unless there was specific teaching to the contrary.
In the specification as filed the term "treatment" is used liberally, but without further interpretation or support. This usage contains no discussion of the mechanism by which therapeutic treatment is achieved or functions, nor does it provide any guidance to the skilled worker as to how such an aspect of the invention should be put into practice. In view of the lack of any prior demonstration of the therapeutic use of antigenic vaccines in the common general knowledge in the field, I do not believe that the skilled worker would have known to prepare or administer such vaccines on the basis of such slender support. Thus, I do not consider that the simple repetition of the word "treatment" provides a "real" disclosure of therapeutic vaccination.
However, the applicant also directed me to two references in the specification as filed and argued that they provided specific disclosure of therapeutic vaccination usage of the broad term "treatment".
The first of these, at page 1, lines 8-10, states that the invention relates to "a method of treatment of humans suffering from gastric infection, its consequences such as chronic gastritis or peptic ulcer, and prevention of gastric cancer" (my emphasis).
While I agree with the applicant that this passage indicates treatment of a person suffering from gastric infection, it does not indicate that antigenic vaccination is contemplated. The specification explicitly discloses a variety of different aspects of the invention including the use of passive antibody vaccines in therapeutic treatment. In view of this disclosure, the above passage might be a reference to the use of such antibody vaccines rather than to antigenic vaccines. Furthermore, this passage alone cannot be said to give any real guidance as to how antigenic vaccination, even if contemplated by the applicant, might be put into effect. Moreover, it occurs at the beginning of the specification as part of a general statement of the invention and the field to which it relates, rather than a detailed consideration of all the aspects it is intended to encompass. Read in the light of the whole of the disclosure, I do not consider that this ambiguous and broad introductory statement to the specification provides a "real and reasonably clear disclosure" of active vaccines used in therapy.
The second reference is at page 23, lines 16ff, of the specification as filed:
"The vaccine can be administered as a primary prophylactic agent in adults or in children, as a secondary prevention, after successful eradication of H. pylori in an infected host, or as a therapeutic agent in the aim to induce an immune response in the host susceptible to contribute to the eradication of H. pylori."
At the hearing there was much dispute as to the meaning of this passage and particularly the meaning of the clause “in the aim to induce an immune response in the host susceptible to contribute…” and the meaning of "susceptible" within it.
From the definitions provided at the hearing, the plain meaning of "susceptible" refers to an item's liability to be affected by an action or agent. In a medical context it normally describes the relationship of a patient to an infection, disease or treatment.
The opponent argued that the phrase refers to a host that had not previously been infected with H. pylori and thus is susceptible to such infection, implying protective vaccination only and that "eradication of H. pylori" relates to eradication from society as a whole rather than from an individual. This seems strained and contrary to the flow of the sentence which moves from consideration of preventative vaccination to secondary prevention and then to "therapeutic" use of the vaccine.
The applicant argued that the word "susceptible” should be read apart from the word "host" and the meaning is that the therapeutic agent is "susceptible to contribute" to the eradication of H. pylori. I consider this to be an unacceptable interpretation due to the strained interpretation applied to "susceptible".
Dr Kleanthous asserts at paragraph 30 of his declaration, that the passage “states unequivocally…that the vaccine of the invention can be used as a therapeutic agent to contribute to the eradication of H. pylori infection”. In support of this assertion he states that the phrase “eradication of H. pylori” clearly refers to the “elimination of an existing infection”. I do not dispute that, today, with the benefit of hindsight, a person skilled in the art could, with some effort, construe this passage to include therapeutic vaccination. At the filing date, however, antigenic therapeutic vaccination was not established as a viable treatment regime. The question is whether the passage is sufficiently clear and explicit that the person skilled in the art, reading it in the context of the specification as a whole, would have interpreted it as a "real and reasonably clear disclosure" of therapeutic vaccination, despite this background understanding in the art.

In my view it is not. I consider that the passage is so poorly constructed and confusing that a person skilled in the art, reading it at the filing date of the application would not understand it to refer to therapeutic vaccination. Consequently I do not consider that it provides a "real and reasonably clear disclosure" of the therapeutic use of the antigenic vaccines of the invention.
I consider that the specification as filed does not provide a "real and reasonably clear" disclosure of therapeutic vaccination and hence I conclude that the claims, insofar as they relate to therapeutic vaccination are not fairly based on the matter disclosed in the priority documents. Consequently Claims 1, 4 to 18 and 23 to 26 in part and Claim 3 in full are not entitled to the claimed priority dates, but should correctly take the priority date of the first disclosure of therapeutic vaccination as a result of amendment, viz. 17 February 1997.
With regard to the remaining claims, these are fairly based on the specification as filed and on the priority documents which are very similar to the specification as filed. The earliest priority document, however, does not disclose vaccines comprising only a subunit of Helicobacter urease rather than the whole protein or sonicates containing it. Such vaccines are first disclosed in the second priority document 08/085938, filed 6 July 1993. I consider therefore, that the claims of the present specification insofar as they are directed to polyaminoacid compositions comprising a single subunit of Helicobacter urease, are not fairly based on the disclosure in 07/970,996 as these embodiments were first disclosed in 08/085938.
I find that Claims 1, 2, 4, 8 to 18, 22 to 24, 26 and 27 in part and Claims 5 to 7 and 25 in full are not entitled to the earliest claimed priority date, but should take the priority date of 08/085938, viz. 6 July 1993. Conversely, Claims 1, 2, 4, 8 to 24, 26 and 27 in part and Claims 19, 20 and 21 in full, insofar as they are directed to vaccines comprising urease antigens generally, sonicates containing them, and to their corresponding antibodies, or their administration, or methods of assessing an immune response in an infected mammal, are entitled to the earliest priority date claimed ie 3 November 1992.
Novelty
The opponents cited seven documents that they argued anticipated claims of the present application, rendering it lacking novelty and/or inventiveness.
D1 Pallen, M.J. and Clayton, C.L. (1990). The Lancet, 336:186-187, and
D2International Patent Publication No. WO 90/04030 (PCT/FR89/00518) in the names of Institut Pasteur National De La Sante Et De La Recerche Medicale
were published before the first claimed priority date of 3 November 1992 and so are relevant to any of the claims in respect of any of the claimed matter.
D1 briefly discusses the remarkable sequence similarity between H. pylori urease and jackbean urease and the suggests the approach of using bacterial or plant urease in a vaccine against ureolytic organisms in man particularly in relation to gastritis and peptic ulceration. While, as noted by the opponent, the citation suggests that "the approach of anti-urease vaccination holds promise", it does not provide a disclosure of either protective or therapeutic vaccination in mammals nor does it disclose mucosal administration. I therefore conclude that this document does not render any of the claims lacking in novelty.
D2 discloses nucleotide sequences coding for polypeptides having urease activity as expressed in Campylobacter pylori (which later became known as H. pylori), vaccines comprising these polypeptides for the prevention of C. pylori infection, mono- and polyclonal antibodies against the proteins, the formulation of these antibodies as a pharmaceutical and their use in a screening method for the presence of C. pylori. The document does not disclose mucosal administration. Consequently, I do not consider that it renders Claims 1 to 22 and 24 to 27 of the present specification lacking in novelty. Claim 23 is not limited to the use of the vaccine for mucosal administration, merely to its suitability for that use. The citation, however, gives no guidance as to methods of formulation. While the applicant argued that mucosal administration was common general knowledge at the priority date, no argument was made that it was common general knowledge at the publication date of D2. On the evidence before me, I therefore conclude that this has not been established. Consequently I consider that the citation does not disclose a vaccine in suitable form for mucosal administration.
D3 Davin, C. et al., Proceedings of DDW, American Gastroenterological Association
(Abstracts of Papers), April 1993, Vol. 104, No. 4, A1035
was published after the first claimed priority date but before the second claimed priority date of 6 July 1993. It is therefore relevant to Claims 1, 2, 4, 8 to 18, 22 to 24, 26 and 27 in part and Claims 5 to 7 and 25 in full insofar as they are directed to protective vaccine compositions comprising a single subunit of Helicobacter urease and any of the claims in respect of antigenic therapeutic vaccination.
Although D3 discloses that urease is a protective antigen of H. pylori that can be used in an oral vaccine against gastric infection it does not disclose either therapeutic antigenic vaccination or vaccines comprising structural subunits of Helicobacter urease. Consequently I do not consider that this document renders any of the claims of the specification lacking in novelty.
D4 AU 679542 (72606/94) dated 28 February 1995;
D5 WO 95/22987 ("Oravax II") dated 31 August 1995;
D6Corthesy-Theulaz, I. et al., Gastroenterology (July 1995); Vol. 109, No. 1, 115-121; and
D7Cuenca, R. et al., Gastroenterology (June 1996); Vol. 110, No. 6, 1770-1775;
were published after the claimed priority dates but before the priority date I have attributed to Claims 1, 4 to 18 and 23 to 26 in part and Claim 3 in full in respect of active therapeutic vaccination viz. 17 February 1997. Consequently they are only relevant to these claims.
I note that the applicant did not make submissions regarding the content D4 to D7 vis a vis the claims of the application, but instead relied upon its argument that the application is entitled to its claimed priority dates.
D4 discloses the treatment of Helicobacter infection in an infected host by active immunisation involving oral administration of Helicobacter antigens optionally in the presence of a mucosal adjuvant and specifically exemplifies cholera toxin. Particular reference is made to the treatment of H. pylori mediated gastrointestinal disorders and the examples are directed to the treatment of mice infected with H. felis by treatment with sonicates of H. pylori. These sonicates would include the urease antigenic components. The citation, while being directed generally to Helicobacter antigens, specifically refers at page 5, to the H. pylori urease antigens as being appropriate for the working of the invention, but makes no reference to the use of H. pylori urease subunits. It furthermore does not disclose the use of antibodies or of the use of the vaccine for assessing the immune response of an infected mammal. The urease disclosed in the document was not recombinant and was not in the form of a fusion protein. I therefore consider that this document renders Claims 1, 3, 4, 12 to 14, 18, 23, 24 and 26 insofar as they relate to a method of treatment of a mammal infected with Helicobacter, lack novelty in the light of D5.
D5 discloses the treatment of gastrointestinal disease in a mammal, specifically including Helicobacter infection, by mucosal administration of a vaccine comprising recombinant Helicobacter urease peptide or subunits thereof, optionally accompanied by a mucosal adjuvant. This embodiment is specifically discussed at pages 26 to 28 of the disclosure and in particular, the citation includes two examples, 4 and 5, directed to the treatment of mice infected with H. felis by oral immunisation with vaccines comprising H. pylori urease B subunit in the presence of cholera toxin and hydroxyapatite. I regard this as providing clear and unmistakable directions to conduct therapeutic vaccination of mammals suffering with Helicobacter infection using vaccines comprising Helicobacter urease peptide or subunits thereof, optionally accompanied by a mucosal adjuvant. The document also discloses the use of anti-idiotypic antibodies. Consequently, I consider that Claims 1, 3 to 5, 7 to 21 and 23 to 27 of the present specification, insofar as they relate to a method of treatment of a mammal infected with Helicobacter, lack novelty in the light of D5.
D6 discloses the oral vaccination of H. felis infected mammalian hosts (mice) with vaccines comprising recombinant H. pylori urease B subunit in the presence of cholera toxin as mucosal adjuvant and hydroxyapatite to aid interepithelial transport. This vaccination resulted in the eradication of the existing infection and ongoing protection from re-infection. The document also notes that the model, using H. felis infection in mice to mimic the corresponding H. pylori infection in humans, is well established in the art. The presence of an immunogenically effective epitope on the B subunit indicates that the same epitope will be present on the whole urease protein that includes this subunit. The document does not disclose vaccination using anti-idiotypic antibodies or the use of urease in the form of a fusion protein. I regard this disclosure as providing clear and unmistakable directions to conduct therapeutic vaccination of mammals suffering with Helicobacter infection using vaccines comprising Helicobacter urease peptide or subunit B thereof, optionally accompanied by a mucosal adjuvant. Consequently, I consider that Claims 1, 3 to 5, 7, 9, 11 to 18 and 23 to 27 of the present specification, insofar as they relate to a method of treatment of a mammal infected with Helicobacter, lack novelty in the light of D6.
D7 discloses the oral vaccination of H. mustelae infected mammalian hosts (ferrets) with vaccines comprising recombinant H. pylori urease in the presence of cholera toxin as mucosal adjuvant. This vaccination resulted in the eradication of the existing infection. H. mustelae is the form of gastric Helicobacter indigenous to ferrets. There was no disclosure of the use of Helicobacter urease subunits in isolation, anti-idiotypic antibodies or the use of a hydroxylated calcium phospholate carrier. I regard this disclosure as providing clear and unmistakable directions to conduct therapeutic vaccination of mammals suffering with Helicobacter infection using vaccines comprising Helicobacter urease peptide, optionally accompanied by a mucosal adjuvant. Consequently, I consider that Claims 1, 3 to 4, 9, 11 to 14, 23 to 24 and 26 of the present specification, insofar as they relate to a method of treatment of a mammal infected with Helicobacter, lack novelty in the light of D7.
Obviousness
The opponent argued that the invention claimed in all claims is obvious and lacks an inventive step in the light of the documents raised under novelty.
The approach most frequently taken in determining inventive step is to determine "whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not". (Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd (1981) 148 CLR 262 at 286)
The Problem
In this case the problem is identified and discussed at length in the background to the invention. The applicant discusses the inadequacies of current antibiotic treatments and indicates that there is a need for improved immunological regimes effective against the variety of gastrointestinal conditions that are associated with Helicobacter infection. The applicant goes on to discuss the lack of knowledge about the mucosal immune system and its apparent inability in many cases to maintain extended immunity against Helicobacter species. The applicant further indicates that Helicobacter urease, while previously suggested as a possible vaccine candidate, had not been confirmed as efficacious in mammals and was generally thought to be inappropriate. In the light of this discussion I consider the problem that the applicant set out to solve to be the identification and characterisation of suitable antigens for the preparation of vaccines effective in eliciting a mucosal immune response against Helicobacter species in mammals.
The Person Skilled in the Art and the Prior Art Base
The problem is concerned with the formulation and testing of vaccines, particularly in relation to the mucosal route. The specification discusses the preparation of bacterial isolates, the preparation of antibodies and recombinant urease, screening for the presence of antibodies and the handling of test animals. I consider that the person skilled in the art would thus be a skilled microbiologist/immunologist with experience in administering animal testing regimes and preparing vaccine formulations, some knowledge of recombinant DNA techniques and interest in matters relating to Helicobacter infection and the mucosal immune response in particular.
At the hearing the applicant submitted that Dr Mitchell and Mr Doidge are too highly qualified to give evidence as to what a person skilled in the art would understand, consider common general knowledge or consider routine. In particular, the applicant pointed to Dr Mitchell’s eminence in scientific research in the field to which the invention relates and Mr Doidge’s inventiveness as evidenced by his being inventor in respect of several patents. The field to which the invention relates, however, is fast moving and inherently complex. Consequently identifying a person with sufficient skills to be competent to comment meaningfully on the matters in dispute will invariably involve persons whose skills are beyond those of a mere technician. Moreover, the evidence supplied by declarants is not limited to what they personally consider to be routine or common general knowledge, but to that which they consider would be routine or common general knowledge to a person skilled in the art. The question is therefore not whether Dr Mitchell or Mr Doidge are themselves persons skilled in the art, but whether they have the requisite skills and experience to be able to make a meaningful assessment of what would be known or done by a person skilled in the art. Given that the applicant has provided no evidence of either Dr Mitchell’s or Mr Doidge’s incapacity in this regard, beyond their technical skill, I do not consider that the applicant has made out its case in this respect. I accept Dr Mitchell and Mr Doidge as being competent to comment on matters relating to persons skilled in the art.
The prior art base in relation to deciding whether or not there exists an inventive step, is defined in the Schedule 1 of Patents Act 1990. In the context of a standard patent application it includes: information contained in any document publicly available either within or outside the patent area, and information made publicly available through the doing of an act anywhere in the patent area; where the patent area includes Australia, the surrounding continental shelf and waters above it and the airspace above either Australia or the continental shelf.
In considering whether or not there exists an inventive step, however, Section 7(3) also requires that for a document to be relevant to such consideration, it must be one that the person skilled in the art, before the priority date, could have been reasonably expected to have ascertained, understood and considered relevant to the art in the patent area.
In this case, I consider that such documents would include journals relating to vaccines, microbiology, especially in relation to microorganisms endemic to the gastric mucosa, animal testing techniques and current practice with regard to biotechnology in general and immunology in particular. The applicant argued at the hearing that, due to the lack of commercial activity in the field at the filing date, the person skilled in the art would not have referred to patent documents and so could not be reasonably expected to have ascertained such documents. I do not agree. In my view the problem addressed and the product sought are clearly of commercial significance. I consider that the patent literature would certainly have been considered. Further, the significant amount of patent literature at the filing date indicates that it was an active medium for publications in the field.
Common General Knowledge
The common general knowledge would include those aspects of immunology, biotechnology and animal testing regimes and the associated techniques that would be known to the person skilled in the art and would include such items as recognised texts in the field and standard laboratory manuals.
The following items were referred to in the statement of grounds and particulars as being common general knowledge in the art. This assertion was not disputed by the applicant.
·    Knowledge of the distinction between prophylactic and therapeutic vaccines; therapeutic use of active vaccines while known in the art had not been successfully demonstrated
·    Knowledge of the production, formulation and use of prophylactic vaccines in prevention of infection in animals, including humans
·    Knowledge of the use of small animal models in research and development relating to prophylactic vaccines and the use thereof in prevention of infection in animals, including humans; particularly the mouse model using H. felis as infective agent, in studying H. pylori infection in humans
The opponent further asserted at the hearing that the prior art documents referred to in the present specification also comprised common general knowledge. The opponent provided no additional evidence to support this contention but argued, on the basis of the following passage in the Federal Court decision of Bristol-Myers Squibb Co v F H Faulding & Co Ltd [2000] FCA 316 (22 March 2000), that mere reference to them in the specification established them as common general knowledge.
"If a patent application, lodged in Australia, refers to information derived from a number of prior publications referred to in the specification or, generally, to matters which are known, in our view the Court - or the Commissioner - would ordinarily proceed upon the basis that the knowledge thus described is, in the language of s 7(2) of the 1990 Act, part of "the common general knowledge as it existed in the patent area". In other words, what is disclosed in such terms may be taken as an admission to that effect. In substance, we think, that is what happened, both in Microcell and in Philips. "
The delegate in The University of Georgia Research Foundation Inc v BioChem Pharma Inc decision, [2000] APO 68, also considered the above passage from the Bristol- Myers (supra) case. He concluded that "if information is stated [in a specification] to be common general knowledge or can reasonably be inferred to be common general knowledge, then the commissioner can accept that conclusion without any further evidence. It is not correct to say that every piece of prior art referred to in the specification is part of the common general knowledge." Furthermore, in Alkermes Controlled Therapeutics Inc. II v Southern Research Institute [2001] APO 41, the delegate in considering the same issue commented that "It seems logical that references to prior documents detailed in a patent specification must have to meet the same requirements as other prior documents put forward as disclosing common general knowledge." He went on to point out that "As there is a requirement in many jurisdictions (although not Australia) for a patent application to acknowledge the existing prior art, a reference to a patent in an application that originates from overseas may exist for this reason alone."

I agree with these comments. I do not consider that the mere presence of a reference to a document in a patent specification is sufficient to say that the document referred to is common general knowledge in the art.
In the present case, the documents to which the opponent has referred are part of the background to the invention claimed. I do not consider that the specification makes a clear acknowledgement or inference that the teaching of these documents is sufficiently widely known and relied upon by persons skilled in the art to be considered part of the common general knowledge.
The opponent also specifically submitted the feature of mucosal administration, in particular oral administration, was common general knowledge. Dr Mitchell states at paragraph 15 of his declaration, in relation to D2, that “conventional formulation types and administration routes for prophylactic vaccines … would be included, including in particular oral administration”. Dr Kleanthous responds at paragraph 38 of his declaration that, at the filing date of the application, while other formulations may have been well known, “Mucosal subunit vaccines, containing a single peptide or soluble protein from a pathogen (e.g., Helicobacter urease), simply were not known at the time, nor were they even considered plausible alternatives”. He explains that mucosal administration was not widely used for vaccines and only known as comprising whole pathogens due to steric requirements at that time thought to prevent their ingestion by antigen trapping cells. In the light of this evidence, I conclude that conventional formulations and administration routes, at the filing date, did not include mucosal administration and that it was not a part of the common general knowledge in this field. It therefore would not have been a routine for the person skilled in the art to formulate a mucosal vaccine based solely on the identification of a suitable antigen.
I note that the dependant claims introduce additional features including, for example, the use of anti-idiotypic antibodies, the presentation of antigens as fusion proteins and the use of recombinant forms of antigens. I consider that these are merely common design parameters that the person skilled in the art could routinely introduce or vary in putting into practice the invention. In the absence of submissions establishing that these features are inventive in the context of the invention, I consider them to be part of the common general knowledge in the art.
Discussion of Citations
All the cited documents referred to above are patent applications or are found in recognised technical journals known in the art. I consider that they would all have been found, understood and considered relevant by the person skilled in the art seeking a solution to the problem outlined above.
Although D1 discusses the possibility of vaccination using urease antigen, it provides no guidance that would lead the person skilled in the art to use mucosal administration. I note that Dr Mitchell, at paragraph 14 of his declaration, states that the method of Claim 1, the formulation involving cholera toxin of Claims 12 and 13, and the vaccine of Claims 23 and 24 lack “inventive ingenuity”. It is evident from his declaration, however, Dr Mitchell reached this conclusion by combining the disclosure in D1 with the admitted prior art documents, treated as common general knowledge as argued by the opponent. Dr Mitchell does not establish that these documents were common general knowledge in their own right. As I have already concluded that the mere citing of these documents as prior art in the specification does not qualify them as common general knowledge, I must give Dr Mitchell’s comments in this regard a low weighting in my considerations. Consequently I consider that the claims are inventive in the light of this D1.
Likewise, D2 provides no teaching that would lead the person skilled in the art to formulate a mucosal vaccine and the opponent has failed to make out a case that mucosal administration was common general knowledge at the relevant date. Consequently I consider that the claims are inventive in the light of this D2.
D3, being published after the filing date of the earlier priority document can only anticipate claims to subunit vaccines and methods. There is, however, no disclosure of subunit vaccines in this document. Furthermore the opponent has made no submissions that the preparation of subunit vaccines would be routine when faced with the disclosure in this document. I therefore consider that the claims are inventive in the light of this document.
D4, D5, D6 and D7 have already been identified as depriving specific claims of novelty as detailed above. I consider that these claims lack an inventive step on the basis of these disclosures. I also consider that the associated dependant claims lack inventiveness as the additional features they disclose are common general knowledge in the art and do not constitute, of themselves, an inventive step.
Manner of Manufacture - Section 18
The majority of the High Court in NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd 32 IPR 449 concluded that the “newness” requirement of Section 18(1)(a) should be interpreted as requiring the exclusion from a “patentable invention” of processes, methods or uses which are not, on the face of the specification, a proper subject for letters patent.
In Bristol-Myers Squibb Co v FH Faulding & Co Ltd (2000) 46 IPR 553, the majority summarised the effect of the Philips case as:
"Philips stands for the proposition (as a matter of construction of the 1990 Act) that if, on the basis of what was known, as revealed on the face of the specification, the invention claimed was obvious or did not involve an inventive step - that is, would be obvious to the hypothetical non- inventive and unimaginative skilled worker in the field (Minnesota at CLR 260 per Barwick CJ) - then the threshold requirement of inventiveness is not met."
[page 564]
The opponent asserted that the claimed invention fails this “threshold test” because the specification discloses prior documents on the basis of which the invention is clearly obvious.
In this case the specification discloses documents that discuss the possibility of urease as a vaccine against Helicobacter infection including D1 and EPO Patent Application 367 644. The specification goes on to indicate at page 3, lines 25 to page 4, line 8, however, that urease would not have been considered a viable antigenic basis for formulating a vaccine based on current knowledge of human H. pylori infection because:
(i)The anti urease immune response was not known to result in clearance or control of the infection;
(ii)H. pylori is known to transport urease out of the cell providing a potential decoy for any immune response based on urease;
(iii)Urease's apparent toxicity to mucosal surface cells
I consider, in reporting on and subsequently assessing these prior art documents in the light of what it states to be "current knowledge of human H. pylori infection", the specification does not indicate that, prime facie, the invention is obvious to the person skilled in the art. On the contrary, it argues that further experimentation and a departure from conventional wisdom was required to formulate the vaccine and method to which the specification is directed.
Consequently I do not consider that the specification fails the threshold test of Section 40.
Fair Basis
The opponent argued that the claims of the specification as accepted are not fairly based on the description of the specification as accepted because they
(i)are not limited to vaccination in the presence of a mucosal adjuvant, and
(ii)they include therapeutic vaccination
As there was some discussion at the hearing as to the appropriate test to apply in determining this "internal fair basis", I shall briefly discuss the law in relation to this issue.
The Law on "Internal" Fair Basis
Under Section 40(3) of the Patents Act 1990, the claim(s) of a specification are required to "be clear and succinct and fairly based on the matter described in the specification".
In determining fair basis, I note that while Section 40(3) requires that the claims be "fairly based on the matter described in the specification", regulation 3.12(1)(b) requires that, for a claim to be fairly based on a basic document, it must be "fairly based on the matter disclosed" in the basic document".
The majority of law on fair basis relates to the latter situation and is assessed by asking whether there has been a "real and reasonably clear disclosure" (for example, Hoffman-La Roche & Co AG v Commissioner of Patents [1973] RPC 34 and CCOM Pty Ltd v Jiejing Pty Ltd (supra)). The question then is whether this law is applicable or whether "described" should be read as requiring a more stringent test than "disclosed".
In Emory University v Biochem Pharma [1999] APO 050, the delegate, in considering the issue of Section 40(3) fair basis ("internal fair basis") referred to this distinction in wording in relation to the available case law. He commented that:
"The small number of cases dealing with internal fair basis have also applied the "real and reasonably clear disclosure" test, but without argument as to whether this is the appropriate test (see Rehm Pty Ltd v Websters Security Systems ( International) Pty Ltd (1988) 81 ALR 79 at 95 and Patent Gesellschaft AG v Saudi Livestock Transport and Trading Co (1997) 37 IPR 523 at 530)"..
In the Emory case the circumstances were such that the delegate was not required to resolve this issue, in order to reach his decision. Nonetheless, in the absence of court consideration of this issue in detail and their tacit acceptance of the "real and reasonably clear disclosure" test in matters of internal fair basis, I consider that, for the time being at least, this is the appropriate test to apply.
In the light of these considerations I shall therefore be seeking a “real and reasonably clear disclosure”, as enunciated in the Rehm case at page 95 in the context of internal fair basis:
"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"
I note also that in determining this issue, it is "necessary to have regard to the description as a whole" (Emory University v Biochem Pharma Inc [1990] APO 050) rather than to engage in "a mere comparison of text in the claim with text in the description".
Administration of a Mucosal Adjuvant
The opponent argued that the specification only provided support for vaccines of the invention when administered in the presence of a mucosal adjuvant and referred me to the specification at page 5, lines 2 to 5:
"The invention provides a method of inducing immunity to Helicobacter infection by administering to a mucosal surface of a mammal a polyaminoacid preparation, i.e., a mixture of peptides and or proteins, together with an appropriate adjuvant."
While this statement is clearly an indication of what is provided by the invention, I do not see that it is a limiting statement of the bounds of the invention. Applicants frequently include such statements in the summary of the invention where they are reciting how their invention came about. It is necessary to read the whole of the specification to determine whether such a limitation is truly conveyed. With the exception of this passage, the remainder of the specification clearly teaches that the use of a mucosal adjuvant is an optional feature, albeit preferred and exemplified. In my opinion the specification contains no "real and reasonably clear disclosure" that a mucosal adjuvant is essential to the invention. Thus, reading the specification as a whole, I do not consider that the use of a mucosal adjuvant is an essential feature of the invention.
Consequently, I conclude that the claims are fairly based on the matter described in respect of their omission of this feature.
Therapeutic Active Vaccination
I have already discussed this issue in relation to the use of the word "treatment" and the specific disclosures on pages 1 and 23 of the specification as filed, when I considered the determination of the priority dates. I found that these disclosures did not provide a "real and reasonably clear" disclosure of therapeutic vaccination. As the test being applied here is the same as that which I applied under the head of fair basis in relation to the priority documents, and the same text occurs in the document as accepted, I will not revisit these issues.
The applicant directed me, however, to additional specific reference to therapeutic vaccination present only in the specification as accepted. This occurs in Claim 3 which is specifically directed to vaccination of an infected host. This disclosure, however, is merely a general statement of the desired monopoly. In the absence of support in the description, I consider that a skilled addressee would not be enabled to carry out the invention in respect of therapeutic use of the antigenic vaccines by this level of disclosure and would, I believe, recognise it merely as an unsubstantiated claim against matter for which no real support, exemplification or direction has been provided.
In the further evidence that I allowed at the hearing the applicant argued that in a declaration made by Dr Mitchell in relation to 694195, he conceded that the claims of the accepted specification are fairly based. The applicant argued that in this declaration, Dr Mitchell “asserts that the claims of AU 694195 lack novelty in the light of the opposed application, indicating that his view is that therapeutic vaccines are taught in the opposed application”. The applicant's submission made particular reference to paragraphs 17 and 18.
In its response, the opponent argued that in the 694195 declaration, Dr Mitchell’s comments were conclusions based upon reference to the matter encompassed by the accepted claims of 678195, rather than an assessment of the specification as a whole. Claim 3, to which Dr Mitchell specifically refers, explicitly claims therapeutic administration. At paragraph 17 of this declaration, Dr Mitchell, referring to 678195 as Document F, states:
"In view of claim 3 of Document F as accepted, I consider that the methods claimed in the claims of the accepted OraVax application are anticipated by and lack novelty in the light of Document F, having regard to the claims made therein, particularly claim 3, since the latter claim is specifically directed to a method wherein a Helicobacter urease antigen is as administered to a mammal infected with Helicobacter." (my emphasis)
I agree with the opponent. It appears from this declaration that Dr Mitchell's assessment of 678195 was based on the claims, and he did not give a detailed consideration as to their fair basis. His reference to Document F in general terms indicates to me that he considered the full disclosure only insofar as assessing that it does not explicitly contradict the matter to which the claims are directed. Thus, he specifically couched his comments in terms indicating that the disclosure to which he was referring was that in the claims and Claim 3 in particular.
Consequently, I do not consider that Dr Mitchell made a concession as to the fair basis of the claims of the specification.
In the light of these considerations I do not believe that the applicant has provided a "real and reasonably clear disclosure" of therapeutic use of an active vaccine for the treatment of mammals infected with Helicobacter in the accepted specification.
Consequently, Claims 1, 3 to 18 and 23 to 26 are not fairly based on the matter described in the specification insofar as they include within their scope active vaccines of the invention used in therapeutic treatment of mammals infected with Helicobacter.
Claims 2, 19 to 22 and 27 are fairly based for the following reasons:
·    Claim 2 is specifically limited to prophylactic vaccination. I therefore consider it to be fairly based on the specification.
·    Claims 19 to 21 are directed to passive vaccination. There has been no dispute on the fair basing of claims to passive vaccination and I regard these claims as fairly based.
·    Although Claim 22 involves the administration of active vaccine to a patient suffering from Helicobacter infection, it is claimed in a method of assessing the patient’s immune response rather than as a therapeutic vaccine. Thus Claim 22 is not in dispute with regard to fair basis in the context of therapeutic active vaccination and I regard it as fairly based on the specification.
·    Since the exemplification of the invention provided in the specification does not include active therapeutic vaccination, I regard the omnibus Claim 27 as being limited to prophylactic use of the vaccines of the invention and therefore not in contention with regard to fair basis.
Section 40
None of the other Section 40 matters raised in the statement of Grounds and Particulars was pursued in the opponent’s submissions and none of these matters appear likely to render the patent invalid. I will not consider them further in this decision.
CONCLUSION
I have found that the opposition has been successful on the grounds of fair basis, novelty and lack of inventive step. In particular, I have found that:
1.   While the description discloses and provides support for vaccines and methods of their use via mucosal administration to generate a protective immune response against Helicobacter infection in mammals, it fails to a "real and reasonably clear disclosure" of therapeutic use of an active vaccine for the treatment of mammals infected with Helicobacter.   Consequently, Claims 1, 3 to 18 and 23 to 26 are not fairly based on the matter described in the specification insofar as they include within their scope active vaccines of the invention used in therapeutic treatment of mammals infected with Helicobacter.
2.   Furthermore, as these claims are also not fairly based on the matter disclosed in the priority documents, Claims 1, 4 to 18 and 23 to 26 in part and Claim 3 in full are not entitled to the claimed priority dates, but should take the priority date of the first disclosure of therapeutic vaccination as a result of amendment, viz. 17 February 1997.
3.   In addition, I find that Claims 1, 2, 4, 8 to 18 and 22 to 24, 26 and 27 in part and Claims 5 to 7 and 25 in full, insofar as they are directed to polyaminoacid compositions comprising a single subunit of Helicobacter urease, are not fairly based on the disclosure in 07/970,996, but should take the priority date of 08/085938, viz. 6 July 1993.
4.   As a result, insofar as they relate to active vaccines used in the treatment of a mammal infected with Helicobacter,
(i)Claims 1, 3, 4, 9, 12 to 14, 18, 23, 24 and 26 lack novelty and Claims 1, 3, 4, 8 to 18, 23, 24 and 26 lack an inventive step in the light of D4.
(ii)Claims 1, 3 to 5, 7 to 21 and 23 to 27 lack novelty and an inventive step in the light of D5.
(iii)Claims 1, 3 to 5, 7, 9, 11 to 18 and 23 to 27 lack novelty and Claims 1, 3 to 5 , 7 to 18 and 23 to 27 lack an inventive step in the light of D6.
(iv)Claims 1, 3, 4, 9, 11 to 14, 23 to 24 and 26 lack novelty and Claims 1, 3, 5, 8 to 18, 23, 24 and 26 lack an inventive step in the light of D7.
5.   The opposition failed on grounds of Manner of Manufacture in that the specification does not indicate prime facie that invention is obvious to the person skilled in the art.
Consequently, I find that the opposition has been made out in part but the specification is clearly capable of amendment to overcome these matters. I allow the applicant sixty days from the date of this decision to propose amendments to that effect.
COSTS

It is a general principle that, in the absence of special factors, costs should follow the event. I can see no special factors in this case that would justify departing from this principle. As the opponent has been successful in this matter, I award costs against the applicant, Oravax, Inc.
Leigh R. Tristram
Delegate for the Commissioner of Patents
Patent Attorneys for the applicant: Davies Collison Cave, Melbourne
Patent Attorneys for the opponent: Spruson & Ferguson, Sydney