QIP Nominees Pty Ltd. v Dana-Farber Cancer Institute, Inc. and the General Hospital Corporation - [2024] APO 33

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
QIP Nominees Pty Ltd. v Dana-Farber Cancer Institute, Inc. and The General Hospital Corporation [2024] APO 33

Patent Application: 2018206769

Title:Compositions and methods of identifying tumor specific neoantigens

Patent Applicant: Dana-Farber Cancer Institute, Inc. and The General Hospital Corporation

Opponent:  QIP Nominees Pty Ltd.
Delegate:  K. Wagg
Decision Date:  7 August 2024
Hearing Date:  19 April 2023

Catchwords: PATENTS – section 59 opposition to the grant of a patent – whether a book chapter contains clear and unmistakable directions or would directly lead a PSA to the claimed invention – quality of disclosure – cancer vaccination using neoepitopes from whole genome of cancer screen against patient’s genome – state of the art at priority date – sufficiency and support considered – method of treating cancer – use of at least 4 neoepitopes with predicted HLA class 1 binding of less than 150 nM – evidence does not satisfy the Commissioner of a ground of Opposition – Costs awarded against the Opponent

Representation: Counsel for the Applicant: Katrina Howard SC
Patent attorney for the Applicant: Dr Leigh Guerin of POF
Patent Attorney and Lawyer for the Applicant: David Longmuir of POF.

Patent attorneys for the Opponent: Dr Mathew Lucas of Davies Collison Cave (Melbourne) and Dr Kian Hoe Khoo of Davies Collison Cave (Singapore).

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2018206769

Title:Compositions and methods of identifying tumor specific neoantigens

Patent Applicant: Dana-Farber Cancer Institute, Inc. and The General Hospital Corporation

Date of Decision: 7 August 2024
DECISION
The Opposition has been unsuccessful on all grounds. Subject to appeal, I direct that the application proceed to grant.
Costs are awarded against the Opponent.
REASONS FOR DECISION
Background

Patent application number 2018206769 (the Opposed application or the Specification) was filed on 19 July 2018 by Dana-Farber Cancer Institute, Inc. and The General Hospital Corporation (the applicant).The application is a divisional application. The Parent is 2015264880, the grand parent is 2011252795 which was filed through the PCT as PCT/US2011/036665 which claims priority from US 61/334,866. The priority date claimed is 14 May 2010. I note that the child application 2021205080 has been accepted.
As a result of the filing date and subsequent later request for examination, the substantive amendments of the Patents Act 1990 brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Raising the Bar Act) apply to the present 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 exists. Any subsequent references to sections of the Patents Act relate to the Patents Act 1990 as amended by the Raising the Bar Act. A similar qualification applies to references to the Patents Regulations 1991.
The application was examined and advertised as accepted by the Commissioner on 15 April 2021. QIP Nominees Pty Ltd (the opponent) filed a notice of opposition to grant on 15 July 2021 under section 59 of the Act. This decision concerns the opposition to grant under section 59 (this opposition).
The Grounds of Opposition
The Statement of Grounds and Particulars (the SGP) filed on 15 October 2021 identified all of the available grounds of opposition. The SGP particularised one document for novelty and five documents for inventive step. The SGP then had a list of 128 mentioned documents said to form part of the common general knowledge with the SGP stating at 3.10:
“At least the following documents form part of the common general knowledge, or in the alternative, are documents that a person skilled in the art could reasonably be expected to have ascertained, understood and regarded as relevant at the priority date of any of the claims, in addition to prior art documents referred to in the specification of the Application”.
That list included D70 which was a declaration by Dr John Castle dated 9 November 2016 and, D71, a declaration by Dr Nir Hacohen on US 13/108,610 dated February 2014.
Upon receipt of the SGP and mentioned documents, a delegate of the Commissioner directed that the accompanying documents are treated as evidence in support.[1] The delegate then set the due date for the Evidence in Support. This practice of directing the mentioned documents be treated as evidence was to streamline the process so that documents did not have to be repeatedly exhibited with declarations and to ensure any documents relied on were filed as evidence.
[1] Letter of acknowledgement of SGP dated 28 October 2021
When the opponent filed their summary of submissions days before the current hearing it was clear that they sought to rely on D70. While the applicant had not treated it as a declaration normally filed as part of evidence in support, and had not filed evidence in answer to it, they were able to respond to the declaration by way of submission. Including a declaration in a list of 128 documents said to be common general knowledge can only be described as a Gish gallop. It should be noted that in cases where a Gish gallop of an SGP is filed, the applicant may request further and better particulars and/or dismissal of the opposition.
The Opponent’s summary of submissions also included eight annexed documents which were not in evidence. This included a decision by the European Patent Office (EPO) on the European equivalent. The Opponent had commented on the EPO decision in their summary of submissions. At the hearing the Opponent presented a slide show, this included several deviations from their written submissions and included references to the annexed documents. I have reviewed the EPO decision and the annexed documents, and I am not convinced they add anything to the Opponent’s case. However, if the Commissioner consults documents not in evidence under regulation 5.23, then the parties must be provided with an opportunity to respond. In the current case I do not consider that these documents would likely affect the outcome of this decision and I therefore will not exercise my discretion under regulation 5.23. Generally, if a party intends to introduce new material they should do so at the earliest opportunity rather than immediately prior to the hearing.
Onus and Standard of Proof
The onus lies with the opponent to satisfy me that a ground of opposition exists on the balance of probabilities.[2] If I am satisfied, then I may refuse the Opposed Application.[3]
[2] Section 60(3A).
[3] Ibid.
Evidence
The evidence in support comprises the following declarations:

Declarant Date Reference Exhibits

Dr Tina Lavranos 12 January 2022 Lavranos #1 TL-1

Dr Tina Lavranos 17 January 2022 Lavranos #2 None

The evidence in answer comprises the following declaration:

Declarant Date Reference Exhibits

Professor Cornelis Melief 18 April 2022 Melief CJMM-1 to CJMM-5

. The evidence in reply comprises the following declaration:

Declarant Date Reference Exhibits

Tina Lavranos 22 June 2022 Lavranos #3 None

As discussed previously, the SGP mentioned many documents and included a declaration by Dr John Castle as D70 and another declaration as D71.
The Specification
Before commencing to construe the specification, I note what Middleton J said about approaching patent specifications in Eli Lilly v Apotex Pty Ltd:
"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.”[4]
[4] Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214, 100 IPR 451 at [139].
To properly construe the specification, it is essential to obtain an idea of the technology the invention relates to and obtain a picture of the person skilled in the art. I will therefore review the background.
Background
The Application begins by stating that it is a divisional of 2015264880 which is in turn is a divisional of 2011252795. The grand parent, 2011252795 is said to be related to the original PCT application PCT/US2011/036665 (it is the national phase entry application) which claims priority from US 61/334,866 and incorporates the disclosures of all of these applications by reference.
Field of the Invention
The specification states that the invention relates generally to the identification of tumour specific neoantigens and the uses of these neoantigens to produce cancer vaccines.
The background then continues by stating that tumour vaccines typically compose both tumour antigens and immunostimulatory molecules.[5] These are said to work together to induce antigen-specific cytotoxic T cells (CTLs) that recognise and lyse tumour cells.[6]
[5] Specification page 1 [0003], from here any reference to page and paragraph numbers in square brackets refers the specification/ the opposed application.
[6] Ibid.
Prof Melief[7] set out some background information from CJMM-4 which reviewed D110 and D121 from a series in the journal, Nature, from 2017. These are said to be clinical trials of the invention. Although this information is from after the priority date, it is useful to provide some background information on the cancer vaccines of the Opposed application, it states:
“The vaccination strategy for triggering a tumor-specific response by immune cells
called T cells can consist of the introduction into the body of peptide fragments known as antigens, which are presented to the immune system when bound by proteins of the major histocompatibility complex (MHC)
…
If an antigen bound to an MHC protein is recognized by a T-cell receptor (found on the surface of a T cell), the T cell can mount a response against any cell that contains the antigen. There are two types of MHC protein, and these present antigens to different types of T cell. MHC class I proteins present antigens to cells known as CD8+ killer T cells, which express the protein CD8 on their surfaces. These T cells can then mount an attack that directly kills cells expressing the specific antigen. Cells other than immune cells, including tumor cells, usually have MHC class I but not MHC class II proteins on their surfaces.
MHC class II proteins are found on the surfaces of cells of the immune system. They present antigens to T cells that express the protein CD4 and are known as CD4+ helper T cells. Tumor-cell antigens can be presented to CD4+ helper T cells by antigen presenting cells that ingest substances from dying cancer cells. Direct recognition of tumor cells by CD4+ helper T cells has been documented, and these cells are also associated with the direct killing of tumor cells [citations omitted]. CD4+ helper T cells have an additional role in optimizing the function of CD8+ T cells [citation omitted], and in aiding the generation of CD8+ T cells with a ‘memory’ capacity [citation omitted] that enables a more robust response on a subsequent encounter with a given antigen”
[7] Melief at [26]
Dr Lavranos[8] stated that at the time of filing the specification almost all vaccines contain either shared tumor antigens or whole tumor cell preparations and explained that there is a third class of tumor antigens that has rarely been used in vaccines due to technical difficulties in identifying them. She went on to explain that this class consists of proteins with tumor-specific mutations that result in altered amino acid sequences. Such mutated proteins have the potential to (a) uniquely mark a tumor (relative to non-tumor cells) for recognition and destruction by the immune system; and (b) avoid central and sometimes peripheral T cell tolerance, and thus be recognized by more effective, high avidity T cell receptors.[9] Dr Lavranos’ comments are consistent with the background of the specification.
[8] Lavranos #2 at [3].
[9] Ibid.
With this background in mind I will now characterise the person skilled in the art.
The Person Skilled in the Art (PSA)
The concept of the person skilled in the art (PSA) has long been considered by the courts when construing patent specifications. Finkelstein J described the PSA with the following words in Root Quality[10]:
“He is the person to whom the patent is addressed and who must construe it. He is the person whose knowledge will determine whether a patent is novel. He is the person who will judge whether a patent is obvious.” [11]
[10] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980; 49 IPR 225
[11]Ibid at [70].
Finkelstein J also cited Lord Diplock in Catnic[12] where he said the PSA is likely to have a practical interest in the subject matter:
“My Lords, a patent specification is a unilateral statement by the patentee, in words of his own choosing, addressed to those likely to have a practical interest in the subject matter of his invention (i.e. ‘skilled in the art’)”[13]
[12] Catinc Industries Inc. v Hill & Smith Limited [1982] RPC 183 at XX
[13] Ibid at 243.
This approach to the PSA having a practical interest in the subject matter was approved by the Full Federal Court with Heerey, Emmett and Dowsett JJ stating:
“The uninventive but skilled worker is likely to have a practical interest in the subject matter of the claimed invention.”[14]
[14] Minnesota Mining & Manufacturing Co v Tyco Electronics Pty Ltd [2002] FCAFC 315; 56 IPR 248 at [39], 257.
Kiefel J (when she was still on the Federal Court) added to this statement that the person would be acquainted with the surrounding circumstances of the art and manufacture and may often work in the art with which the invention is connect.[15]
[15] KD Kanopy Australasia Pty Ltd v Insta Image (2007) 71 IPR 615 at 621, approved on appeal at (2008) 78 IPR 20 at 38 [94]-[96].
In an art such as the present case it would be hard to find a skilled worker whom I would call uninventive, instead the PSA is an artificial construct used as a tool of analysis. This concept of using an artificial construct was articulated in AstraZeneca[16]:
“The notional person is not an avatar for expert witnesses whose testimony is accepted by the court. It is a pale shadow of a real person – 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.”[17]
[16] AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30.
[17] AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30 at [23].
The field of the invention of the application relates to the identification of neoantigens that can be used in cancer vaccines. This field involves immunology and specifically cancer immunology. The PSA would be aware of immunotherapies for cancer at the priority date as well as cancer vaccination.
The Applicant’s declarant, Prof. Melief is an Emeritus Professor and emeritus head of the Department of Immunohematology and Blood Transfusion at the Leiden University Medical Center in Leiden, The Netherlands.[18] Prof. Melief received his PhD in 1967 titled Leukocyte antibodies and immune adherence from the University of Amsterdam and qualified as a Medical Doctor in 1970 before undertaking his research career.[19] Prof. Melief has an extensive career immunology and cancer immunology including immunotherapies and the role of viruses and the immune system in cancer,[20] his work has included synthetic peptide vaccines for the treatment of cancer.[21] I am satisfied that Prof. Melief has a practical interest in the field of the invention and indeed has worked in the field. He is a suitable expert to comment on the knowledge and routine steps of the hypothetical person skilled in the art. The Opponent submitted that the evidence of Dr Lavranos and Dr Castles (D70) should be preferred because they provided evidence before seeing the specification. Indeed evidence on the routine or matter of course steps which would be taken when faced with a particular problem is best provided by a naïve declarant. I note, however, that Prof. Melief’s evidence is in answer and is not making a case for a lack of inventive step. Where his evidence may be tainted by hindsight or a knowledge of the specification, it will be weighted accordingly.
[18] Melief at [1].
[19] Melief [3]-[4]
[20] Melief [4]-[9]
[21] Melief [8].
Dr Lavranos is currently a co-founder and director of Calli Biotech Pty Ltd which is a biotech company focused on cancer therapies.[22] She is also a biotech consultant, CEO and Managing Director of Apop Biosciences.[23] According to her declaration she has been working in the field of immune-oncology for 19 years.[24] Dr Lavranos states that in May 2010 she was Head of Oncology Services Neurofit SAS and examined theses at both Monash and Flinders University. Dr Lavranos also stated that she regularly searched Pubmed and read scientific journals and patents in the field at the time.[25]
[22] Lavranos #1 at [6].
[23] Ibid at [11].
[24] Lavranos #1 at [11].
[25] Lavranos #1 at [13]-[14].
The Applicant argued that although Dr Lavranos is extensively qualified in cancer vascular biology, they can only infer that she was not involved in the relevant field at the priority date with no expertise shown specific to immune-oncology or cancer vaccination. Indeed the papers highlighted by the Applicant from Dr Lavranos’s CV are related to vascularisation and angiogenesis inhibition and involved the use of organic compounds rather than immunology.[26] She used language such as “would be well known” which appeared to indicate that she had not known herself. In my view that specific work does not rule out Dr Lavranos’s practical interest in field. Given Dr Lavranos’s involvement in Biotech companies and universities at the time I am satisfied she had a practical interest in the subject matter of the Opposed Application.
[26] TL-1 see Refereed Journal Articles.
Dr Lavranos was not shown the Opposed Application until her second declaration, Lavranos #2, and showed signs of using hindsight. Indeed this is often the case and such evidence will be weighted accordingly.
The Invention Described in the Specification
The specification outlines background information on other strategies for cancer vaccines by stating:
“Tumor vaccines are typically composed of tumor antigens and immunostimulatory molecules (e.g. cytokines or TLR ligands) that work together to induce antigen- specific cytotoxic T cells (CTLs) that recognize and lyse tumor cells. At this time, almost all vaccines contain either shared tumor antigens or whole tumor cell preparations (Gilboa, 1999). The shared tumor antigens are immunogenic proteins with selective expression in tumors across many individuals and are commonly delivered to patients as synthetic peptides or recombinant proteins (Boon et al., 2006). In contrast, whole tumor cell preparations are delivered to patients as autologous irradiated cells, cell lysates, cell fusions, heat-shock protein preparations or total mRNA (Parmiani et al., 2007). Since whole tumor cells are isolated from the autologous patient, the cells express patient-specific tumor antigens as well as shared tumor antigens. Finally, there is a third class of tumor antigens that has rarely been used in vaccines due to technical difficulties in identifying them (Sensi et al. 2006). This class consists of proteins with tumor-specific mutations that result in altered amino acid sequences. Such mutated proteins have the potential to: (a) uniquely mark a tumor (relative to non-tumor cells) for recognition and destruction by the immune system (Lennerz et al., 2005); (b) avoid central and sometimes peripheral T cell tolerance, and thus be recognized by more effective, high avidity T cells receptors (Gotter et al., 2004).”[27]
[27] Page 1 [0003].

The specification then states that there is a need to identify neoepitopes[28] that are useful as tumor vaccines.[29] The specification then provides a consistory clause of the claims followed by a description of the figures. The specification outlines that autoimmunity needs to be avoided when developing tumor-specific immunotherapy and that identification and selection of tumor antigens is highly restricted.[30]
[28] New epitopes that are specific to the patient’s tumor, this term is discussed later but I consider the PSA will be familiar with the term.
[29] Page 1 [0004].
[30] Page 10 [00045].
The approach of the Opposed Application is to identify tumor-specific neoepitopes using three steps. First is identification of DNA mutations using whole genome or whole exome (i.e. only captured exons) or RNA sequencing of tumor cells and comparing them to normal, or germline, samples from each patient. The second step is to apply validated-peptide-MHC binding prediction algorithms to generate a set of candidate T cell epitopes that may bind patient HLA alleles and are based on non-silent mutations present in tumors; and thirdly optionally demonstrating antigen-specific T cells against peptides or demonstration that a candidate peptide is bound to HLA proteins on the tumor surface.[31] This technique in essence involves comparing the genome of a patient’s tumor with their healthy genome and identifying the mutations in the tumor that are transcribed into mutate peptides. The mutated peptides are then screened with an algorithm to predict immunogenicity. The immunogenic epitopes may then be screened in an assay before being selected for the vaccine. This is both patient and tumor specific and is therefore a personalised cancer treatment.[32]
[31] Ibid.
[32] Melief #1 at [40].
The examples are set out on pages 47-51. Example 1 sets out the three step strategy with example 2 involving the collection of samples from the tumors of patients with chronic lymphocytic leukaemia (CLL) as well as samples from normal cells (skin fibroblasts) from the patient.[33] The tumor cells of the CLL patients were purified. For solid tumor patients, e.g. melanoma, ovarian cancer, tumor cells were cultured to remove healthy cells and PBMCs were used as normal cells. DNA and RNA sequencing was then conducted and sequences screened for non-silent mutations. The cells were preserved with freezing. The screening of the CLL patient’s sequences yielded 23 non-silent mutations—i.e. mutations that cause alterations in the final expressed protein compared to the normal cells. They categorized the mutations (missense, frameshift, read-through, gene fusions). These 23 non-silent mutated peptides were all noted as potential neoepitopes for immunization.[34]
[33] Page 47 [000140].
[34] Page 48 [000142].
Example 3 then took these potential neoepitopes and screened them through algorithms to predict if they have MHC/HLA binding and presentation. RNA for the potential neoepitopes was also confirmed in the cancer cells and 98% of all mutated genes with predicted HLA binding peptides were expressed.[35] The peptides were then screened experimentally for HLA binding. The specification states that with a cut off of an experimental IC₅₀ of <500nM and predicted IC₅₀<150nM true binding peptides were found 40-50% of the time.[36] These were checked against the normal cell peptides to identify differential binding affinity.
[35] Page 48 [000142].
[36] Pate 48-49 [000145].
In example 4 these peptides were screened for T-cell responses with example 5-6 then screening them with the patient’s own T-cells demonstrating that they generate an immune response with T-cells lysing tumor cells in example 6.
The Claims and Clarity
The approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd:
“the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear … 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 … terms in the claim which are unclear may be defined or clarified by reference to the body of the specification” [37]
[37] [2009] FCAFC 70, 81 IPR 228 at [118] – [120].
This approach of reading the specification as whole through the PSA's eyes with the CGK in mind provides context and the intention behind what is meant.[38] This is commonly referred to as a purposive construction.[39]
[38] Catnic Components Ltd v Hill & Smith Ltd [1982] RPC 183 (HC).
[39] Technip France S.A.’s Patent [2004] RPC 46.
It is a requirement of subsection 40(3) of the Act that the claims must be clear. This requirement is understood to be satisfied if a person could ascertain "whether or not what he proposes to do falls within the ambit of the claim".[40] The lack of a precise definition in claims may not be fatal to validity so long as they provide a workable standard suitable to the intended use.[41] However, if the monopoly defined by the claims cannot be determined, then the claims must fail for want of clarity.
[40] Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59.
[41] Minnesota Mining and Manufacturing Co. v Beiersdorf (Australia) Ltd. (1980) 144 CLR 253 at (46).
Claim 1, 13, 21 and 34 are independent claims. Claim 1 and dependent claims 2-12 being directed towards methods of treating cancer with claims 17-20 being dependent on claims 2-12 as an alternative. Claim 1 of the Application is set out below:
A method of treating cancer comprising administering a composition to a subject with cancer or a tumor, wherein the composition is specific to the subject ("subject-specific") and specific to the subject's tumor ("subject tumor specific"), said subject-specific and subject tumor specific composition comprising:
(a) at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific
and subject tumour specific peptides;
(b) one or more polynucleotides encoding the at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16, 17, 18, 19 or 20 subject-specific and subject tumour specific peptides;
(c) antigen presenting cells that have been pulsed with the at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific and subject tumor specific peptides or the one or more polynucleotides encoding the at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific and subject tumor specific peptides; or
(d) T cells from the subject which specifically bind to a complex of (1) a protein
encoded by an HLA allele expressed by the subject and (2) one or more neoepitopes of the at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific and subject tumor specific peptides, wherein the T cells have been stimulated ex vivo with the at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific and subject tumor specific peptides;
and
wherein each of said subject-specific and subject tumor specific peptides has a different tumor neo-epitope that is an epitope specific to the subject and to the tumor of the subject, wherein each neo-epitope binds to or is predicted to bind to a protein encoded by a class I HLA allele of the subject with a predicted IC5o of less than 150 nM, and wherein each neo-epitope represents an expression product of a subject specific and tumour-specific non-silent mutation not present in a non-tumor sample of the subject, wherein the non-silent mutation comprises:
(A) a point mutation,
(B) a splice-site mutation,
(C) a frameshift mutation,
(D) a read-through mutation, or
(E) a gene-fusion mutation,
wherein each non-silent mutation is identified by whole genome or whole exome nucleic acid sequencing of tumor and normal tissue samples from the subject.
The Applicant submitted that the “method of treating cancer” is done by providing the composition and this is how Prof. Melief read this first statement in the claim.[42] The Applicant also submitted that these claims only required the achievement of the desired therapeutic effect. The Applicant contrasted this with a method for treating cancer which they stated may only require that the method is suitable to achieve the desired therapeutic effect. The Applicant further submitted, based on the website “askanydifference.com” that:
The difference between ‘of’ and ‘for’ is that the word ‘of’ is used to show ownership or a distance from something or a result coming from something. On the other hand, the word ‘for’ is used to show a purpose, a destination or an amount of something.
[42] Melief at [51]
The Applicant pointed to Beach’s J reasoning in MLA[43] where he considered a method for identifying a trait and came to the conclusion that:
“In my view, the word “for” in this context means more than that something must be “suitable for” use in the method claimed. The word “for” in the expression “method for identifying a trait” places a limit on what is claimed such that the method claimed must result in being able to identify, in the sense of infer as I have discussed, a trait. It is clear in context that claim 1 stipulates a purpose constraint. It is not simply that the method must be suitable for identifying a trait. Now on MLA’s case, it does not matter if the prior art does not actually teach the claimed method; a disclosure of something that could be used for that purpose would be sufficient. But I agree with Branhaven that this is misconceived. The word “for” might be given such a construction in the context of a product claim, where the word can be understood as intended to characterise the construction of the product by reference to its suitability for the use to which it is to be put. But in the context of a method claim, such a construction is inapposite. Such a construction involves disregarding what is an important limiting and characterising feature of the claim.
In Otsuka, Yates J observed that the reference in a “Swiss type” claim to the use of a substance in the manufacture of a medicament “for” a specified therapeutic purpose is intended to impose the kind of limitation that MLA seeks to avoid, which is a limitation that confers novelty over a disclosure of the substance itself. As Branhaven points out, that is the reason why Swiss type claims were developed. And the point made by Yates J at [172] rather related to a different point. In my view, it is not in doubt that a claim to a method “for” treating a particular condition or disease involves a purpose limitation, such that a product that is merely suitable for that purpose will not infringe the claim, and will not anticipate if it is the subject of a prior disclosure. Similarly, the use of such a product for a different purpose will not infringe or anticipate. What is necessary to consider is a use or disclosure of the method itself. The same considerations apply to the method of claim 1 of the 253 Application.”[44]
[43] Meat & Livestock Australia Limited v Cargill,Inc [2018] FCA 51
[44] Ibid at [282]-[283].
Typically a claim to a product that is said to be “for” use in something, for example a peptide for use in treating cancer, is only considered to be suitable for that specified use and a disclosure of the peptide in a suitable manner would anticipate the claim. Beach J distinguishes that construction from method claims. His Honour’s construction takes the context of the “method” into account. Given this weight put on the context of the method, I do not agree that there is much of a distinction between a “a method of” claim and “a method for” claim. A delegate of the Commissioner has considered whether or not a difference exists between method of or method for the treatment in Astellas Pharma Inc. v Aragon Pharmaceuticals, Inc. [2022] APO 36 (23 May 2022) at [106]-[112]. I agree with the delegate’s analysis in that decision and the conclusion that there is no appreciable difference. However, in every case the claims are to be construed with the context of the specification, the terms used and what it means to the person skilled in the art. With that in mind, I agree with the Applicant’s construction of the current method of treatment claims. The method of treatment indicates that the claim must treat the particular condition.
The method of treating cancer is said to comprise administering a composition to a subject with cancer or a tumor. The mode of administration is not limited and can involve further steps, however, the composition is specific to the subject and specific to the tumor. This specific composition is then set out to be one of four things including at least 4 peptides, one or more nucleotides encoding the at least 4 peptides or cells which present antigens which have been pulsed with the at least 4 peptides or T cells which have been cultured ex vivo to bind at least 4 peptides. I note that in every situation in the claims there must be at least 4 peptides used.
Each peptide has a different neo-epitope which is said to be an epitope specific to the subject and this binds to class I HLA allele of the subject with a predicted IC₅₀ <150 nM, and is expressed by the subject with a non-silent mutation. The types of the non-silent mutations are identified by whole genome comparison of the subject and tumor.
Prof. Melief states that the peptides in part (a) of claim 1 or the nucleotides in part (b) could be considered a vaccine for inducing an immune response against antigens specific to the subject’s tumor.[45] The steps (c) and (d) are essentially means of inducing an immune response or priming immune cells outside of the patient’s body so that when these cells are administered back to the patient the immune cells target the cancer.[46]
[45] Melief at [56].
[46] Melief at [58].
Claims 13 to 16 relate to a composition which comprises T cells from a subject with cancer or a tumor in which the T cells are antigen specific to a protein encoded by a HLA allele expressed by the patient and one or more of the at least 4 peptides wherein each neo-epitope binds to or is predicted to bind to a protein encoded by a class I HLA allele of the subject with a predicted IC₅₀ of less than 150 nM.
Claims 21-33 relate to methods of identifying neoantigens that bind to or are predicted to bind to a class I HLA allele with a particular binding affinity.
Claim 34 is a Swiss style claim.
The Opponent did not file submissions on clarity in either their submissions or in the slide show. For completeness their SGP said the words “neoantigen”, “neoepitope” and “mutant peptide” used in the claims was unclear. This is because they were apparently used interchangeably. I consider that the person skilled in the art would be familiar with the terms antigen, epitope and peptide as well as mutant peptide. A peptide is a sequence of amino acids and in the context of the current claims is one encoded for by DNA and when there is a mutation in the DNA and this is translated into the peptide it becomes a mutant peptide. An antigen in this context is a peptide that induces and immune response. Epitopes are the part of an antigen which binds to the antibody.
The prefix “neo”, which means new, appears to denote it to be specific to the individual tumor or patient in this case and are new. The specification also provides a definition of “neoantigen” at [00066] on page 15 which states:
“Neoantigen” means a class of tumor antigens which arises from tumor-specific mutations in expressed proteins.
The neoepitopes referred to throughout the specification also appear to mean these new tumor specific epitopes.
I note that the Opponent’s submissions appeared to use this construction and they considered neoantigens to be common general knowledge.
The Opponent’s SGP also stated that “at least 4” used in the claims was vague and open ended. Indeed this statement means that a minimum of 4 is used. Therefore, the use of 1, 2 or 3 peptides would be outside of the scope of the claims. A maximum number of peptides is not provided, indeed there is likely to be some practical limitations on the total number of peptides used, however, no evidence is provided that would render this claim unclear to the PSA.
The SGP also stated that the phrases “bind to”, “is predicted to bind”, “the class I HLA allele” and “IC₅₀of less than 150 nM” are unclear. The IC₅₀ of less than 150 does provide some limitation to the binding and that it must be preferential to normal cells but specific affinities are not provided. The examples appear to provide a workable standard of how to achieve this. Class I alleles are also known in the art and to the PSA. There is no evidence that in this technology that specific affinities are required or that these terms are unclear.
Section 40(2)(a)
The amendments brought about by Raising the Bar introduced the following piece of legislation under s 40 (2):
“A complete specification must:
(a) disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art;”
In Merck Sharp & Dohme Corporation v Wyeth LLC (No 3[47]) (MSD), Burley J considered the law of support[48] and also considered s 40(2)(a). His Honour consulted the explanatory memorandum, which discussed how the change brought about by Raising the Bar was intended to align the Australian disclosure requirements with those overseas.[49] His Honour then considered s 40(2)(a) in comparison to the EPC and UK Act. He noted that s 40(2)(a) is expressed in terms that are virtually the same as in s 14(3) of the UK Act[50] but noted that the highest courts of the UK have emphasised the influential effect of the EPO Technical Board. I note that his approach is consistent with the approach taken by this office in CSR Building Products Limited v United States Gypsum Company[51] (CSR) which involves the following three steps:
(1) Construe the claims to determine the scope of the invention as claimed,
(2) construe the description to determine what it discloses to the person skilled in the art, and
[47] [2020] FCA 1477.
[48] Ibid at [502]
[49] Ibid at [513]
[50] Ibid at [521]
[51] [2015] APO 72.
[52] Ibid at [89].
(3) decide whether the specification provides an enabling disclosure of all the things that fall within the scope of the claims.[52]
When deciding the third question the delegate in Evolva[53] included the following two questions:
(4) Is it plausible that the invention can be worked across the full scope of the invention?
[53] Evolva SA [2017] APO 57.
(5) Can the invention be performed across the full scope of the claims without undue experimentation?
In Cytec Industries Inc. v Nalco Company[54] Burley J cited the above office decisions and confirmed that this was the correct approach with the Full Federal Court in Jusand[55] confirming this approach.
[54] [2021] FCA 970 at [145]-[146].
[55] Jusand Nominees Pty Ltd v Rattlejack Innovations Pty Ltd [2023] FCAFC 178
The Opponent submitted that not all peptides that had predicted binding would work and appeared to argue that the IC₅₀ of less than 150 was arbitrary and that it was implausible that everything within the scope of the claims would work. Prof. Melief considered the IC₅₀ value and stated that:
“As shown in Figure 8C, if a predicted IC₅₀ threshold of less that 150nM was chosen the majority of peptides had an experimentally determined IC₅₀of less than 500 nM. This is considered in the field to be sufficient to indicate binding to MHC and therefore presentation to T cells.”[56]
[56] Melief at [46].
I have reproduced Figure 8C below. The predicted score is on the X-axis and the experimentally determined binding score on the Y-axis. There is a hashed line at 500 nM on both axes. If one looks below 150 nM on the predicted score all the except one are below 500 nM on the binding score.

Prof. Melief also noted that there was indeed “all but one” peptide with a predicted IC₅₀<150 that gave an experimental IC₅₀ < 500 nM.[57] However, Dr Lavranos commented that if a large scale test was done that it is likely that more peptides with a predicted IC₅₀ <150 would show an experimentally determined IC₅₀>500. She states that:
“In my opinion, the use of a more stringent IC₅₀threshold of less than 150 nM (as also recited in the claims) merely improves the proportion of peptides that will have an experimentally determined IC₅₀ below a certain value (e.g. less than 500 nM). This would be an expected result to a skilled person.”[58]
[57] Melief at [104].
[58] Lavranos #3 at [15].
Prof. Melief also noted that the claims require at least 4 peptides and that so long as one peptide out of the 4 is effective at generating an immune response then the composition may be useful in treating cancer. [59] The Opponent argued that the limitation of at least 4 does not save the claims plausibility citing Dr Lavranos’ comment that:
“it is possible that all four peptides can fail to demonstrate actual HLA binding. There is also a possibility that a peptide that demonstrates actual HLA binding does not always mean that there will be immunogenicity.”[60]
[59] Melief at at [105].
[60] Lavranos #3 at [17].
The Applicant stated that there is no basis for this statement given that only one peptide was shown to have binding over actually binding over 500 nM. I agree. I do note that Dr Lavranos suggested large scale testing would be required.[61] I disagree. All large scale testing would do is provide a probability that one could end up with a composition where all four peptides in the composition failed. Only one peptide in the specification was shown to have binding above 500 nM and this does not mean that peptide does not work at all in the treatment of cancer. Furthermore, given that there was only one in the current application the probability that four ineffective peptides would be chosen is likely to be quite low. Furthermore, the Opponent has not provided any calculations of this probability or evidence as to additional peptides wherein the predicted and experimental binding affinities are inconsistent. As such, the specification on its face makes the claimed method plausible. I also note that the Applicant pointed out that CJMM-4 is an article from the Journal Nature where in 2017 this method was being used in clinical trials. I do not consider, based on the evidence, that the claims are implausible.
[61] Lavranos #3 at [19].
The Opponent also argued that the claims, being directed to treating “cancer” could not satisfy s 40(3)(a) because it is unlikely that all cancers could be treated this way. Indeed, CJMM-4 demonstrates the method is in clinical studies for the treatment of melanomas-a solid tumor cancer and the specification’s experiments are on CLL which is a type of leukemia. Dr Lavranos states that the experiments on CLL does not mean all haematological cancers can be treated this way because there are many different subtypes. I do not consider the existence of many different types of cancers a reason why this particular technique would not work. The method involves selecting neoepitopes from the cancer at hand which can generate an immune response. This does not rely on a specific mechanism of action that only certain cancers have nor does it rely on a particular biological pathway that is involved in the disease aetiology of a certain cancer. It merely relies on the cancer having mutated peptides expressed which can be screened for neoepitopes. The Opponents have not provided evidence of cancers that do not produce neoepitopes or do not express mutated peptides.
The Opponent also argued that the claims lacked a clear enough and complete enough disclosure since carrying out the invention would be an undue burden. The Opponent cited the following statement by Dr Lavranos:
“The methodology does nothing to reduce the time needed to identify these candidate peptides. Furthermore, a significant amount of work is required to determine whether these candidate peptides actually demonstrate any useful activity in treating cancer.”[62]
[62] Lavranos #3 at [21].
The methodology is given in the Opposed Application and the work involved utilizes genomics, algorithms and assays. It is specific to the patient and is indeed personalised medicine. I do not doubt that this requires work, however, an undue burden will exist where further experimentation is required just to work the invention because the disclosure of the methodology is lacking – for example, the skilled person must carry out research to understand how to perform the invention, . Here the specification provides the methodology. I do not consider the amount of work required to perform the invention is of the type that would give rise to a lack of clear enough or complete enough disclosure.
This ground of opposition has not been made out.
Section 40(3)
The amendments brought about by Raising the Bar introduced the following piece of legislation under s 40 (3):
“The claim or claims must be…supported by matter disclosed in the specification.”
Burley J discussed the law of support in MSD. His Honour accepted the rationale outlined in the CSR decision.[63] In Jusand the Full Federal Court took the same approach[64]
[63] [2020] FCA 1477 at [546].
[64] Jusand Nominees Pty Ltd v Rattlejack Innovations Pty Ltd [2023] FCAFC 178 at [204]-[206] and [222].
In CSR the delegate provided a three-step approach:
(1) construe the claims to determine the scope of the invention as claimed,
(2) construe the description to determine the technical contribution to the art, and
[65] [2015] APO 72 at [110].
(3) decide whether the claims are supported by the technical contribution to the art.[65]
The technical contribution may be a general principle:
“if [the patentee] has disclosed a beneficial property which is common to the class, [the patentee] will be entitled to a patent for all products of that class (assuming them to be new) even though [the patentee] has not himself made more than one or two of them.”[66]
[66] Biogen [1997] RPC 1 at 49 per Lord Hoffman.
The Opponent relied on their submissions on s 40(2)(a) that the claims are directed to a method of treating any cancer and that the specification does not show any cancer has been treated. Indeed the specification itself does not include treatment that one would expect in a clinical study and instead includes cell based assays. It has been shown that this technique has been used in later clinical studies in CJMM-4. Furthermore, although there are many different forms of cancer, the technical contribution involves identifying epitopes in an individual’s own cancer cells then screening them for epitopes with a predicted binding of less than 150 nM then using at least four of them for a vaccine. This would logically work in all cancers that produce epitopes. The Opponent has not filed evidence of cancers that do not produce epitopes. It follows that similar to my conclusion for s 40(2)(a), the claims do not exceed the technical contribution to the art and this ground has not been made out.
Utility
It is a requirement of paragraph 18(1)(c) of the Act that the invention, so far as claimed in any claim, must be useful:
Subject to subsection (2), an invention is a patentable invention for the purposes of a standard patent if the invention, so far as claimed in any claim: …
(c) is useful.
The issue of utility was considered by the Full Court of the Federal Court in H Lundbeck A/S v Alphapharm Pty Ltd.[67] Emmett J stated:
“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.”[68]
[67] [2009] FCAFC 70, 81 IPR 228.
[68] Ibid at [81]; [247].
In Apotex Pty Ltd v AstraZeneca AB (No 4),[69] Jagot J pointed out that lack of utility requires evidence, not just speculation:
“Ultimately, an asserted lack of utility must be established by appropriate evidence, not by mere speculation that the invention will not work or meet the promise set out in the specification.”[70]
[69] [2013] FCA 162; (2013) 100 IPR 285.
[70] Ibid at [352].
An overview of utility, including areas for consideration, is provided by Nicholas J in Apotex Pty Ltd v Warner-Lambert Company LLC (No 2)[71]. The applicant noted his Honour’s statement:
“…much depends upon the proper construction of the claim. Claims are not to be read through the eyes of a skilled addressee purposefully seeking to perform the claimed invention in a manner that would not provide a useful result: see Washex Machinery Corporation v Roy Burton & Co Pty Ltd (1975) 49 ALJR 12 at 19. Nor should claims be construed in a manner that the skilled addressee would appreciate would lead to unworkability if there is another construction that is equally open that avoids that result: Electric & Musical Industries Ltd v Lissen Ltd (1938) 56 RPC 23 at 39; Rehm Pty Ltd v Websters Security Systems (International) Pty Ltd (1988) 81 ALR 79 at 99.”[72]
[71] (2016) 122 IPR 17 at [164] et seq.
[72] Ibid at [168].
Furthermore, his Honour stated:
“A claim may have utility even if a promised advantage cannot be achieved in all cases or with the same degree of success: Rescare Ltd v Anaesthetic Supplies Pty Ltd (1992) 25 IPR 119 at 142-143 (Gummow J) and Sanofi-Aventis Australia Pty Ltd v Apotex Pty Ltd (No 3) (2011) 92 IPR 320 at [245], point 8 (Jagot J). Thus, if a claimed method of treatment for nausea was effective in a substantial proportion of patients experiencing nausea, the claim would not be invalid merely because a small proportion of patients experiencing nausea did not respond to the treatment. This is because the skilled addressee reading the specification would not expect (assuming he or she is not told otherwise) that the claimed treatment will be an effective treatment for every patient suffering nausea resulting from every conceivable condition.”[73]
[73] Ibid at [170].
In Esco Corporation v Ronneby Road Pty Ltd [74] the Full Federal Court accepted that it is necessary to follow the teaching of the complete specification to isolate the promise of the invention and determine whether that results in the promise being produced.[75]
[74] [2018] FCAFC 46
[75] Ibid at [233] and [279].
The Opponent submitted that the claims were inutile and their reasons included:
·     because they do not inevitably meet the promise of treating cancer;
·     that the amount of the peptides used is not in the claim and would thus include amounts which do not work;
·     that there is no data in the specification to support the treatment of all cancers—suggesting that the claims include cancers which cannot be treated with this method;
·     there is no certainty that peptides with a predicted binding of the claims would be effective in a subject;
·     that the “at least 4” peptides are open ended and there is no data to suggest a synergistic effect;
·     there are claims which include combining the composition with additional therapeutics or anti-immunosuppressants and there is no data to suggest that all these combinations work
·     that the neo-peptide in claim 21 with predicted binding might not actually work in practice.
The Opponent appeared to argue that the promise was the treatment of cancer. Applicant construed the problem differently to that of the Opponent by stating that it is being able to identify peptides that might be useful.
Regardless of the problem being solved, utility essentially requires evidence of something within the scope of the claim failing to meet the promise. The Opponent has not provided any such evidence. The Applicant also referred to the clinical trial outlined in CJMM-4 which, in my view, does demonstrate at least something within the scope of the claims has utility.
Without evidence to contrary, this ground of opposition fails.
Novelty
It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, is novel. Subsection 7(1) states that an invention is considered novel unless it is not novel compared to prior art information. The Act then states that prior art information can be information made publicly available in a single document.[76]
[76] ss 7(1)(a).
The well-established test for lack of novelty is the reverse infringement test. The classic formulation of this test is that given by Aickin J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd:
"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".[77]
[77] [1977] HCA 19; 137 CLR 228 at 235.
This test is satisfied if the alleged anticipation discloses all the essential features of the invention as claimed.[78] In reviewing a citation one must look at the citation to determine what it tells the skilled reader to do. Determining what is taught or disclosed can require some treatment.
[78] Nicaro Holdings Pty Ltd v Martin Engineering Co[1990] FCA 40;(1990) 91 ALR 513at 517.
Australian courts have often cited with approval the words of the UK Court of Appeal in the General Tire[79] case which provides guidance on assessing a disclosure for novelty. It is useful to look at that discussion in full from pages 485-486:
“If the prior inventor's publication contains a clear description of, or clear instructions to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee's patent, the patentee's claim will have been shown to lack the necessary novelty, that is to say, it will have been anticipated. The prior inventor, however, and the patentee may have approached the same device from different starting points and may for this reason, or it may be for other reasons, have so described their devices that it cannot be immediately discerned from a reading of the language which they have respectively used that they have discovered in truth the same device; but if carrying out the directions contained in the prior inventor's publication will inevitably result in something being made or done which, if the patentee's patent were valid, would constitute an infringement of the patentee's claim, this circumstance demonstrates that the patentee's claim has in fact been anticipated.
If, on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee's claim, but would be at least as likely to be carried out in a way which would not do so, the patentee's claim will not have been anticipated, although it may fail on the ground of obviousness. To anticipate the patentee's claim the prior publication must contain clear and unmistakeable 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."[80] (citations omitted).
[79] The General Tire & Rubber Company v. The Firestone Tyre and Rubber Company Limited and others [1972] RPC 457.
[80] [1972] RPC 457 at 486.
In General Tire, the requirement for clear and unmistakable directions in the prior publication is well known. However, it also states that if carrying out the directions in the prior art leads inevitably to doing something within the scope of the claim in suit, then there will be a lack of novelty. This inevitable consequence of carrying out the directions in the prior art occurred in Novozymes v Danisco[81] with Jessop J providing the following guidance with Yates J and Greenwood J concurring:
“In my view, 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 the appellants’ case is based on General Tire, it is not sufficient that they be able to point to passages in the Novo patent from which it would appear to the skilled addressee that inactivation was contemplated or intended by the earlier inventors. It is necessary that they show that, if Example 20 were worked as directed, it would inevitably, as a matter of hard fact, have involved inactivation of the enzyme (to the standard set up under Claims 1 and 7 of the patent in suit as identified by the primary Judge) at the baking stage.” [82]
[81] Novozymes A/S v Danisco A/S [2013] FCAFC
[82] Novozymes A/S v Danisco A/S [2013] FCAFC at [145].
The Opponent cited three documents for the ground of lack of novelty. I will discuss each below.
D81: Rammensee et al., (2008) Genomics and Personalized Medicine “Cancer Vaccines: Some Basic Considerations.
D81 is a book chapter that discusses approaches to cancer vaccines. The Opponents alleged that the section entitled, Peptides on page 577-578 anticipates the current claims. In this section the authors outline a possible approach to cancer vaccines:
One step further would be an approach not only matching the HLA alleles of a patient but also the individual antigen expression of the patient's tumor. This would be achieved using a combination of gene expression analysis, with high-throughput sequencing in an analogous fashion as described above, but on a individualized "per tumor" basis (Rammensee, 2006; Rammensee et al., 2002). In this scenario, a piece of the patient's tumor and a piece of normal autologous tissue would be analyzed for (1) genes and peptides overexpressed in tumor tissue, and (2) genes mutated in the tumor (see Figure 50.1). Analysis of such data will be rather complex, since it involves the sequencing of 25,000 genes each from the two sources. We have started working in this direction and have initiated a study in which sets of peptides are selected for the renal cell carcinoma of a given patient, considering all HLA alleles expressed by the patient as far as possible, and used for vaccination. We find that this is logistically possible. The next step will be to search for tumor-specific mutations in a selection of about 30 genes prone to mutations, such as p53, and to add peptides representing the mutations found.[83]
[83] D81 page 578, last sentence column 1-column 2.
In this disclosure an approach is outlined which would involve sequencing and gene-expression analysis to identify mutations and that they have started work in this direction. This strategy is outlined in Figure 50.1 which is reproduced below.
The use of computer databases to identify epitopes is discussed earlier in that section with the following disclosure:
“Identification of such T-cell epitopes is much helped by the knowledge of MHC specificity for peptides, which is available for any, but by far not all of the MHC alleles in the human population (Stevanovic, 2002). For frequent HLA class I alleles (the human MHC is called HLA), for example, HLA-A*0l01, A*0201, _HLA-B*0701, and B*4402, prediction of candidate T-cell epitopes within a sequence of interest is easily possible by tools via internet, for example, wvw.syfpeithi.de”[84]
[84] D81 page 577 column 1 last sentence-column 2.
After Dr Lavranos considered D81 she stated the following:
In view of the above, D81 teaches one to make use of whole genome sequencing to identity subject specific and subject tumor specific peptides as recited in the independent claims. D81 also directs one to determine whether these peptides are predicted to bind to a protein encoded by a class I HLA allele of the subject as recited in the independent claims. Hence, I would think that the invention is disclosed or at least suggested in D81.

This contrasts with Prof. Melief who noted that:
“the flow chart teaches one to use the comparative sequencing of “all expressed genes” to determine a “differential analysis-list of tumor-specific mutations” which is fed into the “design and synthesis of a molecularly defined, personalized vaccine consisting of peptides and mRNA/DNA containing all tumor associated/specific structures”. However, while the flow chart of Figure 50.1 includes these steps, it is important to note that the legend to the figure acknowledges that “sequencing of all expressed genes by techniques, presently still in development is necessary”. That is, such sequencing was not done in D81 and it is instructive in my view that the authors specifically state that such efficient sequencing was not in place in 2008. It is also relevant to note that Figure 50.1 covers a large range of possibilities and approaches none of which expressly take the unbiased approach to mutations of the Opposed Application or provide the precise or technical methodology of the invention described and claimed therein in the Opposed Application.[85]
[85] Melief at [145]
Indeed the context Prof. Melief provides on D81 is helpful. Importantly he notes that sequencing was far less straightforward in 2008 and acknowledges the statement on page 578 that analysis of 25,000 genes from two sources would be complex. That must be taken into consideration given the nature of the disclosure. It is clear that this disclosure is of an ideal vaccine in the future rather than express directions on how to make one.
Prof. Melief ’s argument that the approach outlined in D81 directed the PSA towards a vaccine with shared mutations between patients and peptides that were overexpressed is plausible since sequencing at an individual level was difficult. That is, D81 is more likely directed towards a vaccine for groups of patients rather than a truly individualised vaccine:
“The approach is not confined to mutated antigens but rather a mix of overexpressed antigens, which are a mixed bag of differentiated antigens. Although it may also include mutations there is no indication in D81 that the method or treatment should be applied specifically for mutated sequences in a personalized way. Instead, the authors consider it could be done for groups of patients with shared over expressed or otherwise presented antigens.
While the authors are proposing a more personalised approach, this is based on a preidentified set of peptides for a particular patient and the expression of the gene containing the epitope in the patient. This is a very different approach to that taken in the Opposed Application and is reflective, in my opinion, of the thinking and direction in the field at the time being biased towards a common or shared approach.”[86]
[86] Melief at [157].
Prof. Melief concluded that:
“D81, in its speculation is a long way from the very precise methodology that defines the predictions, validations, vaccine preparative steps and selection methods of all binding peptides (to all available HLA molecules) described and claimed in the Opposed Application.”[87]
[87] Melief at [161]
In my view, Prof. Melief ’s reading of D81 provides context to the state of the art at the time with regard to how far sequencing had been developed.

100. The question is what, if any, clear and unmistakable directions would be followed in D81? The nature of the disclosure in D81 is looking to the future of what an “ideal” vaccine would look like. There are no clear instructions on how to reach this ideal and instead I consider Prof. Melief’s comment about it being speculation somewhat accurate. Furthermore, D81 does not disclose that at least 4 peptides must be used in the vaccine. There is no evidence that a person skilled in the art would inevitably use at least four peptides in such a vaccine.
101. D81 also does not disclose any threshold for predicted binding. The Opponent argued that this was arbitrary with Dr Lavranos stating:
“The IC50 value of less than 150 nM appears to be an arbitrary value and there is no data to show that all peptides that bind or are predicted to bind with a predicted IC50 value of less than 150 nM can be definitely developed into a successful vaccine. Moreover, the prediction of an IC50 value is not the same as an actual IC50 value. There may be peptides that are predicted to bind with an IC50 value of less than 150 nM but have a much weaker affinity to HLA in an actual experiment, thus rendering them unsuitable as vaccines. There are also many other factors that would determine whether a neo-antigen peptide can be developed into a cancer vaccine. For example, some neo-antigen peptides may simply not be capable of inducing a sufficient T cell response in a patient due to a myriad of factors such as structure, length and stability. This may render the neo-peptide unsuitable for development into a vaccine.”[88]
[88] Lavranos #2 at [14]

102. I note there was some concession in reply that this would improve the proportion of peptides in the vaccine that will be effective:
“In my opinion, the use of a more stringent IC50 threshold of less than 150 nM (as also recited in the claims) merely improves the proportion of peptides that will have an experimentally determined IC50 below a certain value (e.g. less than 500 nM). This would be an expected result to a skilled person. This, however, does not mean that the algorithm can predict actual HLA binding with 100% certainty. There is also nothing to suggest that one could predict HLA class I-binding neoepitopes accurately for the first time.”[89]
[89] Lavranos #3 at ]15]

103. I do not consider that an improvement in the proportion of peptides that are effective is arbitrary. I also note that the documents Annexed to the Opponent’s submissions that had not been filed in evidence or in the SGP were to provide evidence that the threshold of an IC₅₀ 150nM is arbitrary. There is no declaratory evidence on these documents from Dr Lavranos. I do not consider the Opponent’s argument compelling or that the documents would change the outcome of the opposition as Dr Lavranos has already said in reply that it would lead to an improvement. D81 does not provide clear and unmistakable directions that would, if followed, produce something that falls within the scope of the current claims.
D20: Parmiani, G. “Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials” The Journal of Immunology (2007) 178:1975-1979

104. D20 is a review article which discusses immunology research on tumor antigens. It also discusses the use of these antigens in cancer vaccines. It begins by discussing known antigens of melanoma cells which are recognized by class I HLA-restricted T lymphocytes.[90]
[90] D20 page 1976 first column second paragraph.
105. Dr Lavranos highlights the following disclosure stating that it discussed the identification of antigens at a specific tumor and patient level:
“Since the race for obtaining a clinical result with the available shared, self-Ags [antigens] first discovered in human tumor cells went on for a decade or so, almost no attention was paid to individual Ags of human tumors as potential targets of both active (vaccination) and adoptive immunotherapy. Admittedly, this was also because of the contention that unique Ags would have been difficult to use in the clinic owing to the lack of rapid methods for their identification and molecular characterization at the single tumor/patient level. Moreover, as in the mouse system, a single human tumor can express multiple unique Ags and generate new ones during progression, making their characterization even more cumbersome.
In the last few years, however, the situation has changed, albeit slowly. In fact, the first molecular description of a T cell-defined unique human melanoma Ag, resulting from a point mutation of cyclin-dependent kinase (CDK4) was reported in 1995.”[91] Citations omitted
[91] D20 page 1976 first column, second and third paragraphs.

106. Dr Lavranos states that D20 directs one to make use of whole genome sequencing to identify subject and tumor specific peptides as recited in the claims[92] and she lastly quotes the following passage:
[92] Lavranos #2 at [22] (e).
“Obviously, the ultimate strategy for targeting such types of Ags will imply sequencing of the whole genome of each individual tumor followed by the selection of mutated peptides whose motifs are predicted to be presented by the HLA alleles of the patient bearing that particular mutated tumor.”[93]
[93] D20 page 1977 first column under implications for immunotherapy

107. This disclosure above does state that an “ultimate” strategy would imply using whole genome sequencing.
108. Prof. Melief read D20 and highlights that this “ultimate strategy” suffers similar technical difficulties of the time.[94] This is supported by the statement in D20:
[94] Melief at [164].
“Admittedly, this was also because of the contention that unique Ags would have been difficult to use in the clinic owing to the lack of rapid methods for their identification and molecular characterization at the single tumor/patient level.”[95]
[95] D20 page 1976 first column second paragraph.

109. Prof. Melief states that:
“The discussion in D20 is indicative of the barriers prior to the approach taken in the Opposed Application. Researchers in the field were instead going down various alternative paths to try to reach a more personalised end but had to do so by a much less elegant and systematic path.”[96]
[96] Melief at [171].

110. When he considered the “ultimate strategy” which I have quoted above Prof. Melief states:
“the authors are hinting at a potential further approach, without specifying any precise method. Relevantly, the authors note (in reference to Sjöblom discussed above) that such an approach “surely requires a massive but not impossible effort in cancer genome analysis” and indicates that in the near future a feasible strategy may be proposed that limits such analysis to a defined set of genes known to be selective targets for mutation in a tumor of a given histology. This reflects the thinking of the field at the time. The ultimate effective pathway is not feasible at the time and so the researchers propose an alternative more feasible strategy focused on driver or shared mutations.”[97]
[97] Melief at [175]-[176].

111. Prof. Melief then goes on to quote a different approach which is proposed in D20 and more pragmatic for the time.
112. In my view, D20’s “ultimate strategy” would involve whole genome sequencing of both the tumor and patient’s cells. However, I do not consider this “strategy” had been fully realised in D20. This is a review article and, like D81, is pointing to a future and does not provide clear and unmistakable directions of how to get there. Furthermore, features of the claims, such as using “at least 4” peptides and a screening to a threshold IC₅₀ of <150 nM have not been outlined and there is no evidence that these would be inherent in following any ultimate strategy. Consequently, D20 is not prejudicial to the novelty of the current claims.
D12: Segal, N. H. et al. (2008) “Epitope Landscape in Breast and Colorectal Cancer” Cancer Research 68(3): 889-892

113. Prof. Melief describes D12 as a theoretical paper that used in silico approaches (computer modelling) to identify cell epitopes to investigate the epitope landscape of breast and colorectal cancer.[98] It is a follow on study from another paper, D13 in the SGP, which identifies a number of mutations in these same cancers.
[98] Melief at [119].
114. Dr Lavranos stated that D12 is aimed at identifying neoantigenic peptides for preparing a subject-specific immunogenic composition.[99] D12 discloses that:
[99] Lavranos at [22](c)
“Among >13,000 genes analyzed, a total of 1,307 somatic mutations were identified in 11 breast and 11 colorectal cancers. Approximately 83% were missense mutations, 6% nonsense, and the remainder were insertions, deletions, duplications, and changes in noncoding regions.”[100]
[100] D12 page 889, right column lines 1-4

115. The Applicant submitted that this passages shows that D12 does not use whole genome sequencing and instead focussed on areas of the genome that could easily be amplified and this was supported by evidence from Prof. Melief :
“Importantly, the authors note that these methods initially “depend on sequencing each patient’s cancer to some extent. Although this is too difficult and expensive to be done routinely at present, improvements in technology will soon make such sequencing feasible, at least for a limited number of genes most likely to harbour missense mutations…”. This statement highlights that the whole genome sequencing utilised by the invention described and claimed in the Opposed Application was not considered feasible at the relevant time.” [101]
[101] Melief at [125].

116. Given that only around 13,000 genes were analysed it does appear that whole genome sequencing was not carried out in D12.
117. Prof. Melief does concede that D12 does suggest ways to exploit these mutations which includes:
“i) administer vaccines to a patient made from their own tumor” (that is whole cell vaccines), ii) “administration of particular epitopes in the context of immune stimulants” such as “synthesized peptide epitopes presented to patients together with adjuvants or the patients’ own antigen-presenting cells”, and an arguably more accessible way, iii) “to exploit the findings during the course of standard anti-tumor therapy”[102]
[102] Melief at [131].

118. The Applicant submitted that the purpose of D12 was to identify these mutants that can contribute to the neoplastic process (so called driver mutations). This would be a “biased” approach, as opposed to using whole genome sequencing where only antigenic peptides are sought. The Applicant’s submission is supported by the disclosure in D12 that:
“Analysis of 1,152 peptides containing missense mutations previously identified in breast and colorectal cancer revealed that individual cancers accumulate on average ~10 and ~7 novel and unique HLA-A*0201 epitopes respectively, including genes implicated in the neoplastic process.”[103] (my emphasis)
[103] D12 Abstract and page 890, right column, fourth paragraph

119. The prediction run in D12 looked at peptides which scored an IC₅₀ of less than or equal to 500 with D12 stating that:
“For ANN, used for HLA-A*0201 prediction, peptide scored positive if IC50 is ≤ 500.”[104]
[104]

120. Dr Lavranos also stated that:
“D12 also discloses the feature of “subject-specific”. It also implies to the skilled person that the mutations do not occur in the genome of normal tissue of the subject through the use of the term “nonself”.”

121. She read that from the following disclosure in D12:
“Because the predicted and potential immune response is patient-specific and directed toward nonself, these mutations are not expected to have triggered tolerance and, in theory, have the capacity to result in potent tumor rejection antigens.”[105]
[105] D12 page 891, left column, second paragraph

122. The Opponent also submitted that the peptides can be used for producing immunological compositions from the conclusions raised in D12, these are:
“These findings encourage both the continued development of augmented immunotherapy in cancer without an absolute requirement for knowledge of the targeted antigens, and also future strategies that incorporate high throughput sequence analysis toward individualized multivalent cancer vaccines.”[106]
[106] D12 page 892.

123. Prof. Melief read this and said:
“it is apparent that these statements and conclusions of the authors are in very general terms and expressed as potential future options and which the authors acknowledge are not feasible at the time. This can be contrasted with the Opposed Application which actually provides a systematic, personal and timely approach in which the identification of the mutations by whole genome or whole exome nucleic acid sequencing is achieved in a completely unbiased manner.[107]
[107] Melief at [133]

124. It does appear that D12 screened a large number of genes from patients’ cancer cells, however, this does not appear to equate to whole genome sequencing, with <13,000 genes screens (which as clear from D81 a whole genome would be >25000 genes). This is different to the current claims. They were screened using an algorithm for HLA allele binding but at a threshold of less than or equal to an IC₅₀ of 500. Furthermore, D12 does not require at least 4 peptides be used in any future immunological composition and method. Taking all these differences into consideration it is clear that D12 does not disclose clear and unmistakable directions to the current claims.
125. The disclosures of D81, D12 and D20 do not contain clear and unmistakable directions to the current claims. Consequently, this ground of opposition fails.
Inventive Step
126. It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, involves an inventive step. Subsection 7(2) states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in the light of the common general knowledge, considered alone or together with the prior art (subsection 7(3)).
127. The test for whether an invention is obvious is to ask whether it would have been a matter of routine to proceed to the claimed invention. In Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd[108] Aickin J stated:
[108] [1981] HCA 12; 148 CLR 262 at 286.
"The test is 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."

128. In Alphapharm,[109] the High Court endorsed the use of the reformulated "Cripps question":
[109] Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59; 212 CLR 411.

“Would the notional research group at the relevant date, in all the circumstances, which include a knowledge of all the relevant prior art and of the facts of the nature and success of [the prior art], directly be led as a matter of course to try [the invention], in the expectation that it might well produce a useful alternative to or better drug than [the prior art] or a body useful for any other purpose?"[110]
[110] Alphapharm at [53].

129. This has been elaborated on in the Full Federal Court’s decision Generic Health Pty Ltd v Bayer Pharma Aktiengesellschaft:
“We do not think that the plurality in Alphapharm were saying that the reformulated Cripps question was the test to be applied in every case. Rather, it is a formulation of the test which will be of assistance in cases, particularly those of a similar nature to Alphapharm. The plurality did not reject as an alternative expression of the test the question whether experiments were of a routine character to be tried as a matter of course (The Wellcome Foundation Limited v VR Laboratories (Aust) Proprietary Limited (1981) 148 CLR 262, at 280‑281, 286, per Aickin J). We do not think there is a divide here in terms of whether an expectation of success is relevant between a test which refers to routine steps to be tried as a matter of course and the reformulated Cripps question. It is difficult to think of a case where an expectation that an experiment might well succeed is not implicit in the characterisation of steps as routine and to be tried as a matter of course.“[111]
[111] [2014] FCAFC 73 at [71].

130. It is clear that this test requires only routine steps to be undertaken and that there is an expectation is that a useful result might come from them. In Nichia Corporation v Arrow Electronics Australia Pty Ltd[112] (Nichia) the Full Federal Court said the expectation does not mean that it is necessary to know or be able to predict that useful result and a useful alternative is one which is useful when compared to the prior art in the field of the invention.[113] This was further elaborated on by the Full Federal Court in Mylan[114]:

[112] [2019] FCAFC 2
[113] Ibid at [80]; [89]; [99].
[114] Mylan Health Pty Ltd (formerly BGP Products Pty Ltd) v Sun Pharma ANZ Pty Ltd (formerly Ranbaxy Australia Pty Ltd) [2020] FCAFC 116.
“The reformulated Cripps question does not require certainty of outcome. It requires that the skilled addressee be directly led as a matter of course to try the claimed invention in the expectation that a particular research path “might well produce” a useful result (Hässle v Alphapharm at [53]). It does not require the skilled addressee to know that the steps will produce a useful result.”[115]
[115] Ibid at [502].

131. I note that more than one thing may be obvious, and other steps or solutions might be tried first.[116]
[116] Ibid at [94].
132. The Opponent submitted that there are other tests for inventive step. I agree, however, the Opponent only quoted the Emmett J in Dynamite Games Pty Limited v Aruze Gaming Australia Pty Limited[117]:
[117] [2013] FCA 163 at [95].
“For there to be an inventive step, there must be some difficulty overcome or some barrier crossed.”

133. The Applicant disagreed with this approach, and I consider that the “barrier to be crossed” statement may be out of context here. In that case Emmett J did not apply such a test and instead appeared to apply the Cripps question.[118] This was confirmed on appeal where the Full Court found that Emmett J had indeed applied the Cripps question from Alphapharm.[119] In Neurim Pharmaceuticals (1991) Ltd v Generic Partners Pty Ltd (No 5) Nicholas J acknowledged the crossing of some barrier test, however, this was in the context where there need only be a scintilla of invention.[120] In practice, the Cripps question is useful in scientific inventions and often used by the Commissioner.
[118] Ibid at [102].
[119] Dynamite Games Pty Limited v Aruze Gaming Australia Pty Limited [2013] FCAFC 96 at [26]
[120] [2024] FCA 360 at [387].
Common general knowledge (CGK)
134. As Aickin J stated in 3M v Beiersdorf[121], common general knowledge is the background knowledge and experience available to all those working in the relevant art:
[121] Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; 1A IPR 231
“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.”[122]
[122] Minnesota Mining & Manufacturing Co v Beiersdorf (Australia) Ltd [1980] HCA 9; 1A IPR 231 at 255-256.

135. However, it is not enough that information is recorded in a document, even if that document is widely circulated – it is only part of the common general knowledge when it is generally known and accepted:
“…information does not constitute common general knowledge merely because it might be found, for example, in a journal, even if widely read by persons in the art … Reference in this regard is made to the words of Luxmoore J in British Acoustic Films (1936) 53 RPC 221 at 250, cited by Lehane J in Aktiebolaget Hässle v Alphapharm Pty Ltd (1999) 44 IPR 593; [1999] FCA 628 at 605 [39]:
In my judgment it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates. A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art.”[123]
[123] Ranbaxy Laboratories Limited v AstraZeneca AB [2013] FCA 368; 101 IPR 11 at [217].

136. The Opponent submitted many documents formed part of the common general knowledge, including D81. The Applicant noted that much of what the Opponent asserts to be common general knowledge is not supported by evidence contemporaneous to the priority date. Indeed, the Opponent has relied on documents cited in the SGP merely as CGK and there does not appear to be any evidence which establishes them as CGK to the PSA. Without evidence of them being widely known and accepted, I cannot consider them to be CGK. I will discuss each point in turn.
Neoantigens
137. The Opponent submitted that mutations that existed in tumor cells which were absent in the subject’s healthy cells were known and that these mutations encoded peptides which provided subject specific tumor antigens. The Opponent’s submissions then go onto discuss D1 and D2 as these documents discuss these antigens. Indeed Dr Lavranos discussed neoantigens after she was asked to elaborate on them after she was shown background which disclosed them.[124] She explains:
[124] Lavranos #1 at [5] and [18]-[19].
“I was asked to elaborate on the types of mutations that can be found on a tumor antigen. My reply was that there could be a mutation in a protein which differs from a wild-type protein, making the protein a potential antigen. Such a mutation could be a substitution in an amino acid in a protein, a deletion in part of the amino acid sequence of the protein or some sort of rearrangement of the amino acid sequence.”[125]
[125] Lavranos #1 at [20}.

138. Indeed Prof. Melief did say that “neoantigens”, or tumor-specific antigens—which are not present in normal cells but present in cancer cells, were known at the priority date, but said the focus in the field was on tumor associated antigens.[126] He described tumor associated antigens as:
[126] Melief at [35]-[36].
“Non-mutated proteins could be associated with a type of cancer by being expressed at a higher rate on cancer cells than normal cells.”[127]
[127] Melief at [35].

139. The specification itself also discusses neoantigens in the background by stating:
“there is a third class of tumor antigens that has rarely been used in vaccines due to technical difficulties in identifying them (Sensi et al. 2006). This class consists of proteins with tumor-specific mutations that result in altered amino acid sequences. Such mutated proteins have the potential to: (a) uniquely mark a tumor (relative to non-tumor cells) for recognition and destruction by the immune system (Lennerz et al., 2005); (b) avoid central and sometimes peripheral T cell tolerance, and thus be recognized by more effective, high avidity T cells receptors (Gotter et al., 2004).”[128]
[128] Page 1 at [0003].

140. Given that even Prof. Melief appeared to acknowledge that neoantigens were known in the field at 2010 and that the specification itself discusses them in the background, citing several documents, I accept that neoantigens did form part of the common general knowledge at the priority date.
Use of neoantigens for cancer vaccination
141. The Opponent asserted that it was widely known before the priority date that tumor-specific neoantigenic peptides can be used for subject-specific cancer treatment. They cited the following from D1:
“Immunogenicity and constitutive expression of the unique tumor antigens provide a strong rationale for the design of novel, patient-tailored therapies that target such determinants.”[129]
[129] D1, Sensi, M & Anichini A. (2006) Unique Tumor Antigens: Evidence for Immune Control of Genome Integrity and Immunogenic Targets for T Cell –Medicated Patient-Specific Immunotherapy. Clin Cancer Res. 12, 5023-

142. The Opponent also cited the following from D2:
“These results document a high degree of individuality for the cellular antitumor response and support the need for individualizing the monitoring and therapeutic approaches to the primary targets of the autologous T cell response, which may finally lead to a more effective cancer immunotherapy.”[130]
[130] D2, Lennerz, V. et al., (2005) The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. PNAS. 102 (44), 16013 – 16018, abstract last sentence.

143. Further to the above D12 was cited as a whole, along with D17:
“different groups have made an argument in favour of personalized immunotherapy targeting the unique antigens caused by mutations that are often only present in the tumor of one patient. These tumor antigens are purely tumor specific, and therefore not tolerogenic, and are believed to be often crucial to the oncogenic process. Furthermore, the natural immune response in some patients was found to be stronger against the unique antigens than the response against the shared antigen.”[131]

[131] D17, Kessler, J. H. & Melief C. J. M. (2007) Identification of T-cell epitopes for cancer immunotheraov. Leukemia. 21, 1859-1874, page 1862 left column.

144. D18 also concludes that:
"[t]he success seen thus far in experimental and clinical setting targeting tumor-specific antigens should spur the further application of high-throughput technologies to the individual analysis of a patient's serum and T cell specificities in order to develop tailored immunotherapy. Cancer immunotherapy is an ideal area for the development of personalized medicine that will allow us to take advantage of tumor-specific antigens for the diagnosis and treatment of cancers."[132]
[132] D18, Schietinger, A., Philip, M & Schreiber, H. (2008) Specificity in cancer immunotherapy. Semin lmmunol. 20, 276-285 page 10 top paragraph.

145. In my view, none of this establishes that the use of neoantigens for cancer vaccines was CGK, instead it shows that at the priority date some researchers in this area appeared to think of it as a promising area of research. How widely this was known has not been established by these citations.
146. The Opponent went onto discuss comments made by Dr Castle in D70 which also discussed the topic as promising and an attractive platform. It does not discuss the impact in the field or how widely it was known.

147. Prof. Melief did comment to a limited extend on what was known in the field at the time, I note that he did this by discussing examples and discussing what was being developed rather than merely asserting “this was known”:
“it was believed by me and others in the field, that therapies could be developed that could induce an immune response to these antigens in order to target cancers across multiple patients. Indeed, vaccines and other treatments (such as antibodies, CAR T cells and T cells transduced with specific T cell receptors) were being developed, and are still being developed, that target these antigens.”[133]
[133] Melief at [36].

148. He noted that the focus was on tumor-associated antigens (i.e. not subject specific):
“As noted above, prior to 2010, most cancer vaccines were being developed for the tumor-associated antigens and a considerable number had been identified by that time.

The results of efforts to target these tumor-associated antigens with vaccines were disappointing and because of this the field had not established that cancer vaccines were a viable treatment for cancer. We now know some of the reasons for this, but prior to 2010 there was little evidence that vaccines were a viable or effective treatment for cancer.”[134]
[134] Melief at [37]-[38].

149. The use of neoantigens in cancer vaccines appeared to be an area of interest to some research groups, how widely known they were or their use in cancer vaccines has not been established as CGK.
Sequencing of cancer genomes
150. Similar to the discussion above, the Opponent cited a number of documents that used sequencing. I do not consider this to be sufficient evidence to establish common general knowledge in the field.
151. The Opponent further relied on evidence from Dr Castle in D70 where he states that:
“Prior to the priority date of the patent, the availability of a large amount of information from the Human Genome Product and many other databases meant that researchers had the understanding and motivation to apply high-throughput sequencing techniques to the identification of novel anti-tumor antigens, as described e.g. in D1 (Wood et al., 2007). Thus, the genome- or exome-wide sequencing feature claimed in the patent was already well understood in the art prior to the priority date of the patent."[135]
[135] D70 Paragraph 12.

152. Prof. Melief responded to Dr Lavranos on this point:
“Dr Lavranos states that whole genome sequencing and HLA binding prediction algorithms were known in the art. This is true. However, as I have stated the invention of the Opposed Application does not lie in the specific techniques used but rather the combination of these techniques to enable a new way of treating cancer.”[136]
[136] Melief at [100].

153. Prof. Melief did not consider the invention to be in the sequencing itself and acknowledged its use was known, however, he did state that:
“Some research groups would use sequencing techniques that were much slower and more cumbersome than the sequencing used in the Opposed Application to look at the sequence of one, or a few, specific genes in cancer and compare those to healthy cells.”[137]
[137] Melief at [98].

154. Prof. Melief went on to cite D12 which, as discussed above, did not conduct whole genome sequencing but instead looked at approximately 13,000 genes.
155. I accept that whole genome sequencing was known at the priority date, and that cancer genes were often sequenced to identify mutations. Prof. Melief appeared to be of the opinion that this was targeted to find mutations, such as driver mutations, that are responsible for the cancer’s development and progression.[138] Prof. Melief states that this is different to the Opposed specification in that looking for driver mutations is a bias—with a focus on the cause of the cancer, whereas the whole genome sequencing used in the current specification is unbiased.
[138] Melief at [78].
Prediction of epitopes for HLA proteins
156. The Opponent presented evidence from D70 and D71 on the algorithms to predict HLA binding. This evidence seems to confirm the existence of the algorithms used to predict binding of HLA proteins. Indeed the current application does not purport the algorithm to be the invention and Prof. Melief also acknowledges they were known.[139] The statements in D70 and D71 do not elaborate on how well known they were to the person skilled in the art and do not establish the algorithms as common general knowledge. The specification states that the algorithms were well established[140] and the two programs used are provided[141]. I therefore accept that HLA binding algorithms were known in 2010 but it is not clear how widely known or used they were to the person skilled in the art.
[139] Melief at [100].
[140] Page 13 at [00055].
[141] Page 13 at [00053].
D81 as common general knowledge
157. The Opponent argued that D81 is CGK and their main case for lack of inventive step in view of the common general knowledge relies on D81. As outlined above:
“A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art.[142]

[142]Aktiebolaget Hässle v Alphapharm Pty Ltd (1999) 44 IPR 593; [1999] FCA 628 at 605 [39

158. The only evidence from a declarant on whether D81 is CGK is from Dr Lavranos where she states:
“I note that D81 is a book chapter while D68 and D20 are review articles. In my opinion, these would represent part of the common general knowledge at the priority date of the application.”[143]
[143] Lavranos #2 at [20]

159. Generally, to establish CGK the declarant would at least be commenting on their own knowledge of the article and perhaps that their peers in the field were also familiar with it and accepted it. In my view, the above statement is insufficient and does not establish that D81 is common general knowledge. Dr Lavranos does not state that the documents were widely known or that its contents were accepted in the art, furthermore Dr Lavranos does not even state that she herself was familiar with it at the priority date.
160. In view of the above I consider that the Opponent has failed to provide evidence to meet the threshold for establishing D81 and many features of the claims that they purport to be CGK. It follows that a lack of inventive step based on the common general knowledge alone has not been established.
Inventive Step in light of 7(3) documents
D81
161. The Opponent also submitted that the current claims lacked an inventive step when compared to D81 and the common general knowledge. I have outlined the disclosure of D81 above including Figure 50.1. In this figure a strategy for the “ideal tumor vaccine” is outlined and it is noted that a further step would be an approach to match a patient’s individual antigens in a tumor.[144] It does go further and say this would require high-throughput sequencing in analogous fashion on an individual per tumor basis. However, D81 also states that analysis of such data would be complex, since it involves the sequencing of 25,000 genes from two sources.[145] It goes on to say that they have started work in this direction with renal carcinoma.
[144] D81 page 578 column last sentence-column 2.
[145] D81 page 578 second column.
162. Separate to this disclosure of the “ideal” composition the use of possible tools via the internet to predict T-cell epitopes is stated and it does say that many tumor-specific antigens have been identified this way.[146]
[146] D81 page 577 second column.
163. The evidence provided on D81 from Dr Lavranos is based on the ground of novelty. It does not outline what routine steps would be involved if following D81. With Dr Lavranos ending with:
“I would think that the invention is disclosed or at least suggested in D81.”[147]
[147] Lavranos #2 at [22](a)

164. In my view D81 does indeed suggest an ideal vaccine that would involve whole genome sequencing of both the cancer cell and normal cell of a patient and the use of an algorithm to find potential epitopes is also suggested. However, the current application has set the limit of binding at an IC₅₀ 150nM which appeared to be taken from figure 8C where it was shown that all but one peptide predicted to bind at an IC₅₀ of 150 nM experimentally showed an IC₅₀ of less than 500 nM. The one exception only being slightly above 500 nM.
165. As outlined above for novelty, the Opponent’s declarant first appeared to state that the choice of IC₅₀ of less than 150 nM was arbitrary and might not work stating:
The IC50 value of less than 150 nM appears to be an arbitrary value and there is no data to show that all peptides that bind or are predicted to bind with a predicted IC50 value of less than 150 nM can be definitely developed into a successful vaccine. Moreover, the prediction of an IC50 value is not the same as an actual IC50 value. There may be peptides that are predicted to bind with an IC50 value of less than 150 nM but have a much weaker affinity to HLA in an actual experiment, thus rendering them unsuitable as vaccines. There are also many other factors that would determine whether a neo-antigen peptide can be developed into a cancer vaccine. For example, some neo-antigen peptides may simply not be capable of inducing a sufficient T cell response in a patient due to a myriad of factors such as structure, length and stability. This may render the neo-peptide unsuitable for development into a vaccine.[148]

[148] Lavranos #2 at [14]

166. In my view, Figure 8C shows that the choice of and IC₅₀ of less than 150 is not arbitrary. In reply, the Opponent’s declarant appeared to admit that the threshold would improve the proportion of peptides that will have an effective IC₅₀with Lavranos stating:
In my opinion, the use of a more stringent IC50 threshold of less than 150 nM (as also recited in the claims) merely improves the proportion of peptides that will have an experimentally determined IC50 below a certain value (e.g. less than 500 nM). This would be an expected result to a skilled person. This, however, does not mean that the algorithm can predict actual HLA binding with 100% certainty. There is also nothing to suggest that one could predict HLA class I-binding neoepitopes accurately for the first time. [149]
[149] Lavranos #3 at ]15]

167. I note that if the person skilled in the art would routinely look for an in silico threshold for the IC₅₀ then experimentally verify that threshold, Dr Lavranos would likely have said it in her evidence in support, rather than in reply after the importance of this feature had been discussed by Prof. Melief.
168. I note that annexed to the Opponent’s submissions for this hearing were documents that purportedly suggested the use of an IC₅₀ of less than 150 nM. However, these were not accompanied by expert evidence that it would be in any way routine or establishing that these documents were well known and that a person skilled in the art would combine this knowledge with D81. I therefore do not consider them to be of assistance in establishing a lack of inventive step for the current claims.

169. The Opponent also referred to the EP Decision in respect of EP2569633. This decision finds that the use of an IC₅₀ of less than 150 nM is arbitrary, however, accepts that there is improvement between prediction and experiment.[150] I do not consider the EP decision to be helpful particularly given that expert evidence has been available to the parties in this opposition. Furthermore, I note that their tests for inventive step are different to those in Australia with EP stating that the person skilled in the art would “try and see”[151].
[150] EP 25696633 decision 18.3.3
[151] EP 25696633 decision at 7.

170. The current claims also state that the at least 4 peptides are to be used. I consider that this would overcome any possibility of there being a peptide with a HLA binding of greater than 500 nM and is similarly not arbitrary. Furthermore there is no evidence from the Opponent that satisfies me that this would not be the case. There is no evidence that a person skilled in the art would arrive at this as a matter of routine.

171. Consequently, a lack of inventive step when the current claims are compared to D81 and the common general knowledge has not been established.
D20
172. D20 has been discussed above for novelty. It is a review article and provides an “ultimate strategy” for cancer vaccines:
“Obviously, the ultimate strategy for targeting such types of Ags will imply sequencing of the whole genome of each individual tumor followed by the selection of mutated peptides whose motifs are predicted to be presented by the HLA alleles of the patient bearing that particular mutated tumor.”[152]
[152] D20 page 1977 first column under implications for immunotherapy

173. As noted above for novelty, this strategy had not been put into practice and, like D81, provides no guidance on the threshold for IC₅₀ binding or to use at least four peptides.
174. Similar to D81, Dr Lavranos stated that she believes the invention is disclosed or suggested in D20. The routine steps are not outlined and consequently there is a similar lack of evidence that the Opponent’s case suffered for D81. It follows that it has not been established that the current claims lack an inventive step when compared to D20 and the common general knowledge.
D12
175. The Opponent submitted that D12 is directed to the same purpose and aims at the same objective as the claimed subject matter as the current specification, namely using neoantigenic peptides for preparing a subject specific immunogenic composition. As I have outlined above, D12 does not carry out whole genomic sequencing and instead sequences approximately 13,000 genes. It does use predictive software for HLA binding. However, D12 sets a threshold of less than 500 nM and does not teach or suggest that at least four peptides are to be used. I have discussed the lack of evidence on this point for D81. It follows that the evidence does not establish that the current claims lack an inventive step when compared to D12.
Manner of Manufacture
176. The Opponent submitted that the claims lack a manner of manufacture because they fail to meet the threshold of an “invention” citing Microcell at [251] where the High Court said:
“We have in truth nothing but a claim for the use of a known material in the manufacture of known articles for the purpose of which its known properties make that material suitable. A claim for nothing more than that cannot be subject matter for a patent and the position cannot be affected either by the fact that nobody thought of doing the thing before, or by the fact that, when somebody did think of doing it, it was found to be a good thing to do.”[153]
[153] Commissioner of Patents v Microcell Ltd [1959] HCA 71; (1959) 102 CLR 232 at [251].

177. The Opponent submits that the methods of identifying subject and tumor specific peptides were known in the art and that a skilled person would have also “thought about” using such peptides for cancer vaccination. However, the threshold of inventiveness form of manner of manufacture is a narrow one and for a claim to fail based on this argument it would need to be clear on the face of the specification. In NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd the High Court stated that:
“If it is apparent on the face of the relevant specification that the subject matter of the claim is, by reason of absence of the necessary quality of inventiveness, not a manner of manufacture for the purposes of the Statute Monopolies. That does not mean that the threshold requirement of “an alleged invention” corresponds with or renders otiose the more specific requirements of novelty and inventive step (when compared with the prior art base) contained in s 18(1)(b). It simply means that, if it is apparent upon the face of the specification, when properly construed, that the quality of inventiveness necessary for there to be a proper subject of letters patent under the Statute of Monopolies is absent, one need go no further.”[154]
[154] (1995) 183 CLR 655 at 663-665.

178. In the current case, the grounds of novelty and inventive step have failed and there is nothing “on the face of the specification” to suggest a lack of inventiveness. The mere assertion that a person skilled in the art would have thought about using neoantigens for a cancer vaccine does not satisfy me that this ground of opposition should succeed.
179. This ground of opposition has not been made out.
Conclusion
180. The opposition has been unsuccessful on all grounds, subject to appeal, I direct that the application proceed to grant.
Costs
181. The Opposition has been unsuccessful, costs are awarded against the Opponent under Schedule 8.
K. Wagg
Delegate of the Commissioner of Patents

5032, abstract, penultimate paragraph.

Declarant	Date	Reference	Exhibits
Dr Tina Lavranos	12 January 2022	Lavranos #1	TL-1
Dr Tina Lavranos	17 January 2022	Lavranos #2	None