Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment to the claims filed after non-final office action on November 26, 2025 is acknowledged. Claims 1, 3, 6, 8, 26, 28, 38, 40 were amended, claim 2, 4-5, 7, 9-25, 27, 29, 32, 35-37, 39, 41-46, 50-55, 58-62, 64-65, 67, 70, 72-74, 76-108, 110-121, 123-124, 126-153 were canceled and claims 1, 3, 6, 8, 26, 28, 30-31, 33-34, 38, 40, 47-49, 56-57, 63, 66, 68-69, 71, 75, 109, 122, 125, 154-155 are pending in the instant application.
The restriction was deemed proper and made FINAL in the previous office action. Claims 30-31, 33-34, 47-49, 56-57, 63, 66, 68-69, 71, 75, 109, 122, 125 and 154-155 are withdrawn as being drawn to a non-elected species/invention. Claims 1, 3, 6, 8, 26, 28, 38 and 40 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The objection to claims 1 and 6 is hereby withdrawn in view of amendment of the claims filed November 26, 2025 to include SEQ ID NOs from the Tables in the specification.
The objection to claims 3 and 38 are withdrawn in view of amendment of the claims filed November 26, 2025.
The rejection of claim(s) 1, 3, 6, 8 under 35 U.S.C. 102(a)(1) as being anticipated by Uniprot (Uniprot Protein Database, protein Accession Q91C14, published 2001, cited in IDS) is withdrawn in view of amendment of the claims to require a pharmaceutical composition and adjuvant filed November 26, 2025.
The rejection of claim(s) 1, 3, 6, 8 under 35 U.S.C. 102(a)(1) as being anticipated by Uniprot* (Uniprot* Protein Database, protein Accession Q0MQN6, published 2006) is withdrawn in view of amendment of the claims to require a pharmaceutical composition and adjuvant filed November 26, 2025.
The rejection of claim(s) 1, 3, 6, 8, 26, 28 under 35 U.S.C. 102(a)(1) as being anticipated by Khanna (WO2018049165 A1, cited in IDS) is withdrawn in view of amendment of the claims filed November 26, 2025.
Maintained/Revised Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3, 6, 8, 26, 28, 38 and 40 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, Claims 1, 3, 6, 8, 26, 28, 38 and 40 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below and is based on MPEP2106.03-MPEP2106.05.
Claim Interpretation
Claim 1 claims “A pharmaceutical composition comprising a peptide comprising at least three of the epitopes set forth in SEQ IDNOs:1-122 and an adjuvant”. Claim 3 claims “The pharmaceutical composition of claim 1, wherein the three or more epitopes comprises JCV epitopes set forth in SEQ ID NOs: 1-21.” Claim 6 claims wherein the peptide comprises a plurality of epitopes set forth in SEQ ID Nos:1-122. Claim 8 claims wherein the plurality comprises a plurality of JCV epitopes as set forth in SEQ ID Nos:1-21. Claims 38 and 40 claims a pool of the peptides comprising at least two or at least 10 of SEQ ID Nos:1-21. Claim 26 claims a pharmaceutical formulation with the peptides and a pharmaceutical carrier. Claim 28 claims a vaccine comprising said peptide and a carrier.
Subject Matter Eligibility Test for Products and Processes
Step 1: Is the claim to a process, machine, manufacture, or composition of matter (see MPEP
2106.03)?
Yes, the instant claims are directed to a statutory patent-eligible subject matter category, namely a composition of matter.
Step 2A (1): Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea
(see 2106.04)?
Yes, the claims are directed to a natural phenomenon, namely a naturally-occurring peptides of JC virus protein (see Table 2, SEQ ID Nos:1-21, 1-122) and adjuvants which can also be naturally occurring (for example microbial products, cytokines etc..). Accordingly, the pending claims are directed to naturally occurring peptides.
As the product(s) are found in nature, consideration is given to whether it is integrated into a practical application or contains other elements that provide a marked difference as compared to the natural counterpart.
Accordingly, the pending claims are directed to a naturally occurring products (naturally occurring peptides).
Step 2A (2): Does the Claim recite additional Elements that integrate the judicial Exception into a Practical Application? (see MPEP 2106.04 (d)) NO. This judicial exception is not integrated into a practical application because it does not provide a treatment that affirmatively recites an action that effects a particular treatment for a disease or medical condition.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception (see MPEP 2106.05))?
No, the claim does not recite additional elements that amount to significantly more than the judicial exception, as explained below. Given the broadest reasonable interpretation of a vaccine and a carrier, this could be the combination of the peptide and water (which is also naturally occurring). The including of water does not amount to significantly more than the judicial exception itself. The same concept applies for instant claims 38 and 40 which requires a “pool” or combination of at least 2 or 10 of the naturally occurring epitopes. There is no evidence that the combination of the naturally occurring peptides results is something functionally different or improved as compared to the judicial exceptions themselves. Furthermore, the addition of an “adjuvant” broadly does not amount to significantly more than the judicial exception. The adjuvant is recited generically (and encompasses naturally occurring substances such as cytokines, microbial products etc..), without limitation to a particular adjuvant, specifical functional amount, mechanism of action or non-conventional interaction with the peptides. Accordingly, the adjuvant does not necessarily add anything beyond another natural product used for its well understood immunostimulatory effect. The mere combination of naturally occurring peptide epitopes with a naturally occurring adjuvant does not impart a new structure, new function, or markedly different characteristic to the peptides.
Factors for determining if the claim directed to a product of nature, as a whole, recites something significantly more than the judicial exception, are provided in MPEP 2106. The JCV peptide epitopes in combination with a “adjuvant” or carrier such as water of the instant claims does not amount to significantly more than the exception.
In sum, when the relevant considerations are analyzed, they weigh against a significant difference. Accordingly, Claims 1, 3, 6, 8, 26, 28, 38 and 40 not qualify as eligible subject matter.
Response to Applicant’s Arguments
Applicant argues “The Office alleges that the claims are directed to a judicial exception (a composition of matter) and that the independent claim does not recite an element that amount to significantly more than the judicial exception under the two-step test of Alice Corp. Pty. Ltd V CLS Bank Int'l, 573 U.S. 208 (2014), hereinafter "Alice". The first step of Alice requires a consideration as to whether the claims at issue are directed to an ineligible concept (e.g., an abstract idea of natural phenomenon). In making this determination, the Supreme Court has emphasized that it is important to "tread carefully in construing this exclusionary principle lest it swallow all of patent law" (Alice, 573 U.S. at 217, citing Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71 (2012)) since "[a]t some level, 'all inventions ... embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas" (Id.). Thus, an invention is not rendered ineligible for patent simply because it involves a natural phenomenon. If the claimed concept is found to be directed to an ineligible concept, then the claimed concept fails step one, and the invention is further analyzed under step two. If the claimed concept is sufficiently different, then the invention is patent eligible under step one, and it is not necessary to analyze step two of the test. The second step of Alice is to "consider the elements of each claim both individually and 'as an ordered combination' to determine whether the additional elements 'transform the nature of the claims' into a patent-eligible application" (Alice, 572 U.S. at 217, citing Mayo, 566 U.S. at 79, 78). As mentioned above, step one of the Alice test requires determining "whether the claims at issue are directed to one of those patent-ineligible concepts" (Alice, 573 U.S. at 217, citing Mayo, 566 U.S. at 77). Accordingly, at step one, "it is not enough to merely identify a patent- ineligible concept underlying the claim; we must determine whether that patent-ineligible concept is what the claim is 'directed to"' (Rapid Litig, Mgmt. Ltd v CellzDirect, Inc., 827 F.3d 1042, 1050 (Fed. Cir. 2016). If the claims are not directed to a patent ineligible concept at step one, we need not address step two of the inquiry (see, Enfish, LLC v Microsoft Corp., 800 F.3d 1327, 1339 (Fed. Cir. 2016)). That is the case here. Applicant submits that the claims are not directed to patent-ineligible subject matter, rather the claims are directed to a pharmaceutical composition comprising a peptide comprising at least three JCV epitopes and an adjuvant. The inclusion of the adjuvant is a human-engineered feature that does not occur in nature and confers new functional properties. As disclosed in the specification (see, e.g., para. [0074]) the adjuvant enhances immunogenicity by mechanisms such as: Increasing antigen persistence at the injection site or directing it to a target tissue (e.g., tumour); Facilitating uptake by antigen-presenting cells; Activating macrophages and lymphocytes; Stimulating cytokine production; and Preventing T-cell exhaustion, thereby improving therapeutic efficacy and safety. These effects represent a marked functional difference from the natural peptide alone. The claimed composition is not merely a product of nature; it is a purposeful combination that achieves an immunological effect unattainable by the peptide in isolation.
Applicant draws attention to Example 28 (Vaccines) in the USPTO's Subject Matter Eligibility Examples: Life Sciences. This example illustrates that combining a peptide with an adjuvant in an immuno-effective amount creates markedly different characteristics from natural components, rendering the claim patent eligible. In Example 28: Claim 3 (Peptide + water) was ineligible because the combination lacked any marked difference. Claim 5 (Peptide + aluminium salt adjuvant) was eligible because the combination
produced a significant functional improvement-enhanced immunogenicity. The USPTO concluded that such a combination constitutes "significantly more" than a product of nature because it introduces a new property (strong immune response) not present in the natural components. Similarly, the claimed composition should be considered patent-eligible because the combination produces a new functional property (enhanced immune response) that does not exist in nature. The claimed composition has different functional characteristics (such as prevented T cell exhaustion and thus increase the effectiveness or safety of a particular immune interacting agent). This difference rises to the level of a marked difference and so the claimed composition does not qualify as a "product of nature" exception. Thus, the claim is not directed to an exception, and qualifies as eligible subject matter.
Applicant’s arguments have been fully considered but not found persuasive. Applicant argues that the claims are not directed to a judicial exception because the inclusion of an adjuvant allegedly creates a human-engineered composition with markedly different functional characteristics, relying on USPTO Subject Matter Eligibility Example 28. These arguments have been considered but are not persuasive. First, the Applicant Misapplies USPTO Eligibility Example 28. Applicant analogizes the claims to Claim 5 of Example 28 (peptide + aluminum salt adjuvant), which was found eligible. However, the present claims are materially distinguishable. In Example 28, eligibility was predicated on a specific, non-naturally occurring adjuvant (aluminum salt),an immune-effective amount of the adjuvant, a specific functional interaction between the peptide and the adjuvant, and a demonstrated new functional property arising from that specific combination. By contrast, the present claims recite “an adjuvant” generically, do not require a particular adjuvant, do not require a non-naturally occurring adjuvant, and do not require any specific immune-effective amount of the adjuvant. Because the claims encompass embodiments in which the adjuvant is naturally occurring or conventional, the reasoning of Example 28 does not apply (see MPEP §2106.04).
Regarding Applicant’s arguments that the combination of the adjuvant and the peptides in the composition has different functional characteristics (such as prevented T cell exhaustion and thus increase the effectiveness or safety of a particular immune interacting agent), the Examiner respectfully disagrees. While the claims recite a pharmaceutical composition comprising naturally occurring peptide epitopes and an adjuvant, the mere addition of an adjuvant broadly does not, by itself, render the claim patent-eligible absent a showing that the claimed combination exhibits a marked difference in characteristics over the natural components as they exist in nature. Here, the claims broadly recite an “adjuvant” without imposing any structural, compositional, or functional limitation on how the adjuvant interacts with the peptide epitopes, nor do the claims require a specific adjuvant, dosage, formulation, mechanism of action, or immunological outcome. As such, the adjuvant is recited at a high level of generality, and functions in its well-understood, routine, and conventional capacity of enhancing immune responses. Importantly, the specification itself acknowledges that adjuvants, including naturally occurring adjuvants, are conventionally used to increase antigen persistence, promote uptake by antigen-presenting cells, activate immune cells, stimulate cytokine production, and modulate immune exhaustion. These effects are inherent properties of adjuvants and do not reflect a transformation of the natural peptides into a composition with characteristics that are markedly different from those found in nature.
Take together, the claims are directed to naturally occurring peptide epitopes and their natural immunogenic properties. The inclusion of a generically recited adjuvant, which may itself be naturally occurring or conventional, does not impart markedly different characteristics nor amount to significantly more than the judicial exception. Accordingly, the claims remain directed to patent-ineligible subject matter under 35 U.S.C. §101.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 6, 26, 28 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Khanna (WO2018049165 A1, cited in IDS).
Regarding claim 1, Khanna teaches of an isolated protein comprising one or more epitopes from SEQ ID Nos:1-122 (see claim 1, tables 1-3) which, epitopes comprise instant SEQ ID Nos:10 and 20 (see Table 2, SEQ ID Nos 77 and 81) and also instant SEQ ID Nos:89-122 (SEQ ID Nos:87-120, all of instant TABLE 4 is Table 3 of Khanna). Khanna further expressly teaches that such polypeptides may comprise at least 1, 2, 3, 4, 5, 10, 20, 25, 30 or more epitopes from tables 1-3 (see page 4, lines 10-14, lines 30-32, page 5, lines 20-22, epitope pools and multiepitope polypeptides). Khanna additionally teaches including an adjuvant in the formulation (see claim 28).
Regarding claims 26 and 28, Khanna teaches a vaccine comprising the protein comprising said epitope peptides and a carrier (see claim 27). Regarding claim 6, Khanna teaches a plurality of JCV epitopes to be used from Table 2 which comprises instant SEQ ID Nos:10 and 20 and also instant SEQ ID Nos:89-122 (SEQ ID Nos:87-120, all of instant TABLE 4 is Table 3 of Khanna).
Regarding claim 38, Khanna teaches administering a vaccine comprising one or more epitopes form JCV epitopes listed in Table 2 and Table 3 (which comprise two sequences from SEQ ID Nos:1-21) which meet the limitations of a “pool” comprising two or more epitopes (see claims 108, 110, 111, 116, 128 “comprises at least two”).
As stated above, Khanna teaches administering a vaccine comprising two or more epitopes from JCV epitopes listed in Table 2 thus meeting the limitations of a “pool” comprising two or more epitopes. Khanna is silent to specifically providing an example wherein the vaccine comprises both SEQ ID Nos:77 and 81 (instant SEQ ID Nos:10 and 20). However, Khanna does teach a large number of epitopes can be included from Table 2 (at least 25, see claim 133). It would have been obvious to try both SEQ ID Nos:77 and 81 as the epitope sequences for creating an immune response in a vaccine for treating/preventing a polyomavirus infection in a subject. On of ordinary skill in the art would have been motivated to do so given Khanna specifically teaches instant SEQ ID Nos:10 and 20 for the purpose of eliciting an immune response and being used in a vaccine for treating/preventing infection. There is a reasonable expectation of success given Khanna teaches use of these epitopes for the purpose of being used in a vaccine.
Furthermore, Khanna is silent to specifically providing an example wherein the peptide in the vaccine/pharmaceutical formulation comprises three or more of SEQ ID Nos:1-122, for example, any three of SEQ ID Nos: 10, 20, 87-120.
However, it would have been obvious before the effective filing date of the claimed invention to include three or more epitopes in the peptide vaccine/pharmaceutical formulations of Khanna. A person of ordinary skill in the art would have been motivated to include three or more epitopes in a single polypeptide in order to broaden immune coverage and enhance immunogenicity, as taught by Khanna’s disclosure of multi-epitope constructs and epitope pools. A reasonable expectation of success would have existed because Khanna teaches that such multiepitope polypeptides are immunogenic and suitable for use in pharmaceutical and vaccine compositions and teaches 10, 20, 25 or 30 or more epitopes can be used.
Khanna expressly teaches polypeptides comprising varying numbers of epitopes, including at least three epitopes. In view of this teaching, a person of ordinary skill in the art would have been motivated to include three or more epitopes in a single polypeptide as an application of a known multi-epitope vaccine design technique to achieve predictable results, namely broadened immune coverage, with a reasonable expectation of success (see MPEP §§2143, 2143(I)(A), and 2144.05; KSR Int’l Co. v. Teleflex Inc.). Furthermore, it would have been obvious to optimize the number of epitopes in a polypeptide or in a pool of peptides to achieve optimal therapeutic effectiveness and immune response.
Response to Applicant’s Arguments
Applicants argue that “The Office asserts that Khanna teaches administering a vaccine comprising one or more epitopes from JCV epitopes listed in Table 2, thus meeting the limitations of a "poof' of epitopes. See, Office Action at page 8. However, the Office acknowledges that Khanna is silent on specifically providing an example wherein the vaccine comprises both SEQ ID NOs: 77 and 81 (instant SEQ ID NOs: 10 and 20), but asserts that Khanna allegedly teaches that a large number of epitopes can be included from Table 2. The Office concludes that therefore, it is allegedly obvious to try both SEQ ID NOs: 77 and 81 as the epitope sequences for creating an immune response in a vaccine for treating/preventing a polyomavirus infection in a subject. Id. Applicant respectfully disagrees.
Polyomavirus epitope immunogenicity is highly unpredictable. Combining epitopes does not guarantee enhanced immune response. While Khanna lists numerous epitopes, it does so without preference or guidance toward selecting SEQ ID NOs: 10 and 20 together. Furthermore, the prior art does not provide any rationale or data suggesting that these specific peptides should be combined for improved immunogenicity. The present claims provide compositions and methods related to a combination of at least three polyomavirus epitopes that are recognized by T lymphocytes, which may be used to prevent and/or treat a polyomavirus infection (e.g., a JCV infection) and/or cancer (e.g., a polyomavirus- associated cancer). At the time of filing there were no drugs to effectively inhibit, or cure polyomavirus infection and treatment relied primarily on reversing or relieving the immunodeficiency of the patient to slow or stop disease progression. However, such strategies require suspending or halting therapy in immunosuppression patients, creating a dilemma that leaves these patients vulnerable to one of their two conditions. Accordingly, the present application provides new therapies to treat and prevent polyomavirus infections and/or associated diseases. The working examples demonstrate that short synthetic peptides (SEQ ID NOs: 1-21), when used individually or in pools, elicit strong CD4+ and CD8+ T-cell responses. For example, Table 6 reports IFN-y expression in CD4+ T cells reaching up to 38.39% for SEQ ID NO: 3, even at low peptide concentrations (0.1 pg/mL). This level of immunogenicity from minimal epitopes was not predictable from Khanna, which generally favored full-length proteins or adoptive transfer of expanded T cells. In addition, the present application demonstrates that T cells expanded with JCV peptides recognize homologous BKV peptides and vice versa (Figure 4). This cross-reactivity was unexpected because epitope homology does not guarantee functional T-cell recognition, which depends on complex TCR-HLA interactions. The ability to target multiple polyomaviruses with a single peptide pool provides a significant therapeutic advantage not taught by Khanna. One advantage of the present application is the specific elucidation of the sensitivity, reactivity and effectiveness of the specifically defined epitopes from JCV. This process for epitope selection has led to a specific group of JCV epitopes that are superior with respect to their immunogenicity as compared to epitopes described in Khanna. Functional data reflecting the superior effects attributed to these epitopes is included in the present specification, for example, in Figure 5 (associated text in Example 6, paras. [0097]-[0098]), which provides IFNy activation in response to the peptide epitopes; as well as IL-2, TNF, and CD107 production (as shown in Example 7 and Figure 6). Furthermore, the mapped epitopes cover multiple HLA class I and II alleles (see, Table 5) enabling the applicability across diverse patient population. Achieving this breadth with a defined peptide set is non-trivial and was not suggested by Khanna, which focuses on donor-derived T- cell therapy rather than rational epitope selection for vaccines. Accordingly, Applicant submits that these results are unexpected and advantageous, particularly in view of the disclosure of Khanna. Khanna does not teach or suggest that short peptide could elicit such potent, polyfunctional immune responses or exhibit cross-reactivity across polyomaviruses. For at least these reasons, the claims are not obvious in light of Khanna and withdrawal of this rejection is respectfully requested.
Applicant argues that polyomavirus epitope immunogenicity is highly unpredictable, that combining epitopes does not guarantee an enhanced immune response, and that Khanna provides no preference or guidance toward selecting SEQ ID NOs: 10 and 20 together. These arguments are not persuasive.
First, a guarantee of enhanced immune response is not required to establish obviousness. The proper inquiry is whether the prior art provides a reasonable expectation of success, not certainty of outcome (see KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007); MPEP §2143). Khanna expressly teaches that the disclosed epitopes are immunogenic and suitable for use in peptide pools and vaccine compositions, and further teaches combining multiple epitopes in peptide pools and multi-epitope polypeptides. Accordingly, Khanna provides a reasonable expectation that combining immunogenic epitopes would elicit an immune response, even if the precise magnitude of the response cannot be guaranteed.
Second, Applicant’s focus on the absence of a specific preference for combining SEQ ID NOs: 10 and 20 is misplaced. The claims are not limited to any particular combination of epitopes, but broadly encompass compositions comprising three or more epitope (from SEQ ID Nos:1-122) and two or epitopes (from SEQ ID Nos:1-21). Khanna expressly teaches selecting multiple epitopes from its disclosed epitope tables, including embodiments comprising at least 1, 2, 3, 4, 5, or more epitopes, and further teaches the use of peptide pools comprising multiple epitopes. The law does not require the prior art to single out the exact combination later claimed where the reference provides a finite, identified set of options and guidance to combine them (see In re Kubin, 561 F.3d 1351 (Fed. Cir. 2009); MPEP §2144.05).
Third, while Applicant asserts that Khanna provides no data suggesting that specific peptides should be combined for improved immunogenicity, Khanna expressly demonstrates that peptide pools comprising multiple epitopes elicit functional immune responses, including IFN-γ production and T-cell activation. Thus, Khanna provides both a rationale and supporting evidence for combining epitopes in peptide pools, even if it does not quantify improvement for every specific combination.
Finally, general allegations that immunogenicity is “highly unpredictable” are insufficient to overcome a prima facie case of obviousness where, as here, the prior art expressly teaches the claimed approach and demonstrates its functionality. Selecting the number of epitopes to include within the ranges taught by Khanna represents a predictable variation and routine optimization of a result-effective variable, rather than an inventive departure from the prior art (see MPEP §2144.05).
Furthermore, Khanna Demonstrates Immunogenicity of Combined Epitopes. Applicant’s general allegations of unpredictability are not persuasive. Khanna demonstrates that peptide pools comprising multiple epitopes elicit functional immune responses, including IFN-γ expression, CD4+ and CD8+ T-cell activation, and expansion of virus-specific T cells (see, e.g., Figures 1, 2, 6, and 7). These disclosures support a reasonable expectation of success for multi-epitope peptide compositions. Obviousness does not require absolute predictability, but at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness (see MPEP 2143.02).
Khanna Teaches Peptide Pools and Multi-Epitope Compositions. Contrary to Applicant’s assertions, Khanna expressly teaches the use of peptide pools comprising multiple epitopes. Khanna describes peptide matrix formats and peptide pools used to stimulate virus-specific T cells (see, e.g., Figures 3 and 7). These peptide pools comprise multiple short synthetic peptides selected from the disclosed epitope tables and are used together to elicit immune responses. Accordingly, Khanna provides explicit guidance toward combining epitopes rather than merely listing them without direction.
Khanna Does Not Teach Away From Short Multi-Epitope Peptides. Applicant asserts that Khanna generally favors full-length proteins or adoptive transfer of expanded T cells. However, Khanna explicitly discloses short synthetic peptides, epitope trimming, HLA-restricted epitopes, and peptide pools for stimulating immune responses. Thus, Khanna does not criticize, discredit, or discourage the use of short multi-epitope peptide compositions and therefore does not teach away from the claimed subject matter.
Applicant asserts that the present application demonstrates unexpected results, including superior immunogenicity, polyfunctional immune responses, cross-reactivity across polyomaviruses, and broad HLA coverage, allegedly not taught or suggested by Khanna. These arguments have been considered but are not persuasive for the following reasons.
The Alleged Unexpected Results Are Not Commensurate in Scope With the Claims (see MPEP 716.02(d)). Applicant relies on functional data generated using specific JCV epitopes (SEQ ID Nos:1-21), specific peptide pools, specific HLA alleles, and specific experimental conditions (e.g., IFN-γ, IL-2, TNF, and CD107 expression in particular assays). However, the claims are not limited to these specific epitopes, peptide combinations, HLA types, concentrations, or experimental conditions. Instead, the claims broadly encompass pharmaceutical compositions comprising three or more epitopes selected from a large group of sequences (SEQ ID Nos:1-122) and two or more from SEQ ID Nos:1-21.
Accordingly, the asserted results are not commensurate in scope with the full breadth of the claims and therefore cannot overcome the prima facie case of obviousness (see In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003); MPEP §716.02). Applicant Has Not Established a Nexus Between the Alleged Results and the Claimed Features. Even assuming the reported data demonstrate enhanced or superior immunogenicity for certain embodiments, Applicant has not established a nexus between the alleged unexpected results and the claimed invention as a whole. The claims do not require the particular epitope selection strategy, peptide pool composition, or experimental conditions relied upon by Applicant to demonstrate the asserted advantages.
Without a demonstrated nexus between the evidence and what is actually claimed, the alleged results cannot rebut the obviousness rejection (see MPEP §716.01(b)).
Khanna Contemplates Multi-Epitope Pools, Short Peptides, and Cross-Reactivity. Applicant argues that the ability to target multiple polyomaviruses with a single peptide pool was unexpected and not taught by Khanna. However, Khanna expressly analyzes epitope homology, consensus sequence alignments, and hybrid epitopes spanning BKV and JCV (see, e.g., Tables 2 and 3 and Figures analyzing sequence alignments). Khanna further teaches the use of short synthetic peptides and peptide pools to elicit virus-specific T-cell responses. Thus, cross-reactivity and the use of pooled short peptides are within the scope of what Khanna teaches and investigates, even if Khanna does not describe the precise experimental outcomes reported by Applicant. Furthermore, Unexpected Results Must Be Truly Unexpected Over the Closest Prior Art (see MPEP 716.02). While Applicant characterizes the reported immune responses as “unexpected,” Khanna expressly teaches that combining multiple immunogenic epitopes in peptide pools elicits functional immune responses, including T-cell activation and cytokine production. Therefore, the general observation that pooled epitopes elicit strong immune responses would have been reasonably expected in view of Khanna’s teachings, even if the magnitude or specific profile of the response differs (see MPEP §716.02(c)).
In addition, selection of two or three or More Epitopes Represents a Predictable Variation. Khanna expressly teaches polypeptides and peptide pools comprising at least 1, 2, 3, 4, 5, 10, or more epitopes selected from Tables 1–3. In view of Khanna’s express disclosure of multi-epitope peptide pools and demonstrated immunogenicity thereof, selecting a composition comprising three or more epitopes or two or more epitopes represents a predictable variation and routine optimization of a result-effective variable, with a reasonable expectation of success (see MPEP §§2143, 2144).
Regarding claim 40, the Office acknowledges that Khanna does not teach or suggest a peptide pool comprising at least ten JCV epitopes selected from SEQ ID NOs: 1–21, and therefore claim 40 is not rejected. This distinction, however, does not apply to claims requiring only two or three or more epitopes.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6 and 8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 is rejected for indefiniteness due to internal inconsistency between the incorporated limitations of Claim 1 and the specific limitations of Claim 6. Because all limitations of Claim 1 are read into Claim 6, Claim 6 effectively reads: "A composition comprising a peptide comprising at least three or more epitopes... wherein the peptide comprises a plurality [two or more] of epitopes." A Person of Ordinary Skill in the Art (PHOSITA) is left with "reasonable uncertainty" as to the metes and bounds of the claim. If the peptide has exactly two epitopes, it satisfies the "plurality" requirement of Claim 6 but violates the "at least three" requirement of Claim 1 (which is incorporated by reference). Because the "wherein" clause in Claim 6 attempts to characterize a structure already defined in Claim 1 using a different numerical standard, the claim is ambiguous and fails to particularly point out and distinctly claim the invention. Claim 8 is also rejected due to its dependence on claim 6 and not further clarifying this point of confusion.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 is dependent on claim 1. Independent Claim 1 requires a peptide comprising "at least three or more" epitopes. Dependent Claim 6 adds the limitation that the peptide comprises a "plurality" of epitopes. Under the Broadest Reasonable Interpretation (BRI), a "plurality" is defined as "two or more." Because "two or more" (plurality) is broader than and encompasses the "three or more" already required by Claim 1, Claim 6 fails to add a narrowing limitation. A dependent claim that is broader than or identical in scope to its parent claim is improper under § 112(d). Claim 8 is also rejected due to its dependence on claim 6 and that it does not cure the underlying failure of claim 6 to properly limit the scope of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 6, 8, 26, 28 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Khanna (WO2018049165 A1, cited in IDS) in view of Scholler (WO20081164648 A2, cited in Applicant’s IDS).
The teachings of Khanna are provided in the above rejection.
Regarding claims 3 and 8, Khanna teaches of two epitopes (instant SEQ ID Nos:10 and 20) but doesn’t specifically teach a third epitope of SEQ ID Nos:1-21. However, Khanna does teach the epitope of RYWLFKGPIDSGKT which is instant SEQ ID NO:7 without a “T” following SGKT. The extra “T” can be seen in the sequence in Figure 8.
Scholler teaches closely related polypeptides differing by the addition of flanking residues are recognized as MHC-restricted epitopes, as evidenced by the disclosure of both RYWLFKGPIDSGKT and RYWLFKGPIDSGKTT as HLA-DRB1*0101 restricted epitopes (Table H page 189, see page 460, 466, 491, ninth sequence down). This demonstrates that inclusion of an additional flanking residue represents a routine and predictable variation in epitope design. Accordingly, it would have been obvious to a person of ordinary skill in the art to try and include a terminal flanking residue (“T”) in the epitope of Khanna (SEQ ID NO:40), with a reasonable expectation that the resulting peptide would retain MHC binding and immunogenicity. MPEP 2143 states when there is a finite number of identified predictable solutions, and a person of ordinary skill has a good reason to pursue the known options, the resulting invention is likely the product of ordinary skill and common sense. Furthermore, modification of the epitope disclosed in Khanna by including an additional terminal residue of the sequence represents a predictable variation resulting from routine optimization (MPEP2144).
Thus, the teachings of Khanna in view of Scholler render obvious instant claims 3 and 8 to include three or more epitopes and wherein the three or more epitopes are selected from SEQ ID Nos:1-21 (in particular, SEQ ID Nos. 7, 10, 20).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654