DETAILED ACTION
Applicant’s amendment and remarks filed April 13, 2026 are acknowledged and entered. Claim 21 remains withdrawn from consideration being directed to a non-elected species. Any prior objection or rejection that is not addressed or repeated below is withdrawn or moot in view of Applicant’s amendment.
Claims Summary
Claim 1 is directed to a method to generate an immunogenic composition against viral pathogen SARS-CoV-2. The method comprises:
Identifying non-virion-integral proteins derived HLAI restricted epitopes (non-VIP-derived HLAI-HRE) from SARS-CoV-2 by:
Using standardized donor vectors for HLA and antigen ORF constructs paired with genomic receiver sites within functionally engineered immortal cell lines that represent programmable engineered APCs (eAPCs)
The eAPCs are then screened by mass spectrometry (MS) methodologies to identify HLA-restricted antigens from integrated ORFs within the background of the intrinsic HLAI restricted repertoire derived from the eAPC proteins themselves which enables systematic analysis of the ORFs in single HLA backgrounds (monoalleleic);
It is noted that a non-VIP is any protein encoded in a viral genome that is expressed within infected host cells during the virus life-cycle and not represented within a virion (see paragraph [0301] of the published application US 2023/0145860).
It is noted that HLAI-HRE is any epitope that may be loaded specifically in an HLAI molecule for export to the cell surface for T-cell sampling (see paragraph [0291] of the published application US 2023/0145860).
It is noted that just because systematic analysis is enabled in single HLA backgrounds, no active method step is actually performed.
In the previous Office action, part a was understood to be a product-by-process type limitation, however, upon further consideration of the claim language, it is clear that the steps of using donor vectors and mass spec are active steps in the method.
Assessing immunogenicity of the identified non-VIP-derived HLAI-HRE in naïve CD8 T-cell populations isolated from donors without prior SARS-CoV-2 infection, and/or in memory CD8 T-cell populations from donors with confirmed active, latent or resolved SARS-CoV-2 infection
wherein multiple non-VIP-derived HLAI-HRE are selected for inclusion as to represent one or more HLAI-HRE in a selection of HLAI alleles that represents those alleles carried by at least 60% of individuals within the target population for which the immunogenic composition is designed (claim 16)
wherein multiple non-VIP-derived HLAI-HRE are selected for inclusion as to represent one or more HLAI-HRE in a selection of one or more HLAI alleles that is carried by an individual for which the immunogenic composition is designed (claim 17); and
Selecting non-VIP-derived HLAI-HRE with confirmed immunogenicity in naïve donors, or with observed CD8 T-cell responses in donors with confirmed active, latent or resolved SARS-CoV-2 infection; and
Providing the selected non-VIP-derived HLAI-HRE in the immunogenic composition; wherein the selected non-VIP-derived HLAI-HRE is included with priority to HLAI-HRE of non-VIP from naïve donors, or with observed CD8 T-cell responses in donors confirmed with active and/or resolved SARS-CoV-2 infection (claim 26).
The immunogenic composition comprises a vaccination vector comprising a recombinant RNA construct, with or without modified nucleotides (claim 18, elected species). The selected non-VIP-derived HLAI-HRE are incorporated into expression constructs which do not allow expression of functional non-VIP proteins in host cells upon vaccination as to avoid immunoevasion activity of said viral non-VIP (claim 19). The method by which the non-VIP proteins are not expressed is by introducing point mutations and/or sequence insertions and/or sequence deletions within full-length non-VIP ORFs that inactivate protein function, among other methods (claim 20). The recombinant RNA construct further encodes one or more B-cell/Immunoglobulin epitopes so as to prime neutralizing Ig responses (claim 22). The recombinant RNA construct further encodes one or more selected HLAII-HRE epitopes so as to prime CD4 T-cell responses to support B-cell maturation and neutralizing antibody production, and/or promote commitment of non-VIP-derived HLAI-HRE-specific CD8 T-cell responses to memory differentiation (claim 23). The one or more B-cell/Immunoglobulin epitopes have been modified to remove HLAI-HRE from the VIP so as to avoid priming CD8 T-cell responses against VIP proteins upon vaccine delivery (claim 24).
Claim Objections
Claims 1, 16-20, 22-24 and 26 are objected to for the following minor informality.
In claim 1, line 1, “a immunogenic” should be “an immunogenic” [emphasis added].
In claim 1, line 3, the phrase “identifying non-virion-integral proteins derived Human Leukocyte Antigen class I restricted epitopes” is missing a word. Suggested language: “identifying non-virion-integral protein-derived Human Leukocyte Antigen class I restricted epitopes” [emphasis added]. This captures the concept of identifying non-VIP epitopes from HLAI.
In claim 1, part a, the phrase spanning “that are then screened…and enables systematic analysis” is grammatically unclear. Suggested language: “that are then screened…which enables systematic analysis”.
In claim 1 parts b and c, and claim 26, the recitations of “target virus” should be changed to “SARS-CoV-2” because there is no other mention of a “target virus”.
In claim 1 parts b and c, the recitation of “latent” virus infection in the context of SARS-CoV-2 should be removed since SARS-CoV-2 does not go latent. It is believed that this is residual language from when the claim was generic to all viruses, some of which go latent.
In claim 1, last line, the phrase “wherein the viral pathogen is SARS-CoV-2” is redundant and should be removed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 18-20 and 22-24 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method to generate an immunogenic composition against SARS-CoV-2, does not reasonably provide enablement for generating a vaccine against SARS-CoV-2. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
It is acknowledged that Applicant’s amendment filed April 13, 2026 removed most instances of “vaccine”, however, all instances of “vaccination vectors”, “vaccination” and “vaccine delivery” should also be removed in claims 18, 19 and 22-24. Suggested language is “vectors” (claims 18, 19, 22 and 23) and “delivery” (claim 19). The rejection is repeated here.
The breadth of the claims encompasses a method to generate a vaccine based on certain HLAI-HRE epitopes from SARS-CoV-2 non-virion-integral proteins, discovered during the process described in claim 1. A vaccine is understood to be capable of inducing protective immunity such that a vaccinated subject will not develop disease as a result of subsequent infection with SARS-CoV-2. The nature of the invention is the generation of a vaccine comprising certain HLAI-HRE epitopes from SARS-CoV-2 non-virion-integral proteins, which will be administered to a subject with the expectation of preventing disease.
The specification provides a method, but no epitopes have been identified, nor tested for efficacy as a vaccine. The state of the art with regard to SARS-CoV-2 epitope vaccination is that it is still under development. Solanki et al. (PeerJ, 2021, 9:e11126, DOI 10.7717/peerj.11126, 29 pages) discloses an immunoinformatic approach to generate a vaccine for SARS-CoV-2 using multiple epitopes to structural and non-structural proteins, noting that while in silico results look promising, the human immune response and efficacy needs to be determined via experimentation (see abstract and page 24, top paragraph). Khan et al. (Front. Immunol, 2023, 13:1001430, DOI 10.3389/fimmu.2022.1001430, 17 pages) reports on epitopes identified through immunoinformatics design for SARS-CoV-2, also noting that in silico results need to be further evaluated in experimentation (see abstract). Basu et al. (bioRxiv, March 2, 2020, https://doi.org/10.1101/2020.02.27.967422, cited in the IDS filed 9/27/2022) also reports on an immunoinformatics method to discover epitopes for vaccination against coronavirus. Basu et al. identified an MHCI restricted epitope and an MHCII restricted epitope from the HKU24, noting that the MHCI restricted epitope is represented in certain percentages in certain populations (see section 3.3), but notes that further experimental study is required (see abstract). Thus, it is clear from the art that immunoinformatic design, while producing promising epitopes, is not predictive of the human response, outside of the epitopes being immunogenic. Challenge experiments in acceptable animal models are evidence of protective efficacy in humans.
In view of the breadth of the claims, the nature of the invention, the high level of skill in the art, the lack of working examples and limited guidance in the specification, the state of the art, and the low level of predictability to extrapolate in silico results to protective efficacy in humans, the claimed method is not enabled by the specification for the generation of vaccines against SARS-CoV-2.
Claim Rejections - 35 USC § 103
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.
Claims 1, 16, 17 and 26 remain rejected under 35 U.S.C. 103 as being unpatentable over Basu et al. (bioRxiv, March 2, 2020, https://doi.org/10.1101/2020.02.27.967422, cited in the IDS filed 9/27/2022, “Basu”) in view of Jarvis et al. (WO 2018/083316 A1, cited in the IDS filed 9/27/2022, “Jarvis”), Wan et al. (J. Virol., February 14, 2020, accepted manuscript published online December 11, 2019, 94:e0215-19, “Wan”) and Jaume et al. (J. Virol., 2011, 85(20):10582-10597). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Basu discloses a method for designing coronavirus vaccines using immunoinformatics to find epitopes from non-structural protein 4 (see abstract). Basu exemplifies the method with HKU24, a betacoronavirus, but also suggests designing the same with 2019-nCoV (SARS-CoV-2), see pages 1-2, bridging paragraph, and page 3 top three paragraphs (claim 1, aspect of generating an immunogenic composition, non-VIP-derived epitopes from SARS-CoV-2). Basu classifies the predicted epitopes, which are inherently immunogenic, being epitopes (claim 1, aspects of classifying and selecting). Further selection of the epitopes is according to MHCI restriction and HLA alleles that are highly represented, e.g., at 58.87% in the population of China (see section 3.3) (claim 1, aspect of HLAI-restricted epitopes, and claim 17).
Basu does not disclose epitopes that are represented by at least 60% of individuals in a given population, however, it would have been obvious to have selected epitopes that are represented at an even higher level that Basu’s 58.87% in order that the epitopes have a higher likelihood of being immunologically relevant and immunogenic in more people (claim 16).
Basu does not disclose the process by which the epitopes are identified as set forth in instant claim 1 step a. However, it would have been obvious to have used Jarvis’ method employing eAPCs to identify epitopes. Jarvis discloses donor vectors paired with genomic receiver sites to introduce ORFs (comprising antigens) into APCs, programmable eAPCs, that are then screened using mass spectrometry in what appears to be the background of the intrinsic HLAI restriction repertoire from the eAPC proteins themselves (see abstract and page 59, second paragraph) (claim 1, part a). One would have been motivated to use Jarvis’ tangible method in place of Basu’s theoretical method of identifying epitopes in order to make an actual determination as to the immunogenicity of the epitopes, with a reasonable expectation of success (claim 1, part c, aspect of assessing and confirming immunogenicity).
Regarding claim 1 parts b and c, and claim 26, Basu does not disclose particular populations of donors or prioritizing epitopes based on populations of donors, however, it would have been obvious to have distinguished between identified epitopes from donors that are naïve, and those that are from donors having confirmed active, latent or resolved SARS-CoV-2 infection. One would have been motivated to make such a distinction because of the problem of antibody dependent enhancement (ADE) associated with prior infection with coronaviruses, as taught by Wan and Jaume. Wan discloses ADE as an important consideration in vaccine design (see abstract), as does Jaume, for SARS-CoV (see abstract). To consider the immune status of patient populations in the determination of relevant epitopes would have been obvious to one of ordinary skill in the art. Therefore, the claimed invention would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Applicant’s arguments filed April 13, 2026 have been carefully considered but fail to persuade. Applicant’s arguments are against each reference individually. The Office acknowledges that no one reference teaches all the limitations of the claimed methods, thus the obviousness rejection and not an anticipation rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
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/STACY B CHEN/Primary Examiner, Art Unit 1672
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