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 .
Applicant's response to the previous Office action, dated August 13, 2026, has been received. By way of this submission, Applicant has amended claim 1, and cancelled claim 8.
Claims 1, 7, 9-24, and 26 are pending in the application. Claim 12 remains withdrawn from consideration, pursuant to the Restriction Requirement mailed January 15, 2026.
Claims 1, 7, 9-11, 13-24, and 26 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated May 14, 2026.
Response to Amendment
Applicant argues that Cai does not teach every aspect of the claims as amended; specifically, Cai does not teach an immunogenic composition comprising neoantigens of about 8 amino acids to 10 amino acids in length and neoantigens of about 13 amino acids to about 25 amino acids in length.
Applicant's amendments to the claims have addressed this issue, and the rejection under 35 U.S.C. 102 to Cai (Mol Cancer. 2021 Dec 13;20(1):164, cited in IDS) is hereby withdrawn.
Applicant argues that Cai and Huang do not teach every aspect of the claims as amended; specifically, Cai and Huang do not teach the claimed method of selecting neoantigens for inclusion in an initial immunogenic composition nor does it disclose any selection process of neoantigens to monitor after administration of an immunogenic composition where that composition does not include identified neoantigens. Applicant further argues that Huang does not motivate one of ordinary skill to modify the teachings of Cai to make an immunogenic composition comprising neoantigens of about 8 amino acids to 10 amino acids in length and neoantigens of about 13 amino acids to about 25 amino acids in length.
Applicant's amendments to the claims have addressed this issue, and the rejection under 35 U.S.C. 103 to Cai (Mol Cancer. 2021 Dec 13;20(1):164, cited in IDS) in view of Huang (US20200368336A1) is hereby withdrawn.
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.
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.
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.
Claims 1, 7, 9-11, 13-24, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Cai (Mol Cancer. 2021 Dec 13;20(1):164, cited in IDS) in view of Huang (US20200368336A1) and Martin (US20210145951A1). This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
Cai teaches administering to a subject an immunogenic composition, comprising a plurality of tumor-specific neoantigens, wherein each tumor-specific neoantigen corresponds to a member of a first set of tumor-associated mutations in the subject, and no tumor-specific neoantigen corresponds to a member of a second set of tumor-associated mutations in the subject (page 4: "Personalized neoantigen long‑peptide vaccine synthesis and vaccination").
Cai further teaches quantification of tumor-associated mutations, including those of the neoantigen vaccine (i.e., the first set of tumor-associated mutations in the subject) and other somatic and neoantigen mutations, both before and after administering the immunogenic composition (page 8, right column, also see Figure 3C and 4A), which is pertinent to claims 1 and 15.
Cai further teaches optimizing the neoantigen vaccination strategy in response to the growth of other tumor cells that do not carry neoantigens which are vaccinated against (page 12, left column, first paragraph: "...some tumor cells might not carry such neoantigens and thus could not be well recognized by activated T cells, resulting in growth superiority during neoantigen vaccination. Therefore, it is necessary to further strengthen the anti-recurrence efficacy and immune durability of neoantigen vaccines by optimizing the neoantigen vaccination strategy and/or combining with other treatment methods...").
Cai further teaches that circulating tumor DNA (ctDNA) can be used to quantify changes in neoantigens (page 8: "The performance of ctDNA for evaluation of immune and clinical responses" and Figure 4), which is pertinent to claim 7.
Cai further teaches that the tumor-associated mutations comprise mutations specific to the patient, and may be hotspot mutations (Figure 1B), which is pertinent for claims 10-11.
Cai further teaches that the immunogenic composition is administered at multiple time points (page 4, left column: "For neoantigen vaccination, patients ... received neoantigen vaccine on days 1, 4, 8, 15 and 22 as the prime phase and on days 90 and 140 as the boost phase."), which is pertinent to claim 16.
Cai further teaches that tumor-associated neoantigens may be quantified by whole exome sequencing (page 4, left column, last paragraph: "personalized neoantigen profiling was firstly performed for each newly diagnosed HCC patient with vascular invasion based on whole exome sequencing data..."), which is pertinent to claim 19.
Cai further teaches that new tumor-associated mutations may arise after vaccination (page 8, left column: "Meanwhile, 9 new neoantigen mutations were also found in recurrent tumor (Supplementary Table S6)."), which is pertinent to claims 18 and 26.
Cai further teaches assessing tumor-associated mutations between two and fourteen months after vaccination (Figure 2E), which is pertinent to claims 20-22.
However, Cai does not teach melanoma, neoantigens of about 8 amino acids to about 10 amino acids in length or about 13 amino acids to about 25 amino acids in length, or a ranked immunogenicity score.
Huang teaches administering personalized cancer vaccines to patients with melanoma (para. 0143). Huang incorporates Ott (Nature. 2017 Jul 13;547(7662):217-221) by reference, which teaches administering a neoantigen vaccine for patients with melanoma, based upon DNA and RNA sequencing to identify tumor-specific mutations (abstract and Figure 1).
Huang further teaches that neoantigens with high immunogenicity scores are preferred in designing a personalized cancer vaccine (para. 0151-0152), which is pertinent to claim 15.
Huang further teaches isolation of ctDNA from at least 10ml of the patient's whole blood (para. 0153), which is pertinent to claims 23-24.
Martin teaches assessing neoantigens for use in a cancer vaccine by determining binding affinity to MHC molecules, with higher likelihood of binding being more desirable for use in said vaccine (para. 0015).
Martin also teaches that suitable neoepitopes may be assessed by activation of CD8+ T cells (para. 0124).
Martin further teaches that suitable neoepitopes administered to the subject may be between 8 and 25 amino acids long (para. 0029).
Martin also teaches that such neoepitopes are useful as a pharmaceutical composition for treating melanoma (para. 0033).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Cai, Huang, and Martin to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of Cai, Huang, and Martin are concerned with personalized cancer neoantigen vaccines. Methods of vaccination with tumor-associated neoantigens and assessment of tumor mutations by whole exome sequencing of ctDNA were known in the art, according to the teachings of Cai. Huang and Martin teach that such methods are applicable to melanoma, and Martin teaches methods to assess the immunogenicity of cancer neoantigens based upon binding affinity to MHC molecules, with higher likelihood of binding being more desirable. Martin also teaches suitable lengths of said neoantigens for use in an immunogenic composition. One of ordinary skill in the art could apply the methods of Cai to the patient population of Huang by known methods, with each component of the combination performing its known, usual function to affect a predictable result.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Borden (J Immunol. 2022 Apr 1;208(7):1813-1827) teaches evaluating immunogenic neoantigens by identifying which neoantigen characteristics best predict immunogenicity, such as binding of the neoantigen with MHC class I, and integrating these characteristics into an immunogenicity score, and that this method results in improved survival for patients with melanoma (abstract).
No claim is 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.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1642
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