DETAILED ACTION
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 .
Claim Status
Applicant’s amendments received 29DEC2025 are acknowledged.
Claims 3, 5-7, 14, and 18 have been canceled.
Claim 1 has been amended.
Claims 1-2, 4, 8-13, 15-17, and 19-20 are pending in the instant application (i.e., Claim(s) 1 is/are independent).
Claims 9, 11-13, 15-17, and 19-20 remain withdrawn.
Claims 1-2, 4, 8, and 10 are examined on the merits.
Priority
The present application claims priority under 35 USC §119(e), which claims benefit of US Provisional Patent Application No. 63/189861, filed 18MAY2021 and US Provisional Patent Application No. 63/308568, filed 10FEB2022. Applicant’s claim for the benefit of prior-filed applications is acknowledged.
Withdrawn Rejections
35 USC §103
Applicant’s arguments, see p 5-7, Claim Rejections—35 USC §103 section, filed 29DEC2025, with respect to the rejection(s) of claim(s) 1-2, 4, 8, and 10 under 35 USC §103 have been fully considered and said rejections of claim(s) 1-2, 4, 8, and 10 have been withdrawn in view of the claim amendments filed as part of said response.
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 1-2, 4, 8, and 10 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 1 recites the limitation "…a transgene encoding a plurality of peptides and a PDL1 miRNA and packaged in the vector, wherein the peptides in order comprise:…wherein the at least one tumor antigen is a shared neoantigen (neoAg) or a neoAg/aeTSA comprising the neoAg and an aberrantly expressed TSA (aeTSA)…wherein the neoAg comprises amino acid sequences of SEQ ID NOs: 25-32; wherein the neoAg/aeTSA comprises amino acid sequences of SEQ ID NOs: 13-19." which in this case lacks antecedent basis because the peptides referred to in 5 of the claim are the plurality of peptides and the neoAg/aeTSA amino acid sequences comprising the neoAg and aeTSA do not comprise the neoAg sequences, which in this instance comprise SEQ ID NOs: 25-32. Claims 2, 4, 8, and 10 are also rejected since they depend from claim 1, but do not remedy this deficiency.
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.
Written Description
Claims 1-2, 4, 8, and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
In this instance, one of ordinary skill in the art would conclude that the Applicant was in possession of:
“A vaccine, comprising:
a vector, wherein the vector is an adeno-associated virus 2 (AAV2) vector or an adeno-associated virus 6 (AAV6) vector;
a transgene encoding a plurality of peptides, wherein the plurality of peptides in order comprise:
an IL12 secretion signal peptide set forth in SEQ ID NO: 11;
at least eight shared neoantigen peptides (neoAg) comprising the amino acid sequences set forth in SEQ ID NOs; 25, 26, 27, 28, 29, 30, 31, and 32 or at least eight shared neoAg and at least eight aberrantly expressed tumor-specific antigen (aeTSA) peptides (neoAg/aeTSA) set forth in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 27, 18, and 19;
at least one co-inhibitory peptide, wherein the at least one co-inhibitory peptide comprises a programmed cell death protein-1 (PD-1) trap set forth in SEQ ID NO: 22; and
a toll-like receptor 9 (TLR9) antagonist peptide set forth in SEQ ID NOs: 20 and 21; and
a PD-L1 miRNA comprising SEQ ID NO: 24;
wherein the plurality of peptides and the PD-L1 miRNA are packaged in the vector” at the time the instant application was filed.
Although claim 1 is drawn to a vaccine comprising essentially any secretion signal peptide, the neoAg/aeTSA peptides comprising SEQ ID NOs: 25-32 and 13-19, any PD1 and/or CTLA4 trap, any TLR9 antagonist, and any PDL1 miRNA all packaged in a single AAV2 or AAV6 vector, the working examples teach a vaccine construct consisting of specific SEQ ID NOs. For example, working examples 16 and 13 support the full neoAg and neoAg/aeTSA vaccine constructs set forth in SEQ ID NOs: 11, 25-32, 22, 20, 21, and 24 or SEQ ID NOs: 11, 1-8, 13-19, 22, 20, 21, and 24, respectively (Fig 11A and ¶0085 and Fig 10A and ¶0077, respectively). The specification further teaches that the shared neoantigens of SEQ ID NOs: 25-32 are profiled from the mouse mammary cell line, 4T1 (Table 12), whereas the neoAg/aeTSA of SEQ ID NOs: 1-8 and 13-19 are profiled from the mouse colon carcinoma cell line, CT26 (Tables 1 and 4). Furthermore, the specification teaches that comparison of tumor volume reduction between Example 16 (i.e., SEQ ID NOs: 11, 25-32, 22, 20, 21, and 24) and Comparison 10 (i.e., SEQ ID NOs: 11, 22, 20, and 21) was negligible (i.e., approximately 1.8 cm3 vs 2.0 cm3) in 4T1 tumors (Fig 11B), which suggests that the efficacy of the vaccine construct of Example 16 alone is minimal in tumors comprising said neoantigen profiles. Although there was a more pronounced effect in tumor volume reduction (i.e., approximately 1.8 cm3 vs 2.5 cm3, Fig 10C) in CT26 tumors upon administration of Example 13 (i.e., SEQ ID NOs: 11, 1-8, 13-19, 22, 20, 21, and 24) vs Comparison 7 (i.e., SEQ ID NOs: 11, 22, 20, and 21) administered alone, it is unclear how substitution of the shared neoantigens profiled from CT26 cells as set forth in SEQ ID NOs: 1-8 to shared neoantigens profiled from 4T1 cells as set forth in SEQ ID NOs: 25-32 combined with aeTSA profiled from CT26 cells would impact the efficacy of the vaccine construct in either CT26 or 4T1 tumors. Furthermore, the prior art supports that peptide vaccines require significant optimization and screening to properly function and overcome immune tolerance, epitope loss, immune suppression, etc. (Peng, et al., Cell Mol Immunol, 2025, 22, 840-868, Peptide vaccine for cancer therapy section and Huang, et al., Cancer Immunol Res, 2023, 11, 123-136, Introduction section).
In this instance, the prior art supports that neoantigen peptide vaccine constructs require specific design strategies and significant screening to effectively function in cancer therapy. As presently written, there is no support for neoAg/aeTSA combination of SEQ ID NOs: 25-32 and 13-19 within the full construct and additionally there is no support that SEQ ID NOs: 25-32 and 13-19 would be effective in treating cancers in either 4T1, CT26, or any mammary or colorectal cancer cell line. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of neoAg/aeTSA vaccine constructs that comprise SEQ ID NOs: 25-32 and 13-19 that are able to effectively function to reduce tumor growth, at the time the instant application was filed.
Allowable Subject Matter
Examiner notes that SEQ ID NO: 19 of the aeTSA peptide sequences profiled from the CT26 cell line, and SEQ ID NOs: 25-27, 29 and 32 of the neoAg peptide sequences profiled from the 4T1 cell line are free of the prior art.
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 SAMANTHA L. HOPKINS whose telephone number is (703)756-4666. The examiner can normally be reached Mon-Thurs 6:00 AM to 4:00 PM EST.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641