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 .
Claims 24-28, 30-31 and 33-38 are under consideration.
Rejections Withdrawn
All 35 USC §112(a) scope of enablement rejection of claims 24-28 and 30-31 has been withdrawn in view of claim amendments.
The 35 USC § 101 rejection of claims 24, 35-36 and 38 has been withdrawn in view of claim amendments.
The 35 USC § 103 rejection of claim 38 as unpatentable over Juneja (Juneja, et al., US 11,793,867 B2; Issued 10/24/2023; Priority to 12/18/2017 by way of US 62/607,148, of record) has been withdrawn in view of claim amendment.
Rejections Maintained
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.
24-28, 30-31 and 33-38
Claim(s) 24-28, 30-31 and 33-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Juneja (Juneja, et al., US 11,793,867 B2; Issued 10/24/2023; Priority to 12/18/2017 by way of US 62/607,148, of record).
Juneja teaches on the subject of immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes as well as polynucleotides encoding said peptides (Juneja, Abstract). Regarding claim 24, Juneja teaches a TP53 peptide sequence having Juneja’s SEQ ID NO: 108, which is a 100% match for instant SEQ ID NO: 6 (Juneja, Table 1, p 103, entry 2) as well as a TP53 peptide having Juneja’s SEQ ID NO: 111, which is a 100% match for instant SEQ ID NO: 4 (Juneja, Table 1, p 104, entry 4) as well as a TP53 peptide having Juneja’s SEQ ID NO: 109, which comprises 85 consecutive amino acids of instant SEQ ID NO: 2 (Juneja, Table 1, p 104, entry 2), with all three peptides having multiple HLA I binding allele examples being listed next to the entries for all three TP53 peptides (this satisfies the MHC limitation of claim 24 because the HLA system is the human version of the MHC system) and with all three peptides being indicated for the same exemplary cancers (e.g., BRCA, CRC, LUAD, etc…; see column 4 in Juneja reference). Regarding claim 34, Juneja teaches that the peptides of Juneja are administered in methods of treating cancers (Juneja, Col. 2, lines 58-65) and as discussed in the previous sentence, the peptides of Juneja’s SEQ ID NOs: 108, 109 and 111 are indicated for the same diseases. Regarding claims 27-28, Juneja teaches that the vaccine of Juneja is a polynucleotide vaccine comprising a vector that is a viral vector (Juneja, Col. 167, lines 1-36). Regarding claim 31, Juneja teaches that the composition of Juneja further comprises a vaccine adjuvant (Juneja, Col. 21, lines 5-25). Regarding claim 30, Juneja teaches that the composition of Juneja further comprises a checkpoint inhibitor, an antibody or a chemotherapeutic agent (Juneja, Col. 28, lines 1-18). Regarding claims 35-36, Juneja teaches that the vaccine of Juneja is an RNA-based vaccine that comprises mRNA (Juneja, Col 167, Lines 18-21). Regarding claim 37, Juneja teaches that the vaccine of Juneja is an RNA replicon (Juneja, Col. 138, Lines 27-29). Juneja also teaches that next generation sequencing (NGS) technology, which is capable of delivering nucleic acid sequence information of a whole genome in very short periods of time are used to identify the tumor-specific mutations in the method of Juneja (Juneja, Col. 105, lines. 38-63). Juneja also teaches compositions comprising multiple different protein (Juneja, col 108, lines 33-37).
Juneja does not teach a single polypeptide comprising the sequences of instant SEQ ID NO: 4 and SEQ ID NO: 6 as well as SEQ ID NO: 109 of Juneja linked to each other. Juneja does not teach a method for providing a vaccine for immunizing a patient against cancer comprising determining the sequence of TP53 in cancer cells of said cancer and, when the determined sequence(s) produce neoantigens having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 6 and SEQ ID NO 109 of Juneja, which comprises 85 consecutive amino acids of instant SEQ ID NO: 2, then providing a vaccine comprising peptides of instant SEQ ID NO: 4 and SEQ ID NO: 6 as well as a peptide of SEQ ID NO: 109 of Juneja.
It would be prima facie obvious to one of ordinary skill in the art to link the peptide of instant SEQ ID NO: 4 taught by Juneja to the peptide of instant SEQ ID NO: 6 also taught by Juneja and the peptide of Juneja’s SEQ ID NO:109 together to form a single polypeptide in view of the teachings of Juneja. One of ordinary skill in the art would be motivated to do this in order to treat the cancers associated with these mutations (BRCA, CRC, LAUD, PRAD, HSNC, etc.… see column 4 of Table 1 of Juneja reference-- 104, entry 4 for SEQ ID NO: instant 4; p 103, entry 2 for instant SEQ ID NO:6; p 104, entry 2 for SEQ ID NO: 109 of Juneja). Juneja teaches that instant SEQ ID NOs 4 and 6 and Juneja’s SEQ ID NO: 109 are all neoantigens arising from TP53 and are associated with the same exemplary cancers. Juneja also teaches that the composition of Juneja may comprising a single polypeptide containing multiple different neoantigen associated with the same protein as the first. One of ordinary skill in the art would have a reasonable expectation of success forming a single polypeptide comprising instant SEQ ID NO: 4, instant SEQ ID NO: 6 and Juneja’s SEQ ID NO: 109 because: 1) Juneja teaches that SEQ ID NO: 4, instant SEQ ID NO: 6 and Juneja’s SEQ ID NO: 109 are all neoantigens of the TP53 gene and are associated with the same exemplary cancers, 2) Juneja teaches single polypeptides containing multiple different neoantigen from the same protein, 3) one of ordinary skill in the art would reasonably deduce that the resultant single peptide comprising the three neoantigens would be useful for treating the cancers associated with these neoantigens because the single polypeptide comprising the three neoantigens would give rise to antibodies against all three neoantigens and that this means the single polypeptide comprising the three neoantigens would produce an anti-cancer immune response against cancer cells having only one of the neoantigens.
It would be prima facie obvious to one of ordinary skill in the art to use the NGS sequencing technology taught by Juneja to determine the sequence of TP53 in cancer cells of a patient and, if the determined sequence(s) produce neoantigens having amino acid sequences of instant SEQ ID NO: 4 and SEQ ID NO: 6 as well as SEQ ID NO: 109 of Juneja linked to each other, then providing the vaccine comprising a peptide of instant SEQ ID NO: 4 and a peptide of instant SEQ ID NO: 6 as well as a peptide of SEQ ID NO: 109 of Juneja also taught by Juneja. One of ordinary skill in the art would be motivated to do this in order to better treat cancer. Juneja teaches vaccines comprising TP53 tumor-specific neoantigenic peptides that are the same as the instant claimed peptides of SEQ ID NO: 4 and SEQ ID NO: 6 as well as a peptide of SEQ ID NO: 109 of Juneja. Juneja also teaches that the NGS sequencing technology also taught by Juneja is used to identify the tumor-specific mutations in the method of Juneja and that the NGS sequencing technology of Juneja is capable of sequencing entire genomes in very short periods of time. One of skill in the art would have a reasonable expectation of success using the NGS sequencing technology taught by Juneja to determine the sequence of TP53 in cancer cells of a patient and then providing a vaccine comprising the peptides of SEQ ID NO: 4 and a peptide of SEQ ID NO: 6 as well as a peptide of SEQ ID NO: 109 of Juneja also taught by Juneja if the NGS sequencing produce(s) neoantigens having amino acid sequences of instant SEQ ID NOs: 4 and 6 as well as Juneja’s SEQ ID NO: 109, because: 1) Juneja teaches that the NGS sequencing technology of Juneja can sequence very large (genome-sized) sequences very quickly, 2) One of ordinary skill in the art would reasonably deduce that the NGS sequencing of Juneja could tell whether or not the cancer cells comprise the mutations that give rise to the sequences of instant SEQ ID NOs: 4 and 6 as well as the sequence of Juneja’s SEQ ID NO: 109 and 3) one of ordinary skill in the art would reasonably deduce that the presence of TP53 mutations giving rise to sequences of instant SEQ ID NOs: 4 and 6 and also Juneja’s SEQ ID NO: 109, then a peptide vaccine comprising instant peptides of SEQ ID NOs: 4 and 6 and Juneja’s SEQ ID NO: 109 would be effective in that specific patient.
Response to Arguments
Applicant's arguments filed 02/23/2026 have been fully considered but they are not persuasive.
Applicant’s arguments are centered around Applicant’s contention that the peptides taught by Juneja comprising amino acid sequences of Juneja’s SEQ ID NOs: 108, and 111, which are 100% matches for SEQ ID NOs: 4 and 6, respectively, as well as Juneja’s SEQ ID NO: 109, which comprises the first 85 amino acids of instant SEQ ID NO: 2, are “mutation sequence contexts” and not neoantigenic peptides suitable for vaccination. Applicant further argues that Juneja’s affirmatively teaches that when multiple neoantigens are combined in the methods of Juneja, they are derived from the same mutation, with Applicant specifically referencing Juneja arguing that Juneja states that:
“a composition may comprise ‘a first peptide comprising a first neoepitope’ and ‘a second peptide comprising a second neoepitope’, ‘wherein the first neoepitope comprises a mutation and the second neoepitope comprises the same mutation’ (Juneja, col. I, II, 63-67, emphasis added)”
(p 6, ¶ 1, Remarks of 02/25/2026)
Note: Plain text = Applicant’s wording; Italicized text = direct quoting of Juneja by Applicant; Underlined text = emphasis added by Applicant
Applicant attempts to differentiate the instant claimed TP53 peptide-based method from the TP53 peptide-based method of Juneja by emphasizing that the claimed TP53 peptides are derived from different frameshift mutations frequently shared among cancer patients. Applicant emphasizes that such a combination of antigens arising from different mutations is not disclosed or suggested by Juneja and that the claimed method comprising confers distinct and nonobvious advantage of Juneja—by targeting multiple prevalent TP53 frameshift mutations, Applicant argues that the claimed vaccine may be prepared and tested in advance, enabling rabid administration following tumor sequencing and diagnosis. Applicant concludes by pointing out that nothing in Juneja teaches or suggests designing a vaccine suitable for patients with different TP53 frameshift mutations nor does Juneja teach the relative frequency of mutations found in cancer patients and that Juneja’s individualized, mutation specific paradigm is fundamentally incompatible with the broad, population-based strategy of the instant claimed invention.
Regarding Applicant’s arguments Applicant’s arguments that the sequences of Juneja articulated in the prior Office Action (Juneja’s SEQ ID NOs: 108, 109 and 111) are “mutation contexts” and not neoantigenic peptide sequences suitable for an anti-cancer vaccine, Juneja teaches regarding longer peptides of Juneja that arise in frameshift mutations, teaching that when sequencing reveals a long (>10 residue) neoantigenic sequence is present due to a frameshift mutation, a longer peptide of Juneja could comprise the entire stretch of tumor-specific amino acids, with the use of such longer peptides presumed to allow for endogenous processing by patient cells, leading to more effective antigen presentation (Juneja, col 107, lines 15-34). These teachings of Juneja clearly demonstrate that longer therapeutic peptides that comprise the entire stretch of the tumor-specific amino acid sequence are not excluded as therapeutic peptides of Juneja.
Regarding Applicant’s arguments that Juneja “teaches away” from vaccines comprising peptides derived from more than one mutation, Juneja also teaches that embodiments of the inventive peptides of Juneja comprise at least one additional mutation that is not a mutation in the first or second neoepitope (Juneja, col 109, line 7-27). As such, Juneja does not teach away from compositions comprising peptides from more than one mutation. Regarding Applicant’s arguments related to the “paradigm” of individualized medicine present in the instant claims, first and foremost this “paradigm” is not a requirement of the instant claims. Additionally, the rejection above is an obviousness type rejection and Juneja teaches three TP53 mutations and indicates each of these mutations as being associated with the same types of cancers (BRCA, CRC, LAUD, PRAD, HSNC, etc.… see column 4 of Table 1 of Juneja reference-- 104, entry 4 for SEQ ID NO: 4; p 103, entry 2 for instant SEQ ID NO:6; p 104, entry 2 for SEQ ID NO: 109 of Juneja).
This shared property taught by Juneja creates sufficient motivation for one of skill in the art to combine these three neoantigenic mutations based on the fact that they are all associated with the same collection of cancers.
Allowable Subject Matter
Claim 38 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Instant claim 38 depends on instant claim 24, with both instant claims 38 and 24 being directed to a vaccine comprising peptides having amino acid sequences of instant SEQ ID NOs: 2, 4 and 6 and a pharmaceutically acceptable excipient as well as an adjuvant or therapeutic agent. The difference between instant claims 24 and 38 is that instant claim 24 permits the vaccine to comprise immunogenic fragments of the peptides of SEQ ID NOs: 2, 4 and 6, provided that the fragments are >= 10 contiguous amino acids in length and instant claim 38 does not permit the vaccine to comprise fragments.
A multi-database sequence search was performed for each of SEQ ID NOs: 2, 4 and 6. For each peptide, the next nearest prior art identified was Juneja (Juneja, et al., US 11,793,876 B2; Issued 10/24/2023; Priority to 12/18/2017 via US 62/607,148, of record).
Juneja teaches a TP53 peptide sequence having Juneja’s SEQ ID NO: 108, which is a 100% match for instant SEQ ID NO: 6 (Juneja, Table 1, p 103, entry 2) as well as a TP53 peptide having Juneja’s SEQ ID NO: 111, which is a 100% match for instant SEQ ID NO: 4 (Juneja, Table 1, p 104, entry 4) as well as a TP53 peptide having Juneja’s SEQ ID NO: 109, which comprises 85 consecutive amino acids of instant SEQ ID NO: 2 (Juneja, Table 1, p 104, entry 2), with all three peptides having multiple HLA I binding allele examples being listed next to the entries for all three TP53 peptides (this satisfies the MHC limitation of claim 24 because the HLA system is the human version of the MHC system) and with all three peptides being indicated for the same exemplary cancers (e.g., BRCA, CRC, LUAD, etc…; see column 4 in Juneja reference).
The Juneja reference teaches 100% matches for instant SEQ ID NOs: 4 and 6 but only teaches a peptide comprising the first 85 amino acids of SEQ ID NO: 2:
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(From DAV; Qy = instant SEQ ID NO: 2 ; Db = Juneja’s SEQ ID NO: 109)
Instant SEQ ID NO: 2 is a 103 amino acid long peptide and Juneja only teaches the first 85 amino acids in length, which is significant as this amounts to Juneja not teaching ~ 20% of the peptide length. There is no teaching, suggestion or motivation in the Juneja reference that would motivate a skilled artisan to envision SEQ ID NO: 109 of Juneja with amino acids RPAFKKKIVKESMKMVL (AA’s 86-103 of instant SEQ ID NO: 2) to the end to form a functional immunogenic peptide. Additionally, an STN subsequence search was performed on amino acids 86-103 of instant SEQ ID NO: 2 to check to see if it is a known sequence and/or is added or present in other immunogenic peptides. No art could be found that met the priority date. As such a vaccine comprising the immunogenic peptide of instant SEQ ID NO: 2 is not an obvious variant of Juneja or anything in the prior art and therefore is free of prior art.
Conclusion
Claims 24-28, 30-31 and 33-37 are rejected.
Claim 38 is objected to.
No claims are 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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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643