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
Claim listing filed on September 19, 2025 is pending. Claims 2, 4, 6-7, 11-26 and 37-85 are canceled. Claims 1, 3, 5, 8, and 27 are amended. Claims 86-91 are new. Claims 1, 3, 5, 8-10, 27-36, and 86-91 are examined upon their merits.
Withdrawn Objections and Rejections
Applicant’s cancelation of Claims 2, 4, and 6-7 have rendered all previous rejections directed to these claims moot.
The specification objections and drawing objections are withdrawn in view of Applicant’s amendments to the specification and the drawings.
The rejection of claims 1, 3, 5, 8-10, and 27-36 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments to Claims 1 and 27. In particular, amino acid SEQ ID NOs are now provided for the first and second HLA-binding peptides which overcomes the indefinite functional language.
The rejection of Claims 1, 3, 5, 8-10, and 27-36 under 35 U.S.C. 103 as being unpatentable over Fritsch et al. US 2018/0153975 in view of Cai et al. BMC Genomics 2018 is withdrawn in view of Applicant’s amendments. Specifically, neither Fritsch or Cai teach an HLA-binding peptide that comprises a L858R mutation and comprises any one of SEQ ID NOs: 365-793 as required by amended Claims 1 and 27.
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claims 1, 3, 5, 8-10, 27-36, and 86-91 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.
Claims 1 and 27 recite wherein the first and second HLA-binding peptides comprise a L858R mutation. Claims 1 and 27 also recite wherein the first HLA-binding peptide comprises at least 80% identity to any one of SEQ ID NOs: 1-364 and the second HLA-binding peptide has at least 80% identity to any one of SEQ ID NOs: 365-793. Specification Tables 2-3 teach that SEQ ID NOs: 19-664 and 686-793 do not comprise a L858R mutation. Therefore, the claims simultaneously require conflicting limitations (a L858R mutation and an amino acid sequence that does not comprise a L858R mutation). The contradictory limitations render the claims indefinite, and the metes and bounds of the claims cannot be readily determined. For the purpose of compact prosecution, Claims 1 and 27 and dependent claims will be interpreted wherein the first HLA-binding peptide comprises at least 80% identity to any one of SEQ ID NOs: 1-18 and the second HLA-binding peptide has at least 80% identity to any one of SEQ ID NOs: 665-685 because SEQ ID NOs: 1-18 and 665-685 comprise the L858R mutation.
Claim Rejections - 35 USC § 112 (Maintained)
The rejection of Claims 1, 3, 5, 8-10, 27-36, and 86-89 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 is maintained. The claims contain 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. Note, the rejection of record applied to Claims 1, 3, 5, 8-10, 27-36 and now applies to Claims 1, 3, 5, 8-10, 27-36, and 86-89 due to Applicant’s amendments.
The claims are directed to a genus of first HLA-binding peptides comprising at least 80% identity to SEQ ID NOs: 1-18 and a genus of second HLA-binding peptides comprising at least 80% identity to any one of SEQ ID NOs: 665-685 (Claims 1 and 27). Claims 86-87 recite wherein the first and second HLA-binding peptides comprise at least 90% identity to SEQ ID NOs: 1-18 and SEQ ID NOs: 665-685, respectively. Claims 88-89 recite wherein the first and second HLA-binding peptides comprise SEQ ID NOs: 1-18 and SEQ ID NOs: 665-685, respectively, with at most 3 amino acid substitutions.
The claims are still directed to a genus of possible HLA-binding peptides with significant variation. For example, 90% sequence identity to SEQ ID NO: 665 means that any combination of 2 amino acids can be inserted, deleted, or substituted with any other amino acid (10% of 21 amino acids). There are thousands of possible variations in SEQ ID NO: 665 alone. The specification provides no guidance for how 20%, 10% or 3 amino acids can be inserted, deleted, or substituted such that the functional properties of the HLA-binding peptides are maintained.
Applicant's arguments filed September 19, 2025 have been fully considered but they are not persuasive. Applicant argues that the amendments further define the claimed peptides with structural specificity by identifying the SEQ ID NOs of the claimed peptides. This argument is not persuasive because the claims encompass at least 80% identity, at least 90% identity, or at most 3 amino acid substitutions to SEQ ID NOs: 1-18 and 665-685 which still encompasses a genus of possible HLA-binding peptides that are not described in the specification in such a way to convey to one of ordinary skill that the inventor was in possession of the claimed genus at the time of filing.
Claims 1, 3, 5, 8-10, 27-36, and 86-89 are 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 HLA-binding peptides comprising 100% identity to SEQ ID NOs: 1-18 and 665-685 (Claims 90-91) and those known in the art prior to the time of filing, does not reasonably provide enablement for the genus of HLA-binding peptides comprising at least 80% identity, at least 90% identity, or at most 3 amino acid substitutions to SEQ ID NOs: 1-18 and 665-685 (Claims 1, 3, 5, 8-10, 27-36, and 86-89). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claims are directed to a genus of first HLA-binding peptides comprising at least 80% identity to SEQ ID NOs: 1-18 and a genus of second HLA-binding peptides comprising at least 80% identity to any one of SEQ ID NOs: 665-685 (Claims 1 and 27). Claims 86-87 recite wherein the first and second HLA-binding peptides comprise at least 90% identity to SEQ ID NOs: 1-18 and SEQ ID NOs: 665-685, respectively. Claims 88-89 recite wherein the first and second HLA-binding peptides comprise SEQ ID NOs: 1-18 and SEQ ID NOs: 665-685, respectively, with at most 3 amino acid substitutions.
The specification is enabled for HLA-binding proteins comprising 100% identity to SEQ ID NOs: 1-18 and 665-685 (Tables 2-3). However, there is no support in the Applicant’s disclosure leading one of ordinary skill to overcome the lack of predictability in the genus of amino acid variations claimed. The specification provides no guidance or direction for which 20%, 10%, or 3 amino acid residues may be inserted, deleted, or substituted such that the functional properties of the invention are preserved (stimulating a therapeutic anti-cancer immune response).
Given that the nature of the claims is in vivo treatment, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials or in animal models, that are predictive of treatment by administering a representative number of HLA-binding peptide variants for each amino acid sequence in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the treatment with a reasonable expectation of success.
Applicant's arguments filed September 19, 2025 have been fully considered but they are not persuasive. Applicant argues that the amendments further define the claimed peptides with structural specificity by identifying the SEQ ID NOs of the claimed peptides. This argument is addressed in the written description rejection above.
Claim Rejections - 35 USC § 103 (New, necessitated by amendment)
Claims 1, 3, 5, 8-10, 27-36, and 86-91 are rejected under 35 U.S.C. 103 as being unpatentable over Fritsch et al. US 2018/0153975 (of record) in view of Cai et al. BMC Genomics 2018 (of record) and Petit WO 2018/102584.
In regard to Claims 1, 8-10, 27, and 32-36, Fritsch teaches a method of treating cancer by administering at least one neoantigenic peptide capable of binding to an HLA protein and comprising a tumor-specific mutation that is present in the patient’s tumor (paragraph [0010]). The patient can be concurrently treated with erlotinib or gefitinib (paragraph [0014]) which are both known EGFR inhibitors. Fritsch specifically teaches wherein the patient has EGFR mutant cancer and can be treated with a range of HLA class I-binding EGFR mutant peptides (paragraph [0760] and Table 4). Fritsch teaches that the therapeutic composition comprises at least one neoantigenic peptide, possibly more than 100 neoantigenic peptides, but preferably includes about 20 neoantigenic peptides (paragraph [0010]). When more than one neoantigenic peptide is used, each peptide can bind to either HLA class I or HLA class II (HLA-A, -B, -C, -DRB) (paragraph [0021] and further supported by paragraphs [0073]-[0075]). Because Fritsch teaches combining a plurality of peptides specific for different HLA classes, the specific combinations of peptides outlined in the instant claims are made obvious. One of ordinary skill would understand that the compositions can vary in exact number of HLA class I-binding peptides and HLA class II-binding peptides.
In regard to Claims 1, 27, and 86-91, Fritsch teaches two HLA class I-binding peptides from EGFR comprising an L858R mutation comprising KITDFGRAK and FGRAKLLGA which are 100% identical to instant SEQ ID NOs: 4 and 6 respectively (Table 9, pages 94 and 100).
In regard to Claims 3 and 30, Fritsch teaches wherein the HLA class I-binding EGFR mutant peptides are 8-10 amino acids in length (Table 4).
In regard to Claims 28-29, the neoantigen peptide compositions can be formulated as pharmaceutical compositions with acceptable carriers such as saline (paragraphs [0553] and [0555]).
Fritsch conceptually teaches compositions comprising both HLA class I-binding peptides and HLA class II-binding peptides, but fails to specifically teach EGFR L858R mutant peptides that bind HLA class II comprising 13-30 amino acids (Claims 5 and 31) and comprising any one of SEQ ID NOs: 665-685 (Claims 1, 27, and 86-91).
However, Cai teaches HLA class II-binding peptides comprising the EGFR L858R mutation comprising ITDFGRAKLLGAEEK which is 15 amino acids in length (Table 3). Further, Petit teaches heteroclitic (antigenic) peptides that generate an immune response by binding to HLA class I or HLA class II molecules (paragraphs [0249]-[0252]). Petit specifically teaches an antigenic peptide comprising the EGFR L858R mutant comprising SEQ ID NO: 405 which is 100% identical to instant SEQ ID NO: 667 (paragraph [00699] and Table 3).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to adapt the method of treating cancer by administering an HLA class I-binding peptide, an HLA class II-binding peptide, and an EGFR inhibitor as taught by Fritsch to specifically comprise the HLA class II-binding peptides taught by Cai and Petit. Cai teaches an HLA class II-binding peptide comprising the EGFR L858R mutation, and Petit teaches an EGFR L858R mutant peptide comprising a sequence that is 100% identical to instant SEQ ID NO: 667. Thus, the method of treatment was known in the art prior to filing and the specific HLA-binding peptides encompassed by the claims were also known in the art prior to the time of filing. One of ordinary skill in the art could have combined the known HLA-binding peptides as claimed by known methods of treatment, and in combination, each element merely performs the same function as it does separately, namely stimulating an anti-cancer immune response against tumor cells comprising an EGFR L858R mutation. As taught by Fritsch, different patient populations have different HLA subtypes, and it is advantageous to use a variety of HLA-binding peptides to stimulate an effective immune response against the cancer cells (Fritsch paragraph [0011]).
Applicant's arguments filed September 19, 2025 have been fully considered but they are not persuasive. Applicant argues that based on Fritsch’s disclosure, a skilled artisan would not have been able to develop a treatment method or composition that comprises a “first HLA-binding peptide from EGFR [that] binds to a HLA class I molecule” and a “second HLA-binding peptide from EGFR [that] binds to a HLA class II molecule.” As outlined above, Fritsch does teach a treatment method and composition comprising a first HLA-binding peptide from EGFR that binds to a HLA class I molecule and a second HLA-binding peptide that binds to a HLA class II molecule. Examiner relies on Cai and Petit to teach wherein the HLA class II-binding peptide is specifically from EGFR. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references (MPEP § 2145.IV), and the argument is not persuasive.
Applicant argues that Cai does not propose any treatment method of composition that comprises both a HLA class I-binding peptide and a HLA class II-binding peptide. Applicant further argues that Cai does not teach a peptide comprising any one of SEQ ID NOs: 365-793. Examiner relies on Fritsch to teach the method of treatment and composition of the instant claims and relies on Petit to teach SEQ ID NO: 667. As stated above, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references (MPEP § 2145.IV). Applicant arguments have been considered but are not persuasive.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675