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 .
Response to Amendment
Applicant’s amendment filed 04/01/2026 is acknowledged. Claims 1, 5-8 and 21 are amended, claims 3 and 32 are newly canceled and claims 39 and 40 are new. Claims 5-8 have been amended to recite the elected species of SEQ ID NO: 3, and therefore are rejoined herein. It is noted that Applicant amended claim 16, but did not indicate the claim was amended. See 37 CFR 1.121, which contains guidance for the manner of making amendments to the claims. Specifically, amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. In the 08/30/2022 claim set, claim 16 recited “[t]he method of claim 14”. In the 04/01/2026 claim set, claim 16 recites “[t]he method of claim 14 or 15”. This change must be marked by underlining “or 15”.
Claims 1, 2, 4-14, 16-18, 20, 21, 39 and 40 are under examination insomuch as they read upon the elected invention.
Objection/Rejections Withdrawn
Any previous rejections over claim 3 is hereby withdrawn in response to Applicant’s cancelation of that claim.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
The objection to claim 1 for minor informalities is withdrawn in response to Applicant’s amendment simplifying the claim language.
Rejection Withdrawn
Claim Rejections - 35 USC § 103
The rejection of claims 1, 2, 4, 14, 16-18, 20 and 21 under 35 U.S.C. 103 as being unpatentable over Lewinsohn (WO2011063283) in view of Bremel (US20130330335) is withdrawn upon further consideration. Applicant argues persuasively at pages 8-10 of the Remarks filed 04/01/2026 that the secondary reference by Bremel lists nearly 200,000 binding peptides from different M. tuberculosis strains. There is nothing in Bremel that points the person of ordinary skill in the art towards the recited peptides over the nearly 200,000 disclosed therein. Further, Applicant presents evidence in the form of reference by Patronov (Open Biol. 2013 Jan 8;3(1):120139) that predicting MHC binding is complex and one having ordinary skill in the art would have no reasonable expectation of success in arriving at the peptides recited in the claims.
Rejection Maintained
Claim Rejections - 35 USC § 112(a)
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.
The rejection of claims 1-4, 11-14, 16-18, 20 and 21 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement is maintained. Further, rejoined claims 5-7 and new claim 39 are hereby included in this rejection. The inclusion of the rejoined and new claim is necessitated by Applicant’s amendment. As noted in the previous Office action mailed 10/07/2025, the specification, while being enabling for the claimed methods in which the 8-18mer Mycobacterium peptides comprise an amino acids sequence having 95% sequence identity to the recited peptide(s), does not reasonably provide enablement for the claims as broadly recited is maintained for reasons of record. Claims 11-13 were inadvertently left out of the statement of the rejection in the previous Office action mailed 10/07/2025 (p. 9), however, they were included in the rejected claims on the PTO-326 form and the issues regarding the scope of enablement of those claims were raised previously (see pages 8-11), therefore no new issues are raised herein. 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 or use the invention commensurate in scope with these claims.
The rejection at pages 8-11 of the Office action mailed 10/07/2025, hereby incorporated, outlines that claims 1-4, 11-14, 16-18, 20 and 21 recite 70% sequence identity to the recited peptides, although the instant specification does not provide any guidance as to how 30% of the peptide(s) can be mutated while preserving the ability to elicit an immune reaction. Amended and rejoined claims 5-7 encompass 75%-85% of the peptides, respectively and new claim 39 recites 90% sequence identity.
Response to Arguments
Applicant argues at p. 11, that the person of ordinary skill in the art can change up to 4 amino acids to the sequence in M. tuberculosis peptides without undue experimentation, citing to a 1987 article by Bjorkman and colleagues. Applicant argues that changes outside the non-amino acid core motif do not “often” disrupt T cell binding and “[n]on-anchor positions are highly permissive, and structural flexibility allows diverse sequences to adopt a binding-competent conformation”.
This argument has been fully considered, but is not found persuasive. The claims are not drawn to the peptides themselves, but rather detecting an immune response to Mycobacterium tuberculosis in a subject. The preponderance of evidence of record suggests that even small changes in immunogenic peptides can alter their contact with T cell receptors (see Fukui et al. (PNAS, 2000; 97(25): 13760-13765—of record; see abstract; p. 13765, whole page). See also Lee et al. (Front. Immunol. 2020 11:565096—of record), who teach that “TCR recognition of pMHC complexes is both cross-reactive, given the high number of total epitopes that could be bound, and at the same time, highly specific considering the low frequency of epitopes that can be recognized by a given TCR” (see paragraph bridging pages 2-3). In addition, while Lee et al. report that advances in in silico techniques for screening antigenic peptides has improved, “the picture is far from complete”, noting that nearly a year following the effective filing date of the instant application, “it is not possible to, (a) predict TCRs recognizing a given antigen, or (b) predict antigens recognized by a given TCR” (see p. 2, left column, 1st full paragraph). Applicant also submitted the paper by Patronov (Open Biol. 2013 Jan 8;3(1):120139) as an appendix in the response filed 04/01/2026. Patronov teaches that “[a]ll T-cell epitopes are good MHC binders, but not all good MHC binders are T-cell epitopes” (see p. 3, left column, 4th paragraph). (Patronov is made of record herein by the examiner).
The article by Bjorkman et al. presented as evidence of enablement is focused on foreign antigen binding site and T cell recognition regions of class I histocompatibility antigen, HLA-A2, and does not address the non-amino acid core motif or non-anchor residues. Patronov discusses the motif-based approach for predicting peptides, but concludes it is outdated, only has an accuracy of about 60-70% and “[i]n many cases, the correlation between the predicted and the experimentally determined affinities is very weak [and] a large number of wrongly identified false positives, while some of the actual epitopes are predicted as non-binders” (see pages 3-5 under 5.1.1 Motif search-based approach).
Applicants have provided little or no guidance beyond the mere presentation of sequence data to enable one of ordinary skill in the art to determine, without undue experimentation, the positions in the protein which are tolerant to change by amino acid substitutions or deletions, and the nature and extent of changes that can be made in these positions. Although the specification outlines art-recognized procedures for producing and screening for active muteins, this is not adequate guidance as to the nature of active derivatives that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation.
Due to the large quantity of experimentation necessary to generate and test the encompassed Mycobacterium peptide(s) capable of eliciting an immune response, the lack of direction/guidance presented in the specification regarding, and the absence of working examples directed to the same, the unpredictability of the effects of mutation on protein structure and function, and the breadth of the claims which fail to recite limitations on the peptide(s), undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
New Rejection
Claim Rejections - 35 USC § 112(b)
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.
Claim 16 is 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. This rejection was necessitated by Applicant’s amendment. Claim 16 has been amended to recite the method depends from claim 15 in the alternative, however, claim 15 is canceled. Therefore, the metes and bounds of this embodiment of claim 16 cannot be known.
Claim Objections
Claims 8-10 and 40 are 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. Further, a comma between “peptides” and “each”, for example, in claim 10, would improve the flow of the claim.
Conclusion
Claims 1, 2, 4-7, 11-14, 16-18, 20, 21 and 39 are rejected and claims 8-10 and 40 are objected to.
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 CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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