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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 13, 2026 has been entered.
Election/Restrictions
Claim 1 is allowable. The restriction requirement between groups of inventions, as set forth in the Office action mailed on 04/02/2024, has been reconsidered in view of the allowability of claims to the elected invention pursuant to MPEP § 821.04(a). The restriction requirement is hereby withdrawn as to any claim that requires all the limitations of an allowable claim. Specifically, the restriction requirement of 04/02/2024 is withdrawn. Claims 8, 13, 16, 18, and 21 directed to non-elected groups of inventions are no longer withdrawn from consideration because the claim(s) requires all the limitations of an allowable claim.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Application Status
Claims 1, 4, 8, 14-16, 18, and 21 are pending and examined on the merits herein.
Grounds of Rejection Withdrawn
Previous rejection of claims 1-3, 13-15, 29, 31, 39-42, 50, 66-70, 72-74, 76, 81,
and 84 under 35 U.S.C. 112(b) are withdrawn in view of claim amendments.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 15-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the statement “use of” or “for use” of an invention without any meaningful steps for that use does not qualify as a process, machine, manufacture or composition of matter.
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.
Claims 15-16 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 15 is drawn to use of a tumor vaccine comprising at least one neoantigenic peptide having the amino acid sequence of SEQ ID NO: 1 for treatment of an MSI-H tumor. As the claim does not set forth any steps involved in the method/ process, it is unclear what method/ process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 16 is drawn to a pharmaceutical composition for use in adoptive cell therapy to treat a tumor comprising a population of T cells expressing one or more CARs or TCRs that are reactive to at least one neoantigenic peptide having the amino acid sequence of SEQ ID NO: 1. As the claim does not set forth any steps involved in the method/ process, it is unclear what method/ process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
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.
Claims 16, 18, and 21 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. This is a written description rejection.
The teachings of the specification and the claimed invention:
Claim 16 is directed to a pharmaceutical composition for use in adoptive cell therapy to treat a tumor comprising a population of T cells expressing one or more CARs or TCRs that are reactive to at least one neoantigenic peptide having the amino acid sequence of SEQ ID NO: 1.
The issue with the claim is the one or more CAR(s) or TCR(s) that are reactive to SEQ ID NO: 1, wherein the antigen binding fragment is defined by the epitope only.
Claims 18 and 20 are dependent from claim 16 without resolving the issue identified above and therefore included in this rejection.
The instant specification does not define the structural features of the paratope-epitope binding and the residues therein that facilitate binding of an antibody to the instant claimed SEQ ID NO: 1. Claim 16, does not define the CDRs comprising the binding paratope of the antigen binding portion of the TCR/ CAR.
The instant specification discloses that treatment with the peptide consisting of SEQ ID NO: 1 will induce CD8+ T cell response and therefore TCRs that are reactive to the peptide (para 0036), but there are no specific TCRs that were determined to be reactive to that specific peptide and no sequences derived therefrom disclosed. The specification further teaches that adoptive cell therapy involved isolating lymphocytes and genetically engineering the lymphocytes to express antitumor TCRs or CARs before expansion and administration (para 0045) that in one embodiment, the subject has MSI-H endometrial cancer and the CAR or TCR is reactive to SEQ ID NO: 1 (para 0046). The instant specification further teaches that the neoantigen specific targeting region of the CAR comprises an antibody (para 0048).
The instant specification further teaches a rapid T cell activation protocol wherein healthy PBMCs were cultured and stimulated with peptides and then tested INF gamma production after restimulation (para 0084). The instant specification further teaches testing of the immunogenicity of the instant claimed peptides by priming T cells from random healthy donors with long overlapping peptide libraries and then expanding the cells, which were then tested for IFN gamma production (para 0086, Fig 2A).
There is no previous art teaching a neoantigen consisting of SEQ ID NO: 1, but that does not exclude any previously developed antibody from binding to an epitope within SEQ ID NO: 1 which would need to be determined experimentally.
As detailed below the state of the art does not recognize that a person of ordinary skill in the art could envision a genus of antibodies defined by epitope or function. This is because when antibodies are raised to an antigen each monoclonal antibody raised comes from one unique cell with unique CDRs which are responsible for antibody binding, such that the structure of CDRs for one antibody cannot be considered representative of other antibodies with different CDRs that bind the same antigen or even substantially the same epitope. Notably, the epitope structure that one antibody binds on an antigen, do not inform the skilled artisan as to what other antibodies would bind the same or substantially the same structure.
Claim analysis:
As detailed below, one skilled in the art would be unable to envision the entire genus of TCRs/ CARs that would bind the neoantigen consisting of SEQ ID NO: 1.
The state of the art as it applies to the claimed invention:
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Biodrugs (2007), 21 (3): 145-156; page 146, section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al. Protein Science (2005), 14:246–248; page 246). 3D structural analyses of antibody-epitope binding highlights the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al. J Comput Chem (2005), 26(9):879-87; page 879).
Ladner (Biotechnology and Genetic Engineering Reviews (2007), 24(1): 1-30) teaches that competitive binding assays demonstrate that two antibodies bind to overlapping or non-overlapping epitopes but not the same epitope (page 3; paragraph 3), so for accurate epitope mapping techniques that can be used are large energy transfer between labeled antibody to an antigen, antigen fragment binding, competitive peptide and antigen binding to antibody, antigen or antibody mutation, antigen-antibody complex analysis by NMR, determination of the 3D crystal structure of the antigen-antibody complex or electron microscopy (pages 5-7).
Rooney (WO 2017/173321 A1; IDS entered April 29, 2021) teaches an isolated neoantigenic peptide comprising a tumor-specific neoepitope, wherein the isolated neoantigenic peptide is not a native polypeptide, wherein the neoepitope comprises at least 8 contiguous amino acids of an amino acid sequence represented by: AXByCZ (claim 1), wherein AxByCz is
NIMEIRQLPSSHALEAKLSRMSYPVKEQESILKTVGKLTATQVAKISFFFALCGFWQICHIKKHFQTHKLL (claim 3, z), that can be used, for example, to stimulate an immune response to a tumor associated antigen, to create an immunogenic composition or cancer vaccine for use in treating disease (paragraph 0099). Which contains 100% of the instant claimed SEQ ID NO: 1. Rooney further teaches provided herein is a T cell receptor (TCR) capable of binding at least one neoantigenic peptide described herein or an MHC -peptide complex comprising at least one neoantigenic peptide described herein (para 0020) or a chimeric antigen receptor comprising: (i) a T cell activation molecule; (ii) a transmembrane region; and (iii) an antigen recognition moiety capable of binding at least one neoantigenic peptide described herein (para 0021). Rooney further teaches that Provided herein is a modified cell transfected or transduced with a nucleic acid described herein. In embodiments, the modified cell is a T cell, tumor infiltrating lymphocyte, NK-T cell, TCR-expressing cell, CD4+ T cell, CD8+ T cell, or NK cell (para 0030) or a composition comprising the T cell receptor or chimeric antigen receptor described herein (para 0031). It is possible that a TCR or CAR generated by Rooney would be reactive to the neoantigen consisting of SEQ ID NO: 1 as one of the claimed sequences in Rooney contains 100% of the of the instant claimed SEQ ID NO: 1.
Accordingly, one skilled in the art would be unable to predict or envision a genus of TCRs/CARs that bind to the neoantigenic peptide consisting of SEQ ID NO: 1. Since the disclosure fails to describe a sufficient number of species to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Allowable Subject Matter
Claims 1, 4, 8, and 14 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
The neoantigen consisting of SEQ ID NO : 1 has been found free of the prior art as recited in claims 1 and 14 and therefore the cancer vaccine and isolated peptide of these claims are allowable.
Claims 4 and 8 depend from claim 1 and are therefore also allowable.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643