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 .
Election/Restrictions
Claim 1 and 67 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claim 70 and new claims 115-118, directed to the process of using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 08OCT2024 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are 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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Claim Status
Applicant’s amendments received 30SEP2025 are acknowledged.
Claims 2-16, 18, 20-24, 26, 28-31, 33-36, 38-59, 61-66, 68-69, and 71-108 have been canceled.
Claims 1, 17, 19, 25, and 37 have been amended.
Claims 109-118 are new.
Claims 1, 17, 19, 25, 27, 32, 37, 60, 67, 70, and 109-118 (i.e., claims 1 and 37 are independent) are pending in the instant application and examined on the merits.
Priority
The present application is a 371 National Stage of PCT International Application No. PCT/IB2020/051812, filed 03MAR2020, which claims the benefit of US Provisional Patent Application No. 62/813650, filed 04MAR2019. Applicant’s claim for the benefit of prior-filed application is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 30SEP2025 is/are acknowledged and the references cited therein have been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). The sequences of issue are recited in ¶0049-0050 and ¶0181.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
Upon further consideration, the disclosure is objected to because of the following informalities:
CROSS-REFERENCES TO RELATED APPLICATIONS section needs to updated to reflect that the instant application is a 371 National Stage Application
REFERENCE TO SEQUENCE LISTING SUBMITTED section needs to be updated to reflect the new byte size of the file.
The specification recites “SEQ ID NO: 14” at ¶0038 and “SEQ ID NO: 11” at ¶0048; however each of these sequences correspond to “000” or a skipped sequence in the sequence listing. As such, it is unclear what these sequence identifiers are referencing. Applicant is required to amend the specification, and the sequence listing and CRF to fix the sequences for SEQ ID NO: 14 and SEQ ID NO: 11 without introducing new matter.
Typographical error-p 53, “he” should be updated to “the” in line 1.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see ¶0159, for example). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of and to catalog all possible minor errors. Applicant’s assistance and cooperation in finding and correcting any errors of which the applicant may become aware of in the specification is appreciated.
Claim Objections
Applicant’s arguments, see p 9-10, Objection to the claims section, filed 30SEP2025, with respect to objections to claim(s) 11 and 17 (claim 11 has been cancelled) for minor informalities have been fully considered and said objections to claim(s) 17 have been withdrawn in view of claim amendments filed as part of said response.
Applicants claim amendments and newly added claims received as part of the 30SEP2025 response have necessitated the following new objections.
Claims 19 and 114 are objected to because of the following informalities:
Claim 19 contains a typographical error in section (b)(ii) “…set forth SEQ in ID NO: 2;…” should be updated to “set forth in SEQ ID NO: 2;…” in the last line of the (b)(ii) section.
Claim 114 contains the acronym “ILC.” While acronyms are permissible as shorthand in the claims, the first recitation of the term should include the full recitation followed by the acronym in parentheses.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Indefiniteness
Applicant’s arguments, see p 10-11, Rejection under 35 USC §112 (b) section, filed 30SEP2025, with respect to the rejection(s) of claim(s) 1, 3-4, 6, 11, 17, 19, 25, 27, 31-32, 37, 60, and 67 (claims 3-4, 6, 11, and 31 have been cancelled) under 35 USC §112(b) have been fully considered and said rejections of claims 1, 17, 19, 25, 27, 32, 37, 60, and 67 have been withdrawn in view of the claim amendments filed as part of said response.
Applicant’s claim amendments and newly added claims received as part of the 30SEP2025 response have necessitated the following new grounds of rejection.
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 118 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.
Claim 118 recites the limitation "the cells are" in line 1 of the claim. In this instance, the method of claim 70, upon which claim 118 is dependent recites “the cell of claim 67” and therefore there is insufficient antecedent basis for this limitation in the claim.
Dependency
Applicant’s arguments, see p 11-12, Rejection under 35 USC §112(d) section, filed 30SEP2025, with respect to the rejection(s) of claim(s) 17, 19, 25, 31, 37 and 60 (claim 31 has been cancelled) under 35 USC §112(b) have been fully considered and said rejections of claims 17, 19, 25, 37, and 60 have been withdrawn in view of the claim amendments filed as part of said response.
Scope of Enablement and Written Description
Applicant’s arguments, see p 12-13, Rejections under 35 USC §112(a) section, filed 30SEP2025, with respect to the rejection(s) of claim(s) 1, 3-4, 6, 11, 17, 19, 25, 27, 31-32, 37, 60, and 67 (claims 3-4, 6, 11, and 31 have been cancelled) under 35 USC §112(a) - enablement and written description have been fully considered and said rejections of claims 1, 17, 19, 25, 27, 32, 37, 60, and 67 have been withdrawn in view of the claim amendments filed as part of said response.
Applicant’s claim amendments received as part of the 30SEP2025 response have necessitated the following new grounds of rejection.
Scope of Enablement
Claims 70 and 115-118 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
“A method of treating skin cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the cell of claim 67, wherein the cell is a T cell;” does not reasonably provide enablement for more.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Scope of the claim:
In the instance of claim 70, drawn to a method of treating any cancer in a subject in need thereof, comprising administering any cell comprising the nucleic acid molecule of claim 1 (i.e., a nucleic acid molecule comprising (a) a first nucleotide sequence encoding a TCR or antigen binding portion thereof that specifically binds human gp100, comprising ß chain CDRs1-3 set forth in SEQ ID NOs: 6, 9, and 10 and αchain CDRs1-3 set forth in SEQ ID NOs: 5, 8, and 7, respectively and (b) a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR) is not fully enabled. Claim 70 is not fully enabled because:
The specification and working examples support the efficacy of a T-cell modified to express the TCR of claim 1 to treat a human melanoma cell cancer (i.e., A375) in vitro, utilizing a therapeutically effective amount of the specific T cell;
The prior art supports the expression of gp100 or PMEL in malignant melanoma (i.e., skin cancer), while remaining cancer tissues were negative; and
Therefore, it would require one of ordinary skill in the art undue experimentation to make any modified host cell for use to treat any cancer.
Claims 115-118 are also rejected since they depend from claim 70, but do not remedy this deficiency.
Direction provided by the inventor and existence of working examples:
The specification and working example discloses that C*07:01/gp100 TCR-transduced T cells are able to recognize melanoma cells that have both C*07:01 and gp100 genes (i.e., A375 melanoma cells transduced with C*07:01 and gp100 genes) and that they are melanoma-reactive (¶0182 and Fig 7-9). Although, this example supports the efficacy of C*07:01/gp100 TCR-transduced T cells in vitro against a melanoma C*07:01+ and gp100+ cell line it is unclear whether the same effect could be observed if a different cell were used or in an alternative cancer that is not C*07:01/gp100-positive (i.e., anything other than skin cancer). In this instance, there is no disclosure or guidance provided regarding using the TCR in any other cell other than a T cell for treating any other cancer than C*07:01/gp100-positive skin cancer.
State of prior art and level of predictability in the art:
Furthermore, the literature teaches that while gp100 or PMEL is highly expressed in skin cancer, specifically melanomas (Zhang, et al., J Immuno, 2021, 44, 214-223, see abstract) and negligibly expressed in other cancers (Human Protein Atlas, accessed 2025). Therefore, the literature supports that cancers of the skin, specifically melanomas are the only cancers with significant gp100 expression, and would enable a C*07:01/gp100 TCR-transduced T cell to be used to treat the specific cancer.
Quantity of experimentation needed to make or use the invention based on the disclosure:
Thus, one skilled in the art would be unable to make and use any cell comprising the C*07:01/gp100 TCR to treat any cancer upon administration. Therefore, the implementation of the invention in view of the lack of working examples in the specification and the predictability in the prior art, would require undue experimentation for one of ordinary skill in the art to make and use the instantly claimed invention.
Furthermore, claim 115 is not fully enabled to use the method to treat bone cancer, pancreatic cancer, cancer of the head or neck, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin’s Disease, non-Hodgkin’s lymphoma, primary mediastinal large B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, transformed follicular lymphoma, etc. because gp100 is negligibly expressed in cancers other than skin cancer and specifically melanoma cancers (Human Protein Atlas, accessed 2025).
In the instance of claims 116 and 117, drawn to wherein the cancer is locally advanced, advanced, or metastatic, or wherein the cancer is relapsed or refractory; are not fully enabled because the support for metastatic uveal melanoma, uses a bispecific T cell engager comprising a soluble TCR recognizing gp100 antigen fused to a scFv anti-CD3 that redirects T cell lysis of melanoma cells expressing gp100 in the context of HLA-A*02:01 molecules, which is not the cell that is currently claimed in claim 70.
Allowable Subject Matter
Claims 1, 17, 25, 27, 32, 37, 60 and 109-113 are allowed.
Applicant has claimed a nucleic acid molecule comprising: a nucleic acid molecule comprising (a) a first nucleotide sequence encoding a TCR or antigen binding portion thereof that specifically binds human gp100, comprising ß chain CDRs1-3 set forth in SEQ ID NOs: 6, 9, and 10 and αchain CDRs1-3 set forth in SEQ ID NOs: 5, 8, and 7, respectively and (b) a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR, a bispecific TCR, and a cell comprising the nucleic acid molecule.
The prior art, such as that of US2011/0318380 A1 (Brix, et al., 29DEC2011), teaches MHC-peptide complexes (i.e., SEQ ID NO: 13711 is a 100% query match to SEQ ID NO: 13 of the instant application) and their uses to detect and isolate antigen-specific TCR T cells in a sample (see entire document, ¶0164, and ¶0721). However the sequences of the TCR T cell populations that are enriched by the MHC-peptide complexes are not taught. Therefore, US2011/0318380 A1 does not teach or suggest a TCR comprising an alpha and beta chain comprising the instantly claimed CDR sequences and thus claims 1, 17, 25, 27, 32, 37, 60, and 109-113 are free of the prior art of record.
Conclusion
Claims 1, 17, 25, 27, 32, 37, 60 and 109-113 are allowed.
Claim 19 is objected to.
Claims 70 and 114-118 are rejected.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641