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 .
Detailed Action
This action is in response to the papers filed July 20, 2026.
Amendments
Applicant's response and amendments, filed July 20, 2026, is acknowledged. Applicant has cancelled Claims 1-8, 10-12, and 14-68, amended Claims 9 and 13, and added new claims, Claims 69-82.
Claims 9, 13, and 69-82 are pending.
Election/Restrictions
Applicant has elected without traverse the invention of Group IV, claim(s) 9 and 13, drawn to a TCR polypeptide comprising the amino acid SEQ ID NO recited in the Markush Group, and a nucleic acid encoding said TCR polypeptide.
Within Group IV, Applicant has elected without traverse the following species, wherein:
i) the alternative peptide SEQ ID NO is SEQ ID NO:44, as recited in Claim 1;
ii) the alternative TCR polypeptide SEQ ID NO is TCRalpha chain SEQ ID NO:29 and TCRbeta chain SEQ ID NO:30, as recited in Claim 9;
iii) the alternative method step is in vitro, as recited in Claim 21;
iv) the alternative means of genetic modification is lipid-based particles, as recited in Claim 53;
v) the alternative structural modification is particles functionalized with a targeting molecule on their surface, as recited in Claim 53(i);
vi) the alternative additional method step is administering a polynucleotide encoding the antigen, as recited in Claim 44; and
vii) the alternative method step is administering the immune effector cells genetically modified to express the TCR, as recited in Claim 34(i).
Claims 9, 13, and 69-82 are pending and under consideration.
Priority
This application is a 371 of PCT/EP2021/056559 filed on March 15, 2021.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d) of the foreign patent application PCT/EP2020/057108 filed on March 16, 2020, a certified copy of which has been filed with the instant application.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on July 20, 2026 that has been considered.
The information disclosure statement filed July 20, 2026 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
NPL citations have been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
Specification
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
See amended specification filed November 21, 2025, e.g.:
pg 19, Figure 10 legend, “SSX241-49”; and
pg 110, para 3, “NY-ESO-196-104”.
Each nucleotide and/or amino acid sequence that meets the minimum length threshold must have its SEQ ID NO: in parenthesis next to each occurrence.
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.
Response to Arguments
Applicant argues that the amended specification to provide SEQ ID NO’s renders the prior objection moot.
Applicant’s argument(s) has been fully considered, but is not persuasive. While Applicant provided SEQ ID NO’s for most of the previously cited deficiencies, Applicant did not amend the specification to provide SEQ ID NO’s for all of the previously cited deficiencies. See outstanding deficiencies:
pg 19, Figure 10 legend, “SSX241-49”; and
pg 110, para 3, “NY-ESO-196-104”.
Allowable Subject Matter
1. Claim 73 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: the claim is directed to a single chain TCR polypeptide (e.g. specification, pg 34, para 2) comprising:
i) a CDR3 sequence of a TCR alpha-chain selected from SEQ ID NO:29 (elected species), to wit, CAVWATGNQFYF (SEQ ID N:67);
ii) a CDR3 sequence of a TCR beta-chain selected from SEQ ID NO:30 (elected species), to wit, CATSFDRGYEQYF (SEQ ID NO:68); or
iii) the combination of (i) and (ii) above.
GenBank F3480 (TCR alpha-chain, clone TIL 5, 1999; of record) is considered relevant prior art for having taught a TCR alpha-chain that binds to melanoma tumor antigen, said TCR alpha-chain comprises a CDR3 motif whose amino acid is 92% identical (1 mismatch) to the TCR alpha-chain CDR3 motif of instant SEQ ID NO:29 (upper line), as shown below:
CAVWATGNQFYF
||| ||||||||
CAVGATGNQFYF
GenBank AVK78626 (TCR beta-chain, partial, 2018; of record) is considered relevant prior art for having taught a TCR beta-chain that binds to melanoma tumor antigen, said TCR beta-chain comprises a CDR3 motif whose amino acid is 84% identical (2 mismatches) to the TCR beta-chain CDR3 motif of instant SEQ ID NO:30 (upper line), as shown below:
CATSFDRGYEQYF
|||: ||||||||
CATTRDRGYEQYF
Robbins et al (U.S. 20140378389; of record) is considered relevant prior art for having disclosed a TCR beta-chain (SEQ ID NO:25) that binds to melanoma tumor antigen, said TCR beta-chain comprises a CDR3 motif whose amino acid is 93% identical (1 mismatch) to the TCR beta-chain CDR3 motif of instant SEQ ID NO:30 (upper line), as shown below:
CATSFDRGYEQYF
||||:||||||||
CATSWDRGYEQYF
The prior art does not appear to teach or fairly suggest single chain TCR polypeptide comprising the CDR3 sequence of a TCR alpha-chain selected from SEQ ID NO:29 (elected species), to wit, CAVWATGNQFYF (SEQ ID N:67) and/or a CDR3 sequence of a TCR beta-chain selected from SEQ ID NO:30 (elected species), to wit, CATSFDRGYEQYF (SEQ ID NO:68).
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.
2. Claims 9, 13, 69-72, and 74-82 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
With respect to Step 1, the claim is directed to a product, which is a statutory category of invention (Step 1: YES).
Claim 9 recites a TCR polypeptide comprising at least a TCR alpha-chain polypeptide comprising at least one of the CDR3 sequences of SEQ ID NO:29.
With respect to Step 2A, prong one, the judicial exception, the claim(s) is/are directed to a product of nature, and thus directed to a judicial exception (Step 2A, prong one: YES).
The instant specification discloses said alpha- and beta-chains naturally produced in a human in response to exposure to the naturally occurring tumor antigens (e.g. Figure 3 legend, “post-treatment PBMCs of patient A2-009”), followed by sorting those antigen-reactive T cells and cloning said TCR (e.g. Figure 5 legend, “sorting…. for TCR cloning”).
Thus, instant TCR polypeptide(s) is/are naturally occurring products of nature.
With respect to Step 2A, prong two, the claim does not recite additional elements that integrate the judicial exception into a practical application.
The claims do not integrate the judicial exception into a practical application (Step 2A, prong two: NO).
With respect to Step 2B, instantly recited TCR polypeptide(s) do not have markedly different characteristics from what exists in nature. Thus, isolated, but otherwise unchanged TCR polypeptides are not markedly different from what exists in nature.
Claims 13 and 74-82, dependent on Claim 9, recites a nucleic acid encoding the TCR polypeptide. However, those of ordinary skill in the art immediately recognize that it is natural law of cell biology that the patient’s B cells inherently and naturally comprise genomic nucleic acids and mRNA encoding said TCR polypeptide(s). The claimed nucleic acid does not have different functional characteristics as the natural gene and/or mRNA, as it encodes the same polypeptide. Thus, isolated, but otherwise unchanged nucleic acids are not markedly different from what exists in nature. Thus, the claims are not considered to recite additional elements that amount to significantly more than the judicial exception itself (Step 2B: NO).
Response to Arguments
Applicant argues that the claims have been amended to recite the polypeptide is “engineered”.
Applicant’s argument(s) has been fully considered, but is not persuasive. The recitation of a process limitation in the claim(s) is not viewed as positively limiting the claimed product absent a showing that the process of making recited in claims imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The burden is placed upon the applicants to establish a patentable distinction between the claimed and referenced products. The method in which the T cell receptor polypeptide(s) were produced is immaterial to their patentability.
"Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). See also MPEP §2113.
The instant specification discloses said alpha- and beta-chains naturally produced in a human in response to exposure to the naturally occurring tumor antigens (e.g. Figure 3 legend, “post-treatment PBMCs of patient A2-009”), followed by sorting those antigen-reactive T cells and cloning said TCR (e.g. Figure 5 legend, “sorting…. for TCR cloning”).
Applicant admits (Remarks Made in Amendment, pgs 7-8 joining para) that the engineered T-cell receptor polypeptides of the claims “resulted from vaccination of patients with the melanoma FixVac vaccine and analysis of biological materials derived from them”, clearly evidencing that the claimed polypeptides are naturally occurring products of nature.
The claim(s) is/are directed to a product of nature, and thus directed to a judicial exception (Step 2A, prong one: YES).
With respect to Step 2A, prong two, the claim does not recite additional elements that integrate the judicial exception into a practical application. The claims do not integrate the judicial exception into a practical application (Step 2A, prong two: NO).
With respect to Step 2B, instantly recited TCR polypeptide(s) do not have markedly different characteristics from what exists in nature. Thus, isolated, but otherwise unchanged TCR polypeptides are not markedly different from what exists in nature.
Claim Rejections - 35 USC § 112
3. The prior rejection of Claims 9 and 13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of Applicant’s amendment to Claim 9 cancelling dependency upon cancelled Claim 1.
4. The prior rejections of Claims 9 and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in light of Applicant’s amendment to Claim 9 cancelling recitation of the functional language “is reactive with a peptide of claim 1” and “a variant thereof”.
Claim Rejections - 35 USC § 102
5. The prior rejection of Claim(s) 9 and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Bertoletti et al (U.S. 2011/0070208) is withdrawn in light of Applicant’s amendment to the independent Claim 9 cancelling recitation of “or a variant thereof” and requiring the CDR3 sequence of the referenced SEQ ID NO(s), a limitation Bertoletti et al do not disclose.
6. The prior rejection of Claim(s) 9 and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Alten et al (U.S. 2018/0051080) is withdrawn in light of Applicant’s amendment to the independent Claim 9 cancelling recitation of “or a variant thereof” and requiring the CDR3 sequence of the referenced SEQ ID NO(s), a limitation Alten et al do not disclose.
7. The prior rejection of Claim(s) 9 and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Alten et al (U.S. 2018/0161396) is withdrawn in light of Applicant’s amendment to the independent Claim 9 cancelling recitation of “or a variant thereof” and requiring the CDR3 sequence of the referenced SEQ ID NO(s), a limitation Alten et al do not disclose.
8. The prior rejection of Claim(s) 9 and 13 under 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) as being anticipated by Yee et al (WO 19/204683; filed April 19, 2019; priority to April 19, 2018) is withdrawn in light of Applicant’s amendment to the independent Claim 9 cancelling recitation of “or a variant thereof” and requiring the CDR3 sequence of the referenced SEQ ID NO(s), a limitation Yee et al do not disclose.
9. The prior rejection of Claim(s) 9 and 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Robbins et al (U.S. 2014/0378389) is withdrawn in light of Applicant’s amendment to the independent Claim 9 cancelling recitation of “or a variant thereof” and requiring the CDR3 sequence of the referenced SEQ ID NO(s), a limitation Robbins et al do not disclose.
Conclusion
10. Claims 9, 13, 69-72, and 74-82 are rejected.
Claim 73 is objected.
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 KEVIN K. HILL whose telephone number is (571)272-8036. The examiner can normally be reached 12pm-8pm EST.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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