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
The restriction requirement for species of further antigen-binding domain that can bind an effector cell receptor [species C), claims 23-26] is withdrawn in view of the allowability of the molecule of claim 1 and of which further comprises a CD3 antigen-binding domain and of which CD3-binding domain comprises the amino acid sequence of SEQ ID NO:404.
Response to Amendment
The rejections of claims 2-3 are moot in view of the cancellation of the claims.
The rejection of claim 14 under 35 USC 112(b) is withdrawn in view of the amendment replacing “antigen-binding fragment” with “antigen-binding domain”.
The rejection of claims 1-3 and 21-14 under 35 USC 112(a) as failing to comply with the written description requirement is withdrawn in view of the cancellation of claims 2-3 and the amendment of claim 1 to recite specific heavy and light chain CDR1-3 sequences of the antigen-binding domain.
The rejection of claims 1-3 and 21-22 under 35 U.S.C. 102(a)(1) as being anticipated by Skora et al. (Proc. Natl. Acad. Sci, 112(82):9967-9972, Aug. 2015, cited in the IDS filed 5/28/2024) is withdrawn in view of the cancellation of claims 2-3 and the amendment of claim 1 to recite specific heavy and light chain CDR1-3 sequences of the antigen-binding domain. Skora et al. does not recite the sequence of the isolated antibodies and the KRAS G12V peptide target of the antibodies of Skora et al. (KLVVVGAVGV, p. 9968, col. 2, first full paragraph) is different than either instant SEQ ID NO:22 or the sequence shown in Table 1. (See US 2018/0086832, cited in the IDS filed 3/30/2023, for disclosure of antibodies made by the method of Skora et al.; n.b., some authors of Skora et al. are inventors on this pregrant publication.)
The rejection of claims 1-3 and 21-22 under 35 U.S.C. 102(a)(1) as being anticipated by WO 2016/085904 A1 (WO ‘904, cited in the IDS filed 5/28/2024) is withdrawn in view of the cancellation of claims 2-3 and the amendment of claim 1 to recite specific heavy and light chain CDR1-3 sequences of the antigen-binding domain. The reference does not teach or suggest an antigen-binding domain comprising the CDRs of instant claim 1.
The rejection of claims 1-3 and 21-23 under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over US 11,401,332 B2 (Lim) is withdrawn in view of the cancellation of claims 2-3 and the amendment of claim 1 to recite specific heavy and light chain CDR1-3 sequences of the antigen-binding domain. Lim et al. does not teach or suggest an antigen-binding domain comprising the CDRs of instant claim 1.
The rejection of claims 1-3 and 21-24 under 35 U.S.C. 103 as being unpatentable over WO 2016/085904 A1 (WO ‘904) as applied to claims 1-3 and 21 above, and further in view of US 9,718,893 B2 (Jung) is withdrawn in view of the cancellation of claims 2-3 and the amendment of claim 1 to recite specific heavy and light chain CDR1-3 sequences of the antigen-binding domain and for the reasons discussed above for the rejection of WO ‘904 under 35 USC 102(a)(1).
The provisional rejection of claims 1-3 and 21-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 19, 20, 25-26 and 29 of copending Application No. 18/351,087 (‘087) in view of US 9,718,893 B2 (Jung) is withdrawn in view of the cancellation of claims 2-3 and the amendment of claim 1 to recite specific heavy and light chain CDR1-3 sequences of the antigen-binding domain, which are not recited or encompassed by the products of the claims of ‘087.
Information Disclosure Statement
The information disclosure statement filed 09/08/2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. Because only the abstract and not the full copy of CN110382550A was submitted, though an English translated abstract was, that reference has not been considered.
Claim Interpretation
Independent claim 1 recites SEQ ID NO:22 as the modified peptide comprised by the peptide that is complexed with HLA-beta-2 microglobulin (b2M), which complex is bound by an antigen-binding domain as set forth in sections (i)-(xiv) of the claim. SEQ ID NO:22 has the sequence set forth in the Sequence Listing, which is “VVGAVGVGK”, regardless of the sequence shown for SEQ ID NO:22 in Tables 1-3 of the specification.
Claim Objections
Claim 24 is objected to because of the following informalities: as amended, claim 24 recites, “wherein molecule” and is missing the word --the--- before molecule.
Appropriate correction is required.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING 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 - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
The specification has been amended in the paragraph beginning p. 1, line 11, to recite a sequence listing size of 375,854 bytes created August 19, 2025, however, no sequence listing created on that date has been submitted. The only Sequence Listing submitted was created in September 2023. Even though Applicant’s response filed 9/8/25 says a substitute Sequence Listing was filed with the response, there is no record of a sequence listing being filed.
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 incorporation by reference paragraph, 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 and/or Sequence Listing Error
The disclosure is objected to because of the following informalities: There is a discrepancy between the specification and Sequence listing. In the Sequence Listing SEQ ID NO:22 has the 9 amino acid-long sequence of VVGAVGVGK, but in the specification, e.g., Table 1 (p. 14) and p. 14, line 20, SEQ ID NO:22 is listed as the 10 amino acid-long sequence of VVVGAVGVGK (10 amino acids). It is unclear which is correct/intended. Only one sequence may be associated with SEQ ID NO:22.
Appropriate correction is required.
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 21 and 24-26 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 21 depends from claim 1 and recites the molecule is selected from one of a list of binding structures. It is indefinite because as claim 1 has been amended to recite specific antigen-binding domains by sequence and is no longer drawn merely to a molecule comprising a generic antigen-binding domain that can bind a peptide-HLA-b2M complex, the molecule cannot be part of a T cell receptor (TCR), which is a naturally occurring receptor with a particular structure, including an intracellular signaling domain. The molecule may, nevertheless, have one of the other structures listed in the claim.
Claim 24 is indefinite because of the use of the word “further”. Claim 24 depends from claim 23, which recites the molecule of claim 1 further comprises an antigen-binding domain that can bind an effector cell receptor selected from a list of 12 receptors. Claim 24 recites the molecule further comprising one of a list of particular sequences, all of which are for anti-human CD3 scFv antibodies. It is unclear if the “further” refers to one of the anti-CD3 sequences in addition to both the peptide-HLA-2bM complex and one of the effector cell receptor-binding domains of claim 23 (e.g., in addition to a CD28-binding domain; i.e., a trispecific binding molecule) or is further describing the CD3-binding domain. If the latter meaning is intended, the rejection could be obviated by using phrasing such as , “wherein the antigen-binding domain that can bind an effector cell receptor comprises an amino acid sequence selected from the group consisting of….”
Claims 25 and 26 recite the limitation "antigen-binding domain that can bind to an effector cell". There is insufficient antecedent basis for this limitation in the claims. These claims depend from claim 23, which recites that the antigen-binding domain can bind to an effector cell receptor instead of merely an effector cell.
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.
Claim 14 is 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.
As amended, claim 1 recites particular heavy and light chain antibody sequences defined by CDR1-3 of both chains. Dependent claim 14 further recites that the antigen-binding domain is selected from a list of 17 sequences. However, SEQ ID NO:338-340 do not comprise any of the listed CDR sets of claim 1. Nor is there a disclosure of any of the antigen-binding domains of SEQ ID NO:338-340 binding a peptide-HLA-b2M complex wherein the peptide comprises the sequence of SEQ ID NO:22. Instead, these antigen-binding domain sequences are disclosed as binding the HLA complex wherein the peptide has the sequence of SEQ ID NO:18, which comprises part but not all of SEQ ID NO:22, having at least one additional N-terminal amino acid and missing 2 C-terminal amino acids. Further, SEQ ID NO:338-340 bind peptide-HLA targets wherein the target is HLA-A2 instead of HLA-A3 or -A11, comprised by peptide-HLA complexes to which antigen-binding domains comprising SEQ ID NO:341-348 and 369-374 bind. For claim 14, SEQ ID NO:338-340 do not meet the written description provision of 35 USC 112(a).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
With the exception of the antigen-binding domain sequences referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed antigen-binding domains, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
Therefore, only wherein the antigen-binding domain comprises the sequence of one of SEQ ID NO:341-348 and 369-374, but not the full breadth of the claim, meets the written description provision of 35 U.S.C. § 112(a). Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Allowable Subject Matter
Claims 1, 22 and 23 are allowed.
Conclusion
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 Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Official papers filed by fax should be directed to (571) 273-8300. NOTE: If applicant does submit a paper by fax, the original signed copy should be retained by the applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
December 9, 2025