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 .
1. The Amendment filed January 9, 2025 in response to the Office Action of July 24, 2025, is acknowledged and has been entered. Claims 1 and 3-44 are now pending and being examined. Claim 2 is canceled. Claims 1, 3, 9, 11, 13-16 are amended.
Claim Objection
2. Claim 23 is objected to because of the following informalities: There is a typo in claim 23 where the word “unit” is missing after the phrase “fist antigen binding”. Appropriate correction is required.
Maintained Rejection
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
3. Claims 1 and 3-44 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,732,045 in view of US Patent Application Publication 2018/0066059, Sentman et al, published March 8, 2018; in view of Wu et al (J. Immunology, 2015, 194:5305-5311); Osada et al (Cancer Immunol. Immunother., 2015; 64:677-688); Krupka et a (Leukemia, 2016, 30:484-491); and WO2017/198741, Zettl et al, published 2017.
The US Patent claims recite a protein comprising a first antigen binding unit specifically binding to B7H6 and a second antigen binding unit specifically binding to CD3, wherein said first antigen binding unit specifically binding to B7H6 is selected from the group consisting of i) to xxiv) of claim 1 that recites the same B7H6 heavy and light chain CDR sequences recited in instant claims 1 and 7;
wherein said first antigen binding unit specifically binding to B7H6 is selected from the group consisting of i) to xxiv) of claim 2 that comprises the same heavy and light chain variable domain SEQ ID NOs comprised by instant claim 3;
wherein aid second antigen binding unit specifically binding to CD3 is selected from the group consisting of i)-vi) of claim 3 that comprises the same heavy and light chain CDR sequence recited in instant claim 4 and 7;
wherein said second antigen binding unit specifically binding to CD3 is selected from the group consisting of i) to vi) of claim 4 that comprises the same heavy and light chain variable domain SEQ ID NOs recited in instant claim 5;
wherein i) said first antigen binding unit specifically binding to B7H6 comprises from its N- to C-terminus a first light chain variable domain, a first light chain constant domain, a first peptide linker, a first heavy chain variable domain and a first heavy chain constant CH1 domain; and
ii) said second antigen binding unit specifically binding to CD3 comprises from its N- to C-terminus a second light chain variable domain, a second light chain constant domain, a second peptide linker, a second heavy chain variable domain and a second heavy chain constant CH1 domain;
wherein the protein is comprised in a pharmaceutical composition.
The US Patent does not claim:
the pharmaceutical composition comprising the protein is administered to a patient to treat cancer expressing B7H6;
treating mCRC, HNSCC, NSCLC;
further administering anti-PD-1/PD-L1 antibody PD1-1 to 5.
Sentman teaches utilizing anti-B7H6 antibody and anti-CD3 antibody to construct a bispecific antibody (protein) T cell engager (BiTE), and methods of administering the bi-specific T-cell engager (BiTE) to cancer patients having cancer expressing B7H6, as set forth above. Sentman suggests treating a variety of cancers including myeloid leukemia, acute nonlymphocytic leukemia, T-cell acute lymphoblastic leukemia, T- or B-cell lymphoma, cervical cancer, gastric sarcoma (e.g., colon cancer), breast cancer, pancreatic cancer, melanoma, or prostate cancer, by administering a pharmaceutical composition comprising the BiTE, as set forth above. Sentman demonstrates the B7H6xCD3 BiTE successfully engaged both T cells and tumors cells expressing B7H6, resulting in IFN-γ secretion, activating T cells to kill B7H6+ tumor cells.
Wu (J. Immunol. 2015) teaches several intrinsic advantages of BiTE therapy: (1) confers antitumor specificity to T cells without having to genetically engineer T cells; therefore, avoids the cost and time associated with ex vivo cell manipulation; (2) BiTEs have shown potent therapeutic efficacy in treating lymphoma and leukemia; and (3) BiTE strategy can be used to potentially target any tumor cell surface antigen (p. 5305, col. 1). Wu demonstrates a B7H6xCD3 BiTE successfully triggers T cell effector responses against B7H6+ tumors, to secrete IFN-γ and specifically kill B7H6-expressing tumor cells (p. 5307, col. 1-2; Figure 2 and 3), and the BiTE successfully mediated therapeutic efficacy against lymphoma, melanoma, and ovarian cancer models expressing B7H6 (Figures 4 and 5). Wu concludes that “B7H6-specific BiTE activates host T cells and has the potential to treat various B7H6+ hematological and solid tumors” (abstract).
Administering the protein to a patient to treat cancer expressing B7H6
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the pharmaceutical composition comprising the bispecific B7H6xCD3 protein of the US Patent to patients having B7H6-expressing cancer for treatment. One would have been motivated to, and have a reasonable expectation of success to, given: (1) the US Patent claims the protein is in a pharmaceutical composition, indicating pharmaceutical use; and (2) Sentman and Wu suggest and teach known, successful application of bispecific B7H6xCD3 protein pharmaceutical to treat patients having tumors expressing B7H6.
Treating HNSCC, mCRC, NSCLC:
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat any solid cancers expressing B7H6 antigen, including NSCLC, HNSCC, and metastatic colorectal cancer. One would have been motivated to, and have a reasonable expectation of success to given: (1) the US Patent claims the protein is in a pharmaceutical composition, indicating pharmaceutical use; (2) Sentman suggests treating cancer expressing B7H6; (3) Sentman and Wu demonstrate successfully targeting and killing B7H6-expressing tumor cells or treating B7H6-expressing tumors in vivo, by administration of B7H6xCD3 BiTEs, wherein the cancers treated encompassed a wide variety of etiologically distinct hematological or solid tumors, all expressing B7H6 targeted by the therapy; and (4) Wu suggests treating solid tumors in general with anti-B7H6-targeted therapy, based on their demonstrated success for treating a variety of cancers expressing B7H6.
Administering anti-PD-1/PD-L1 antibody PD1-1 to 5
Osada; Krupka; and Zettl teach as set forth above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to add PD-L1/PD-1 antibody blockade therapy to the method of treating cancer with BiTE obviated by the US Paten, Sentman, and Wu. One would have been motivated to, and have a reasonable expectation of success to, given: (1) Sentman suggests adding additional anti-cancer therapy to the method of cancer treatment; and (2) Osada and Krupka teach and successfully demonstrate that anti-PD1/anti-PD-L1 antibody blockade enhances BiTE tumor cell killing, and suggest such combinations clinically to treat cancer.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the PD-1 antibody of Zettl as the PD-1 blockade therapy of the US Patent and combined references. One would have been motivated to, and have a reasonable expectation of success to, given: (1) Osada and Krupka teach and demonstrate that anti-PD-1 antibody inhibition enhances BiTE killing of tumor cells; and (2) Zettl suggests administering their PD-1 antibodies in combination therapy to treat cancer, and demonstrates that their PD1 antibodies inhibit PD-1 and treat tumors in vivo in combination cancer therapy. Further, it is well within the level of the skilled artisan to substitute one functionally equivalent inhibitory anti-PD-1 antibody for another, and to treat cancer with a reasonable expectation of success.
Response to Arguments
4. Applicants argue that the instant application is directed to a patentably distinct invention that was restricted from the US Patent (application 17/060,111). Applicants argue the US Patent is directed the invention of the protein binding to B7H6 and CD3, and does not claim methods of threating cancer. Applicants argue that method of treating cancer (Group III) was restricted from the protein binding to B7H6 and CD3 (Group I) on July 13, 2022 in the parent application 17/060,111. Applicants argue that the instant claims are consistent with restricted Group III and during prosecution of 17/060,111, the method claims of Group III were never rejoined with the product claims of Group I.
5. The arguments have been considered but are not persuasive. Although the method claims of the instant application were restricted as a separate invention in the parent application, the instant application was filed as a continuation (CON) of the parent application, and not filed as a divisional. There is no prohibition of double patenting on applications filed as a CON from the parent application resulting from a restriction.
35 U.S.C. 121 prohibition on double patenting states:
“A patent issuing on an application with respect to which a requirement for restriction under this section has been made, or on an application filed as a result of such a requirement, shall not be used as a reference either in the Patent and Trademark Office or in the courts against a divisional application or against the original application or any patent issued on either of them, if the divisional application is filed before the issuance of the patent on the other application.”
Therefore, the double patenting rejection is maintained.
6. All other objections and rejections recited in the Office Action mailed July 24, 2025 are hereby withdrawn in view of amendments.
7. Conclusion: No claim is allowed.
Conclusion
8. THIS ACTION IS MADE FINAL. 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.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642