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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02 September 2026 has been entered.
Status of Application, Amendments and/or Claims
Claims 1, 2, 4, 6-8, 11-13, 16, 18, 21-25, 27, 29, 46, and 55 are pending and under consideration in the instant application.
Withdrawn Objections and/or Rejections
1. The rejection of claims 1, 2, 4, 6, 7, 8, 11-13, 16, 18, 21-25, 27, 29, 46, and 55 on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 11,795,225 in view of Johannes et al. (J Med Chem 64: 14498-14512, 2021), and Yap et al. (JCO Precision Oncol 6: e2100456, 09 February 2022) as set forth at pages 4-8 and 11-15 of the previous Office Action of 03 March 2026 is withdrawn in view of the submission of a terminal disclaimer (02 September 2026).
2. The provisional rejection of claims 1, 2, 4, 6, 7, 8, 11-13, 16, 18, 21-25, 27, 29, 46, and 55 on the ground of nonstatutory double patenting as being unpatentable over claims 46-69 of copending Application No. 18/467,137 in view of Johannes et al. (J Med Chem 64: 14498-14512, 2021), and Yap et al. (JCO Precision Oncol 6: e2100456, 09 February 2022) as set forth at pages 8-15 of the previous Office Action of 03 March 2026 is withdrawn in view of the submission of a terminal disclaimer (02 September 2026).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
3. Claims 1, 2, 4, 6, 7, 8, 11-13, 18, 21-25, 27, 29, 46, and 55 are rejected under 35 U.S.C. 103 as being obvious over Schmidt et al. (US 2024/0302348; priority to 12 September 2020), Johannes et al. (J Med Chem 64: 14498-14512, 2021), and Yap et al. (JCO Precision Oncol 6: e2100456, 09 February 2022; cited on the PTO-892 of 09 September 2024).
The applied reference of Schmidt et al. has a common Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Schmidt et al. teach a method of treating cancer comprising administering to a human subject an effective amount of an antibody-drug conjugate comprising:
(i) an antibody or antigen binding fragment thereof which binds to a B7-H4 polypeptide, comprising a heavy chain CDR1 (HCDR1), a HCDR2, a HCDR3, a light chain CDR1 (LCDR1), a LCDR2, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively;
ii. a cleavable linker; and
iii. a cytotoxic agent that is a topoisomerase inhibitor (page 5, [0086-0087]; pages 5-6, [0090]; pages 7-8, [0106, 0109]; pages 15-18, [0191-0197]; page 24, [0259-0263]; page 30, [0313]; Figures 4-9, 38D).
It is noted that the amino acid sequences of SEQ ID NOs: 4-9 of Schmidt et al. are 100% identical to the amino acid sequences of SEQ ID NOs: 7-12 of the instant application, meeting the limitations of instant claims 1 and 12 (see Figures 4-9 of Schmidt et al.). Additionally, the VH amino acid sequence of SEQ ID NO: 10 of Schmidt et al. is 100% identical to the VH amino acid sequence of SEQ ID NO: 45 of the instant application, meeting the limitations of instant claims 11 and 13 (see Figure 10 of Schmidt et al.). The VL amino acid sequence of SEQ ID NO: 11 of Schmidt et al. is 100% identical to the amino acid sequence of SEQ ID NO: 34 of the instant application, meeting the limitations of instant claims 11 and 13 (see Figure 11 of Schmidt et al.). Lastly, the heavy chain comprising the amino acid sequence of SEQ ID NO: 12 of Schmidt et al. is 100% to the instant amino acid sequence of SEQ ID NO: 51 while the light chain comprising the amino acid sequence of SEQ ID NO: 13 of Schmidt et al. is 100% to the instant amino acid sequence of SEQ ID NO: 44, meeting the limitations of instant claim 18 (see Figures 12 and 13 of Schmidt et al.).
Schmidt et al. disclose that the cancer comprises a cancer cell that expresses B7-H4, meeting the limitations of instant claim 4 (page 24, [0259-0263]). Schmidt et al. teach that the cancer is selected from breast cancer (including HR+, HER2+, and TNBC), ovarian cancer, endometrial cancer, hematological cancer, cholangiocarcinoma, NSCLC, pancreatic cancer, gastric cancer, and colon cancer, meeting the limitations of instant claims 6, 7, and 55 (page 24, 52-53, [0261-0263]).
Schmidt et al. teach that the cleavable linker and topoisomerase inhibitor are together selected from the compounds SG3932, SG4010, SG4057, and SG4052, meeting the limitations of instant claims 24, 25, and 46 (page 5, [0089]; page 7, [0106]; page 8, [0109]; page 15, [0191] through page 18, [0197]; page 30, [0313]; Figure 38D). Schmidt et al. disclose that the antibody-drug conjugate (DAR) is from 1 to 20, meeting the limitation of claim 27 (page 7, [0102]). Schmidt et al. also teach that the B7-H4 may be a humanized monoclonal antibody, meeting the limitations of instant claim 21 (page 20, [0224]; page 22, [0242]).
Schmidt et al. do not teach a method of treating cancer comprising administering the antibody-drug conjugate and an additional agent, wherein the additional agent is a PARP1 inhibitor (such as AZD5305).
Johannes et al. disclose that PARP inhibitors have demonstrated widespread success as a therapeutic class for the treatment of a variety of cancers (page 14498, column 1). Johannes et al. indicate that BRCA mutant tumors are sensitive to PARP1/PARP2 inhibitors (page 14499, column 1, 1st paragraph). Johannes et al. state that in spite of their success, PARP1/2 inhibitors have shown significant hematological toxicities, including anemia, neutropenia, and thrombocytopenia (page 14499, column 1, 2nd paragraph). Johannes et al. teach the generation of compound 25, “AZD5305”, a potent and selective PARP1 inhibitor, with excellent in vivo efficacy and reduced effects on human bone marrow progenitor cells (abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”). Johannes et al. disclose that AZD5305 is a next-generation PARP inhibitor with multiple clinical options, including combination approaches (page 14506, bottom of column 1 through column 2).
Yap et al. teach that tumors characterized by homologous recombination deficiency, such as BRCA1/2-mutated cancers, are sensitive to inhibition of poly(ADP-ribose) polymerases (PARPs) (page 1, column 1, 1st paragraph). Yap et al. also disclose that in human tumor cell lines, topoisomerase I (Topo1) inhibitors have demonstrated synergy with PARP inhibitors (page 1, column 1, 2nd paragraph). Yap et al. state that PARP inhibition may augment Topo1-mediated DNA damage or delay repair (page 1, column 1, 2nd paragraph). Yap et al. review the SEASTAR study, which investigated the combination of (i) PARP inhibitor, rucaparib, and (ii) sacituzumab govitecan (SG), a conjugate of SN-38 (the active metabolite in topoisomerase inhibitors irinotecan and topotecan) and a humanized anti-Trop-2 antibody (page 1, 2nd and 3rd paragraphs). Yap et al. state that the results provide proof-of-concept clinical evidence supporting further development of PARP1 inhibitors in combination with ADCs carrying Topo1-inhibitor payloads (page 5, column 2). Yap et al. also teach that combination with other selective PARP inhibitors, such as PARP1-targeted inhibitor AZD5305, may improve tolerability (page 5, column 2).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the composition comprising a B7-H4 antibody-topoisomerase I drug conjugate and methods of treating cancer by administering the B7-H4 antibody-topoisomerase I drug conjugate taught by Schmidt et al. in combination with a PARP1 inhibitor, such as ADZ5305, as taught by Johannes et al. and Yap et al. The person of ordinary skill in the art would have been motivated to make that modification to generate synergism between the topoisomerase inhibitor present in the antibody-drug conjugate of Schmidt et al. and the PARP1 inhibitor, to in turn enhance anti-tumor efficacy and improve patient tolerability (see Joannes et al., abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”);; Yap et al., page 1, column 1, 2nd paragraph; page 5, column 2). The person of ordinary skill in the art reasonably would have expected success because (i) PARP inhibitors had widespread success as a therapeutic class for the treatment of a variety of cancers, including BRCA1/BRCA2 mutated tumors, at the time the instant invention was made (see Johannes et al; page 14498, column 1); (ii) “AZD5305” is a potent and selective PARP1 inhibitor, with excellent in vivo efficacy, reduced effects on human bone marrow progenitor cells, and multiple clinical options (including combination approaches) (see Johannes et al. abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”; (page 14506, bottom of column 1 through column 2); and (iii) topoisomerase I (Topo1) inhibitors have demonstrated synergy with PARP inhibitors (see Yap et al., page 1, column 1, 2nd paragraph; page 5, column 2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
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.
Copending Application No. 18/025,883
4. Claims 1, 2, 4, 6-8, 11-13, 18, 21-25, 29, 46, and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over amended claims 80, 98, and 117-134 of copending Application No. 18/025,883 in view of Johannes et al. (J Med Chem 64: 14498-14512, 2021), and Yap et al. (JCO Precision Oncol 6: e2100456, 09 February 2022; cited on the PTO-892 of 09 September 2024).
Claim 1 of the instant application is directed to a method of treating cancer in a human subject in need thereof, comprising administering to the human subject: (A) an antibody-drug conjugate (ADC) comprising (i) an antibody or antigen binding fragment thereof which binds to a B7-H4 polypeptide, wherein the antibody comprises specific heavy and light CDR sequences; (ii) a cleavable linker; and (iii) a cytotoxic agent; and (B) an additional agent, wherein the additional agent is a PARP1 inhibitor.
Meanwhile, claim 80 of the ‘883 application, for example, recites a method of treating cancer in a cancer patient, wherein step (vi) recites administering a therapy comprising ADC that includes an ADC payload and an ADC antibody that targets a protein on a cancer cell, wherein the protein is B7-H4. Claim 134 of the ‘883 application also recites that the ADC is an anti-B7H4 antibody conjugated to a drug-linker, and wherein the drug-linker.
Claims 1, 11-13, 18, 29, and 46 of the instant application and claim 123 of the ‘883 patent application recite antibody sequences for the ADC conjugate. Specifically, the amino acid sequences of SEQ ID NOs: 4-9 of ‘883 are 100% identical to the amino acid sequences of SEQ ID NOs: 7-12 of the instant application. Additionally, the VH amino acid sequence of SEQ ID NO: 10 of the ‘883 application is 100% identical to the VH amino acid sequence of SEQ ID NO: 45 of the instant application. The VL amino acid sequence of SEQ ID NO: 11 of the ‘883 application et al. is 100% identical to the amino acid sequence of SEQ ID NO: 34 of the instant application. Lastly, the heavy chain comprising the amino acid sequence of SEQ ID NO: 12 of the ‘883 application is 100% to the instant amino acid sequence of SEQ ID NO: 51 while the light chain comprising the amino acid sequence of SEQ ID NO: 13 of ‘883 is 100% to the instant amino acid sequence of SEQ ID NO: 44.
Claims 6 and 55 of the instant application and claims 125 and 133 of the ’883 application recite that the cancer is breast cancer, ovarian cancer, endometrial cancer, cholangiocarcinoma, lung cancer, pancreatic cancer, and gastric cancer.
Claims 23-25 and 46 of the instant application and claims 124, 132, 134 of the ‘883 application recite that the ADC payload is a topoisomerase I inhibitor, wherein the topoisomerase inhibitor is selected from the compounds SG3932, SG4010, SG4057, and SG4052.
The claims of the ‘883 application do not recite a method of treating cancer comprising administering the antibody-drug conjugate and an additional agent, wherein the additional agent is a PARP1 inhibitor (such as AZD5305).
Johannes et al. disclose that PARP inhibitors have demonstrated widespread success as a therapeutic class for the treatment of a variety of cancers (page 14498, column 1). Johannes et al. indicate that BRCA mutant tumors are sensitive to PARP1/PARP2 inhibitors (page 14499, column 1, 1st paragraph). Johannes et al. state that in spite of their success, PARP1/2 inhibitors have shown significant hematological toxicities, including anemia, neutropenia, and thrombocytopenia (page 14499, column 1, 2nd paragraph). Johannes et al. teach the generation of compound 25, “AZD5305”, a potent and selective PARP1 inhibitor, with excellent in vivo efficacy and reduced effects on human bone marrow progenitor cells (abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”). Johannes et al. disclose that AZD5305 is a next-generation PARP inhibitor with multiple clinical options, including combination approaches (page 14506, bottom of column 1 through column 2).
Yap et al. teach that tumors characterized by homologous recombination deficiency, such as BRCA1/2-mutated cancers, are sensitive to inhibition of poly(ADP-ribose) polymerases (PARPs) (page 1, column 1, 1st paragraph). Yap et al. also disclose that in human tumor cell lines, topoisomerase I (Topo1) inhibitors have demonstrated synergy with PARP inhibitors (page 1, column 1, 2nd paragraph). Yap et al. state that PARP inhibition may augment Topo1-mediated DNA damage or delay repair (page 1, column 1, 2nd paragraph). Yap et al. review the SEASTAR study, which investigated the combination of (i) PARP inhibitor, rucaparib, and (ii) sacituzumab govitecan (SG), a conjugate of SN-38 (the active metabolite in topoisomerase inhibitors irinotecan and topotecan) and a humanized anti-Trop-2 antibody (page 1, 2nd and 3rd paragraphs). Yap et al. state that the results provide proof-of-concept clinical evidence supporting further development of PARP1 inhibitors in combination with ADCs carrying Topo1-inhibitor payloads (page 5, column 2). Yap et al. also teach that combination with other selective PARP inhibitors, such as PARP1-targeted inhibitor AZD5305, may improve tolerability (page 5, column 2).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the method of treating cancer comprising administering a B7-H4 antibody-topoisomerase I drug conjugate of the ‘883 application claims by administering the conjugate in combination with a PARP1 inhibitor, such as ADZ5305, as taught by Johannes et al. and Yap et al. The person of ordinary skill in the art would have been motivated to make that modification to generate synergism between the topoisomerase inhibitor present in the antibody-drug conjugate of the ‘883 claims and the PARP1 inhibitor, to in turn enhance anti-tumor efficacy and improve patient tolerability (see Joannes et al., abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”);; Yap et al., page 1, column 1, 2nd paragraph; page 5, column 2). The person of ordinary skill in the art reasonably would have expected success because (i) PARP inhibitors had widespread success as a therapeutic class for the treatment of a variety of cancers, including BRCA1/BRCA2 mutated tumors, at the time the instant invention was made (see Johannes et al; page 14498, column 1); (ii) “AZD5305” is a potent and selective PARP1 inhibitor, with excellent in vivo efficacy, reduced effects on human bone marrow progenitor cells, and multiple clinical options (including combination approaches) (see Johannes et al. abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”; (page 14506, bottom of column 1 through column 2); and (iii) topoisomerase I (Topo1) inhibitors have demonstrated synergy with PARP inhibitors (see Yap et al., page 1, column 1, 2nd paragraph; page 5, column 2).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Copending Application No. 19/478,530
5. Claims 1, 2, 4, 6-8, 11-13, 16, 18, 21-25, 27, 29, 46, and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over amended claims 1-86 of copending Application No. 19/478,530 in view of Johannes et al. (J Med Chem 64: 14498-14512, 2021), and Yap et al. (JCO Precision Oncol 6: e2100456, 09 February 2022; cited on the PTO-892 of 09 September 2024).
Claim 1 of the instant application is directed to a method of treating cancer in a human subject in need thereof, comprising administering to the human subject: (A) an antibody-drug conjugate (ADC) comprising (i) an antibody or antigen binding fragment thereof which binds to a B7-H4 polypeptide, wherein the antibody comprises specific heavy and light CDR sequences; (ii) a cleavable linker; and (iii) a cytotoxic agent; and (B) an additional agent, wherein the additional agent is a PARP1 inhibitor.
Meanwhile, claim 1 of the ‘530 application, for example, recites a method of treating cancer in a subject, comprising administering to the subject an antibody-drug conjugate (ADC) that specifically binds to B7-H4 in an amount from about 0.8 mg/kg to about 4.8 mg/kg, the ADC comprising (i) an antibody or antigen binding fragment with specific CDR sequences; (ii) a cleavable linker; and (iii) a cytotoxic agent.
Claims 1, 11-13, 16, 18, 29, and 46 of the instant application and claims 1, 13-15, 17-21, 31, 36, 45, 50, 51, 54, 65, 76, and 77 of the ‘530 patent application recite antibody sequences for the ADC conjugate. Specifically, the amino acid sequences of SEQ ID NOs: 1-47, 51, and 52 of ‘530 are 100% identical to the same respective amino acid sequences of SEQ ID NOs: 1-47, 51, and 52 of the instant application.
Claims 6 and 55 of the instant application and claims 8, 39, 60, and 71 of the ’530 application recite that the cancer is selected from ovarian cancer, biliary tract cancer, breast cancer, pancreatic cancer, prostate cancer, hematological cancer, endometrial cancer, cholangiocarcinoma, NSCLC (squamous and/or adenocarcinoma), gastrointestinal cancer (such as gastric cancer and colorectal cancer), and lung cancer.
Claim 7 of the instant application and claims 9, 40, 61, and 72 of the ’530 application recite that the cancer is a breast cancer selected from hormone receptor-positive (HR+) breast cancer, human epidermal growth factor receptor 2 positive (HER2+) breast cancer, and triple negative breast cancer (TNBC).
Claim 8 of the instant application and claims 10-12, 41-43, 62-64, and 73-76 of the ’530 application recite that the cancer is homologous recombination deficient (HRD) cancer and wherein the cancer comprises one or more cells having a mutation in an HRD gene selected from BRCA1, BRCA2, ATM, BRIP1, BARDI, CDK12, CHEKI, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L.
Claim 21 of the instant application and claims 23 and 79 of the ‘530 application recite that the antibody is a humanized monoclonal antibody.
Claim 22 of the instant application and claims 24 and 80 of the ‘530 application recite that the cleavable linker is an mp-PEG8-val-ala linker.
Claims 23-25 and 46 of the instant application and claims 25-28, 31, 45, 53, and 81-84 of the ‘530 application recite that the ADC payload is a topoisomerase I inhibitor, wherein the topoisomerase inhibitor is selected from the compounds SG3932, SG4010, SG4057, and SG4052.
Claim 27 of the instant application and claims 29, 30, 85, and 86 of the ‘530 application recite that the ADC has a drug to antibody ratio of between about 1 and about 8.
The claims of the ‘530 application do not recite a method of treating cancer comprising administering the antibody-drug conjugate and an additional agent, wherein the additional agent is a PARP1 inhibitor (such as AZD5305).
Johannes et al. disclose that PARP inhibitors have demonstrated widespread success as a therapeutic class for the treatment of a variety of cancers (page 14498, column 1). Johannes et al. indicate that BRCA mutant tumors are sensitive to PARP1/PARP2 inhibitors (page 14499, column 1, 1st paragraph). Johannes et al. state that in spite of their success, PARP1/2 inhibitors have shown significant hematological toxicities, including anemia, neutropenia, and thrombocytopenia (page 14499, column 1, 2nd paragraph). Johannes et al. teach the generation of compound 25, “AZD5305”, a potent and selective PARP1 inhibitor, with excellent in vivo efficacy and reduced effects on human bone marrow progenitor cells (abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”). Johannes et al. disclose that AZD5305 is a next-generation PARP inhibitor with multiple clinical options, including combination approaches (page 14506, bottom of column 1 through column 2).
Yap et al. teach that tumors characterized by homologous recombination deficiency, such as BRCA1/2-mutated cancers, are sensitive to inhibition of poly(ADP-ribose) polymerases (PARPs) (page 1, column 1, 1st paragraph). Yap et al. also disclose that in human tumor cell lines, topoisomerase I (Topo1) inhibitors have demonstrated synergy with PARP inhibitors (page 1, column 1, 2nd paragraph). Yap et al. state that PARP inhibition may augment Topo1-mediated DNA damage or delay repair (page 1, column 1, 2nd paragraph). Yap et al. review the SEASTAR study, which investigated the combination of (i) PARP inhibitor, rucaparib, and (ii) sacituzumab govitecan (SG), a conjugate of SN-38 (the active metabolite in topoisomerase inhibitors irinotecan and topotecan) and a humanized anti-Trop-2 antibody (page 1, 2nd and 3rd paragraphs). Yap et al. state that the results provide proof-of-concept clinical evidence supporting further development of PARP1 inhibitors in combination with ADCs carrying Topo1-inhibitor payloads (page 5, column 2). Yap et al. also teach that combination with other selective PARP inhibitors, such as PARP1-targeted inhibitor AZD5305, may improve tolerability (page 5, column 2).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the method of treating cancer comprising administering a B7-H4 antibody-topoisomerase I drug conjugate of the ‘530 application claims by administering the conjugate in combination with a PARP1 inhibitor, such as ADZ5305, as taught by Johannes et al. and Yap et al. The person of ordinary skill in the art would have been motivated to make that modification to generate synergism between the topoisomerase inhibitor present in the antibody-drug conjugate of the ‘530 claims and the PARP1 inhibitor, to in turn enhance anti-tumor efficacy and improve patient tolerability (see Joannes et al., abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”);; Yap et al., page 1, column 1, 2nd paragraph; page 5, column 2). The person of ordinary skill in the art reasonably would have expected success because (i) PARP inhibitors had widespread success as a therapeutic class for the treatment of a variety of cancers, including BRCA1/BRCA2 mutated tumors, at the time the instant invention was made (see Johannes et al; page 14498, column 1); (ii) “AZD5305” is a potent and selective PARP1 inhibitor, with excellent in vivo efficacy, reduced effects on human bone marrow progenitor cells, and multiple clinical options (including combination approaches) (see Johannes et al. abstract; page 14504 through page 14505, column 1 and column 2 (last full paragraph above “conclusions”; (page 14506, bottom of column 1 through column 2); and (iii) topoisomerase I (Topo1) inhibitors have demonstrated synergy with PARP inhibitors (see Yap et al., page 1, column 1, 2nd paragraph; page 5, column 2).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 2, 4, 6-8, 11-13, 16, 18, 21-25, 27, 29, 46, and 55 are rejected.
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BEB
Art Unit 1647
18 September 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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