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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6 February 2026 has been entered.
Response to Amendment
The amendment filed 6 February 2026 is acknowledged. Claims 3 and 4 are cancelled and claims 5-9 are new. Claim 1 is amended.
Claim Status
Claims 1 and 5-9 are pending and under examination in the instant office action.
Withdrawal of Objections
The objection to the specification for improperly demarcated trade names or trademarks is withdrawn in view of the amendment to the specification.
Withdrawal of Rejections
The rejection of claims 1, 3, and 4 under 35 U.S.C. 103 as being unpatentable over WO2014179664 to King et. al. published 6 November 2014 (cited in IDS dated 2/1/2022 Foreign Patent No. 108) in view of U.S. 20140341902 to Maecker et. al published 20 November 2014 as evidenced by Westdorp et al., "Opportunities for immunotherapy in microsatellite instable colorectal cancer," Cancer Immunol. Immunother., 2016, 65(10):1249-1259 (cited in IDS dated 2/1/2022, NPL No. 250) is withdrawn in view of the amendment to the claims.
The rejection of claim 1 under 35 U.S.C. 101 as claiming the same invention (statutory double patenting) as that of claim 4 of prior U.S. Patent No. 11155624 as evidenced by Genpept, Chain H, Immunoglobulin gamma-4 heavy chain [Homo sapiens] (2019) and Genpept, immunoglobulin kappa chain V-J-C, partial [Homo sapiens] (1985) is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 3, and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 21-22, 33-34 of U.S. Patent No. 9815897 (cited in IDS dated 2/1/2021 No. 27) in view of U.S. 20140341902 to Maecker et. al published 20 November 2014 as evidenced by Westdorp et al., "Opportunities for immunotherapy in microsatellite instable colorectal cancer," Cancer Immunol. Immunother., 2016, 65(10):1249-1259 (cited in IDS dated 2/1/2022, NPL No. 250) is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 3, and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11155624 (cited in IDS dated 2/1/2021 No. 29) in view of Westdorp et al., "Opportunities for immunotherapy in microsatellite instable colorectal cancer," Cancer Immunol. Immunother., 2016, 65(10):1249-1259 (cited in IDS dated 2/1/2022, NPL No. 250) as evidenced by Genpept, immunoglobulin kappa chain V-J-C, partial [Homo sapiens] (1985) and Genpept, Chain H, Immunoglobulin gamma-4 heavy chain [Homo sapiens] (2019) is withdrawn in view of the amendment to the claims.
The provisional rejection of claims 1, 3, and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of U.S. Patent No. 12415855 (formerly copending Application No. 17812933) as evidenced by Genpept, immunoglobulin kappa chain V-J-C, partial [Homo sapiens] (1985) is withdrawn in view of the amendment to the claims.
The following NSDP and provisional NSDP rejections are withdrawn in view of the amendment to the claims:
Additional Non-Statutory Double Patenting (NSDP) Rejections:
Patent No:
Rejected over Application Claims:
SEQ ID NOs identical to instant SEQ ID NO: 1 and 2:
Application/Patent with similar NSDP rejections:
11661453*
1-6
SEQ ID NO: 9 and 10
U.S. Patent No. 11155624 in view of Westdorp
11926665
1-10
SEQ ID NO: 13 and 14
U.S. Patent No. 11155624 in view of Westdorp
11407830 (cited in IDS dated 1/13/2023 No. 1)
1-2
SEQ ID NO: 3 and 4
Application No. 17812933
11753472*
3, 5, 7, and 10
N/A*
U.S. Patent No. 11155624 in view of Westdorp
10738117 (cited in IDS dated 2/1/2021, No. 28)
1-8
SEQ ID NO: 23 and 40
U.S. Patent No. 11155624 in view of Westdorp
*Starred patents or applications contain claims to TSR-042, which is identical to the instant anti-PD-1 antibody, as evidenced by U.S. 11661453 col 2 line 63- col 3 line 23.
Additional Provisional NSDP Rejections:
Application No:
Rejected over Application Claims:
SEQ ID NOs identical to instant SEQ ID NO: 1 and 2:
Application/Patent with similar prov. NSDP rejections:
17273680*
1, 6-10, 19-22
SEQ ID NO: 9 and 10
U.S. Patent No. 11155624 in view of Westdorp
17785506
1, 5-7, 23, 42
SEQ ID NO: 9 and 10
U.S. Patent No. 11155624 in view of Westdorp
18430835
247, 261
SEQ ID NO: 13 and 14
Application No. 17812933
Claim Rejections - 35 USC § 103- New, necessitated by amendment
Claims 1 and 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over WO2014179664 to King et. al. published 6 November 2014 (cited in IDS dated 2/1/2022 Foreign Patent No. 108) in view of U.S. 20140341902 to Maecker et. al published 20 November 2014 (PTO-892 dated 2/21/2025) and Dudley, Jonathan C., et al. "Microsatellite instability as a biomarker for PD-1 blockade." Clinical Cancer Research 22.4 (2016): 813-820 published 14 February 2016.
King et. al. teaches methods of treating a disease or disorder wherein the improper expression or increased activity of PD-1 causes or contributes to the disease, the disease including cancer, selected from a long list of cancers such as melanoma, bladder, breast, and cervical cancer among others [0080]. The method comprises administering a therapeutically effective amount of the PD-1 binding agent, and the therapeutically effective amount may for example be an amount which decreases the PD-1 protein bioactivity in a human ([0081], see also [0085]). The methods of treating cancer by administration of the composition comprising a PD-1 binding agent wherein the cancer is selected from a group are also in claims 43-45. King et. al. teaches anti-PD-1 binding agents that are antibodies comprising a heavy chain variable region (VH) of SEQ ID NO: 22 or 25 and light chain variable region (VL) of SEQ ID NO: 40, which are 100% identical to the VH and VL comprised by SEQ ID NO: 1 and 2, respectively. King et. al. teaches that the binding agent is an antibody or antibody fragment and that it comprises a heavy chain constant region of a suitable class including IgG4 [0054]. King et. al. also teaches that the light chains comprise a C-terminal constant region, either kappa or lamda [0020]. Lastly, King et. al. teach humanization of the antibody via CDR grafting of mouse CDRs into human variable or constant region sequences [0058, 0103].
King et. al. does not teach the anti-PD-1 binding protein is an antibody comprising SEQ ID NO: 1 and SEQ ID NO: 2. The main difference between the instant claims and the methods as taught by King is that King does not teach the full SEQ ID NO: 1 and 2 comprising the same constant domains. This deficiency is resolved by U.S. 20140341902 to Maecker et. al.
Maecker et. al. teaches a method of treating cancer using PD-1 axis binding antagonists and MEK inhibitors (Title, abstract); wherein the PD-1 binding antagonist is an antibody [0014]; and wherein the antibody comprises heavy chain sequence of SEQ ID NO: 22 and a light chain sequence of SEQ ID NO: 23, wherein the constant domain of SEQ ID NO: 22 is identical to residues 117- 443 of instant SEQ ID NO: 1 and the constant domain of SEQ ID NO: 23 is identical to residues 108-214 of instant SEQ ID NO: 2. These are humanized antibodies with IgG4 and kappa constant domains, respectively [0049, 0081].
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to use the sequence of the IgG4 constant domain as taught by Maecker et. al. to benefit from a particular embodiment of IgG4 constant domains to make the antibody of King et. al. with a suitable class of constant domain such as IgG4 as taught by King et. al. This would have a reasonable expectation of success because King et. al. teaches that the different subclasses of IgG including IgG4 are suitable for the anti-PD-1 antibody and an artisan would be able to choose the appropriate subclass for the desired method of treatment.
King et. al. in view of Maecker et. al. do not teach a method of treatment cancer using the anti-PD-1 antibody comprising SEQ ID NO: 1 and SEQ ID NO: 2 wherein the cancer is endometrial cancer, ovarian cancer, or head and neck cancer, and whereupon the cancer is treated in the human (claim 1); wherein the cancer is endometrial cancer (claim 5); wherein the endometrial cancer is microsatellite instability high (MSI-H) or another trait as claimed (claim 6); wherein the cancer is ovarian cancer (claim 7); wherein the ovarian cancer is microsatellite instability high (MSI-H) or another trait as claimed (claim 8); wherein the cancer is head and neck cancer (claim 9).
This deficiency is resolved by Dudley et. al.
Dudley et. al. teaches that “By analyzing the genetics and immune microenvironment of colorectal cancer specimens in parallel, Llosa and colleagues demonstrated, consistent with previous studies, that tumors with a high Th1/CTL infiltrate had defects in mismatch repair (MMR), resulting in microsatellite instability (MSI; ref. 6). Following previous studies (7), the authors suggested that the increased mutational burden in such tumors created neoepitopes responsible for the immune response. Most significantly, they found that tumors with MSI had significant upregulation of immune checkpoint proteins, including PD-1 and PD-L1, enabling them to survive” (p. 814 left column ¶2); A follow-up clinical trial demonstrated the utility of MSI status as a predictive marker for response to PD-1 blockade in stage IV cancer patients. The article reported on 11 patients with MMR-deficient (dMMR) colorectal cancer, 21 with MMR-proficient colorectal cancer, and 9 with dMMR noncolorectal cancer (4 ampullary or cholangiocarcinomas, 2 endometrial carcinomas, 2 small bowel carcinomas, and 1 gastric carcinoma). Patients were stage IV and had failed multiple other chemotherapies. They were treated with pembrolizumab, an anti–PD-1 antibody. MSI was a significant predictor of the immune-related objective response rate (40% in dMMR colorectal cancer, 71% in dMMR noncolorectal cancer, 0% in MMR-proficient colorectal cancer) and also the immune-related progression-free survival rate (78%, 67%, and 11%, respectively) (p. 814 right column ¶1; emphasis is the Examiner’s); “Immune checkpoint blockade inhibition is less toxic than chemotherapeutic regimens and has potential for durable responses in advanced cancer patients who would otherwise live a few months. About 4% of advanced colorectal, 18% of advanced endometrial, and 11% of advanced ovarian cancers have been estimated to harbor MMR deficiency (p. 815 left column ¶1; emphasis is the Examiner’s); “Many causes of somatic hypermutation exist other than MSI: mutations in the DNA polymerases encoded by POLE or POLD1, exposure to external mutagens (cigarette smoke, UV radiation), and endogenous mutagens (reactive oxygen species; refs. 10, 11). It can be predicted that tumors with hypermutation caused by these alternative mechanisms would also have enhanced sensitivity to checkpoint blockade. Indeed, Rizvi and colleagues demonstrated a strong correlation between response to PD-1 blockade and burden of nonsynonymous mutations in non–small cell lung cancer (12)” (p. 815 left column ¶2).
Dudley et. al. teaches that the frequency endometrial cancer has an MSI-H frequency great than 10% (22% or 33%, see Table 1) and that ovarian and head and neck SCC have an MSI-H frequency between 2% and 10% (10% and 3%, respectively, see Table 2).
Dudley et. al. teaches “Further studies are needed to assess the potential for MSI status to guide immunotherapy across tumor types. If initial results are validated, however, it would represent a significant advance in precision medicine. If the mechanism proposed for the efficacy of MSI-guided immunotherapy is correct (Fig. 1), the ultimate biomarker for immunotherapeutic response is not MSI or even the mutational burden but the presence of immunogenic neoepitopes. This could potentially be assessed more directly with future assays, leading to more precise guidance of immunotherapy, but at present, MSI status is a practical surrogate” (p. 818 right column ¶1).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to perform the method of treating cancer as taught by King et. al. using the anti-PD-1 binding antibody comprising an IgG4 binding domains as taught by King et. al. in view of Maecker et. al. on the patient population with MSI-H endometrial cancer, MSI-H ovarian cancer, or MSI-H head and neck cancer in order to benefit from treating a population that is expected to more strongly benefit from anti-PD-1 therapy due to the increased immunogenicity of MSI-H cancers as taught by Dudley et. al. on the cancers that have among the highest portion of MSI-H tumors as taught by Dudley et. al. This would have a reasonable expectation of success because Dudley et. al. teaches that patients with MSI-H non-colorectal cancer tumors had a 71% objective response rate to anti-PD-1 therapy; further, Dudley et. al. cites studies from across multiple cancer subtypes that suggest a mechanism by which MSI-H would lead to increased response rate to immunotherapy such as PD-1 blockade, and therefore a person of ordinary skill in the art would have a reasonable expectation of successfully treating the patients of Dudley et. al. using the method of treatment of King et. al. in view of Maecker.
Response to Arguments
Applicant argues that the amendments to claim 1 render the rejection moot (Remarks 2/6/2026 p. 1). This has been fully considered; however, King et. al., Maecker et. al., and Dudley et. al. make obvious the newly amended claims as described in the new 103 rejection, necessitated by amendment, above and the argument is moot in view of the new rejection.
Double Patenting- New, necessitated by amendment
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.
U.S. Patent No. 11155624
Claims 1, 5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 11155624. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of the '624 patent.
‘624 teaches a method of treating cancer (claim 4) in a human that is responsive to PD-1 inhibition, which method comprises administering to the human an effective amount of an antibody that binds PD-1 comprising a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO: ID NO: 1 (identical to instant SEQ ID NO: ID NO: 1) and a light chain polypeptide comprising the amino acid sequence of SEQ ID NO: ID NO: 2 (identical to instant SEQ ID NO: ID NO: 2)(claim 1), whereupon the cancer is treated in the human. Claim 5 recites the method of claim 4 wherein the cancer is selected from the group consisting of endometrial cancer, breast cancer, ovarian cancer, and lung cancer (emphasis is the Examiner’s).
Claims 6, 8, and 9 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 111155624 as applied to claims 1, 5, and 7 and in further view of Dudley, Jonathan C., et al. "Microsatellite instability as a biomarker for PD-1 blockade." Clinical Cancer Research 22.4 (2016): 813-820 published 14 February 2016.
The teachings of the ‘624 claims as applied to claims 1, 5, and 7 are in the NSDP rejection above.
The ‘624 claims do not teach the method of treating endometrial cancer wherein the cancer is MSI-H or has a trait as claimed (claim 6); the method of treating ovarian cancer wherein the cancer is MSI-H or has a trait as claimed (claim 8); or wherein the cancer is head and neck cancer. These deficiencies are resolved by Dudley et. al.
The teachings of Dudley et. al. are in the 103 rejection above and are incorporated by reference herein. Briefly, Dudley et. al. teaches that MSI-H may act as a biomarker for susceptibility to immunotherapy such as PD-1 blockade and that endometrial cancer, ovarian cancer, and head and neck cancer are cancers with a high percent of MSI-H detected.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to perform the method of treating cancer and specifically endometrial or ovarian cancer as taught by ‘624 on the patient population with MSI-H endometrial cancer, MSI-H ovarian cancer, or MSI-H head and neck cancer in order to benefit from treating a population that is expected to more strongly benefit from anti-PD-1 therapy due to the increased immunogenicity of MSI-H cancers as taught by Dudley et. al. on the cancers that have among the highest portion of MSI-H tumors as taught by Dudley et. al. This would have a reasonable expectation of success because Dudley et. al. teaches that patients with MSI-H non-colorectal cancer tumors had a 71% objective response rate to anti-PD-1 therapy; further, Dudley et. al. cites studies from across multiple cancer subtypes that suggest a mechanism by which MSI-H would lead to increased response rate to immunotherapy such as PD-1 blockade, and therefore a person of ordinary skill in the art would have a reasonable expectation of successfully treating the patients of Dudley et. al. using the method of treatment of ‘624.
U.S. Patent No. 9815897
Claims 1 and 5-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 21-22, 33-34 of U.S. Patent No. 9815897 (cited in IDS dated 2/1/2021 No. 27) in view of Dudley, Jonathan C., et al. "Microsatellite instability as a biomarker for PD-1 blockade." Clinical Cancer Research 22.4 (2016): 813-820 published 14 February 2016.
Patent ‘897 teaches an PD-1 binding agent that is an antibody with the heavy chain immunoglobulin sequence comprising SEQ ID NO: 23 and light chain immunoglobulin comprising SEQ ID NO: 40 (claims 1-4, 100% identical to the heavy and light chain variable regions of instant SEQ ID NO: 1 and 2). Claim 5 teaches that the binding agent is an antibody or antigen-binding fragment thereof. Claim 6 and 7 teach that the antibody comprises SEQ ID NO: 23, 40, and an IgG4 heavy chain constant region (Fc). Claim 21 teaches a method of treating cancer in a human comprising administering to the human an effective amount of the PD-1 binding agent of claim 1. Claim 22 teaches a method of enhancing an immune response or increasing the activity of an immune cell comprising contacting an effective amount of the PD-1 binding agent of claim 1 to the immune cell. Claim 33 teaches the method of claim 21 wherein the cancer is selected from a group of cancer subtypes.
The ‘624 claims do not teach the method of treating wherein the cancer is endometrial cancer, ovarian cancer, or head and neck cancer (claim 1); wherein the cancer is endometrial cancer (claim 5); wherein endometrial cancer wherein the cancer is MSI-H or has a trait as claimed (claim 6); wherein the cancer is ovarian cancer (claim 7); the method of treating ovarian cancer wherein the cancer is MSI-H or has a trait as claimed (claim 8); or wherein the cancer is head and neck cancer (claim 9). These deficiencies are resolved by Dudley et. al.
The teachings of Dudley et. al. are in the 103 rejection above and are incorporated by reference herein. Briefly, Dudley et. al. teaches that MSI-H may act as a biomarker for susceptibility to immunotherapy such as PD-1 blockade and that endometrial cancer, ovarian cancer, and head and neck cancer are cancers with a high percent of MSI-H detected.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to perform the method of treating cancer generically as taught by ‘897 on the patient population with MSI-H endometrial cancer, MSI-H ovarian cancer, or MSI-H head and neck cancer in order to benefit from treating a population that is expected to more strongly benefit from anti-PD-1 therapy due to the increased immunogenicity of MSI-H cancers as taught by Dudley et. al. on the cancers that have among the highest portion of MSI-H tumors as taught by Dudley et. al. This would have a reasonable expectation of success because Dudley et. al. teaches that patients with MSI-H non-colorectal cancer tumors had a 71% objective response rate to anti-PD-1 therapy; further, Dudley et. al. cites studies from across multiple cancer subtypes that suggest a mechanism by which MSI-H would lead to increased response rate to immunotherapy such as PD-1 blockade, and therefore a person of ordinary skill in the art would have a reasonable expectation of successfully treating the patients of Dudley et. al. using the method of treatment of ‘897.
U.S. Patent No. 12415855
Claims 1 and 5-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of U.S. Patent No. 12415855 (formerly copending Application No. 17812933) in view of Dudley, Jonathan C., et al. "Microsatellite instability as a biomarker for PD-1 blockade." Clinical Cancer Research 22.4 (2016): 813-820 published 14 February 2016.
The claims 1, 2, and 4 of ‘855 recite a method of treating colorectal cancer in a human subject, the method comprising an IgG4 humanized monoclonal anti-PD-1 antibody at a specified dose, wherein the anti-PD-1 antibody comprises a heavy chain sequence of SEQ ID NO: 3 (identical to instant SEQ ID NO: 1) and a light chain of instant SEQ ID NO: 4, wherein the human has not had surgery for colorectal cancer (claim 1). The claims also teach wherein the colorectal cancer of claim 1 is associated with a high tumor mutational burden, microsatellite instability (MSI), has a high MSI status, has defective DNA mismatch repair, or is homologous recombination repair deficient (claim 2 and 4).
The ‘855 claims do not teach the method of treating wherein the cancer is endometrial cancer, ovarian cancer, or head and neck cancer (claim 1); wherein the cancer is endometrial cancer (claim 5); wherein endometrial cancer wherein the cancer is MSI-H or has a trait as claimed (claim 6); wherein the cancer is ovarian cancer (claim 7); the method of treating ovarian cancer wherein the cancer is MSI-H or has a trait as claimed (claim 8); or wherein the cancer is head and neck cancer (claim 9). These deficiencies are resolved by Dudley et. al.
The teachings of Dudley et. al. are in the 103 rejection above and are incorporated by reference herein. Briefly, Dudley et. al. teaches that MSI-H may act as a biomarker for susceptibility to immunotherapy such as PD-1 blockade and that endometrial cancer, ovarian cancer, and head and neck cancer are cancers with a high percent of MSI-H detected.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to perform the method of treating colorectal cancer as taught by ‘855 on the patient population with MSI-H endometrial cancer, MSI-H ovarian cancer, or MSI-H head and neck cancer in order to benefit from treating a population that is expected to strongly benefit from anti-PD-1 therapy due to the increased immunogenicity of MSI-H cancers (such as colorectal cancer and non-colorectal cancers like endometrial cancer) as taught by Dudley et. al. on the cancers that have among the highest portion of MSI-H tumors as taught by Dudley et. al. This would have a reasonable expectation of success because Dudley et. al. teaches that patients with MSI-H non-colorectal cancer tumors had a 71% objective response rate to anti-PD-1 therapy; further, Dudley et. al. cites studies from across multiple cancer subtypes that suggest a mechanism by which MSI-H would lead to increased response rate to immunotherapy such as PD-1 blockade and ‘855 suggests treating the particular colorectal cancer patients that are MSI-H, and therefore a person of ordinary skill in the art would have a reasonable expectation of successfully treating the patients of Dudley et. al. using the method of treatment of ‘855.
U.S. Patent No. 11407830
Claims 1 and 5-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11407830 in view of Dudley, Jonathan C., et al. "Microsatellite instability as a biomarker for PD-1 blockade." Clinical Cancer Research 22.4 (2016): 813-820 published 14 February 2016.
The ‘830 claims recite a method of treating cancer in a human subject, the method comprising administering an IgG4 humanized monoclonal anti-PD-1 antibody at particular doses and schedules wherein the anti-PD-1 antibody comprises SEQ ID NO: 3 and SEQ ID NO: 4, which are identical to instant SEQ ID NO: 1 and 2. Claim 2 recites wherein the cancer is a cancer associated with high mutational burden, a cancer that is characterized by microsatellite instability, a cancer that has high microsatellite instability, a cancer associated with high TMB and MSI-H, and cancer that has defective DNA mismatch repair, a cancer comprising a mutations in polymerase epsilon (POLE), among others.
The ‘830 claims do not explicitly teach the method of treating wherein the cancer is endometrial cancer, ovarian cancer, or head and neck cancer. These deficiencies are resolved by Dudley et. al.
The teachings of Dudley et. al. are in the 103 rejection above and are incorporated by reference herein. Briefly, Dudley et. al. teaches that MSI-H may act as a biomarker for susceptibility to immunotherapy such as PD-1 blockade and that endometrial cancer, ovarian cancer, and head and neck cancer are cancers with a high percent of MSI-H detected.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to perform the method of treating colorectal cancer as taught by ‘830 on the patient population with MSI-H endometrial cancer, MSI-H ovarian cancer, or MSI-H head and neck cancer in order to benefit from particular embodiments of MSI-H cancers as taught by Dudley et. al. to make a particular embodiment of treating MSI-H cancer as taught by the ‘830 claims. This would have a reasonable expectation of success because Dudley et. al. teaches that patients with MSI-H non-colorectal cancer tumors had a 71% objective response rate to anti-PD-1 therapy; further, Dudley et. al. cites studies from across multiple cancer subtypes that suggest a mechanism by which MSI-H would lead to increased response rate to immunotherapy such as PD-1 blockade and ‘830 suggests treating cancer patients that are MSI-H, and therefore a person of ordinary skill in the art would have a reasonable expectation of successfully treating the patients of Dudley et. al. using the method of treatment of ‘830.
Additional Non-Statutory Double Patenting (NSDP) Rejections:
Patent No:
Rejected over Application Claims:
SEQ ID NOs identical to instant SEQ ID NO: 1 and 2:
Application/Patent with similar NSDP rejections:
11661453*
1-6
SEQ ID NO: 9 and 10
U.S. Patent No. 11155624 in view of Dudley
11926665
1-10
SEQ ID NO: 13 and 14
U.S. Patent No. 12415855 in view of Dudley
11753472*
3, 5, 7, and 10
N/A*
U.S. Patent No. 9815897 in view of Dudley
10738117 (cited in IDS dated 2/1/2021, No. 28)
1-8
SEQ ID NO: 23 and 40
U.S. Patent No. 9815897 in view of Dudley
*Starred patents or applications contain claims to TSR-042, which is identical to the instant anti-PD-1 antibody, as evidenced by U.S. 11661453 col 2 line 63- col 3 line 23.
**Double starred patents or applications contain claims to dostarlimab, which is identical to the instant anti-PD-1 antibody, as evidenced by Drugbank “DB15627- Dostarlimab”. Web, accessed 16 March 2026.
Additional Provisional NSDP Rejections:
Application No:
Rejected over Application Claims:
SEQ ID NOs identical to instant SEQ ID NO: 1 and 2:
Application/Patent with similar prov. NSDP rejections:
17273680*
1, 6-10, 19-22
SEQ ID NO: 9 and 10
U.S. Patent No. 11155624 in view of Dudley
17785506
53-75
SEQ ID NO: 9 and 10
U.S. Patent No. 9815897 in view of Dudley
18430835
247, 261
SEQ ID NO: 13 and 14
U.S. Patent No. 9815897 in view of Dudley
19532649
1-5
SEQ ID NO: 1 and 2
U.S. Patent No. 9815897 in view of Dudley
19237504
1-10
N/A**
U.S. Patent No. 9815897 in view of Dudley
19304196
1-18
SEQ ID NO: 3 and 4
U.S. Patent No. 11407830 in view of Dudley
19132920
1, 4, 6-7, 13, 14, 16-18, 22, 25, 30, 38, 39, 41-43, 55, 72-74, 77-78
N/A**
U.S. Patent No. 11155624 and U.S. Patent No. 11155624 in view of Dudley
*Starred patents or applications contain claims to TSR-042, which is identical to the instant anti-PD-1 antibody, as evidenced by U.S. 11661453 col 2 line 63- col 3 line 23.
**Double starred patents or applications contain claims to dostarlimab, which is identical to the instant anti-PD-1 antibody, as evidenced by Drugbank “DB15627- Dostarlimab”. Web, accessed 16 March 2026.
Response to Arguments
Applicant argues that the amendments to claim 1 render the rejection moot (Remarks 2/6/2026 p. 2-3). This has been fully considered; however, the new NSDP rejections, necessitated by amendment, are above and the argument is moot in view of the new rejection.
Conclusion
No claims are allowed.
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/KATHLEEN CUNNINGCHEN/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678