CTNF 18/580,255 CTNF 101787 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Status Claims 3-5, 7-12, 15-31, 35, 38, 41, 45-47, 51-52, 54-57, 60, 64-65, 67-68, and 70-82 are cancelled. Claims 1-2, 6, 13-14, 32-34, 36-37, 39-40, 42-44, 48-50, 53, 58-59, 61-63, 66, and 69 are pending and currently under consideration for patentability under 37 CFR 1.104. Priority This application is a 371 of PCT/US2022/037414 (filed 07/18/2022) which claims benefit of Provisional U.S. Application No. 63/223,739 (filed 07/20/2021). Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-2, 6, 13-14, 32-34, 36-37, 39-40, 42-44, 48-50, 53, 58-59, 61-63, 66, and 69 have an effective filing date of 07/20/2021 corresponding to Provisional U.S. Application No. 63/223,739. Information Disclosure Statement The information disclosure statements filed on 04/25/2024 and 05/30/2025 have been considered. Signed copies are enclosed. Specification 06-16-01 AIA The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. Claim Rejections - 35 USC § 112(a) 07-30-01 AIA 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. 07-31-03 AIA Claim s 1-2, 32-34, 36-37, 39-40, 42-44, 48-50, and 53 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a method of treating mesothelioma and non-small cell lung cancer in a human subject comprising administering MK-4830 , pembrolizumab , cisplatin, and pemetrexed , does not reasonably provide enablement for a method of treating all cancer in a human subject comprising administering any ILT4 antagonist (¶ 0221), any PD-1 antagonist (¶ 0220), cisplatin, and pemetrexed . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370. The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444. (1) The nature of the invention and (5) the breadth of the claims Claim 1 is drawn to “[a] method of treating cancer, comprising administering to a human patient in need thereof: (a) a PD-1 antagonist; (b) an ILT4 antagonist; (c) cisplatin; and (d) pemetrexed” (lines 1-6). The field of invention resides in the fields of biochemistry and protein chemistry, complex and unpredictable arts. Claim 1 is broad and inclusive of all types of cancer in humans generally. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claim is directed. The claim is extremely broad due to the vast number of possible cancer types and tumor cell growth mechanisms represented by the terms “treating cancer”. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level. They can occur in pretty much every part of the body. Here are some assorted categories as examples: CNS cancers cover a very diverse range of cancers in many categories and subcategories. There are an immense range of neuroepithelial tumors. Gliomas, the most common subtype of primary brain tumors, most of which are aggressive, highly invasive, and neurologically destructive tumors are considered to be among the deadliest of human cancers. Leukemia is any malignant neoplasm of the blood-forming tissues. Leukemia can arise from many different sources. These include viruses such as EBV, which causes Burkitt's lymphoma, and HTLV-1, linked to certain T cell leukemias. Others are linked to genetic disorders, such as Fanconi's anemia, which is a familial disorder, and Down's Syndrome. Other leukemias are caused by exposure to carcinogens such as benzene, and some are actually caused by treatment with other neoplastic agents. Still other leukemias arise from ionizing radiation, and many are idiopathic. Carcinomas of the Liver include hepatocellular carcinoma, combined hepatocellular cholangiocarcinoma, cholangiocarcinoma (intrahepatic), bile duct cystadenocarcinoma and undifferentiated carcinoma of the liver. There is also cancer of the blood vessels in the liver (hemangioendothelioma), primary non-Hodgkin’s lymphoma of the liver, undifferentiated liver sarcoma (also known as undifferentiated embryonal sarcoma), primary pleomorphic liver sarcoma, angiosarcoma of the liver, and primary malignant melanoma of the liver. Most liver cancers are secondary, especially those originating in the breast, lung, or gallbladder, as well as both Hodgkin's or non-Hodgkin's lymphoma. The main types of lung and pleural cancer are small cell (i.e. oat cell, including combined oat cell), adenocarcinomas, bronchioloalveolar carcinomas (nonmucinous, mucinous, and mixed mucinous and nonmucinous or indeterminate cell type), acinar, papillary carcinoma, solid adenocarcinoma with mucin, adenocarcinoma with mixed subtypes, well-differentiated fetal adenocarcinoma, mucinous (colloid) adenocarcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma, and clear cell adenocarcinoma), squamous cell (papillary, clear cell, small cell and basaloid), mesothelioma (including epithelioid, sarcomatoid, desmoplastic and biphasic) and large cell carcinoma (which include large-cell neuroendocrine carcinoma, combined large-cell neuroendocrine carcinoma, basaloid carcinoma, clear cell carcinoma lymphoepithelioma-like carcinoma, and large-cell carcinoma with rhabdoid phenotype). Thyroid cancer comes in four forms: papillary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer. Based on the special definitions given in the specification, “’PD-1 antagonist’ means any chemical compound or biological molecule that blocks binding of PD-L1 to PD-1” (¶ 0220) and “’ILT4 antagonist’ means any chemical compound or biological molecule that blocks binding of ILT4 to HLA-G, HLA-A, HLA-B, HLA-F, or angiopoietin-like protein” (¶ 0221). Protein antagonists include but are not limited to antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules. These chemical and biological compounds are varied. For example, full-length antibodies are ~150 kDa and bivalent while single-domain antibodies are ~15 kDa and monovalent (Smith, New Horizons in Therapeutic Antibody Discovery: Opportunities and Challenges versus Small-Molecule Therapeutics, Journal of Biomolecular Screening, 2015, Pg. 438, Fig. 1). Compared to biologics like antibodies and their derivatives, small molecules are low molecular weight compounds that are less fragile and susceptible to degradation (Ngo and Garneau-Tsodikova, What are the drugs of the future?, MedChemComm, 2018; Pg. 757, column 1, ¶ 2; Pg. 758, column 1, ¶ 3). Consequently, claim 1 is directed to complex and unpredictable fields, where the successful treatment of all cancer cannot be readily extrapolated from a combination therapy of any ILT4 antagonist, any PD-1 antagonist, cisplatin, and pemetrexed. As such, claim 1 generally reads on a method of treating all cancer in a human subject comprising administering any ILT4 antagonist (¶ 0221), any PD-1 antagonist (¶ 0220), cisplatin, and pemetrexed, the full scope of which is not enabled by the method as instantly claimed. (2) The state of the prior art While the state of the art is relatively high with regard to the treatment of specific cancer types, the state of the art with regard to treating cancer broadly is underdeveloped. In particular, there is no known anticancer agent that is effective against all cancer cell types. Even within a given cancer type, “[i]ntertumor and intratumor heterogeneity are important obstacles to overcome when designing the most effective therapeutic strategies for patients with cancer. The genotypic and phenotypic variability of tumors can have important consequences for diagnosis, prognosis, and treatment” (Lovly et al., Pg. e586, Integrating the Heterogeneity of Cancer in Clinical Decision Making, first paragraph). Therefore, the variability among tumors within a cancer type makes it difficult to predict whether a therapeutic approach effective in one tumor type will be effective in another. Accordingly, the treatment of all cancer remains an unpredictable field in which efficacy cannot be readily extrapolated across different cancers or tumor subtypes. Protein antagonists include but are not limited to antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules. These chemical and biological compounds are varied. For example, full-length antibodies are ~150 kDa and bivalent while single-domain antibodies are ~15 kDa and monovalent (Smith, New Horizons in Therapeutic Antibody Discovery: Opportunities and Challenges versus Small-Molecule Therapeutics, Journal of Biomolecular Screening, 2015, Pg. 438, Fig. 1). Compared to biologics like antibodies and their derivatives, small molecules are low molecular weight compounds that are less fragile and susceptible to degradation (Ngo and Garneau-Tsodikova, What are the drugs of the future?, MedChemComm, 2018; Pg. 757, column 1, ¶ 2; Pg. 758, column 1, ¶ 3). In regard to antagonistic antibodies, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, March 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Colman (Research in Immunology, 145:33-36, 1994) teaches that even a very conservative substitution may abolish binding or may have very little effect on the binding affinity (Pg. 35, top of left column; Pg. 33, right column). Taken together, the specific sequences for an antagonistic anti-ILT antibody and antagonistic anti-PD-1 antibody are needed as it would require undue experimentation to reproduce the claimed antagonists. Therefore, a person having ordinary skill in the art would not recognize which PD-1 and ILT4 antagonists are required in combination with cisplatin and pemetrexed to treat cancer because (i) antagonists are varied including antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules and (ii) even within a category of antagonists such as antagonistic antibodies, there is too much unpredictably in this field to ascertain the identity of an antibody without its sequence. Merck Sharp & Dohme LLC (referred to as Merck; Study: NCT03564691, Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab [MK-3475] in Participants With Advanced Solid Tumors [MK-4830-001], ClinicalTrials.Gov, first submitted 06/11/2018, last update 06/17/2020) teach MK-4830, pembrolizumab, carboplatin, and pemetrexed in the treatment of non-small cell lung cancer. Carboplatin is a platinum-containing compound that is equivalent to cisplatin and can therefore be substituted for cisplatin (see 103 rejection for more information). (3) The relative skill of those in the art and (4) the predictability or unpredictability of the art , This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). While the use of ILT4 and PD-1 antagonists in combination with cisplatin and pemetrexed to treat cancer is well known by a person having ordinary skill in the art, i.e. someone with a PhD and/or MD ( the relative skill of those in the art ), the use of any ILT4 antagonist and any PD-1 antagonist in combination with cisplatin and pemetrexed to treat all cancer within the scope of claim 1 is not predictable. The predictability of applying ILT4 and PD-1 antagonists in combination with cisplatin and pemetrexed to treat cancer would be low given that 1) it is not established that any ILT4 antagonist and any PD-1 antagonist in combination with cisplatin and pemetrexed treats all cancer (i.e. this combination is not a universal anticancer agent as no such agent is known, see Lovly et al. explanation in the state of the prior art section) and 2) the instant application fails to demonstrate treatment of all cancer with any ILT4 antagonist and any PD-1 antagonist in combination with cisplatin and pemetrexed ( the predictability or unpredictability of the art ) . (6) The amount of direction or guidance presented, (7) the presence or absence of working examples, and (8) the quantity of the experimentation Prior art teaches MK-4830, pembrolizumab, cisplatin, and pemetrexed in a method of treating non-small cell lung cancer. The specification shows a method of treating mesothelioma in a human subject comprising administering MK-4830, pembrolizumab, cisplatin, and pemetrexed (¶ 0731, “Arm L is to test the combination of 800 mg MK-4830 Q3W, 200 mg pembrolizumab Q3W, 75 mg/m 2 cisplatin and 500 mg/m 2 pemetrexed Q3W in mesothelioma patients”). The specification does not provide any additional examples or guidance on how to use ILT4 and PD-1 antagonists other than MK-4830 and pembrolizumab to treat any other cancer besides mesothelioma as recited in the claim ( the amount of direction or guidance presented and the presence or absence of working examples ). The amount of experimentation would not be reasonable because it would require determining which ILT4 and PD-1 antagonists to use to treat various cancers. Protein antagonists include but are not limited to antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules. These chemical and biological compounds are varied as evidenced by Smith and Ngo and Garneau-Tsodikova (see nature of the invention and breadth of the claims). In regard to antagonistic antibodies, even minor changes in the amino acid sequences of an antibody may dramatically affect antigen-binding function as evidenced by Rudikoff et al. and Colman (see nature of the invention and breadth of the claims). Taken together, the specific sequences for an antagonistic anti-ILT antibody and antagonistic anti-PD-1 antibody are needed as it would require undue experimentation to reproduce the claimed antagonists. Therefore, a person having ordinary skill in the art would not recognize which PD-1 and ILT4 antagonists are required in combination with cisplatin and pemetrexed to treat cancer because (i) antagonists are varied including antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules and (ii) even within a category of antagonists such as antagonistic antibodies, there is too much unpredictably in this field to ascertain the identity of an antibody without its sequence. It is not routine to determine how such a broad class of molecules would treat all cancer. Undue experimentation would be required to determine whether ILT4 and PD-1 antagonists of any biological or chemical makeup in combination with cisplatin and pemetrexed would treat all cancer ( the quantity of the experimentation , see MPEP 2164.06). The scope of claim 1 is extremely broad; it recites multiple cancers and the use of various ILT4 and PD-1 antagonists that require the specification of the instant application to provide support for the entire scope of the claim. The specification fails to show that a person having ordinary skill in the art could treat all recited diseases without undue experimentation. Moreover, as described above, cancer is not known to be treated generically. Evidence of efficacy of administering MK-4830, pembrolizumab, cisplatin, and pemetrexed in a method of treating mesothelioma and non-small cell lung cancer in a human subject is provided in the specification and prior art. Therefore, the method of treating mesothelioma and non-small cell lung cancer in a human subject comprising administering MK-4830 , pembrolizumab , cisplatin, and pemetrexed is supported. The method of treating all cancer in a human subject comprising administering any ILT4 antagonist , any PD-1 antagonist , cisplatin, and pemetrexed is not supported. Claim 1 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to treat all cancer in a human subject comprising administering any ILT4 antagonist , any PD-1 antagonist , cisplatin, and pemetrexed with a predictability of success for the reasons outlined above. Claims 2, 32-34, 36-37, 39-40, 42-44, 48-50, and 53 are included in this rejection as they depend on and/or incorporate claim 1. 07-31-03 AIA Claim s 13-14, 58-59, 61-63, 66, and 69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a method of treating ovarian cancer and triple-negative breast cancer in a human subject comprising administering (i) an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 of the instant application or MK-4830 , (ii) pembrolizumab , and (ii) paclitaxel or docetaxel , does not reasonably provide enablement for a method of treating all cancer in a human subject comprising administering any ILT4 antagonist (¶ 0221), any PD-1 antagonist (¶ 0220), and any mitosis inhibitor (¶ 0239) . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. See previous 112(a) rejection for information regarding scope of enablement and Wands factors. (1) The nature of the invention and (5) the breadth of the claims Claim 13 is drawn to “[a] method of treating cancer, comprising administering to a human patient in need thereof: (a) a PD-1 antagonist; (b) an ILT4 antagonist; and (c) a mitosis inhibitor” (lines 1-5). The field of invention resides in the fields of biochemistry and protein chemistry, complex and unpredictable arts. Claim 13 is broad and inclusive of all types of cancer in humans generally. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claim is directed. The claim is extremely broad due to the vast number of possible cancer types and tumor cell growth mechanisms represented by the terms “treating cancer”. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level. They can occur in pretty much every part of the body. Here are some assorted categories as examples: CNS cancers cover a very diverse range of cancers in many categories and subcategories. There are an immense range of neuroepithelial tumors. Gliomas, the most common subtype of primary brain tumors, most of which are aggressive, highly invasive, and neurologically destructive tumors are considered to be among the deadliest of human cancers. Leukemia is any malignant neoplasm of the blood-forming tissues. Leukemia can arise from many different sources. These include viruses such as EBV, which causes Burkitt's lymphoma, and HTLV-1, linked to certain T cell leukemias. Others are linked to genetic disorders, such as Fanconi's anemia, which is a familial disorder, and Down's Syndrome. Other leukemias are caused by exposure to carcinogens such as benzene, and some are actually caused by treatment with other neoplastic agents. Still other leukemias arise from ionizing radiation, and many are idiopathic. Carcinomas of the Liver include hepatocellular carcinoma, combined hepatocellular cholangiocarcinoma, cholangiocarcinoma (intrahepatic), bile duct cystadenocarcinoma and undifferentiated carcinoma of the liver. There is also cancer of the blood vessels in the liver (hemangioendothelioma), primary non-Hodgkin’s lymphoma of the liver, undifferentiated liver sarcoma (also known as undifferentiated embryonal sarcoma), primary pleomorphic liver sarcoma, angiosarcoma of the liver, and primary malignant melanoma of the liver. Most liver cancers are secondary, especially those originating in the breast, lung, or gallbladder, as well as both Hodgkin's or non-Hodgkin's lymphoma. The main types of lung and pleural cancer are small cell (i.e. oat cell, including combined oat cell), adenocarcinomas, bronchioloalveolar carcinomas (nonmucinous, mucinous, and mixed mucinous and nonmucinous or indeterminate cell type), acinar, papillary carcinoma, solid adenocarcinoma with mucin, adenocarcinoma with mixed subtypes, well-differentiated fetal adenocarcinoma, mucinous (colloid) adenocarcinoma, mucinous cystadenocarcinoma, signet ring adenocarcinoma, and clear cell adenocarcinoma), squamous cell (papillary, clear cell, small cell and basaloid), mesothelioma (including epithelioid, sarcomatoid, desmoplastic and biphasic) and large cell carcinoma (which include large-cell neuroendocrine carcinoma, combined large-cell neuroendocrine carcinoma, basaloid carcinoma, clear cell carcinoma lymphoepithelioma-like carcinoma, and large-cell carcinoma with rhabdoid phenotype). Thyroid cancer comes in four forms: papillary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer. Based on the special definitions given in the specification: “’PD-1 antagonist’ means any chemical compound or biological molecule that blocks binding of PD-L1 to PD-1” (¶ 0220), “’ILT4 antagonist’ means any chemical compound or biological molecule that blocks binding of ILT4 to HLA-G, HLA-A, HLA-B, HLA-F, or angiopoietin-like protein” (¶ 0221), and “’Mitosis inhibitor’ refers to a compound that inhibits mitosis or division of cells” (¶ 0239). Protein antagonists include but are not limited to antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules. These chemical and biological compounds are varied. For example, full-length antibodies are ~150 kDa and bivalent while single-domain antibodies are ~15 kDa and monovalent (Smith, New Horizons in Therapeutic Antibody Discovery: Opportunities and Challenges versus Small-Molecule Therapeutics, Journal of Biomolecular Screening, 2015, Pg. 438, Fig. 1). Compared to biologics like antibodies and their derivatives, small molecules are low molecular weight compounds that are less fragile and susceptible to degradation (Ngo and Garneau-Tsodikova, What are the drugs of the future?, MedChemComm, 2018; Pg. 757, column 1, ¶ 2; Pg. 758, column 1, ¶ 3). Mitosis inhibitors include but are not limited to eribulin, docetaxel, paclitaxel, vincristine, teniposide, etoposide, vinblastine, vinorelbine, cabazitaxel, ixabepilone, and estramustine. These medications have ranges of tolerability in patients and dosing regimens. For example, paclitaxel administered weekly is better tolerated in breast cancer patients compared to docetaxel administered once every three weeks (Bachinschi et al., Pg. 1419, Abstract, Introduction, “Weekly Ptx [paclitaxel] is better tolerated than q3w Dtx [docetaxel]” in breast cancer treatment). Consequently, claim 13 is directed to complex and unpredictable fields, where the successful treatment of all cancer cannot be readily extrapolated from a combination therapy of any ILT4 antagonist, any PD-1 antagonist, and any mitosis inhibitor. As such, claim 13 generally reads on a method of treating all cancer in a human subject comprising administering any ILT4 antagonist (¶ 0221), any PD-1 antagonist (¶ 0220), and any mitosis inhibitor (¶ 0239), the full scope of which is not enabled by the method as instantly claimed. (2) The state of the prior art While the state of the art is relatively high with regard to the treatment of specific cancer types, the state of the art with regard to treating cancer broadly is underdeveloped. In particular, there is no known anticancer agent that is effective against all cancer cell types. Even within a given cancer type, “[i]ntertumor and intratumor heterogeneity are important obstacles to overcome when designing the most effective therapeutic strategies for patients with cancer. The genotypic and phenotypic variability of tumors can have important consequences for diagnosis, prognosis, and treatment” (Lovly et al., Pg. e586, Integrating the Heterogeneity of Cancer in Clinical Decision Making, first paragraph). Therefore, the variability among tumors within a cancer type makes it difficult to predict whether a therapeutic approach effective in one tumor type will be effective in another. Accordingly, the treatment of all cancers remain an unpredictable field in which efficacy cannot be readily extrapolated across different cancers or tumor subtypes. Protein antagonists include but are not limited to antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules. These chemical and biological compounds are varied. For example, full-length antibodies are ~150 kDa and bivalent while single-domain antibodies are ~15 kDa and monovalent (Smith, New Horizons in Therapeutic Antibody Discovery: Opportunities and Challenges versus Small-Molecule Therapeutics, Journal of Biomolecular Screening, 2015, Pg. 438, Fig. 1). Compared to biologics like antibodies and their derivatives, small molecules are low molecular weight compounds that are less fragile and susceptible to degradation (Ngo and Garneau-Tsodikova, What are the drugs of the future?, MedChemComm, 2018; Pg. 757, column 1, ¶ 2; Pg. 758, column 1, ¶ 3). In regard to antagonistic antibodies , even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, March 1982). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Colman (Research in Immunology, 145:33-36, 1994) teaches that even a very conservative substitution may abolish binding or may have very little effect on the binding affinity (Pg. 35, top of left column; Pg. 33, right column). Taken together, the specific sequences for an antagonistic anti-ILT antibody and antagonistic anti-PD-1 antibody are needed as it would require undue experimentation to reproduce the claimed antagonists. Therefore, a person having ordinary skill in the art would not recognize which PD-1 and ILT4 antagonists are required in combination with a mitosis inhibitor to treat cancer because (i) antagonists are varied including antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules and (ii) even within a category of antagonists such as antagonistic antibodies, there is too much unpredictably in this field to ascertain the identity of an antibody without its sequence. Mitosis inhibitors include but are not limited to eribulin, docetaxel, paclitaxel, vincristine, teniposide, etoposide, vinblastine, vinorelbine, cabazitaxel, ixabepilone, and estramustine. These medications have ranges of tolerability in patients and dosing regimens. For example, paclitaxel administered weekly is better tolerated in breast cancer patients compared to docetaxel administered once every three weeks (Bachinschi et al., Pg. 1419, Abstract, Introduction, “Weekly Ptx [paclitaxel] is better tolerated than q3w Dtx [docetaxel]” in breast cancer treatment). US 20180298096 A1 (referred to as US ‘096, published 2018-10-18) teaches a method of treating cancer with (i) an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 of the instant application, (ii) pembrolizumab, and (iii) paclitaxel or docetaxel (see 102 rejection for more information). Cancer includes breast and ovarian cancer (¶ 0003). (3) The relative skill of those in the art and (4) the predictability or unpredictability of the art, This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). While the use of ILT4 antagonists, PD-1 antagonists, and mitosis inhibitors to treat cancer is well known by a person having ordinary skill in the art, i.e. someone with a PhD and/or MD ( the relative skill of those in the art ), the use of any ILT4 antagonist, any PD-1 antagonist, and any mitosis inhibitor to treat all cancer within the scope of claim 13 is not predictable. The predictability of applying ILT4 antagonists, PD-1 antagonists, and mitosis inhibitors to treat cancer would be low given that 1) it is not established that any ILT4 antagonist and any PD-1 antagonist in combination with a mitosis inhibitor treats all cancer (i.e. this combination is not a universal anticancer agent as no such agent is known, see Lovly et al. explanation in the state of the prior art section) and 2) the instant application fails to demonstrate treatment of all cancer with any ILT4 antagonist, any PD-1 antagonist, and any mitosis inhibitor ( the predictability or unpredictability of the art ) . (6) The amount of direction or guidance presented, (7) the presence or absence of working examples, and (8) the quantity of the experimentation Prior art teaches a method of treating breast and ovarian cancer comprising (i) an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 of the instant application, (ii) pembrolizumab, and (iii) paclitaxel or docetaxel The specification shows a method of ovarian cancer and treating triple-negative breast cancer in a human subject comprising administering MK-4830, pembrolizumab, and paclitaxel (¶ 0730, “Arm J is to test the combination of 800 mg MK-4830 Q3W, 200 mg pembrolizumab Q3W, and 80 mg/m 2 paclitaxel on Day 1, 8, and 15 of each Q3W cycle in ovarian cancer patients; Arm K is to test the combination of 800 mg MK-4830 Q3W, 200 mg pembrolizumab Q3W, and 90 mg/m 2 paclitaxel on Day 1, 8, and 15 of each Q4W cycle in TNBC patients”). The specification does not provide any additional examples or guidance on how to use ILT4 antagonists, PD-1 antagonists, and mitosis inhibitors other than MK-4830, pembrolizumab, and paclitaxel to treat any other cancer besides ovarian cancer and treating triple-negative breast cancer as recited in the claim ( the amount of direction or guidance presented and the presence or absence of working examples ). The amount of experimentation would not be reasonable because it would require determining which ILT4 and PD-1 antagonists to use to treat various cancers. Protein antagonists include but are not limited to antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules. These chemical and biological compounds are varied as evidenced by Smith and Ngo and Garneau-Tsodikova (see nature of the invention and breadth of the claims). In regard to antagonistic antibodies, even minor changes in the amino acid sequences of an antibody may dramatically affect antigen-binding function as evidenced by Rudikoff et al. and Colman (see nature of the invention and breadth of the claims). Taken together, the specific sequences for an antagonistic anti-ILT antibody and antagonistic anti-PD-1 antibody are needed as it would require undue experimentation to reproduce the claimed antagonists. Therefore, a person having ordinary skill in the art would not recognize which PD-1 and ILT4 antagonists are required in combination with cisplatin and pemetrexed to treat cancer because (i) antagonists are varied including antibodies (Fabs, scFvs, nanobodies, etc.), antigen-binding fragments, and small molecules and (ii) even within a category of antagonists such as antagonistic antibodies, there is too much unpredictably in this field to ascertain the identity of an antibody without its sequence. In addition, mitosis inhibitor include but are not limited to eribulin, docetaxel, paclitaxel, vincristine, teniposide, etoposide, vinblastine, vinorelbine, cabazitaxel, ixabepilone, and estramustine. These medications have ranges of tolerability in patients and dosing regimens. It is not routine to determine how such a broad classes of molecules would treat all cancer. Undue experimentation would be required to determine whether ILT4 antagonists, PD-1 antagonists, and mitosis inhibitors of any chemical makeup would treat all cancer ( the quantity of the experimentation , see MPEP 2164.06). The scope of claim 13 is extremely broad; it recites multiple cancers and the use of various ILT4 antagonists, PD-1 antagonists, and mitosis inhibitors that require the specification of the instant application to provide support for the entire scope of the claim. The specification fails to show that a person having ordinary skill in the art could treat all recited diseases without undue experimentation. Moreover, as described above, cancer is not known to be treated generically. Evidence of efficacy of administering (i) an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 of the instant application or MK-4830, (ii) pembrolizumab, and (ii) paclitaxel or docetaxel in a method of treating ovarian cancer and triple-negative breast cancer in a human subject is provided in the specification and prior art. Therefore, the method of treating ovarian cancer and triple-negative breast cancer in a human subject comprising administering (i) an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 of the instant application or MK-4830 , (ii) pembrolizumab , and (ii) paclitaxel or docetaxel is supported. The method of treating all cancer in a human subject comprising administering any ILT4 antagonist , any PD-1 antagonist , and any mitosis inhibitor is not supported. Claim 13 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to treat all cancer in a human subject comprising administering any ILT4 antagonist , any PD-1 antagonist , and any mitosis inhibitor with a predictability of success for the reasons outlined above. Claims 14, 58-59, 61-63, 66, and 69 are included in this rejection as they depend on and/or incorporate claim 13. Claim Rejections - 35 USC § 112(b) 07-30-02 AIA 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 32-34, 36-37, 39-40, 42-44, 48-50, 53, 58-59, 61-63, 66, and 69 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. Regarding claims 32-34, 36-37, 39-40, 42-44, 53, 58-59, and 66 , the phrase "antibody or antigen binding fragment thereof" render the claims indefinite because it is unclear whether the claim refers to a full-length antibody or a fragment of an antibody. Claims 48-49, 50, 53, 61-63, and 69 are included in this rejection as they incorporate and/or depend on claims 32-34, 36-37, 39-40, 42-44, 53, 58-59, and 66. For the purposes of claim interpretation, the phrase "antibody or antigen binding fragment thereof" will be interpretated as optionally both a full-length antibody and an antigen binding fragment thereof. Regarding claims 43-44 , the phrase "an amino acid sequence" render the claims indefinite because it is unclear the exact identity of the antibody as this recitation includes a large number of fragments. For the purposes of claim interpretation, the phrase “an amino acid sequence” will include fragments. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (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. 07-15 AIA Claim s 13-14 and 58 are rejected under 35 U.S.C. 102( a)(1) and 102(a)(2 ) as being anticipated by US 20180298096 A1 (referred to as US ‘096, published 2018-10-18) as evidenced by Ahamadi et al. (Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors, CPT Pharmacometrics Syst Pharmacol, 2017 Jan;6[1]:49-57) and Pichiri et al. (Kojic Acid Derivative as an Antimitotic Agent That Selectively Kills Tumour Cells, Pharmaceuticals [Basel], 2024 Dec 25;18[1]:11) . Claims 13-14 and 58 Regarding claim 13 , US ‘096 teaches a method of treating cancer with an ILT4 antibody and an anti-PD1 antibody in a human subject (Abstract, “present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 [immunoglobulin-like transcript 4] and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject”; ¶ 0047, “a human subject”; claim 13 ). Regarding claim 13 , US ‘096 further teaches an antagonistic anti-human ILT4 monoclonal antibody (¶ 0005, “antibodies or antigen-binding fragments thereof that bind to human ILT4”; ¶ 0072, “the term ‘antibody’ includes, but is not limited to, monoclonal antibodies”; ¶ 0046, “present invention provides a method for blocking binding of ILT4”; claim 13 ). Regarding claim 58 , US ‘096 further teaches the antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 of the instant application (SEQ ID NOs: 1-3 and 6-8 of the instant application encompassed in SEQ ID NOs: 7 and 2 of US ‘096 respectively) and pembrolizumab (¶ 0296, “[i] an antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in SEQ ID NO:7 and each heavy chain consists of the amino acid sequence set forth in SEQ ID NO:2, and [ii] pembrolizumab”; claim 58 ). Regarding claim 14 , US ‘096 further teaches paclitaxel or docetaxel (¶ 0365, “an anti-ILT4 antibody… is in association with a further chemotherapeutic agent” and “the further chemotherapeutic agent is… paclitaxel, docetaxel”; ¶ 0366, in association means “can be formulated into a single composition”; claim 14 ). Regarding claim 13 , US ‘096 does not explicitly state paclitaxel and docetaxel are mitosis inhibitors nor pembrolizumab is a PD-1 antagonist. However, paclitaxel and docetaxel are known mitosis inhibitors (Pichiri et al., Pg. 2, ¶ 2, paclitaxel and docetaxel target microtubules to disrupt mitosis) and pembrolizumab is a known antagonistic anti-human PD-1 monoclonal antibody (Ahamadi et al., Pg. 49, column 1, ¶ 1, “anti–PD-1 humanized monoclonal antibody” for treatment of PD-L1 expressing cancers in patients by blocking PD-1). A person having ordinary skill in the art would recognize paclitaxel and docetaxel as mitosis inhibitors and pembrolizumab as a PD-1 antagonist ( claim 13 ). Accordingly, claims 13-14 and 58 are anticipated by US ‘096 as evidenced by Ahamadi et al. and Pichiri et al . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-21-aia AIA Claim s 1-2, 32, 34, 36-37, 39, 48, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Merck Sharp & Dohme LLC (referred to as Merck; Study: NCT03564691, Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab [MK-3475] in Participants With Advanced Solid Tumors [MK-4830-001], ClinicalTrials.Gov, first submitted 06/11/2018, last update 06/17/2020) in view of Ho et al. (Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies, Critical Reviews in Oncology/Hematology, Volume 102, 2016, Pages 37-46) as evidenced by Siu et al. (First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors, Clin Cancer Res, 2022 Jan 1;28[1]:57-70) and Ahamadi et al . Claims 1-2, 32, 34, 36-37, and 39 Regarding claims 1-2 and 39 , Merck teaches a method of treating non-small cell lung cancer (NSCLC) comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin (Pg. 5, column 1, first row in table, “Combination therapy… of MK-4830, pembrolizumab, and carboplatin/pemetrexed ( claims 1 and 39 ) in participants with advanced non-squamous non-small-cell-lung-cancer” ( claims 1-2 )). Regarding claims 1, 32, 34, and 36-37, Merck does not explicitly state MK-4830 is a human ( claim 37 ), antagonistic ( claim 1 ) anti-human ILT4 monoclonal antibody ( claim 36 ) and pembrolizumab is a humanized ( claim 34 ), antagonistic ( claim 1 ) anti-human PD-1 monoclonal antibody ( claim 32 ). However, Siu et al. teach MK-4830 is a human, antagonistic anti-human ILT4 monoclonal antibody (Pg. 58, column 1, ¶ 2, “MK-4830 is a fully human ( claim 37 ) monoclonal antibody of the immunoglobulin G4 subclass that specifically binds to ILT4 and blocks its interaction with HLA-G and other ligands” in patients ( claims 1 and 36 )) and Ahamadi et al. teach pembrolizumab is a humanized, antagonistic anti-human PD-1 monoclonal antibody (Pg. 49, column 1, ¶ 1, “anti–PD-1 humanized ( claim 34 ) monoclonal antibody” for treatment of PD-L1 expressing cancers in patients by blocking PD-1 ( claims 1 and 32 )). A person having ordinary skill in the art would recognize the properties of the aforementioned antibodies ( claims 1, 32, 34, and 36-37 ). Merck does not teach the administration of cisplatin. Ho et al. teach a method of treating NSCLC comprising administering to human patients pemetrexed and either cisplatin or carboplatin (Pg. 39, column 1, ¶ 2, “trials with platinum containing regimens in NSCLC”; Pg. 39, column 1, ¶ 3, “cisplatin-pemetrexed and carboplatin-pemetrexed” administered to human patients). Ho et al. further teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed, stating cisplatin-pemetrexed is favored for its efficacy in treatment (Pg. 39, column 1, ¶ 3, “median [overall survival] of 11.7 & 8.9 months for cisplatin-pemetrexed and carboplatin-pemetrexed respectively” and “the overall efficacy and toxicity observed favoured the cisplatin-pemetrexed doublet”). Ho et al. do no teach the administration of an ILT4 antagonist nor a PD-1 antagonist. Treating NSCLC with either cisplatin or carboplatin in a pemetrexed combination therapy was known and used prior to the effective filing date of the application. In addition, both Merck and Ho et al. are in analogous arts (i.e. methods of treating NSCLC with pemetrexed combination therapies). Since Ho et al. teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed, stating cisplatin-pemetrexed is favored for its efficacy in treatment, there is motivation for using cisplatin instead of carboplatin in a method of treating NSCLC comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin. MPEP § 2143(I)(B) states: “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” The simple substitution of one known element for another (i.e. administering cisplatin instead of carboplatin) would be expected to obtain predictable results with a reasonable expectation of success (i.e. treating NSCLC with either cisplatin or carboplatin in a pemetrexed combination therapy was known and used prior to the effective filing date of the application; both Merck and Ho et al. are in analogous arts of methods of treating NSCLC with pemetrexed combination therapies). A person having ordinary skill in the art would be motivated to make this substitution to modify a method of treating NSCLC comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck using the teaching of Ho et al. that cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed, stating cisplatin-pemetrexed is favored for its efficacy in treatment. It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to substitute carboplatin for cisplatin in a method of treating NSCLC comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin. Claim 48 Regarding claim 48 , Merck further teaches pembrolizumab is administered at 200 mg once every three weeks (Pg. 5, column 2, first row in table, “pembrolizumab will be dosed at 200 mg IV Q3W”; Pg. 2, column 1, last line, Q3W means every three weeks; claim 48 ). Claim 53 Regarding claim 48 , Merck further teaches MK-4830 is administered once every three weeks, with the exact dosage determined via a dose escalation protocol to ensure the drug is safe and tolerable (Pg. 5, column 2, first row in table, “MK-4830 will be administered intravenously [IV] Q3W… Dose escalation will proceed based on emerging safety and tolerability data of MK-4830” and “For each dose level, an assessment will be made of the safety and tolerability data in order to define the next dose level to be tested”; Pg. 2, column 1, last line, Q3W means every three weeks; claim 53 ). Merck does not teach the exact dosage of MK-4830 is 100-1600 mg. MPEP 2144.05(II)(A) states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It is a common objective in the art to optimize result effective variables (i.e. dosage of MK-4830 in mg once every three weeks), so as to achieve optimal effect and maximal benefit (i.e. ensure safety and tolerability of MK-4830 in patients as taught in Merck). See In re Boesch , 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) “[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Therefore, any optimization of dosage in mg for MK-4830 would be seen as routine optimization––and thus a person having ordinary skill in the art prior to the effective filing date of the instant application would immediately envisage the claimed dosage range of 100-1600 mg and achieve it without undue experimentation in order to ensure safety and tolerability of MK-4830 in patients as taught in Merck. Accordingly, claims 1-2, 32, 34, 36-37, 39, 48, and 53 are rendered obvious over Merck in view of Ho et al. as evidenced by Siu et al. and Ahamadi et al . 07-21-aia AIA Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Merck in view of Ho et al. and Lala et al. (A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation, Eur J Cancer, 2020 May;131:68-75) as evidenced by Siu et al. and Ahamadi et al . Claim 49 As fully described in the 103 rejection of claims 1, 32, and 39 : Merck teaches a method of treating NSCLC comprising administering to human patients pembrolizumab (a humanized, antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.), MK-4830 (a human, antagonistic anti-human ILT4 monoclonal antibody as evidenced by Siu et al.), pemetrexed, and carboplatin. Merck further teaches pembrolizumab is administered at 200 mg once every three weeks. Merck does not teach the administration of cisplatin nor pembrolizumab administered at 400 mg once every six weeks. Ho et al. teach a method of treating NSCLC comprising administering to human patients pemetrexed and either cisplatin or carboplatin, indicating cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment. Ho et al. do no teach the administration of an ILT4 antagonist nor a PD-1 antagonist in particular dosage regimen. Regarding claim 49 , Lala et al. teach a meta-analysis of pembrolizumab dosages, indicating 200 mg once every three weeks and 400 mg once every six weeks are both effective and safe for the treatment of NSCLC (Pg. 69, Abstract, Conclusions, pembrolizumab “clinical efficacy and safety of 400 mg Q6W would be similar to the 200 mg and 2 mg/ kg Q3W doses across tumour types”; Pg. 71, “data from melanoma and NSCLC indications”; claim 49 ). Lala et al. do not teach administration of an ILT4 antagonist, cisplatin, nor pemetrexed. Treating NSCLC with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) pembrolizumab at 200 mg once every three weeks and 400 mg once every six weeks as taught in Lala et al. were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and Lala et al. are in analogous arts (i.e. methods of treating NSCLC). Since (i) Ho et al. teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment and (ii) Lala et al. teach pembrolizumab at 200 mg once every three weeks and 400 mg once every six weeks are both effective and safe for the treatment of NSCLC, there is motivation for using cisplatin instead of carboplatin and pembrolizumab at 400 mg once every six weeks instead of 200 mg once every three weeks in a method of treating NSCLC comprising administering to human patients pembrolizumab at 200 mg once every three weeks, MK-4830, pemetrexed, and carboplatin as taught in Merck. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of NSCLC as taught in Ho et al.; pembrolizumab at 200 mg once every three weeks and 400 mg once every six weeks are both effective and safe for the treatment of NSCLC as taught in Lala et al.) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating NSCLC comprising administering to human patients pembrolizumab at 200 mg once every three weeks, MK-4830, pemetrexed, and carboplatin as taught in Merck wherein cisplatin is used instead of carboplatin and pembrolizumab is administered at 400 mg once every six weeks instead of at 200 mg once every 3 weeks) to arrive at the claimed invention. There is a reasonable expectation of success as treating NSCLC with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) pembrolizumab at 200 mg once every three weeks and 400 mg once every six weeks as taught in Lala et al. were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and Lala et al. are in analogous arts (i.e. methods of treating NSCLC). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to use cisplatin instead of carboplatin as taught in Ho et al. and pembrolizumab at 400 mg once every six weeks instead of at 200 mg once every three weeks as taught in Lala et al. in a method of treating NSCLC comprising administering to human patients pembrolizumab at 200 mg once every three weeks, MK-4830, pemetrexed, and carboplatin as taught in Merck. Accordingly, claim 49 is rendered obvious over Merck in view of Ho et al. and Lala et al. as evidenced by Siu et al. and Ahamadi et al . 07-21-aia AIA Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Merck in view of Ho et al. and Chin et al. (Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1 immunotherapy, Ann Oncol, 2017 Jul 1;28[7]:1658-1666) as evidenced by Siu et al. and Ahamadi et al . Claim 33 As fully described in the 103 rejection of claim 1 : Merck teaches a method of treating cancer comprising administering to human patients pembrolizumab (a humanized, antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.), MK-4830 (a human, antagonistic anti-human ILT4 monoclonal antibody as evidenced by Siu et al.), pemetrexed, and carboplatin. Merck does not teach the administration of cisplatin nor an antagonistic anti-human PD-L1 monoclonal antibody. Ho et al. teach a method of treating cancer comprising administering to human patients pemetrexed and either cisplatin or carboplatin, indicating cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment. Ho et al. do no teach the administration of an ILT4 antagonist nor an antagonistic anti-human PD-L1 monoclonal antibody. Regarding claim 33 , Chin et al. teach avelumab is an antagonistic anti-human PD-L1 monoclonal antibody used for treating cancer (Pg. 1, column 1, ¶ 2, avelumab is a “human immunoglobulin G1 [IgG1] anti-PD-L1 monoclonal antibody ” for treating cancer in human patients; Pg. 1, column 2, ¶ 2, “Avelumab is thought to specifically bind to PD-L1, preventing the interaction between PD-L1 and the inhibitory T-cell receptor PD-1”; claim 33 ). Chin et al. further teach avelumab is unique from anti-PD-1 antibodies as it induces tumor-directed antibody-dependent cell-mediate cytotoxicity (ADCC), noting pembrolizumab does not have this ability (Pg. 1, column 2, ¶ 2, “Unlike other anti-PD-L1 or anti-PD-1 antibodies, avelumab has a wild-type IgG1 crystallizable fragment [Fc] region, which enables avelumab to engage with Fc-γ receptors on natural killer cells and induce tumour-directed antibody-dependent cell-mediated cytotoxicity” and pembrolizumab has been engineered to “to minimise or disable ADCC”). Chin et al. do not teach administration of an ILT4 antagonist, pemetrexed, nor cisplatin. Treating cancer with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) antagonistic anti-human PD-1/PD-L1 monoclonal antibodies as taught in Chin et al. and Merck were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and Chin et al. are in analogous arts (i.e. methods of treating cancer). Since (i) Ho et al. teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of cancer and (ii) Chin et al. teach the antagonistic anti-human PD-L1 monoclonal antibody avelumab can induce ADCC for enhanced destruction of cancer cells unlike pembrolizumab, there is motivation for using cisplatin instead of carboplatin and avelumab instead of pembrolizumab in a method of treating cancer comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of cancer as taught in Ho et al.; the antagonistic anti-human PD-L1 monoclonal antibody avelumab can induce ADCC for enhanced destruction of cancer cells unlike pembrolizumab as taught in Chin et al.) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating cancer comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck wherein cisplatin is used instead of carboplatin and avelumab is used instead of pembrolizumab) to arrive at the claimed invention. There is a reasonable expectation of success as treating cancer with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) antagonistic anti-human PD-1/PD-L1 monoclonal antibodies as taught in Chin et al. and Merck were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and Chin et al. are in analogous arts (i.e. methods of treating cancer). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to use cisplatin instead of carboplatin as taught in Ho et al. and avelumab instead of pembrolizumab as taught in Chin et al. in a method of treating cancer comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck. Accordingly, claim 33 is rendered obvious over Merck in view of Ho et al. and Chin et al. as evidenced by Siu et al. and Ahamadi et al . 07-21-aia AIA Claim s 40 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Merck in view of Ho et al. and Zhao et al. (Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors, Ann Oncol, 2017 Aug 1;28[8]:2002-2008) as evidenced by Siu et al. and Ahamadi et al . Claim 40 As fully described in the 103 rejection of claims 1 and 32 : Merck teaches a method of treating NSCLC comprising administering to human patients pembrolizumab (a humanized, antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.), MK-4830 (a human, antagonistic anti-human ILT4 monoclonal antibody as evidenced by Siu et al.), pemetrexed, and carboplatin. Merck does not teach the administration of cisplatin nor nivolumab. Ho et al. teach a method of treating NSCLC comprising administering to human patients pemetrexed and either cisplatin or carboplatin, indicating cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment. Ho et al. do no teach the administration of MK-4830 nor nivolumab. Zhao et al. teach nivolumab is an antagonistic anti-human PD-1 monoclonal antibody used in a method of treating NSCLC, showing it is safe and effective in human patients by prolonging survival (Pg. 1, column 1, ¶ 1, “Nivolumab is a highly selective anti-programmed death 1 [PD-1] human monoclonal IgG4 antibody that potentiates T-cell responses by blocking the binding of PD-1 on activated T cells” in human patients; Pg. 5, “safety and efficacy of nivolumab in… NSCLC…. is well established by prolonged survival”). Zhao et al. do not teach the administration of MK-4830, cisplatin, nor pemetrexed. Treating NSCLC with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) antagonistic anti-human PD-1 monoclonal antibodies pembrolizumab as taught in Merck and nivolumab as taught in Zhao et al. were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and Zhao et al. are in analogous arts (i.e. methods of treating NSCLC). Since (i) Ho et al. teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of NSCLC and (ii) Zhao et al. teach the antagonistic anti-human PD-1 monoclonal antibody nivolumab for the treatment of NSCLC is safe, effective, and prolongs survival, there is motivation for using cisplatin instead of carboplatin and nivolumab as the specific antagonistic anti-human PD-1 monoclonal antibody in a method of treating NSCLC comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of NSCLC as taught in Ho et al.; the antagonistic anti-human PD-1 monoclonal antibody nivolumab for the treatment of NSCLC is safe, effective, and prolongs survival as taught in Zhao et al.) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating NSCLC comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck wherein cisplatin is used instead of carboplatin and nivolumab is used as the specific antagonistic anti-human PD-1 monoclonal antibody) to arrive at the claimed invention. There is a reasonable expectation of success as treating NSCLC with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) antagonistic anti-human PD-1 monoclonal antibodies pembrolizumab as taught in Merck and nivolumab as taught in Zhao et al. were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and Zhao et al. are in analogous arts (i.e. methods of treating NSCLC). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to use cisplatin instead of carboplatin as taught in Ho et al. and nivolumab as the specific antagonistic anti-human PD-1 monoclonal antibody as taught in Zhao et al. in a method of treating NSCLC comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck. Claim 50 Zhao et al. further teach the flat dose of 240 mg nivolumab once every two weeks (Pg. 1, Abstract, Conclusion, “the benefit–risk profile of nivolumab 240mg Q2W was comparable to 3mg/kg Q2W” with both dosages being safe and effective). Accordingly, claim 40 and 50 are rendered obvious over Merck in view of Ho et al. and Zhao et al. as evidenced by Siu et al. and Ahamadi et al . 07-21-aia AIA Claim s 6 and 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over Merck in view of Ho et al. and US ‘096 as evidenced by Siu et al. and Ahamadi et al . Claims 42-44 As fully described in the 103 rejection of claims 1 and 36 : Merck teaches a method of treating cancer comprising administering to human patients pembrolizumab (a humanized, antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.), MK-4830 (a human, antagonistic anti-human ILT4 monoclonal antibody as evidenced by Siu et al.), pemetrexed, and carboplatin. Merck does not teach the administration of cisplatin nor SEQ ID NOs: 1-10. Ho et al. teach a method of treating cancer comprising administering to human patients pemetrexed and either cisplatin or carboplatin, indicating cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of cancer. Ho et al. do no teach the administration of an ILT4 antagonist nor SEQ ID NOs: 1-10. US ‘096 teaches an antagonistic anti-human ILT4 monoclonal antibody (¶ 0005, “antibodies or antigen-binding fragments thereof that bind to human ILT4”; ¶ 0072, “the term ‘antibody’ includes, but is not limited to, monoclonal antibodies”; ¶ 0046, “present invention provides a method for blocking binding of ILT4”) comprising SEQ ID NOs: 1-10 (see table below, note that CDRs in SEQ ID NOs: 1-3 and 6-8 of the instant application are encompassed fully in their corresponding sequences in US ‘096). Instant application SEQ ID NO US ‘096 SEQ ID NO 1-3 58 and 7 4 58 5 7 6-8 57 and 2 9 57 10 2 US ‘096 further teaches a method of treating cancer with the anti-human ILT4 monoclonal antibody and pembrolizumab (¶ 0047, “a method of treating a cancer in a subject… comprising administering to the subject an effective amount of the antibody” and “method of treating a cancer further comprises administering… pembrolizumab”). US ‘096 does not teach the administration of cisplatin nor pemetrexed. Treating cancer with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) antagonistic anti-human ILT4 monoclonal antibodies, specifically ones comprising SEQ ID NOs: 1-10, in a pembrolizumab combination therapy as taught in US ‘096 were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and US ‘096 are in analogous arts (i.e. methods of treating cancer). Since (i) Ho et al. teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of cancer and (ii) US ‘096 teaches the antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 and pembrolizumab are useful for the treatment of cancer, there is motivation for using cisplatin instead of carboplatin and an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 in a method of treating cancer comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of cancer as taught in Ho et al.; an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 and pembrolizumab are useful for the treatment of cancer as taught in US ‘096) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating cancer comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck wherein cisplatin is used instead of carboplatin and an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 is used instead of MK-4830) to arrive at the claimed invention. There is a reasonable expectation of success as treating cancer with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) antagonistic anti-human ILT4 monoclonal antibodies, specifically ones comprising SEQ ID NOs: 1-10, in a pembrolizumab combination therapy as taught in US ‘096 were known and used prior to the effective filing date of the application. In addition, Merck, Ho et al., and US ‘096 are in analogous arts (i.e. methods of treating cancer). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to use cisplatin instead of carboplatin as taught in Ho et al. and the antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-10 as taught in US ‘096 in a method of treating cancer comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin as taught in Merck. Claim 6 US ‘096 further teaches a kit (¶ 0366,“anti-ILT4 antibody… along with another agent… can be formulated into a single composition, e.g., for simultaneous delivery, or formulated separately into two or more compositions [e.g., a kit]”). Accordingly, claims 6 and 42-44 are rendered obvious over Merck in view of Ho et al. and US ‘096 as evidenced by Siu et al. and Ahamadi et al . 07-21-aia AIA Claim s 59 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over US ‘096 in view of Renner et al. (Immune Checkpoint Inhibitor Dosing: Can We Go Lower Without Compromising Clinical Efficacy?, JGO 5, 1-5[2019]) as evidenced by Ahamadi et al. and Pichiri et al . Claim 59 As fully described in the 102 rejection of claims 13-14 and 58 , US ‘096 teaches a method of treating cancer comprising an antagonistic anti-human ILT4 monoclonal antibody (comprising SEQ ID NOs: 1-3 and 6-8 of the instant application), pembrolizumab (an antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.) and paclitaxel (a mitosis inhibitor as evidenced by Pichiri et al.) in a human subject. US ‘096 does not teach nivolumab in the above combination. Renner et al. teach dose selection strategies for checkpoint inhibitors, specifically pembrolizumab and nivolumab, in oncology (Pg. 1, Abstract, immune checkpoint inhibitor administration in oncology; Pg. 1, column 1, “comparative clinical efficacy for different dosing strategies: pembrolizumab and nivolumab”). Renner et al. further teach nivolumab is an antagonistic PD-1 antibody (Pg. 2, column 2, ¶ 2, “Nivolumab, similar to pembrolizumab, is a humanized immunoglobulin G4 monoclonal antibody directed to the PD-1 receptor, blocking it from binding to its ligands”). Renner et al. further teach “both pembrolizumab and nivolumab have significant efficacy” when compared to traditional chemotherapy (Pg. 3, column 2, last ¶, last 2 lines), indicating the antibodies can be interchanged. Renner et al. do not teach an ILT4 antagonist nor a mitosis inhibitor. Equivalents known for the same purpose can be substituted. MPEP 2144.06 states: “In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art.” Here, that burden is met as Renner et al. teach pembrolizumab and nivolumab both show significant efficacy in the treatment of cancer compared to traditional chemotherapy. There is a reasonable expectation of success as both pembrolizumab and nivolumab are both immune checkpoint inhibitors that serve the same function of blocking PD-1 to halt cancer progression. It would be obvious to a person of ordinary skill in the art prior to the effective filing date of the instant application to substitute pembrolizumab for nivolumab when administering in a method of treating cancer in a human subject comprising an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8, pembrolizumab, and paclitaxel as taught in US ‘096 since substituting one PD-1-based immune checkpoint inhibitor for another would have yielded predictable results. Claim 63 Renner et al. further teach nivolumab is administered at “240 mg once every 2 weeks” (Pg. 3, column 1, ¶ 3, line 3). Accordingly, claims 59 and 63 are rendered obvious over US ‘096 in view of Renner et al. as evidenced by Ahamadi et al. and Pichiri et al . 07-21-aia AIA Claim 66 is rejected under 35 U.S.C. 103 as being unpatentable over US ‘096 as evidenced by Ahamadi et al., Pichiri et al., and Walpole et al. (The weight of nations: an estimation of adult human biomass, BMC Public Health, 2012 Jun 18;12:439) . Claim 66 As fully described in the 102 rejection of claims 13-14 and 58 , US ‘096 teaches a method of treating cancer comprising an antagonistic anti-human ILT4 monoclonal antibody (comprising SEQ ID NOs: 1-3 and 6-8 of the instant application), pembrolizumab (an antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.) and paclitaxel (a mitosis inhibitor as evidenced by Pichiri et al.) in a human subject. US ‘096 further teaches administration of the antagonistic anti-human ILT4 monoclonal antibody at 0.05-30 mg/kg body weight weekly (¶ 0305, “effective dose of an anti-ILT4 antibody or antigen-binding fragment thereof of the present invention, is from about 0.05 mg/kg [body weight] to about 30 mg/kg [body weight]” and “weekly” administration). This dose is equivalent to 3.1-1860 mg based on the average body weight globally (Walpole et al., Pg. 3, column 2, ¶ 2, last 2 lines, “Average body mass globally was 62kg”). 0.05 m g k g b o d y w e i g h t × 62 k g b o d y w e i g h t = 3.1 m g 30 m g k g b o d y w e i g h t × 62 k g b o d y w e i g h t = 1860 m g US ‘096 further teaches “in determining the dose, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved relative to any negative side effects” (¶ 0306). US ‘096 does not teach 100-1600 mg antagonistic anti-human ILT4 monoclonal antibody is administered once every three weeks. MPEP 2144.05(II)(A) states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It is a common objective in the art to optimize result effective variables (i.e. dosage of antagonistic anti-human ILT4 monoclonal antibody), so as to achieve optimal effect and maximal benefit (i.e. produce positive treatment effects with minimal negative side effects). See In re Boesch , 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) “[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Therefore, any optimization of dosage would be seen as routine optimization––and thus a person having ordinary skill in the art prior to the effective filing date of the instant application would immediately envisage the claimed dosage to achieve them without undue experimentation in order to produce positive treatment effects with minimal negative side effects. Accordingly, claim 66 is rendered obvious over US ‘096 as evidenced by Ahamadi et al., Pichiri et al., and Walpole et al . 07-21-aia AIA Claim s 61-62 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over US ‘096 in view of Kim et al. (A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer, Lung Cancer, Volume 136, 2019, Pages 122-128) as evidenced by Ahamadi et al. and Pichiri et al . Claim 61 As fully described in the 102 rejection of claims 13-14 and 58 , US ‘096 teaches a method of treating cancer comprising an antagonistic anti-human ILT4 monoclonal antibody (comprising SEQ ID NOs: 1-3 and 6-8 of the instant application), pembrolizumab (an antagonistic anti-human PD-1 monoclonal antibody as evidenced by Ahamadi et al.) and paclitaxel (a mitosis inhibitor as evidenced by Pichiri et al.) in a human subject. Kim et al. teach pembrolizumab and paclitaxel in a method of treating cancer in human patients, showing favorable tumor response, prolonged survival, and manageable safety profile (Pg. 127, column 1, ¶ 2, “combination therapy with pembrolizumab and paclitaxel showed a favorable tumor response, prolonged survival, and manageable safety profile in [extensive disease small-cell lung cancer] patients”). Kim et al. further teach pembrolizumab is administered at 200 mg once every three weeks (Pg. 123, column 1, last ¶, “pembrolizumab… at a dose of 200mg” and “administered on day 1 of each 3-week cycle”). Kim et al. do not teach an ILT4 antagonist. Treating cancer with 200 mg pembrolizumab once every three weeks was known and used prior to the effective filing date of the application. In addition, US ‘096 and Kim et al. are in analogous arts (i.e. methods of treating cancer with pembrolizumab). Since Kim et al. teach 200 mg pembrolizumab once every three weeks showed favorable tumor response, prolonged survival, and manageable safety profile when treating cancer in combination with paclitaxel, there is motivation for using this dosage in a method of treating cancer in a human subject comprising an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8, pembrolizumab, and paclitaxel as taught in US ‘096. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. 200 mg pembrolizumab once every three weeks showed favorable tumor response, prolonged survival, and manageable safety profile when treating cancer in combination with paclitaxel as taught in Kim et al.) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating cancer in a human subject comprising an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8, pembrolizumab, and paclitaxel as taught in US ‘096) to arrive at the claimed invention. There is a reasonable expectation of success treating cancer with 200 mg pembrolizumab once every three weeks was known and used prior to the effective filing date of the application. In addition, US ‘096 and Kim et al. are in analogous arts (i.e. methods of treating cancer with pembrolizumab). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to administer pembrolizumab at 200 mg once every three weeks as taught in Kim et al. in a method of treating cancer in a human subject comprising an antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8, pembrolizumab, and paclitaxel as taught in US ‘096. Claims 62 and 69 US ‘096 further teaches “in determining the dose, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved relative to any negative side effects” (¶ 0306). US ‘096 does not teach the specific dose of paclitaxel nor pembrolizumab. Kim et al. further teach administration of paclitaxel at 175 mg/m 2 on day 1 of each 3-week cycle (Pg. 123, column 1, last ¶, “paclitaxel at a dose of… 175mg/m 2 , respectively, were administered on day 1 of each 3-week cycle”). Kim et al. do not teach administration of paclitaxel at 175 mg/m 2 on days 8 and 15 ( claim 62 ) nor administration of pembrolizumab at 400 mg once every six weeks ( claim 66 ). MPEP 2144.05(II)(A) states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It is a common objective in the art to optimize result effective variables (i.e. dosage of pembrolizumab and paclitaxel), so as to achieve optimal effect and maximal benefit (i.e. produce positive treatment effects with minimal negative side effects as taught in US ‘096). See In re Boesch , 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) “[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Therefore, any optimization of dosages would be seen as routine optimization––and thus a person having ordinary skill in the art prior to the effective filing date of the instant application would immediately envisage the claimed dosages to achieve them without undue experimentation in order to produce positive treatment effects with minimal negative side effects as taught in US ‘096. Accordingly, claims 61-62 and 69 are rendered obvious over US ‘096 in view of Kim et al. as evidenced by Ahamadi et al. and Pichiri et al . Double Patenting 08-33 AIA 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. 08-37 AIA Claim 1-2, 32-34, 36-37, 39-40, 42, 48-49, and 53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 13, 15-16, 20-21, 24, 38-39 of copending Application No. 18/245,590 (referred to as copending ‘590) in view of Merck, US ‘096, and Ho et al. as evidenced by Siu et al., Ahamadi et al., and Chin et al. Instant claims 1, 36, 42, and 53 Instant claim 1 teaches a method of treating cancer comprising administering to a human patient in need thereof a PD-1 antagonist, an ILT4 antagonist, cisplatin and pemetrexed. Instant claim 36 teaches the ILT4 antagonist is an anti-human ILT4 monoclonal antibody or antigen binding fragment thereof. Instant claim 42 teaches the anti-human ILT4 monoclonal antibody or antigen binding fragment thereof comprises SEQ ID NOs: 1-3 for LCDRs 1-3 and SEQ ID NOs: 6-8 for HCDRs 1-3. Instant claim 53 teaches the anti-human ILT4 monoclonal antibody or antigen binding fragment thereof is administered from about 100-1600 mg once every three weeks. Claim 13 of copending ‘590 teaches a method for treating cancer in a patient comprising administering to the patient a PD-1 antagonist and an anti-ILT4 antibody ( instant claim 1 ), wherein the anti-ILT4 antibody comprises SEQ ID NOs: 11, 21, and 13 for LCDRS 1-3 respectively and SEQ ID NOs: 16, 22, and 18 for HCDRs 1-3 respectively (copending ‘590 SEQ ID NOs: 11, 21, and 13 correspond to instant SEQ ID NOs: 1-3; copending ‘590 SEQ ID NOs: 16, 22, and 18 correspond to instant SEQ ID NOs: 6-8; instant claim 42 ) and is administered from 3-1600 mg ( instant claim 53 ). Regarding instant claims 1 and 36 , claim 13 of copending ‘590 does not explicitly state the anti-ILT4 antibody is antagonistic ( instant claim 1 ) nor an anti-human ILT4 monoclonal antibody ( instant claim 36 ). However, as the ILT4 antibodies of instant application and copending ‘590 have the same SEQ ID NOs (see claim 13 of copending ‘590 and instant claim 42 ), these identical ILT4 antibodies have the same functional characteristics. “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present” (MPEP 2112.01). The functions of instant claims 1 and 36 are inherent characteristics of the ILT4 antibodies as taught in claim 13 of copending ‘590 , inseparable from its chemical structure. Therefore, despite the fact that the functions are not stated in claim 13 of copending ‘590 , a person having ordinary skill in the art would recognize these ILT4 antibodies have the same properties i.e. they are antagonistic anti-human ILT4 monoclonal antibodies ( instant claims 1 and 36 ). Regarding instant claim 53 , claim 13 of copending ‘590 does not teach 100-1600 mg antagonistic anti-human ILT4 monoclonal antibody is administered once every three weeks. Claim 13 of copending ‘590 teaches an overlapping range of 3-1600 mg however. US ‘096 teaches an antagonistic anti-human ILT4 monoclonal antibody (¶ 0005, “antibodies or antigen-binding fragments thereof that bind to human ILT4”; ¶ 0072, “the term ‘antibody’ includes, but is not limited to, monoclonal antibodies”; ¶ 0046, “present invention provides a method for blocking binding of ILT4”). US ‘096 further teaches, referring to the ILT4 antibody, “in determining the dose, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved relative to any negative side effects” (¶ 0306). US ‘096 does not teach 100-1600 mg antagonistic anti-human ILT4 monoclonal antibody is administered once every three weeks. MPEP 2144.05(II)(A) states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It is a common objective in the art to optimize result effective variables (i.e. dosage of antagonistic anti-human ILT4 monoclonal antibody), so as to achieve optimal effect and maximal benefit (i.e. produce positive treatment effects with minimal negative side effects). See In re Boesch , 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) “[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Therefore, any optimization of dosage would be seen as routine optimization––and thus a person having ordinary skill in the art prior to the effective filing date of the instant application would immediately envisage the claimed dosage to achieve them without undue experimentation in order to produce positive treatment effects with minimal negative side effects. Regarding instant claim 1 , claim 13 of copending ‘590 does not teach administration of cisplatin and pemetrexed. Regarding instant claim 1 , Merck teaches a method of treating non-small cell lung cancer (NSCLC) comprising administering to human patients pembrolizumab, MK-4830, pemetrexed, and carboplatin (Pg. 5, column 1, first row in table, “Combination therapy… of MK-4830, pembrolizumab, and carboplatin/pemetrexed in participants with advanced non-squamous non-small-cell-lung-cancer”; instant claim 1 ). Merck does not explicitly state MK-4830 is an ILT4 antagonist and pembrolizumab is a PD-1 antagonist ( instant claim 1 ). However, Siu et al. teach MK-4830 is an ILT4 antagonist (Pg. 58, column 1, ¶ 2, “MK-4830 is a fully human monoclonal antibody of the immunoglobulin G4 subclass that specifically binds to ILT4 and blocks its interaction with HLA-G and other ligands” in patients ( instant claim 1 )) and Ahamadi et al. teach pembrolizumab is a PD-1 antagonist (Pg. 49, column 1, ¶ 1, “anti–PD-1 humanized monoclonal antibody” for treatment of PD-L1 expressing cancers in patients by blocking PD-1 ( instant claim 1 )). A person having ordinary skill in the art would recognize the properties of the aforementioned antibodies ( instant claim 1 ). Merck further teaches pembrolizumab and MLK-4830 can also be administered alone (Pg. 3, column 1, row 3, “combination therapy of MK-4830 and pembrolizumab). This teaching indicates pemetrexed and carboplatin can be added and removed from an PD-1 antagonist and an ILT4 antagonist combination therapy. Merck does not teach the administration of cisplatin. Regarding instant claim 1 , Ho et al. teach a method of treating NSCLC comprising administering to human patients pemetrexed and either cisplatin or carboplatin (Pg. 39, column 1, ¶ 2, “trials with platinum containing regimens in NSCLC”; Pg. 39, column 1, ¶ 3, “cisplatin-pemetrexed and carboplatin-pemetrexed” administered to human patients; cisplatin-pemetrexed administration is applicable to instant claim 1 ). Ho et al. further teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed, stating cisplatin-pemetrexed is favored for its efficacy in treatment (Pg. 39, column 1, ¶ 3, “median [overall survival] of 11.7 & 8.9 months for cisplatin-pemetrexed and carboplatin-pemetrexed respectively” and “the overall efficacy and toxicity observed favoured the cisplatin-pemetrexed doublet”). Ho et al. do no teach the administration of an ILT4 antagonist nor a PD-1 antagonist. Treating cancer with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) ILT4 antagonist and PD-1 antagonist in combination with carboplatin and pemetrexed as taught in Merck et al. were known and used prior to the effective filing date of the application. In addition, copending ‘590 , Merck, and Ho et al. are in analogous arts (i.e. methods of treating cancer with combination therapies). Since (i) Ho et al. teach cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed, stating cisplatin-pemetrexed is favored for its efficacy in treatment, and (ii) Merck teaches pemetrexed and carboplatin can be added and removed from an PD-1 antagonist and an ILT4 antagonist combination therapy, there is motivation for (i) using cisplatin instead of carboplatin as taught in Ho et al. and (ii) including pemetrexed and carboplatin as taught in Merck et al. in a method of treating cancer comprising administering to human patients a PD-1 antagonist and an ILT4 antagonist. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. cisplatin-pemetrexed showed a longer overall survival compared to carboplatin-pemetrexed and cisplatin-pemetrexed is favored for its efficacy in treatment of cancer as taught in Ho et al.; pemetrexed and carboplatin can be added and removed from an PD-1 antagonist and an ILT4 antagonist combination therapy as taught in Merck) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating cancer comprising administering to patients a PD-1 antagonist and ILT4 antagonist as taught in copending ‘590 wherein [i] cisplatin is used instead of carboplatin and [ii] pemetrexed and carboplatin are added) to arrive at the claimed invention. There is a reasonable expectation of success as treating cancer with (i) either cisplatin or carboplatin in a pemetrexed combination therapy as taught in Ho et al. and (ii) ILT4 antagonist and PD-1 antagonist in combination with carboplatin and pemetrexed as taught in Merck et al. were known and used prior to the effective filing date of the application. In addition, copending ‘590 , Merck, and Ho et al. are in analogous arts (i.e. methods of treating cancer with combination therapies). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to (i) use cisplatin instead of carboplatin as taught in Ho et al. and (ii) add pemetrexed and carboplatin as taught in Merck in a method of treating cancer comprising administering to human patients a PD-1 antagonist and ILT4 antagonist as taught in copending ‘590 ( instant claim 1 ). Instant claim 2 Instant claim 2 teaches the cancer is selected from the group consisting of osteosarcoma, rhabdomyosarcoma, neuroblastoma, kidney cancer, leukemia, renal transitional cell cancer, bladder cancer, Wilm's cancer, ovarian cancer, pancreatic cancer, breast cancer, prostate cancer, bone cancer, lung cancer, non-small cell lung cancer (NSCLC), pleural mesothelioma, gastric cancer, colorectal cancer, cervical cancer, synovial sarcoma, head and neck cancer, squamous cell carcinoma, lymphoma, diffuse large B- cell lymphoma, non-Hodgkin lymphoma, multiple myeloma, renal cell cancer, retinoblastoma, hepatoblastoma, hepatocellular carcinoma, melanoma, rhabdoid tumor of the kidney, Ewing's sarcoma, chondrosarcoma, brain cancer, glioblastoma, meningioma, pituitary adenoma, vestibular schwannoma, primitive neuroectodermal tumor, medulloblastoma, astrocytoma, anaplastic astrocytoma, oligodendroglioma, ependymoma, choroid plexus papilloma, polycythemia vera, thrombocythemia, idiopathic myelofibrosis, soft tissue sarcoma, thyroid cancer, endometrial cancer, and carcinoid cancer. Claim 38 of copending ‘590 teaches the cancer is selected from a group identical to instant claim 2 . Claim 39 of copending ‘590 teaches the cancer is selected from a subset of instant claim 2 , including head and neck cancer, squamous cell cancer, pancreatic cancer, glioblastoma, renal cell cancer, and non-small cell lung cancer. Instant claims 32, 34, 39, and 48-49 Instant claims 32, 34, and 39 teach the PD-1 antagonist is a humanized ( instant claim 34 ) anti-human PD-1 monoclonal antibody ( instant claim 32 ), specifically pembrolizumab ( instant claim 39 ). Instant claims 48 and 49 teach pembrolizumab is administered 200 mg once every three weeks ( instant claim 48 ) and 400 mg once every six weeks ( instant claim 49 ). Claims 15 and 20 of copending ‘590 teach the PD-1 antagonist is a PD-1 antibody ( claim 15 of copending ‘590 ), specifically pembrolizumab ( claim 20 of copending ‘590 ) ( instant claim 39 ). Claim 25 of copending ‘590 teaches the PD-1 antibody is administered 200 mg once every three weeks ( instant claim 48 ) and 400 mg once every six weeks ( instant claim 49 ). Copending ‘590 does not explicitly state pembrolizumab is a humanized anti-human PD-1 monoclonal antibody ( instant claims 32 and 34 ). Ahamadi et al. teach pembrolizumab is a humanized anti-human PD-1 monoclonal antibody (Pg. 49, column 1, ¶ 1, “anti–PD-1 humanized monoclonal antibody” for treatment of PD-L1 expressing cancers in patients by blocking PD-1 ( instant claims 32 and 34 )). A person having ordinary skill in the art would recognize the properties of pembrolizumab. Instant claim 33 Instant claim 33 teaches the PD-1 antagonist is an anti-human PD-L1 monoclonal antibody. Claims 16 and 24 of copending ‘590 teach the PD-1 antagonist is an anti-PD-1 antibody ( claim 16 of copending ‘590 ), specifically avelumab ( claim 24 of copending ‘590 ). Copending ‘590 does not explicitly state avelumab is an anti-human PD-L1 monoclonal antibody. However, Chin et al. teach avelumab is an antagonistic anti-human PD-L1 monoclonal antibody used for treating cancer (Pg. 1, column 1, ¶ 2, avelumab is a “human immunoglobulin G1 [IgG1] anti-PD-L1 monoclonal antibody ” for treating cancer in human patients; Pg. 1, column 2, ¶ 2, “Avelumab is thought to specifically bind to PD-L1, preventing the interaction between PD-L1 and the inhibitory T-cell receptor PD-1”; instant claim 33 ). A person having ordinary skill in the art would recognize the properties of avelumab. Instant claim 37 Instant claim 37 teaches the ILT4 antagonist is a humanized anti-human ILT4 monoclonal antibody. Regarding instant claim 37 , US ‘096 teaches an antagonistic human anti-human ILT4 monoclonal antibody (¶ 0005, “antibodies or antigen-binding fragments thereof that bind to human ILT4”; ¶ 0072, “the term ‘antibody’ includes, but is not limited to, monoclonal antibodies… [and] fully human antibodies”; ¶ 0046, “present invention provides a method for blocking binding of ILT4”; instant claim 37 ) comprising instant SEQ ID NOs: 1-3 and 6-8 (SEQ ID NOs: 1-3 and 6-8 of the instant application encompassed in SEQ ID NOs: 7 and 2 of US ‘096 respectively). Claim 13 of copending ‘590 also teaches the anti-ILT4 antibody comprises comprising instant SEQ ID NOs: 1-3 and 6-8 (copending ‘590 SEQ ID NOs: 11, 21, and 13 correspond to instant SEQ ID NOs: 1-3; copending ‘590 SEQ ID NOs: 16, 22, and 18 correspond to instant SEQ ID NOs: 6-8). Regarding instant claim 37 , claim 13 of copending ‘590 does not explicitly state the anti-ILT4 antibody is an antagonistic human anti-human ILT4 monoclonal antibody ( instant claim 37 ). However, as the ILT4 antibodies of instant application, copending ‘590, and US ‘096 have the same SEQ ID NOs, these identical ILT4 antibodies have the same functional characteristics. “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present” (MPEP 2112.01). “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence” (MPEP 2131.01). The function of instant claim 37 is an inherent characteristic of the ILT4 antibodies as taught in claim 13 of copending ‘590 , inseparable from its chemical structure, as evidenced by US ‘096. Therefore, despite the fact that the function is not stated in claim 13 of copending ‘590 , a person having ordinary skill in the art would recognize these ILT4 antibodies have the same properties i.e. they are antagonistic human anti-human ILT4 monoclonal antibodies ( instant claim 37 ). Instant claim 40 Instant claim 40 teaches the PD-1 antagonist is nivolumab or cemiplimab. Claim 21 of copending ‘590 teaches the PD-1 antagonist is nivolumab or cemiplimab ( instant claim 40 ) . This is a provisional nonstatutory double patenting rejection. 08-37 AIA Claim 13-14, 58-59, 61-62, and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13, 15, 20-21, and 25 of copending Application No. 18/245,590 (referred to as copending ‘590) in view of US ‘096 and Pichiri et al. as evidenced by Ahamadi et al. Instant claims 13-14, 58, and 66 Instant claims 13-14 teach a method of treating cancer comprising administering to a human patient a PD-1 antagonist, an ILT4 antagonist, and a mitosis inhibitor ( instant claim 13 ), specifically paclitaxel or docetaxel ( instant claim 14 ). Instant claim 58 teaches the PD-1 antagonist is pembrolizumab and the ILT4 antagonist is a monoclonal antibody comprising SEQ ID NOs: 1-3 for LCDRs 1-3 and SEQ ID NOs: 6-8 for HCDRs 1-3. Instant claim 66 teaches the anti-human ILT4 monoclonal antibody or antigen binding fragment thereof is administered from about 100-1600 mg once every three weeks. Claim 13 of copending ‘590 teaches a method for treating cancer in a patient comprising administering to the patient a PD-1 antagonist and an anti-ILT4 antibody ( instant claim 13 ), wherein the anti-ILT4 antibody comprises SEQ ID NOs: 11, 21, and 13 for LCDRS 1-3 respectively and SEQ ID NOs: 16, 22, and 18 for HCDRs 1-3 respectively (copending ‘590 SEQ ID NOs: 11, 21, and 13 correspond to instant SEQ ID NOs: 1-3; copending ‘590 SEQ ID NOs: 16, 22, and 18 correspond to instant SEQ ID NOs: 6-8; instant claim 58 ) and is administered from 3-1600 mg ( instant claim 66 ). Claims 15 and 20 of copending ‘590 teach the PD-1 antagonist is a PD-1 antibody ( claim 15 of copending ‘590 ), specifically pembrolizumab ( claim 20 of copending ‘590 ) ( instant claim 58 ). Regarding instant claim 13 , claim 13 of copending ‘590 does not explicitly state the anti-ILT4 antibody is antagonistic ( instant claim 13 ). However, as the ILT4 antibodies of instant application and copending ‘590 have the same SEQ ID NOs (see claim 13 of copending ‘590 and instant claim 58 ), these identical ILT4 antibodies have the same functional characteristics. “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present” (MPEP 2112.01). The function of instant claim 13 is an inherent characteristic of the ILT4 antibodies as taught in claim 13 of copending ‘590 , inseparable from its chemical structure. Therefore, despite the fact that this function is not stated in claim 13 of copending ‘590 , a person having ordinary skill in the art would recognize these ILT4 antibodies have the same properties i.e. they are antagonistic ( instant claim 13 ). Regarding instant claim 66 , claim 13 of copending ‘590 does not teach 100-1600 mg antagonistic anti-human ILT4 monoclonal antibody is administered once every three weeks. Claim 13 of copending ‘590 teaches an overlapping range of 3-1600 mg however. US ‘096 teaches an antagonistic anti-human ILT4 monoclonal antibody (¶ 0005, “antibodies or antigen-binding fragments thereof that bind to human ILT4”; ¶ 0072, “the term ‘antibody’ includes, but is not limited to, monoclonal antibodies”; ¶ 0046, “present invention provides a method for blocking binding of ILT4”). US ‘096 further teaches, referring to the ILT4 antibody, “in determining the dose, the dose begins with an amount somewhat less than the optimum dose and it is increased by small increments thereafter until the desired or optimum effect is achieved relative to any negative side effects” (¶ 0306). US ‘096 does not teach 100-1600 mg antagonistic anti-human ILT4 monoclonal antibody is administered once every three weeks. MPEP 2144.05(II)(A) states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). It is a common objective in the art to optimize result effective variables (i.e. dosage of antagonistic anti-human ILT4 monoclonal antibody), so as to achieve optimal effect and maximal benefit (i.e. produce positive treatment effects with minimal negative side effects). See In re Boesch , 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) “[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Therefore, any optimization of dosage would be seen as routine optimization––and thus a person having ordinary skill in the art prior to the effective filing date of the instant application would immediately envisage the claimed dosage to achieve them without undue experimentation in order to produce positive treatment effects with minimal negative side effects. Regarding instant claims 13-14 , copending ‘0590 does not teach a mitosis inhibitor. Regarding instant claim 13 , US ‘096 teaches a method of treating cancer with an ILT4 antibody and an anti-PD1 antibody in a human subject (Abstract, “present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 [immunoglobulin-like transcript 4] and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject”; ¶ 0047, “a human subject”; claim 13 ). Regarding instant claim 13 , US ‘096 further teaches an antagonistic anti-human ILT4 monoclonal antibody (¶ 0005, “antibodies or antigen-binding fragments thereof that bind to human ILT4”; ¶ 0072, “the term ‘antibody’ includes, but is not limited to, monoclonal antibodies”; ¶ 0046, “present invention provides a method for blocking binding of ILT4”; claim 13 ). Regarding instant claim 58 , US ‘096 further teaches the antagonistic anti-human ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 of the instant application (SEQ ID NOs: 1-3 and 6-8 of the instant application encompassed in SEQ ID NOs: 7 and 2 of US ‘096 respectively) and pembrolizumab (¶ 0296, “[i] an antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in SEQ ID NO:7 and each heavy chain consists of the amino acid sequence set forth in SEQ ID NO:2, and [ii] pembrolizumab”; claim 58 ). Regarding instant claim 14 , US ‘096 further teaches paclitaxel or docetaxel (¶ 0365, “an anti-ILT4 antibody… is in association with a further chemotherapeutic agent” and “the further chemotherapeutic agent is… paclitaxel, docetaxel”; ¶ 0366, in association means “can be formulated into a single composition”; claim 14 ). Regarding instant claim 13 , US ‘096 does not explicitly state paclitaxel and docetaxel are mitosis inhibitors nor pembrolizumab is a PD-1 antagonist. However, paclitaxel and docetaxel are known mitosis inhibitors (Pichiri et al., Pg. 2, ¶ 2, paclitaxel and docetaxel target microtubules to disrupt mitosis) and pembrolizumab is a known antagonistic anti-human PD-1 monoclonal antibody (Ahamadi et al., Pg. 49, column 1, ¶ 1, “anti–PD-1 humanized monoclonal antibody” for treatment of PD-L1 expressing cancers in patients by blocking PD-1). A person having ordinary skill in the art would recognize paclitaxel and docetaxel as mitosis inhibitors and pembrolizumab as a PD-1 antagonist ( claim 13 ). Pichiri et al. teach paclitaxel or docetaxel are microtubule targeting agents that are “effective in various cancers… therapeutically inhibiting microtubule function during cancer cell mitosis” (Pg. 2, ¶ 3), giving motivation for administration of either paclitaxel or docetaxel in a cancer treatment. Pichiri et al. do not teach a PD-1 antagonist nor an ILT4 antagonist. Treating cancer with an ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 and pembrolizumab in combination with paclitaxel or docetaxel as taught in US ‘096 was known and used prior to the effective filing date of the application. In addition, copending ‘590 and US ‘096 are in analogous arts (i.e. methods of treating cancer with combination therapies). Since Pichiri et al. teach paclitaxel or docetaxel are microtubule targeting agents that are effective in various cancers by therapeutically inhibiting microtubule function during cancer cell mitosis, there is motivation for including paclitaxel or docetaxel as taught in US ‘096 in a method of treating cancer comprising administering to human patients an ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 and pembrolizumab. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. Pichiri et al. teach paclitaxel or docetaxel are microtubule targeting agents that are effective in various cancers by therapeutically inhibiting microtubule function during cancer cell mitosis) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating cancer comprising administering to patients an ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 and pembrolizumab as taught in copending ‘590 wherein paclitaxel or docetaxel are added as taught in US ‘096) to arrive at the claimed invention. There is a reasonable expectation of success as treating cancer with an ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 and pembrolizumab in combination with paclitaxel or docetaxel as taught in US ‘096 was known and used prior to the effective filing date of the application. In addition, copending ‘590 and US ‘096 are in analogous arts (i.e. methods of treating cancer with combination therapies). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to add paclitaxel or docetaxel as taught in US ‘096 in a method of treating cancer comprising administering to human patients an ILT4 monoclonal antibody comprising SEQ ID NOs: 1-3 and 6-8 and pembrolizumab as taught in copending ‘590 ( instant claims 13-14 ). Instant claim 59 Instant claim 59 teaches the PD-1 antagonist is nivolumab or cemiplimab. Claim 21 of copending ‘590 teaches the PD-1 antagonist is nivolumab or cemiplimab ( instant claim 59 ). Instant claims 61-62 Instant claims 61-62 teach pembrolizumab is administered 200 mg once every three weeks ( instant claim 61 ) and 400 mg once every six weeks ( instant claim 62 ). Claim 25 of copending ‘590 teaches pembrolizumab is administered 200 mg once every three weeks ( instant claim 61 ) and 400 mg once every six weeks ( instant claim 62 ) . This is a provisional nonstatutory double patenting rejection. Conclusion 12-151-07 AIA 07-97 12-51-07 Claim s 1-2, 6, 13-14, 32-34, 36-37, 39-40, 42-44, 48-50, 53, 58-59, 61-63, 66, and 69 are pending. Claims 1-2, 6, 13-14, 32-34, 36-37, 39-40, 42-44, 48-50, 53, 58-59, 61-63, 66, and 69 are rejected. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jessica M Priest whose telephone number is (571)272-8469. The examiner can normally be reached Mon-Fri 8am-5pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /J.M.P./Examiner, Art Unit 1642 /SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642 Application/Control Number: 18/580,255 Page 2 Art Unit: 1642 Application/Control Number: 18/580,255 Page 3 Art Unit: 1642 Application/Control Number: 18/580,255 Page 4 Art Unit: 1642
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