DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
Two information disclosure statements (IDS) submitted: one on October 27th, 2025; one on December 8th, 2025; filed after the mailing date of the non-final rejection on June 26th, 2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are pending in this application. Claims 2, 4-6, 8-9, 12-15, 19, 21-32, 34, 36-41, 43-44, and 46-47 have been cancelled by applicant.
Claim Rejections - 35 USC § 103
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.
Claims 1, 3, 7, 10-11, 16-18, 20, 45, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Martinez-Garcia et al. (Clin. Cancer Res.; 18, 2012, 4806 – From IDS – previously cited) (“Martinez-Garcia”); in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8 – previously cited) (“Gong”).
Regarding claims 1 and 18, Martinez-Garcia teaches RO5126766 (a.k.a. VS-6766) as a first-in-class dual RAF/MEK inhibitor, showing three partial responses: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma (abstract).
Martinez-Garcia does not teach: (i) administration of the RAF/MEK inhibitor in combination with an anti-PD-1 antibody (claim 1); or (ii) with an anti-PD-L1 antibody (claims 18-20). The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 and ligand protein receptor 1 (PD-1 and PD-L1, respectively) blockade as effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor (page 1, col. 2, last para.; page 7, col. 2, para. 3; and Table 1) and discloses pembrolizumab in combination with other chemotherapeutic agents (Table 3, entry 3, page 6). Gong further teaches atezolizumab as a PD-L1 inhibitor (page 1, col. 2, last para.; page 7, col. 2, para. 3; and Table 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat a cancer by administering a combination regimen of Martinez-Garcia’s VS-6766 with Gong’s PD-1 or PD-L1 immunotherapies, as recited in instant claims 1 and 18. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma and that oral VS-6766 showed manageable toxicity, favorable pharmacokinetics, and around 40% tumor shrinkage of patients across all dose levels and tumor types (abstract); further because Gong teaches PD-1 and/ or PD-L1 blockade as effective cancer immunotherapies.
Applicant is advised the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents, both of which are known cancer therapies, to arrive at a composition capable of treating cancer.
Regarding claim 3, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, with dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2). Martinez-Garcia also teaches that VS-6766 has a half-life of about 60 hours (<3 days) (page 4815, col. 2, lines 1-4) and the benefits and drawbacks of daily, 4 on/ 3 off, and 7 on/ 7 off dosing regimens (page 4815, col. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer the RAF/MEK inhibitor VS-6766 twice a week, depending on the initial dose given to the subject. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in cancer treatment in view of Martinez-Garcia’s teachings on the half-life of VS-6766 and the dose-limiting toxicities observed during clinical trials. Applicant is advised, a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 [R-6] KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
Regarding administration of about 3.2 mg to about 4 mg of VS-6766 per administration, as recited in claim 7, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2), however, they also disclose dosing at 4.0 mg (4 days on/ 3 off).
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Further regarding instant claims 3, 7, 11, and 16, Applicant is advised, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). Where 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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
Regarding claims 45 and 48, Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma (abstract). Martinez-Garcia also teaches ovarian cancer with HRAS mutations (Table 1, page 4809).
Claims 33 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Martinez-Garcia et al. (Clin Cancer Res; 18, 2012, 4806 – From IDS – previously cited) (“Martinez-Garcia”); and Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8 – previously cited) (“Gong”); as applied to claims 1, 3, 7, 10-11, 16-18, 20, 45, and 48; further in view of Shimizu et al. (Cancer Chemother Pharmacol (2016) 77:997–1003 – From IDS – previously cited) (“Shimizu”).
The teachings of Martinez-Garcia and Gong are disclosed above and incorporated herein.
Martinez-Garcia in view of Gong does not teach coadministration of a FAK inhibitor. The teachings of Shimizu are relied upon for these disclosures.
Shimizu teaches VS-6063 (a.k.a. defactinib) as an inhibitor of focal adhesion kinase (FAK) for patients with advanced solid tumor malignancies (abstract). Shimizu further discloses VS-6063 was administered orally twice daily (methods-abstract) at 200 to 600 mg daily (results-abstract) and no dose-limiting toxicities were observed. Shimizu specifically discloses that FAK inhibitors are not overly cytotoxic and are expected to be most effective when used in combination with other chemotherapeutic drugs (page 1002, col. 2, para. 2, lines 10-15), specifically mentioning combination with PD-1 and PD-L1 inhibitors (page 1003, col. 1, lines 1-4).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat a cancer by administering a combination regimen comprising Martinez-Garcia’s and Gong’s VS-6766/ PD-1 or PD-L1 therapy further comprising Shimizu’s FAK inhibitor, as recited in instant claim 33. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because: (i) Martinez-Garcia teaches that treatment with VS-6766 alone showed manageable toxicity, favorable pharmacokinetics, and around 40% tumor shrinkage of patients across all dose levels and tumor types (abstract); (ii) Gong teaches PD-1 and/ or PD-L1 blockade as effective cancer immunotherapy; (iii) and Shimizu teaches VS-6063 (a.k.a. defactinib) as a FAK inhibitor, and discloses that FAK inhibitors are not overly cytotoxic and are expected to be most effective when used in combination with other chemotherapeutic drugs, like PD-1 or PD-L1 inhibitors.
Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the three agents, all of which are known cancer therapies, to arrive at a composition capable of treating cancer.
Regarding claim 35, Shimizu teaches VS-6063 was administered orally twice daily in clinical trials.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Martinez-Garcia et al. (Clin Cancer Res; 18, 2012, 4806 – From IDS – previously cited) (“Martinez-Garcia”); and Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8 – previously cited) (“Gong”); further in view of Shimizu et al. (Cancer Chemother Pharmacol (2016) 77:997–1003 – From IDS – previously cited) (“Shimizu”).
Regarding claim 42, Martinez-Garcia teaches RO5126766 (a.k.a. VS-6766) as a first-in-class dual RAF/MEK inhibitor, showing three partial responses: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma (abstract).
Martinez-Garcia does not teach coadministration of a PD-1 or PD-L1 inhibitor, and FAK inhibitor VS-6063. The teachings of Gong and Shimizu are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 and ligand protein receptor 1 (PD-1 and PD-L1, respectively) blockade as effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor (page 1, col. 2, last para.; page 7, col. 2, para. 3; and Table 1) and discloses pembrolizumab in combination with other chemotherapeutic agents (Table 3, entry 3, page 6). Gong further teaches atezolizumab as a PD-L1 inhibitor (page 1, col. 2, last para.; page 7, col. 2, para. 3; and Table 1).
Shimizu teaches VS-6063 (a.k.a. defactinib) as an inhibitor of focal adhesion kinase (FAK) for patients with advanced solid tumor malignancies (abstract). Shimizu further discloses VS-6063 was administered orally twice daily (methods-abstract) at 200 to 600 mg daily (results-abstract) and no dose-limiting toxicities were observed. Shimizu specifically discloses that FAK inhibitors are not overly cytotoxic and are expected to be most effective when used in combination with other chemotherapeutic drugs (page 1002, col. 2, para. 2, lines 10-15), specifically mentioning combination with PD-1 and PD-L1 inhibitors (page 1003, col. 1, lines 1-4).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat a cancer by administering a combination regimen comprising Martinez-Garcia’s and Gong’s VS-6766/ PD-1 or PD-L1 therapy further comprising Shimizu’s FAK inhibitor, as recited in instant claim 42. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because: (i) Martinez-Garcia teaches that treatment with VS-6766 alone showed manageable toxicity, favorable pharmacokinetics, and around 40% tumor shrinkage of patients across all dose levels and tumor types (abstract); (ii) Gong teaches PD-1 and/ or PD-L1 blockade as effective cancer immunotherapy; (iii) and Shimizu teaches VS-6063 (a.k.a. defactinib) as a FAK inhibitor, and discloses that FAK inhibitors are not overly cytotoxic and are expected to be most effective when used in combination with other chemotherapeutic drugs, like PD-1 or PD-L1 inhibitors.
Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the three agents, all of which are known cancer therapies, to arrive at a composition capable of treating cancer.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 9,962,385 B2 (US ‘385) – From IDS, in view of Martinez-Garcia et al. (Clin Cancer Res; 18(17) September 1, 2012, 4806 – From IDS) and Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, US ‘385 claims a method of treating cancer comprising administration of FAK inhibitor VS-6063 in combination with an MEK inhibitor.
US ‘385 does not teach: (i) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-1 antibody without a FAK inhibitor (instant claims 1, 3, 7, 10-11, 16-17); (ii) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-L1 antibody without an FAK inhibitor (instant claims 18 and 20); (iii) administration of the FAK inhibitor with a RAF/MEK dual inhibitor and an anti-PD-1 inhibitor (instant claims 33 and 35); (iv) administration of the FAK inhibitor with a RAF/MEK dual inhibitor and an anti-PD-L1 inhibitor (instant claim 42); (v) wherein the cancer has KRAS, HRAS, NRAS, or BRAF mutation (instant claim 45); or (vi) the specific cancers listed in instant claim 48. The teachings of Martinez-Garcia and Gong are relied upon for these disclosures.
Martinez-Garcia teaches RO5126766 (a.k.a. VS-6766) as a first-in-class dual RAF/MEK inhibitor, showing three partial responses: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma (abstract).
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a RAF/MEK inhibitor and anti-PD-1 antibody or anti-PD-L1 antibody, as recited in instant claims 1, 3, 7, 10-11, 16-18, and 20, or administration of an FAK inhibitor in combination with a dual RAF/MEK inhibitor and an anti-PD-1 or PD-L1 inhibitor, as recited in instant claims 33, 35, and 42, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of US ‘385 method for the treatment of cancer with an MEK inhibitor with the disclosures of Martinez-Garcia and Gong to arrive at the instant invention.
Regarding claim 3, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, with dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2). Martinez-Garcia also teaches that VS-6766 has a half-life of about 60 hours (<3 days) (page 4815, col. 2, lines 1-4) and the benefits and drawbacks of daily, 4 on/ 3 off, and 7 on/ 7 off dosing regimens (page 4815, col. 1).
Regarding administration of about 3.2 mg to about 4 mg of VS-6766 per administration, as recited in claim 7, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2), however, they also disclose dosing at 4.0 mg (4 days on/ 3 off). Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Further regarding claims 3 and 7, the courts have found that where 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
Regarding claims 45 and 48, Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma (abstract). Martinez-Garcia also teaches ovarian cancer with HRAS mutations (Table 1, page 4809).
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,406,158 B2 (US ‘158) – From IDS, in view of Martinez-Garcia et al. (Clin Cancer Res; 18(17) September 1, 2012, 4806 – From IDS) and Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, US ‘158 claims a method of treating cancer comprising administration of FAK inhibitor VS-6063 in combination with an MEK inhibitor (US ‘158’s claim 1), and wherein treatment comprises administration of an additional chemotherapy or immunotherapy (US ‘158’s claim 11).
US ‘158 does not specifically claim: (i) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-1 antibody without a FAK inhibitor (instant claims 1, 3, 7, 10-11, 16-17); (ii) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-L1 antibody without an FAK inhibitor (instant claims 18 and 20); (iii) administration of the FAK inhibitor with a RAF/MEK dual inhibitor and an anti-PD-1 inhibitor (instant claims 33 and 35); (iv) administration of the FAK inhibitor with a RAF/MEK dual inhibitor and an anti-PD-L1 inhibitor (instant claim 42); (v) wherein the cancer has a KRAS, HRAS, NRAS, or BRAF mutation (instant claim 45); or (vi) the specific cancers listed in instant claim 48. The teachings of Martinez-Garcia and Gong are relied upon for these disclosures.
Martinez-Garcia teaches RO5126766 (a.k.a. VS-6766) as a first-in-class dual RAF/MEK inhibitor, showing three partial responses: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma (abstract).
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a RAF/MEK inhibitor and anti-PD-1 antibody or anti-PD-L1 antibody, as recited in instant claims 1, 3, 7, 10-11, 16-18, and 20, or administration of an FAK inhibitor in combination with a dual RAF/MEK inhibitor and an anti-PD-1 or PD-L1 inhibitor, as recited in instant claims 33, 35, and 42, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of US ‘158 method for the treatment of cancer with an MEK inhibitor with the disclosures of Martinez-Garcia and Gong to arrive at the instant invention.
Regarding claim 3, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, with dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2). Martinez-Garcia also teaches that VS-6766 has a half-life of about 60 hours (<3 days) (page 4815, col. 2, lines 1-4) and the benefits and drawbacks of daily, 4 on/ 3 off, and 7 on/ 7 off dosing regimens (page 4815, col. 1).
Regarding administration of about 3.2 mg to about 4 mg of VS-6766 per administration, as recited in claim 7, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2), however, they also disclose dosing at 4.0 mg (4 days on/ 3 off). Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Further regarding claims 3 and 7, the courts have found that where 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
Regarding claims 45 and 48, Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma (abstract). Martinez-Garcia also teaches ovarian cancer with HRAS mutations (Table 1, page 4809).
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 10,532,056 B2 (US ‘056) – From IDS, in view of Martinez-Garcia et al. (Clin Cancer Res; 18(17) September 1, 2012, 4806 – From IDS).
Regarding claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, US ‘056 claims a method of treating cancer comprising administering to a subject an effective amount of FAK inhibitor VS-6063 in combination with an anti-PD-1 antibody (US ‘056 claim 1) or anti-PD-L1 antibody (US ‘056 claim 20).
US ‘056 does not specifically claim: (i) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-1 antibody without a FAK inhibitor (instant claims 1, 3, 7, 10-11, 16-17); (ii) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-L1 antibody without an FAK inhibitor (instant claims 18 and 20); (iii) wherein the cancer has a KRAS, HRAS, NRAS, or BRAF mutation (instant claim 45); or (iv) the specific cancers listed in instant claim 48. The teachings of Martinez-Garcia et al. are relied upon for these disclosures.
Martinez-Garcia teaches RO5126766 (a.k.a. VS-6766) as a first-in-class dual RAF/MEK inhibitor, showing three partial responses: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma (abstract).
Regarding co-administration or combination therapy of a RAF/MEK inhibitor and anti-PD-1 antibody or anti-PD-L1 antibody, without an FAK inhibitor, as recited in instant claims 1, 3, 7, 10-11, 16-18, and 20, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of US ‘056 method for the treatment of cancer with an MEK inhibitor with the disclosures of Martinez-Garcia and Gong to arrive at the instant invention.
Regarding claim 3, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, with dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2). Martinez-Garcia also teaches that VS-6766 has a half-life of about 60 hours (<3 days) (page 4815, col. 2, lines 1-4) and the benefits and drawbacks of daily, 4 on/ 3 off, and 7 on/ 7 off dosing regimens (page 4815, col. 1).
Regarding administration of about 3.2 mg to about 4 mg of VS-6766 per administration, as recited in claim 7, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2), however, they also disclose dosing at 4.0 mg (4 days on/ 3 off). Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Further regarding claims 3 and 7, the courts have found that where 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
Regarding claims 45 and 48, Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma (abstract). Martinez-Garcia also teaches ovarian cancer with HRAS mutations (Table 1, page 4809).
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11,564,927 B2 (US ‘927) – From IDS; in view of Martinez-Garcia et al. (Clin Cancer Res; 18(17) September 1, 2012, 4806 – From IDS); and Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, US ‘927 claims a method of treating cancer comprising administering to a subject an effective amount of FAK inhibitor VS-6063 in combination with an anti-PD-1 antibody (US ‘927 claim 1). US ‘927 speaks to cell lung and ovarian cancers (US ‘927 claim 18) reading on instant claims 45 and 48.
US ‘927 does not teach: (i) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-1 antibody without a FAK inhibitor (instant claims 1, 3, 7, 10-11, 16-17); (ii) administration of a dual RAF/MEK inhibitor in combination with an anti-PD-L1 antibody without an FAK inhibitor (instant claims 18 and 20); or (iii) administration of the FAK inhibitor with a RAF/MEK dual inhibitor and an anti-PD-L1 inhibitor (instant claim 42). The teachings of Martinez-Garcia and Gong et al. are relied upon for these disclosures.
Martinez-Garcia teaches RO5126766 (a.k.a. VS-6766) as a first-in-class dual RAF/MEK inhibitor, showing three partial responses: two in BRAF-mutant melanoma tumors and one in an NRAS-mutant melanoma (abstract).
Gong teaches programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a RAF/MEK inhibitor and anti-PD-1 antibody or anti-PD-L1 antibody, without an FAK inhibitor, as recited in instant claims 1, 3, 7, 10-11, 16-18, and 20, or administration of an FAK inhibitor in combination with a dual RAF/MEK inhibitor and an anti-PD-L1 inhibitor, as recited in instant claim 42, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of US ‘927 method for the treatment of cancer with an MEK inhibitor with the disclosures of Martinez-Garcia and Gong to arrive at the instant invention.
Regarding claim 3, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, with dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2). Martinez-Garcia also teaches that VS-6766 has a half-life of about 60 hours (<3 days) (page 4815, col. 2, lines 1-4) and the benefits and drawbacks of daily, 4 on/ 3 off, and 7 on/ 7 off dosing regimens (page 4815, col. 1).
Regarding administration of about 3.2 mg to about 4 mg of VS-6766 per administration, as recited in claim 7, Martinez-Garcia teaches different dosing regimens, with the 4 days on/ 3 days off treatment regimen, dosing at 2.7 mg being the best tolerated of all dose regimens (page 4813, col. 2, para. 2), however, they also disclose dosing at 4.0 mg (4 days on/ 3 off). Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists.
Further regarding claims 3 and 7, the courts have found that where 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
Regarding claims 45 and 48, Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma (abstract). Martinez-Garcia also teaches ovarian cancer with HRAS mutations (Table 1, page 4809).
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 32, 36, 41-43, 46-47, 52-53-54 of copending Application No. 17/795,402 (Copending ‘402); in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding instant claims 1, 3, 7, 10-11, 16-20, 33, 35, 42, 45, and 48, Copending ‘402 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766 dosed at least once a week at about 0.1 to 100 mg (instant claims 3 and 7) (Copending ‘402 claims 32, 36, 41-43, and 46-47). Copending ‘402 also speaks to coadministration with a FAK inhibitor, specifically defactinib (instant claims 33, 35, and 42) for the treatment of the same cancers as instant claim 48 with KRAS mutations (Copending ‘402 claims 53-54).
Copending ‘402 does not teach coadministration with a PD-1 antibody or PD-L1 antibody inhibitor. The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a FAK inhibitor with a RAF/MEK inhibitor and anti-PD-1 antibody or PD-L1 antibody, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Copending ‘402 with the disclosures of Gong to arrive at the instant invention.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3-4, 11, 13, 16-17, 19, 20-23, 27-29, and 37 of copending Application No. 17/921,509 (Copending ‘509); in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding instant claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, Copending ‘509 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766, dosing twice a week at about 0.5-10 mg (instant claims 3 and 7) (Copending ‘509 claims 3-4, 11, 13, 16-17, 19, 20-22). Copending ‘509 also speaks to coadministration with a FAK inhibitor - defactinib (Copending ‘509 claims 28-29). Copending ‘509 also speaks to cancers with KRAS mutations such as ovarian cancer, etc. (Copending ‘509 claim 37).
Copending ‘509 does not teach coadministration with a PD-1 antibody or PD-L1 antibody inhibitor. The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a FAK inhibitor with a RAF/MEK inhibitor and anti-PD-1 antibody or PD-L1 antibody, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Copending ‘509 with the disclosures of Gong to arrive at the instant invention.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2-5, 9-14, 24-26, 48, 53, and 57 of copending Application No. 18/704,267 (Copending ‘267) in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding instant claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, Copending ‘267 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766, administered at 3.2 mg, twice a week (instant claims 3 and 7) (Copending ‘267 claims 1, 5, 9-11 and 53). Copending ‘267 also speaks to coadministration with a FAK inhibitor - defactinib (Copending ‘267 claims 3-4). Copending ‘267 claims treatment of melanoma, etc. (Copending ‘267 claim 57).
Copending ‘267 does not teach coadministration with a PD-1 antibody or PD-L1 antibody inhibitor. The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a FAK inhibitor with a RAF/MEK inhibitor and anti-PD-1 antibody or PD-L1 antibody, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Copending ‘267 with the disclosures of Gong to arrive at the instant invention.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8, 11-16, 25, 52, 55-57, 60-61, 67, and 77 of copending Application No. 18/702,569 (Copending ‘569) in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding instant claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, Copending ‘569 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766 twice a week at about 0.5-10 mg (instant claims 3 and 7) (Copending ‘569 claims 1, 8, and 11-16). Copending ‘569 also speaks to coadministration with a FAK inhibitor - defactinib (Copending ‘569 claims 67 and 77); for treating a cancer with a KRAS, HRAS, etc. mutation (instant claims 45 and 48) (Copending ‘569 claims 45 and 61).
Copending ‘569 does not teach coadministration with a PD-1 antibody or PD-L1 antibody inhibitor. The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a FAK inhibitor with a RAF/MEK inhibitor and anti-PD-1 antibody or PD-L1 antibody, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Copending ‘569 with the disclosures of Gong to arrive at the instant invention.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 4-5, 7-8, 11-12, 40, 56-58, 62, 64, 70-71, and 74-77 of copending Application No. 18/292,086 (Copending ‘086).
Regarding instant claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, Copending ‘086 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766, administered twice a week, at about 3.2 mg (Copending ‘086 claims 1-2). Copending ‘086 also speaks to coadministration with a FAK inhibitor - defactinib (Copending ‘086 claims 62 and 64) and coadministration with an anti-PD-L1 antibody – atezolizumab (Copending ‘086 claim 40). Copending ‘086 speaks to the treatment of cancer with KRAS mutations – ovarian, etc. (Copending ‘086 claims 74-77).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-52 of copending Application No. 18/718,137 (Copending ‘137) in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding instant claims 1, 3, 7, 10-11, 16-20, 33, 35, 42, 45, and 48, Copending ‘137 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766, administered twice a week at 0.5-10 mg (instant claims 3 and 7) (Copending ‘137 claims 13-25). Copending ‘137 also speaks to coadministration with a FAK inhibitor - defactinib (Copending ‘137 claims 43-52). Copending ‘137 speaks to treatment of HRAS, KRAS, etc. mutated cancers, like ovarian, etc. (Copending ‘137 claims 2 and 33).
Copending ‘137 does not teach coadministration with a PD-1 antibody or PD-L1 antibody inhibitor. The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a FAK inhibitor with a RAF/MEK inhibitor and anti-PD-1 antibody or PD-L1 antibody, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Copending ‘137 with the disclosures of Gong to arrive at the instant invention.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-57 of copending Application No. 18/730,905 (Copending ‘905) in view of Gong et al. (Journal for ImmunoTherapy of Cancer, 2018, 6:8).
Regarding instant claims 1, 3, 7, 10-11, 16-18, 20, 33, 35, 42, 45, and 48, Copending ‘905 claims a method of treating cancer comprising coadministration of RAF/MEK inhibitor VS-6766, administered twice a week at about 0.5-10 mg (instant claims 3 and 7) (Copending ‘905 claims 19-31). Copending ‘905 also speaks to coadministration with a FAK inhibitor - defactinib (Copending ‘905 claims 48-57). Copending ‘905 speaks to treatment of KRAS, HRAS, etc. mutated cancers, like melanoma, etc. (instant claims 45 and 48) (Copending ‘905 claims 2 and 40).
Copending ‘905 does not teach coadministration with a PD-1 antibody or PD-L1 antibody inhibitor. The teachings of Gong et al. are relied upon for these disclosures.
Gong teaches programmed cell death protein receptor 1 (PD-1) blockade and programmed cell death ligand protein receptor 1 (PD-L1) blockade as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2). Furthermore, Gong teaches pembrolizumab as a PD-1 inhibitor and atezolizumab as a PD-L1 inhibitor as an effective cancer immunotherapy (page 1, end of col. 1, top col. 2).
Regarding co-administration or combination therapy of a FAK inhibitor with a RAF/MEK inhibitor and anti-PD-1 antibody or PD-L1 antibody, applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Copending ‘905 with the disclosures of Gong to arrive at the instant invention.
Regarding claim 10, Gong teaches pembrolizumab as a PD-1 inhibitor and anticancer agent (page 1, col. 2, last para. and Table 1).
Regarding claim 11, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg every 2 weeks for 24 months (page 10, col. 2, para. 1).
Regarding claim 16, Gong teaches that, in clinical trials, patients received pembrolizumab 10 mg/ kg per administration every 2 weeks (page 10, col. 2, para. 1). Considering the average weight of a human subject to be about 70 kg, that would mean a dose of about 700 mg per administration.
Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, the courts have found that where 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.
Regarding claim 17, Gong teaches intravenous administration of pembrolizumab (page 3, col. 1, line 8-9).
Regarding claim 20, Gong teaches atezolizumab as a PD-L1 inhibitor (page 7, col. 2, para. 3; and Table 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been added.
Specification
Amendments to the specification are acknowledged. No new matter has been added. Changes have been entered.
Objections to the Claims
Applicant’s arguments, see page 6, filed October 27th, 2025, with respect to objection to claim 16 have been fully considered and are persuasive. The objection of claim 16 has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed October 27th, 2025 have been fully considered but they are not persuasive.
Applicant states Martinez-Garcia (hereafter M-G) discloses VS-6766 as a monotherapy, not as a dual therapy with a PD-1 or PD-L1 inhibitor. Applicant states M-G does not disclose or suggest the claimed dosing regimen, and is silent about specifically 3.2 mg of VS-6766 and doesn’t suggest any modification to the dosing. Applicant states Gong also fails to disclose the claimed combination and states it is unclear how one of ordinary skill would arrive at the claimed combination from M-G in view of Gong.
Applicant states that Shimizu doesn’t disclose the claimed triple combination of VS-6766, an anti-PD-1 or anti-PD-L1, and VS-6063, asserting that ‘a vague reference to combination of VS-6063 with additional therapeutic agents does not render the instant claims obvious, and that it is unclear how one of ordinary skill would arrive at the instant combination.’ Applicant states there is no teaching, suggestion, or motivation in the cited references that would motivate one of ordinary skill to arrive at the instant claims.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In the present case, the individual components of the instantly claimed therapeutic agent combination are known in the art for the treatment of cancer. Therefore, as stated in the rejections above, it is prima facie obvious to combine compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP 2144.06. It is therefore obvious to provide a mixture of the agents in the absence of significant unexpected results.
With regards to the dosing regimens of 3.2 mg; M-G teaches 2.7 mg being the best tolerated of all dose regimens for their clinical trials (page 4813, col. 2, para. 2), however, they also disclose dosing at 4.0 mg (4 days on/ 3 off). Applicant is reminded, the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. Furthermore, where 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.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case: (i) Martinez-Garcia teaches that treatment with VS-6766 alone showed three partial responses: two in BRAF-mutant melanoma and one in NRAS-mutant melanoma and that oral VS-6766 showed manageable toxicity, favorable pharmacokinetics, and around 40% tumor shrinkage of patients across all dose levels and tumor types (abstract); (ii) Gong teaches pembrolizumab as a PD-1 inhibitor, atezolizumab as PD-L1 inhibitor, and teaches that PD-1 and PD-L1 blockade are effective for cancer immunotherapy, further disclosing pembrolizumab in combination with other chemotherapeutic agents; and (iii) Shimizu teaches VS-6063 (a.k.a. defactinib) as an inhibitor of focal adhesion kinase (FAK) for patients with advanced solid tumor malignancies, specifically mentioning combination with PD-1 and PD-L1 inhibitors.
Per MPEP 2144.06, as stated above; “[T]he idea of combining them flows logically from their having been individually taught in the prior art” (that the two claimed types of active agents were known to be useful for the same purpose alone can serve as a motivation to combine).
Applicant states the instant claims demonstrate unexpected technical effects, citing Figures 4A and 4B (shown below for convenience) to allegedly demonstrate that combination of VS-6766 and an anti-PD-1 antibody delayed tumor growth and reduced tumor volume, and that the further addition of a FAK inhibitor amplified these results. Applicant further cites Figures 3A and 3B to allegedly show a specific and durable antitumor T-cell response by the claimed combination that is not expected or predictable based on the cited references.
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In the present case, instant claims are not drawn to VS-4718 as the FAK inhibitor of the tri-component composition (they are drawn to defactinib – VS-6063), and therefore, the results shown in the Figures do not demonstrate unexpected results relevant to the scope of the claims. Applicant would need to demonstrate the effects of combination with FAK inhibitor VS-6063, as claimed. Furthermore, it is unclear if the results provided demonstrate an additive effect of the combination of three drugs or if synergy is present. While the figures demonstrate that a tri-combination of drugs works better than a combination of two drugs or each drug individually, an additive effect is not entirely unexpected, at least in view of Shimizu, who teaches that VS-6063 (a.k.a. defactinib) is a FAK inhibitor which should be administered in combination with PD-1 and PD-L1 inhibitors.
Regarding the results shown in Figures 3A and 3B, no comparative data is provided with the activity of the individual compounds, so as to demonstrate a synergistic effect arising from combination therapy. Therefore, arguments are not persuasive, and the instant claims stand rejected.
Double Patenting
Applicant's arguments filed October 27th, 2025 have been fully considered but they are not persuasive.
Applicant requests obviousness-type double patenting rejections be held in abeyance until instant application is deemed allowable. Instant claims stand rejected over US Patent No. 9,962,385 B2; 10,406,158 B2; 10,532,056 B2; 11,564,927 B2; and Copending Application No. 17/795,402; 17/921,509; 18/704,267; 18/702,569; 18/292,086; 18/718,137; and 18/730,905 for reasons of record.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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