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 .
All previous objections and rejections not reiterated herein were overcome by claim amendments and arguments, filed May 18th, 2026, have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180; cited in the office action dated November 19th, 2025) in view of Rossi et. al. ((2012), Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data, J Clin Oncol, 30, 1692 – 1698; cited in the office action dated November 19th, 2025).
Regarding claims 1 – 16, Chakravarty’180 teach novel combination therapies for the treatment of proliferative disorders comprising administering an MEK inhibitor in combination with a selective inhibitor of Aurora Kinase inhibitor (page 3 paragraph 0022). More specifically, Chakravarty’180 teach an embodiment wherein the selective inhibitor of Aurora Kinase A is sodium 4-((9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl)amino)-2-methoxybenzoate, that is Alisertib (claim 1) (page 35 paragraphs 0180). Additionally, Chakravarty’180 teach that the new combination therapies can be used for the treatment of various cancers including gastric, breast, and small cell lung cancer (claims 1 – 3) (page 38 paragraphs 0200).
Furthermore, Chakravarty’180 teach that other therapeutic agents can be used in combination with MEK and selective aurora A kinase inhibitors, such as platinum compounds which includes carboplatin (claims 4 – 6) and cisplatin (claim14) (page 42 paragraph 0241) and taxanes which includes paclitaxel and docetaxel (page 43 paragraph 0245). Additionally, Chakravarty’180 teach that in certain embodiments the frequency in which any therapeutic agent, which includes the selective Aurora Kinase inhibitor and platinum compounds, can be administered can be once or more than once over a period of about 28 days and can be administered daily (page 40 paragraphs 0221 – 0222).
Furthermore, Chakravarty’180 teach in some embodiments, that the MEK inhibitor and the selective Aurora A kinase inhibitor are cyclically administered to a patient wherein a first agent is administered for a period of time, followed by the administration of a second agent and/or third agent for a period of time and repeating this sequential administration (page 41 paragraph 0228). Moreover, Chakravarty’180 teach that cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment (page 41 paragraph 0228). Furthermore, Chakravarty’180 teach an embodiment of cycling therapy wherein the selective Aurora A kinase inhibitor is administered for a particular length of time prior to administration of the MEK inhibitor (page 41 paragraph 0229). Specifically, Chakravarty’180 teach an embodiment for a 21-day cycle, wherein the selective Aurora A kinase inhibitor may be administered on days 1 to 5, days 1 to 7, days 1 to 10, or days 1 to 14, and the MEK inhibitor may be administered on days 6 to 21, days 8 to 21, days 11 to 21, or days 14 to 21 (page 41 paragraph 0229).
Moreover, Chakravarty’180 teach that the therapeutically effective amounts or suitable dosage mounts for MEK or the Aurora kinase inhibitor or Alisertib in combination depends on a number of factors, including the severity of the condition, the particular inhibitor, the route of administration, age, weight, general health or response of the individual and can range from 20 mg (claim 8), 25 mg (claim 9), 30 mg (claim 10), 40 mg (claim 11), and 50 mg (page 42 paragraph 0237) and dictate the administration regimen (page 41 paragraph 0232). Furthermore, Chakravarty’180 teach that the present disclosure, that is for a method comprising an MEK and Aurora kinase inhibitor can be provided in a kit which can further comprise additional therapeutic agents (page 44 paragraph 0257).
Regarding claim 7 limitation for a method where 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid or a pharmaceutically acceptable salt thereof is administered twice a day on each of days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 28 day schedule; this limitation is obvious over the teachings above. In particular, as taught above, Chakravarty’180 does teach an example cycling therapy (page 41 paragraph 0228) that Chakravarty’180 further teach can be optimized based on a serious of factors for the individual patient such as weight that can dictate the administration regimen (page 41 paragraph 0232). Moreover, Chakravarty’180 teach that cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment (page 41 paragraph 0228). Additionally, Chakravarty’180 teach that in certain embodiments the frequency in which any therapeutic agent, which includes the selective Aurora Kinase inhibitor and platinum compounds, can be administered can be once or more than once over a period of about 28 days and can be administered daily (page 40 paragraphs 0221 – 0222).
Therefore, it would have been obvious before the effective filing date of the instant application to modify and optimize the exemplified cycling regimen of Chakravarty’180 to administer 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid or a pharmaceutically acceptable salt thereof is administered twice a day on each of days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 28 day schedule. One of ordinary skill in the art would be motivated to make the modification and have a reasonable expectation of success because the prior art teach that cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment.
However, Chakravarty’180 fails to explicitly teach a method wherein the platin is administered on day 1 of a 28 day schedule (claims 1, and 12), wherein the platin is administered on each of days 1, 8 and 15 of a 28 day schedule (claims 1, and 13). Moreover, Chakravarty’180 fails to explicitly teach a method wherein the cisplatin is administered from about 75 mg/m2 to about 100 mg/m2 per dose (claim 15), and wherein the cisplatin is administered from about 50 mg/m2 to about 70 mg/m2 per dose (claim 16).
Nevertheless, Rossi et. al. teach that small cell lung cancer accounts for 15% of all lung cancers and most patients present with extensive disease at first diagnosis (page 2 paragraph 2). Furthermore, Rossi et. al. teach that both cisplatin and carboplatin are known to be used in the treatment of small cell lung cancer (SCLC) but their toxicity remains a point of contention (page 2 paragraph 3). Additionally, Rossi et. al. teach that depending on the tumor type, whether ovarian, germ cell, head and neck, cisplatin or carboplatin might be superior since both platins have serious side effects that include for cisplatin neurotoxicity wand for carboplatin myelosuppression (page 2 paragraphs 3 – 4).
Moreover, Rossi et. al. teach that in the case of SCLC, several studies have found that cisplatin based regimens resulted in slightly superior outcomes compared to carboplatin in terms of objective response rate (ORR) and in certain subgroups, prolonged overall survival (OS), without being associated with a significant increase in toxic effects (page 2 paragraph 4). Specifically, Rossi et. al. teach that in various studies a comparison of cisplatin vs. carboplatin at various dosages were done which included the administration of cisplatin 25 mg/m2 on days 1 – 3; 30 mg/m2 on days 1 – 3; 50 mg/m2 (claim 16) on days 1 – 2 and 60 mg/m2 (claims 15) on day 1 (claim 12) (pages 15 – 27 Table 1 expanded).
Regarding claim 15 recitation, wherein the cisplatin is administered from about 75 mg/m2 to about 100 mg/m2 per dose given that the recites the term “about” signals a broader value; thus the prior art recitation of 60 mg/m2 is relatively close to the value of 75 mg/m2. Therefore, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)(MPEP 2144.05(I)).
Moreover, regarding the recitation of claim 13 wherein the platin is administered on each of days 1, 8 and 15 of a 28 day schedule, Chakravarty’180 teach an example cycling therapy (page 41 paragraph 0228) that Chakravarty’180 further teach can be optimized based on a serious of factors for the individual patient such as weight that can dictate the administration regimen (page 41 paragraph 0232). Moreover, Chakravarty’180 teach that cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment (page 41 paragraph 0228). Additionally, Rossi et. al. does teach that in various studies cisplatin was administered in a variety of regimens such as 25 mg/m2 on days 1 – 3; 30 mg/m2 on days 1 – 3; 50 mg/m2 on days 1 – 2 and 60 mg/m2 on day 1 (pages 15 – 27 Table 1 expanded).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify and optimize the exemplified cycling regimen of Chakravarty’180 to in view of Rossi et. al. to administer cisplatin on each of days 1, 8 and 15 of a 28 day schedule. One of ordinary skill in the art would be motivated to make the modification and have a reasonable expectation of success because the prior art teach that cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment.
Additionally, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to combine the method of Chakravarty’180 with the cisplatin of Rossi et. al. given that Chakravarty’180 teach addition of other therapeutic agents for treating various cancers including small cell lung cancer and in light of Rossi et. al. who teach that cisplatin is effective for treating SCLC and led to an overall higher survival rate in certain subgroups of patients. Given the teachings of Chakravarty’180 and Rossi et. al., one of ordinary skill would have been motivated to combine the method of Chakravarty’180 with the cisplatin of Rossi et. al. with the reasonable expectation of providing a method that is not only effective in treating small cell lung cancer but also effective in prolonging overall survival.
Response to Arguments
Applicant's arguments filed May 18th, 2026 have been fully considered but they are not persuasive.
Applicant argues that Rossi does not mention anything about the claimed compound at all. See Applicant’s remarks page 6 paragraph 4. Furthermore, applicant argues that there is no guarantee that a dosing schedule used in monotherapy or in a combination can be used in different combination. See Applicant’s remarks page 6 paragraph 4.
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 above rejection the combination of Chakravarty’180 in view of Rossi et. al. is used to render obvious claims 1 – 16. As stated above the prior art of Chakravarty’180 teach the administration of 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid in combination with other therapeutic agents for treating various cancers which include small cell lung cancer and in light of Rossi et. al. that taught cisplatin is effective for treating SCLC and led to an overall higher survival rate in certain subgroups of patients. Moreover, the prior art of Chakravarty’180 taught dosing amounts and regimens for 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid and other therapeutic agents while the prior art of Rossi et. al. taught dosage amounts and regimens of cisplatin or carboplatin for overlapping cancers.
Furthermore, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988). See MPEP 2144 (I). Additionally, where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success. The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016). Moreover, reasonable expectation of success can be implicitly shown via the prior art teachings or as part of the obviousness analysis. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1376-77, 2023 USPQ2d 1100 (Fed. Cir. 2023). See MPEP 2143.02 (I).
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 – 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 16 of U.S. Patent No. US 10213436 B2 to Ecsedy et. al. (herein after Ecsedy’436) in view US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180; cited in the office action dated November 19th, 2025) and Rossi et. al. ((2012), Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data, J Clin Oncol, 30, 1692 – 1698; cited in the office action dated November 19th, 2025).
Ecsedy’436 recites a method of treating small-cell lung cancer in a subject in need thereof, consisting of administering to the subject on a 28-day dose schedule a twice-daily dose of an Aurora A kinase inhibitor, wherein the Aurora A kinase inhibitor is 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxybenzoic acid, or a pharmaceutically acceptable salt thereof, in combination with a once-weekly dose of paclitaxel, wherein the administered twice-daily dose of the Aurora A kinase inhibitor is about 30 mg, about 35 mg, about 40 mg, or about 45 mg, and is administered on days 1-3, 8-10, and 15-17 of the 28-day schedule; and the administered once-weekly dose of paclitaxel is from about 40 mg/m2 to about 80 mg/m2, and is administered on days 1, 8, and 15 of the 28-day schedule (reference claim 1); wherein the Aurora A kinase inhibitor is sodium 4-{ [9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[ 5,4-d] [2]benzazepin-2-yl]amino }-2-methoxybenzoate (reference claim 9); wherein the twice-daily dose of the Aurora A kinase inhibitor is about 30 mg (reference claim 3; instant claim 8 – 10), about 35 mg (reference claim 4), about 40 mg (reference claim 5; instant claim 11), about 45 mg (reference claim 6).
However, Ecsedy’436 fails to explicitly recite a method wherein a platin was added (instant claim 1); wherein the platin is administered on day 1 of a 28 day schedule (instant claim 12), wherein the platin is administered on each of days 1, 8 and 15 of a 28 day schedule (instant claim 13), wherein the cisplatin is administered from about 75 mg/m2 to about 100 mg/m2 per dose (instant claim 15), and wherein the cisplatin is administered from about 50 mg/m2 to about 70 mg/m2 per dose (instant claim 16).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 16 are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the invention of Ecsedy’436 treating small-cell lung cancer in a subject in need thereof, in view of Chakravarty’180 and Rossi et. al. that is in combination with a cisplatin. One of ordinary skill in the art would have been motivated to make this modification to with the reasonable expectation of providing a method that is not only effective in treating small cell lung cancer but also effective in prolonging overall survival.
Claims 1 – 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10 of U.S. Patent No. US 12042499 B2 to Ecsedy et. al. (herein after Ecsedy’499) in view US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180; cited in the office action dated November 19th, 2025) and Rossi et. al. ((2012), Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data, J Clin Oncol, 30, 1692 – 1698; cited in the office action dated November 19th, 2025).
Ecsedy’499 recite a method of treating small cell lung cancer, comprising administering to a patient having the small cell lung cancer (instant claims 1 – 3) a combination consisting of 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxybenzoic acid or a pharmaceutically acceptable salt thereof, and a platin (instant claims 1, 4 – 6, and 14), wherein 4-{ [9-chloro-7-(2-fluoro-6-methoxyphenyl)-5Hpyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxybenzoic acid or a pharmaceutically acceptable salt thereof is administered at about 48.6 mg (instant claims 8, and 9) per dose twice daily; wherein the platin is cisplatin (instant claim 14) or carboplatin (instant claim 6), wherein cisplatin is administered at about 12 mg/m2 per day, or carboplatin is administered at an AUC (area under the plasma concentration versus time curve) of about 4.6 mg/mL/min; and provided that 4-{ [9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[ 5,4-d] [2]benzazepin-2-yl]amino }-2-methoxybenzoic acid or a pharmaceutically acceptable salt thereof and the platin are the only active ingredients used in the method (reference claim 1).
Moreover, Ecsedy’499 recite a method wherein 4-{[9-chloro-7-(2-fluoro-6-methoxypheny l)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a pharmaceutically acceptable salt thereof is administered twice a day on each of days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 28 day schedule (reference claim 2; instant claim 7); wherein the platin is administered on day 1 of a 28 day schedule (reference claim 3; instant claim 12); wherein the platin is administered on each of days 1 , 8 and 15 of a 28 day schedule (reference claim 4; instant claim 13); wherein the platin is cisplatin (reference claim 5) or carboplatin (reference claim 6); wherein 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a pharmaceutically acceptable salt thereof and the platin are administered sequentially (reference claim 7) or simultaneously (reference claim 8).
However, Ecsedy’499 fails to explicitly recite a method wherein the cisplatin is administered from about 75 mg/m2 to about 100 mg/m2 per dose (instant claim 15), and wherein the cisplatin is administered from about 50 mg/m2 to about 70 mg/m2 per dose (instant claim 16).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 16 are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the invention of Ecsedy’499 treating small-cell lung cancer in a subject in need thereof, in view of Chakravarty’180 and Rossi et. al. that is in combination with a cisplatin. One of ordinary skill in the art would have been motivated to make this modification to with the reasonable expectation of providing a method that is not only effective in treating small cell lung cancer but also effective in prolonging overall survival.
Claims 1 – 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 4, and 7 of U.S. Patent No. US 11958855 B2 to Claiborne et. al. (herein after Claiborne’855) in view US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180; cited in the office action dated November 19th, 2025) and Rossi et. al. ((2012), Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data, J Clin Oncol, 30, 1692 – 1698; cited in the office action dated November 19th, 2025).
Claiborne’855 recite a method for treating lung cancer in a patient having the lung cancer, comprising administering to the patient a therapeutically effective amount of a compound of formula:
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298
240
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or a pharmaceutically acceptable salt thereof in combination with a therapeutic agent selected from the group consisting of cytotoxic agents, radiotherapeutic agent, and immune therapeutic agent, and wherein the therapeutic agent administered as a separate dosage form (reference claim 1); wherein the compound is sodium 4-{[9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxyben-zoate (reference claim 2); wherein the therapeutic agent paclitaxel (reference claim 4), docetaxel, cisplatin (instant claim 4 – 5, and 14), carboplatin (instant claim 6) (reference claim 3); wherein the therapeutic agent is administered following the administration of the compound or a pharmaceutical salt thereof (reference claim 7).
However, Claiborne’855 fails to explicitly recite a method wherein the platin is administered on day 1 of a 28 day schedule (instant claim 12), wherein the platin is administered on each of days 1, 8 and 15 of a 28 day schedule (instant claim 13), wherein the cisplatin is administered from about 75 mg/m2 to about 100 mg/m2 per dose (instant claim 15), and wherein the cisplatin is administered from about 50 mg/m2 to about 70 mg/m2 per dose (instant claim 16).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 16 are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the invention of Claiborne’855 for treating lung cancer in combination with cisplatin in view of Chakravarty’180 and Rossi et. al. that is in the dosage ranges and dosage regimens recited. One of ordinary skill in the art would have been motivated to make this modification to with the reasonable expectation of providing a method that is not only effective in treating small cell lung cancer but also effective in prolonging overall survival.
Claims 1 – 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 of U.S. Patent No. US Patent No. US 9724354 B2 to Brake et. al. (herein after Brake’354) in view US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180; cited in the office action dated November 19th, 2025) and Rossi et. al. ((2012), Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data, J Clin Oncol, 30, 1692 – 1698; cited in the office action dated November 19th, 2025).
Brake’354 recites a method of treating a patient suffering from breast cancer, comprising administering to the patient an mTORCl/2 inhibitor in combination with a selective inhibitor of Aurora A kinase, wherein the mTORCl/2 inhibitor is 3-(2-amino-1,3-benzoxazol-5-yl)-1-(propan-2-yl)-1H-pyrazolo
[3, 4-d] pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof, and the selective inhibitor of Aurora A kinase is 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5Hpyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxyben-zoic acid, or a pharmaceutically acceptable salt thereof (reference claim 1); wherein the pharmaceutically acceptable salt is sodium 4-{[9-chloro-7-(2-fluoro-6-methoxypheny 1)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate (reference claim 2; instant claim 1).
However, Brake’354 fails to explicitly recite a method wherein a platin was added (instant claim 1); wherein 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid or a pharmaceutically acceptable salt thereof is administered twice a day on each of days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 28 day schedule (instant claim 7); wherein the platin is administered on day 1 of a 28 day schedule (instant claim 12), wherein the platin is administered on each of days 1, 8 and 15 of a 28 day schedule (instant claim 13), wherein the cisplatin is administered from about 75 mg/m2 to about 100 mg/m2 per dose (instant claim 15), and wherein the cisplatin is administered from about 50 mg/m2 to about 70 mg/m2 per dose (instant claim 16).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 16 are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the invention of Brake’354 treating breast cancer, using 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid in view of Chakravarty’180 and Rossi et. al. that is in combination with a cisplatin, at the recited dosages and regimen. One of ordinary skill in the art would have been motivated to make this modification to with the reasonable expectation of providing a method that is not only effective in treating small cell lung cancer but also effective in prolonging overall survival.
Response to Arguments
Applicant's arguments filed May 18th, 2026 have been fully considered but they are not persuasive.
Applicant argues that for the NSDP rejection of the examined claims against Ecsedy’436 and Brake’354 should be withdrawn because Ecsedy’436 directs the combination of the claimed compound 4-{[9-chloro- 7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxybenzoic acid with paclitaxel while Brake’354 directs to a method of treating breast cancer. See Applicant’s arguments page 7 paragraph 3 and page 9 paragraph 2.
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, the examiner contends that the both the invention of Ecsedy’436 and Brake’354 direct to methods of treating species of cancers while the examined claims direct to methods of treating the broad genus of cancer. Thus as taught in the prior art rejection of Chakravarty’180 and Rossi et. al.; Chakravarty’180 taught that the new combination therapies can be used for the treatment of various cancers including gastric, breast, and small cell lung cancer, Moreover, the use of comprising in both the inventions of Ecsedy’436 and Brake’354 allow for the addition of additional therapeutic agents into the methods.
Additionally, Applicant argues that the NSDP rejection of the examined claims against Ecsedy’499, and Claiborne’855 be withdrawn because both the inventions of Ecsedy’499, and Claiborne’855 do not recite the specific dosage of 4-{ [9-chloro-7-(2-fluoro-6-methoxyphenyl)-5Hpyrimido[5,4-d][2]benzazepin-2-yl]amino }-2-methoxybenzoic acid or a pharmaceutically acceptable salt thereof, in combination with a specific dosage of cisplatin or carboplatin, which are different from the instant claims. See Applicant’s arguments page 8 paragraph 3 and 5.
As restated above, in the response to the prior art rejection, 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 above rejection the combination of Ecsedy’499 in view of Chakravarty’180 and Rossi et. al. is used to render obvious claims 1 – 16.
As stated above the prior art of Chakravarty’180 and Rossi et. al. teach the administration of 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid in combination with other therapeutic agents for treating various cancers which include small cell lung cancer and in light of Rossi et. al. that taught cisplatin is effective for treating SCLC and led to an overall higher survival rate in certain subgroups of patients. Moreover, the prior art of Chakravarty’180 taught dosing amounts and regimens for 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoicacid and other therapeutic agents while the prior art of Rossi et. al. taught dosage amounts and regimens of cisplatin or carboplatin for overlapping cancers.
Furthermore, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988). See MPEP 2144 (I). Additionally, where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success. The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016). Moreover, reasonable expectation of success can be implicitly shown via the prior art teachings or as part of the obviousness analysis. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1376-77, 2023 USPQ2d 1100 (Fed. Cir. 2023). See MPEP 2143.02 (I). Thus the NSDP rejection against Ecsedy’499, and Claiborne’855 in view of Chakravarty’180 and Rossi et. al. are maintained.
Conclusion
Claims 1 – 16 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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