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 .
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 – 2, 4 – 5, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sehdev et. al. ((May 2011), MLN-8237 Treatment Alone and in Combination With Cisplatin Suppresses In Vitro and In Vivo Progression of Gastrointestinal Cancer Cells, Gastroenterology, DDW Abstract Supplement, Conference Abstracts, S-121).
Regarding claims 1 – 2, 4 – 5, and 14, Sehdev et. al. teach that gastric cancers (claim 1 – 2) respond poorly to conventional therapy (column 2 paragraph 2 lines 1 – 2). Additionally, Sehdev et. al. teach that AURKA overexpression facilitates oncogenic transformation by causing chromosomal instability, aberrant mitosis, and aneuploidy (column 2 paragraph 2 lines 2 – 3). Furthermore, Sehdev et al. teach that AURKA induces pro-survival mechanisms through activation of AKT and β–catenin and inhibition of p53 mediated apoptotic pathways in gastrointestinal adenocarcinomas (column 2 paragraph 2 lines 5 – 7). Moreover, Sehdev et al. teach that various gastric cell lines, such as AGS, KATO-III, MKN28, FLO-1, and OE33 were treated with the AURKA specific inhibitor, MLN-8237, that is Alisertib or 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4- d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid (claim 1) either alone and/or in combination with cisplatin (claims 1, 4 – 5, and 14) (column 2 paragraph 2 lines 7 – 8 and 12 – 13). Furthermore, Sehdev et al. teach that for the cell viability assay and survival assay the combination treatment of MLN-8237 and cisplatin significantly increased inhibition of cellular viability and survival in AGS, KATO-III, MKN28, FLO-1, and OE33 cell lines as compared to the monotherapy of either MLN-8237 or cisplatin (column 2 paragraph 2 lines 10 – 14).
Additionally, Sehdev et al. teach that in the western blot analysis treatment with both cisplatin and MLN-8237 in combination resulted in the cleavage of caspase-3, an apoptotic indicator, AGS, FLO-1, and OE33 cell lines (column 2 paragraph 2 lines 14 – 17). Furthermore, Sehdev et al. teach that tumor growth was further assessed in a OE33 mouse xenograft study wherein 40 mg/kg of MLN-8237) was used along with 2 mg/kg of cisplatin (column 2 paragraph 2 lines 17 – 22).
Thus, Sehdev et al. teach that the combination of MLN-8237 with cisplatin is an effective therapeutic strategy for inducing apoptosis and suppressed growth of gastrointestinal cancer cells (column 2 paragraph 2 lines 26 – 28). Moreover, Sehdev et al. teach that the inclusion of cisplatin enhances the anti-tumor activity of MLN-8237 against gastrointestinal cancers, that is gastric cancers (column 2 paragraph 2 lines 28 – 30).
Claims 1 – 6, 8 – 11, 14, and 17 – 18 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180).
Regarding claims 1 – 6, 8 – 11, 14, and 17 – 18, 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 (claim 17) 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 (claim 18) 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).
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.
Claim 7 is 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) US Patent Application Publication US 2014/0336180 A1 to Chakravarty et. al. (herein after Chakravarty’180) as applied to claims 1 – 6, 8 – 11, 14, and 17 – 18 above.
The teachings of Chakravarty’180 as they relate to claim 1, from which claim 7 depend, are given previously in this office action and are fully incorporated here.
However, Chakravarty’180 fails to explicitly teach a method 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 (claim 7).
Nevertheless, 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).
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.
Claim 19 is 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) as applied to claims 1 – 11, 14, and 17 – 18 above.
The teachings of Chakravarty’180 as they relate to claim 1, are given previously in this office action and are fully incorporated here.
However, Chakravarty’180 fails to explicitly teach a kit comprising 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 (claim 19).
Nevertheless, as taught above, Chakravarty’180 does 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). Furthermore, Chakravarty’180 does teach that additional therapeutic agents includes platinum compounds which includes carboplatin and cisplatin (page 42 paragraph 0241). Therefore, it would have been prima facie obvious before the effective filing date of the instant application to modify the kit of Chakravarty’180 to include a platinum compound.
Claims 12 – 13, and 15 – 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) as applied to claims 1 – 11, 14, and 17 – 18 above, and further 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).
The teachings of Chakravarty’180 as they relate to claim 1, from which claims 12 – 13, and 15 – 16 depend, are given previously in this office action and are fully incorporated here.
However, Chakravarty’180 fails to explicitly teach a method wherein the platin is administered on day 1 of a 28 day schedule (claim 12), wherein the platin is administered on each of days 1, 8 and 15 of a 28 day schedule (claim 13), 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.
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 – 19 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) 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).
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). Moreover, Ecsedy’436 fails to explicitly recite a kit comprising 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 claim 19).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 19 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, and 19 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) 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).
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 (claim 14) or carboplatin (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). Moreover, Ecsedy’436 fails to explicitly recite a kit comprising 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 claim 19).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 19 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 – 19 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) 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).
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:
PNG
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298
240
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Greyscale
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; instant claim 18), docetaxel (instant claim 18), 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). Moreover, Ecsedy’436 fails to explicitly recite a kit comprising 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 claim 19).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 19 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 – 19 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) 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).
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 (instant claim 17), 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 claims 1, and 17).
However, Brake’354 fails to explicitly recite a method wherein a platin was added (instant claim 1 and 17); 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 (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). Moreover, Ecsedy’436 fails to explicitly recite a kit comprising 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 claim 19).
Nevertheless, the teachings of Chakravarty’180 and Rossi et. al. as they relate to the prior art rejections of instant claims 1 – 19 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.
Conclusion
Claims 1 – 19 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
/JULIET C SWITZER/Primary Examiner, Art Unit 1682