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 .
Election/Restrictions
Applicant’s election without traverse of KRAS mutation as the "single species of mutation status" of Species A and mitotic inhibitor as the "single species of anti-tumor or anti-cancer agent" of Species B in the reply filed on 09/26/2025 is acknowledged.
Claims 65 and 66 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/26/2025.
A search of the prior art led to the conclusion that the species of anti-tumor agents are obvious variants, therefore the requirement for election of species of anti-tumor agent is withdrawn. The requirement for election of type of mutation remains in effect.
Claims 61-64 to 67-81 are under current examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Provisional Application No. 61925467, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The examiner was unable to locate support for the full scope of a method of treating any cancer having mutation in a gene selected from the group consisting of KRAS, INK4a/Arf, and p53. The examiner was unable to locate support for a method of treating NSCLC having mutation in a gene selected from INK4a/Arf or p53. Clarification is requested.
As such, claims 61-63 and 65- 81 are afforded a priority date of 01/09/2015, the filing date of US Serial No. 14593468 to which the instant application claims priority via the parent application, US Serial No. 16298907.
Claim 64 is fully supported in Provisional Application No. 61925467 and is therefore afforded a priority date of 01/09/2014.
Information Disclosure Statement
The information disclosure statement filed 09/26/2025 fails to comply with the provisions of 37 CFR 1.97(a) because it lacks the appropriate size fee set forth in 37 CFR 1.17(v). It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
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.
Claims 61-64, 67, 70, and 71 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gerber (Phase II Study of VS-6063 in patients with kras mutant non-small cell lung cancer; CinicalTrials.gov ID NCT 01951690; available online from 09/27/2013).
With regard to claim 64, which has been afforded an effective filing date 01/09/2014, the applied reference has common inventors with the instant application. Based upon the earlier publication date of the reference, it constitutes prior art under 35 USC 102(a)(1), but falls within the grace period afforded the instant claims. Please refer to MPEP 717.01 for information regarding how a reference may be disqualified as prior art under 102(b)(1)(A) or (B).
Claims 61-63, 67, 70, and 71 have been afforded an effective filing date of 01/09/2015 as of the writing of this Office action, and therefore Gerber was not disclosed within grace period for these claims.
See page 11, where the Principal Investigator is identified as David E Gerber.
With regard to claims 61-64, on pages 5-6, Gerber discloses: This is a Phase II, open-label, multicenter, multi cohort, study of VS-6063 (defactinib), a focal adhesion kinase inhibitor, in patients with KRAS mutant non-small cell lung cancer (NSCLC). NSCLC with a KRAS mutation is required for study entry and subjects will be enrolled into 1 of 4 cohorts based on the status of their INK4a/Arf and p53 mutations. The purpose of this study is to demonstrate if VS-6063 (defactinib) improves PFS within each cohort. The safety and tolerability of VS-6063, tumor response rate, progression free survival and overall survival will also be assessed. The pharmacodynamic effects of VS-6063 (defactinib) will be examined in a tumor biopsy and a blood sample. Eleven subjects will be enrolled into one of four cohorts: Cohort A (KRAS mutation, wild type INK4a/ARF and wildtype p53), Cohort B (KRAS mutation, INK4s/ARF mutation and wild type p53), Cohort C (KRAS mutation, wild type INK4a/ARF and p53 mutation), and Cohort D (KRAS mutation, INK4a/ARF mutation and p53 mutation). If >/= 4 patients demonstrate PFS at 12 weeks in each cohort, an additional 23 subjects will be enrolled.
With regard to claim 67, patients having metastatic disease are included (page 9).
With regard to claims 71 and 71, Verastem discloses that VS-6063 will be administered orally BID (twice day; page 7).
Claim Rejections - 35 USC § 103
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 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 61-64, 67-76, 78, 80 and 81 are rejected under 35 U.S.C. 103 as being unpatentable over Gerber (Phase II Study of VS-6063 in patients with kras mutant non-small cell lung cancer; CinicalTrials.gov ID NCT 01951690; available online from 09/27/2013) in view of Luzzio et al. (US20110166120; publication date: 07/07/2011).
With regard to claim 64, which has been afforded an effective filing date 01/09/2014, the applied reference has common inventors with the instant application. Based upon the earlier publication date of the reference, it constitutes prior art under 35 USC 102(a)(1), but falls within the grace period afforded the instant claims. Please refer to MPEP 717.01 for information regarding how a reference may be disqualified as prior art under 102(b)(1)(A) or (B).
Claims 61-63, 67, 70, and 71 have been afforded an effective filing date of 01/09/2015 as of the writing of this Office action, and therefore Gerber disclosure was made publicly available prior to the grace period for these claims.
As noted in the anticipation rejection above Gerber anticipates claims 61-64, 67, and 70-74 and so in anticipating these claims, said claims are also considered obvious under 35 USC 103(a) over Gerber for the reasons set forth below ("lack of novelty is the epitome of obviousness" May, 574 F.2d at 1089, 197 USPQ at 607 (citing In re Pearson, 494 F.2d 1399, 1402, 181 USPQ 641, 644 (CCPA 1974))).
Luzzio discloses preparation of the active agent:
PNG
media_image1.png
219
636
media_image1.png
Greyscale
This structure represents VS-6063 (CAS Registry No. 1073154-85-4).
With regard to claims 68-69, Luzzio discloses that active agents according to their invention may be combined with a variety of anti-cancer agents such as antitumor agents, alkylating agents, antimetabolites, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons, and/or biological response modifiers (0403). It would have been prima facie obvious to combine VS-6063 with any of the additional anti-cancer agents disclosed by Luzzio for combination with this agent in Gerber’s method of treating kras mutant NSCLC. One having ordinary skill would have been motivated to do so in order to increase efficacy of the treatment and would have had reasonable expectation of success because such was proposed by Luzzio.
With regard to claims 72-74, Luzzio discloses that the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disorder indicated, and the daily dosage may range from 1 mg to 1 g (0432). This range in dose overlaps with the range recited in the instant claims. It would have been merely routine for one of ordinary skill to optimize the dosage to treat kras mutant NSCLC as disclosed by Gerber using the range for this compound disclosed by Luzzio as a starting point. See MPEP 2144.05.
With regard to claims 75, 76, 78, 80 and 81, Luzzio discloses further that the actives disclosed therein may be formulated into a carrier such as a tablet including conventional excipients (0568). The carrier, and particularly the tablet may include fillers, disintegrants and lubricants, such as magnesium stearate (0568). Therefore it would be prima facie obvious to formulate VS-6063 into a tablet containing an excipient, a filler, a disintegrant, and a lubricant. With regard to the amount of VS-6063 required by the instant claims, the examiner considers it a matter of routine for one having ordinary skill in the art to optimize the quantity of therapeutically active agent. With regard to claim 76, which requires “a mixture of two fillers”, it is prima facie obvious to combine to compositions known to serve the same purpose, therefore the examiner considers it prima facie obvious to combine any two fillers or any two of any particular type of excipient, as required by claim 76. See MPEP 2144.06.
Claims 77 and 79 are rejected under 35 U.S.C. 103 as being unpatentable over Gerber (Phase II Study of VS-6063 in patients with kras mutant non-small cell lung cancer; CinicalTrials.gov ID NCT 01951690; available online from 09/27/2013) in view of Luzzio et al. (US20110166120; publication date: 07/07/2011) as applied to claims 61-64, 67-76, 78, 80 and 81 above, and further in view of Cumming et al. (US 2010/0028421; publication date: 02/04/2010; cited in the IDS filed 05/11/2023).
The relevant disclosures of Gerber and Luzzio are set forth above. Luzzio discloses further that the composition containing active compounds may further comprise lactose as a filler, and Luzzio discloses including starch in the composition; however, Luzzio does not disclose microcrystalline cellulose or modified starch, as required by instant claims 77 and 79.
Cumming discloses that microcrystalline cellulose pH102 and lactose monohydrate (0049) were both known to function as fillers at the time the instant invention was filed therefore it would have been prima facie obvious to combine these species of filler in the tablet contemplated by Luzzio. See MPEP 2144.06.
Cumming discloses sodium starch glycolate was known to function as a disintegrant (0051) at the time the instant invention was filed, therefore it would have been prima facie obvious to use these species of filler in the tablet disclosed by Luzzio because one having ordinary skill would have recognized this species to fall within the genus “disintegrant” disclosed by Luzzio and therefore to have been suitable. See MPEP 2144.07.
Claims 61-64 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013) in view of Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012).
With regard to instant claims 61-64, Konstantinidou discloses inter alia that suppression of FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells, specifically NSCLC, and that inhibition of FAK caused tumor regression in high grade lung cancer developed in Kras;Cdkn2a null mice. Konstantinidou concludes that this provides a rationale for rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer (abstract).
Thus Konstantinidou proposes treating patients with kras mutant NSCLC with a FAK inhibitor.
Pfizer discloses that VS-6063 is a clinically well-tolerated FAK inhibitor. Pfizer discloses that VS-6063 can inhibit primary tumor mass and metastasis.
It would have been prima facie obvious to use VS-6063 as the FAK inhibitor in Konstantinidou’s method of treating kras-mutant NSCLC. The skilled artisan would have been motivated to do so because this drug has already been established as a potent inhibitor of FAK with an acceptable toxicity profile. The skilled artisan would have had a reasonable expectation of success for this reason as well, and also because FAK inhibition had been shown to be effective in mouse models of kras deficient NSCLC tumors.
With regard to claim 67, as noted above, Pfizer discloses treatment of metastasis.
Claims 68-76, 78, 80 and 81 are rejected under 35 U.S.C. 103 as being unpatentable over Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013) in view of Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012) as applied to claims 61-64 and 67 above and further in view of Luzzio et al. (US20110166120; publication date: 07/07/2011).
The relevant disclosures of Konstantinidou and Pfizer are set forth above.
Neither reference discloses coadministration with other antitumor agents, a dosing schedule or dose, or the formulation details as recited in instant claims.
Luzzio discloses preparation of the active agent:
PNG
media_image1.png
219
636
media_image1.png
Greyscale
This structure represents VS-6063 (CAS Registry No. 1073154-85-4).
With regard to claims 68-69, Luzzio discloses that active agents according to their invention may be combined with a variety of anti-cancer agents such as antitumor agents, alkylating agents, antimetabolites, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons, and/or biological response modifiers (0403). It would have been prima facie obvious to combine VS-6063 with any of the additional anti-cancer agents disclosed by Luzzio for combination with this agent in a method of treating kras mutant NSCLC. One having ordinary skill would have been motivated to do so in order to increase efficacy of the treatment and would have had reasonable expectation of success because such was proposed by Luzzio.
With regard to claims 70 and 71, Luzzio discloses daily dosing (0564). It would have been a matter of routine for one of ordinary skill to optimize the dose schedule for best clinical outcome. See MPEP 2144.05.
With regard to claims 72-74, Luzzio discloses that the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disorder indicated, and the daily dosage may range from 1 mg to 1 g (0432). This range in dose overlaps with the range recited in the instant claims. It would have been merely routine for one of ordinary skill to optimize the dosage to treat kras mutant NSCLC as disclosed by Konstantinidou/Pfizer using the range for this compound disclosed by Luzzio as a starting point. See MPEP 2144.05.
With regard to claims 75, 76, 78, 80 and 81, Luzzio discloses further that the actives disclosed therein may be formulated into a carrier such as a tablet including conventional excipients (0568). The carrier, and particularly the tablet may include fillers, disintegrants and lubricants, such as magnesium stearate (0568). Therefore it would be prima facie obvious to formulate VS-6063 into a tablet containing an excipient, a filler, a disintegrant, and a lubricant. With regard to the amount of VS-6063 required by the instant claims, the examiner considers it a matter of routine for one having ordinary skill in the art to optimize the quantity of therapeutically active agent. With regard to claim 76, which requires “a mixture of two fillers”, it is prima facie obvious to combine to compositions known to serve the same purpose, therefore the examiner considers it prima facie obvious to combine any two fillers or any two of any particular type of excipient, as required by claim 76. See MPEP 2144.06.
Claims 77 and 79 are rejected under 35 U.S.C. 103 as being unpatentable over Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013), Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012), and Luzzio et al. (US20110166120; publication date: 07/07/2011) as applied to claims 61-64, 67-76, 78, 80 and 81 above and further in view of Cumming et al. (US 2010/0028421; publication date: 02/04/2010; cited in the IDS filed 05/11/2023).
The relevant disclosures of Konstantinidou, Pfizer, and Luzzio are set forth above. Luzzio discloses further that the composition containing active compounds may further comprise lactose as a filler, and Luzzio discloses including starch in the composition; however, Luzzio does not disclose microcrystalline cellulose or modified starch, as required by instant claims 77 and 79.
Cumming discloses that microcrystalline cellulose pH102 and lactose monohydrate (0049) were both known to function as fillers at the time the instant invention was filed therefore it would have been prima facie obvious to combine these species of filler in the tablet contemplated by Luzzio. See MPEP 2144.06.
Cumming discloses sodium starch glycolate was known to function as a disintegrant (0051) at the time the instant invention was filed, therefore it would have been prima facie obvious to use these species of filler in the tablet disclosed by Luzzio because one having ordinary skill would have recognized this species to fall within the genus “disintegrant” disclosed by Luzzio and therefore to have been suitable. See MPEP 2144.07.
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 61-64 and 67-74 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-16 of U.S. Patent No. 9962385;
claims 1-11 of U.S. Patent No. 10406158;
claims 1-27 of U.S. Patent No. 10532056; and
claims 1-18 of U.S. Patent No. 11564927
in view of Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013) in view of Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012).
Inter alia, the claims of the ‘385, ‘158, ‘056, and ‘927 patents embrace a method of treating cancer, including NSCLC, by administering VS-6063 in amounts and on a dosing schedule overlapping with the ranges in those parameters recited in the instant claims. See MPEP 2144.05.
The claims of the cited patents are silent with respect to treating NSCLC having a mutation status in the gene kras.
Konstantinidou discloses inter alia that suppression of FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells, specifically NSCLC, and that inhibition of FAK caused tumor regression in high grade lung cancer developed in Kras;Cdkn2a null mice. Konstantinidou concludes that this provides a rationale for rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer (abstract).
Thus Konstantinidou proposes treating patients with kras mutant NSCLC with a FAK inhibitor.
Pfizer discloses that VS-6063 is a clinically well-tolerated FAK inhibitor. Pfizer discloses that VS-6063 can inhibit primary tumor mass and metastasis.
It would have been prima facie obvious to use VS-6063 as the FAK inhibitor in patented method of treating cancer. The skilled artisan would have been motivated to do so because this drug has already been established as a potent inhibitor of FAK with an acceptable toxicity profile and has been shown to be particularly effective in NSCLC bearing mutation in the kras gene. The skilled artisan would have had a reasonable expectation of success for this reason as well, and also because FAK inhibition had been shown to be effective in mouse models of kras deficient NSCLC tumors.
With regard to claim 67, as noted above, Pfizer discloses treatment of metastasis, therefore it would have been obvious to extend the patented methods to metastatic cancer.
Claims 75, 76, 78, 80, and 81 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-16 of U.S. Patent No. 9962385;
claims 1-11 of U.S. Patent No. 10406158;
claims 1-27 of U.S. Patent No. 10532056; and
claims 1-18 of U.S. Patent No. 11564927
in view of Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013) and Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012) as applied to claims 61-64 and 67-74 above, and further in view of Luzzio et al. (US20110166120; publication date: 07/07/2011).
The relevant limitations of the ‘385, ‘158, ‘056, and ‘927 patents and the disclosures of Konstantinidou and Pfizer are set forth above.
None disclose coadministration with other antitumor agents, a dosing schedule or dose, or the formulation details as recited in instant claims.
Luzzio discloses preparation of the active agent:
PNG
media_image1.png
219
636
media_image1.png
Greyscale
This structure represents VS-6063 (CAS Registry No. 1073154-85-4).
With regard to claims 68-69, Luzzio discloses that active agents according to their invention may be combined with a variety of anti-cancer agents such as antitumor agents, alkylating agents, antimetabolites, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons, and/or biological response modifiers (0403). It would have been prima facie obvious to combine VS-6063 with any of the additional anti-cancer agents disclosed by Luzzio for combination with this agent in a method of treating kras mutant NSCLC. One having ordinary skill would have been motivated to do so in order to increase efficacy of the treatment and would have had reasonable expectation of success because such was proposed by Luzzio.
With regard to claims 70 and 71, Luzzio discloses daily dosing (0564). It would have been a matter of routine for one of ordinary skill to optimize the dose schedule for best clinical outcome. See MPEP 2144.05.
With regard to claims 75, 76, 78, 80 and 81, Luzzio discloses further that the actives disclosed therein may be formulated into a carrier such as a tablet including conventional excipients (0568). The carrier, and particularly the tablet may include fillers, disintegrants and lubricants, such as magnesium stearate (0568). Therefore it would be prima facie obvious to formulate VS-6063 into a tablet containing an excipient, a filler, a disintegrant, and a lubricant. With regard to the amount of VS-6063 required by the instant claims, the examiner considers it a matter of routine for one having ordinary skill in the art to optimize the quantity of therapeutically active agent. With regard to claim 76, which requires “a mixture of two fillers”, it is prima facie obvious to combine to compositions known to serve the same purpose, therefore the examiner considers it prima facie obvious to combine any two fillers or any two of any particular type of excipient, as required by claim 76. See MPEP 2144.06.
Claims 77 and 79 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-16 of U.S. Patent No. 9962385;
claims 1-11 of U.S. Patent No. 10406158;
claims 1-27 of U.S. Patent No. 10532056; and
claims 1-18 of U.S. Patent No. 11564927
in view of Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013), Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012), and Luzzio et al. (US20110166120; publication date: 07/07/2011) as applied to claims 61-64 and 67-76 68, 80, and 81 above, and further in view of Cumming et al. (US 2010/0028421; publication date: 02/04/2010; cited in the IDS filed 05/11/2023).
The relevant limitations of the ‘385, ‘158, ‘056, and ‘927 patents and the disclosures of Konstantinidou, Pfizer, and Luzzio are set forth above. Luzzio discloses further that the composition containing active compounds may further comprise lactose as a filler, and Luzzio discloses including starch in the composition; however, Luzzio does not disclose microcrystalline cellulose or modified starch, as required by instant claims 77 and 79.
Cumming discloses that microcrystalline cellulose pH102 and lactose monohydrate (0049) were both known to function as fillers at the time the instant invention was filed therefore it would have been prima facie obvious to combine these species of filler in the tablet contemplated by Luzzio. See MPEP 2144.06.
Cumming discloses sodium starch glycolate was known to function as a disintegrant (0051) at the time the instant invention was filed, therefore it would have been prima facie obvious to use these species of filler in the tablet disclosed by Luzzio because one having ordinary skill would have recognized this species to fall within the genus “disintegrant” disclosed by Luzzio and therefore to have been suitable. See MPEP 2144.07.
Claims 61-64 and 67 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 32-38, 40-43, 46-54 of copending Application No. 17795402;
claims 3, 4, 11, 13, 16, 17, 19-23, 27, 28, 29, 37of copending Application No. 17921509;
claims 1, 2, 4-6, 11-17, 25, 28-34 of copending Application No. 17989006;
claims 1-3, 7, 10, 11, 16-20, 33-35, 42, 44, 45, 48 of copending Application No. 18005012;
claims 1, 2, 4, 5, 7-, 8, 11, 12, 40, 49-51, 56-58, 62, 64, 70-72, 74-77 of copending Application No. 18292086;
claims 1, 8, 11-17, 19-23, 25, 45-50, 52, 55-57, 60, 61, 67, 77 of copending Application No. 18702569;
claims 2-2, 9-14, 24-26, 28, 29, 31, 35, 38, 42, 43, 48, 50, 53, 57 of copending Application No. 18704267;
claims 1, 2, 4-7, 9-13, 16, 19-29, 31, 33, 34, 41-44 of copending Application No. 18718137;
in view of Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013) in view of Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012).
Inter alia, the claims of the applications listed in the rejection statement above embrace a method of treating kras mutant cancer by administering VS-6063.
The claims of the cited patents are silent with respect to treating NSCLC specifically having a mutation status in the gene kras.
Konstantinidou discloses inter alia that suppression of FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells, specifically NSCLC, and that inhibition of FAK caused tumor regression in high grade lung cancer developed in Kras;Cdkn2a null mice. Konstantinidou concludes that this provides a rationale for rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer (abstract).
Thus Konstantinidou proposes treating patients with kras mutant NSCLC with a FAK inhibitor.
Pfizer discloses that VS-6063 is a clinically well-tolerated FAK inhibitor. Pfizer discloses that VS-6063 can inhibit primary tumor mass and metastasis.
It would have been prima facie obvious to use VS-6063 as the FAK inhibitor in claimed method of treating cancer of the applications cited in the rejection statement above. The skilled artisan would have been motivated to do so because this drug has already been established as a potent inhibitor of FAK with an acceptable toxicity profile and has been shown to be particularly effective in NSCLC bearing mutation in the kras gene. The skilled artisan would have had a reasonable expectation of success for this reason as well, and also because FAK inhibition had been shown to be effective in mouse models of kras deficient NSCLC tumors.
With regard to claim 67, as noted above, Pfizer discloses treatment of metastasis, therefore it would have been obvious to extend the patented methods to metastatic cancer.
This is a provisional nonstatutory double patenting rejection.
Claims 68-76, 78, 80, and 81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 32-38, 40-43, 46-54 of copending Application No. 17795402;
claims 3, 4, 11, 13, 16, 17, 19-23, 27, 28, 29, 37of copending Application No. 17921509;
claims 1, 2, 4-6, 11-17, 25, 28-34 of copending Application No. 17989006;
claims 1-3, 7, 10, 11, 16-20, 33-35, 42, 44, 45, 48 of copending Application No. 18005012;
claims 1, 2, 4, 5, 7-, 8, 11, 12, 40, 49-51, 56-58, 62, 64, 70-72, 74-77 of copending Application No. 18292086;
claims 1, 8, 11-17, 19-23, 25, 45-50, 52, 55-57, 60, 61, 67, 77 of copending Application No. 18702569;
claims 2-2, 9-14, 24-26, 28, 29, 31, 35, 38, 42, 43, 48, 50, 53, 57 of copending Application No. 18704267;
claims 1, 2, 4-7, 9-13, 16, 19-29, 31, 33, 34, 41-44 of copending Application No. 18718137;
in view of Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013) in view of Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012) as applied to claims 61-64 and 67 above, and further in view of Luzzio et al. (US20110166120; publication date: 07/07/2011).
The relevant limitations of the applications listed in the rejection statement above and the disclosures of Konstantinidou and Pfizer are set forth above.
None disclose coadministration with other antitumor agents, a dosing schedule or dose, or the formulation details as recited in instant claims.
Luzzio discloses preparation of the active agent:
PNG
media_image1.png
219
636
media_image1.png
Greyscale
This structure represents VS-6063 (CAS Registry No. 1073154-85-4).
With regard to claims 68-69, Luzzio discloses that active agents according to their invention may be combined with a variety of anti-cancer agents such as antitumor agents, alkylating agents, antimetabolites, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons, and/or biological response modifiers (0403). It would have been prima facie obvious to combine VS-6063 with any of the additional anti-cancer agents disclosed by Luzzio for combination with this agent in a method of treating kras mutant NSCLC. One having ordinary skill would have been motivated to do so in order to increase efficacy of the treatment and would have had reasonable expectation of success because such was proposed by Luzzio.
With regard to claims 70 and 71, Luzzio discloses daily dosing (0564). It would have been a matter of routine for one of ordinary skill to optimize the dose schedule for best clinical outcome. See MPEP 2144.05.
With regard to claims 72-74, Luzzio discloses that the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disorder indicated, and the daily dosage may range from 1 mg to 1 g (0432). This range in dose overlaps with the range recited in the instant claims. It would have been merely routine for one of ordinary skill to optimize the dosage to treat kras mutant NSCLC as disclosed by Gerber using the range for this compound disclosed by Luzzio as a starting point. See MPEP 2144.05.
With regard to claims 75, 76, 78, 80 and 81, Luzzio discloses further that the actives disclosed therein may be formulated into a carrier such as a tablet including conventional excipients (0568). The carrier, and particularly the tablet may include fillers, disintegrants and lubricants, such as magnesium stearate (0568). Therefore it would be prima facie obvious to formulate VS-6063 into a tablet containing an excipient, a filler, a disintegrant, and a lubricant. With regard to the amount of VS-6063 required by the instant claims, the examiner considers it a matter of routine for one having ordinary skill in the art to optimize the quantity of therapeutically active agent. With regard to claim 76, which requires “a mixture of two fillers”, it is prima facie obvious to combine to compositions known to serve the same purpose, therefore the examiner considers it prima facie obvious to combine any two fillers or any two of any particular type of excipient, as required by claim 76. See MPEP 2144.06.
This is a provisional nonstatutory double patenting rejection.
Claims 77 and 79 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 32-38, 40-43, 46-54 of copending Application No. 17795402;
claims 3, 4, 11, 13, 16, 17, 19-23, 27, 28, 29, 37of copending Application No. 17921509;
claims 1, 2, 4-6, 11-17, 25, 28-34 of copending Application No. 17989006;
claims 1-3, 7, 10, 11, 16-20, 33-35, 42, 44, 45, 48 of copending Application No. 18005012;
claims 1, 2, 4, 5, 7-, 8, 11, 12, 40, 49-51, 56-58, 62, 64, 70-72, 74-77 of copending Application No. 18292086;
claims 1, 8, 11-17, 19-23, 25, 45-50, 52, 55-57, 60, 61, 67, 77 of copending Application No. 18702569;
claims 2-2, 9-14, 24-26, 28, 29, 31, 35, 38, 42, 43, 48, 50, 53, 57 of copending Application No. 18704267;
claims 1, 2, 4-7, 9-13, 16, 19-29, 31, 33, 34, 41-44 of copending Application No. 18718137;
in view of Konstantinidou et al. (Cancer Discovery Vol 3(4) pages 444-457; publication date April 2013), Pfizer Press Release (Verastem Acquires Clinical-Stage FAK Inhibitor from Pfizer; publication date: 07/11/2012), and Luzzio et al. (US20110166120; publication date: 07/07/2011) as applied to claims 61-64 and 67-76, 78, 80, and 81 above, and further in view of Cumming et al. (US 2010/0028421; publication date: 02/04/2010; cited in the IDS filed 05/11/2023).
The relevant limitations of the applications listed in the rejection statement above and the disclosures of Konstantinidou, Pfizer, and Luzzio are set forth above. Luzzio discloses further that the composition containing active compounds may further comprise lactose as a filler, and Luzzio discloses including starch in the composition; however, Luzzio does not disclose microcrystalline cellulose or modified starch, as required by instant claims 77 and 79.
Cumming discloses that microcrystalline cellulose pH102 and lactose monohydrate (0049) were both known to function as fillers at the time the instant invention was filed therefore it would have been prima facie obvious to combine these species of filler in the tablet contemplated by Luzzio. See MPEP 2144.06.
Cumming discloses sodium starch glycolate was known to function as a disintegrant (0051) at the time the instant invention was filed, therefore it would have been prima facie obvious to use these species of filler in the tablet disclosed by Luzzio because one having ordinary skill would have recognized this species to fall within the genus “disintegrant” disclosed by Luzzio and therefore to have been suitable. See MPEP 2144.07.
This is a provisional nonstatutory double patenting rejection.
Claims 61-64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-11, 21-32 of copending Application No. 18/085,792 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims.
Inter alia, the claims of the ‘792 application embrace a method of treating kras mutant NSCLC by administering VS-6063.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 67-76, 78, 80, and 81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-11, 21-32 of copending Application No. 18/085,792 (reference application) as applied to claims 61-64 above, and further in view of Luzzio et al. (US20110166120; publication date: 07/07/2011).
The relevant limitations of the application listed in the rejection statement above and the disclosures of Konstantinidou and Pfizer are set forth above.
None disclose coadministration with other antitumor agents, a dosing schedule or dose, or the formulation details as recited in instant claims.
Luzzio discloses preparation of the active agent:
PNG
media_image1.png
219
636
media_image1.png
Greyscale
This structure represents VS-6063 (CAS Registry No. 1073154-85-4).
With regard to claim 67, Luzzio discloses that the compound above (VS-6063) can be used to treat metastatic cancers (0378), it would have been prima facie obvious to do so because such was suggested by the prior art.
With regard to claims 68-69, Luzzio discloses that active agents according to their invention may be combined with a variety of anti-cancer agents such as antitumor agents, alkylating agents, antimetabolites, antibiotics, plant-derived antitumor agents, camptothecin derivatives, tyrosine kinase inhibitors, antibodies, interferons, and/or biological response modifiers (0403). It would have been prima facie obvious to combine VS-6063 with any of the additional anti-cancer agents disclosed by Luzzio for combination with this agent in a method of treating kras mutant NSCLC. One having ordinary skill would have been motivated to do so in order to increase efficacy of the treatment and would have had reasonable expectation of success because such was proposed by Luzzio.
With regard to claims 70 and 71, Luzzio discloses daily dosing (0564). It would have been a matter of routine for one of ordinary skill to optimize the dose schedule for best clinical outcome. See MPEP 2144.05.
With regard to claims 72-74, Luzzio discloses that the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disorder indicated, and the daily dosage may range from 1 mg to 1 g (0432). This range in dose overlaps with the range recited in the instant claims. It would have been merely routine for one of ordinary skill to optimize the dosage to treat kras mutant NSCLC as disclosed by Gerber using the range for this compound disclosed by Luzzio as a starting point. See MPEP 2144.05.
With regard to claims 75, 76, 78, 80 and 81, Luzzio discloses further that the actives disclosed therein may be formulated into a carrier such as a tablet including conventional excipients (0568). The carrier, and particularly the tablet may include fillers, disintegrants and lubricants, such as magnesium stearate (0568). Therefore it would be prima facie obvious to formulate VS-6063 into a tablet containing an excipient, a filler, a disintegrant, and a lubricant. With regard to the amount of VS-6063 required by the instant claims, the examiner considers it a matter of routine for one having ordinary skill in the art to optimize the quantity of therapeutically active agent. With regard to claim 76, which requires “a mixture of two fillers”, it is prima facie obvious to combine to compositions known to serve the same purpose, therefore the examiner considers it prima facie obvious to combine any two fillers or any two of any particular type of excipient, as required by claim 76. See MPEP 2144.06.
This is a provisional nonstatutory double patenting rejection.
Claims 77 and 79 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-11, 21-32 of copending Application No. 18/085,792 (reference application) and Luzzio et al. (US20110166120; publication date: 07/07/2011) as applied to claims 61-64, 67-76, 78, 80, and 81 above, and further in view of Cumming et al. (US 2010/0028421; publication date: 02/04/2010; cited in the IDS filed 05/11/2023).
The relevant limitations of the application listed in the rejection statement above and the disclosures of Konstantinidou, Pfizer, and Luzzio are set forth above. Luzzio discloses further that the composition containing active compounds may further comprise lactose as a filler, and Luzzio discloses including starch in the composition; however, Luzzio does not disclose microcrystalline cellulose or modified starch, as required by instant claims 77 and 79.
Cumming discloses that microcrystalline cellulose pH102 and lactose monohydrate (0049) were both known to function as fillers at the time the instant invention was filed therefore it would have been prima facie obvious to combine these species of filler in the tablet contemplated by Luzzio. See MPEP 2144.06.
Cumming discloses sodium starch glycolate was known to function as a disintegrant (0051) at the time the instant invention was filed, therefore it would have been prima facie obvious to use these species of filler in the tablet disclosed by Luzzio because one having ordinary skill would have recognized this species to fall within the genus “disintegrant” disclosed by Luzzio and therefore to have been suitable. See MPEP 2144.07.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617