DETAILED ACTION
Claims 1-13 are pending.
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 .
Priority
The instant application, filed 11/21/2023 is a Divisional of 16644902, filed 3/5/2020, now U.S. Patent 11859252 and having 1 RCE-type filing therein. 16644902 is a National Stage entry of PCT/US2018/050056, International Filing Date 9/7/2018. PCT/US2018/050056 Claims Priority from Provisional Application 62556277, filed 9/8/2017.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 3/11/2024 and 8/16/2024, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
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 1-5, 7-10, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Atefi et al. “Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma,” Molecular Cancer (2015) 14:27; in view of Rodrıguez-Antona et al. “Pharmacogenomic biomarkers for personalized cancer treatment,” J Intern Med 2015; 277: 201–217.
Instant claim 1 is directed towards a method of treating an individual having a cancer, the method comprising:(a) screening a sample from the individual for an NRAS activating mutation, wherein the individual has been determined to have an NRAS activating mutation; and (b) administering a therapeutically effective amount of a pan-RAF dimer inhibitor and a MEK inhibitor to the individual based on the presence of an NRAS activating mutation determined in step (a).
Atefi teaches combining a pan-RAF inhibitor and a MEK inhibitor in treating NRAS mutant melanoma. Atefi teaches one of the mutations is cell line M244 NRAS Q61K heterozygous, this is an activating mutation, see Table 1. Atefi teaches pan-RAF inhibitor is Amgen Compound A. Atefi teaches the MEKi can be trametinib.
Therefore Atefi teaches the skilled artisan that one should treat melanoma with these mutations with a combination of a pan-RAF inhibitor and a MEK inhibitor and could expect to get better treatment and potentially synergistic results in killing these cancer cells.
Rodrıguez-Antona is brought in to show that one would need to then screen the patient for the mutation prior to treatment to get the best result. Rodrıguez-Antona discusses this in the area of using a targeted drug based on the relevant driver mutations. This is outlined in both Figure 2, and Table 1. This shows that certain drugs are known to interdict specific targets with specific mutations.
A person of ordinary skill in the art would know from Atefi that certain cancers, melanoma with NRAS mutations (including activating mutations) would be sensitive to the combination of a pan-RAF inhibitor and a MEK inhibitor. One would then look to treat patients with this knowledge by “screening a sample from the individual for an NRAS activating mutation” as required by instant claim 1 and 2 because Rodrıguez-Antona shows that there is a long-established track record of using this data/knowledge to improve patient outcomes by giving the appropriate drug for the specific cancer mutation profile.
Instant claim 3 states, “wherein screening comprises amplifying and sequencing all or a portion of the NRAS gene.” Atefi teaches, “Presence of mutations in the genes of interest was checked by OncoMap 3 or Iontrone, and was confirmed by PCR and Sanger sequencing.” Meeting this limitation.
Instant claims 4-5, and 9-10 are directed to a specific MEKi including trametinib. This compound is taught by Atefi as a MEKi.
Instant claims 7 and 12 require wherein the sample is a tissue sample, a cell sample, a whole blood sample, a plasma sample, a serum sample, or a combination thereof. Atefi teaches sampling the cancer sample, which is a cell.
Instant claims 7 and 13 require “a melanoma,” this is taught by Atefi.
Claims 1-5, 7-10, and 12-13 are found obvious based on the art above.
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 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Atefi et al. “Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma,” Molecular Cancer (2015) 14:27; and Rodrıguez-Antona et al. “Pharmacogenomic biomarkers for personalized cancer treatment,” J Intern Med 2015; 277: 201–217; as applied to claims 1-5, 7-10, and 12-13 in further view of Peng et al., “Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers,” 2015, Cancer Cell 28, 384–398.
This rejection is in regards to instant claims 6 and 11 which require wherein the pan-RAF dimer inhibitor is selected from the group consisting of HM95573, LY-3009120, AZ-628, LXH-254, MLN2480, BeiGene-283, RXDX-105, BAL3833, regorafenib, and sorafenib, or a pharmaceutically acceptable salt thereof.
Atefi teaches combining a pan-RAF inhibitor and a MEK inhibitor in treating NRAS mutant melanoma. Atefi teaches one of the mutations is cell line M244 NRAS Q61K heterozygous, this is an activating mutation, see Table 1. Atefi teaches pan-RAF inhibitor is Amgen Compound A. Atefi teaches the MEKi can be trametinib.
Therefore Atefi teaches the skilled artisan that one should treat melanoma with these mutations with a combination of a pan-RAF inhibitor and a MEK inhibitor and could expect to get better treatment and potentially synergistic results in killing these cancer cells.
Atefi teaches that the pathway is important and that while the specific compounds are used, Amgen Compound A and trametinib, the reference is teaching the pathway interdiction via the mechanism and that the compounds themselves are simply a tool that an be replaced with known equivalents in the art.
Rodrıguez-Antona is brought in to show that one would need to then screen the patient for the mutation prior to treatment to get the best result.
These 2 references do not teach the known inhibitors of pan-RAF inhibitor, as they only teach Amgen Compound A as the pan-RAF inhibitor.
Peng teaches LY3009120 as a known inhibitors of pan-RAF. Peng states ,” LY3009120 is a pan-RAF and RAF dimer inhibitor that inhibits all RAF isoforms and occupies both protomers in RAF dimers. Biochemical and cellular analyses revealed that LY3009120 inhibits ARAF, BRAF, and CRAF isoforms with similar affinity.
A person of ordinary skill in the art would know from Atefi that certain cancers, melanoma with NRAS mutations (including activating mutations) would be sensitive to the combination of a pan-RAF inhibitor and a MEK inhibitor. One would then look to treat patients with this knowledge by “screening a sample from the individual for an NRAS activating mutation” as required by instant claim 1 and 2 because Rodrıguez-Antona shows that there is a long-established track record of using this data/knowledge to improve patient outcomes by giving the appropriate drug for the specific cancer mutation profile. Lastly, one would know that a pan-RAF inhibitor includes both Amgen Compound A and LY3009120, and both or either one individually could be used to interdict the RAF pathway and be effective in combination with the MEK pathway in treating cancer. As such one could replace Amgen Compound A with LY3009120 because they have the same mechanism of action and would lead to a predictable outcome. Therefore the instant claims 1-13 are obvious at the time of filing.
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 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46-65 of copending Application No. 18554041 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘041 app is directed towards an anticipatory species to the instant claims by using belvarafenib (a pan RAFi) and cobimetinib (a MEKi) together to treat NRAS mutant cancers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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