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 .
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/8/25 has been entered.
Claims 1, 9-12, 15-20 have been cancelled. Claims 2-8, 13-14, 21-27 are pending. Claim 2 has been amended. Claims 7-8, 21, 24-25, 27 have been withdrawn. Claims 2-6, 13-14, 22-23, 26 are examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and repeated below for Applicant’s convenience.
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 CFR 1.114 and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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. See 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); and 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 2-6, 13-14, 22-23, 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-12 of U.S. Patent No. 11,407,831 in view of Proia et al. (WO 2016/130502, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite a method of treating colon cancer by administering a compound of formula I, for example N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide in combination with an anti-PD-1 antibody. The referenced claims do not specifically teach the anti-PD-L1 antibody, MPDL3280A.
Proia et al. teach that a method of treating colon cancer by administering the anti-PD-1 antibody, MPDL3280A (paragraph 0031 and claims 1-7, 13).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to combine the anti-PD-L1 antibody, MPDL3280A, as taught by Proia et al., with N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide in the method of treating colon cancer.
A person of ordinary skill in the art would have been motivated to combine MPDL3280A with N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide because both are individually known to be useful for treating colon cancer. Furthermore, the referenced claims teach that additional anti-cancer agents may be combined with N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide. Therefore, the skilled artisan would have had a reasonable expectation of success in the methods of treating colon cancer by administering the therapeutically additive effect of a combination of N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide and the anti-PD-L1 antibody, MPDL3280A.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... The idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Response to Arguments
The terminal disclaimer over US Patent 11,407,831 has not been approved because the power of attorney filed on 10/8/25 has not been accepted. The communication filed on 10/14/25 explains that the power of attorney must be signed by the applicant for patent. See 37 CFR 1.32(b)4). The person or entity attempting the change to power of attorney is not the applicant of record in the application.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 2-6, 13-14, 22-23, 26 are rejected under 35 U.S.C. 103 as being unpatentable over Iwase et al. (WO 2016/204153 A1, of record) in view of Proia et al. (WO 2016/130502, of record).
The instant claims are directed to a method for treating cancer by administering a compound of formula II and an anti-PD-L1 antibody.
Iwase et al. teach a method of treating or preventing cancer, such as colon cancer, by administering a pharmaceutical composition (claims 23 and 26) comprising N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide (claim 12) and other drugs, such as anticancer agents, immune checkpoint inhibitors, or atezolizumab (claims 34-38).
However, Iwase et al. fail to disclose the anti-PD-L1 antibody, MPDL3280A.
Proia et al. teach that a method of treating colon cancer by administering the anti-PD-1 antibody, MPDL3280A (paragraph 0031 and claims 1-7, 13).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to combine the anti-PD-L1 antibody, MPDL3280A, as taught by Proia et al., with N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide in the method of treating colon cancer, as taught by Iwase et al.
A person of ordinary skill in the art would have been motivated to combine MPDL3280A with N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide because both are individually known to be useful for treating colon cancer. Furthermore, Iwase et al. teach that additional anti-cancer agents may be combined with N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide. Therefore, the skilled artisan would have had a reasonable expectation of success in the methods of treating colon cancer by administering the therapeutically additive effect of a combination of N-(2-chloro-6-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide and the anti-PD-L1 antibody, MPDL3280A.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... The idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Response to Arguments
The Ram Declaration under 37 CFR 1.132 filed 10/8/25 is insufficient to overcome the rejection of claims 2-6, 13-14, 22-23, 26 based upon Iwase et al. (WO 2016/204153 A1, of record) in view of Proia et al. (WO 2016/130502, of record) as set forth in the last Office action.
The declaration allegedly provides unexpectedly superior results in treating cancer that could not reasonably have been expected based on the teachings in the cited prior art. Support comes from Tables 13-15 in Examples 2-4 for the unexpectedly superior results from the claimed combination of compounds of formula II and an anti-PD-1 antibody.
This is not persuasive for the following reasons. Firstly, the results in Tables 13-15 do not reflect unexpected superior results but therapeutically additive effects. Table 13 shows a tumor volume inhibition rate of 30-50% for the anti-PD-1 antibody alone and 50-70% for compound II-215 alone. The combination of anti-PD-1 antibody and compound II-215 showed a rate of 70-90% which is more reflective of therapeutically additive effects rather than unexpected synergy since the effect of each individual active agent was so pronounced. The same logic applies to Tables 14 and 15.
Secondly, the results are not commensurate with the scope of the claims. Applicant is reminded that independent claim 2 recites the treatment of any and all cancers by administering a large genus of compounds according to formula II in combination with 4 anti-PD-L1 antibodies. However, the data presented in Tables 13-15 only account for melanoma and cancer of the large intestine. Furthermore, three compounds (II-215, II-379, and II-1063) are insufficient to support the large genus of compounds recited in formula II. Lastly, with regard to the anti-PD-1 antibody, the data in the specification does not clearly define which of the 4 claimed anti-PD-L1 antibodies it is, if in fact it is even one of them. Regardless, a showing of a single anti-PD-1 antibody is insufficient to support all 4 claimed anti-PD-L1 antibodies. Therefore, the limited data in Tables 13-15 is not commensurate with the full scope of the claims.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Regarding the establishment of unexpected results or synergism, a few notable principles are well settled. The Applicant has the initial burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02 (b). It is applicant’s burden to present clear and convincing factual evidence of nonobviousness or unexpected results, i.e., side-by-side comparison with the closest prior art in support of nonobviousness for the instant claimed invention over the prior art. The claims must be commensurate in the scope with any evidence of unexpected results. See MPEP 716.02 (d). With regard to synergism, a prima facie case of synergism has not been established if the data or result is not obvious. The synergism should be sufficient to overcome the obviousness, but must also be commensurate with the scope of the claims. Further, if the Applicant provides a DECLARATION UNDER 37 CFR 1.132, it must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case of obviousness. See MPEP 716.02 (e).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623