DETAILED ACTION
The present application is a domestic application filed 07 August 2023, which is a continuation of US 17/222,873 (now US Patent No. 11,717,523), filed 05 April 2021, which is a continuation of US 16/112,360 (now US Patent No. 10,966,984), filed 24 August 2018, which is a continuation of US 15/342,990 (now US Patent No. 10,085,992), filed 03 November 2016, which is a continuation of US 14/212,430 (now US Patent No. 9,487,530), filed 14 March 2014, which claims priority to US Provisional Application Nos. 61/949,786, filed 07 March 2014, US Provisional Application No. 61/911,354, filed 03 December 2013, US Provisional Application No. 61/861,374, filed 01 August 2013 and US Provisional Application No. 61/798,772, filed 15 March 2013.
Claims 1-18 are pending in the current application and are examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 1-9 and 12-18 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sharpless et al. (WO 2010/039997, cited in IDS submitted 01 September 2023) in view of Tavares et al. (WO 2012/061156, published 10 May 2012, priority to 25 October 2010, cited in PTO-892).
Sharpless et al. teach a method of reducing or preventing the effects of a cytotoxic compound on healthy cells in a subject who has been exposed to, shall be exposed to, or is at risk of incurring exposure to a cytotoxic compound, wherein said healthy cells are hematopoietic progenitor cells, the method comprising administering to the subject an effective amount of a CDK4/CDK6 inhibitor (claims 1, 2, 5, and 6). The cytotoxic compound is a DNA damaging compound, and the DNA damaging compound includes doxorubicin, etoposide and carboplatin (claim 41). Other chemotherapeutic agents whose toxic effects can be mitigated include cisplatin, taxol (i.e. paclitaxel), campothecin, cyclophosphamide and gemcitabine (p.4:3-10; p.31:4-20; and p.32:17-24). Sharpless exemplify administering doxorubicin, and then administering it again after 7 days (i.e., days 1 and 8; figure 18, p.17). Sharpless teach treating subjects having cancer, including triple negative breast cancer and bladder cancer (p.46-47). Sharpless et al. teach protecting patients from myelosuppression (p.6:17-22).
Sharpless et al. do not expressly disclose a CDK4/CDK6 inhibitor having the structure of present claim 1.
Tavares et al. is concerned with preparing CDK inhibitors of formula I, II or III (abstract). Tavares et al. exemplify CDK inhibitor compound 27:
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(p.80, para 0258). In some embodiments the cancer is characterized by increased activity of cyclin-dependent kinase 1 (CDK1), increased activity of cyclin-dependent kinase 2 (CDK2), increased cyclin E and increased cyclin A (p.8:20-25). In some embodiments, the inhibitor compound is administered to the subject 24 hours or less prior to exposure to the cytotoxic compound (p.7-8, bridging para). Tavares et al. teach compound 27 an IC50 value of 1-100 µM towards CDK2/cyclinE.
The recitation “reducing chemotherapy-induced myelosuppression in a human receiving chemotherapy for the treatment of bladder cancer” in present claim 8 will necessarily occur upon performing the positively recited steps, wherein administering the combination of CDK4/6 inhibitor and chemotherapeutic agent to treat bladder cancer was known at the time the invention was made.
It would have been obvious at the time the invention was made to substitute the CDK4/CDK6 inhibitor of Sharpless with one exemplified by Tavares et al. because they are recognized equivalents in the art of treating cancer using a combination of CDK4/6 inhibitor and antineoplastic agent. See MPEP 2144.06.
From the combined teaching of Sharpless and Tavares et al., the ordinary artisan would have been motivated to administer a CDK4/6 inhibitor in combination with a chemotherapeutic agent to mitigate the negative side effects of the chemotherapeutic agent, including for treating a subject with triple negative breast cancer or bladder cancer, as taught by Sharpless et al. From Sharpless, the skilled artisan would have been motivated to administer the CDK4/6 inhibitor less than 24 hours prior to administering the chemotherapeutic agent. A range of “less than 24 hours prior to exposure to the cytotoxic compound” encompasses “wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of the chemotherapeutic agent” in claims 1 and 8, and “1/2 hour or less” in claim 9.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claims 10 and 11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sharpless et al. (cited above) in view of Tavares et al. (cited above) as applied to claims 1-9 and 12-18 above, and further in view of Ciomei et al. (US Patent Application Publication No. 2011/0312909, cited in PTO-892).
Sharpless et al. teach as discussed above.
Sharpless et al. do not expressly disclose administering the chemotherapeutic agent on day 1 every 21 days (present claim 10), or on days 1 and 8 every 21 days (present claim 11).
Tavares et al. teach as discussed above.
Ciomei et al. is concerned with administering an antineoplastic agent and CDK inhibitor (title). Ciomei et al. teach preferably administering gemcitabine on days 1 and 8 of a 21-day, or on day 1 of a 21-day cycle (para [0033]). Ciomei et al. teach administering the compounds sequentially (para [0015]). Ciomei et al. teach administering the CDK inhibitor with the antineoplastic agent to lower the side effects caused by said antineoplastic agents (claim 14).
It would have been obvious at the time the invention was made to administer a chemotherapeutic agent on days 1 and 8 every 21 days, or on day 1 every 21 days.
From the combined teaching of Sharpless, Tavares et al. and Ciomei et al., the ordinary artisan would have been motivated to administer a CDK4/6 inhibitor in combination with a chemotherapeutic agent to mitigate the negative side effects of the chemotherapeutic agent. From Sharpless, the skilled artisan would have been motivated to administer the CDK4/6 inhibitor less than 24 hours prior to administering the chemotherapeutic agent. From Ciomei et al., the ordinary artisan would have been motivated to administer the chemotherapeutic agent on days 1 and 8 of a 21-day cycle, or on day 1 of a 21-day cycle because this was a known schedule for treating cancer with chemotherapeutic agents like gemcitabine, including when used in combination with a CDK inhibitor.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
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.
I. Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,717,523 in view of Sharpless et al. (WO 2010/039997, cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are drawn towards administering at least one chemotherapeutic agent and a CDK4/6 inhibitor of the same structure as the present claims. The claims of the reference Patent are directed towards treating small cell lung cancer.
The claims of the reference Patent do not expressly disclose treating triple negative breast cancer (present claim 1), or bladder cancer (present claim 8).
Sharpless et al. teach as discussed above.
It would have been obvious at the time the invention was made to sequentially administer the CDK4/6 inhibitor prior to a chemotherapeutic agent to treat triple negative breast cancer or bladder cancer, because in the same field of endeavor, Sharpless et al. teach this method can be used to treat patients with triple negative breast cancer or bladder cancer.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
II. Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,966,984.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims. The cancer is bladder cancer (claim 9), and triple negative breast cancer (claim 19). The CDK4/6 inhibitor is administered 4 hours or less prior to administration of the chemotherapeutic agent, or ½ hour or less (claims 2 and 27). The chemotherapeutic agent is selected from etoposide, carboplatin, gemcitabine, paclitaxel, doxorubicin, cisplatin, and cyclophosphamide (claims 2 and 30).
The present claims are overlapping with respect to patient population and number of hours in which the CDK4/6 inhibitor is administered prior to administration of the chemotherapeutic agent. The various time frames and patient populations are recited in the claims of the reference Patent.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
III. Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,925,878 in view of Sharpless et al. (WO 2010/039997, cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims.
The claims of the reference Patent do not expressly disclose treating triple negative breast cancer (present claim 1), or bladder cancer (present claim 8).
Sharpless et al. teach as discussed above.
It would have been obvious at the time the invention was made to sequentially administer the CDK4/6 inhibitor prior to a chemotherapeutic agent to treat triple negative breast cancer or bladder cancer, because in the same field of endeavor, Sharpless et al. teach this method can be used to treat patients with triple negative breast cancer or bladder cancer.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
IV. Claims 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,085,992 in view of Sharpless et al. (WO 2010/039997, cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims in combination with etoposide and carboplatin.
The claims of the reference Patent do not expressly disclose treating triple negative breast cancer (present claim 1), or bladder cancer (present claim 8). The claims of the reference Patent do not expressly disclose the chemotherapeutic agents cisplatin, paclitaxel, doxorubicin, cyclophosphamide, gemcitabine (present claims 3-7) or campothecin (present claim 14).
Sharpless et al. teach as discussed above.
It would have been obvious at the time the invention was made to sequentially administer the CDK4/6 inhibitor prior to a chemotherapeutic agent to treat triple negative breast cancer or bladder cancer, because in the same field of endeavor, Sharpless et al. teach this method can be used to treat patients with triple negative breast cancer or bladder cancer.
The ordinary artisan would have been motivated to substitute the carboplatin and etoposide with cisplatin, paclitaxel, doxorubicin, cyclophosphamide, gemcitabine or campothecin, because in the same field of endeavor, Sharpless et al. teach the CDK4/6 inhibitor can mitigate the negative side effects caused by the aforementioned chemotherapeutic agents.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
V. Claims 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of U.S. Patent No. 9,487,530 in view of Sharpless et al. (cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims in combination with at least one chemotherapeutic agent (claims 2 and 3). The cancer is triple negative breast cancer of bladder cancer (claim 10). The claims recite chemotherapeutic agent includes etoposide, cisplatin, or carboplatin.
The claims of the reference Patent do not expressly disclose the chemotherapeutic agents doxorubicin, cyclophosphamide, gemcitabine (present claims 3-7) or campothecin (present claim 14).
Sharpless et al. teach as discussed above.
The ordinary artisan would have been motivated to substitute the etoposide, cisplatin, or carboplatin with cisplatin, paclitaxel, doxorubicin, cyclophosphamide, gemcitabine or campothecin, because in the same field of endeavor, Sharpless et al. teach the CDK4/6 inhibitor can mitigate the negative side effects caused by the aforementioned chemotherapeutic agents.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
VI. Claims 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,616,062 in view of Sharpless et al. (cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims in combination with at least one chemotherapeutic agent. The subject is undergoing treatment for triple negative breast cancer (claim 11). Claim 7 is drawn to a list of chemotherapeutic agents.
The claims of the reference Patent do not expressly disclose gemcitabine (present claim 7) or treating bladder cancer (present claim 8).
Sharpless et al. teach as discussed above.
It would have been obvious at the time the invention was made to sequentially administer the CDK4/6 inhibitor prior to a chemotherapeutic agent to treat triple negative breast cancer or bladder cancer, because in the same field of endeavor, Sharpless et al. teach this method can be used to treat patients with triple negative breast cancer or bladder cancer.
The ordinary artisan would have been motivated to substitute any one of the listed chemotherapeutic agents with gemcitabine, because in the same field of endeavor, Sharpless et al. teach the CDK4/6 inhibitor can mitigate the negative side effects caused by the aforementioned chemotherapeutic agents.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
VII. Claims 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of U.S. Patent No. 11,529,352 in view of Sharpless et al. (cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims in combination with at least one chemotherapeutic agent. The cancer to be treated includes triple negative breast cancer or bladder caner (claim 13). The chemotherapeutic agent includes gemcitabine, cyclophosphamide, paclitaxel and etoposide (claim 10). Additionally, it includes carboplatin, and cisplatin (claim 33). It also includes doxorubicin (claim 37)
The claims of the reference Patent do not expressly disclose campothecin (present claim 15).
Sharpless et al. teach as discussed above.
The ordinary artisan would have been motivated to substitute any one of the listed chemotherapeutic agents with campothecin, because in the same field of endeavor, Sharpless et al. teach the CDK4/6 inhibitor can mitigate the negative side effects caused by the aforementioned chemotherapeutic agents.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
VIII. Claims 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,527,798 in view of Sharpless et al. (cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Patent are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having the same structure as the present claims in combination with at least one chemotherapeutic agent. The cancer to be treated includes triple negative breast cancer or bladder cancer (claim 13). The chemotherapeutic agent includes gemcitabine, cyclophosphamide, paclitaxel and etoposide (claim 10). Additionally, it includes carboplatin, and cisplatin (claim 11). It also includes doxorubicin (claim 37)
The claims of the reference Patent do not expressly disclose campothecin (present claim 15).
Sharpless et al. teach as discussed above.
The ordinary artisan would have been motivated to substitute any one of the listed chemotherapeutic agents with campothecin, because in the same field of endeavor, Sharpless et al. teach the CDK4/6 inhibitor can mitigate the negative side effects caused by the aforementioned chemotherapeutic agents.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
IX. Claims 1-18 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of copending Application No. 18/117,983 in view of Sharpless et al. (cited above) and Tavares et al. (cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference Application are directed towards a method of treating a human with cancer comprising administering to the human an effective amount of a selective CDK4/6 inhibitor having a similar structure as the present claims in combination with at least one chemotherapeutic agent. Chemotherapeutic agents include carboplatin, cisplatin, and doxorubicin (claims 25 and 36).
The claims do not expressly disclose treating triple negative breast cancer (present claim 1), or bladder cancer (present claim 8). The structure of the CDK4/6 inhibitor differs at the piperazine moiety, where the present claim contains a methyl-substituted piperazine while the reference Application contains an isopropyl-substituted piperazine.
Sharpless et al. teach as discussed above.
Tavares et al. teach as discussed above.
It would have been obvious at the time the invention was made to substitute the CDK4/CDK6 inhibitor of the present claims with one exemplified by Tavares et al. because they are recognized equivalents in the art of treating cancer using a combination of CDK4/6 inhibitor and antineoplastic agent. See MPEP 2144.06.
From Sharpless, the skilled artisan would have been motivated to administer the CD4/6 inhibitor less than 24 hours prior to administering the chemotherapeutic agent. A range of “less than 24 hours prior to exposure to the cytotoxic compound” encompasses “wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of the chemotherapeutic agent” in claims 1 and 8, and “1/2 hour or less” in claim 9.
From Sharpless, the skilled artisan would have known doxorubicin, etoposide, carboplatin, cisplatin, taxol (i.e. paclitaxel), campothecin, cyclophosphamide and gemcitabine are recognized equivalents of chemotherapeutic agents, any of which can be administered in combination with a CDK4/6 inhibitor, including for treating patients with triple negative breast cancer and bladder cancer.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699