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 .
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 70 – 72, and 74 – 76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 14, 16, and 26 – 28 of U.S. Patent No. US 12098144 B2 to Mills et. al. (Mills’144).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the invention of Mills’144 and copending examined application direct to the genus of piperazine indazole glucocorticoid receptor modulators. The genus of compounds recited by claims 1 – 14, and 16 of Mills’144 is identical to that taught by examined claims 70 and 74. Further, the issued patent claims exemplify the compound specie of examined claims 70 and 74. In particular, Mills’144 recite the compound of (reference) claim 1, or a pharmaceutically acceptable salt thereof is the compound having the structure of
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. See reference claims 1 – 14, and 16. See examined claim 74. Moreover, Mills’144 recite a pharmaceutical composition comprising a compound of (reference) claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. See reference claim 26. See examined claim 70. Furthermore, Mills’144 recite a method of treating a disorder or condition through modulating a glucocorticoid receptor, the method comprising administering to a subject in need of such treatment, a therapeutically effective amount of a compound of (reference) claim 1, or a pharmaceutically acceptable salt thereof, thereby treating the disorder or condition. See reference claim 27. See examined claims 71 and 75. Additionally, Mills’144 recite a method of treating a disorder or condition through antagonizing a glucocorticoid receptor, the method comprising administering to a subject in need of such treatment, a therapeutically effective amount of a compound of (reference) claim 1, or a pharmaceutically acceptable salt thereof. See reference claim 28. See examined claims 72 and 76.
Claims 71, 73, 75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27 of U.S. Patent No. US 12098144 B2 to Mills et. al. (Mills’144) in view of Arora et. al. ((2013), Glucocorticoid Receptor Confers Resistance to Anti-Androgens by Bypassing Androgen Receptor Blockade, Cell, 155, 1309 – 1322).
Mills’144 recite a method of treating a disorder or condition through modulating a glucocorticoid receptor, the method comprising administering to a subject in need of such treatment, a therapeutically effective amount of a compound of (reference) claim 1, or a pharmaceutically acceptable salt thereof, thereby treating the disorder or condition. See reference claim 27. See examined claims 71 and 75.
However, Mills’144 fails to recite a method where the disorder or condition is antipsychotic induced weight gain, cancer, Cushing Disease, Cushing's Syndrome, major psychotic depression, nonalcoholic steatohepatitis, and obesity. See examined claims 73 and 77.
Nevertheless, Arora et. al. teach that a common mechanism that has emerged from these kinase inhibitor studies is reactivation of the signaling pathway targeted by the drug, directly by mutation of the kinase target or indirectly by bypassing pathway inhibitor blockade through amplification of an alternative kinase. See page 2 paragraph 1. Arora et. al. teach a novel and potentially more prevalent mechanism of resistance by which tumors bypass androgen receptor (AR) blockade through upregulation of the glucocorticoid receptor (GR). See page 2 paragraph 3. Additionally, Arora et. al. teach that LREX’ cells were infected with a shRNA targeting GR (shGR) and stable knockdown of GR protein was confirmed (Figure 2F). See page 3 paragraph 5. Moreover, Arora et. al. teach that tumor growth of shGR infected LREX’ cells was significantly delayed relative to shNT (non targeted)-infected cells in castrated mice treated with enzalutamide (Figure 2D). See page 3 paragraph 5. Furthermore, Arora et.al. teach that in contrast, shGR had no impact on the growth of GRnegative CS1 xenografts, diminishing the possibility of an off-target effect (Figure 2E). See page 3 paragraph 5. Thus, Arora et. al. suggest that GR drives enzalutamide resistance in vivo. See page 4 paragraph 1. Specifically, Arora et.al. teach that clinical studies of the GR antagonist mefipristone in patients with excess glucocorticoid production (Cushing syndrome) demonstrate that GR can be inhibited in humans with an acceptable risk-benefit profile. See page 10 paragraph 3. Additionally, Arora et.al. teach that both mefipristone and a related GR antagonist ORG34517 activate AR target gene expression, likely by direct AR agonism since mefipristone binds and activates AR. See page 10 paragraph 3. Furthermore, Arora et.al. teach that the ability of compound 15 to overcome GR driven resistance should stimulate further efforts to optimize GR-specific antagonists that lack “off target” AR effects for use in preventing or overcoming enzalutamide resistance. See page 10 paragraph 3.
Therefore, it would obvious before the effective filing date of the instant application to modify the invention of Mills’144 for a method of treating a disorder or condition through modulating a glucocorticoid receptor comprising administering a pharmaceutical composition comprising
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in view of Arora et. al. to either treat Cushing syndrome or combine with an AR inhibitor to specifically treat prostate cancer. One of ordinary skill in the art would have been motivated to make either modification to overcome prostate cancer resistance or to mitigate disease where excess glucocorticoid production is an issue. One of ordinary skill in the art would have had a reasonable expectation of success because GR drives enzalutamide resistance in vivo and because the GR antagonist mefipristone demonstrates acceptable risk-benefit profile in patients with excess glucocorticoid production, such as Cushing syndrome.
Conclusion
Claims 70 – 77 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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