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 .
Claim Status
Claims 1-13 and 16-17 are pending. Claims 1-3, 5, 7, 9, and 11-13 are rejected. Claims 4, 6, 8 and 10 are objected to. Claims 16-17 are allowed.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-3, 5, 7 and 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims recite crystalline forms characterized by X-ray powder diffraction patterns with specific peaks at “about” 2-theta = …˚ plus or minus 0.2˚ 2-theta. It is unclear what values would be embraced for the claimed peaks as the term “about” introduces ambiguity given that the plus or minus 0.2˚ 2-theta already accounts for small shifts in 2-theta positions that may occur with X-ray powder diffraction.
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, 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.
Claims 1 and 11-13 are rejected under 35 U.S.C. 103 as being obvious over WO 2022122876 A1 by Terstiege et al. cited in the IDS filed 02/24/2025.
The applied reference has a common joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Terstiege et al. teach N-imidazo[1,2-b]pyridazine-3-yl)-cyclohexyl-2H-indazole-5-carboxamide derivatives as IRAK4 inhibitors and disclose the compound of instant claim 1 (page 75):
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The prior art further teaches that the compound may be supplied in crystalline form (page 28, lines 25-27).
Regarding instant claims 11-13, the prior art discloses a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient as well as a method of treating diseases such as asthma, atopic dermatitis, etc. by administering the prior art compound (page 28, lines 15-17; page 32, lines 23-31).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art discloses N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((lr,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide and suggest preparation of crystalline forms but does not include an embodiment in which the crystalline form was prepared.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
A person of ordinary skill seeking to prepare pharmaceutical compositions of the prior art would have been motivated to prepare crystalline forms of the prior art compound to test various formulations for the treatment of disclosed conditions such as asthma.
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 and 11-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11866405 in view of Cote et al. Crystal Growth & Design (2020) 20 (12): 7568–7581.
The patent discloses pharmaceutical compositions comprising a pharmaceutically acceptable excipient and compounds such as N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((lr,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide in claims 12 and 13 (Col. 191 and 196). However, the patent is silent to crystalline forms of the compound.
Cote et al. provide “Perspectives on the Current State, Challenges, and Opportunities in Pharmaceutical Crystallization Process Development” (title) and state (page 7568, paragraph 3):
Crystallization is an essential unit operation in the development and production of most synthetic small-molecule pharmaceutical products, i.e., active pharmaceutical ingredients (APIs). Its two most critical purposes are chemical purification and establishment of physical attributes and associated performance characteristics (e.g., dissolution, stability, down stream processing) of APIs.
Accordingly, a person of ordinary skill seeking to optimize the properties of the patent’s pharmaceutical composition would have been motivated to prepare crystalline forms of the active compound corresponding to instant claims 1 and 11.
Regarding instant claims 12-13, with respect to the fact that the claims of U.S. Patent No. 11866405 are drawn to compounds and compositions while the instant claims are drawn to methods of treating diseases such as asthma, Applicant is directed to Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co. 95 USPQ2d 1797, Geneva Pharmaceuticals, Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 [68 USPQ2d 1865] (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353 [86 USPQ2d 1001] (Fed. Cir. 2008) for analogous situations. The instantly claimed utilities are disclosed in Col. 6, lines 12-15. A person of ordinary skill seeking to use the pharmaceutical compositions would be motivated to test the formulations according to their disclosed utility such as administering for the treatment of asthma.
Claims 1 and 11-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12448385 in view of Cote et al. Crystal Growth & Design (2020) 20 (12): 7568–7581.
The patent discloses pharmaceutical compositions comprising a pharmaceutically acceptable excipient and compounds such as N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((lr,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide (Col. 185, claim 11, lines 39-41; Col 187, claim 12). However, the patent is silent to crystalline forms of the compound.
Cote et al. provide “Perspectives on the Current State, Challenges, and Opportunities in Pharmaceutical Crystallization Process Development” (title) and state (page 7568, paragraph 3):
Crystallization is an essential unit operation in the development and production of most synthetic small-molecule pharmaceutical products, i.e., active pharmaceutical ingredients (APIs). Its two most critical purposes are chemical purification and establishment of physical attributes and associated performance characteristics (e.g., dissolution, stability, down stream processing) of APIs.
Accordingly, a person of ordinary skill seeking to optimize the properties of the patent’s pharmaceutical composition would have been motivated to prepare crystalline forms of the active compound corresponding to instant claims 1 and 11.
Regarding instant claims 12-13, with respect to the fact that the claims of U.S. Patent No. 12448385 are drawn to compounds and compositions while the instant claims are drawn to methods of treating diseases such as asthma, Applicant is directed to Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co. 95 USPQ2d 1797, Geneva Pharmaceuticals, Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 [68 USPQ2d 1865] (Fed. Cir. 2003), and Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353 [86 USPQ2d 1001] (Fed. Cir. 2008) for analogous situations. The instantly claimed utilities are disclosed in Col. 6, lines 16-19. A person of ordinary skill seeking to use the pharmaceutical compositions would be motivated to test the formulations according to their disclosed utility such as administering for the treatment of asthma.
Claims 1 and 11-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-34 of copending Application No. 19343252 in view of Cote et al. Crystal Growth & Design (2020) 20 (12): 7568–7581.
Copending claims 1 and 34 disclose a method of treating a disease in which inhibition of IRAK4 is beneficial comprising administering N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((lr,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide which overlaps with instant claims 1 and 12-13. The copending claims are silent to administration of crystalline forms of the compounds; however, Cote et al. provide “Perspectives on the Current State, Challenges, and Opportunities in Pharmaceutical Crystallization Process Development” (title) and state (page 7568, paragraph 3):
Crystallization is an essential unit operation in the development and production of most synthetic small-molecule pharmaceutical products, i.e., active pharmaceutical ingredients (APIs). Its two most critical purposes are chemical purification and establishment of physical attributes and associated performance characteristics (e.g., dissolution, stability, down stream processing) of APIs.
Accordingly, a person of ordinary skill seeking to optimize the therapeutic outcomes following administration of the patent compound would have been motivated to prepare crystalline forms of the active compound in a pharmaceutical composition corresponding to instant claims 1 and 11.
Regarding instant claim 13, copending claims 19 and 20 further specify diseases such as asthma, atopic dermatitis, etc.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claims 16-17 are allowed.
Claims 4, 6, 8 and 10 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Closest Prior Art
With regards to instant claim 16, the closest prior art is WO 2022122876 A1 by Terstiege et al. cited above, which shares a common joint inventor. The prior art discloses a method of preparing N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((lr,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide however the compound is prepared by reacting tert-Butyl((1r,4r)-4-(5-bromo-6-methoxy-2H-indazol-2-yl)cyclohexyl)(methyl)carbamate shown below with imidazo[1,2-b]pyridazine-3-amine, and catalyst Pd(OAc)2, under carbon monoxide (pages 55-56):
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Tert-Butyl((1r,4r)-4-(5-bromo-6-methoxy-2H-indazol-2-yl)cyclohexyl)(methyl)carbamate differs from the indazole intermediates of claim 16 in that it has a BOC group where the instant compounds have an acetyl group. Additional steps were taken to produce Int V-3 shown below which was ultimately reacted with TEA and DCM to produce N-(Imidazo[1,2-b]pyridazin-3-yl)-6-methoxy-2-((lr,4r)-4-(N-methylacetamido)cyclohexyl)-2H-indazole-5-carboxamide (page 76):
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The prior art provides no motivation or guidance for modifying the method of preparing that would lead a person of ordinary skill to react imidazo[1,2-b]pyridazine-3-amine with an indazole intermediate of the instant claim therefore the prior art neither anticipates nor renders obvious the instant claim.
The closest prior art with respect to claim 17 is WO2023152349A1 by Terstiege et al. which claims priority to U.S. Provisional No. 63/267,956 filed February 14th, 2022, and shares a common joint inventor. The prior art discloses the following intermediate in a process of preparing an IRAK4 inhibitor via the following intermediate (page 44 of WIPO and priority doc):
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The compound above differs from the compound of instant claim 17 by the presence of a methyl substituent on the cyclohexyl ring. Terstiege et al. disclose the compound in a multi-step method of preparation that results in compounds such as the following where the methyl substituent is present (page 46 of WIPO and priority doc):
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The prior art provides no motivation or guidance for modifying the intermediate to result in the compound of claim 17 therefore the reference neither anticipates nor renders obvious the instant claim.
Conclusion
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/A.A.C./Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626
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