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 present application claims priority to the applications, 63/174,415 and PCT/US2022/024684, with effective filing dates of 13 April 2021 and 13 April 2022, respectively.
Claim Status
This Office Action is in response to Applicant’s Amendment filed, 10 June 2024, wherein the Applicant amended claims 6, 7, 10, 16, and 20 and canceled claim 21.
Claims 1-20 are pending.
Information Disclosure Statement
The Information Disclosure Statements filed on 15 February 2024 and 8 January 2025 and the references cited therein have been considered, unless indicated otherwise.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
1. Claims 9, 15, and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 9, 15, and 19 specify immunomodulatory agents: an IFN-β 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other S1P1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide. While the specification broadly describes methods of treating neurodegenerative, demyelinating, and neuropathic diseases via combination of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile and one or more immunomodulatory agents, the specification refers to several of the immunomodulatory agents by their antigen ([0185]).
Regarding reference to immunomodulatory agents by their antigen, the disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). See MPEP § 2163(II)(3)(a).
Thus, the specification does not describe the claimed subject matter that would reasonably convey to one of skill in the art a method of treating a neurodegenerative, demyelinating, or neuropathic disease via combination of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile and the following immunomodulatory agents: an antibody or fragment thereof against alpha-4 integrin; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25); an antibody against CD52; or an antibody against CD20.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
2. Claims 1-20 are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Baccei (WO 2021/071843, filed 7 Oct 2020).
Baccei teaches compounds with activity against muscarinic acetylcholine receptor M1 (mAChR M1) and their utility in treatment of movement disorders, such as Parkinson’s disease (page 1, paragraph 2).
Baccei specifically teaches Example 138:
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, which is 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile (the IUPAC name of the crystalline compound of claim 1; [0516]). Baccei further specifies that Example 138 was afforded as a white solid ([0517]).
Regarding claim 1, Baccei teaches the compound:
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, and its collection as a white solid ([0516], [0517]). While Baccei is silent to if 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile is crystalline, the Examiner cannot determine whether or not Baccei inherently possesses properties which would anticipate or render obvious the claimed invention, because a solid can be crystalline, as evidenced by Gardner (Computers and Chemical Engineering, 2004, 28, 943-953). Gardner teaches high throughput techniques to evaluating crystals via utilization of optical imaging and in situ Raman spectroscopy to characterize a large number of solid forms (page 948, paragraph 2). Further, Gardner specifies that almost without exception, small molecular weight drugs are isolated as crystalline materials principally for two reasons: purity and reproducibility (page 944, paragraph 2). Thus, as Baccei discloses the isolation of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile as a white solid, this can be reasonably interpreted to be a crystalline solid. Further, the specification discloses multiple methods to produce only one polymorph of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile, which is Form A (Table 5, page 39; Table 6, page 40; Table 7, pages 40 and 41; Table 8, pages 41 and 42; Table 9, pages 42 and 43; Table 10, page 43; Table 11, page 44; Table 12, page 45; Table 13, page 45; Table 14, page 46). Because only one polymorph of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile is obtained through a variety of methods and solvents, one of ordinary skill in the art would reasonably infer that the crystal obtained from Baccei would be the same polymorph: Form A. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Thus, it is reasonable to infer that the crystal of Example 148 in Baccei would give the same XRPD pattern, because the XRPD pattern is the fingerprint to Form A of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile. Thus, Baccei teaches a crystalline compound having the formula:
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, characterized by an x-ray powder diffraction pattern with peaks at 13.4 ± 0.150 2θ, 14.0 ± 0.150 2θ, 15.2 ± 0.150 2θ, 19.3 ± 0.150 2θ, 20.0 ± 0.150 2θ and 21.2 ± 0.150 2θ.
Regarding claim 2, Baccei teaches isolation of a white solid of
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([0516], [0517]). As Baccei is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of Baccei possesses the same XRPD pattern. Thus, Baccei teaches the compound is characterized by an x-ray powder diffraction pattern with peaks at 6.7 ± 0.150 2θ, at 13.4 ± 0.15 2θ, 14.0 ± 0.15 2θ, 15.2 ± 0.15 2θ, 17.7 ±0.15 2θ, 18.1 ±0.15 2θ, 18.8 ± 0.15 2θ,19.3 ± 0.15 2θ, 19.8 ±0.15 2θ, 20.0 ±0.15 2θ, 21.0 ± 0.15 2θ, 21.2± 0.150 2θ, and 24.1 ± 0.150 2θ ([0516], [0517]).
Regarding claim 3, Baccei teaches isolation of a white solid of
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([0516], [0517]). As Baccei is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of Baccei possesses the same XRPD pattern. Thus, Baccei teaches the compound is characterized by an x-ray powder diffraction pattern with peaks at 6.7 ± 0.150 2θ, 10.7 ± 0.150 2θ, 13.4 ± 0.15 2θ, 14.0 ± 0.15 2θ, 15.2 ±0.15 2θ, 17.7 ± 0.15 2θ, 18.1 ± 0.15 2θ, 18.8±0.15 2θ, 19.3 ±0.15 2θ, 19.8 ± 0.15 2θ, 20.0 ±0.15 2θ, 20.7 ±0.15 2θ, 21.0 ± 0.15 2θ,21.2 ± 0.15 2θ, 24.1 ±0.15 2θ, 25.9± 0.150 2θ, 27.8 ± 0.150 2θ, and 30.6 ±0.15 2θ ([0516], [0517]).
Regarding claim 4, Baccei teaches isolation of a white solid of
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([0516], [0517]). As Baccei is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of Baccei possesses the same XRPD pattern. Thus, Baccei teaches the compound is characterized by an x-ray powder diffraction pattern with peaks at 6.7 ± 0.150 2θ, 10.7 ± 0.150 2θ, 13.4 0.15 2θ, 14.0 0.15 2θ, 15.2 ±0.15 2θ, 16.6 0.15 2θ, 17.7 0.15 2θ, 18.1 ± 0.15 2θ, 18.4 ±0.15 2θ, 18.8 0.15 2θ, 19.3 ±0.15 2θ, 19.8 ±0.15 2θ, 20.0 0.15 2θ,20.7 ±0.15 2θ, 21.0 ±0.15 2θ, 21.2 ±0.15 2θ, 24.10.15 2θ, 25.9 ±0.150 2θ, 26.3 ±0.150 2θ, 26.6 0.150 2θ, 27.0 0.150 2θ, 27.8± 0.150 2θ, and 30.6 ±0.15 2θ ([0516], [0517]).
Regarding claim 5, Baccei teaches isolation of a white solid of
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([0516], [0517]). As Baccei is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of Baccei possesses the same differential scanning calorimetry endotherm onset. Thus, Baccei teaches the compound is further characterized as having a differential scanning calorimetry endotherm onset at about 117 C ([0516], [0517]).
Regarding claim 6, Baccei teaches a pharmaceutical composition comprising a crystal of been motivated to make such a selection, to predictably arrive at a composition of a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile and a pharmaceutically acceptable excipient ([0286]).
Regarding claim 7, Baccei teaches a method of treating a neurodegenerative disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of compound ([0288]).
Regarding claim 8, Baccei teaches the administration of one or more immunomodulatory agents ([0295]).
Regarding claim 9, Baccei teaches one or more immunomodulatory agents are selected from: an IFN-β 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other SlP1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide ([0296]).
Regarding claim 10, Baccei teaches a method of treating a demyelinating disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of compound ([0289]).
Regarding claim 11, Baccei teaches the demyelinating disease is a demyelinating disease of the central nervous system ([0290]).
Regarding claim 12, Baccei teaches the demyelinating disease is multiple sclerosis ([0291]).
Regarding claim 13, Baccei teaches the demyelinating disease is a demyelinating disease of the peripheral nervous system ([0292]).
Regarding claim 14, Baccei teaches the administration of one or more immunomodulatory agents ([0295]).
Regarding claim 15, Baccei teaches one or more immunomodulatory agents are selected from: an IFN-3 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other SlP1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide ([0296]).
Regarding claim 16, Baccei teaches a method of treating a neuropathic disease, optionally a peripheral neuropathy, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of compound ([0293]).
Regarding claim 17, Baccei teaches the neuropathic disease is diabetic neuropathy ([0294]).
Regarding claim 18, Baccei teaches the administration of one or more immunomodulatory agents ([0295]).
Regarding claim 19, Baccei teaches one or more immunomodulatory agents are selected from: an IFN-3 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other SlP1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide ([0296]).
Regarding claim 20, Baccei teaches a method of modulating muscarinic acetylcholine receptor Mi activity in a subject comprising administering to the subject ([0297]).
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.
3. Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-38 of copending Application No. 17/762,683 (US2023/0089921, filed 22 Mar 2022). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U.S. Application No. 17/762,683 claims compounds with activity against muscarinic acetylcholine receptor M1 (mAChR M1) and their utility in treatment of movement disorders, such as Parkinson’s disease (claim 1-20).
‘683 specifically teaches the compound,
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, which is taught as Example 138 and afforded as a white solid (claim 23, page 237; [0517]).
Regarding claim 1, ‘683 teaches the compound:
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, and its collection as a white solid ([0516], [0517]). While ‘683 is silent to if 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile is crystalline, the Examiner cannot determine whether or not ‘683 inherently possesses properties which would anticipate or render obvious the claimed invention, because a solid can be crystalline, as evidenced by Gardner (Computers and Chemical Engineering, 2004, 28, 943-953). Gardner teaches high throughput techniques to evaluating crystals via utilization of optical imaging and in situ Raman spectroscopy to characterize a large number of solid forms (page 948, paragraph 2). Gardner further specifies that almost without exception, small molecular weight drugs are isolated as crystalline materials principally for two reasons: purity and reproducibility (page 944, paragraph 2). Thus, as ‘683 discloses the isolation of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile as a white solid, this can be reasonably interpreted to be a crystalline solid. Further, the specification discloses multiple methods to produce only one polymorph of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile, which is Form A (Table 5, page 39; Table 6, page 40; Table 7, pages 40 and 41; Table 8, pages 41 and 42; Table 9, pages 42 and 43; Table 10, page 43; Table 11, page 44; Table 12, page 45; Table 13, page 45; Table 14, page 46). Because only one polymorph of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile is obtained through a variety of methods and solvents, one of ordinary skill in the art would reasonably infer that the crystal obtained from ‘683 would be the same polymorph: Form A. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Products of identical chemical composition cannot have mutually exclusive properties. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Thus, it is reasonable to infer that the crystal of Example 148 in ‘683 would give the same XRPD pattern, because the XRPD pattern is the fingerprint to Form A of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile. Thus, ‘683 teaches a crystalline compound having the formula:
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, characterized by an x-ray powder diffraction pattern with peaks at 13.4 ± 0.150 2θ, 14.0 ± 0.150 2θ, 15.2 ± 0.150 2θ, 19.3 ± 0.150 2θ, 20.0 ± 0.150 2θ and 21.2 ± 0.150 2θ.
Regarding claim 2, ‘683 teaches isolation of a white solid of
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([0516], [0517]). As ‘683 is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of ‘683 possesses the same XRPD pattern. Thus, ‘683 teaches the compound is characterized by an x-ray powder diffraction pattern with peaks at 6.7 ± 0.150 2θ, at 13.4 ± 0.15 2θ, 14.0 ± 0.15 2θ, 15.2 ± 0.15 2θ, 17.7 ±0.15 2θ, 18.1 ±0.15 2θ, 18.8 ± 0.15 2θ,19.3 ± 0.15 2θ, 19.8 ±0.15 2θ, 20.0 ±0.15 2θ, 21.0 ± 0.15 2θ, 21.2± 0.150 2θ, and 24.1 ± 0.150 2θ (claim 23 of ‘683).
Regarding claim 3, ‘683 teaches isolation of a white solid of
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([0516], [0517]). As ‘683 is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of ‘683 possesses the same XRPD pattern. Thus, ‘683 teaches the compound is characterized by an x-ray powder diffraction pattern with peaks at 6.7 ± 0.150 2θ, 10.7 ± 0.150 2θ, 13.4 ± 0.15 2θ, 14.0 ± 0.15 2θ, 15.2 ±0.15 2θ, 17.7 ± 0.15 2θ, 18.1 ± 0.15 2θ, 18.8±0.15 2θ, 19.3 ±0.15 2θ, 19.8 ± 0.15 2θ, 20.0 ±0.15 2θ, 20.7 ±0.15 2θ, 21.0 ± 0.15 2θ,21.2 ± 0.15 2θ, 24.1 ±0.15 2θ, 25.9± 0.150 2θ, 27.8 ± 0.150 2θ, and 30.6 ±0.15 2θ (claim 23 of ‘683).
Regarding claim 4, ‘683 teaches isolation of a white solid of
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([0516], [0517]). As ‘683 is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of ‘683 possesses the same XRPD pattern. Thus, ‘683 teaches the compound is characterized by an x-ray powder diffraction pattern with peaks at 6.7 ± 0.150 2θ, 10.7 ± 0.150 2θ, 13.4 0.15 2θ, 14.0 0.15 2θ, 15.2 ±0.15 2θ, 16.6 0.15 2θ, 17.7 0.15 2θ, 18.1 ± 0.15 2θ, 18.4 ±0.15 2θ, 18.8 0.15 2θ, 19.3 ±0.15 2θ, 19.8 ±0.15 2θ, 20.0 0.15 2θ,20.7 ±0.15 2θ, 21.0 ±0.15 2θ, 21.2 ±0.15 2θ, 24.10.15 2θ, 25.9 ±0.150 2θ, 26.3 ±0.150 2θ, 26.6 0.150 2θ, 27.0 0.150 2θ, 27.8± 0.150 2θ, and 30.6 ±0.15 2θ (claim 23 of ‘683).
Regarding claim 5, ‘683 teaches isolation of a white solid of
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([0516], [0517]). As ‘683 is reasonably interpreted to disclose a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile having Form A, it flows naturally that the crystal of ‘683 possesses the same differential scanning calorimetry endotherm onset. Thus, ‘683 teaches the compound is further characterized as having a differential scanning calorimetry endotherm onset at about 117 C (claim 23 of ‘683).
Regarding claim 6, ‘683 teaches a pharmaceutical composition comprising a crystal of been motivated to make such a selection, to predictably arrive at a composition of a crystal of 6-(3-(4,4-difluoro-4-(2-methoxypyridin-4-yl)butanoyl-3,8-diazobicyclo[3.2.1]octan-8-yl)nicotinonitrile and a pharmaceutically acceptable excipient (claim 24 of ‘683).
Regarding claim 7, ‘683 teaches a method of treating a neurodegenerative disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of compound (claim 25 of ‘683).
Regarding claim 8, ‘683 teaches the administration of one or more immunomodulatory agents (claim 26 of ‘683).
Regarding claim 9, ‘683 teaches one or more immunomodulatory agents are selected from: an IFN-β 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other SlP1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide (claim 27 of ‘683).
Regarding claim 10, ‘683 teaches a method of treating a demyelinating disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of compound (claim 28 of ‘683).
Regarding claim 11, ‘683 teaches the demyelinating disease is a demyelinating disease of the central nervous system (claim 29 of ‘683).
Regarding claim 12, ‘683 teaches the demyelinating disease is multiple sclerosis (claim 30 of ‘683).
Regarding claim 13, ‘683teaches the demyelinating disease is a demyelinating disease of the peripheral nervous system (claim 31 of ‘683).
Regarding claim 14, ‘683 teaches the administration of one or more immunomodulatory agents (claim 32 of ‘683).
Regarding claim 15, ‘683 teaches one or more immunomodulatory agents are selected from: an IFN-3 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other SlP1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide (claim 33 of ‘683).
Regarding claim 16, ‘683 teaches a method of treating a neuropathic disease, optionally a peripheral neuropathy, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of compound (claim 34 of ‘683).
Regarding claim 17, ‘683 teaches the neuropathic disease is diabetic neuropathy (claim 35 of ‘683).
Regarding claim 18, ‘683 teaches the administration of one or more immunomodulatory agents (claim 36 of ‘683).
Regarding claim 19, ‘683 teaches one or more immunomodulatory agents are selected from: an IFN-3 1 molecule; a corticosteroid; a polymer of glutamic acid, lysine, alanine and tyrosine or glatiramer; an antibody or fragment thereof against alpha-4 integrin or natalizumab; an anthracenedione molecule or mitoxantrone; a fingolimod or FTY720 or other SlP1 functional modulator; a dimethyl fumarate or other NRF2 functional modulator; an antibody to the alpha subunit of the IL-2 receptor of T cells (CD25) or daclizumab; an antibody against CD52 or alemtuzumab; an antibody against CD20 or ocrelizumab; and an inhibitor of a dihydroorotate dehydrogenase or teriflunomide (claim 37 of ‘683).
Regarding claim 20, ‘683 teaches a method of modulating muscarinic acetylcholine receptor Mi activity in a subject comprising administering to the subject (claim 38 of ‘683).
Conclusion
No claim is allowed.
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622