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
This application, filed 04/14/2023 is a National Stage entry of PCT/SG2021/050625, International Filing Date: 10/15/2021. PCT/SG2021/050625 claims foreign priority to 10202010254Q, filed 10/15/2020; and claims foreign priority to 10202012817S, filed 12/21/2020. Certified copies of the foreign priority applications are of record.
Status of Claims
Claims 19-32 are currently pending, claims 1-18 have been canceled.
Claims 19-32 were examined and are rejected.
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 27-28 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.
Claim 27 is replete with the phrases “such as” and “for example”. These phrases render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Similarly, claim 28 is rejected as it includes the phrase “such as”.
To provide compact prosecution, the claims were given the broadest claim interpretation and examined as if “such as” and “for example”, and the limitations following these phrases were not present.
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.
The factual inquiries 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 19 and 21-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perez Garcia, EP 2228367 A1, publ. 9/15/2010.
Perez Garcia teaches addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives, having activity as dihydroorotate dehydrogenase (DHODH) inhibitors (title & abstract; para [0001]). Perez Garcia teaches DHODH inhibitors to be known to be used in the treatment of diseases susceptible to improvement by inhibition of DHODH, such as autoimmune diseases (para [0002]). Perez Garcia teaches the addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives to be water soluble and non-hygroscopic, wherein the compounds have the following structural formula (para [0009-0010]):
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. Perez Garcia teaches in particular embodiments wherein the above described compounds are administered in a therapeutically effective amount for the treatment of autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel diseases (IBS), including Crohn’s disease and ulcerative colitis (para [0012], [0020], [0120]). Perez Garcia further exemplifies the compound 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as the meglumine, tromethamine, and L-arginine salts (para [0060], [0064-0066]). This compound is otherwise known as 2-(3,5-difluoro-3’-methoxybiphenyl-4-ylamino)nicotinic acid. Oral administration is taught (para [0121], [0126]), and a therapeutically effective amount is taught to range from 2-2000 mg/day, administered from one to four times per day (para [0136]). Perez Garcia exemplifies tablets comprising 100 mg or 300 mg. of the tromethamine salt of 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid (para [0139], [0141-0142]). Perez Garcia further teaches the compound can be administered in combination with one or more other therapeutic agents, including corticosteroids such as prednisone, purine nucleoside phosphorylase inhibitors such as forodesine HCl, and monoclonal antibodies such as interferon beta-1 (para [0115-0116]).
As such, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the instantly claimed method of treating an autoimmune disease such as IBS comprising orally administering the DHODH inhibitor, 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as an amine addition salt in an amount from 10 mg to 400 mg. once or twice daily, in view of the teachings of Perez Garcia. As discussed above, Perez Garcia teaches 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid in an amine salt for the treatment of autoimmune diseases such as MS and IBS as well as oral administration, wherein the effective dose ranges from 2-2000 mg/day, administered from one to four doses daily. Notably, Perez Garcia doesn’t teach combination therapy is required, therefore meeting the limitation of instant claim 19, wherein the compound is not administered in combination with methotrexate. However, Perez Garcia does teach the compound can be administered in combination with agents such as corticosteroids and a purine synthesis inhibitor, forodesine HCl. One of ordinary skill in the art would have therefore arrived at the instantly claimed method of treatment and have had a reasonable expectation of success.
Regarding instant claim 23, “wherein the autoimmune disease is characterized by aberrant T cell and/or B cell activation”, this is a characteristic of the autoimmune disease. As Perez Garcia teaches the treatment of autoimmune diseases, including inflammatory bowel disease, this feature would have been inherently present. Regarding instant claim 24, although Perez Garcia doesn’t explicitly teach treating “severe” autoimmune disease, Perez Garcia does teach treatment encompasses causing regression of the disease in a patient as well as alleviating symptoms of the disease in a patient (para [0018]). As such, one of ordinary skill in the art would have been motivated to have orally administered a therapeutically effective amount of 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as an amine addition salt to treat severe IBS that has not been controlled by other therapies, with the reasonable expectation that treatment with 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as an amine addition salt would have resulted in regression of the disease.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perez Garcia, EP 2228367 A1, publ. 9/15/2010 as applied to claims 19 and 21-32 above, and further in view of Turkyilmaz et. al., WO 2020005189 A2, publ. 1/2/2020.
The teachings of Perez Garcia as discussed previously are incorporated herein. Although Perez Garcia includes multiple sclerosis as one of the preferred autoimmune diseases to be treated, treatment of relapse-remitting MS is not explicitly taught.
Turkyilmaz teaches teriflunomide as a known DHODH inhibitor that is orally used for the treatment of relapsing-remitting MS (p. 1, lines 22-30).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the instantly claimed method of treating relapsing-remitting MS by orally administering the DHODH inhibitor, 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as an amine addition salt in an amount from 10 mg to 400 mg. once or twice daily, wherein the therapy is not combined with methotrexate, in consideration of the combined teachings of Perez Garcia and Turkyilmaz. Perez teaches the compound 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as an amine addition salt as a DHODH inhibitor for the treatment of autoimmune diseases including MS, along with oral administration at a daily dose that overlaps with the claimed range. Turkyilmaz further teaches another DHODH inhibitor, teriflunomide, is used for the treatment of relapsing-remitting MS. As such, one of ordinary skill in the art would have been motivated to have applied the method of treatment as taught by Perez Garcia for the treatment of relapsing-remitting MS, in light of Turkyilmaz’s teaching that another DHODH inhibitor is used for treating relapsing-remitting MS, and have had a reasonable expectation of success.
Claim Rejections-Nonstatutory 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 1-2, 23-26, and 29-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20-21, and 23-26 of U.S. Patent No. 8258308 B2 in view of Perez Garcia, EP 2228367 A1 and Turkyilmaz et. al., WO 2020005189 A2. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims encompass treatment of an autoimmune disease, multiple sclerosis, by administration of 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid. The patented claims are drawn to compounds of the following structural formula, and a composition comprising a compound as described:
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. The compound 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid is included within the structural formula shown above, having M=hydrogen or cation; G3=N; G4=CH; R1=hydrogen; G1=CRe; Ra, Rb=fluoro; G2=CRd; Rd=methoxy; and R2=hydrogen. While the patented claims don’t explicitly recite oral administration at a daily dose between 10-400 mg., or treatment of relapsing-remitting MS, it would have been prima facie obvious to have done so in view of the cited prior art. Perez Garcia teaches addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives, having activity as dihydroorotate dehydrogenase (DHODH) inhibitors (title & abstract; para [0001]). Perez Garcia teaches DHODH inhibitors to be known to be used in the treatment of diseases susceptible to improvement by inhibition of DHODH, such as autoimmune diseases (para [0002]). Perez Garcia teaches the addition salts of amines containing hydroxyl and/or carboxylic groups with amino nicotinic acid derivatives to be water soluble and non-hygroscopic, wherein the compounds have the following structural formula (para [0009-0010]):
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. Perez Garcia teaches in particular embodiments wherein the above described compounds are administered in a therapeutically effective amount for the treatment of autoimmune diseases such as multiple sclerosis and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis (para [0012], [0020], [0120]). Perez Garcia further exemplifies the compound 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid, as the meglumine, tromethamine, and L-arginine salts (para [0060], [0064-0066]). This compound is otherwise known as 2-(3,5-difluoro-3’-methoxybiphenyl-4-ylamino)nicotinic acid. Oral administration is taught (para [0121], [0126]), and a therapeutically effective amount is taught to range from 2-2000 mg/day, administered from one to four times per day (para [0136]). Perez Garcia exemplifies tablets comprising 300 mg. of the tromethamine salt of 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid. Perez Garcia further teaches the compound can be administered in combination with one or more other therapeutic agents, including corticosteroids such as prednisone, purine nucleoside phosphorylase inhibitors such as forodesine HCl, and monoclonal antibodies such as interferon beta-1 (para [0115-0116]). Turkyilmaz teaches teriflunomide as a known DHODH inhibitor that is orally used for the treatment of relapsing-remitting MS (p. 1, lines 22-30).
As such, it would have been prima facie obvious to have applied the method of the patented claims to treat relapsing-remitting MS as Turkyilmaz teaches another compound having DHODH inhibiting activity is used for treating this condition. Moreover, Perez Garcia teaches 2-[(3,5-difluoro-3’-methoxy-1,1’-biphenyl-4-yl)amino]nicotinic acid for treating autoimmune conditions such as MS by oral administration from one to four times daily, at a dose ranging from 1-2000 mg. For these reasons, the instant and patented claims are obvious variants of each other and are not patentably distinct.
Correspondence
Claims 19-32 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627