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 .
Status of the Claims
Per Applicant’s amendment to the claims, submitted on 12/04/2023, claims 11 and 15-17 are amended, and claims 1-10 are canceled. Currently, claims 11-17 are pending in the instant application.
Priority
The instant application claims priority to provisional application 63/218,032, filed on 07/02/2021, and is a 371 of PCT/US2022/033471, filed on 06/14/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/04/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 15 is objected to because of the following informalities: Spelling. The instant claim recites “where in”. The recitation should be amended to recite “wherein” as a single word. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: Spelling. The instant claim recites “where in”. The recitation should be amended to recite “wherein” as a single word. Appropriate correction is required.
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.
Claim(s) 11-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glicklich (WO 2016/112075 A1) in view of Guerard (Basic & Clinical Pharmacology & Toxicology, 2016, 118, 356–368).
Claim 11 recites a method of treating an S1P1 receptor-associated disorder in a patient having mild, moderate, or severe hepatic impairment, the method comprising: administering to the patient having mild, moderate, or severe hepatic impairment an oral dosage form comprising a dose of Compound 1 or a salt thereof equivalent to 1 mg to 5 mg of Compound 1, wherein the dose is not adjusted for the patient having mild, moderate, or severe hepatic impairment, wherein said Compound 1 is (R)-2-(7-(4- cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]lndol-3-yl)acetic acid.
Glicklich teaches a method of treating S1P1 receptor associated disorders by administration of (R)-2-(7-(4- cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]lndol-3-yl)acetic acid in an amount between about 1.5 to about 2.5 mg (page 1, lines 30-34)1. Furthermore, Glicklich suggests oral forms of administration (page 74 claim 35)2. Both the condition being treated and the compound being administered are identical in the teachings of Glicklich. Glicklich, however, does not explicitly teach the method wherein the patient has mild, moderate, or severe hepatic impairment. However, it would be obvious to treat a patient also having hepatic impairment because Guerard teaches the administration of S1P1 receptor modulators to patients suffering from hepatic impairment.
Guerard provides a study wherein patients suffering from mild, moderate, or severe hepatic impairment were administered an oral dose of 10 mg of the S1P1 receptor modulator ponesimod (page 357)3. Guerard’s findings indicate that, when compared to healthy control individuals, subjects having hepatic impairment had increased ponesimod AUC0-inf and half-life, with the magnitude of said increases corresponding to the severity of impairment (page 359)4. Furthermore, Guerard indicates that subjects having moderate and severe hepatic impairment show higher AUC0-inf for ponesimod metabolites. The results are generally summarized in the following Fig. 1 A-C:
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Guerard’s findings generally indicate that patients having hepatic impairment are subject to greater exposure to administered ponesimod when compared to healthy patients not having hepatic impairment. Given the teachings of Guerard, it would be obvious to modify the teachings of Glicklich because:
One of ordinary skill would reasonably expect that (R)-2-(7-(4- cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]lndol-3-yl)acetic acid (i.e., etrasimod) would have similar effect with regards to hepatic impairment as ponesimod as both are the same class of compound (i.e., S1P1 receptor modulators)
There would be reasonable expectation that administering etrasimod to a patient suffering from hepatic impairment would provide greater exposure and potentially greater efficacy
Accordingly, it would have been prima facie obvious at the time of invention for a person of ordinary skill in the art to combine the teachings of Glicklich and Guerard to arrive at the method of the instant claim.
Claim 12 further limits the method of claim 11 wherein the patient has mild hepatic impairment.
As discussed previously, Guerard teaches the treatment of patients having mild hepatic impairment.
Claim 13 further limits the method of claim 11 wherein the patient has moderate hepatic impairment.
As discussed previously, Guerard teaches the treatment of patients having moderate hepatic impairment.
Claim 14 further limits the method of claim 11 wherein the patient has severe hepatic impairment.
As discussed previously, Guerard teaches the treatment of patients having severe hepatic impairment.
Claim 15 further limits the method of claim 11 wherein the dose comprises an amount equivalent to 2 mg of Compound 1.
Glicklich provides an example wherein a double blind study is conducted. One of the dosing cohorts is indicated to have been provided 2 mg doses of Compound 1 for 21 days (page 64 line 4)5.
Claim 16 further limits the method of claim 11 wherein the dose comprises an amount equivalent to 3 mg of Compound 1.
Glicklich provides an example wherein a double blind study is conducted. One of the dosing cohorts is indicated to have been provided 0.5 mg doses of Compound 1 for 7 days, then escalated to 3 mg doses of Compound 1 for the following 14 days (page 64 lines 5-6)6.
Claim 17 further limits the method of claim 11 wherein the S1P1 receptor-associated disorder is selected from the group consisting of ulcerative colitis, atopic dermatitis, alopecia areatea, eosinophilic esophagitis, and Crohn's disease.
Glicklich teaches the treatment of S1P1 associated disorders such as ulcerative colitis and Crohn’s disease (page 36 lines 3-8)7.
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 11-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/722,707 (reference application) in view of Glicklich (previously referenced). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are overlapping in subject matter and are obvious variants of one another.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 11 of the instant application recites a method of treating an S1P1 receptor-associated disorder in a patient having mild, moderate, or severe hepatic impairment, the method comprising: administering to the patient having mild, moderate, or severe hepatic impairment an oral dosage form comprising a dose of Compound 1 or a salt thereof equivalent to 1 mg to 5 mg of Compound 1, wherein the dose is not adjusted for the patient having mild, moderate, or severe hepatic impairment, wherein said Compound 1 is (R)-2-(7-(4- cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]lndol-3-yl)acetic acid.
Claim 1 of the reference application recites a method of treatment of an S1P1 receptor-associated disorder in a subject, said method comprising administering (R)-2-(7-(4-cyclopentyl-3- (trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indo3-yl)aceticadid. (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, to said subject, wherein the subject is also being administered a hormone treatment.
As can be seen in the recitations above, both claims are directed towards the treatment of the same conditions (i.e., S1P1 receptor associated disorder) by administering of the same compound (Compound 1). The main difference between the claims being that the reference application recites the co-administration of a hormone treatment. Looking towards the teachings of Glicklich, Glicklich teaches the treatment of S1P1 receptor associated disorders by administration of a compound identical to Compound 1. Furthermore, Glicklich teaches that said compound may be administered alongside a corticosteroid such as prednisone or budesonide (page 29 lines 11-14)8. Under broadest reasonable interpretation, corticosteroids such as prednisone and budesonide are considered as hormones, and administration of such hormones would be considered as hormone therapy. Given that Glicklich teaches the combination administration of Compound 1 and hormones in the form of corticosteroids, it would have been obvious for a person of ordinary skill in the art to combine each of these elements to arrive at the invention of the reference application.
Conclusion
Claims 11-17 are rejected.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “Provided is a method of treatment of a sphingosine 1-phosphate subtype I (S1P1) receptor associated disorder comprising prescribing and/or administering to an individual in need thereof a standard dose of (/?)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-l,2,3,4- tetrahydrocyclopenta[b]indol-3-ylJacctic acid (Compound I), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, in an amount equivalent to about 1.5 to about 2.5 mg of Compound I.”
2 “wherein the Compound I, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is formulated as a capsule or tablet suitable for oral administration.”
3 “One tablet of10 mg ponesimod was administered in the morning of day 1 in a fasted state.”
4 “AUC 0–∞ and t1/2 of ponesimod increased in individuals with HFI compared to healthy individuals, in a manner related to the severity of the hepatic impairment.”
5 “Cohort 3 was dosed with 2.0 mg for 21 days.”
6 “Cohort 5 was dosed with 0.5 for 7 days and then with 3.0 mg (by administering both a I mg formulation and a 2 mg formulation) for 14 days.”
7 “In some embodiments, the sphingosine 1-phosphate subtype I (S1P1) receptor-associated disorder is selected from: a disease or disorder mediated by lymphocytes, an autoimmune disease or disorder, an inflammatory disease or disorder, ankylosing spondylitis, biliary cirrhosis, cancer, psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn’s disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, ulcerative colitis, type I diabetes, hypertensive nephropathy, glomerulosclerosis, myocardial ischemia-reperfusion injury and acne.”
8 “In some embodiments, the individual also is administered a therapeutic dose of an oral corticosteroid therapy. In some embodiments, the corticosteroid is prednisone, e.g., prednisone at a dose < 20 mg/day, or an equivalent steroid. In some embodiments, the corticosteroid is budesonide, e.g., at a dose < 9 mg/day, or an equivalent steroid.”