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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/US21/33746, filed 05/21/2021, which claims the priority benefit of PRO Application No. 63/146,556, filed 02/05/2021, of PRO Application No. 63/113,119, filed 11/12/2020, of PRO Application No. 63/030,213, filed 05/26/2020, and of PRO Application No. 63/029,364, filed 05/22/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/16/2025, and 01/30/2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant's election without traverse of Group I, drawn to a method of treating non-alcoholic steatohepatitis (NASH), with a species election of the statin atorvastatin in claims 1, 4, 6, 10, 15, 16, 27, and 28 in the reply filed 01/30/2026 is acknowledged.
Status of the Application
Claims 1-4, 6, 10, 15-16, 27-28, and 45-54 are pending. Claims 5, 79, 11-14, 17-26 and 29-44 been cancelled by applicant without prejudice or disclaimer. Claims have been withdrawn from further consideration as being drawn to a non-elected species. Claims 1, 4, 6, 10, 15, 16, 27, and 28 are examined herein insofar as they read on the elected invention and species.
Claim Objections
Claim 4 objected to because of the following informalities: Claim 4, line 2 contains the repeated phrase “orally administering”. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: Claim 10, line 2 contains the repeated phrase “orally administering”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The limitations of dependent claim 16 wherein the 25HC3S or salt thereof of independent claim 1 is further limited to a 25HC3S salt does not serve to further limit the scope of the claims. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements. This rejection may be overcome by amending claim 16 to indicate which salt form applicant intends.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 4, 6, 10, 15, 16, 27, and 28 rejected under 35 U.S.C. 103 as being unpatentable over Ren (US 2012/0264816A1) in view of Athyros (The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement).
The instant claims are directed to a method of treating non-alcoholic steatohepatitis (NASH) in a human subject comprising orally administering 5-cholesten-3,25-diol, 3-sulfate (25HC3S) or salt thereof in an amount ranging from 100 mg/day to 300 mg/day with a pharmaceutically acceptable carrier and the statin atorvastatin.
Ren et al. teach methods and compositions for the prevention and treatment of liver damage or disease in a subject in need thereof comprising administering 25-hydroxycholesterol-3-sulfate (25HC3S) to a subject (Abstract). Ren teaches an embodiment, 25HC3S is administered in an amount ranging from 0.1 mg/kg to 100 mg/kg, based on body mass of said subject [0010]. Ren also teaches a method for treating hyperlipidemia, fatty liver disease or malady resulting from hyperlipidemia or fatty liver disease wherein the malady is non-alcoholic steatohepatitis (NASH) [0012]. Ren also discloses an embodiment in which the subject being treated is a human [0067]. Ren also teaches “[t]he active ingredients may be mixed with excipients which are pharmaceutically acceptable and compatible with the active ingredients. Suitable excipients are, for example, water, saline, dextrose, glycerol, ethanol and the like, or combinations thereof. In addition, the composition may contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and the like. If it is desired to administer an oral form of the composition, various thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders and the like may be added.” [0063] Ren also teaches a chemical synthesis of 25HC3S in which the sodium salt of 25HC3S is obtained [0075].
However, Ren et al. fail to disclose administering a statin for the treatment of NASH.
Athyros et al. teach studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and that physicians should consider statin use in those with NAFLD/ NASH (Abstract). Athyros discloses atorvastatin in table 1 “Analysis of the principal studies with statins on human NAFLD/NASH: the 5 post hoc analyses of randomized controls trial and the 5 biopsy-based studies are discussed in the text” which show a significant reduction in cardiovascular disease events (CVD) and mortality/liver transplants as clinical outcomes. (pg. 21)
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to orally administering 100-300 mg/day of 25HC3S for the treatment of NAFLD/NASH as taught by Ren in combination with Athyros’s disclosure of atorvastatin which are both administered for the treatment of NAFLD/ NASH because a skilled artisan . Examiner notes a 50 kg human would require a 25HC3S dose of between 5-5,000 mg pre day base on the teachings of Ren. See MPEP 2131.03 and MPEP 2144.05 (I-II).
A person of ordinary skill in the art would have been motivated to administer 100-300 mg 25HC3S, a medication administered for the treatment of liver damage or disease in a combination therapy with atorvastatin, a medication used in the treatment of NASH to a human patient for the treatment of NASH because of the cumulative effects of combining both medications would give a skilled artisan a reasonable expectation of success in treating NASH.
Conclusion
All claims are rejected, no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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