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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/18/2026 has been entered.
Status of Claims
Claims 1, 3-5, 13, 17-18, 29-30, 48-51, and 53-56 are pending.
Priority
Instant application 17/924,101, filed 11/08/2022 claims priority as follows:
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Information Disclosure Statement
All references from IDS(s) received 12/29/2025, 01/15/2025, 05/11/2026, and 06/18/2026 have been considered unless marked with a strikethrough.
Response to Amendment/Arguments
The amendment filed 06/18/2026 has been entered. Applicant has amended claims 1, 3, 4, 13, 48, and 53. Claims 2, 6-12, 14-16, 19-28, 31-47, and 52 are cancelled.
Claims 13, 47-48, and 52-53 were previously rejected under 35 U.S.C. 112(d) as being of improper dependent form. In view of the amendment filed 06/18/2026, applicant has overcome the rejection under section 112(d) raised in the Office action dated 03/18/2026. Therefore, the previous rejection under 35 U.S.C. 112(d) is withdrawn.
Claim Rejections - 35 USC § 112 - New
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 13, 48, and 53 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 13 recites the method of claim 1, wherein the doses are orally administered at a frequency ranging from once weekly for a period of at least 14 days to three times a day for a dosing period of at least 7 days. Claim 13 is indefinite because it is unclear what the “frequency range” covers. At the low-frequency end of the range, the claim recites “once weekly for a period of at least 14 days”. At the high-frequency end of the range, the claim recites “three times a day for a period of at least 7 days”. It is unclear when the minimum dosing period should transition from 14 days to 7 days in the recited range. Is the minimum period of at least 14 days only required when the doses are administered once weekly?
For example, if the dosing frequency is twice weekly for a period of 7 days, should this read on the frequency range in claim 13? Or is it only if the dosing frequency is twice weekly for a period of 14 days? What if the dosing frequency is twice daily for a period of 7 days? It is unclear which of these dosing frequencies read on the recited range and which do not, because it is unclear where the transition between the minimum period of “at least 14 days” and the minimum period of “at least 7 days” occurs in the range.
Claims 48 and 53 are indefinite for the same reasons articulated above. Therefore, claims 13, 48, and 53 are rejected.
Claim Rejections - 35 USC § 103 – Maintained
In view of the cancelation of claims 47 and 52 in the amendment filed 06/18/2026, the statement of rejection has been modified to remove claims 47 and 52.
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.
Claims 1, 3-4, 12-13, 48, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over:
KIM (Emerging Trends Conference: Emerging Trends in Non-alcoholic Fatty Liver Disease. 2017; cited previously); as evidenced by
PUBCHEM (Larsucosterol. https://pubchem.ncbi.nlm.nih.gov/compound/11583880); and in view of
KEMP (EASL International Liver Congress. 2017; cited previously).
KIM teaches that DUR-928 (which is 25HC3S as evidenced by PUBCHEM) exhibits anti-inflammatory and anti-fibrotic activity in a mouse model of NASH. KIM teaches orally administering daily doses of 10 or 50 mg/kg DUR-928 for a period of four weeks (page 2, “Dosing regimen”). Additionally, KIM teaches the following conclusions of the study (page 6, “Summary and Conclusions”):
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The differences between KIM and the instant claims are that (i) KIM discloses administering DUR-928 to mice rather than human subjects; and (ii) KIM discloses doses in units of mg/kg rather than mg.
However, KEMP teaches that pre-clinical data have demonstrated that DUR-928 is well tolerated and can reverse certain histopathological changes associated with Non-alcoholic Steatohepatitis (NASH); and that previous studies in healthy subjects indicated that DUR-928 was well-tolerated with no significant drug-related adverse events (page 1, “Introduction”). Further, KEMP teaches orally administering DUR-928 to biopsy-confirmed human NASH patients in a dose of 50 mg or 200 mg (page 2, “Methods”), and teaches that such doses were well tolerated (page 3, “Results”).
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (G), it would have been prima facie obvious to modify the method of KIM to treat human subjects having NASH using the doses taught by KEMP. A person having ordinary skill would have been motivated to modify KIM in view of KEMP’s teaching of doses that are safe and tolerable in human subjects, and in view of the improvement in biomarkers disclosed by KEMP. The modification would have resulted in a method comprising administering a plurality of doses at a dosing frequency of once per day, over a period of at least 28 days, in a dose of 50 mg or 200 mg to human subjects with NASH.
In addition to the individual teachings identified in the cited references, please also note that differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. In the instant case, the dose of 25HC3S and the dosing period of 25HC3S are considered result-effective variables which, absent a showing of criticality, a person having ordinary skill could have optimized by routine experimentation.
Therefore, in view of the foregoing, claims 1, 3-4, 13, 48, and 53 are prima facie obvious.
Claims 5, 17-18, 49-50, and 54-55 are rejected under 35 U.S.C. 103 as being unpatentable over:
KIM as evidenced by PUBCHEM, in view of KEMP applied to claims above, and further in view of
REN (US 20100273761 A1; cited in IDS).
The teachings of KIM in view of KEMP are disclosed above and at least those teachings are incorporated herein by reference.
With respect to claim 5, the difference is that KIM and KEMP are silent about the human subject having serum triglycerides greater than or equal to 200 mg/dL prior to treatment.
However, REN teaches 25HC3S to treat and prevent of conditions associated with high levels of serum lipids, wherein serum lipids include cholesterol and triglycerides (see e.g. claims 3-9 and para. [0010]). In particular, REN teaches treating the condition NASH (see e.g. claim 9), and teaches that the terms “high lipid level” and “high triglyceride level” generally related to cholesterol levels in the serum in the range of about 200 mg/dl or more, and triglyceride levels in the serum greater than 150 mg/dl or more (see e.g. [0055]).
Finding of prima facie obviousness
Applying KSR example rationale (G), it would have therefore been prima facie obvious to modify the method of KIM in view of KEMP to administer 25HC3S to human subjects having serum triglycerides greater than or equal to 200 mg/dL prior to treatment. A skilled artisan would have been motivated to modify the method of KIM in view of KEMP because REN teaches that 25HC3S is effective for lowering high triglyceride levels and for treating lipid-associated inflammation in a patient with NASH.
Therefore claim 5 is prima facie obvious.
With respect to claims 17-18, 49-50, and 54-55, the difference is that KIM and KEMP are silent about administering 25HC3S in a formulation comprising a pharmaceutically acceptable carrier, or administering 25HC3S as a salt.
However, it is routine in the pharmaceutical arts to administer compounds in formulations comprising a carrier, and to administer compounds as pharmaceutically acceptable salts. Moreover, REN teaches that 25HC3S may be administered in a pharmaceutically acceptable formulation including suitable carriers, or as pharmaceutically acceptable salts (see para. [0058]).
It would have therefore been prima facie obvious to formulate 25HC3S in the method taught by KIM in view of KEMP as a salt or with a carrier.
Therefore claims 17-18, 49-50, and 54-55 are prima facie obvious.
Claims 29-30, 51, and 56 are rejected under 35 U.S.C. 103 as being unpatentable over:
KIM as evidenced by PUBCHEM, in view of KEMP applied to claims above, and further in view of
HARADA (US 20160030378 A1, cited in IDS).
The teachings of KIM in view of KEMP are disclosed above and at least those teachings are incorporated herein by reference.
With respect to claims 29-30, 51, and 56, the difference is that KIM and KEMP are silent about the human subject taking a lipid lowering drug or statin selected from those in the claims.
However, the lipid lowering drugs and statins recited in the claims were previously taught in the prior art for treating NASH. For example, HARADA teaches compositions and methods for treating NASH, and teaches those recited in the instant claims for treating NASH (see e.g. para. [0222], para. [0230], para. [0275], para. [0286]).
Finding of prima facie obviousness
As recognized in MPEP 2143, examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results.
Moreover, as recognized by MPEP § 2144.06(I):
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Therefore, applying KSR example rationale (A), it would have been prima facie obvious to combine 25HC3S with the lipid lowering drugs and statins taught by HARADA to treat patients with NASH. As noted above, the motivation to combine flows logically from their having been individually taught in the prior art for treatment of the same disorder(s).
Accordingly, claims 29-30, 51, and 56 are prima facie obvious.
Response to Arguments
In the Remarks filed 06/18/2026 (“Remarks”), applicant argues that (i) Kemp does not provide a reasonable expectation that administration of DUR-928 according to the presently claimed dosing regimen would achieve meaningful therapeutic effects in NASH and (ii) Example 1 of the present application provides empirical evidence of the superior results of this specific claimed dosage for treating NASH. Applicant additionally argues that (iii) the evidence demonstrates that a skilled artisan would not have had a reasonable expectation of predicting the claimed regimen or its therapeutic profile, and that (iv) neither Kim nor Kemp identifies the claimed dosage range as preferred.
Applicant's arguments have been fully considered but they are not persuasive.
With respect to point (i), applicant argues that Kemp does not provide a reasonable expectation but the rejection is based on the combination of Kim and Kemp as evidenced by Pubchem. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
With respect to point (ii) applicant argues that example 1 of the application provides empirical evidence of the superior results and states “The Office Action acknowledges that the 50 mg dose demonstrated greater reductions in serum triglycerides and greater improvements in liver stiffness than the higher-dose regimens. The Office Action nevertheless concludes that these results are not persuasive because higher doses showed advantages with respect to other biomarkers.”
Applicant’s characterization of the previous Office Action as acknowledging that “the 50 mg dose demonstrated greater reductions in serum triglycerides and greater improvements in liver stiffness than the higher-dose regimens” is not accurate. Regarding the reductions in serum triglycerides, the prior Office Action stated (Final Rejection 03/18/2026, page 11):
Moreover, applicant’s own data disclosed in the Specification contradicts the inverse dose-response argument. At page 34, the Specification states that patients with elevated baseline triglycerides (
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≥200 mg/dL; n=16) achieved a 24% reduction “across all dose groups at day 28 from baseline”, demonstrating that in the subpopulation targeted by claim 5, the triglyceride-lowering effect was dose-independent.
The evidence in the specification identified above suggests that the triglyceride-lowering effect was dose-independent. Applicant’s response does not address the discrepancy identified above, and characterizing the above passage as an acknowledgement by the Office that “the 50 mg dose demonstrated greater reductions in serum triglycerides than the higher-dose regimens” is not accurate.
Regarding the reductions in liver stiffness, the prior Office Action stated (Final Rejection , page 12):
Similarly, the inverse dose-response for liver stiffness (Fibroscan) disappears entirely in the ≥10% MRI-PDFF responder subgroup, where the 150 mg dose (-9%) matched or exceeded the 50 mg dose (-7%), and the 300 mg BID dose (-9%) performed equally well (Specification, page 34):
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Even accepting the low-dose advantage argument at face value, a 13% median reduction in serum triglycerides is of marginal clinical significance. Note that REN cited above defines a “high triglyceride level” as ≥150 mg/dL (REN, [0055]). A 13% reduction in a patient with triglycerides of 200 mg/dL yields a post-treatment level of approximately 174 mg/dL, which is still above the 150 mg/dL threshold considered clinically normal.
The evidence in the specification identified above suggests that the reduction in liver stiffness was dose-independent in the 43% of patients with ≥10% liver fat reduction by PDFF. Applicant’s response does not address the discrepancy identified above, and characterizing the above passage as an acknowledgement by the Office that “the 50 mg dose demonstrated greater improvements in liver stiffness than the higher-dose regimens” is not accurate. The present claims do not exclude the above-identified patient population. Applicant has also not addressed the examiner’s argument that a 13% reduction of triglycerides from 200 mg/dL is not practically significant when it yields a post-treatment level of approximately 174 mg/dL, which is still above the 150 mg/dL threshold considered clinically normal.
With respect to point (iii), applicant argues that the evidence demonstrates that a skilled artisan would not have had a reasonable expectation of predicting the claimed regimen or its therapeutic profile, but the prior art teaches a therapeutic regimen reading on the claims. While the prior art may not have measured each clinical endpoint measured in the present application, these endpoints are the result of administering the therapeutic regimen taught by the prior art to the claimed patient population (which is currently any patient who has NASH). If there is a subpopulation of patients who respond to an unexpectedly low dose, the present claims do not presently capture that subpopulation. Additionally, as noted in section 2 above, the results which are presented as “unexpected” for the lowest tested dose (50 mg) are contradicted by other evidence which shows that the higher doses (150 mg and 300 mg) achieve equivalent endpoints in patient populations reading on the claims.
With respect to point (iv), applicant argues that neither Kim nor Kemp identifies the claimed dosage range as preferred, but a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See MPEP 2123. Kim teaches daily doses of 10 or 50 mg/kg DUR-928 as effective; and Kemp teaches doses of 50 mg or 200 mg as safe. KEMP notes that a single oral dose of DUR-928 at both low (50 mg) and high (200 mg) doses resulted in reduction of CK-18 and ilirubin, especially in NASH patients; and concludes that the findings thereof support the ongoing development of DUR-928 as a potential therapy for NASH (Kemp, conclusions).
Reconsidering the entire record and weighing applicant’s arguments and evidence together with the evidence in favor of obviousness, the examiner finds that the rebuttal arguments and evidence do not outweigh the evidence supporting the rejection. Accordingly, in view of the foregoing, the rejection is maintained.
Double Patenting
In view of the cancelation of claims 47 and 52 in the amendment filed 06/18/2026, the statement of rejection has been modified to remove claims 47 and 52.
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.
Copending Application No. 17/924,103
Claims 1, 3-5, 13, 17-18, 29-30, 48-51, and 53-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 10, 15-16, 27-28, and 45-54 of copending Application No. 17/924,103 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims a method of treating NASH in a human subject comprising orally administering 25HC3S or salt thereof in an amount ranging from 100 mg/day to 300 mg/day. Dependent claims are directed to the same limitations recited in the instant claims (e.g. serum triglyceride levels, lipid lowering drugs, etc.). The claims therefore encompass subject matter overlapping with the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
In the Remarks filed 06/18/2026, applicant requests that the provisional nonstatutory double patenting rejection be held in abeyance until the claims are found allowable. The rejection is still deemed proper and is therefore maintained.
Conclusion
Claims 1, 3-5, 13, 17-18, 29-30, 48-51, and 53-56 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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