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 .
Request for Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 3, 2026 has been entered.
Application and Claims Status
In the amendment as filed on July 25, 2024, applicants have amended no claims; cancelled no claims; and added new claims 23-24. Therefore, claims 21-24 are currently pending and presently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 06/03/2026 is in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Withdrawn Rejections
Claim Rejection – 35 USC § 103
Applicant’s arguments with respect to claim(s) 21-24 have been considered but are moot because the new ground of rejection does not rely on U.S. Patent No. 8,871,790 or D’Arcangelis et al. applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed on 6/3/2026 with respect to U.S. Patent No. 8,614,238 (hereinafter, the “ ‘238 Patent”) have been fully considered but they are not persuasive.
Applicant argues, on page 7 of Remarks filed on 6/3/2026, that “the ‘238 Patent would not have led one of skill in the art to have a reasonable expectation of success for treating acne” because Applicant claims the lead compound in the ‘238 Patent had significant adverse effects on the skin in an animal model of Female Wistar Rats (e.g. cranial alopecia, reddened/swollen skin of mouth and eyelid), and thus teaches away from the use of a FASN inhibitor in the treatment of acne. Examiner respectfully disagrees for the following reason:
The reported adverse skin events of the “238 Patent cited by Applicant occur when compound is administered at the highest dose (‘238 Patent, col 18, lines 3-5): ““Beginning with day 4 of treatment, at the highest dose effects on skin and coat of the animals could be detected.” One of ordinary skill in the art would recognize that there are dose-escalation studies across any therapeutic treatment in order to find a drug’s proper therapeutic index, and this does not mean it is the dose of drug that will be administered thusly. It is simply part of the preclinical protocol to find the maximum therapeutic dose (MTD). Dose-escalation studies are, in fact, done in both animal models and human clinical trials.
Applicant argues, on page 7 of Remarks filed on 6/3/2026, that “two structurally unrelated FASN inhibitors [FT-4101 and BI 99179] developed by different companies both produced or anticipated the same effects demonstrates that these would be recognized as class-wide, target-mediated consequences of FASN inhibition” and “identified skin and eye effects as ‘potential on-target risks” (emphasis added). An on-target risk (versus off-target risk) is exactly the sort of risk that would not discourage or teach away use of the compound. On-target toxicity is predictable and dose-dependent (the whole point of phase 1 is to find a working tolerable dose). On-target toxicities suggest that adjusting the dose could alleviate the problems while still maintaining a therapeutic effect and minimizing harm—the so-called therapeutic window. On the other hand, off-target effects are unpredictable, not dose-dependent, and would require discontinuation of the drug in order to manage any adverse event. Thus, the suggestion of an on-target risk would not discourage or teach away the claimed use of the compounds for alleviating the symptoms of acne, but rather, offers the promise that dose-adjustment could circumvent any reported adverse event.
Double Patenting Rejection
Applicant’s arguments with respect to claim(s) 21-24 have been considered but are moot because the new ground of rejection does not rely on U.S. Patent No. 8,871,790 or D’Arcangelis et al. applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed on 6/3/2026 with respect to U.S. Patent No. 8,614,238 (hereinafter, the “ ‘238 Patent”) have been fully considered but they are not persuasive for the same reasons discussed in above 103 discussion.
New Objections/Rejections
Claim Objections
Claim 24 is objected to for the following minor informality: the word “composition” is misspelled. Appropriate correction is required.
Claim Rejection – 35 USC § 112(b)
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.
Claim 21-24 are rejected as vague. The claims generally recite, “a method of alleviating symptoms of acne in a subject in need thereof, the method comprising administering to the subject a fatty acid synthase inhibitor having a formula of…”. Is Applicant administering any amount (which could be suboptimal and have no therapeutic benefit), or a therapeutically effective amount? Examiner recommends adding a “therapeutically effective amount” into the claim language.
Claim Rejection – 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.
Claims 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Infante et al. (“Initial Report of a First-In-Human Study of the First-In-Class Fatty Acid Synthase (FASN) Inhibitor, TVB-2640”, published November 19, 2014)(hereinafter, ‘Infante’) and Kley et al. (US 8,614,238 B2, published December 24, 2013, cited by Examiner on 892 Form filed 2/4/2026)(hereinafter, the ‘238 Patent’) in view of Press Release 2014 (“3-V Biosciences Announces Presentation of First Human Clinical Data for Lead Oral FASN Inhibitor Candidate at EORTC-NCI-AACR 2014”, published November 19, 2014)(hereinafter, “Press Release 2014”).
Infante discloses the initial report of a potent, reversible FASN inhibitor, TVB-2640, as a first-in-class lead oncology candidate in a Phase 1 study of 14 patients. TVB-2640, also referred to as denifanstat, is the same compound of instant claims 21-24, as evidenced by MedChemExpress.
Press Release 2014 writes, “the preliminary results we have seen from this TVB-2640 Phase 1 trial have demonstrated favorable safety, tolerability, and pharmacokinetics” and, “other toxicities reported were generally mild and, notably, there were no signs of gastrointestinal or hematological toxicity, and no QTc prolongation noted” and later, refer to this study as “initial positive clinical feedback.”
Indeed, Applicants were even optimistic about the results of this Phase 1 study and include, in Press Release 2014, the forward-looking statement: “As we approach dose selection for Phase 2 and initiate expansion cohorts…”. This suggests company optimism to continue with TVB-2640 development and certainly does not teach away its use.
Infante and Press Release 2014 do not teach TVB-2640 for use in the treatment of acne.
‘238 Patent teaches, “FAS is also highly expressed in human sebocytes, the lipid producing cells of the sebaceous glands. Acne is the most common disorder involving the sebaceous gland. The pathogenesis of acne involves lipid (over)production by the sebaceous gland and it has been reported that inhibitors of mammalian FAS inhibit the production of sebum in sebocytes...Acne cannot occur without sebum lipids. There is an unmet medical need in the treatment of acne for agents that reduce sebum production.” (col 1, lines 36-44). Altogether, ‘238 Patent teaches that inhibition of FAS would reduce sebum production, which would treat acne.
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time before the effective filing date of the claimed the invention, to practice the disclosed utility of ‘238 Patent with the claimed compound and pharmaceutical composition of Infante and Press Release 2014 to treat acne. A person of ordinary skill in the art would have been motivated to use the FAS inhibitor of Infante for treating acne because the compound is particularly known as a FAS inhibitor. Further ‘238 Patent teaches that FAS is highly expressed in sebocytes, acne is caused by lipid overproduction of sebaceous glands, and that inhibitors of mammalian FAS inhibit the production of sebum. Thus, treatment of the underlying etiology (sebum overproduction) would have a reasonable expectation of ameliorating the symptom (acne).
Thus, said claims are obvious.
Applicant’s arguments of an “unexpected result” (Declaration, filed 6/3/2026, pages 5-6, para 13-15) of an improved safety profile when compared to known FAS inhibitors is not found persuasive,
Applicant writes:
13. The safety profile of denifanstat in this trial was favorable and, in my opinion, unexpected in light of the references of record. All denifanstat-related adverse events were mild or moderate in severity; there were no denifanstat-related Grade 3 or 4 adverse events, no adverse event-related permanent discontinuations, and no deaths. There were no denifanstat related
serious adverse events. Only two categories of treatment-emergent adverse events had an
incidence of 5% or more: dry eye syndrome (5.5%) and dry skin (5.2%). Critically, hair thinning,
the adverse event that Beysen and the Examiner's '238 Patent collectively establish as a
recognized on-target class-wide concern for systemically administered FASN inhibitors ------ was
observed in only a single patient out of 240, was Grade 1 in severity, and resolved within eight
weeks while the patient remained in the study without any change in dose. (See, Exhibit E,
Sagimet Press Release, dated February 2, 2026).
14. The near-complete absence of alopecia in the ASC40-304 trial was, in my opinion, not
predictable from the references of record. As set forth above, the FT-4101 clinical team
specifically adopted intem1ittent dosing "to minimize anticipated safety issues with systemic (dry skin, dry eye and alopecia)" (Beysen, p. 708), yet FT-4101 was still ultimately discontinued. The '238 Patent, cited by the Examiner, discloses that a structurally distinct FASN inhibitor produced progressive cranial alopecia and cutaneous lesions in preclinical rat studies (Col. 18, lines 5-9), and Batchuluun confirms that the field recognized "FAS inhibition is associated with alopecia" (Batchuluun, p. 300). Based on the collective teachings of these references, a skilled artisan would not have predicted that denifanstat, administered continuously at 50 mg once daily for up to 52 weeks, a regimen more aggressive than the intermittent schedule adopted for FT-4101, would produce hair thinning in only one of 240 patients, with that single event resolving within eight weeks without any change in dose. This result was, in my opinion, unexpected in light of the references of record.
15. The efficacy results in ASC40-304 were equally unexpected, in my opinion, in light of the
references of record. Subjects showed continued improvements beyond those observed at 12
weeks across all secondary efficacy endpoints which generally did not plateau until week 24,
including: the number of subjects achieving an Investigator's Global Assessment (IGA) score
decrease of at least 2 points from baseline; the number of subjects dropping from an IGA score
of 3 to a score of 0 (clear) or 1 (almost clear); the percentage reduction in total skin lesion count;
and the percentage reduction in inflammatory skin lesion count. (See, Exhibit E, Sagimet Press
Release, dated February 2, 2026).
Examiner responds:
Infante discloses, on slide 9, that there were no dose limiting toxicities (DLT) at 60 or 120 mg/m2 dosages of TVB-2640 (the instantly claimed compound), and that even at dosages where there were DLTs, they were reversible. Any skin-related adverse events occurred at a dose of 120 mg/m2, resolved approximately 35 days later (slide 12-13), and were mostly Grade 1 (mild symptoms). Any ocular-related adverse events occurred at 240 mg/m2, resolved approximately 5 days later (slides 14-15), and were mostly Grade 1 and Grade 2 (mild to moderate symptoms). These ophthalmological and skin-related toxicities were occurring at doses much higher than the projected maximum therapeutic dose (MTD). Again, these adverse events are for drug dosages tested at 60, 120, and 240 mg/m2 in a Phase 1 study, where the primary purpose of a Phase 1 study is to identify any potential adverse events from a drug and determine the MTD that patients can safely receive. By necessity and definition, this determination requires approaching and exceeding the upper limits of the safety threshold to determine the safety profile of a given drug, and therefore, any Phase 1 reporting of serious adverse events must be viewed in light of the fact that Phase 1 studies may potentially breach these safety limits.
On slide 17, Infante discloses “skin and eye toxicity are on-target and reversible”. This is an important point because, as explained above (see: Withdrawn Rejections: USC § 103 Rejection), on-target toxicity is predictable and dose-dependent. On-target toxicities suggest that lowering the dose could alleviate the problems while still maintaining a therapeutic effect and minimizing harm.
Furthermore, Infante discloses, on slide 17, that “exposures at 60 mg/m2 exceed those found to be efficacious in preclinical models”. This is an important point: plasma levels of TVB-26450 after oral administration exceed the threshold for preclinical efficacy, even at the lowest tested dose (60 mg/m2) in vivo, suggesting that the dose could be further lowered whilst still maintaining efficacy and reducing likelihood of any on-target adverse event. This is illustrated by Infante, on slide 16, shown below:
PNG
media_image1.png
497
709
media_image1.png
Greyscale
The ASC40-303 double-blind trial cited by Applicant to demonstrate an “unexpected result” requires oral administration of denifanstat at a 50 mg once daily dose (see page 5, Declaration, filed 6/3/2026). This 50 mg dose is well below the doses tested in the Examiner’s cited Phase I study that led to AEs, and this highlights the Examiner’s conclusion that there was ample room to lower the lowest tested dose to mitigate adverse events, which indeed was the case in the ASC40-303 trial.
Altogether, the prior art of Infante suggests the mitigation of skin- or eye-related adverse events was entirely predictable and not an unexpected result. Infante reports no DLTs at 60 mg/m2, mild to moderate adverse events (the same reported for Applicant’s cited ASC40-303), and on-target toxicities at high doses that were resolved after discontinued drug use. Further, the lowest dose (60 mg/m2) exceeded the threshold for preclinical safety, suggesting the dose de-escalation could mitigate any on-target adverse events.
Regarding “unexpected results”, Examiner refers to MPEP 716.02(d), which states:
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (emphasis added)
In the instance case, the scope of the claim is not commensurate in scope with the alleged unexpected result.
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 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 18 of copending Application No. 19/709,813 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant application is drawn to a method of alleviating the symptoms of acne in a subject in need thereof, the method comprising administering to the subject the fatty acid synthase inhibitor known as denifanstat, or a pharmaceutically acceptable salt thereof; or administering a pharmaceutical composition comprising denifanstat, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
Claim 18 of reference application ‘813 is drawn to the same method: a method of treating acne in a subject in need thereof, the method comprising administering denifanstat (emphasis added).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-24 are rejected on the ground of nonstatutory double patenting as being
unpatentable over at least claims 20 and 21 of U.S. Patent No. 8,871,790 B2 in view of ‘238 Patent. Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating acne of instant independent claims 21-22 overlap in claimed matter with at least claim 20 and the disclosed utility in the reference disclosure of the issued U.S. patent.
In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001
(Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference
disclosure to determine the overall question of obviousness in a nonstatutory double patenting context.
See also Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008);Geneva
Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir.
2003).
Here, the same compounds are recited in both the instant application and the reference patent.
‘790 Patent discloses, (col 17, lines 46-51), “the present disclosure provides methods of treating a condition characterized by disregulation of a fatty acid synthase function in subject, the method comprising administering to the subject in need of such treatment an effective amount of a compound of any one of the Structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI)”, where instantly claimed compound reads on at least one of Structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI).
‘790 Patent does not claim a method of treating acne using the compound of instant claims 21-24. As with the explanation for the USC § 103 rejection above, ‘238 teaches that a FAS inhibitor reduces sebum production, where excess sebum production by the sebaceous glands is associated with acne.
The ordinary artisan would recognize as obvious that determination of whether acne is treatable
with an FAS inhibitor is present, per instant claims 21-24, is implicit in the patented claim in view of Sun
Pharmaceutical Industries, LTD. v. Eli Lilly and Company which states the following: “Similarly, in Pfizer,
the earlier patent claimed several compounds and the specification disclosed their use in treating
inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see 5,563,165 (“’165
patent”), at [57], col.1 11.11-14, col.3 11.3-27. The later patent then claimed a method of using these
compounds for treating inflammation, inflammation-associated disorders, and specific inflammation
associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent
No. 5,760,068 (“’068 patent”) col.97 1.49- col. 108 1.29. After rejecting the patentee’s objection to our
consideration of the specification of the earlier patent, we determined that the later patent “merely
claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier]
patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later
patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent
was invalid for obviousness-type double patenting. Id. at 1368.
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, at the time before the effective filing date of the claimed the invention, to practice the disclosed utility of ‘238 Patent with the claimed compounds and pharmaceutical composition: treating acne. A person of ordinary skill in the art would have been motivated to use the compound of ‘238 Patent for inhibiting FAS activity and use it to treat acne, which is another condition that can be ameliorated through inhibition of FAS activity.
Conclusion
All claims are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/L.A.B./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
Prosecution Insights