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 371 of PCT/CN2022/081686 03/18/2022. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN-202110298570.3, filed on 03/19/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Examiners Response to Traversal
Examiner finds Applicant’s argument persuasive and is withdrawing restriction between product and method, based on current claims, in light of formula (I) being free of the art.
Election/Restrictions
The Examiner thanks Applicant’s representative, Liangang Ye, for electing Group I, corresponding to claims 1-9, 11-15, 17, and 18, drawn to a compound of formula (I), as well as electing the compound species Example 1, on 2/12/2026. As noted previously, Examiner is withdrawing restriction between product and method.
Status of Claims
Claims 1-9, and 11-18 are pending and under examination.
Allowable Subject Matter
Claim 15 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 1-8 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.
The metes and bounds of claims 1-8 are rendered uncertain by the recitation of Rc in the context of Ring A in claim 1. Claim 1, and the dependent claims 2-8, recite a variable Rc as an optional substitution on ring A. Ring A is defined to include various ring structures such as phenyl, 5 to 6 membered heteroaryl, which contain sp2 hybridized carbon atoms incapable of being substituted by double-bond additions such as =O and =N-C1-3 alkoxy. The lack of clarity renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 11-14, and 16-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for example compounds 1, 2, 3, 4, 5, 6, 7, 8, and 9 of formula (I), as well as a method of reducing LDL-C levels in rat plasma by administering example compound 1 (WX001) to rats, does not reasonably provide enablement for the full-scope of compounds of formula (I), or of any of the rejected claims depending therefrom, or a method of treating Non-alcoholic steatohepatitis in all subjects using the full-scope of compounds of formula (I). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
(Of Note: Example compound 2 is enabled by working example disclosing synthesis, but does not read on any of the current claims, as written.)
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: The nature of the invention is complex in that claims 1-9, 11-14, and 16 are drawn to a broad range of compounds of formula (I), as well as a method of treating non-alcoholic steatohepatitis in a subject in need thereof, comprising: administering the broad range of compounds of formula (I) or the pharmaceutically acceptable salt thereof according to claim 1 to the subject.
However, the Applicant only discloses the synthesis of select compounds of formula (I), including example compounds 1, 2, 3, 4, 5, 6, 7, 8, and 9. Further, Applicant only demonstrates that example compound 1 (WX001), lowers LDL-C levels in rat plasma. The claims are not commensurate in scope to what the Applicant discloses.
Breadth of the Claims: The claims are broad in that the claims recite a broad range of compounds of formula (I), as well as a method of treating non-alcoholic steatohepatitis in a subject in need thereof, comprising: administering the broad range of compounds of formula (I) or the pharmaceutically acceptable salt thereof according to claim 1 to the subject.
However, the Applicant only discloses the synthesis of select compounds of formula (I), including example compounds 1, 2, 3, 4, 5, 6, 7, 8, and 9. Further, Applicant only demonstrates that example compound 1 (WX001), lowers LDL-C levels in rat plasma. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
For further illustration of the breadth of the species claimed by the Applicant, shown below is Applicant’s formula (I), followed by two varying species of the Applicant’s formula (I).
The last structure shown contains group additions that are not exemplified by way of working example, in contrast to that of the second structure shown, which was the Applicant’s original elected species fully exemplified by synthesis steps shown in the specification.
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Guidance of the Specification and Existence of Working Examples: The specification describes synthesis for select example compounds 1, 2, 3, 4, 5, 6, 7, 8, and 9. Further, Applicant only demonstrates that example compound 1 (WX001), lowers LDL-C levels in rat plasma.
However, no working examples are given for synthesis of the full-scope of compounds of formula (I), or of any of the rejected claims depending therefrom. Further, no working examples are given for treatment of a subject with established non-alcoholic steatohepatitis, using the full-scope of compounds of formula (I), or of any of the rejected claims depending therefrom.
While it is noted that the applicant has shown synthesis for select species of compounds of formula (I), as well as data showing a lowering of LDL-C in rat plasma, Applicant is not enabled for the full-scope of compounds of formula (I), or of any of the rejected claims depending therefrom, or a method of treating Non-alcoholic steatohepatitis in any and all subjects using the full-scope of compounds of formula (I).
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped.
In regards to the Applicant’s enablement for select species, and in light of the broad range of species, including non-exemplified groups and substitutions as illustrated previously in the Breadth of the Claims portion of this rejection, it is known in the art that synthesis of one species of a genus, does not necessarily enable one in the art to synthesize any and all species within that genus, without undue experimentation (MPEP 2164.08).
In regards to the Applicant’s enablement for a method of use of the claimed compounds, structural changes of biologically active compounds can lead to unpredictable changes to their activity, as taught by Roy, Kunal, and Arkaprava Banerjee. Activity Cliffs. SpringerBriefs in Molecular Science, Cham, Springer Nature Switzerland, 2025. Accessed 16 Mar. 2026.
Further, it is known in the art that reduction of LDL-C alone, observed in a subject population without non-alcoholic steatohepatitis at baseline, is not sufficient to enable treatment of non-alcoholic steatohepatitis, as claimed. Applicant does not provide a definition as to what constitutes “treatment”, nor a subject for treatment, and a mere lowering of LDL-C in rat plasma is not understood in the art to be the standard of measuring the treatment of non-alcoholic steatohepatitis in all subjects.
Harrison, S.A., (A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis), The New England Journal of Medicine, Vol.390, no.6, pp. 497-509 (Year: 2024) – teaches that the primary endpoints for determining treatment efficacy in non-alcoholic steatohepatitis include evaluations of hepatocellular ballooning, lobular inflammation, NAFLD activity, all associated with a scoring system. Subjects with baseline non-alcoholic steatohepatitis are evaluated and scored in these categories as a measurement of treatment and disease progression. While Harrison notes that LDL-C was a secondary endpoint, this further gives context and provides associative value to the primary endpoints of the study, as is not understood to be sufficient on its own, to be enabling of treatment of non-alcoholic steatohepatitis.
Amount of Experimentation Necessary: The quantity of experimentation necessary to carry out the claimed invention is high, as the skilled artisan could not rely on the prior art or instant specification to teach how to make the full-scope of compounds of formula (I), or of any of the rejected claims depending therefrom, or a method of treating Non-alcoholic steatohepatitis in any and all subjects using the full-scope of compounds of formula (I).
In order to carry out the claimed invention, one of ordinary skill in the art would have to
determine synthesis steps for the full-scope of compounds of formula(I), as well as determine treatment, as claimed, requiring administration of the full-scope of compounds claimed to the full-scope of subjects claimed.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 1-9, 11-14, and 16 are not considered to be fully enabled by the instant specification.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OROD MOTEVALLI whose telephone number is (571)272-6026. The examiner can normally be reached Monday - Friday 10:00AM - 6:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OROD MOTEVALLI/ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628