Detailed Action
Claims 5-6, 9-11, 13-14, 16-25, 29-31 are rejected and under examination.
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 .
Claim Rejections - 35 USC § 112
Claim 11 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. In claim 11, “anti-NASH compound” is not defined in the specification with reasonable clarity as to what entities the applicant is intending to reference.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the “written description” inquiry, is “whatever is now claimed” (See page 1117).
A review of the language of the claim indicates that these claims are drawn to an “anti-NASH compound”. A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the ingredients requires more than a mere statement that it is an anti-NASH compound.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984). Accordingly, stating that “Another embodiment provides a method of treating the patient with an amount of an anti-NASH compound effective to inhibit progression of, or to effect resolution of, NASH”, in the absence of knowledge as to what constitutes an anti-NASH compound, is not a description. In the instant case, on page 5, paragraph 023, Applicant discloses an “anti-NASH compound”. However, other than the mere mention on page 5, paragraph 023, wherein Applicant simply states “anti-NASH compound”, Applicant does not provide any examples of an anti-NASH compound.
There are no species of the claimed genus disclosed that is within the scope of the claimed genus.
One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus of what constitutes an “anti-NASH compound”. The specification does not clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed (see Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
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 5-6, 9-11, 13-14, 16-25, and 29-31 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 claim 5 are rendered uncertain by the phrase “comprises topically applying to the patient's skin an amount of an SCD-1 inhibitor compound effective to reduce the extent of fibrosis in the patient” in claim 5 because it is not clear whether the Applicant is claiming that the compound will reverse existing fibrosis or if the compound will reduce further development of fibrosis. 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.
The metes and bounds of claim 14 are rendered uncertain by the phrase “results in an improvement in the patient's liver condition associated with increased levels of liver triglycerides as determined by histology; or no worsening of the patient's liver condition associated with increased levels of liver triglycerides as determined by histology” because it is not clear whether the Applicant is claiming that the improvement or lack of worsening of the patient’s liver condition is associated with increased levels of liver triglycerides, or that the liver condition before and independent from the improvement, was already associated with increased levels of liver triglycerides. 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.
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 5-6, 9-11, 13-14, 16-25, and 29-31 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 a method of treating a patient with NASH and later-stage fibrosis using compound 25 as listed in the specification in table 1 and as shown below,
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does not reasonably provide enablement for a method of treating or preventing NASH and later-stage fibrosis or components thereof, using all the compounds that are currently claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
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: Claims 5-6, 9-11, 13-14, 16-25, and 29-31 are drawn to a method of treating a patient with NASH and with later-stage fibrosis which comprises topically applying to the patient's skin an amount of an SCD-1 inhibitor compound effective to reduce the extent of fibrosis in the patient, wherein the compound has the structure:
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wherein: X is 0; W is CH; Z is CH; and wherein each of R1, R2, and R3 is independently selected from the group consisting of H, C1 to C6 straight chain or branched chain alkyl, CF3, CH2CH2F, 0- (Cl-CE alkyl), and OCF3.
Additionally, claims 16-22 are further drawn to a method of prevention of NASH and later-stage fibrosis or components thereof.
However, the nature of the invention is complex in that the compounds as claimed are highly varied and prevention of NASH and later-stage fibrosis, or components thereof, is not a guaranteed or determinable outcome. The Applicant’s disclosure does not teach one skilled in the art how to use the claimed method of treatment with the full scope of compounds claimed, or prevention in general.
Breadth of the Claims: The claims are broad in that the claims recite methods for treatment and prevention using many compounds. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the Specification and Existence of Working Examples: The specification includes experiments conducted using one species (compound 25) in rat and human liver microsomes. However, no working examples are given for other species that the Applicant has claimed, or any instance of guaranteed prevention.
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped. It is known in the art that demonstration of activity of a single compound does not guarantee that same activity in an alternate compound. In addition, the development of NASH and later-stage fibrosis, or components thereof, is highly dependent on multiple unpredictable factors including individual genetic disposition, demographic, environmental exposures, and that any claims to prevent or guarantee prevention of diseases such as NASH and later-stage fibrosis, or components thereof, are undeterminable and not guaranteed.
Cruz-Monteagudo, M. Activity cliffs in drug discovery: Dr Jekyll or Mr Hyde, Elsevier, Vol. 19, no. 8, pp. 1069-1080 (Year: 2014) - explains that functional groups in combination can have unexpected effects on overall activity of a compound.
“Steatotic (Fatty) Liver Disease" [Online]. Cleveland Clinic. Published 2020. Retrieved from Internet on December 4, 2025. URL:https://my.clevelandclinic.org/health/diseases/15831-fatty-liver-disease#overview (Year: 2020) - explains that there are multiple causes of NASH contributing to an increased risk.
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 a method of preventing NASH and later-stage fibrosis, or components thereof, or a method of treating a patient with NASH and with later-stage fibrosis with the range of compounds claimed. In order to carry out the claimed invention, one of ordinary skill in the art would have to determine the activity of all claimed compounds to treat a patient with NASH and with later-stage fibrosis, and administer the claimed range of compounds as a regular, prophylactic dosing over the course of a long enough period of time under conditions where it would be certain that NASH and later-stage fibrosis, or components thereof, would develop, which would be an impossible experimental setup due to the duration and the lack of a true control group.
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 5-6, 9-11, 13-14, 16-25, 29-31 are not considered to be fully enabled by the instant specification.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 5-6, 9-11, 13-14, 16-25, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Kurikawa, N. (A Novel Inhibitor of Stearoyl-CoA Desaturase-1 Attenuates Hepatic Lipid Accumulation, Liver Injury and Inflammation in Model of Nonalcoholic Steatohepatitis, Biological and Pharmaceutical Bulletin, Vol. 36, no. 2 (February 1, 2013), pp. 259-267, in view of Li, J., et. al. (US Patent No. 8,242,286 B2; Issued 08/14/2012).
(Of Note: Applicant defines the patient receiving the claimed method to be any mammal, and claims any amount of medicament effective to reduce the extent of fibrosis in the patient. All references in this rejection are encompassed by the Applicant’s definitions.)
Regarding claims 5, 29, 30, and 31, Kurikawa teaches that SCD-1 is implicated in hepatic lipid accumulation (See e.g. page 259; paragraph 2), demonstrates that SCD-1 inhibition with an alternate compound reduces triglyceride accumulation in the liver of rats (See e.g. page 261; paragraph 5), and suggests SCD-1 as a promising target for the treatment of NASH (See e.g. page 259; Abstract).
However, Kurikawa does not teach the Applicant’s claimed compound and its activity as an SCD-1 inhibitor.
Li teaches the following structure, (S)-2-(4-(hydroxymethyl)phenoxy)-1-(3-(2-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)ethenone, which anticipates the Applicant’s structure (See e.g. col. 2; lines 40-50).
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Li also teaches that this structure has demonstrated activity as a stearoyl-CoА desaturase (SCD1) inhibitor (See e.g. col. 2; lines 30-37), topical application of the compound to the skin (See e.g. col. 2; line 67), and that SCD-1 is present in the liver of rats (See e.g. col. 18; lines 4-5).
It would have been obvious to one having ordinary skill in the art to combine Kurikawa’s teaching that SCD1 inhibition is beneficial in NASH and Li’s teaching of the Applicant’s claimed structure and its activity as an SCD1 inhibitor, as well as its topical application in a subject, to arrive at the Applicant’s claimed method of treating a patient with NASH and with later-stage fibrosis, by applying the Applicant’s claimed compound, (S)-2-(4-(hydroxymethyl)phenoxy)-1-(3-(2-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)ethenone, topically to a patient’s skin in an amount effective to reduce the extent of fibrosis in the patient.
Claims 6, 9, 10, and 13 require the subject of the method to satisfy certain thresholds in the NASH CRN fibrosis score. This is a routine scoring system used for scoring NASH and its symptom severity, and any improvement seen through this score would be an intrinsic property of the method’s efficacy. It would have been obvious to one skilled in the art before the Applicant’s effective filing date, that the Applicant’s compound would be effective in treating NASH and fibrosis in a patient, and so any specific scoring thresholds and time constraints regarding the NASH CRN fibrosis score claimed to characterize the patient’s outcomes would have been arrived at by one skilled in the art through routine experimentation in a patient using the NASH CRN fibrosis score.
Claim 11 requires the addition of an anti-NASH compound, which would have beneficial effects in treating NASH independent of administering the Applicant’s claimed structure. "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).
Claim 14 has been previously rejected to for containing indefinite language. In an effort to move prosecution forward, the Examiner will evaluate the claim to the extent that the subject’s liver condition at baseline is associated with increased levels of triglycerides, and that any improvements thereof are associated with decreased levels of triglycerides.
Claims 14, 16, 17, 18, 19, 20, 21, 22 requires improvement in liver triglycerides, which is a relevant biomarker in NASH assessment, as well as improvements in conditions related to NASH such as: ratio of lipid-containing to non-lipid containing hepatocytes, hepatic inflammation, fibrillar and matrix forming collagens, hepatic stellate cell activation, hepatocellular ballooning, hepatic steatosis. These are all known symptoms and conditions implicated in NASH and arise from a common mechanism affected by SCD1 inhibition, such that treatment of NASH through SCD1 inhibition would be expected to affect all of these intrinsic symptoms, and thus treating these symptoms with the Applicant’s claimed method are also obvious.
Claims 23-25 require certain ranges of body surface area to be treated by the Applicant’s claimed method, as well as certain frequencies of administration to a subject. Any specific ranges of body surface area or treatment frequency would have been arrived at by one skilled in the art through routine experimentation and optimization, once the mechanism of SCD1 inhibition of the Applicant’s claimed compound was identified as a result-effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis). Axonics, Inc. v. Medtronic, Inc., 73 F.4th 950, 957-58, 2023 USPQ2d 795 (Fed. Cir. 2023) (the court found an erroneous framing of the motivation inquiry led to an incorrect conclusion of nonobviousness). A "motivation to combine may be found explicitly or implicitly in market forces; design incentives; the ‘interrelated teachings of multiple patents’; ‘any need or problem known in the field of endeavor at the time of invention and addressed by the patent’; and the background knowledge, creativity, and common sense of the person of ordinary skill." Zup v. Nash Mfg., 896 F.3d 1365, 1371, 127 USPQ2d 1423, 1427 (Fed. Cir. 2018) (quoting Plantronics, Inc. v. Aliph, Inc., 724 F.3d 1343, 1354 [107 USPQ2d 1706] (Fed. Cir. 2013) (citing Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324, 1328 [92 USPQ2d 1849] (Fed. Cir. 2009) (quoting KSR, 550 U.S. at 418-21)). See MPEP § 2143 regarding the need to provide a reasoned explanation even in situations involving common sense or ordinary ingenuity. See also MPEP § 2144.05, subsection II, B.
In the instant case, Kurikawa and Li provide adequate teaching, suggestion, and motivation to use the Applicant’s compound taught by Li to be an SCD1 inhibitor, in methods to treat NASH as taught by Kurikawa to be a disease state affected by SCD1 inhibitors. It is known that SCD1 is present in the liver and is implicated in the development of NASH and later-stage fibrosis. The Applicant’s claimed structure is known to inhibit SCD1 and be capable of topical absorption. It is also known in the art that compounds that are able to absorb topically are exposed to systemic blood flow and thus capable of affecting end-targets systemically, to an extent characterized by the dose. One skilled in the art would have been motivated and have had reasonable expectation of success to combine the teachings in these references prior to the applicant’s effective filling date. Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to combine these teachings and develop the claimed method of treating a patient with NASH and with later-stage fibrosis through topically applying the claimed structure.
Conclusion
No claims are allowed.
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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
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628