DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Status of the Claims
Claims 1-11 are pending. Claims 10 and 11 are withdrawn. Claims 1-9 are under consideration in this action.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9) in the reply filed on November 10, 2025 is acknowledged.
Claims 10 and 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 10, 2025.
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 1-6 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 treating cirrhosis, does not reasonably provide enablement for preventing cirrhosis. 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.
An analysis based upon the most relevant Wands factors is set forth below.
To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993),. See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman (230 USPQ 546, 547 (Bd. Pat App Int 1986)). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and (8) the breadth of the claims.
Breadth of Claims
The claims are broad in that the claims encompass prevention of cirrhosis regardless of the cause. Applicant defines “prevention” to mean inhibiting the occurrence of a disorder or a disease in a subject who has never been diagnosed as having the disorder or disease, but is likely to suffer from such disorder or disease (P.G. Pub., para.0024). The definition encompasses subjects who have diseases and disorders with no known causes, which can cause cirrhosis.
Nature of the Invention/State of the Prior Art
The invention encompasses the scope of prevention of cirrhosis, by administration to subject in need thereof a composition comprising a compound of Formula I as shown in claim 1, or a pharmaceutically acceptable salt thereof. However, the instant application is not enabled for the full scope of preventing cirrhosis because the causes of some disorders or diseases that result in cirrhosis are unknown.
For example, Mayo Clinic (Primary biliary Cholangitis; © 1998-2026) discloses that primary biliary cholangitis is an autoimmune disease in which the bile ducts are inflamed and slowly destroyed. Ongoing inflammation in the liver can lead to bile duct inflammation and damage known as cholangitis. At times, this can lead to cirrhosis (p.1, Overview). Mayo Clinic discloses that it is not clear what causes primary biliary cholangitis (p.1, Causes). Thus, because the cause of primary biliary cholangitis is unknown, absent evidence to the contrary, cirrhosis in subjects with primary biliary cholangitis, for example, would not able to be prevented.
Level of One of Ordinary Skill & Predictability/Unpredictability in the Art
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
There is a general lack of predictability in the pharmaceutical art. In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970).
Guidance/Working Examples
While Applicant discloses examples of administration of ML323 to mice to demonstrate, for example, control of hepatic fibrosis, a decrease in liver weight, a decrease in liver function indicators in blood, and reduction in expression of hepatic fibrosis inducers and in turn control of inflammation and fibrosis of liver tissue (e.g., P.G. Pub., para.0083-0093), such results are indicative to treatment or amelioration of the claimed liver diseases, not prevention. There appears to be no guidance or working examples on the prevention of cirrhosis, particularly in subjects having diseases or disorders with no known cause but are associated with cirrhosis.
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, 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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Chun et al. (Chun) (WO 2019/027293 A1; published Feb. 7, 2019; citations from English machine translation) and Currie (US 2009/0312302 A1; published Dec. 17, 2009).
Chun discloses a pharmaceutical composition for preventing or treating obesity comprising ML323 or a salt thereof as an active ingredient; and a functional health food composition for preventing or improving obesity (abstract).
With regards to Claims 1-3, Chun discloses a method for preventing or treating obesity comprising administering to a subject a pharmaceutical composition comprising ML 323 (reading on instant claim 1’s compound of Formula 1 wherein R1 is C1 alkyl, R2 is hydrogen, and R3 is an isopropyl group) as an active ingredient (p.1, para.3 to p.2, para.1). The composition may be administered to mammals such as rats, mice, livestock, and humans in various routes (p.4, para.10).
Chun discloses that ML323 is effective against obesity (p.3, para.6-8). Specifically, the ML323 can inhibit the activity and/or expression of USP1 (ubiquitin specific protease 1). In addition, the ML323 may be used for various factors that inhibit lipid synthesis, lipid accumulation, or differentiation of adipocytes such as FASN (fatty acid synthase), PPARɣ (Peroxisome Proliferator Receptor gamma), C/EBPα (CCAAT-enhancer-binding proteins) or FABP4 (fatty acid binding protein 4), thereby preventing or treating obesity (p.4, para.4).
The dosage of the pharmaceutical composition may be from 0.0001 to 2,000 mg/kg per day. The preferred dosage of the pharmaceutical composition for preventing or treating obesity varies depending on the condition of the patient, the body weight, the degree of disease, the drug form, the administration route, and the period, but can be appropriately selected by those skilled in the art (p.4, para.9).
With regards to Claims 5 and 6, the instant Specification discloses treatment with ML323 at concentrations of 0, 1, 5, 10, and 25 µM (para.0068). The instant Specification discloses that ML323-administered mice showed a decrease in levels of AST and ALT in the blood (para.0091; Fig.4) and a decrease in expression levels of CCl2, TGF-β, and F4/80 in liver tissue compared to the control (para.0093; Figs. 5A and 5B).
Chun discloses that the concentration of the ML323 may be 0.1 to 100 µM (p.3, para.4). Because the prior art disclosed range of ML323 overlaps with the concentrations disclosed in the Specification as having shown the actions recited in the instant claims 5 and 6, absent evidence to the contrary, Chun’s composition discussed above will also demonstrate the actions recited in the instant claims 5 and 6.
With regards to Claims 7-9, Chun also discloses providing a health functional food composition for preventing or ameliorating obesity comprising ML323 (reading on instant claim 7’s compound of Formula 1 wherein R1 is C1 alkyl, R2 is hydrogen, and R3 is an isopropyl group) as an active ingredient (p.3, para.5-6). In the health functional food composition, the ML323 is used as an additive for health functional food, and may be added as is or may be used together with other foods or food ingredients (p.4, para.13 to p.5, para.4).
Chun does not appear to explicitly disclose wherein the method is for preventing or treating liver disease selected from the group consisting of steatohepatitis, hepatic fibrosis, and cirrhosis (Claim 1), wherein the steatohepatitis is non-alcoholic steatohepatitis (Claim 4), or wherein the method is for ameliorating a liver disease selected from the group consisting of steatohepatitis, hepatic fibrosis, and cirrhosis (Claim 7). Currie is relied upon for this disclosure. The teachings of Currie are set forth herein below.
Currie discloses that non-alcoholic fatty liver disease (NAFLD) describes a spectrum of liver diseases ranging from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH) with progressive fibrosis and liver failure. Hyperglycemia with or without evidence of hyperlipidemia is commonly associated with NAFLD. All of the stages of NAFLD have in common the accumulation of fat in the liver cells (para.0003).
Currie discloses NASH as “the lynchpin” between hepatic steatosis and cirrhosis in the spectrum of NAFLD. In NASH, the fat accumulation is associated with varying degrees of inflammation and fibrosis. Among the conditions most commonly associated with NAFLD is obesity (para.0003).
Currie disclose that 6 to 15 million Americans have NASH. Left untreated, the condition can lead to cirrhosis. General recommendations for treatment of NAFLD include improving metabolic risk factors by controlling diet and exercise, and reducing alcohol intake (para.0004).
With regards to the preambles of Claims 1 and 7 and the limitation of Claim 4, as discussed above, Chun discloses administration of a pharmaceutical composition or a health functional food composition comprising ML323, which is known to inhibit, inter alia, lipid synthesis and lipid accumulation, to prevent or treat obesity. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the teachings of Chun and Currie administer Chun’s pharmaceutical composition or health functional food composition comprising ML323 to subjects who have, or are at risk of, obesity and also have, or are predisposed to have, NAFLD, such as NASH, or looking to prevent NASH. One of ordinary skill in the art would have been motivated to do so as obesity is known as a disorder which is associated with NAFLD such as NASH. Furthermore Currie discloses that in NASH, fat accumulation is associated with varying degrees of inflammation and fibrosis, and Chun discloses that ML323 is known to inhibit lipid synthesis and lipid accumulation. Thus, ML323 would treat and ameliorate an aspect of NASH. One of ordinary skill in the art would have had a reasonable expectation of success in doing so as obesity is among the conditions most commonly associated with NAFLD and Currie disclose that NASH discloses that fat accumulation is associated with varying degrees of inflammation and fibrosis, and ML323 is known to be used to prevent or treat obesity and is known to inhibit lipid synthesis and lipid accumulation.
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Conclusion
Claims 1-9 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MONICA A. SHIN whose telephone number is (571)272-7138. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM EST).
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/MONICA A SHIN/Primary Examiner, Art Unit 1616