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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 22, 2026, has been entered.
Response to Arguments
Suggestions for Allowance:
If Applicant amends the claims to the following, it will overcome the cited prior art.
A method of treating non-alcoholic steatohepatitis in a patient in need thereof, the method consisting of administering a therapeutically effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, or tautomer thereof.
Such limitation to the transitional phrase will likely obviate the applicability of prior art that is directed to combination therapy.
In response to Applicant’s traversal of the rejection of record, the examiner responds.
Applicant argues that Wang teaches Bcl-2 inhibitors for treating liver cancers not NASH.
The examiner notes that Wang is cited to show that the claimed compound is a Bcl-2 inhibitor.
Applicant argues that Kwak teaches Bcl-2 inhibitors and Mcl-1 inhibitors are need to have a senolytic effect.
The examiner notes that even if this were the case, the instant claims are open-ended and do not exclude additional agent.
Applicant argues that Kwak picks and chooses NASH from many conditions.
The examiner notes that Kwak claims NASH (claim 22), describes NASH through (par.’s 286, 289-292) and includes a hepatic model of NASH. Prior art claim 22 recites:
22. The method of claims 1-16, wherein the senescence-associated disease or disorder is a liver disease, such as non-alcoholic steatohepatitis (NASH), primary biliary cholangitis (PBC), or primary sclerosing cholangitis (PSC).
Thus, there is limited picking and choosing to arrive at a method of using a Bcl-2 inhibitor to treat NASH.
Applicant argues that unexpected results are shown because a Bcl-2 inhibitor was not shown to treat NASH prior to this application.
The examiner notes that the claims are open-ended. The prior art teaches administering a Bcl-2 inhibitor with an Mcl-1 inhibitor to treat NASH. Thus, there is a reasonable basis to conclude that a known Bcl-2 inhibitor would treat NASH- if combined with a Mcl-1 inhibitor. Kwak teaches Bcl inhibitors and demonstrates that Bcl-2 inhibitors can be used in a method to treat NASH. The claimed agent is a Bcl-2 inhibitor as taught by the prior art. This established a reasonable expectation of success. Thus, treatment efficacy alone cannot constitute an unexpected result as compared to the closest prior art. The closest prior art includes Kwak which teaches administering Bcl-2 inhibitor to a subject with NASH.
As such, the rejections of record are maintained.
Status of the Claims
Claims 1, 3-5, 7, and 14-24 are pending and examined.
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.
Claims 1, 3-5, 7, and 14-24 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., (US2018/0354950), in view of Kwak et al., (US2021/0379078), in view of Liu et al., (US20190083459).
Wang teaches the following claimed compound at page 11. See compounds 6 and 13, e.g.
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451
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As such, the claimed compounds are known for treating diseases and disorders wherein Bcl-2 inhibition provides a benefit. See par. 2. They are Bcl-2 inhibitors. Cancers that can be treated include liver cancer and hepatocellular carcinoma, among others. See par.’s 156 and 160. The compounds can be administered once or more times daily in a dosage that ranges from 0.01mg to 10 mg, 100mg, or 500 mg, e.g. See par. 164. While the claimed isomers are taught in this case, “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.” In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious).
Wang does not teach using Bcl-2 inhibitors to treat other claimed liver conditions.
Kwak teaches treating senescence-associated diseases and disorders with a Bcl-2 inhibitor. See par.’s 17 and 22. The methods treat conditions including liver disease or disorders including NASH, primary biliary cholangitis (PBC), or primary sclerosing cholangitis (PSC). See par. 37. The treatment is to eliminate senescent cells that reside in and around the liver or site of disease. See par. 287. There is an increase in burden and distribution of senescent cells in mouse model of NASH that mirrors human patients. See par. 290. Further, the NASH model ablates pancreatic cells to induce metabolic diseases and insufficient insulin formation. See par. 289. There is an elevation of p16 cells though to progress disease into cirrhosis and HCC. The compounds of the invention can be used to treat or prevent liver disease at any stage including hepatitis, NAFLD, or NASH, e.g. See par. 292. Senolytic treatment will change AST and ALT scores, among others. See par. 293. Further, the disease or disorder to be treated can also be atherosclerosis. See prior art claim 18. Overall treatment can include atherosclerosis, liver disease, and kidney disease, as non-limiting examples. See par. 253. Chronic liver disease is a result of loss of hepatocytes, fibrosis, and ultimately an increased risk for liver cancer. Further, NASH and NAFLD and these can arise from a combination of metabolic disease, diet, and predisposition. See par. 286. See Hepatic Conditions discussion par.’s 285-293. Treatment can be shown by a reduction of fibrosis. See par. 291. With respect to atherosclerosis, claimed compounds can decrease lipid concentrations of atherosclerotic plaques. See par. 298.
Wang and Kwak do not teach obeticholic acid.
Liu teaches treating and preventing NAFLD, diabetes, cardiovascular diseases, hepatitis, liver fibrosis, liver cirrhosis, NASH, and hyperlipidemia by administering a farnesoid receptor agonist, wherein said agonist compound is obeticholic acid. See prior art claims 2 and 15. In one example 5 mg/kg obeticholic acid was administered. See Example 5.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Wang, Kwak, and Liu. One would be motivated to do so because Zhang teaches the claimed compounds to be inhibitors of Bcl-2. Kwak teaches using inhibitors of Bcl-2 to treat and prevent NASH, NAFLD, hepatitis, atherosclerosis, and others. Even further, Liu teaches administering obeticholic acid to treat and prevent NAFLD, diabetes, cardiovascular diseases, hepatitis, liver fibrosis, liver cirrhosis, NASH, and hyperlipidemia. "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). Further, in view of the known mechanism of Bcl-2 inhibition as well as understand the claimed agents to be result effective variables in achieving the same, it would obvious to arrive at the claimed dosages that are effective for treating claimed conditions. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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). This would include administering both medicines together, sequentially or otherwise, absent a known or expected drug-drug interaction (DDI). It would also yield an optimized dosage that would have an effect secondary to the administration of the same. This would include reducing fibrosis, ballooning, and inflammation, absent evidence to the contrary.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 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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/JARED BARSKY/Primary Examiner, Art Unit 1628
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