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
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to Taiwan application 112144931, filed 11/21/2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Response to Amendments/Arguments
Applicant’s amendments and arguments filed 8/18/26 are acknowledged and have been considered. Claims 1, 3, and 7-9 are pending. Claims 2, 4-6, and 10-20 have been cancelled.
Applicant has incorporated the limitation of claim 5 into claim 1, amongst other amendments. In light of the amendment, and upon further consideration, the rejection is withdrawn in favor of the new rejections set forth below. The new combinations address the relationship of the instant compound, lumichrome, to ascorbic acid, which applicant had pointed to being absent in the analysis of the art previously.
In view of the amendments, the 112b rejection of claim 7 is withdrawn.
Claim Objections
Claims 1,3, and 7-10 are objected to because of the following informalities: The claims use non-standard terminology “medical composite”, which appears to be a substitute for “pharmaceutical composition”, and appears that it may be an artifact of the translation of a foreign document. Appropriate correction is required.
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.
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) 1, 3, and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over HSAI (US 2001/0000028 A1) in view of ZABRECKY (US 2005/0123628 A1), QAIS (IDS 5/9/24) and MA (PTO-892 5/26/26).
The instant claims are drawn generally to treating NAFLD with lumichrome.
Hsai teaches treatment of treating chronic liver disease, chronic HCV, or NASH with a composition comprising ascorbic acid (e.g. claim 37). The ascorbic acid is administered between 500 and 10000 mg (e.g. claim 45), and the composition is in the form of a capsule (e.g. claim 1). In treating NASH, for 20 weeks subjects were given four 500 mg ascorbic acid capsules as part of the therapy (e.g. para [0304]). Hsai teaches the total daily doses are 500 to 10000 mg, and preferably 6000mg, ascorbic acid (para [0189]) and that it may be necessary to use dosages outside of the specified ranges. Hsai teaches the course of treatment can vary (para [0194]). Hsai teaches that the subject is preferably a human (e.g. para [0174]).
Zabrecky teaches a composition for the treatment of NASH comprising lecithin, vitamin B, and antioxidants (e.g. claim 1). Zabrecky teaches that the composition can contain vitamin B-2 (riboflavin), and that the antioxidant is at least one of vitamins C or E, “any preferably include other known antioxidants such as vitamin A and certain forms of selenium.” (para [0021]). Zabrecky furth states, “as with the B vitamin complex, analogs, precursors, functional metabolites,... may be used.” (para [0021]).
Qais teaches that lumichrome is an antioxidant having free-radical scavenging activity, and that it exhibited superior activity to ascorbic acid. Qais states that, “DPPH free radical scavenging assay is one of the commonly used method for measuring the antioxidant property of a substance.” (page 52) and from the testing, Qais determined that lumichrome “can be developed as a new potential antioxidant drug for treating the pathological states caused by oxidative stress.” (page 53).
Ma teaches that, “Nonalcoholic Fatty Liver Disease (NAFLD) is the most common chronic liver disease… Although the exact cause of NAFLD is not defined, recent studies have shown that oxidative stress (OS) due to insulin resistance and hepatic steatosis may be major causes of NAFLD and may play an important role in the progression to NASH [6]. The first stage of NAFLD/NASH is characterized by liver damage due to insulin resistance, increased fat load on hepatocytes [7].” (page 1 of 25). Ma further taches, “In the NAFLD patients, the overload intake of free fatty acids increases fatty acid f3-oxidation and electron transport chain activity in the mitochondria. This ultimately leads to an increased release of ROS as byproduct of metabolism. The lots of ROS can directly target mitochondria, resulting in decreased energy metabolism, increased release of mtDNA and mitochondrial dysfunction.” (page 7 of 25). As a whole, Ma teaches that oxidative stress and excess ROS are key contributors to NAFLD progression, promoting hepatic steatosis, inflammation, hepatocyte injury, Kupffer-cell and stellate-cell activation, fibrosis, and progression to NASH; accordingly, Ma identifies antioxidant treatment as a potential therapeutic strategy.
While Hsai teaches treatment of NASH, a form of NAFLD, with enteral/oral compositions of antioxidants, Hsai does not teach the use of lumichrome. Zabrecky provides teachings that alternate antioxidants are contemplated for use in compositions to treat NASH, and Ma provides teachings that antioxidants are considered for treatment of NASH.
In light of the teachings of Qais that lumichrome is a better antioxidant than ascorbic acid and contemplates the use in therapeutics as an antioxidant, it would have been obvious to have substituted lumichrome for the ascorbic acid in the treatment of Hsai to treat NASH, with the expectation that a simple substitution would result in a composition with the same therapeutic effect. Alternatively, it would have been obvious to have added lumichrome to the antioxidant composition for treatment of NASH with ascorbic acid, to obtain, and use a composition with the very same properties. As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.” Further, with regards to the dose ranges, it would have been obvious to one skilled in the art at the time of invention to determine all optimum and operable conditions (e.g.dose administered), because such conditions are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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). See MPEP § 2145.05). Here, the prior art recognizes the variability of the amount of antioxidant to administer, and the artisan would recognize that based on patient responsiveness different dosages would be necessary.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Andrew D Kosar whose telephone number is (571)272-0913. The examiner can normally be reached Monday-Friday, 7am-3:30pm.
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/Andrew D Kosar/ Supervisory Patent Examiner, Art Unit 1625
