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 .
Applicant’s Response Dated August 6, 2026
In the Response dated August 6, 2026, claims 1-2, 7-9, 25, and 30-34 were amended, and claims 10-12 were canceled. Claims 1-2, 7-9, and 21-34 are pending. An action on the merits of claims 1, 7-9, and 21-34 is contained herein.
The rejection of claims 1-2, 25, and 30-34 under 35 U.S.C. 102(a)(1) as being anticipated by Amante, Daniel J., et al. "Uridine ameliorates the pathological phenotype in transgenic G93A-ALS mice." Amyotrophic Lateral Sclerosis 11.6 (2010): 520-530 (Amante) has been rendered moot in view of applicant’s amendment dated August 6, 2026. In the amendment, the claims were amended to limit the PGC-1a expression promoting agent to an agent comprising cytidylic acid, uridylic acid and/or cytidine. Amante does not explicitly teach a method comprising administration of cytidylic acid, uridylic acid and/or cytidine. Therefore, the rejection has been withdrawn; however, this deficiency would have been obvious in view of the teachings of Von Borstel US 2001/0005719 A1 (Von Borstel) for the reasons set forth herein below.
The rejection of claims 21, 23, 26, and 28 under 35 U.S.C. 103 as being unpatentable over Amante, Daniel J., et al. "Uridine ameliorates the pathological phenotype in transgenic G93A-ALS mice." Amyotrophic Lateral Sclerosis 11.6 (2010): 520-530 (Amante) as applied to claims 1-2, 10-12, 25, and 30-34 above, and further in view of Logroscino, Giancarlo, et al. "Amyotrophic lateral sclerosis: an aging-related disease." Current Geriatrics Reports 4.2 (2015): 142-153 (Logroscino) has been rendered moot in view of applicant’s amendment dated August 6, 2026. In the amendment, the claims were amended to limit the PGC-1a expression promoting agent to an agent comprising cytidylic acid, uridylic acid and/or cytidine. Amante does not explicitly teach a method comprising administration of cytidylic acid, uridylic acid and/or cytidine. Therefore, the rejection has been withdrawn; however, this deficiency would have been obvious in view of the teachings of Von Borstel US 2001/0005719 A1 (Von Borstel) for the reasons set forth herein below.
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) 1-2, 9, 25, and 30-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Amante, Daniel J., et al. "Uridine ameliorates the pathological phenotype in transgenic G93A-ALS mice." Amyotrophic Lateral Sclerosis 11.6 (2010): 520-530 (Amante) and Von Borstel US 2001/0005719 A1 (Von Borstel) in combination.
Claim(s) 1-2, 9, 25, and 30-34 are drawn to a method for suppressing or ameliorating muscle loss by promoting muscle-building in an individual suffering from a disease or condition causing or resulting in muscle loss, wherein the method comprises: (a) providing a food, feed, drug or quasi-drug comprising a PGC-1a expression promoting agent, wherein the PGC-1a expression promoting agent comprises cytidylic acid, uridylic acid and/or cytidine; (b) selecting an individual suffering from a disease or condition causing or resulting in muscle loss as an individual in need thereof; and (c) administering the food, feed, drug or quasi-drug to the individual in need thereof, wherein the administration to the individual in need thereof results in muscle-building, thereby suppressing or ameliorating the muscle loss.
Claims 25 and 30 are drawn to a method for promoting muscle-building in an individual in need thereof, wherein the method comprises: (a) providing a food, feed, drug or quasi-drug comprising a PGC-1a expression promoting agent, wherein the PGC-1a expression promoting agent comprises cytidylic acid, uridylic acid and/or cytidine; and (b) administering the food, feed, drug or quasi-drug to the individual in need thereof, wherein the administration to the individual in need thereof results in promoting muscle-building.
Claims 31-32 are drawn to a method for promoting muscle-building by promoting myotube cell differentiation in an individual in need thereof, wherein the method comprises: a) providing a food, feed, drug or quasi-drug comprising a PGC-1a expression promoting agent, wherein the PGC-1a expression promotinq agent comprises cytidylic acid, uridylic acid and/or cytidine; and (b) administering the food, feed, drug or quasi-drug to the individual in need thereof, wherein the administration to the individual in need thereof results in myotube cell differentiation, thereby promoting muscle-building.
Claims 33-34 are drawn to a method for increasing myotube cell diameter in an individual in need thereof, wherein the method comprises: a) providing a food, feed, drug or quasi-drug comprising a PGC-1a expression promoting agent, wherein the PGC-1a expression promotinq agent comprises cytidylic acid, uridylic acid and/or cytidine; and (b) administering the food, feed, drug or quasi-drug to the individual in need thereof, wherein the administration to the individual in need thereof results in increasing myotube cell diameter.
Amante teaches that amyotrophic lateral sclerosis (ALS) is a clinically severe, fatal neurodegenerative disorder characterized by a loss of upper and lower motor neurons, resulting in progressive muscle wasting and paralysis (page 520). Amante teaches that the goal of the current study was to determine whether uridine provided protective effects in the behavioral and neuropathological phenotype observed in the transgenic G93A-SOD 1 ALS mouse model (page 521). Uridine treatment extended survival in the G93AALS mice in a dose-dependent manner, compared to untreated G93A mice (Figure 1; page 524). The survival curve of the lowest uridine dose (0.5 g/kg) paralleled the untreated G93A mice. Although not significant, uridine administration at the 0.5 g/kg dose extended survival by 6.3% (untreated G93A mice: 126.4 ± 3.5 days; 0.5 g/kg uridine-treated G93A mice: 134.3 ± 3.5 days, p < 0.27). The 1 g/kg dose resulted in a significant extension of survival by 15.1 %, compared to the untreated G93A mice (145.5 ± 8.1 days, p < 0.01). The highest dose used in the study (2 g/kg) resulted in the greatest extension of survival at 17.4%, compared to the untreated G93A mice (148.4 ± 7.6 days, p < 0.01). Consistent with the survival data, body weight loss was significantly ameliorated from 112 days in both the 1 g/kg and 2 g/kg doses to end-stage disease compared to the untreated G93A mice (p < 0.01) (Figure 2). Amante teaches that this study tested the effect of uridine in the G93A mouse model of ALS based upon its potential neuroprotective properties (page 528). Compared to compounds that have entered into human clinical trials, based upon the efficacy found in preclinical mouse trials, uridine measures well against those potential therapeutic agents.
Amante differs from the instantly claimed invention in that Amante does not explicitly teach a method comprising administration of cytidylic acid, uridylic acid and/or cytidine; however, this deficiency would have been obvious in view of the teachings of Von Borstel US 2001/0005719 A1 (Von Borstel).
In the instant case, the references may be combined to show obviousness because Amante and Von Borstel are each drawn to methods for treatment and prevention of diseases, developmental delays, and symptoms related to mitochondrial dysfunction comprising the administration of a pyrimidine nucleotide precursor. They are from the same field of endeavor, and/or are reasonably pertinent to a method for suppressing or ameliorating muscle loss by promoting muscle-building in an individual suffering from a disease or condition causing or resulting in muscle loss.
Von Borstel teaches that administration of pyrimidine nucleotide precursors is effective in treatment of a large variety of symptoms and disease states related to mitochondrial dysfunction [0042]. Von Borstel teaches that tissue pyrimidine nucleotide levels are increased by administration of any of several precursors [0043]. Uridine and cytidine are incorporated into cellular nucleotide pools by phosphorylation at the 5' position; cytidine and uridine nucleotides are interconvertible through enzymatic amination and de-amination reactions. Compounds, compositions, and methods of Von Borstel are useful for treatment of ALS, for reversing or slowing the progression of clinical Symptoms [0134 – 0135]. “Pyrimidine nucleotide precursors” in the context of Von Borstel are intermediates in either the de novo or salvage pathways of pyrimidine nucleotide synthesis that enter into pyrimidine synthesis either distal to DHODH (e.g. orotate) or which do not require DHODH activity for conversion to pyrimidine nucleotides (e.g. cytidine, uridine, or acyl derivatives of cytidine or uridine) [0041].
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
It would have been obvious to substitute uridine employed in the method for treating ALS of Amante with cytidine in view of the teachings Von Borstel. Von Borstel teaches that pyrimidine nucleotides (e.g. cytidine, uridine, or acyl derivatives of cytidine or uridine) may be used to treat ALS. Von Borstel further teaches that cytidine and uridine nucleotides are interconvertible through enzymatic amination and de-amination reactions. The simple substitution of one known element (pyrimidine nucleotide precursor(s)) for another to obtain predictable results is prima facie obvious. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.
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 would have been 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.
All of the instant limitations are taught by the combination of Amante and Von Borstel. A person of ordinary skill in the art would have had a reason to combine the teachings of Amante and Von Borstel. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Amante and Von Borstel. Thus, claims 1-2, 9, 25, and 30-34 would have been obvious based on the preponderance of the evidence.
Claim(s) 21, 23, 26, and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Amante, Daniel J., et al. "Uridine ameliorates the pathological phenotype in transgenic G93A-ALS mice." Amyotrophic Lateral Sclerosis 11.6 (2010): 520-530 (Amante) and Von Borstel US 2001/0005719 A1 (Von Borstel) in combination as applied to claims 1-2, 9, 25, and 30-34 above, and further in view of Logroscino, Giancarlo, et al. "Amyotrophic lateral sclerosis: an aging-related disease." Current Geriatrics Reports 4.2 (2015): 142-153 (Logroscino).
Amante and Von Borstel in combination differs from the instantly claimed invention in that said combination does not explicitly teach a method wherein the individual is elderly and/or suffering from muscle loss; however, these deficiencies would have been obvious in view of the teachings of Logroscino.
In the instant case, the references may be combined to show obviousness because Amante, Von Borstel, and Logroscino are each drawn to the treatment of ALS. They are from the same field of endeavor, and/or are reasonably pertinent to a method for suppressing or ameliorating muscle loss by promoting muscle-building an individual suffering from a disease or condition causing or resulting in muscle loss.
Logroscino teaches that ALS is an age-related disease with age incidence curve similar to other age-dependent neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease (page 142). The peak of incidence is in the eighth decade and declines thereafter, first in men and then in women. In the majority of cases, ALS is sporadic while 5–10 % of the disease is familiar.
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
Amante and Von Borstel in combination teaches or reasonably suggests the administration of cytidine to an individual having ALS. Amante teaches or reasonably suggests that ALS is characterized by progressive muscle wasting; Logroscino teaches that ALS is an age-related disease with peak of incidence in the eighth decade and declines thereafter. Thus, it would have been prima facie obvious to employ the method of Amante wherein the individual is elderly and/or suffering from muscle loss as these conditions are characteristic of ALS patients.
All of the instant limitations are taught by the combination of Amante, Von Borstel, and Logroscino. A person of ordinary skill in the art would have had a reason to combine the teachings of Amante, Von Borstel, and Logroscino. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings Amante, Von Borstel, and Logroscino. Thus, claims 21, 23, 26, and 28 would have been obvious based on the preponderance of the evidence.
Conclusion
Claims 1-2, 7-9, and 21-34 are pending. Claims 1-2, 9, 21, 23, 25-26, 28, and 30-34 are rejected. Claims 7-8, 22, 24, 27, and 29 are 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. No claims are allowed.
Contacts
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PATRICK T LEWIS whose telephone number is (571)272-0655. The examiner can normally be reached Monday to Friday, 10 AM to 4 PM EST (Maxi Flex).
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/PATRICK T LEWIS/Primary Examiner, Art Unit 1691
/PL/
