Prosecution Insights
Last updated: April 19, 2026
Application No. 18/555,106

SIRTUIN OR KLOTHO ACTIVATOR OR EXPRESSION ENHANCER, NAD+ INCREASING AGENT, AND SENOLYTIC AGENT

Non-Final OA §102§112
Filed
Oct 12, 2023
Examiner
NEAGU, IRINA
Art Unit
1629
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Wakunaga Pharmaceutical Co. Ltd.
OA Round
1 (Non-Final)
47%
Grant Probability
Moderate
1-2
OA Rounds
2y 9m
To Grant
99%
With Interview

Examiner Intelligence

Grants 47% of resolved cases
47%
Career Allow Rate
324 granted / 696 resolved
-13.4% vs TC avg
Strong +58% interview lift
Without
With
+58.1%
Interview Lift
resolved cases with interview
Typical timeline
2y 9m
Avg Prosecution
52 currently pending
Career history
748
Total Applications
across all art units

Statute-Specific Performance

§101
1.5%
-38.5% vs TC avg
§103
39.5%
-0.5% vs TC avg
§102
11.7%
-28.3% vs TC avg
§112
23.1%
-16.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 696 resolved cases

Office Action

§102 §112
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 . DETAILED ACTION Applicant’s preliminary amendment of 12 October 2023, in which claims 1-26 have been cancelled, and new claims 27-41 have been added, are acknowledged. Claims 27-41 are pending in the instant application. Claims 27-41 are examined herein. Priority This application is a National Phase entry of International Application No. PCT/JP2022/017713, filed on 13 April 2022, which claims the benefit of Japan Patent Application No. 2021-067931, filed on 13 April 2021. A certified copy of the priority document, in Japanese, has been submitted on 16 March 2024. Information Disclosure Statement The information disclosure statements (IDS) submitted on 12 October 2023 and 11 April 2025 are acknowledged and considered. Claim Rejections - 35 USC § 112 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 27, 28, 33, 34, 36, 37, 39, 40 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. Independent claim 27 is drawn to a method for enhancing expression of sirtuins or Klotho, comprising administering S-1 -propenylcysteine or a salt thereof to an animal in need thereof. Independent claim 28 is drawn to a method for increasing NAD+, comprising administering S-1- propenylcysteine or a salt thereof to an animal in need thereof. It is unclear how the enhancing (in claim 27) or the increase (in claim 28) is to be measured, as the claim fails to establish a standard or threshold level. For example, the increase could be relative to another sample taken from the same subject previously. Alternatively, the increase could be relative to a healthy subject, i.e., a different subject than the subject currently treated with S-1 -propenylcysteine or a salt thereof. In other words, it appears that claims 27, 28 (and dependent claims 33, 34, 36, 37, 39, 40) are directed towards measuring levels of biological molecules in two different biological samples and comparing said levels between the two different biological samples; however, the claims fail to clearly establish the origins of the two different biological samples, or the reference or standard by which one would make a comparison of levels of the one or more biological molecules. One wishing to practice the instantly claimed invention would thus not recognize the metes and bounds for which Applicant seeks protection. For these reasons, the metes and bounds of the present claims cannot be determined and one having ordinary skill in the art would not necessarily be reasonably apprised of the scope of the claims. Further, claim 36 depends on claim 27, and recites that the method prevents, treats or ameliorates symptoms that result from low activity or low expression of sirtuins or Klotho, or symptoms that result from accumulation of senescent cells. Claim 27 teaches enhancing expression of sirtuins or Klotho in a patient in need thereof (who is a patient having low expression of sirtuins or Klotho, and expected to have symptoms that result from such low activity or low expression of sirtuins or Klotho), comprising administering to the patient S-1 -propenylcysteine or a salt thereof. Yet, claim 27 does not teach accumulation of senescent cells. There is insufficient antecedent basis for the limitation “symptoms that result from accumulation of senescent cells” of claim 36, in claim 27. The claims lack clarity because are unclear because it is thus unclear what the patient population actually is. Claim 36 lacks clarity because it is unclear how and why a subject suffering from low expression of sirtuins or Klotho would be treated for symptoms that result from accumulation of senescent cells. A similar analysis applies to claim 37. Further, regarding claim 39, which depends on claim 27, and recites that the method treats symptoms of kidney disorders or cognitive disorders, the claims lack clarity because it is unclear what the patient population actually is. In claim 39, it is unclear how and why a subject suffering from low expression of sirtuins or Klotho would be treated for symptoms of cognitive /memory disorders. A similar analysis applies to claim 40. Appropriate clarification is required. Claims 29, 38, 41 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. Claim 38 depends on claim 29, and recites that the method prevents, treats or ameliorates symptoms that result from low activity or low expression of sirtuins or Klotho, or symptoms that result from accumulation of senescent cells. Claim 29 is drawn to a method for suppressing senescent cells in an animal in need thereof (who is an animal having senescent cells, and expected to have symptoms that result from accumulation of senescent cells), comprising administering to the animal S-1 -propenylcysteine or a salt thereof. Yet, claim 29 does not teach that the animal has low activity or low expression of sirtuins or Klotho, and associated symptoms. There is insufficient antecedent basis for the limitation “symptoms that result from low activity or low expression of sirtuins or Klotho” of claim 38, in claim 29. The claims lack clarity because are unclear because it is thus unclear what the patient population actually is. In claim 38, it is unclear how and why a subject suffering from accumulation of senescent cells would be treated for symptoms that result from low expression of sirtuins or Klotho. Further, regarding claim 41, which depends on claim 29 and recites that the method treats symptoms of kidney disorders or cognitive disorders, the claims lack clarity because it is unclear what the patient population actually is. In claim 41, it is unclear how and why a subject suffering from accumulation of senescent cells (which is the patient population in claim 29) would be treated for symptoms of cognitive /memory disorders. Appropriate clarification is required. Claim Rejections - 35 USC § 102 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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 27-41 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Suzuki et al. (WO 2019/235597, published 12 December 2019, cited in IDS, US 2021/0228521 used as English equivalent, cited in PTO-892), as evidenced by Michan et al. (The Journal of Neuroscience 2010, 30 (29), 9695-9707, cited in IDS), Imai et al. (Trends Cell Biol. 2014, 24 (8), 464-471, cited in IDS) and Zhang et al. (Nature Neuroscience 2019, 22, 719-728, cited in PTO-892). Suzuki teaches (US 2021/0228521, [0048]-[0050]) a method of preventing, treating, or ameliorating a neurodegenerative disease, or a food for preventing or ameliorating a neurodegenerative disease comprising administering S-1-propenylcysteine or a salt thereof to a subject in need thereof. Suzuki teaches (claim 20) that the neurodegenerative disease is selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, muscular dystrophy, heart failure, dilated cardiomyopathy, infectious disease, autoimmune disease, obesity, diabetes, arteriosclerosis, or steatohepatitis. Thus, Suzki teaches administering S-1-propenylcysteine or a salt thereof to a subject who suffers from Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, muscular dystrophy, heart failure, dilated cardiomyopathy, infectious disease, autoimmune disease, obesity, diabetes, arteriosclerosis, or steatohepatitis, to prevent or treat said disease, which is synonymous with preventing, treating, or ameliorating symptoms of these diseases. It is noted that Alzheimer's disease is a cognitive/memory disorder. As such, Suzuki teaches that administration of S-1-propenylcysteine or a salt thereof to a subject who suffers from Alzheimer's disease, is effective to prevent or treat Alzheimer's disease, which is synonymous with preventing, treating, or ameliorating symptoms of a cognitive/memory disorder which is Alzheimer's disease, as in instant claims 39-41. Since Alzheimer's disease is a CNS disease, Suzuki implicitly teaches that the method acts in the brain, as in instant claims 33-35. While Suzuki does not teach that administration of S-1-propenylcysteine or a salt thereof to a subject who suffers from Alzheimer's disease activates or enhances the expression of sirtuins or Klotho, as in instant claim 27, increases NAD+, as in instant claim 28, suppresses or delays cellular senescence, as in instant claims 29-31, and suppresses cells expressing p16 in the subject, as in instant claim 32, these processes inherently occur upon administration of S-1-propenylcysteine or a salt thereof. Administration of the same therapeutic agent, S-1-propenylcysteine or a salt thereof, to the same patient population, patients suffering from Alzheimer’s disease, will inherently have the same effect on the expression of sirtuins, Klotho, NAD+, and cell senescence in the body of the patient. Even though Suzuki does not specifically teach that administering S-1-propenylcysteine enhances the expression of sirtuins in the Alzheimer’s patient in the method of treatment, as in instant claim 27, such increase in expression of sirtuins inherently occurs in the method of treating Alzheimer’s disease with S-1-propenylcysteine, as evidenced by Michan et al. (The Journal of Neuroscience 2010, 30 (29), 9695-9707, cited in IDS). Michan teaches that SIRT1 is essential for normal cognitive function and synaptic plasticity; that cognitive functions including immediate memory, spatial learning are impaired in SIRT1 knockout mice; that overexpression of SIRT1 is observed to exhibit ordered synaptic plasticity and memory; and that SIRT1 acts on normal learning, memory and synaptic plasticity. Even though Suzuki does not specifically teach that administering S-1-propenylcysteine increases NAD+ in the Alzheimer’s patient in the method of treatment, as in instant claim 28, such increase in NAD+ inherently occurs in the method of treating Alzheimer’s disease with S-1-propenylcysteine, as evidenced by Michan et al. (The Journal of Neuroscience 2010, 30 (29), 9695-9707, cited in IDS) and Imai et al. (Trends Cell Biol. 2014, 24 (8), 464-471, cited in IDS). Michai is as above. Imai teaches that NAD+ functions as a coenzyme for dehydrogenases and a substrate for sirtuins in living bodies; an increase in NAD+ amount enhances sirtuin activity. Thus, Michan and Imai teach the link between cognitive function, sirtuin expression and NAD+ amount. Improved cognitive function (that occurs in the treatment of AD) correlates with enhanced expression of sirtuins, and an increase in NAD+ amount. Even though Suzuki does not specifically teach that administering S-1-propenylcysteine suppresses senescent cells in the Alzheimer’s patient in the method of treatment, as in instant claims 29-31, and suppresses cells expressing p16 genes, as in claim 32, such suppressing of senescent cells inherently occurs in the method of treating Alzheimer’s disease with S-1-propenylcysteine, as evidenced by Zhang et al. (Nature Neuroscience 2019, 22, 719-728, cited in PTO-892). Zhang teaches that cellular senescence is involved in the pathogenesis of Ab plaques and associated with cognitive impairment in AD. Zhang teaches (Abstract) that, in the brains of patients with AD and in AD mouse models, Aβ plaque-associated cells exhibit a senescence-like phenotype characterized by the upregulation of p16/INK4/CDKN2A proteins. As such, a method of instant claims 27-41 is anticipated by Suzuki. Conclusion Claims 27-41 are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S. LUNDGREN can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /IRINA NEAGU/Primary Examiner, Art Unit 1629 /JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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Prosecution Timeline

Oct 12, 2023
Application Filed
Jan 10, 2026
Non-Final Rejection — §102, §112 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
47%
Grant Probability
99%
With Interview (+58.1%)
2y 9m
Median Time to Grant
Low
PTA Risk
Based on 696 resolved cases by this examiner. Grant probability derived from career allow rate.

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