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 .
Status of the Application
This Office Action is in response to applicant’s arguments filed on 8/28/26. Claims 1-13, 16, 19-42 have been cancelled. Claims 43-49 have been added. Claims 14-15, 17-18, 43-49 are pending. Claim 14 has been amended. Claims 14-15, 17-18, 43-49 are examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and modified below due to the claim amendments.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 14-15, 17-18, 43-49 are rejected under 35 U.S.C. 103 as being unpatentable over Clay et al. (“Triosephosphate Isomerase Deficiency,” Am. J. Dis. Child, 1982, 136, pages 800-802, of record) in view of Valentin et al. (“Triose phosphate isomerase deficiency in 3 French families: two novel null alleles, a frameshift mutation (TPI Alfortville) and an alteration of the initiation codone (TPI Paris),” Blood, 2000, vol. 96, issue 3, 1130-1135, of record) and Alway et al. (“Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women,” Journals of Gerontology, 2017, 72, 12, 1595-1606, of record).
The instant claims are directed to a method of treating a subject with TPI deficiency by administering an agent that promotes stability of a mutant form of the human TPI protein.
Clay et al. teach that triosephosphate isomerase (TPI) deficiency is an autosomal recessive disease of infancy and childhood (page 800, left column, first paragraph). A marked deficiency of TPI is demonstrated in the skeletal muscle of patients (page 800, middle column, first full paragraph). In a case study of a female child, by 19 months, deterioration of motor performance was noted, for example being unable to sit without support. By 26 months, she did not verbalize, had poor head control, and had atrophy in both legs. By 9 years of age, she was unable to walk and muscle tone was decreased in the arms, while the lower extremities were spastic and hyperreflexic (pages 800-801).
Valentin et al. teach that TPI deficiency is marked by progressive and severe neuromuscular dysfunction as a major clinical feature (page 1130, left column, second paragraph). Valentin et al. also teach that TPI E105D is the most frequently occurring TPI mutation, affecting subjects of diverse geographic and ethnic origins. The predominance of the E105D mutation has practical significance because questions concerning prenatal diagnosis are often paramount among the concerns of affected families (page 1133, left column, paragraph 4)
However, Clay and Valentin et al. fail to disclose resveratrol.
Alway et al. teach that resveratrol enhances resistance exercise more than placebo or exercise alone in muscle peak torque, average peak torque, and power on skeletal muscle (title and abstract).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have administered resveratrol along with exercise, as taught by Alway et al., in a subject with TPI deficiency with E105D mutation, as taught by Clay and Valentin et al.
A person of ordinary skill in the art would have been motivated to administer resveratrol along with exercise because this treatment regimen has beneficial effects on skeletal muscle in a subject in need thereof. Since TPI deficiency is marked by progressive and severe skeletal muscle dysfunction as a major clinical feature, administration of resveratrol along with exercise would obviously treat a subject with TPI deficiency.
The Examiner notes that the limitations regarding “an agent that promotes stability of a mutant form of the human TPI protein” and “increasing the amount of TPI proteins in cells” are obvious since all elemental steps of the method claim has been met by the cited prior art. Specifically, administration of resveratrol would obviously promote the stability of TPIE105D and amount of TPI protein in the claimed percentages.
Response to Arguments
Applicant argues that enhancing exercise-induced skeletal muscle in a subject with TPI Df is not a treatment for the disease, because it would not prevent hemolytic anemia, neurological dysfunction, and the recurrent infections that often lead to death or disability in subjects with TPI Df.
This is not persuasive because this argument is not reflected in any limitation in the claims. Applicant is reminded that the prior art teaches and suggests the need for enhancing exercise-induced skeletal muscle because TPI deficiency is marked by progressive and severe skeletal muscle dysfunction as a major clinical feature.
Applicant also argues that Alway et al. describes healthy older adults, who do not have TPI Df. In contrast, patients with TPI Df are typically infants or young children who have severe neuromuscular dysfunction that leads to severely impaired locomotor function requiring mobility aids that would prohibit them from normal exercise.
This is not persuasive because the Alway et al. reference was merely used to show that resveratrol enhances resistance exercise more than placebo or exercise alone. Furthermore, Applicant has not presented any evidence that supports that infants and young children with TPI Df would be unable to perform normal exercise at all due to their condition.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623
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