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 .
Response to Arguments
Applicant's arguments filed 02/20/2026 have been fully considered but they are not persuasive. Applicant argues (page 2) the enantiopure preparation of di-NACA is different from the synthetic pathway taught by prior art of Goldstein. Applicant additionally argues NAC, also has enantiomeric forms, and are known to not have little to no activity, thus having activity. Applicant further emphasizes (Page 3) the study of Wong BK, Chan HC and Corcoran GB on the unnatural D-isomer of NACA failed to increase hepatic glutathione. It is noted from the previous office action Goldstein teaches NACA solely and its D and L isomer forms, in which NACA has activity against diseases and disorders associated to oxidative stress. Additionally, applicant argues only the enantiopure of di-NACA not of NACA. For the above reasons the 103 rejection of record is maintained.
Applicant has overcome the nonstatutory double patenting rejection of claims 1-6 and 12-15 by the filing of a terminal disclaimers for application # 17156560 and Patent No. 11753370.
Applicant has canceled claims 3-14. Claims 1-6, 12 and 15-16 is pending. Claims 1-6, 12 and 15-16 is now evaluated on its merits.
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 1-6, 12 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Goldstein (US Patent No. 8937099) in view of MedChem News, Deuterium Medicinal Chemistry: A New Approach to Drug Discovery and Development, May 2014, Pages 8-22, Campochiaro et al. Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?, Antioxidants & Redox signaling, November 2015, Pages 643-648 and Shoham et al. Oxidative stress in diseases of the human cornea, Free Radical Biology & Medicine, August 2008, Pages 1047-1055.
Regarding claims 1-6, 12 and 15-16, Goldstein teaches methods and compositions comprising N-acetylcysteine amide (NACA) and derivatives thereof that are used in treatments and therapies for human and non-human mammalian diseases, disorders, conditions and pathologies associated to oxidative stress (abstract, Page 10, 2nd para.). Of the diseases or disorders associated to oxidative stress, Goldstein teaches neurodegenerative diseases, Alzheimer disease, HIV/AIDS, Parkinson’s disease, dermatological disorders and pulmonary disease (relevant to claim 4) (Page 15 last para.).
Goldstein additionally teaches the NACA as enantiomers of the compounds and in an embodiment compounds
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(relevant to claims 1) (Page 40, 42) and the administration of the compounds by route of oral, inhalation, intracutaneous, subcutaneous, intravenous at a dose of 25-500 mg (relevant to claims 6 and 15) (Page 27, 3rd para.).
Goldstein fails to teach the compounds to treat retinitis pigmentosa, cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and the compound of NACA being NACA-d3 with at least 91% purity.
MedChem teaches deuterium substitution for hydrogen decreased acidity of carboxylic acids and phenols, increase basicity of amines, low toxicity and increase tolerability and efficacy of a drug (page 10, 2nd and last para.). MedChem additionally teaches specific examples of CH3 to CD3 substitution results in a longer half-life as shown in example 11
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and example 13
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which provided improved metabolic stability (Page 13).
Campochiaro teaches retinitis pigmentosa (RP), a large mutation that causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. The study of animal models of RP has demonstrated that oxidative damage is a major contributor to cone cell death. Campochiaro additionally teaches a study on patients with RP and control patients, in which the results indicated patients with RP have ocular oxidative stress and damage in the absence of manifestations of systemic oxidative stress and/or damage indicating that demonstrations of oxidative damage-induced cone cell death in animal models of RP may translate to human RP (relevant to claims 2-3 and 12) (abstract).
Shoham teaches a study of the roles of oxidative stress in diseases of the human cornea and their management. The results as taught by Shoham implicate oxidative/nitrosative stress in the pathogenesis of numerous traumatic, metabolic, inflammatory, iatrogenic diseases of the cornea (relevant to claim 5) (Page 1053, 1st para.) and cause age-related cataracts (Page 3, right column, 2nd to last para.).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filing to have administered NACA-d3 to treat a disease of oxidative stress, in particular retinitis pigmentosa and cataracts. One would have been motivated to do so from the teachings of Goldstein in the treatment of diseases associated with oxidative stress comprising
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and the teachings of MedChem on CH3 to CD3 substitution is known in the art to improve metabolic stability and increase half-life of the compound/drug. One would have been motivated to treat the above conditions from the teachings of Campochiaro and Shoham of retinitis pigmentosa and cataracts being a disease associated with oxidative stress. There is a reasonable expectation of treating retinitis pigmentosa and cataracts comprising NACA-d3 from the teachings of Goldstein, MedChem, Campochiaro and Shoham.
It is therefore additionally obvious to have the NACA-d3 taught at a purity of at least 91% or 96%. As the compound taught by Goldstein is the same as instant claims and is of the same utility to treat the same conditions, it is obvious the compound taught by Goldstein is at least 91% or 96% pure unless proven otherwise.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627