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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 11, 2025 has been entered.
Detailed Action
This office action is a response to applicant’s communication submitted November 11, 2025, wherein claims 1, 2, 7, and 138-140 are amended and claims 6, 8, and 11 are canceled. This application is a national stage application of PCT/GB2019/050715, filed March 13, 2019, which claims benefit of foreign applications GB1804021.2, filed March 13, 2018, and GB1820236.6, filed December 12, 2018.
Claims 1, 2, 7, 55, and 138-140 are pending in this application.
Claims 1, 2, 7, 55, and 138-140 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted November 11, 2025, with respect to the rejection of claims 1, 6-8, 11, 55, and 138-140 under 35 USC 112(b) for omitting essential elements, has been fully considered and found to be persuasive to remove the rejection as the claims have been amended so as to clearly describe administration to a specific subject. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted November 11, 2025, with respect to the rejection of claims 8, 11, and 139 for lacking antecedent basis, has been fully considered and found to be persuasive to remove the rejection as claims 8 and 11 have been canceled and claim 139 has been amended to depend form claim 138 which includes antecedent basis for a NAD precursor and NAD promoter. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted November 11, 2025, with respect to the rejection of claims 6 and 8 under 35 USC 112(d) for failing to further limit the base claim, has been fully considered and found to be persuasive to remove the rejection as claims 6 and 8 have been canceled. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted November 11, 2025, with respect to the rejection of claims 1, 2, 6-8, 11, 55, and 138-140 under 35 USC 103 for being obvious over Wyss-Coray et al. in view of Alvarez et al. in view of Robertson et al. in view of Horn et al., has been fully considered and found to be persuasive to remove the rejection as the claims have been amended to no longer refer to a method of augmenting plasma. Therefore the rejection is withdrawn.
The following new grounds of rejection are introduced:
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.
Claim 55 is 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. Regarding claim 55, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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, 2, 7, 55, and 138-140 are rejected under 35 U.S.C. 103 as being unpatentable over Alvarez et al. (US pre-grant publication 2014/0065099, of record in previous action) in view of Robertson et al. (US pre-grant publication 2017/0027902, of record in previous action) in view of Horn et al. (PCT international publication WO2016/149277, Reference of record in previous action)
Independent claim 1 is directed to a method comprising administering exogenous NAD to an individual in combination with a number of other compounds. Dependent claims 2 and 55 are directed to methods of “mitigating the effects of ageing” comprising administering the same combination of therapeutic compounds to a subject. Dependent claims 7 and 139 specify that the augmentation of the plasma comprises adding NAD or a precursor of NAD to the plasma. Dependent claims 138 and 140 specify the route of administration of the compound.
Alvarez et al. discloses methods of treating disorders associated with mitochondrial dysfunction comprising administering to a subject in need thereof one or more compounds that increase intracellular NAD+ in an amount sufficient to activate SIRT1 or SIRT3. (p. 1 paragraph 7) In one embodiment the compound that increases intracellular NAD+ is the NAD precursor nicotinamide riboside, as recited in present claims 5, 8-10, and 17. (p. 1 paragraphs 9-10) In one embodiment the compound includes a NAD booster, a PARP-1 inhibitor, an AMPK activator, or a combination thereof, as recited in present claim 13. (p. 1 paragraphs 12-13) Other specific compounds that can be administered include alpha-lipoic acid, resveratrol, quercetin, curcumin, and epigallocatechin-3-gallate, as recited in the present claims. (p. 1 paragraph 16) Disorders treatable with these compositions include neurodegenerative disorders, such as dementia, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. (p. 7 paragraph 60) These therapeutic compositions can be prepared and administered by many routes including intravenous injection. (p. 9 paragraphs 87-89) The disclosure of Alvarez et al. differs from the present claims in that it does not describe administering NAD+, rutin, and apigenin.
Robertson et al. discloses a method of treating oxidative injury resulting from mitochondrial dysfunction, comprising administering to a subject in need thereof a composition comprising a flavan-3-ol, a flavonoid, and a fatty acid. (p. 2 paragraph 6) The oxidative injury can be a neurodegenerative disorder, such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, or multiple sclerosis. (p. 2 paragraph 8) Flavonoids usable in this composition include rutin and apigenin, among others. (p. 5 paragraph 46)
Horn et al. discloses compositions for improving mitochondrial energy production, comprising an NAD+ precursor and an ADP booster. (p. 2 paragraphs 7-8) The NAD precursor can be NAD itself, as recited in the present claims. (p. 2 paragraph 9) The composition can also include an ADP cycle enhancer such as alpha-lipoic acid, (p. 3 paragraph 16) and a mitochondria protecting nutrient such as for example resveratrol, catechin, kaempferol, quercetin, or rutin as recited in present claims 12-17, 21-23, 25, 37, and 53. (p. 3 paragraphs 15-18) This composition can be used to treat conditions including Alzheimer’s and Parkinson’s disease. (p. 4 paragraph 25) In one preferred embodiment the dosage of the NAD precursor nicotinamide riboside is 83.35 mg. (p. 6 paragraph 40) While these compositions are described primarily as nutritional compositions, they are also disclosed as being in any form suitable for systemic administration, (p. 9 paragraph 62) such as intravenous administration. (p. 10 paragraph 65)
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the therapeutic compositions described by Alvarez et al., with the additional agents NAD+, rutin, and apigenin. One of ordinary skill in the art would have found it to be obvious to add these ingredients because the disclosures of Robertson and Horn suggest that they are useful for the same purpose of treating mitochondrial dysfunction, and therefore would all be useful for administration to the same subject population.
Regarding claim 55, this claim is directed to methods wherein the condition related to aging being treated is selected from a number of skin conditions. While the cited references do not specifically describe the method of treating a skin condition in the subject, the phrase “age-related skin conditions” as recited in claim 55 is interpreted as including the effects of the natural process of aging on the skin. This is supported by p. 21 lines 6-11 of the disclosure, which describe age related skin conditions as including effects such as sagging, wrinkles, elasticity, and moisture, which are simply effects of aging that would be generally present in aging subjects, and reasonably be expected to be treated by administering the same active agents to the same subjects recited in the claims.
Regarding the specific amount of NAD recited in present claim 7, while Horn et al. does not specifically describe the amount of NAD to include in the composition, the reference does disclose using an amount of 83.5mg of the related NAD precursor nicotinamide riboside. It would have been obvious to one of ordinary skill in the art at the time of the invention to determine the effective amount of NAD to use in the composition, with the expectation that the dosage of this active agent would be a result-effective variable.
Regarding the specific dosage ranges recited in claim 139, as discussed above, Horn describes a dosage of about 83mg for the NAD precursor nicotinamide riboside. Horn et al. furthermore describes a describes a dosage of 50 mg for alpha-lipoic acid. (p. 18 paragraph 98) Robertson et al. describes dosages of 10-250 mg epicatechin and 10-250mg flavonoid. (p. 4 paragraph 42) One of ordinary skill in the art would have reasonably considered the dosages of these and any other compounds included in the compositions as result-effective variables and determined the appropriate dosage for each compound.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 55 is rejected under 35 U.S.C. 103 as being unpatentable over Alvarez et al. in view of Robertson et al. in view of Horn et al. as applied to claims 1, 2, 7, 55, and 138-140 above, and further in view of Krutmann et al. (Reference included with PTO-892)
The disclosures of Alvarez et al., Robertson et al., and Horn et al. are discussed above. While previously it was determined that claim 55 would be infringed simply be administering a composition according to the cited references to a subject undergoing normal aging including the associated skin changes related to aging, even assuming for the sake of argument that this were not true it would still have been obvious to one of ordinary skill in the art at the time of the invention to administer said compositions to a subject specifically suffering from skin conditions recited in present claim 55 further in view of Krutmann et al.
Krutmann et al. discloses that solar radiation is the most important factor in premature skin ageing. (p. 44 left column last paragraph) Krutmann et al. furthermore describes the link between mitochondrial damage and photoaging of skin. (p. 44 right column third paragraph) Photoaged skin is characterized by damage to the mitochondrial genome. (p. 45 right column) Krutmann et al. furthermore suggests that mitochondrially targeted interventions would be effective in prevention and/or treatment of photoaging of the skin.
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the mitochondrially targeted therapy described by Alvarez in view of Robertson in view of Horn to a subject suffering from photoaging of the skin. One of ordinary skill in the art would have expected based on the disclosure of Krutmann et al. that such a therapy would have been useful in this subject population.
For these reasons the invention taken as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 7, 55, and 138-140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-95 and 97-103 of copending Application No. 16/980187 (US pre-grant publication 2021/0015788, of record in September 8, 2023 PTO-892, herein referred to as ‘187) as evidenced by Pubchem CID 5892. (Reference included with PTO-892)
Claim 49 of ‘187 claims a composition comprising two or more of a NAD precursor, a NAMPPT upregulator, a NQO1 upregulator, and a NNMT downregulator, with the intended use of mitigating, alleviating, or improving the effects of ageing. Dependent claims 46-95 further define the specific compounds present, in particular including the compounds niacin (claims 61, 64, 70, 80) apigenin (claims 64, 70, 71, 77, 80) epigallocatechin-3-gallate, (claims 61, 70, 73, 80) and rutin. (claims 70, 80) In particular, claim 93 defines the composition as comprising apigenin, rutin, niacinamide, alpha-lipoic acid, and EGCG, which are compounds recited in claims 1 and 2, for example. Claims 85 and 86 further require the presence of a NAD synthase I upregulator which can be nadide. According to PUBCHEM CID 5892, “nadide” is a synonym for NAD+. Therefore one of ordinary skill in the art would have seen the claims of ‘187 as suggesting the same compositions recited in the present claims. Furthermore claims 97-103 of ‘187 claim methods of treating conditions including effects of ageing and skin conditions using these compositions, which would infringe the presently pending claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 7, 55, and 138-140 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 168, 216, 218, 221, and 222 of copending Application No. 18/937848 (US pre-grant publication 2025/0057804, cited in PTO-892, herein referred to as ‘848) in view of Horn et al. (PCT international publication WO2016/149277, Reference of record in previous action)
Claim 168 of ‘848 claims a method of mitigating, alleviating, or improving the effects of aging in a subject comprising administering to the subject a composition comprising niacinamide, rutin, alpha lipoic acid, EGCG, and apigenin. Dependent claim 216 specifies a particular dosage range for the composition. Dependent claims 218amd 222 specify that the subject is suffering from certain skin conditions. Claim 221 specifies that the subject is suffering from one of a number of diseases including Alzheimer’s disease. The claims of ‘848 differ from the present claims in that they do not include NAD in the compositions described therein.
Horn et al. discloses compositions for improving mitochondrial energy production, comprising an NAD+ precursor and an ADP booster. (p. 2 paragraphs 7-8) The NAD precursor can be NAD itself, as recited in the present claims. (p. 2 paragraph 9) The composition can also include an ADP cycle enhancer such as alpha-lipoic acid, (p. 3 paragraph 16) and a mitochondria protecting nutrient such as for example resveratrol, catechin, kaempferol, quercetin, or rutin as recited in present claims 12-17, 21-23, 25, 37, and 53. (p. 3 paragraphs 15-18) This composition can be used to treat conditions including Alzheimer’s and Parkinson’s disease. (p. 4 paragraph 25) In one preferred embodiment the dosage of the NAD precursor nicotinamide riboside is 83.35 mg. (p. 6 paragraph 40) While these compositions are described primarily as nutritional compositions, they are also disclosed as being in any form suitable for systemic administration, (p. 9 paragraph 62) such as intravenous administration. (p. 10 paragraph 65)
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the therapeutic compositions described in the claims of ‘848 with NAD+ as an additional agent. One of ordinary skill in the art would have found it to be obvious to add these ingredients because the disclosure of Horn suggests that they are useful for the same purpose of treating mitochondrial dysfunction, and therefore would all be useful for administration to the same subject population.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 7, 55, and 138-140 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 66-70, 73, 75, and 76 of copending Application No. 19/255485 (unpublished, cited in PTO-892, herein referred to as ‘485) as evidenced by Pubchem CID 5892. (Reference included with PTO-892)
Claim 66 of ‘187 claims a composition comprising two or more components selected from a list including alpha-lipoic acid, apigenin, epigallocatechin gallate, nadide, niacin, and rutin. According to Pubchem CID 5892, “nadide” is a synonym for NAD+. Dependent claim 67 further specifies the amounts of each component present. Dependent claims 68-70 claim methods of enhancing resistance to DNA damage, oxidative stress, and mitochondrial dysfunction. Claims 73, 75, and 76 claim methods of treating conditions including effects of ageing and skin conditions using these compositions, which would infringe the presently pending claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/Primary Examiner, Art Unit 1693 12/11/2025