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
This office action is a response to applicant’s communication submitted June 16, 2026, wherein claims 2, 55, and 138-140 are amended. This application is a national stage application of PCY/GB2019/050715, filed March 13, 2019, which claims benefit of foreign applications 1804021.2, filed March 13, 2018, and GB1820236.6, filed December 12, 2018.
Claims 1, 2, 7, 55, and 138-140 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Withdrawn Rejections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 June 16, 2026, with respect to the rejection of claim 55 under 35 USC 112(b) for including the indefinite phrase, “such as,” has been fully considered and found to be persuasive to remove the rejection as claim 55 has been amended to remove the indefinite phrase. Therefore the rejection is withdrawn.
The rejections of claims 1, 2, 7, 55, and 138-140 for claiming the same invention as claims 49-95 and 970103 of US application 16/980107, of claims 1, 2, 7, 55, and 138-140 for claiming the same invention as claims 168, 216, 218, 221, and 222 of US application 18/937848, and of claims 1, 2, 7, 55, and 138-140 for claiming the same invention as claims 66-70, 73, 75, and 76 of US application 19/255485, are withdrawn in view of the terminal disclaimer submitted June 16, 2026,
The following rejections of record in the previous action are maintained:
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) NAD boosters can include nicotinamide. (p. 1 paragraph 16) 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 of record in previous action)
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.
Response to Arguments
Applicant’s arguments, submitted Jun 16, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejections. With respect to the rejection of base claim 1 under 35 USC 103, Applicant simply states that they believe that the person skilled in the art would not be drawn to combine the teachings of Alvarez, Robertson, and Horn, and would additionally not be motivated to include the additional agents NAD+, rutin, and apigenin. This is not a substantive argument, and does not provide a detailed explanation as to why Applicant arrived at this conclusion. Therefore This argument is not persuasive.
Regarding claim 55, Applicant further argues that one of ordinary skill in the art would not have been motivated to take the compositions of Alvarez and apply them to a method of treating a skin condition in a subject. However, as mentioned above with respect to claim 1, no specific reasoning is provided for this conclusion. As discussed in the body of the rejection, the disclosure of Alvarez generally describes the disclosed invention as a method of treating mitochondrial dysfunction in order to treat aging related disorders and consequences of aging. Considering that claim 55 still includes the broadly defined subject population suffering from age-related skin conditions, it is reasonably considered to be infringed by methods wherein the subject is an aged subject suffering from the typical consequences of aging on their skin. Therefore in the absence of further reasoning, this claim is also seen to be obvious.
Regarding the rejection of claim 7, Applicant argues that the nicotinamide riboside administered by Horn is a precursor of NAD, and therefore the dosage of NR described in Horn’s disclosure is not representative of an appropriate dosage for NAD+. However, while one of ordinary skill in the art would have expected the exact optimal dose of NAD+ to be different from the suggested dose of NR, the fact that specific doses of NR, both the exact dose of 83.3 and the range of 0.1-1000 mg, are described would have suggested to one of ordinary skill in the art that the dosage of the NAD or NAD precursor is a result-effective variable, and that therefore it would be appropriate to determine the optimal dosage using the stated dosage of NR as a starting point.
Regarding the rejection of claim 139, Applicant argues that the prior art does not establish a relationship between the dosage of any of the particular compounds described by the cited references and any particular result. However, the fact that a reference describes a specific dose or dose range for a compound would indicate to one of ordinary skill in the art that the dose of that particular component is important in determining the effectiveness of the final composition. Therefore based on the fact that the prior art references are concerned with naming particular doses of the different components, one of ordinary skill in the art would have reasonably been motivated to find optimal doses for all of the specific compounds recited in the presently claimed invention.
Regarding the specific rejection of claim 55 further in view of Krutmann, Applicant argues that Krutmann’s disclosure has no relevance to the present claims because Krutmann suggests treating photoaging of the skin using a different composition comprising a mitochondrial telomerase reverse transcriptase, rather than a combination of small molecules as presently claimed. However, a reference is prior art for everything it discloses and not merely for the most suggested or preferred teaching. In the present case, Krutmann suggests one specific therapy to protect or restore mitochondrial function. Based on a rationale for substituting equivalents usable for the same purpose, this would be seen as also suggesting using other therapies known to protect or restore damaged mitochondria, such as those described by the presently cited references.
For these reasons the rejections are deemed proper and maintained.
Conclusion
No claims are allowed in this action. 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 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.
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 7/28/2026
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