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
The office acknowledges Applicants filing of the claim amendments and supplemental amendments, arguments, declaration by the inventor (12/22/2025, 1/13 and 1/15/2026) and terminal disclaimers (1/13/2026). The supplemental response filed on 1/15/2026 contains the latest claim amendments. Claims 1, 15, 19 has been amended. Claim 3 has been cancelled. Claims 1-2, 4-21 are pending.
Applicants arguments and declaration have been fully considered. Rejections not reiterated from previous office actions are hereby withdrawn. Arguments, which are directed to withdrawn rejections, are thus rendered moot. The arguments in regards to the reiterated rejections/references from the previous office action are addressed below. In view of Applicant's claim amendments, the following rejections and/or objections are either reiterated, modified or newly applied. It is noted that Applicants previously elected citicoline (non-caffeine stimulant or nootropic), beta-hydroxybutyric acid (ketone body) and epicatechins (vasodilator) (See Response to Restriction election dated 2/3/2025). Claim 7 is withdrawn from further consideration pursuant to 37 C.F.R. 1.142(b), as being drawn to non-elected subject matter. The claims corresponding to the elected subject matter are 1-2, 4-6, 8-21 and are herein acted on the merits.
Response to Applicants Arguments
Applicants argue that the combination of a non-caffeine stimulant or nootropic, a ketone body, and a vasodilator is not known from or obvious over the prior art. This specific combination provides the following benefits in a single composition not found in the prior art: (1) the non-caffeine stimulant or nootropic provides mental clarity without providing any metabolic energy source; (2) the ketone body or ketone body precursor provides the body with readily available metabolic energy source that complements and enhances the effects of the ketone body or ketone body precursor; and (3) the vasodilator increases blood circulation to the brain and tissues, which further enhances the effects of both the non-caffeine stimulant or nootropic and the ketone body
or ketone body precursor. This triple combination of benefits is not known from or obvious over the prior art.
The ketone body or ketone body precursor provides a completely different effect
(metabolic energy to make ATP) on the body compared to either the non-caffeine stimulant or nootropic (CNS stimulant, and no metabolic energy to make ATP) or the vasodilator, which provides a completely different effect than either of the other two components. The result is a combination that provides unique benefits.
In response, Lowery is explicit in teaching beta-hydroxybutyrate for improving cognitive function. Wurtman is explicit in teaching the use of citicoline in treating cognitive dysfunction or memory impairment. French is explicit in teaching the use of epicatechin composition in enhancing executive cognitive function in a subject in need thereof. Thus a skilled artisan would have found it obvious to combine the agents that are known in the art to be useful for improving or treating cognitive function, herein BHB, and citicoline. The prior art is explicit in teaching the agents individually, BHB citicoline, and epicatechin for use in cognitive function. One of ordinary skill in the art would have been motivated to incorporate the agents herein in a single combination pharmaceutical composition because combining the agents herein each of which is known to be useful to treat cognitive function individually into a single composition useful for the very same purpose is prima facie obvious. See In re Kerkhoven 205 USPQ 1069. The strongest rationale for combining references is a recognition, expressly or implicitly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. See In re Sernaker 17 USPQ 1, 5-6 (Fed. Cir. 1983) and MPEP 2144. It is settled law that the teaching or suggestion to combine references’ disclosures need not be explicitly stated in the prior art, but may be implicit from the state of the prior art considered as a whole. In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006); cited with approval in KSR, 127 S.Ct. at 1741. A skilled artisan would have been motivated to combine BHB, citicoline and epicatechin for use in improving cognition with a reasonable expectation of success and to attain additive and/or synergistic benefits.
As to the argument in regards to triple combination of benefits, the composition comprising the same agents as in the instant claims would provide the same benefits as the properties are an inherent result of a particular composition having the same list of components.
As to applicants arguments that the components provide completely different effects, it is the property of the agents or the components. If the composition comprising the same components as claimed is formulated from the prior art for treating cognitive function then the claim is addressed. As to the effects or to the limitation of increasing neurological and physiological performance, the properties are an inherent result of a particular composition having the same list of components. Further they are to an intended use. The intended use of the claimed composition does not patentably distinguish the composition, per se, since such undisclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. Further the motivation of a skilled artisan to combine different agents to arrive at a composition as claimed need not be the same. As stated in the rejection below a person skilled in the art would have found it obvious to arrive at the claimed composition with a reasonable expectation of success. One skilled in the art would have been motivated to arrive at the composition comprising BHB, citicoline and epicatechins to use them to enhance cognitive function in a subject.
As to the declaration data, the data is in regards to paraxanthine and BHB, caffeine and BHB and paraxanthine, caffeine and BHB (See Figures, Tables 2-3 of instant specification). There is no data for any other combination of nootropic agent with BHB and the third agent as claimed. Applicants have not provided any data or evidence to support the unexpected or unpredictably superior effects for any other combination other than paraxanthine and BHB.
Applicants have not shown any comparison data with that of the prior art, even for elected species, for e.g. BHB alone, citicoline alone, citicoline with BHB, BHB+citicoline+vasodilator component to provide evidence that it would have been unexpected and unobvious. Further single point data (paraxanthine+BHB) cannot be extrapolated to hundreds of non-caffeine stimulant or nootropic +BHB and a vasodilator component as claimed.
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.
The factual inquiries 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.
Claim(s) 1, 2, 4-6, 8-21 are rejected under 35 U.S.C. 103 as being unpatentable over Lowery et al. (US 20170296501 A1) in view of Wurtman (US 20030114415) and further in view of French (US 20080161386).
Lowery teachings are to a composition comprising beta-hydroxybutyrate (0.5-10 g) for administration to individuals for improving ketosis, energy, focus, mood and cognitive function ((see abstract) [0004], [0011], [0040], example 14). R-beta-hydroxybutyrate (e.g., greater than 90 percent purity of R-beta-hydroxybutyrate and less than 10 percent L-beta-hydroxybutyrate) and/or mixtures with R-beta-hydroxybutyrate may be administered to humans. In some implementations, one or more specific chiralities of beta-hydroxybutyrate may be utilized [0039]. The composition can include salt(s) of beta-hydroxy butyrate for e.g. sodium beta-hydroxybutyrate, potassium beta-hydroxybutyrate [0038]. Lowery teaches addition of niacin to the composition [0053]. The described composition may be provided in a powdered form that allows the described composition to be sprinkled on food, mixed with a liquid to provide a beverage, and/or directly administered [0093]. The composition may include approximately 0.5 g to approximately 10 g of R-beta-hydroxybutyrate [0006-0007]. Lowery further teach that the composition can be administered parenterally [0093].
The above prior art is not explicit in teaching a nootropic agent, e.g. citicoline in the composition.
Wurtman teachings are to treating cognitive dysfunction or memory impairment with an effective amount of a composition that comprises citicoline or pharmaceutically acceptable salts (Abstract, claim 1). The citicoline dosage may be from about 10 mg to about 1000 mg from one to about 4 times per day [0057] and the formulations include solid, e.g. powder, or liquid (solution or suspension) [0059] and the composition can contain pharmaceutical carriers [0060]. Wurtman teach that the active ingredient also may be in the form of a bolus, electuary, or paste. Formulations of the active ingredient suitable for parenteral administration may comprise a sterile, aqueous preparation of the active ingredient [0059]. Wurtman teach addition of neuroprotective agents, e.g. magnesium [0061].
In summary, Lowery teach composition comprising beta-hydroxybutyrate (0.5-10 g) for administration to individuals for improving ketosis, energy, focus, mood and cognitive function and additional agent, niacin can be added. Wurtman teach effective amount of a composition comprising citicoline treating cognitive dysfunction or memory impairment. Also taught by Wurtman is additional neuroprotective agent magnesium can be added.
Lowery and Wurtman do not teach that the composition further comprises a vasodilator, e.g. epicatechins.
French is explicit in teaching epicatechin composition and its use in a method of enhancing executive cognitive function in a subject in need thereof (See Claims 1, 6, Table 3).
From the teachings of the prior art a person skilled in the art before the effective filing date of the invention would have found it obvious to combine beta-hydroxy butyrate, citicoline and epicatechins into a single composition as instantly claimed. A person skilled in the art would have been motivated to do so is to combine the agents known in the art for same purpose, herein for treating or improving cognitive function. "It is prima facie obvious to combine the compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Further a skilled person would have been motivated to combine the three agents beta-hydroxybutyrate acid, citicoline and epicatechins into a composition for synergistic or additive benefits. As to the limitation of the composition is free of sugar components, it is noted that the composition formulated from the prior art comprises beta-hydroxybutyrate acid, citicoline and epicatechins and is free of sugar components. As to the amount of BHB, Lowery teach 0.5-10 g of BHB acid or salt. Wurtman teach 10-1000 mg of citicoline. If for example 1000 mg of BHB acid/salt is formulated with 100 mg of citicoline the ratio is about 10:1 of BHB : citicoline and such amounts in the composition addresses the synergistic limitation as the instant specification teach 50-500 mg of the non-caffeine stimulant or nootropic (see [0033], [0037]). It is noted that though French do not teach epicatechin as a vasodilator compound, it is the inherent property of the agent whether it is explicitly taught or not. As to the limitation of ‘increasing neurological and physiological performance’, they are to intended use. The prior art structure is capable of performing all of the intended uses in applicant's claimed composition even if they are not specifically disclosed. The intended use of the claimed composition does not patentably distinguish the composition, per se, since such undisclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. Additionally, a person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. (“[T]he motivation in the prior art to combine the references does not have to be identical to that of the applicant to establish obviousness.” Accordingly, claims 1, 4-6, 10-11, 17 are addressed.
As to claims 2, 18, the composition do not contain caffeine and BHB is the sole caloric source of energy. As to claim 15, if BHB acid is 1000 mg and nootropic, citicoline is 100 mg in the composition, the ratio is at least about 10:1 and BHB is the sole caloric source of energy. As to claim 16, if BHB acid is 1000 mg and nootropic, citicoline is about 70 mg in the composition, the ratio is about 15:1.
As to claim 8, Lowery teach the composition can comprise BHB acid salts, e.g. sodium, potassium etc. Hence it would have been obvious to a skilled artisan to formulate the composition comprising BHB anions and sodium, potassium ions and its mixtures. Claim 9 is addressed by the combined prior art teaching of the composition as a beverage, powder, liquid etc. As to claims 12-13, Lowery teach ketone body (BHB acid), enriched R-enantiomer or enriched S-enantiomer can be utilized in the composition. As to claim 14, Lowery teaches the composition can be mixed with a liquid to provide beverage and Wurtman teach addition of pharmaceutical carriers to the composition. As to claims 19-20, a person skilled in the art would have found it obvious to arrive at a dosage form, e.g. liquid comprising BHB acid (1000 mg) and a nootropic, e.g. citicoline (100 mg), epicatechins and a pharmaceutically acceptable carrier to arrive at claimed 10:1 ratio from the teachings of the prior art. The composition formulated from the prior art is free of sugar components. As to claim 21, a skilled artisan would have found it obvious that the composition can be administered parenterally (via injection) as both Lowery and Wurtman teach that the active agents can be delivered parenterally. Hence a skilled artisan would have found it obvious to configure the composition to be administered via injection.
Note: TW 200305371 A teach infant formula composition comprising BHB, arginine, phenylalanine, tryptophan and tyrosine (claim 7). The reference is drawn to non-elected species with regard to the composition comprising BHB, a non-caffeine stimulant or nootropic and a vasodilator and was found during the search for the elected species. It should not be interpreted that a comprehensive search was performed for all non-elected species.
Conclusion
Applicant's amendment necessitated the modified 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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/Umamaheswari Ramachandran/Primary Examiner, Art Unit 1627