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 .
This Office action is responsive to Applicant’s amendment and remarks, filed 12 Feb 2026, in which claim 3 is amended to change the scope and breadth of the claim.
This application is a domestic application, filed 15 March 2023; and claims benefit of provisional application 63/319,997, filed 15 March 2022.
Claims 1-18 are pending in the current application and are examined on the merits herein.
Rejections Withdrawn
The terminal disclaimer, filed 12 Feb 2026, with respect that claims 1-8, 10-12, and 14-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-14 of U.S. Patent No. 9,975,915 (reference patent) in view of Migaud et al. (US 9,975,915, issued 22 May 2018, provided by Applicant in IDS filed 20 April 2023) has been fully considered and is persuasive, as the terminal disclaimer is recorded.
This rejection has been withdrawn.
The terminal disclaimer, filed 12 Feb 2026, with respect that claims 1-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/015,302 (reference application) has been fully considered and is persuasive, as the terminal disclaimer is recorded.
This provisional rejection has been withdrawn.
The terminal disclaimer, filed 12 Feb 2026, with respect that claims 1-8, 10-12, and 14-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/015,302 (reference application) in view of Migaud et al. (US 9,975,915, issued 22 May 2018, provided by Applicant in IDS filed 20 April 2023) has been fully considered and is persuasive, as the terminal disclaimer is recorded.
This provisional rejection has been withdrawn.
The following are modified grounds of rejection necessitated by Applicant’s amendment, filed 12 Feb 2026, in which claim 3 is amended to change the scope and breadth of the claim
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Amended Claims 1-7 and 16-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Migaud et al. (US 9,975,915, issued 22 May 2018, provided by Applicant in IDS filed 20 April 2023).
Migaud et al. discloses crystalline forms of nicotinoyl riboside compounds or derivatives and methods of preparation thereof (abstract). In one embodiment compound is the crystalline Form I of nicotinamide riboside triacetate (NRTA) chloride of formula (IX)
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(column 7, line 65 to column 8, line 30), meeting limitations of claims 1-5. According to particular embodiments, the compounds are substantially free of solvents or other by-products, most preferably quantitatively free of solvents or by-products (column 103, lines 25 to 65), meeting limitations of claims 1 and 5. The compound may be formulated into nutritional compositions including carriers and excipients (column 239, lines 30-55), meeting limitations of claim 6. The compounds together with a conventional adjuvant, carrier, or diluents, may thus be placed into the form of pharmaceutical compositions, including for oral administration (column 237, lines 30-55), meeting limitations of claim 7. The compounds are useful for supplementation to treat vitamin B3 deficiency and cellular NAD(P)+ depletion (column 1, lines 30-55). Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable additives as desired (column 239, lines 50-60), meeting limitations of claim 18.
Migaud et al. does not explicitly disclose the method of treating a condition comprising orally delivering to a mammal in need of such treatment the claimed compound (claim 16). However, Migaud et al. discloses the intended use of the compound is for treating vitamin B3 deficiency and cellular NAD(P)+ depletion, and discloses the oral administration of the compound or composition, leading one of skill in the art to readily envision all limitations of the method of claims 16-17.
Response to Applicant’s Remarks:
Applicant’s Remarks, filed 12 Feb 2026, have been fully considered and not found to be persuasive.
Applicant traverses the rejection of claims 16-17 based on the disclosure of Migaud et al. and asserts all elements of these claims are not described in the cited reference. However, MPEP 2131.02 at III. provides “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination.” Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015)” In this case, by similar reasoning, Migaud et al. discloses that the patentable utility of the disclosed compound is for treating vitamin B3 deficiency and cellular NAD(P)+ depletion, and discloses the compound in the form of the form of pharmaceutical compositions for oral administration, which is to say that the reference describes the limitations but not expressly spell out the limitations as arranged or combined as in the examined claim. However, a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination, because Migaud et al. discloses the compound formulated for oral administration and having a patentable utility for treating vitamin B3 deficiency and cellular NAD(P)+ depletion. Therefore the rejection of claims 16-17 over the disclosure of Migaud et al. is proper.
Applicant remarks that Migaud et al. does not describe the compound having a chemical purity of greater than about 90% (w/w) and containing less than about 5000 ppm ethanol. However, as detailed in the rejection of record, “According to particular embodiments, the compounds are substantially free of solvents or other by-products, most preferably quantitatively free of solvents or by-products (column 103, lines 25 to 65).” MPEP 2131 provides “The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).” In this case the most preferred embodiment which is quantitatively free of solvents or by-products describes the claimed features of the compound “having a chemical purity of greater than about 90% (w/w) and containing less than about 5000 ppm ethanol” arranged as required by the claim, and the identical terminology is not required. However, Migaud et al. at column 103, lines 25 to 65 as cited in the rejection of record further describes the terminology of “even more preferably greater than about 99.99% free of solvents or by-products” and “even more preferably less than 5 ppm of solvents or by-products”, indicating that the most preferred embodiment which is quantitatively free of solvents or by-products describes the claimed features arranged as required by the claim.
Amended Claims 1-2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alvarez et al. (Cryst. Growth Des., 2019, 19, p4019−4028, provided by Applicant in IDS filed 20 April 2023).
Alvarez et al. discloses nicotinamide-β-D-riboside triacetate bromide crystallized using vapor diffusion (page 4019, abstract and figure 1). Single crystals were obtained by vapor diffusion of the compound dissolved in ethanol against a reservoir of cyclohexane or by vapor diffusion of the compound dissolved in methanol against a reservoir of tetrahydrofuran. The chloride salt described in patent application US20180134743A1 (which is a patent family member of US 9,975,915) and the bromide of nicotinamide-β-D-riboside triacetate presented in this work are isostructural (section 2.4 spanning pages 4023-4024), meeting limitations of claims 1-3 and 5.
Alvarez et al. is silent to the chemical purity of the crystallized compound or the amount of ethanol present. MPEP 2112.01 especially at I. citing In re Best, 562 F.2d 1252, 195 USPQ 430 (C.C.P.A. 1977) and In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly recited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to show the products of the applicant and the prior art are not the same or that the prior art products do not necessarily possess the characteristics of the claimed product. In this case Alvarez et al. discloses a claimed crystalline compound, and one of skill in the art would understand crystallization to be a method of preparing the pure compound. Further, there is reason to believe that the crystalline compound prepared by vapor diffusion of the compound dissolved in methanol against a reservoir of tetrahydrofuran would not contain ethanol.
Response to Applicant’s Remarks:
Applicant’s Remarks, filed 12 Feb 2026, have been fully considered and not found to be persuasive.
Applicant’s amendment is persuasive regarding claim 3 because the alternative of bromide has been canceled from claim 3. However, amended claims 1-2 and 5 do not exclude this alternative, and the crystallized nicotinamide-β-D-riboside triacetate bromide disclosed in Alvarez et al. is still encompassed within the scope of claims 1-2 and 5 and anticipates these claims for the reasons detailed in the rejection of record.
Applicant remarks that Alvarez et al. does not describe the compound having a chemical purity of greater than about 90% (w/w) and containing less than about 5000 ppm ethanol. However, for the reasons detailed in the rejection of record, there is reason to believe the prior art products necessarily possess the characteristics of the claimed product. For example, the packing diagram of the crystallized nicotinamide-β-D-riboside triacetate bromide shown in figure 7 and referenced in section 2.4 spanning pages 4023-4024 as cited in the rejection of record does not indicate the presence of any impurities. Regarding the characterization of the compound in terms of ethanol, as detailed in the rejection of record, there is reason to believe that the crystalline compound prepared by vapor diffusion of the compound dissolved in methanol against a reservoir of tetrahydrofuran would not contain ethanol. There is reason to believe the crystalline compound prepared without using ethanol would not contain ethanol because no ethanol would be present, establishing a logical connection between the conditions using methanol and tetrahydrofuran to prepare the compound and the claimed subject matter characterizing the compound in terms of containing less than about 5000 ppm or 1000 ppm ethanol.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8-15 are rejected under 35 U.S.C. 103 as being unpatentable over Migaud et al. (US 9,975,915, issued 22 May 2018, provided by Applicant in IDS filed 20 April 2023).
Migaud et al. as applied to claims 1-7 and 16-18 teaches as above. Migaud et al. further teaches the crystalline Form I can be prepared by a method that can include the steps of (a) adding a volume of acetonitrile to the compound or derivative having formula (IX), or salt or solvate thereof, at room temperature, so as to dissolve the compound or derivative having formula (IX), or salt or solvate thereof, in the volume of acetonitrile; (b) adding a volume of acetone, which is at least equal in volume to the volume of acetonitrile, to the solution of the compound or derivative having formula (IX), or salt or solvate thereof, so as to precipitate the crystalline Form I; and (c) isolating the crystalline Form I (column 8, lines 30-40). Migaud et al. further teaches the general conditions of making crystalline forms of the compounds (column 109-171). For example, Migaud et al. teaches the embodiment in which the compound is dissolved in 95:5 methanol:water at room temperature, heated at 50 °C, and cooling to -10 °C to precipitate the crystalline form (column 109, lines 35-65). Migaud et al. teaches the example where the compound is dissolved in ethanol and water, stirred at room temperature, and cooled to -10 °C to precipitate the crystalline form (column 141, lines 20-55). Migaud et al. further teaches the state of the art in searching for alternate solid forms of drug candidates includes conventional solution crystallization and seeding (column 98, line 55 to column 99, line 15).
Migaud et al. does not specifically disclose the method of making a substantially crystalline NRTA comprising (c) cooling the reaction mixture (claim 8). Migaud et al. does not specifically disclose the method further comprising (b1) adding a third solvent immediately after step (b) (claim 9). Migaud et al. does not specifically disclose the method (c1) seeding the reaction mixture with crystalline compound Nicotinamide Riboside Triacetate, or a salt, or a solvate thereof after step (c) (claim 10). Migaud et al. does not specifically disclose the method wherein the first solvent is selected from water, ethanol, or a mixture thereof (claim 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Migaud et al. through routine experimentation to determine the optimum or workable crystallization conditions. MPEP 2144.05 at II.A. provides “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) In this case Migaud et al. teaches solution crystallization techniques are conventional to one of ordinary skill in the art, and suggests it would have been routine experimentation for the ordinary artisan to vary the conditions of the crystallization to discover the optimum or workable ranges, such as solvent choice, heating or cooling of the solution, and the use of seed crystals in the crystallization. Further, Migaud et al. provides guidance for producing the crystalline NRTA form I from acetonitrile and acetone, as well as general conditions of solvent and temperature selections for the crystallization of related compounds.
Response to Applicant’s Remarks:
Applicant’s Remarks, filed 12 Feb 2026, have been fully considered and not found to be persuasive.
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). In this case, as detailed in the rejection of record Migaud et al. further teaches the state of the art in searching for alternate solid forms of drug candidates includes conventional solution crystallization and seeding (column 98, line 55 to column 99, line 15), and teaches the general conditions of making crystalline forms of the compounds (column 109-171), suggesting it would have been routine experimentation for the ordinary artisan to vary the conditions of the crystallization to discover the optimum or workable ranges, such as solvent choice, heating or cooling of the solution, and the use of seed crystals in the crystallization.
Applicant asserts that the specific steps of the method are key to establishing a patentable difference over Migaud et al. Applicant further remarks that the production of a particular polymorphic form of the crystal would not have been the result of routine experimentation. However, as detailed in the rejection of record, Migaud et al. teaches the general methods for preparing crystalline Form I of nicotinamide riboside triacetate chloride, suggesting that one of ordinary skill in the art would have had a reasonable expectation of success to modify these conditions through routine experimentation based on the general conditions of making crystalline forms of the compounds taught within Migaud et al. to prepare the desired crystalline Form I of nicotinamide riboside triacetate chloride. Applicant asserts that the specific steps of the claimed method result in a patentable difference over Migaud et al., however Applicant does not cite evidence of criticality for the steps of the claimed method compared to the closest prior art embodiment disclosed in Migaud et al.
Conclusion
No claim is found to be allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan S Lau whose telephone number is (571)270-3531. The examiner can normally be reached Monday-Friday 9a-5p Eastern.
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/JONATHAN S LAU/ Primary Examiner, Art Unit 1693
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