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 . 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.
Election/Restrictions
Applicants elected group I (nicotinic acid and derivatives) with traverse in the response of 6 Dec, 2021. The response was found unpersuasive, and the election/restriction requirement made final in the office action of 25 March, 2022.
Claims Status
Claims 22-24, 26, 28, 30-39, and 41-46 are pending.
Claims 22 and 41 have been amended.
Claims 28, 34-39, and 42-46 are withdrawn due to an election/restriction requirement.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 22- 24, 26, 30- 33 and 41 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claim(s) contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
The response filed Nov. 16, 2023 has introduced NEW MATTER into the claims. Amended claims 22 and 41 recite "the only active ingredient is selected from the group consisting of non-protonated nicotinic acid, non-protonated nicotinamide, tryptophan, tryptophan dipeptide, or a combination of two or more thereof".
In addition, claim 26 recites “the only active ingredient is selected from the group consisting of non-protonated nicotinic acid, non-protonated nicotinamide, tryptophan, tryptophan dipeptide” Insufficient support is found in the instant application for this limitation for multiple reasons as follows. Nowhere does the application as-filed provide support for the concept of positively excluding an (undefined-see the indefiniteness rejection below) set of other ingredients from the claimed composition, whether those ingredients are "active" or not.
Applicant has not specifically pointed to support for this amendment. The disclosure has been searched “throughout the application as originally filed”, and the examiner has been unable to identify support. There is no mention/discussion of excluding other active agent(s) from the composition.
As such, independent claims 22 and 41; as well as, dependent claim 26 now recite limitations that were not clearly disclosed in the specification as filed and that change the scope of the instant disclosure as filed. Such limitations recited in claims 22, 26, and 41, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. Applicants are required to provide sufficient written support for the limitations recited in present claims 22, 26, and 41 in the specification or claims, as-filed, or remove these limitations from the claims in response to this Office Action.
Dependent claims 23- 24 and 30- 33 ultimately depend from claim 22, and are rejected also.
response to applicant’s arguments
Applicants argue that ipsis verbis recitation is not necessary, and that unambiguous possession is not the legal standard.
Applicant's arguments filed 26 Sept, 2025 have been fully considered but they are not persuasive.
It is agreed that word for word matching is not necessary to provide support, but the concept must be in the disclosure. For a negative limitation, such as applicant’s amendment, applicants must have support for the concepts being excluded (MPEP 2173.05(i). The point of the rejection is that they do not. Applicants argue that they do not need unambiguous possession. However, a person of skill in the art would not read applicant’s application as showing possession of the amendment.
Claim Rejections - 35 USC § 112(b)
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.
Claims 22- 24, 26, 30- 33 and 41 are 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 pre-AIA the applicant regards as the invention.
Claims 22- 24, 26, 30- 33 and 41 are rejected as indefinite in the recitation “a composition for positively influencing intestinal microbiota, comprising an active ingredient wherein the only active ingredient is selected from the group consisting of non-protonated nicotinic acid, non-protonated nicotinamide, tryptophan, tryptophan dipeptide". This limitation is indefinite because it is unclear what qualifies as an active ingredient. It is unclear what property or properties are required for an active ingredient to qualify as being "an active ingredient" within the meaning of the instant claims. In other words, it is unclear what activity (or activities) the active ingredient of the claims is allowed to have in order to be considered an active ingredient. Thus, it is unclear exactly what ingredients are included/excluded by the claims.
Further, the limitation is unclear because almost any substance can be considered to have an activity of one type or another (for example, water can be considered to be a lubricant, emollient, or an essential nutrient). In addition, lactose and starch are a sugar source for bacterium, and mannitol is known to protect bacteria during conditions of stress. Thus, lactose and mannitol (taught as acceptable coating ingredients on p. 11 of the specification as-filed) could reasonably be considered active agents and it is unclear if the newly added language excludes these components or not. The interpretation of this claim is confounded by the numerous different intestinal microbiota, which may be “positively influenced” in a variety of different ways (measured by different outcomes) in the presence of any number of suitable coating agents, binders, fillers, glidants, lubricants, and flow regulating agents disclosed. Further, as stated above, it is unclear if the “active ingredient(s)” allowed by the claim are even required to be active to “positively influence intestinal microbiota” or if some other measure of activity is intended. Since one of ordinary skill in the art could not be expected to make a reasonable distinction in the absence of further definitions and/or guidance in the specification, the metes and bounds of these claims are indefinite. As such, the claims are rejected.
response to applicant’s arguments
Applicants argue that a person of skill in the art knows what an active ingredient is, cites 21 CFR 314.3(b), and argues that the active ingredient is “for topical efficacy in the terminal ileum where the intestinal microbiota to be influenced are located to thereby positively influence the intestinal microbiota” based on the claims and disclosure of the application
Applicant's arguments filed 26 Sept, 2025 have been fully considered but they are not persuasive.
21 CFR 314.3(b) is a list of definitions for the FDA, including that of an active ingredient:
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Applicants also argue that the ingredient is “for topical efficacy in the terminal ileum where the intestinal microbiota to be influenced are located to thereby positively influence the intestinal microbiota.” Note that this is two different definitions that give different genera of active ingredients. Both of these definitions are indefinite in the context of this application. The FDA definition defines the active ingredient in terms of the intent of the user. A person who makes up a boric acid buffered salt solution could be intending it for cell culture work, so none of the ingredients are an active ingredient. Or it could be an eye wash formulation (McKesson Eye Wash package insert, approved 1981). Applicant argues that this has no active ingredients, but water is the active ingredient (McKesson Eye Wash, product insert, approved 1981, previously cited). Applicant’s definition limits active ingredients to those intended to positively influence intestinal microbiota. But for many compounds, we do not know the effect of the drug on intestinal microbiota.
Rejection 35 U.S.C. §102
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.
first rejection
Claims 22- 24, 26, 30- 33, and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KUHRTS et al., WO 96/32942, Pub: Oct. 24, 1996.
Regarding claims 22- 26 and 29- 33, KUHRTS et al. discloses compositions of sustained release niacin (p. 10, last paragraph before the Brief Description of the Drawings section) in doses between 50- 5000 mg. (p. 10, final paragraph; p. 14, final paragraph, 2nd sentence), overlapping with the range of the examined claims. KUHRTS et al. defines Niacin to include nicotinic acid and all congeners. (p. 1, first sentence; p. 1, last complete sentence; p. 6, line 3). The enteric coating of Niacin is specifically disclosed with particular coatings which would have been known to the artisan (e.g., Eudragit S-100 {designed for bypassing the stomach for release in the colon}. (See p. 20; and the sentence spanning pp. 20- 21; p. 24, 2nd to last paragraph).
Thus, claims 22- 24, 26, and 30- 33 are anticipated by the compositions of KUHRTS et al.
response to applicant’s arguments
Applicants argue that the document does not meet the limitation of “the active ingredient consists of” a Markush group, because the NSAIDs of the document are an additional active ingredient. Applicants also argue that the reference is silent on the release being in the terminal illium.
Applicant's arguments filed 26 Sept, 2025 have been fully considered but they are not persuasive.
In response to the rejection under 35 USC 112(b), above, applicants argue that an active ingredient is “for topical efficacy in the terminal ileum where the intestinal microbiota to be influenced are located to thereby positively influence the intestinal microbiota.” By this definition, the NSAIDs of Kuhrts et al is not an active ingredient, because it is not intended to influence intestinal microbiota, but rather to control flushing.
Applicants argue that the reference does not disclose release in the terminal illium. While the reference does not explicitly state where it is released, it uses the same methods that applicants do to control the release, so this limitation is inherent.
second rejection
Claim(s) 22-24, 26, 30-33, and 41 are rejected under 35 U.S.C. 102(a)(1 and 2) as being anticipated by Vooturi et al (US 20110123575).
Vooturi et al discuss modified release niacin formulations (title), a synonym of nicotinic acid (paragraph 3). These formulations can comprise a barrier coating and an enteric coating (paragraphs 26-28) for modified release (paragraph 48). Note that these coatings are pH sensitive, and will release the drug when the formulation arrives at an area with a pH higher than the stomach (paragraph 97), i.e. the ileum. Niacin is intended to be interpreted broadly enough to include prodrugs, such as nicotinamide (paragraph 50). While additional drugs are intended to be used with this formulation, they are administered separately (paragraph 41), i.e. are not part of the formulation of the invention. Dosage is around 2-3 g/day (paragraph 7) with pills comprising 375, 500, and 750 mg (paragraph 17) mentioned.
Vooturi et al discuss coated niacin formulations for modified release (interpreted as synonymous with selective release of the claims), and dosages overlapping with the claimed amounts. Thus, the reference anticipates claims 22 and 23.
The reference discusses pH sensitive coatings that release upon leaving the stomach, anticipating claims 24 and 30-33.
Niacin is defined so as to include nicotinamide, anticipating claim 26.
response to applicant’s arguments
Applicants have not argued this rejection.
Double patenting (Maintained).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 22- 24, 26, and 30-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No.US 10,758,552 B2 (‘552).
Regarding claims 22-24, 26, and 30-33, claim 1 of ‘552 recites: A pharmaceutical product for beneficially influencing the intestinal microbiota, comprising as separate compounds: (i) 10-3000 mg 5-aminosalicylic acid or a prodrug thereof formulated for oral administration and comprising one or more of (a) a coating for controlled and/or delayed release, wherein the coating is resistant to gastric juice and dissolves depending on the pH, (b) a matrix for controlled and/or delayed release, and (c) a carrier for controlled and/or delayed release; and (ii) 10-3000 mg nicotinamide (NAM) formulated for oral administration and formulated to selectively release the NAM in the lower small intestine, the colon, or both, for topical efficacy where the intestinal micro biota to be influenced are located, for beneficially influencing the intestinal microbiota, wherein the NAM comprises one or more of (a') a coating for controlled and/or delayed release, wherein the coating is resistant to gastric juice and dissolves depending on the pH, (b') a matrix for controlled and/or delayed release, and ( c') a carrier for controlled and/or delayed release.
Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the ‘552 claims anticipate instant claims 22-27 and 30-33.
response to applicant’s arguments
Applicants state that they will defer this issue until the application is otherwise in condition for allowance. However, until the rejection is overcome, it will remain.
Claims 22-24, 26, and 30-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 16 of U.S. Patent No.US 10,888,555 B2 (‘555).
Regarding claims 22-23, 25-26, and 30-33, claim 1 of ‘555 recites: A pharmaceutical composition for beneficially influencing blood and/or plasma and/or serum lipid levels by beneficially modifying the intestinal microbiota, comprising an active substance selected from nicotinic acid, nicotinamide, nicotinic acid esters, and combinations of any two or more thereof, wherein the composition is formulated for oral administration with controlled and/or delayed release for selective local release of the active substance for topical efficacy in the lower small intestine and/or colon where the intestinal microbiota to be modified are located, thereby beneficially modifying the intestinal microbiota, in an amount effective to increase high density lipoprotein (HDL) blood levels, decrease liver fat content, and/or beneficially influence blood and/or plasma and/or serum lipid levels, wherein the composition is provided with a coating and wherein the controlled and/or delayed release is achieved by the coating.
Regarding claim 24, claim 16 of ‘555 recites: wherein the composition is provided with a coating resistant to gastric juice that dissolves depending on the pH and/or a film coating,
Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the patented compositions could be read as embodiments of the instant claims.
response to applicant’s arguments
Applicants state that they will defer this issue until the application is otherwise in condition for allowance. However, until the rejection is overcome, it will remain.
Claims22-24, 26, and 30-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,622,938.
Regarding claims 22-26, and 30-33, claim 78 of ‘654 recites: A unit dose pharmaceutical product for the oral administration of nicotinamide to a subject, comprising: (a) a plurality of delayed-immediate release minitablets comprising a compressed matrix comprising nicotinamide provided with a pH-dependent enteric coating, wherein the delayed-immediate release minitablets selectively release nicotinamide in the distal ileum; and (b) a plurality of delayed-extended release mini tablets comprising a compressed matrix comprising nicotinamide provided with an inner pH-independent extended release coating and an outer pH-dependent enteric coating, wherein the delayed-extended release minitablets selectively release nicotinamide in the colon; optionally, wherein (a) and (b) are provided in a sachet, capsule, or vial; wherein: the relative amounts of (a) and (b) in the unit dose pharmaceutical product are such that from 10 to 90% w/w of the nicotinamide provided in the unit dose pharmaceutical is present in the delayed-extended release mini tablets of (b ); and the total amount of nicotinamide in the unit dose pharmaceutical product is from 0.25 to 6 g.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘654 could be read as dependent claims of the instant claim set.
response to applicant’s arguments
Applicants state that they will defer this issue until the application is otherwise in condition for allowance. However, until the rejection is overcome, it will remain.
Claims 22- 24, 26, and 30- 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US-10,426, 765 (‘765).
Regarding claims 22-24, 26, and 30-33; specifically 22 and 31, claim 1 of ‘765 recites: An oral pharmaceutical composition for positively influencing intestinal microbiota, comprising an active substance selected from the group consisting of nicotinic acid, nicotinamide; tryptophan; nicotinic acid esters; nicotinamide adenine dinucleotide (NAD); nicotinamide adenine dinucleotide phosphate (NADP); an intermediate in the biosynthesis of NAD or NADP selected from N-formylkynurenine, L-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilate, 2-amino-3-carboxymuconate semi-aldehyde, quinolinate, and beta-nicotinate D-ribonucleotide·a tryptophan dipeptide; or a combination of two or more thereof, formulated for selective release in the terminal ileum, the colon, or both, for topical efficacy in the terminal ileum, the colon, or both, where the intestinal microbiota to be influenced are located, wherein the oral pharmaceutical composition is formulated for oral administration and comprises (a) a matrix that comprises the active substance(s), wherein the matrix comprises one or more selected from microcrystalline cellulose, gelatin, and polyvinylpyrrolidone, and, optionally, (b) a coating, wherein the oral pharmaceutical composition selectively releases the active substance(s) in the terminal ileum, the colon, or both for topical efficacy in the terminal ileum, the colon, or both, to thereby positively influence intestinal microbiota.
Regarding claims 23, Claim 22 of ‘765 recites: The pharmaceutical composition according to claim 1, wherein the oral composition is formulated with the coating, wherein the coating selectively releases the active substance(s) in the terminal ileum, the colon, or both, for topical efficacy in the terminal ileum, the colon, or both.
Regarding claim 26, claim 3 of ‘765 recites: The pharmaceutical composition according to claim 1, wherein the composition comprises nicotinamide as an active substance.
Regarding claim 30, claim 6 of ‘765 recites: The pharmaceutical composition according to claim 1, wherein the oral composition is formulated for oral administration to provide delayed release of the active substance(s) for specific local effect in the terminal ileum and/or colon.
Regarding claim 32, claim 7 of ‘765 recites: The pharmaceutical composition according to claim 1, wherein the oral composition is formulated for oral administration to provide controlled release of the active substance(s) for specific local effect in the terminal ileum and/or colon.
Regarding claims 24 and 33, claim 23 of ‘765 recites: The pharmaceutical composition according to claim 22, wherein the coating releases the active substance(s) at pH>6.4.
Thus, the present claims embody obvious variants of the compositions of ‘765.
response to applicant’s arguments
Applicants state that they will defer this issue until the application is otherwise in condition for allowance. However, until the rejection is overcome, it will remain.
Conclusion
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658