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 .
Election/Restrictions
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Amended claims 1-6, 8-20 are pending.
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.
Claim(s) 1-6, 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over NPL Document A7 Drks00021214: 2020-04-06, NPL Document A17 Shakoor, Maturitas, vol. 144, 15 August 2020, pages 108-111, NPL Document A8, Jiang, Research Square 23 October 2020 (Document D10), NPL Document A16 Mario, "Nicotinamide Riboside - The Current State of Research and Therapeutic Uses", NUTRIENTS, vol. 12, no. 6, 31 May 2020, page 1-22, Schwarz WO2017182347, Georg US10426765 and Wätzig US10758552, Heer, J.Biol. Chem. (2020)295(52) 17986–17996, Schentag US 20150071994, Hulley, Designing Clinical Research, 4th Edition, pages 1-367, 2013; and Chidambaram Pediatr Invest 2019 Dec; 3(4): 245-252.
Drks00021214 (German clinical trial) titled Improvement of the nutritional status regarding nicotinamide (vitamin B3) and the course of COVID-19 disease", teaches that a nutritional intervention with nicotinamide can support the therapy of COVID-19. In particular the frequency of severe disease progression in COVID-19 patients can decrease if they supplement 1,000 mg of nicotinamide. D1 also teaches that nicotinamide can reduce virus replication and support the body's defense mechanisms for a wide variety of virus types, e.g. vaccinia, HIV, enteroviruses of hepatitis B.
Shakoor, titled "Be well: A potential role for vitamin B in COVID-19", teaches a composition comprising nicotinamide or nicotinic acid for use in the treatment of viral infections, such as influenza, severe acute respiratory syndrome (SARS) or HIV (page 4, line 3 - line 4; page 7, line 5 - line 1O; page 7, line 25 - line 26;
Jiang, titled "Treatment of SARS-CoV-2 induced pneumonia with NAO+ in a mouse model", teaches the use of the use of nicotinamide adenine dinucleotide (NAO) in the treatment of COVID-19 patients.
Mario titled "Nicotinamide Riboside - The Current State of Research and Therapeutic Uses" teaches the antiviral effect of nicotinamide riboside (NR) in patients with HIV or hepatitis B. NR is also described as a potential therapeutic against COVID-19.
The teachings of Schwarz, Georg, Wätzig, Heer, Schentag, Hulley and Chidambaram
even though, not drawn to the treatment of the specific disease states of instant claim, as explained below do teach the formulation characteristics of the instant claim 1 and do suggest the use of the formulation in the treatment of Covid.
Schwarz teaches a microcapsule, comprising a core containing vitamin B3, the use of such a microcapsule as a medicament, nutraceutical, dietary supplement, food ingredient or food, and the use of such a microcapsule in the therapy and/or prophylaxis of a multitude of diseases. The present invention further relates to formulations and compositions comprising such a microcapsule and a method for producing for such a microcapsule. According to Schwarz at page 1, line 8-20 administration of vitamin B3 [comprising nicotinic acid (NA) and nicotinamide (NAM)] has recently and surprisingly been demonstrated to have beneficial effects beyond nutritional vitamin supplementation. When delivered in controlled release formulations targeting the lower small intestine and/or colon, vitamin B3 has been shown to have beneficial effects on the intestinal microbiota, resulting in a significant amelioration of intestinal inflammation and substantial changes in the intestinal microbiota in mouse models
The teachings of Wätzig and Georg are drawn to efficacy of NAM controlled-release formulations. Wätzig and Georg teach pharmaceutical composition comprising one, two or more active substance(s) selected from nicotinic acid; nicotinamide; tryptophan; a compound that converts in the body of an animal (e.g., a human body) into nicotinic acid, nicotinamide or tryptophan; nicotinamide adenine dinucleotide (NAD); nicotinamide adenine dinucleotide phosphate (NADP); an intermediate in the biosynthesis of NAD or NADP; and a tryptophan dipeptide, for positively influencing the intestinal microbiota, wherein the pharmaceutical composition is designed for a delayed release so that it releases (e.g., partially releases, selectively releases) in the lower small intestine, the colon or both.
Highlighted below are details of the Wätzig and Georg formulations as applicable to the limitations of the recited formulations of base claim 1 (details of the limitations of (a), (b) and (c) ):
Georg teaches
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and Wätzig teaches
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As such the position taken is that the claimed elements/ limitations with respect to
disease states (claims (1,) 2, 13, 15, 14, 11, 19, 20),
controlled delayed, oral claim 8, 9, 17
breakfast! In the morning , daily activity, claims 10, 12
dosage and two formulations (more on this below) claim 4, 5, 6, 11, 16, 18
are taught in the cited references and within the purview of one of skill in the art, for example, Drks00021214 is clinical trial refence.
Further claim language such as
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are found in the teachings of Schentag, Hulley and Chidambaram; also see
https://shms-prod.s3.amazonaws.com/media/editor/147459/L3_Pharmaceutical_Excipients__Types_of_Tablets.pdf.
and https://www.organicfacts.net/health-benefits/cereal/barley-grass.html;
Schentag teaches invention provides oral vaccine formulations which deliver an antigen in the vicinity of the distal ileum and the area of the ileal Brake and/or the appendix. These vaccines are useful in the treatment and/or prevention of variety of disorders, including viral and bacterial infections and cancers. Related methods of treatment which use the oral vaccine formulations of the invention are also provided. ). Schentag is directed to microencapsulation of microparticles [0132, 0144], thus making microcapsules, where the formulation comprises a plurality of cores comprising an antigen and optional adjuvant and a pharmaceutically excitable excipient with a first shellac enteric coating encapsulates the antigen and a second enteric coating of shellac encapsulates the first coating (claim 1). Schentag also teach adding a nutritional substance (claims 9 and 12) which is synonymous with “ileal break hormone releasing substance” [0040, 0052]. Schentag teach nutritional substances include barley grass, which as evidenced by Nagdeve, M., contains niacin (vitamin B3), alfalfa and chlorella which both with contain B complex, which include vitamin B3 as well. Schentag teach adding sodium carbonate as an excipient as well as buffering agents [0058]. Schentag teach coating the nutritional substance with an enteric coating such as shellac which can comprise two or more compositions [0054]. Schentag teach a “pill within a pill” composition in Figure 5 with inner membrane and outer membrane as shown below:
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Hulley and Chidambaram teach how and what of designing clinical research
Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. The differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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).
Also note that the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the “use” is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the applicants had merely found a new property of the compound and such a discovery did not constitute a new use.
As MPEP 2112 Requirements of Rejection Based on Inherency; Burden of Proof [R-10.2019], "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer."
All the claimed limitations of active agent, disease targets and the(why (biochemical mechanism) and how formulating for intestinal/colon delivery are taught in the prior art.
As such nothing unobvious is seen in the claims.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
Qin, Gut ACE2 Expression, Tryptophan Deficiency, and Inflammatory Responses The Potential Connection That Should Not Be Ignored During SARS-CoV-2 Infection Cellular and Molecular Gastroenterology and Hepatology (2021), 12(4), 1514-1516.e4.
Lines, WO 2008/011363 Document D6 discloses a composition comprising nicotinamide or nicotinic acid for use in the treatment of viral infections, such as influenza, severe acute respiratory syndrome (SARS) or HIV (page 4, line 3 - line 4; page 7, line 5 - line 1O; page 7, line 25 - line 26;claims 1,13,32,35,36).
and the following Applicant provided NPL documents See IDS 05/25/2023.
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.
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.
Claim(s) 1-6, 8-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. US10426765, further in view of NPL Document A7 Drks00021214: 2020-04-06, NPL Document A17 Shakoor, Maturitas, vol. 144, 15 August 2020, pages 108-111, NPL Document A8, Jiang, Research Square 23 October 2020 (Document D10), NPL Document A16 Mario, "Nicotinamide Riboside - The Current State of Research and Therapeutic Uses", NUTRIENTS, vol. 12, no. 6, 31 May 2020, page 1-22, Schwarz WO2017182347, Heer, J.Biol. Chem. (2020)295(52) 17986–17996, Schentag US 20150071994, Hulley, Designing Clinical Research, 4th Edition, pages 1-367, 2013 and Chidambaram Pediatr Invest 2019 Dec; 3(4): 245-252.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims contain overlapping subject matter.
Claim 10 and claim 1 of US10426765 are
10. A
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comprising orally administering a composition according to claim 1 to a subject in need thereof,
wherein claim 1 is
1. 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-formyl kynurenine, L-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilate, 2-amino-3-carboxymuconate semialdehyde, 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.
Claims of US10426765 do not teach the specific diseases listed in the instant claim 1, even though the claim 10 does recite, therapeutic method a subject in need thereof.
This deficiency of US10426765 is cured by the teachings of Drks00021214, Shakoor, Jiang, Mario, because these references (and other NPL documents) teach the use of the nicotinamide in the
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claim 10 of US10426765.
Further the teachings of Heer, Schentag and Hulley and Chidambaram are invoked how to use the active ingredient of claim 10 of US10426765, that is nicotinamide containing composition of claim 1 of US10426765 for
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Drks00021214 (German clinical trial) titled Improvement of the nutritional status regarding nicotinamide (vitamin B3) and the course of COVID-19 disease", teaches that a nutritional intervention with nicotinamide can support the therapy of COVID-19. In particular the frequency of severe disease progression in COVID-19 patients can decrease if they supplement 1,000 mg of nicotinamide. D1 also teaches that nicotinamide can reduce virus replication and support the body's defense mechanisms for a wide variety of virus types, e.g. vaccinia, HIV, enteroviruses of hepatitis B.
Shakoor, titled "Be well: A potential role for vitamin B in COVID-19", teaches a composition comprising nicotinamide or nicotinic acid for use in the treatment of viral infections, such as influenza, severe acute respiratory syndrome (SARS) or HIV (page 4, line 3 - line 4; page 7, line 5 - line 1O; page 7, line 25 - line 26;
Jiang, titled "Treatment of SARS-CoV-2 induced pneumonia with NAO+ in a mouse model", teaches the use of the use of nicotinamide adenine dinucleotide (NAO) in the treatment of COVID-19 patients.
Mario titled "Nicotinamide Riboside - The Current State of Research and Therapeutic Uses" teaches the antiviral effect of nicotinamide riboside (NR) in patients with HIV or hepatitis B. NR is also described as a potential therapeutic against COVID-19.
Note: The above NPL documents as well as several other NPL documents in IDS filed 5/25/2025 not in the rejection statement here teach the use of nicotinamide in the treatment of COVID-19.
The above citations do not explicitly teach the critical limitation(s) of base claim that is not explicitly taught in the above teachings is
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and particulars of how the formulation of the administered active substance (nicotinamide) and dosage.
Heer teaches that coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. More specifically to the point is Heer teachings at page 17991 bottom of Column A, under section : NAD boosting compounds decrease replication of a CARH-mutant MHV’ and at page 17991 section under Discussion SARS-CoV-2 is a highly infectious agent that constitutes a
severe threat to public health. Morbidity and mortality data make it clear that age, smoking status, and multiple preexisting conditions greatly increase the frequency of serious illness and death. There is an abundance of data from model systems
and humans that age and conditions of metabolic stress including obesity and type 2 diabetes, smoking, heart failure, nerve damage, and central brain injury challenge the NAD system in affected tissues.
Schentag teaches invention provides oral vaccine formulations which deliver an antigen in the vicinity of the distal ileum and the area of the ileal Brake and/or the appendix. These vaccines are useful in the treatment and/or prevention of variety of disorders, including viral and bacterial infections and cancers. Related methods of treatment which use the oral vaccine formulations of the invention are also provided. ). Schentag is directed to microencapsulation of microparticles [0132, 0144], thus making microcapsules, where the formulation comprises a plurality of cores comprising an antigen and optional adjuvant and a pharmaceutically excitable excipient with a first shellac enteric coating encapsulates the antigen and a second enteric coating of shellac encapsulates the first coating (claim 1). Schentag also teach adding a nutritional substance (claims 9 and 12) which is synonymous with “ileal break hormone releasing substance” [0040, 0052]. Schentag teach nutritional substances include barley grass, which as evidenced by Nagdeve, M., contains niacin (vitamin B3), alfalfa and chlorella which both with contain B complex, which include vitamin B3 as well. Schentag teach adding sodium carbonate as an excipient as well as buffering agents [0058]. Schentag teach coating the nutritional substance with an enteric coating such as shellac which can comprise two or more compositions [0054]. Schentag teach a “pill within a pill” composition in Figure 5 with inner membrane and outer membrane as shown below:
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Hulley and Chidambaram teach how and what of designing clinical research
Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. The differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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).
Also note that the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the “use” is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the applicants had merely found a new property of the compound and such a discovery did not constitute a new use.
As MPEP 2112 Requirements of Rejection Based on Inherency; Burden of Proof [R-10.2019], "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer."
As such one of skill in the art would have reasonable expectation of success in using the formulation of claims 1 of US10426765, in the claimed method.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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