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. This office action is a response to applicant’s communication submitted November 3, 2023 , wherein claims 1-3 and 5-13 were preliminarily amended . Claims 1-13 are pending in this application. Priority This application is a 371 of PCT/EP2022/061950 filed 05/04/2022 and claims foreign priority to IN 202121020313 filed 05/04/2021 . Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received. Claim Objections Claim s 1, 4 -5 , and 12 are objected to because of the following informalities: In claims 1 and 12 the phrase “which process comprises” should read “comprising” or “comprising the steps of” or the like. Claim 4 recites “2,3,4,5-tetra-O-acetyl-D-ribose” however claim 1, of which claim 4 depends, refers to this compound as “ribose tetraacetate (RTA)”. The terms should be consistent to avoid confusion. In claims 2-11 and 13, the phrase “in claim 1, wherein, the” should read “in claim 1, wherein the”. In claim 10 the acronym “TBA” should be defined. In claim 12 the a bbreviation TMSOTf should be defined. Appropriate correction is required. Claim Interpretation Claim 7 recites the limitations “ f reshly prepared dry HCl or anhydrous HCl” and “commercially available dry HCl or anhydrous HCl”. These limitations are more akin to product-by-process limitations wherein so long as the structure of the HCl reagent is the same as the instant claim, the limitation is met. The Examiner notes that, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process" In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (See MPEP 2113 (I)). Thus even if a prior art reference does not disclose freshly preparing HCl solution or a commercial source, so long as HCl is in the recited solvents is used it infringes the claim. Specification The disclosure is objected to because of the following informalities: The instant specification uses improper capitalization throughout the disclosure, for example: The chemical name “ Tri-O-acetyl ribofuranosyl chloride ” should read ”t ri-O-acetyl ribofuranosyl chloride ” (pg. 3, line 20). The chemical names “Methyl Ethyl Ketone, Methyl Isobutyl Ketone” should read “methyl ethyl ketone, methyl isobutyl ketone” (pg. 7, line 6). T he chemical name “1 -Chloro-2,3,5-tri-O-acetyl- β -D-ribose ” should read “1 - c hloro-2,3,5-tri-O-acetyl- β -D-ribose (pg. 7, lines 14-16, 21-22, 24, pg. 8, line 16). The phrase “insitu” should read “in situ” or be hyphenated ( pg. 4, lines 12, 23, 31, pg. 6, line s 4, 15 , pg. 8, line 5, pg. 11, line 2, pg. 26, lines 14, 24 ) The acronym “TBA” should be defined the first time it appears (pg. 8, line 20). Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. Appropriate correction is required. 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. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claim s 1 -2 and 4 - 13 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Regarding claims 1, 4-11 and 13: Claim 1 recites inter alia, “….chlorinating ribose tetraacetate (RTA) by treating with dry HCl either in acetone or in acetonitrile followed by in situ coupling of chloro derivative either with nicotinamide or with 3-cyanopyridine respectively in the presence of an organic base to obtain tri-O-acetyl B-nicotinamide riboside chloride or tri-O-acetyl B-nicotinonitrile riboside chloride respectively…”. The phrase “respectively” renders the claim indefinite because it is unclear whether the phrase is meant to separate two reaction conditions (i.e. relating acetone and nicotinamide in one condition and relating acetonitrile and 3-cyanopyridine in a separate condition) or is merely used to end a list of possible alternatives . Additionally in dependent claim 7, the dry HCl solvent is not particularly limiting, including both acetone and acetonitrile as viable options , further leading to the interpretation that respectively is not meant to separate reaction conditions . A person of ordinary skill in the art would be unable to ascertain the metes and bounds of the invention due to a lack of clarity, thereby rendering claim 1 indefinite. Claims 4-11 and 13 which depend from claim 1 are similarly rejected. For Examination purposes, based on dependent claim 7, claim 1 will be interpreted such that the solvents are alternatives. Regarding claims 2 and 7: Claims 2 and 7 recite the phrases “dry HCl” and “anhydrous HCl”. Usage of both phrases within the same claim renders the claim indefinite because it is unclear what the difference is between them, leading to a lack of clarity. According to the instant specification, the phrases are interchangeable references to HCl gas (pg. 14, lines 1-5). Thus, it is unclear if they are meant to describe a property of the starting reagent (HCl gas) , or to the reaction mixture being anhydrous. The multiple possible interpretations that arise render the claims indefinite. Regarding claim 4: Claim 4 recites inter alia the phrase “wherein, the chlorination of 2,3,4,5-tetra-O-acetyl-D-ribose can also be performed in a solvent….”. The phrase “can also be performed” renders the claim indefinite because it is unclear whether the claim is reciting an optional limitation of the chlorination reaction (wherein it can be performed in the solvent), or reciting a method step as a limitation (wherein the reaction is carried out with this solvent). For Examination purposes, the claim will be interpreted as an optional limitation. Regarding claim 5: Claim 5 recites inter alia the phrase “wherein, the chlorination reaction can be conveniently carried out at a temperature…”. The phrase “ can be conveniently” renders the claim indefinite because it is unclear whether the claim is reciting an optional limitation of the chlorination reaction (wherein it can be run at this temperature), or reciting a method step as a limitation (wherein the reaction is carried out at this temperature). For Examination purposes, the claim will be interpreted as an optional limitation. Regarding claim 6: Claim 6 recites, “the process as claimed in claim 1, wherein, the reaction of step a) is carried out at a temperature range of 0 ° C to 50 ° C.” However, step a) as recited in instant claim 1 recites two separate reactions, a “chlorination” and a n “ in situ coupling reaction. It is unclear whether the temperature range is applicable to one or both of the reactions occurring within the claimed temperature range. The multiple interpretations that arise leads to a lack of clarity, thereby rendering the claim indefinite. Regarding claims 5-6 and 11: Claims 5-6 and 11 recite inter alia, “at a temperature range of”. Claim 5 recites “carried out at a temperature range of 0-5°C”. Claim 6 specifically recites “carried out at a temperature of 0°C to 50°C. Claim 11 recites “carried out at a temperature of 0 to 25°C. In each case, it is unclear whether the claims are reciting that a temperature within each range is encompassed (i.e. at 10°C), or whether the reaction is carried out from one temperature to another temperature (i.e. from 0 to 25 °C). The multiple interpretations leads to a lack of clarity, rendering the claims indefinite. Regarding claim 7: Claim 7 recites “The process as claimed in claim 1, wherein, the dry HCl or anhydrous HCl”. There is a lack of antecedent basis for the phrase “anhydrous HCl” in the claim thereby rendering the claim indefinite. For examination purposes the “anhydrous HCl” will be interpreted to be referring to “HCl in an alcoholic solvent” as recited by instant claim 1. Regarding claim 7: Claim 7 recites inter alia the phrase “wherein, the dry HCl or anhydrous HCl” used in a solvent can be selected from the group selected from….” The phrase “can be” renders the claim indefinite because it is unclear whether the claim is reciting an optional limitation of the dry HCl or anhydrous HCl (wherein it can be the specific HCl or anhydrous HCl reagents), or reciting a method step as a limitation (wherein the reaction is carried out with these reagents). For Examination purposes, the claim will be interpreted as an optional limitation. Regarding claim 7: Claim 7 recites the phras e “commercially available” to limit the structure of dry or anhydrous HCl absorbed in a solvent. The claim scope is uncertain as the phrase is in reference to a changeable standard. Thus claim 7 is rendered indefinite. Regarding claim 11: Claim 11 recites inter alia the phrase “wherein, the reaction of step b) can be performed at a temperature range of 0 to 25°C.” The phrase “can be” renders the claim indefinite because it is unclear whether the claim is reciting an optional limitation of the reaction of step b) (wherein it can be run at this temperature), or reciting a method step as a limitation (wherein the reaction is carried out at this temperature). For Examination purposes, the claim will be interpreted as an optional limitation. Regarding claim 12: Claim 12 recites inter alia “….b) hydrolyzing followed by deacetylation of tri-O-acetyl B-niconitrile riboside triflate using HCl in ethanol to afford nicotinamide riboside chloride. As recited the claim could be interpreted as two steps (i.e. hydrolyzing then deacetylation), however according to the instant specification this one step wherein hydrolyzing and deacetylation occur simultaneously (pg. 12, lines 15-17, scheme 4 , pg. 13, lines 6-7 ). Thus, it is unclear whether the claim is stating two separate steps or is meant to be a single step in which both hydrolyzing and deacetylation occur simultaneously. Claim Rejections - 35 USC § 112 (d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim s 4 and 7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 4, which depends from claim 1, recites “wherein, the chlorination of 2,3,4,5-tetra-O-acetyl-D-ribose can also be performed in a solvent selected from the group consisting of methyl ethyl ketone, methyl isobutyl ketone, and C4 to C6 ketonic solvents.”. However claim 1 recites inter alia, “…. chlorinating ribose tetraacetate (RTA) by treating with dry HCl either in acetone or in acetonitrile…”. Claim 1 already limited the solvent to acetone or acetonitrile, thus claim 4 expands, rather than limits, instant claim 1. Claim 7, which depends from claim 1, recites inter a alia, “….dry HCl or anhydrous HCl absorbed in a solvent….wherein, the solvents are selected from acetone, acetonitrile, methanol, ethanol and isopropanol.” However, the dry HCl in claim 1 is limited to “either acetone or in acetonitrile”, which does not include methanol, ethanol, and isopropanol. As best understood in view of the 112(b) issues described above, the second recitation of HCl is meant to be “anhydrous HCl”. However, this HCl is limited to “HCl in an alcoholic solvent”, which does not include acetonitrile or acetone. Thus, claim 7 expands, rather than limits instant claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 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. Claims 1, 4 - 1 1 , and 13 are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) as being anticipated by FILLIN "Insert the prior art relied upon." \d "[ 4 ]" Marcotulli (WO 2019/006262, cited on PTO-892) . Regarding claims 1, 4 - 1 1 , and 13 : Marcotulli teaches the following reaction: (pg. 42, lines 5-7, example 5). According to the instant specification TBA as recited by instant claim 10 is tributylamine (pg. 25, line 4). Marcotulli teaches the ratio of D-ribose tetraacetate is 1:1.1 (i.e. 1.1 equivalents of nicotinamide, pg. 42, lines 8-9 and 18). Marcotulli teaches the tetraacetate groups can be hydrolyzed in the following reaction (pg. 43, lines, 17-20, example 6). Wherein HCl is a gas it is dry, as described in the instant specification (pg. 14, lines 1-5 ) . Triethylamine is an organic base according to the instant specification (pg. 8, lines 16-17). Marcotulli teaches the chlorination reaction occurs between 0-5 °C (pg. 42, line 11). Marcotulli teaches the coupling reaction occurs at 15 °C and 25 °C (pg. 42, lines 19-22). Marcotulli teaches the product obtained was a pale yellow powder (i.e. amorphous form, pg. 44, lines 8-15). According to the instant specification the reaction can be run in methyl ethyl ketone as a solvent, thus the limitation as recited by instant claim 4 is satisfied. 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 7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over FILLIN "Insert the prior art relied upon." \d "[ 4 ]" Marcotulli (WO 2019/006262, cited on PTO-892) as applied to claims 1, 4 -1 1 , and 13 above in view of Spitz (WO 2019/219895, cited on PTO-892) . Regarding claims 7 and 11: Even if assuming for the sake of argument claims 7 and 11 were to be interpreted as non-optional limitations, the claims would still have been rendered obvious over Spitz. As discussed above, Marcotulli teaches the process of claim 1. Marcotulli teaches that the deacetylation reaction occurs via the addition of prepared HCl in aqueous solution to a reaction in methanol (i.e. in the presence of HCl in alcoholic solvent, pg. 43-44, bridging para.). Marcotulli teaches the reaction occurs between -5 to 0 ° C. Marcotulli does not teach wherein the HCl is anhydrous HCl absorbed in a solvent wherein the solvent is ethanol. Marcotulli does not teach wherein the reaction of step b) is performed at a temperature range of 0 to 25 ° C. However, Spitz teaches a comparable deacetylation reaction for the preparation of nicotinamide ribofuranoside chloride vie the deacetylation of nicotinamide-2,3,5-tri-O-acetyl ribofuranoside chloride (pg. 50, example 8, para. 00175). Spitz teaches the reaction can be accomplished in methanol solvent via the addition of HCl in ethanol at room temperature (i.e. approx. 25 °C, pg. 50, para. 00175). Taken together it would have been prima facie obvious a person of ordinary skill in the art to modify the process of Marcotulli by substituting the aqueous HCl with ethanolic HCl and performing the reaction at room temperature as taught by Spitz (pg. 50, para. 0050). A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as both aqueous and ethanolic HCl are established reagents for this type of reaction and it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)). Additionally, Spitz recognizes that this reaction can be performed at room temperature which falls within the claimed temperature range. Wherein temperatures as low as -5 and a high as room temperature are known in the art for this type of reaction, it is not inventive to discover the optimum or workable ranges by routine experimentation (See MPEP 2144.05 (II)). Wherein Spitz teaches an HCl in ethanol solution, it necessarily has the structure of freshly prepared or commercially available HCl in ethanol solution, absent evidence to the contrary. Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over FILLIN "Insert the prior art relied upon." \d "[ 4 ]" Marcotulli (WO 2019/006262, cited on PTO-892) and Spitz (WO 2019/219895, cited on PTO-892) as applied to claims 1, 4-11, and 13 abov e in view of Xie (Polymer Testing, 2017, cited on PTO-892). Regarding claim 2: As discussed above Marcotulli teaches the process of method claim 1. Marcotulli and Spitz render obvious a method deacetylating in the presence of HCl in an alcoholic solvent. Marcotulli teaches that exemplary chlorinating agents include sources of HCl, such as HCl gas or HCl in a solvent such as ethanol or dioxane (pg. 4, lines 15-16). They do not teach wherein step a) the chlorination reaction is performed with dry HCl in acetone. However, Xie teaches that acetone can serve as a solvent for HCl reagents in chlorination reactions (pg. 114, col. 1, para. 5, col. 2, para. 1). Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the method such that dry HCl is provided in acetone as taught by Xie . A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as acetone is a known solvent in the art to facilitate reacting with HCl gas. A person of ordinary skill in the art would understand that acetone, a polar aprotic solvent, can serve as a reaction medium. Allowable Subject Matter The following is a statement of reasons for the indication of allowable subject matter: Claim 3 is objected to for minor informalities as discussed above and is objected to as being dependent upon a rejected base claim , but would be allowable over the prior art following correction if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The closest prior art is FILLIN "Insert the prior art relied upon." \d "[ 4 ]" Marcotulli (WO 2019/006262, cited on PTO-892) as applied to claims 1, 4-11, and 13 in view of OECD SIDS (3-pyridinecarboxamide (nicotinamide), 2002 , cited on PTO-892 ). As discussed above, Marcotulli teaches the process of claim 1 wherein an in situ coupling of nicotinamide is utilized . Marcotulli does not teach wherein the process comprises in situ coupling with 3-cyanopyridine. OECD SIDS teaches that nicotinamide can be synthesized via hydrolysis of 3-cyanopyridine in water in the presence of a catalyst (pg. 30, para. 1). It would be improper hindsight to suggest it would have been prima facie obvious to a person of ordinary skill in the art to modify the reaction by coupling the chloro derivative of ribose tetraacetate with 3-cyanopyridine in situ in the presence of HCl followed by deacetylating to afford nicotinamide riboside chloride. A person of ordinary skill would lack the motivation to do so as there is no teaching in the art that such a reaction would be successful . Conclusion No claims are allowed in this action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT SAMUEL L GALSTER whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0933 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 8:00 AM - 5:00 PM . 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, FILLIN "SPE Name?" \* MERGEFORMAT Scarlett Y Goon can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-5241 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /SAMUEL L GALSTER/ Examiner, Art Unit 1693