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. Priority This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/IN2022/050166 , filed 02/25/2022 , which claims the priority benefit of INDIA Application No. 202121008622 , filed 03/01/2021 . Information Disclosure Statement The information disclosure statements (IDS) submitted on 01/29/2024 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Election/Restrictions Applicant's election with traverse of Group I, claims 1-3, 6, 8, and 21-22, drawn to a crystalline Form Cl of tafamidis . in the reply filed on 03/02/2026 is a cknowledged . The traversal is on the ground(s) that Groups I, II, and III have a single general inventive concept under PCT Rule 13.1. Specifically, all three groups are directed to a crystalline Form Cl of tafamidis , or the manufacture or use thereof . This is not found persuasive because xxx teaches that 1) “the use of any of the solid state forms of tafamidis and salts thereof described according to any embodiment herein, for the preparation of a pharmaceutical composition or a pharmaceutical formulation of tafamidis , wherein the tafamidis in the pharmaceutical composition or formulation is in a solid form, wherein the solid form may be any crystalline form or an amorphous form” [0015], and 2) “the use of the solid state forms of tafamidis of the present disclosure, or at least one of the above pharmaceutical compositions or formulations for the manufacture of a medicament for treating transthyretin-mediated amyloidosis ” [00103]. (emphasis added) Examiner notes from restriction requirement dated 12/29/2025 , a s provided in 37 CFR l.475(b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories: (1) A product and a process specially adapted for the manufacture of said product; or (2) A product and process of use of said product; or (3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or (4) A process and an apparatus or means specifically designed for carrying out the said process; or (5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process. Otherwise, unity of invention might not be present. See 37 CFR l.475(c). In this case claim 23 in the instant application directed “[a] method of prevention and/or treatment of transthyretin mediated amyloidosis comprising administering to a patient in need thereof a therapeutically effective amount of crystalline Form Cl of Tafamidis according to claim 1. ” Which falls into category (2) whereas claims 9-20 drawn to “ A process for preparing crystalline Form Cl of Tafamidis of claim 1, the process comprising the steps of: a) slurrying Tafamidis in a suitable non polar solvent; b) stirring for sufficient time, c) isolating the solid; and d) drying the solid. ” fall into categories (1), and (5). The requirement is still deemed proper and is therefore made FINAL. Status of claims Claims 1-3, 6, and 8-23 are currently pending in this application. Claims 4-5, 7, are cancelled. Claims 9-20 and 23 are withdrawn. Applicant’s arguments, filed 03/02/2026 , have been fully considered. Claims Group I, claims 1-3, 6, 8, and 21-22 are currently under examination. Claim Objections Claims 2 and 3 are objected to because of the following informalities: the term “characteristics ” appears in line 2 of each claims and should be –characteristic— . Appropriate correction is required. Specification The use of the term Vyndamax , Vyndaqel , (pg. 2) which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Claim Rejections - 35 USC § 112 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 6, 8, 21 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as failing to set forth 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. The term “ around ” in claim 6 , line s 2 and 3 is a relative term which renders the claim indefinite. The term “ around ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 6 indicate values of small endotherm onset with deviations of ±5°C , a skilled artisan would be unable to determine if the term “around” adds further deviation to the small endotherm values cited in the instant claim. Accordingly, the claim is indefinite and Examiner cannot ascertain the metes and bounds of the claimed scope of derivatives . The term “ about ” in claim 8 , lines 3 , 5, and 8 is a relative term which renders the claim indefinite. The term “ about ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 8 indicate values of X-ray powder diffraction pattern with deviations of ±0.2° θ and a first endothermic peak ±5°C , a skilled artisan would be unable to determine if the term “ about ” adds further deviation to the small endotherm values cited in the instant claim. Accordingly, the claim is indefinite and Examiner cannot ascertain the metes and bounds of the claimed scope of derivatives . Regarding claim 21 , the phrase "or the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d). The term “ other ” in claim 22 , line 4 is a relative term which renders the claim indefinite. The term “ other ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. A person of ordinary skill would be unable to determine which other pharmaceutical forms are meant by applicant, for example a topical formulation . Accordingly, the claim is indefinite and Examiner cannot ascertain the metes and bounds of the claimed scope of derivatives. 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 of this title, 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 set forth in Graham v. John Deere Co. , 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . Claim s 1 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Matecic (WO 2020/232325A1) in view of Barseghyan (WO 2019/175263 Al) . The instant claims are directed to a c rystalline Form C 1 of t afamidis in a pharmaceutical composition . Matecic et al. teach “ VYNDAQEL ( tafamidis meglumine) and VYNDAMAX ( tafamidis ), are both capsules for oral administration and contain tafamidis as the active moiety. The U.S. Food and Drug Administration ("FDA") has approved VYNDAQEL and VYNDAMAX for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. EMA has approved VYNDAQEL for the treatment of transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment. ” [0004] . Matecic also teaches “Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single compound, like tafamidis , may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g. measured by thermogravimetric analysis - "TGA", or differential scanning calorimetry - "DSC"), powder X-ray diffraction (PXRD) pattern, infrared absorption fingerprint, Raman absorption fingerprint, and solid state ( 13 C-) NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound . ” [0007]. Matecic discloses an embodiment that provides the use of any of the solid state forms of tafamidis and salts thereof, for the preparation of a pharmaceutical composition or a pharmaceutical formulation of tafamidis , wherein the tafamidis in the pharmaceutical composition or formulation is in a solid form, wherein the solid form may be any crystalline form or an amorphous form [0015]. Matecic also discloses an embodiment in which provides the use of any of the solid state forms of tafamidis and salts thereof described according to any embodiment herein, for the preparation of a pharmaceutical composition or a pharmaceutical formulation of tafamidis , wherein the tafamidis in the pharmaceutical composition or formulation is in a solid form, wherein the solid form may be any crystalline form or an amorphous form [0017]. However, Matecic et al. fail to disclose a C1 crystalline form of tafamidis . Barseghyan et al. teach the preparation of crystalline tafamidis polymorphs Step 2 - Compound E: Tafamidis acetic acid adduct and Step 3 - Compound F: Tafamidis meglumine – amorphous (pg. 23) and Crystalline Form of Tafamidis Meglumine starting from the Acetic acid adduct (pg. 26) . Matecic also discloses Crystalline Form of Tafamidis trifluoroacetic formic acid (TFAA) adduct starting from the Acetic acid adduct, Crystalline Form of Tafamidis free acid starting from the Acetic acid adduct and a Pressure resistance crystalline Form (pg. 26) Barseghyan discloses a pharmaceutical composition comprising crystalline tafamidis adducts is within the scope of the invention and t hese pharmaceutical compositions comprise at least the inventive Tafamidis meglumine polymorph as an API (Active Pharmaceutical Ingredient) and optionally further pharmaceutical acceptable excipients (pg. 11, 2 nd para.). Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application , to optimize the crystalline form of tafamidis to achieve better bioavailability in a pharmaceutical composition suited for the method of administration such as oral or intravenous . See MPEP 2144.05(II). A skilled artisan in the pharmaceutical industry would have reasonably applied the techniques disclosed by Matecic and Barseghyan regarding the syntheses of tafamidis crystalline polymorphic forms, while simultaneously seeking desirable properties concerning the solubility, bioavailability, density, melting point, or chemical reactivity of tafamidis crystal form for administration in desired pharmaceutical forms . A person of ordinary skill in the art would have been motivated to administer a crystalline form of tafamidis in a pharmaceutical composition formulated with an excipient following the teachings of tafamidis polymorphic crystal forms by Matecic and Barseghyan’s syntheses of tafamidis polymorphic crystal forms . A skilled artisan following the teachings of Matecic and Barseghyan would have had a reasonable expectation of success in forming a pharmaceutical composition of tafamidis and an excipient in various pharmaceutical forms. Allowable Subject Matter Claims 2 and 3 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The following is a statement of reasons for the indication of allowable subject matter: Applicants compound of a c rystalline Form Cl of 2-(3,5-Dichlorophenyl)-l,3-benzoxazole-6-carboxylic acid commonly known as " Tafamidis " with a XRPD diffractogram with characteristics peaks at 5.48, 6.44, 7.51, 9.57, 11.80, 13.65, 18.51 and 20.53 ± 0.2° 2 θ or with peaks at 16.24, 19.36, 23.68 and 27.55 ± 0.2° 2 θ . The closet prior art is Labaudiniere ( US-9249112B2 ) , Matecic ( WO2020232325A1 ) and Barseghyan (WO 2019/175263 Al) who each teach crystalline forms of t afamidis (2-(3,5-dichlorophenyl)-l,3-benzoxazole- 6-carboxylic acid but do not fairly teach or suggest the specific 2θ angles disclosed by the applicant. Conclusion Claims 1, 6, 8, and 21-22 are rejected, claims 2-3 are objected to. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ERNESTO VALLE JR whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-5356 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 0730-1700 M-F EST, 1st Friday off . 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 Adam C Milligan can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-7674 . 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