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 .
Status of the Claims
Claims 5 – 8, 11 – 21 and the newly added claims 22 – 23 are pending.
Claims 5 – 7, 11 – 14 and 21 are rejected.
Claims 8, 15 – 20 and 22 – 23 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 5 – 7, 11 – 14 and 21, in the reply filed on October 29, 2025 is acknowledged.
On page 8, Applicant states that the present application overcome the drawbacks associated with hazardous and highly toxic reagents that are employed in the preparation of the compound of Formula (I) in Girard et al.. The instant application discloses stable crystalline forms of the compound and its pharmaceutically acceptable salt that have enhanced stability, handling, and formulation characteristics for potential pharmaceutical applications. Further, Example 2 of Girard et al. describes the preparation of Form 4 from the starting material Form 1, which is structurally different than the starting material in the present application. Thus, the overall process disclosed in Girard et al. is technically distinct from the claims invention and Applicant disagrees with the Examiner’s observation that the present invention lacks any special technical feature over the prior art. However, as noted in paragraph 6 of the restriction requirement dated August 29, 2025, the groups of inventions do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. Emphasis added. The distinction between the process or invention of Girard et al. and the present application is not discussed in the requirement of unity of invention as required under 37 CFR 1.475(a). Thus, the requirement is still deemed proper and is therefore made FINAL.
Examination: The election invention of Group I is not allowable over the prior art.
The newly added claim 22 is directed to the base salt of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole of formula (II) according to the claim 11, and further recites limitations of the base salt.
The newly added claim 23 is directed to the base salt of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole of formula (II) according to the claim 11, and further recites limitations of specific PXRPD pattern peaks. Emphasis added.
It is noted that claim 11 is directed towards a process for preparation of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole. The invention of base salt of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole of formula (II) is claimed in withdrawn claim 8. Thus, claims 8, 15 – 20 and 22 – 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Noncompliant Amendment
The Amendment filed on October 29, 2025 is not compliant with the requirements of 37 CFR 1.121(c)(1) which states in part that “The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment”. Claims 9 and 10 have been identified as Canceled in the status identifiers. However, said claims also include text after the status identifiers. Amendment is required to delete all text in the claims after the “Canceled” status. Since Applicant’s reply appears bona fide, the amendment has been entered; however, appropriate correction is required in replying to this Office Action.
Priority
PNG
media_image1.png
108
380
media_image1.png
Greyscale
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 2, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 5 – 7, 11 – 12, 14 and 21 are objected to because of the following informalities:
Claim 5:
Line 2 of the claim: The structure of the compound, 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole of formula (I), is not recited in the preamble of the claim. In order to overcome the objection, Applicant may amend to insert the structure of formula (I) after the phrase “… 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole of formula (I)”.
Line 7 of the claim: The claim improperly recites a period (.) at the end of line 7 in step d). In order to overcome the objection, Applicant may amend to replace the period (.) with a comma (,) at the end of line 7.
Line 11 of the claim: The limitation “or a combination thereof” is grammatically incorrect because it does not recite proper punctuations for the claimed group of alternatives in the combination. In order to overcome the objection, Applicant may amend the limitation as follows: “… phosphoric acid and polyphosphoric acid, or a combination thereof, and suitable solvent…”.
Line 15 of the claim: The limitation “or a combination thereof” is grammatically incorrect because it does not recite proper punctuation for the claimed group of alternatives in the combination. In order to overcome the objection, Applicant may amend the limitation as follows: “… cyclohexane and heptane, or a combination thereof”.
Claim 6:
Line 1 of the claim: The limitation “The process according to the claim 5 wherein…” is grammatically incorrect because it does not recite proper punctuation (comma (,)) between the preamble and the body of the claim. In order to overcome the objection, Applicant may amend the limitation as follows: “The process according to the claim 5, wherein…”.
Claim 7:
Lines 2 – 4 of the claim: The structure of the compound, 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole meglumine salt of Formula (IA), is not recited in the context of the claim. In order to overcome the objection, Applicant may amend to insert the structure of Formula (IA).
Claim 11:
Page 3, line 2 of the claim: The limitation “and its pharmaceutically acceptable salt thereof” is grammatically incorrect because it does not recite proper language and punctuations (comma (,)) for the claimed group of alternatives for the pharmaceutically acceptable salt. In order to overcome the objection, Applicant may amend the limitation as follows: “… benzoxazole of formula (I), or [[and]] its pharmaceutically acceptable salt thereof, comprising…”.
Page 4, lines 12 – 13 of the claim: The limitation “and its pharmaceutically acceptable salt thereof” is grammatically incorrect because it does not recite proper language and punctuation (comma (,)) for the claimed group of alternatives for the pharmaceutically acceptable salt. In order to overcome the objection, Applicant may amend the limitation as follows: “… benzoxazole of formula (I), or [[and]] its pharmaceutically acceptable salt thereof”.
Claim 12:
Line 2 of the claim: The limitation “The process according to the claim 11 wherein the esterification…” is grammatically incorrect because it does not recite proper punctuation (comma (,)) between the preamble and the body of the claim. In order to overcome the objection, Applicant may amend the limitation as follows: “The process according to the claim 11, wherein the esterification…”.
Lines 2 – 3 of the claim: The limitation “…the activating agent is selected from thionyl chloride or oxalyl chloride and the alkanol…” is grammatically incorrect because it does not recite proper language for the group of alternatives and punctuation in the claim. In order to overcome the objection, Applicant may amend the limitation as follows: “…the activating agent is selected from thionyl chloride [[or]] and oxalyl chloride, and the alkanol…”.
Claim 14:
Lines 1 – 4 of the claim: The limitation “… wherein the pharmaceutically acceptable salts of… formula (I) prepared by without isolation of… formula (I)” (emphasis added) is grammatically incorrect because it does not recite proper usage of verb in the sentence. In order to overcome the objection, Applicant may amend the limitation as follows: “… wherein the pharmaceutically acceptable salts of… formula (I) are prepared [[by]] without isolation of… formula (I)”.
Claim 21:
Line 2 of the claim: The claim improperly recites a period (.) after the term “80° C”. In order to overcome the objection, Applicant may amend to delete the period (.) after said term.
Appropriate correction is required.
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.
Claims 5 – 7 and 21 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 5 recites the limitation “the reaction mass”. See, line 5 of the claim. However, prior to said recitation, the claim does not establish the basis of the reaction mass. It is unclear whether Applicant regards providing compound of formula (V) in step a) as a reaction mass, or if there is another interpretation for said limitation. Further, merely providing compound of formula (V) would not considered as a reaction mass. There is insufficient antecedent basis for this limitation in the claim. Dependent claims 6 – 7 and 21 do not remedy the issue and also considered indefinite.
In order to overcome the rejection, Applicant may amend line 5 of the claim as follows: “adding an acid to form a [[the]] reaction mass”. If claim 5 is amended, Applicant is requested to also amend the specification to reflect the appropriate amendments.
Claims 6 – 7 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 6 recites the limitations “the acid used for cyclisation” and “the cyclisation reaction”. See, lines 1-2 of the claim. However, claim 5 or 6 do not establish the basis of said limitations. It is unclear whether Applicant regards the acid in step b) of claim 5 as the acid used for cyclisation and the cyclisation reaction, or if there is another interpretation for said limitations. There is insufficient antecedent basis for these limitations in the claim. Dependent claim 7 also does not remedy the issue and is considered indefinite.
Claims 11 – 14 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 11 is directed to a process for preparation of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole of formula (I), comprising 2-(3,5-dichlorophenyl)-benzoxazole-6-carboxylic acid methyl ester of Formula (VIII)
PNG
media_image2.png
133
294
media_image2.png
Greyscale
, and base salt of formula (II)
PNG
media_image3.png
116
273
media_image3.png
Greyscale
. However, the claim fails to properly define the limitations of the variables R and HB(+). Thus, the metes and bounds of the claims cannot be ascertained with respect to said variables and renders the claim indefinite. Dependent claims 12 – 14 also do not remedy the issues and are considered indefinite.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 5 and 7 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rathnakar Reddy et al. WO 2021/019448 A1 (effect. filed August 1, 2019).
With respect to claim 5, Rathnakar Reddy et al. teach a process of Example 1 for the preparation of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole, comprising adding methanesulfonic acid to a reaction mixture comprising a starting compound, 4-[(3,5-Dichlorobenzoyl)amino]-3-hydroxybenzoic acid (instant formula (V)). The reaction mixture is co-distilled with toluene (solvent in step c) in the instant claims) at 106 °C. The process further comprises adding isopropanol to the reaction mixture, heated, filtered, washed with isopropanol and dried to obtain the final product, Tafamidis meglumine (meglumine salt of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole). See, e.g., page 12, paragraphs 1-2).
With respect to claim 7, Rathnakar Reddy et al. also teach a process of Example 3 for converting Tafamidis (6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole in the instant claims) and isolating a solid form of potassium salt of Tafamidis. See, e.g., bridging paragraph between pages 12-13.
Thus, the prior art Rathnakar Reddy et al. WO 2021/019448 A1 anticipates the instant claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sagar Patel whose telephone number is (571)272-1317. The examiner can normally be reached Monday - Friday: 9am to 5pm 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, Amy L. Clark can be reached at (571) 272-1310. 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.
/Sagar Patel/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626