CTNF 18/027,511 CTNF 88635 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION This Office action is responsive to Applicant's Response to Election/Restriction, filed 21 November, 2025. As filed, claims 1-9, 11-21 are pending. Claim 10 is canceled. Priority This application filed 03/21/2023 is a National Stage entry of PCT/CN2022/129235 , International Filing Date: 11/02/2022 claims foreign priority to 202211028536.5, filed 08/25/2022 claims foreign priority to 202211027266.6, filed 08/25/2022 claims foreign priority to 202211027271.7, filed 08/25/2022. Information Disclosure Statement Applicants' information disclosure statements (IDS) filed on 3/11/2025 and 7/02/2025 have been considered except where lined through. Please refer to Applicants' copy of the 1449 submitted herewith. Election/Restrictions 08-25-02 AIA Applicant’s election of Group I, claims 1-5, 11-12, drawn to compounds of formula I in the reply filed on 11/21/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). Applicant’s elect the species of the compound I-2 described on example 3 [0087] of the specification and instant claim 12 which corresponds to formula (I) wherein R is ethyl; n is 1 and X is C6-aryl substituted with iodine. PNG media_image1.png 200 400 media_image1.png Greyscale The Applicants indicated claims 1-5, 11-12 read on the elected species. Claims 6-9, 13-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-5, 11-12 will be examined on the merits herein. Applicants’ elected species is not allowable due to the following obviousness type rejection. In searching for the elected species, prior art was identified which reads on the broader genus of the instantly claimed compound of formula (I). Solely in an effort to expedite prosecution, the examiner has applied the prior art. Claim Objections 1.Claims 1-5, 11-12 are objected to because of the following informalities: the recitation in claims: “compound having iodoaryl or iodoheteroaryl” should be revised to indicate that the iodoaryl or iodoheteroaryl are chemical groups of the compound of formula I t avoid potential indefiniteness issue. Potential amendments include “compound having iodoaryl or iodoheteroaryl groups” or simply “compound of formula I”. Appropriate correction is required. 2. In claim 1, the recitation: “C5-12 aryl-C1,4 alkylene” contains extra spaces before “aryl” and “alkylene. Similarly, for “C5-12 aryloxy-C1,4 alkylene”. Appropriate correction is required. 3. Claim 1, 2, 5, 11, 12 are objected for reciting improper Markush language: the recitation in claim 1 for definition of variables X of Markush formula I “is” -or in claim 11 for definition of variable R or n in claim 2 “is equal” - should be changed to “selected from the group consisting of”. Similarly, the recitation in claims 5, 12 “selected from any one of the” or “any one of the” should be changed to “selected from the group consisting of”. See MPEP 803.02. “A Markush-type claim recites alternatives in a format such as "selected from the group consisting of A, B and C." Appropriate correction is required.4. In claim 5, the recitation “wherein the wavy line represents a linkage site of a group.” should be revised to clearly indicate that the chemical bonding is between X and the carbonyl of amide in formula I. Appropriate correction is required.5. In claim 5, the amendment to cross over the compounds appears to be incomplete in crossing the structure- although it looks that the claims end period is after “linkage site of a group” Appropriate correction is required. Claim Rejections - 35 USC § 112 07-30-02 AIA 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 applicant regards as his invention. 07-34-01 AIA Claim s 1-5, 11-12 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. 1. In claim 1 formula I, variable X is defined as “C5-12 aryloxy-C1,4alkylene”; “C5- 12 aryl-C1,4alkylene” which does not indicate the connectivity site to the carbonyl of the amide compound. Therefore, the connectivity to the (CO) unit of the core structure to the C5-12 aryloxy-C1,4alkylene group can be either at the alkylene site C5-12aryloxy-C1,4alkylene- or at the aryloxy site -C5-12aryloxy-C1,4alkylene, resulting in different types of compounds. Because there are two or more plausible claim constructions, said claim and its dependents are indefinite. See, e.g., Ex Parte Miyazaki 89 U.S.P.Q.2d 1207, 2008 WL 5105055 (BPAI 2008) (holding "if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite."). 2.In claim 1, the variable n of formula I is defined either as “n is an integer greater than or equal to 0” rendering said claim indefinite because the upper limit is not indicated in the claim language. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-12-aia AIA (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. 1.Claim(s) 1-5, 11-12 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by CN 114262279, April 01, 2022 by Zhang et al. (“the ‘279 publication”; cited by Applicants in IDS). The ‘279 publication teaches compounds of formula I and specifically teaches the compound shown below as displayed in registry data base: Benzamide, N-(2,2-dimethoxyethyl)-2,3,5-triiodo RN 2766852-88-2: PNG media_image2.png 279 308 media_image2.png Greyscale The compound of prior art corresponds to the claimed formula I in which variables n is 0, R is methyl, X is C5-7 aryl substituted with iodine- 2,3,5-triiodophenyl and the species in claim 12 (see claims 1-2, and [0013] of the cited reference; instant claims 1-5, 11 and 12). Therefore, the prior art teaches the limitations of instant claims. 2.Claim(s) 1-5, 11 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by Bacalhau et al. Bioorganic Chemistry (2016), 67, 1-8 (cited by Applicants in IDS). The article by Bacalhau teaches on Scheme 1 page 2 and scheme 2on page 3 compounds falling within the scope of claimed formula I. Shown below as displayed in registry data base: RN 1251224-85-7 CAPLUS CN Benzamide, N-(2,2-dimethoxyethyl)-2-iodo- (CA INDEX NAME) PNG media_image3.png 246 291 media_image3.png Greyscale RN 1801971-30-1 CAPLUS CN Benzamide, N-(3,3-diethoxypropyl)-2-iodo- (CA INDEX NAME) PNG media_image4.png 279 348 media_image4.png Greyscale The compounds of prior art correspond to the claimed formula I in which variables n is 0 or 1, R is methyl, or ethyl X is C5-7 aryl substituted with iodine; instant claims 1-5, 11). Therefore, the prior art teaches the limitations of instant claims. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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 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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-21-aia AIA Claim s 1-5, 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over CN 114262279, April 01, 2022 by Zhang et al. (“the ‘279 publication”; cited by Applicants in IDS) . The ‘279 publication teaches amide compound having iodoaryl groups of formula I in which R1 is iodo-substituted phenyl and R2 is acetal from which overlap in scope with compounds of formula I as claimed with the same utility -used to prepare an X-ray imaging embolic material for imaging (abstract; see claims 1-5 of the ‘279 publication). PNG media_image5.png 200 400 media_image5.png Greyscale PNG media_image6.png 200 400 media_image6.png Greyscale n 1 is 0-3; R3 is C1-2 alkylene. Regarding the elected species, the amide compound having iodoaryl groups of formula I in which R1 is iodo-substituted phenyl and R2 is acetal group in PNG media_image6.png 200 400 media_image6.png Greyscale in which n 1 is 0; R3 is C2 alkylene – encompasses the elected species. Although the prior art does not teach preparative example of compound corresponding to the elected species, the prior art relied upon, and the knowledge generally available in the art before the effective filing date provide the suggestion that would have motivated the skilled artisan to make the structural modification and have reasonable expectation of success in arriving at the claimed invention. Moreover, the prior art specifically teaches the compound shown below as displayed in registry data base: benzamide, N-(2,2-dimethoxyethyl)-2,3,5-triiodo RN 2766852-88-2: The compound of prior art corresponds to the claimed formula I in which variables n is 0, R is methyl, X is C5-7 aryl substituted with iodine- 2,3,5-triiodophenyl and is structurally similar to the claimed elected species (see claims 1-2, and [0013] of the cited reference; instant claims 1-5, 11 and 12). As shown below in the table for facile comparison, the compound of the prior art by the ‘279 publication share the same core structure with instantly claimed compounds, and can be used as therapeutic agents. Prior art RN 2766852-88-2: Elected species RN 2944105-11-5 PNG media_image2.png 279 308 media_image2.png Greyscale PNG media_image7.png 258 370 media_image7.png Greyscale The amide compound explicitly taught by the cited prior art differs from the instant claimed elected species by a methylene unit at the same loci of the molecule: for instant claimed species variable R of formula I is ethyl group while for the compound of prior art is methyl; n is 0 for the for the compound of the prior art instead of 1 ( i.e. methylene unit difference). "Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties." The motivation to make a substitution of an ethyl group for methyl stems from the fact that a person having ordinary skill in the art would expect that the compounds could be prepared by the same method as taught by the prior art and have the same utility as the compounds taught by the prior art. In the interest of generating additional compounds, a person having ordinary skill in the art would seek to make additional compounds that are most closely related to compounds specifically taught by the prior art that have already been demonstrated to have applicability as X-ray imaging materials. As discussed supra, the well-established doctrine of homology, which assumes that homologous compounds are likely to have similar properties. Therefore, the instantly claimed elected species compound, which is suggested by the prior art and differ by ethyl instead of methyl at same loci of the structure over compound of prior art is unpatentable absent a showing of unexpected results. MPEP 2144.09 (VII) states "A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)." In the instant case, Applicant has not established unexpected properties between the instantly claimed compounds and the closest prior art compounds. Thus, the claimed invention as a whole is prima facie obvious over the teachings of the prior art. Conclusion Claims 1-5, 11-12 are rejected. Claims 6-9, 13-21 are withdrawn from further consideration. Telephone Inquiry Any inquiry concerning this communication or earlier communications from the examiner should be directed to: Ana Muresan (571) 270-7587 (phone) (571)270-8587 (fax) 07-100 Ana.Muresan@uspto.gov The examiner can normally be reached Monday - Friday (9:00AM - 5:30PM). 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, Scarlett Goon can be reached at 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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. 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If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ANA Z MURESAN/Primary Examiner, Art Unit 1692 Application/Control Number: 18/027,511 Page 2 Art Unit: 1692 Application/Control Number: 18/027,511 Page 3 Art Unit: 1692 Application/Control Number: 18/027,511 Page 4 Art Unit: 1692 Application/Control Number: 18/027,511 Page 5 Art Unit: 1692 Application/Control Number: 18/027,511 Page 6 Art Unit: 1692 Application/Control Number: 18/027,511 Page 7 Art Unit: 1692 Application/Control Number: 18/027,511 Page 8 Art Unit: 1692 Application/Control Number: 18/027,511 Page 9 Art Unit: 1692 Application/Control Number: 18/027,511 Page 10 Art Unit: 1692 Application/Control Number: 18/027,511 Page 11 Art Unit: 1692 Application/Control Number: 18/027,511 Page 12 Art Unit: 1692