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 .
DETAILED ACTION
This Office action is responsive to Applicant's Remarks/Amendment after Non-Final Rejection, supplemental amendment filed April 13, 2026. As filed, claims 1, 3-4, 6-9, 11-22 are pending of which claims 1, 3, 4, 6, 11, 12 are amended; claim 22 is newly added. Claims 2, 5, 10 are cancelled.
Claims 6-9, 13-21 are withdrawn from further consideration.
Claims 1, 3-4, 11-12, 22 are examined.
A complete response to this Office Action should include cancellation of non-elected subject matter or other appropriate action.
Rejections Withdrawn
Applicants’ amendment, have been fully considered and are entered. The status for each rejection and/or objection in the previous Office Action is set out below.
1. The rejection of claims 1-5, 11-12 under 35 U.S.C. § 112(b) is withdrawn in view of claim amendment to specify the connection site.
2. The rejection of claims 1-5, 11-12 under 35 U.S.C. § 102(a)(1) and 102(a)(2) as being anticipated by CN 114262279, April 01, 2022 by Zhang et al. is withdrawn in view of claim amendments to define variable n as 1-3.
3. The rejection of claims 1-5, 11-12 under 35 U.S.C. § 102(a)(1) as being anticipated by Bacalhau et al. Bioorganic Chemistry (2016), 67 is withdrawn in view of claim amendments to define variable n as 1-3.
4. The rejection of claims 1-5, 11-12 under 35 U.S.C. § 103 over CN 114262279, April 01, 2022 by Zhang et al. is maintained/modified in view of cancellation of claims 2, 5, and to incorporate newly added claim 22. Applicant's arguments filed 4/13/2026 have been fully considered but they are not persuasive.
Applicant's argue that:”
as shown in Tables I and 2, when n=O (with only one carbon atom between
the acetal and the nitrogen atom), the acetal group is relatively reactive and can be hydrolyzed by
acid to form compound III, which can be further hydrolyzed to amide compound IV. As the
carbon chain length increases, the aldehyde compound III becomes more stable and is less prone
to be hydrolyzed into compound IV. By increasing the carbon chain length, the generation of the
amide impurity IV in the reaction solution is significantly reduced, thereby lowering the
difficulty of the purification process. Due to the reduction in side reactions, more contrast agent
molecules can be conjugated to the microspheres, leading to a significantly increased iodine
content in the developed microspheres…. In other words, only when n=l, 2, or 3
can one obtain a radiopague embolic material with sufficient stability (impurity IV content
in the reaction solution <1 mg/mL) and high iodine content..”( Remarks page 12).
The arguments are more relevant to process of making the compounds of formula I. Applicants’ claimed limitations are drawn to a compound of formula (I). Regardless of how the prior art prepared the compound, the cited teachings of the prior art still discloses the instantly claimed compound of formula (I).
As outlined before and reiterated herein, the prior art teaches amide compounds having iodoaryl groups of formula I in which R1 is iodo-substituted phenyl, bearing at least two iodine atoms 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.
MPEP 2141 provides that exemplary rationales that may support a conclusion of
obviousness include (E) " Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success.
The compound of instant application is structurally similar to compound disclosed by the cited reference RN 2766852-88-2, the only structural difference is a methylene group tailored on the core structure and with the same utility, and suggest the modification of alkyl length at the same loci of the chemical structure. Therefore, contrary to Applicant’s argument with respect to the impurity of the reaction, yield of synthesis of the instantly compound is not relevant when assessing the patentability distinction of the instantly claimed compound versus compound of prior art. The structural similarity provides the requisite motivation to modify known compounds to obtain new compounds with expectation that such compounds would have similar properties.
Per MPEP 716.02 guidance:” Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).”
In the instant case, the prior art by ‘279 publication specifically teach compound of formula as required by instant claims, for imaging applications.
A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. “An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See MPEP § 2144.09.
This rejection is still deemed proper, and is therefore maintained.
5.The objection to claims has been addressed.
The following are modified or new grounds of rejections necessitated by Applicants’ amendment, filed on 4/13/2026 wherein the limitations in pending claims as amended now have been changed. The limitations in the amended claims have been changed and the breadth and scope of those claims have been changed.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1, 3-4, 11-12, 22 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, bearing at least two iodine atoms (instant claims 1, 22) 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).
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n 1 is 0-3; R3 is C1-2 alkylene- which corresponds to claimed formula I in which n is 1.
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
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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. 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 an analog of the claimed formula I in which variables, n is 1, 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, 3, 4 11 and 12, 22).
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, is an analogue with the only structural difference of a CH2-unit and can be used as imaging agents.
Prior art RN 2766852-88-2:
Elected species RN 2944105-11-5
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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, 3-4, 11-12, 22 are rejected. Claims 6-9, 13-21 are withdrawn from further consideration.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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)
Ana.Muresan@uspto.gov
The examiner can normally be reached Monday - Friday (9:00AM - 5:30PM).
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/ANA Z MURESAN/Primary Examiner, Art Unit 1692
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