DETAILED ACTION
This office action is in response to the Applicant’s filing dated July 2nd, 2026.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 2nd, 2026 has been entered.
Status of Claims
Claims 41 and 60 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed on July 2nd, 2026. Acknowledgement is made of Applicant’s amendment of claims 41 and 60; and cancelation of claims 1-40, 42-59 and 61-68
Claim 60 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
This application is a CON of PCT/US2021/043171 filed on July 26th, 2021; and has a PRO 63/058,283 filed on July 29th, 2020.
Response to Affidavit
The affidavit under 37 CFR 1.132 filed July 2nd, 2026 is insufficient to overcome the rejection of claim 41 as set forth in the last Office action of record as discussed below.
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 (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.
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.
The factual inquiries 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Ahmed et al. (Journal of Medicinal Chemistry, (2007), 50(7), 1584-1597), cited in a previous Office Action.
Regarding claim 41, Ahmed teaches Compound 47 (page 1590, Figure 5):
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Compound 47 differs from the elected compound by the bonding position of the terminal indazole; as well as the absence of a fluorine atom at the ortho position (opposite of the methyl substituent) of the opposite terminal 3-methylphenyl group.
Ahmed further teaches that fluorination at the ortho position of a terminal aryl ring improved pharmacokinetic properties stating, “Possessing a 2-fluoro-5-methylphenyl group, compound 17p was extremely potent (ED50) 0.5 mg/kg). As was mentioned before, the fluoro group in 17p had no impact on the KDR enzymatic potency in comparison to 17b; however, 17p showed a significantly enhanced UE potency, which is consistent with its much improved mouse oral plasma exposure (AUC at an oral dose of 10 mg/kg: 24.5 µM•h for 17p vs 6.5 µM•h for 17b). Incorporation of a fluoro group on the urea terminal aryl group also led to an improved mouse oral pharmacokinetic (PK) profile” (page 1590, right column, last paragraph).
Moreover, moving the attachment point of the core scaffold around the terminal indazole’s phenyl ring is a routine isomeric modification, creating a positional isomer of Compound 47.
MPEP § 2144.09(II) states:
"Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.)”
It would have been prima facie obvious to a person of ordinary skill in the art to modify the core scaffold’s attachment point to the terminal indazole’s phenyl ring, creating a positional isomer of Compound 47 of Ahmed; furthermore fluorinating the ortho position, creating a terminal 2-fluoro-5-methylphenyl ring motivated by Ahmed’s teachings that this modification would result in an improved pharmacokinetic profile and improved oral bioavailability; thereby arriving at the claimed compound with a reasonable expectation of success in retaining the function of the Compound 47 with improved pharmacokinetic properties.
Taken together, all this would result in the elected compound of instant claim 41 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
The structure-activity relationship of the claimed compound Example 4 (herein referred to as IACS-13743) is highly unpredictable. Applicant particularly points out and compares compounds IACS-13741 and IACS-13724; noting their ineffectiveness in comparison to IACS-13743.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
While data is presented for miR-10b-compound interactions against GA0518 and U251 cells comparing Example 4 (herein referred to as IACS-13743) to similar compounds, the closest prior art is not compared, namely Compound 47 of Ahmed. “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness.” In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979); see MPEP 716.02(e).
The comparison of instantly claimed IACS-13743 to IACS-13741 and IACS-13724 merely illustrates the importance of the unsubstituted indazole ring contained in both IACS-13743 and Compound 47 of Ahmed; because while the core scaffolds are similar, IACS-13724 contains an exocyclic amino group attached to the indazole ring and IACS-13741 replaces the indazole ring entirely with a benzo-fused lactam ring system. One of ordinary skill in the art would expect such significant differences (the aforementioned modifications of IACS-13741 and IACS-13724 to the unsubstituted indazole ring) to result in a difference in properties.
Applicant argues:
The claimed compound has unexpected positive effects against models of miR-10b-mediated cancer as seen in models of glioma and gastric cancer.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The evaluation of related compounds fails to compare instantly claimed IACS-13743 to the closest prior art, namely Ahmed’s Compound 47. “Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims.” See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980); see MPEP 716.02(b)(III). The Declaration presents separate experimental results for different compounds, without a direct comparison between the instantly claimed compound IACS-13743 and closest prior art, Ahmed’s Compound 47, and without statistical analysis sufficient to demonstrate whether the asserted differences represent a statistically significant improvement over the closest prior art or merely experimental variability.
Furthermore, the data presented in Figures 2-4, is largely illegible. Therefore, the Examiner cannot properly evaluate the numerical values, error bars or statistical significance underlying the asserted unexpected results in a meaningful way due to the manner in which the data is presented. Moreover, the Applicant appears to be comparing IACS-13743 to DMSO control, which is not sufficient to overcome prima facie obviousness as it is not a comparison to the closest prior art, specifically Ahmed’s Compound 47. “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness.” In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979); see MPEP § 716.02(e).
Conclusion
Claim 41 is rejected.
No claim is allowed.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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