DETAILED ACTION
This office action is in response to the Applicant’s filing dated December 11th, 2025.
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 Claims
Claims 5, 8-9, 13, 15, 18, 21, 23-25, 27, 29-30, 33, 36, 38, 41, 54 and 60 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed on December 11th, 2025.
Claims 5, 8-9, 13, 15, 18, 21, 23-24 and 60 remain withdrawn. Claims 25, 27, 29-30, 33, 36, 38, 41 and 54 are presently under examination as they relate to the elected species.
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.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Maintained Objections and/or Rejections
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.
Claims 25, 27, 29-30, 33, 36, 38, 41 and 54 are 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 claims 25, 27, 29-30, 33, 36, 38, 41 and 54, Ahmed teaches Compound 47 (page 1590, Figure 5):
PNG
media_image1.png
268
552
media_image1.png
Greyscale
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 claims 25, 27, 29-30, 33, 36, 38, 41 and 54 with a reasonable expectation of success.
Applicant argues:
There is no reason to shift the indazole nitrogen of Compound 47 of Ahmed to the instantly claimed compound’s orientation.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The nitrogen was not shifted, but rather the binding position changed of the indazole ring to the core scaffold. It is well established that moving the attachment point of the core scaffold around the terminal indazole’s phenyl ring is a routine isomeric modification, thus 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.)”
Applicant argues:
The teaching of Ahmed that the incorporation of the 2-fluoro group increases potency involves compounds with another structural difference than Compound 47, the presence of an amino substituent on the terminal indazole ring. The effect of the amino group substituent on potency is not well understood.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Compounds 17b and 17p are identical, except for the fluorine substituent present on the terminal phenyl ring of Compound 17p. Ahmed 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).
One of ordinary skill in the art would have recognized that fluorinating the ortho position of Compound 47, creating a terminal 2-fluoro-5-methylphenyl ring, would predictably result in an improved pharmacokinetic profile and improved oral bioavailability; just as it had in Compound 17p as compared to 17b.
Applicant argues:
Ahmed’s compounds are taught to have activity against receptor tyrosine kinases. The instant application discloses compounds with inhibition activity against miRNA 10b to ultimately treat various cancers.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Ahmed discloses that the compounds taught have anticancer properties, and are tested as such
against an HT1080 human fibrosarcoma tumor model (page 1584, Abstract).
MPEP § 2144.09(I) states:
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)
Conclusion
Claims 25, 27, 29-30, 33, 36, 38, 41 and 54 are rejected.
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L JOHNSON whose telephone number is (571)272-1672. The examiner can normally be reached Monday - Friday 08:00AM - 5:00PM EST with Flex on Fridays.
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, Renee Claytor can be reached at (571) 272-8394. 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.
/C.L.J./Examiner, Art Unit 1691
/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691