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 .
Election/Restrictions
Applicant’s election of Group (I) with the addition of compound (I-1)
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as the elected compound species in the reply filed on 04/23/2025 is maintained.
Priority
This application is a national stage filing under 35 U.S.C. § 371 of International PCT Application No. PCT/US2020/043132, filed July 22, 2020, which claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 62/877,788, filed July 23, 2019.
Claims Status
Claims 1, 43, 75, 80, 85, 103-104, 106, 115, and 124-125 are pending. Claims 2-42, 44-74, 76-79, 81-84, 86-102, 105, 107-114, and 116-123 are canceled. Claims 85, 103, 104, and 106 are withdrawn. Claims 1, 43, 75, 80, 115, and 124-125 are examined in accordance to the elected species and invention.
Summary of Rejection
Claims 1, 43, 75, 80, 115, and 124-125 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in light of claim amendment.
Claim(s) 1, 43, 75, 80, 115, and 124-125 rejected under 35 U.S.C. 103 as being unpatentable over Gray et al (WO2016105528A2), are maintained.
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 non-
obviousness.
Claim(s) 1, 43, 75, 80, 115, and 124-125 remain rejected under 35 U.S.C. 103 as being unpatentable over Gray et al (WO2016105528A2).
Gray teaches a compound of Formula (I):
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a pharmaceutically acceptable salt thereof, wherein: R5 is independently hydrogen, optionally substituted Ci-C6 alkyl, or a nitrogen protecting group. (See claim 1.) Moreover, Gray teaches these compounds CDK7 inhibitors. (See paragraph [0014].) Gray also teaches Compound 214 and Compound 41
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.(See Tables 3 and Example 41 of page 173.) Gray further teaches a pharmaceutical composition and a Kit comprising the compound or a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable excipient; and instructions for using the compound. (See claims 57 and 105, Tables 3, and Example 41 of page 173.)
Gray does not teach the elected compound species:
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It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to select compound 214 and substituting the hydrogen atom on the nitrogen atom of the pyrazole ring with a methyl to give Applicant’s claimed compound. The motivation to make such substitution is because not only Gray teaches hydrogen and methyl are interchangeable at that position, but also because Gray teaches compound 41 that contains a methyl group at that position. One would reasonably expect the modified compound to exhibit CDK7 inhibitory activity with success.
Acknowledgement is made of the receipt and entry of Applicant’s arguments/remarks filed on June 24, 2026.
Applicant’s argument
Applicant argues Gray provides no motivation to select compound 214 as a starting point because Gray disclosed numerous compounds exhibit comparable CDK7 inhibitory activity. Applicant contends that the Examiner selected compound 214 only because of its structural similarity to the presently claimed compound, thereby relying upon impermissible hindsight.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the present case, Gray expressly identifies compound 214 as a potent CDK7 inhibitor and reports that compound 214 exhibits an IC50 value designated as “A.” corresponding to an IC50 pf less than 100 nM. Thus, Gray, affirmatively teaches compound 214 to be an active member of the claimed genus and not merely an arbitrary disclosure. The fact that Gray disclosed additional compounds possessing similar inhibitory activity does not diminish the suitability of compound 214 as a starting point for further medicinal chemistry optimization. Obviousness does not require that the prior art identify a single preferred or optimal lead compound. Rather, one of ordinary skill in the art would have reasonably considered any of the disclosed potent inhibitors, including compound 214, as suitable candidates for further structural modification in an effort to maintain or improve biological activity. Applicant has not identified any teaching withing Gray that criticizes, discourages, or otherwise discredits the use of compound 214 as starting point. Instead, Applicant merely argues that the other compounds also possess potent activity. Such argument does not negate the fact that Gray expressly teaches compound 214 to possess excellent CDK7 inhibitory activity and therefore provides a reasonable starting point for routine structural optimization. Accordingly, the Examiner’s selection of compound 214 is based upon Gray’s express disclosure and biological evaluation rather than impermissible hindsight reconstruction.
Applicant argues that Gray fails to teach the equivalence of hydrogen and methyl substitution on the pyrazole nitrogen and instead teaches that such modification is highly unpredictable.
In response, this argument is not persuasive. The rejection is not predicated upon a finding that hydrogen and methyl substituents are universally interchangeable or equivalent in every molecular context. Rather, Gray teaches that methyl substitution at the pyrazole nitrogen constitutes one of the structural variations explored within the disclosed class of CDK7 inhibitors. For example, Gray expressly discloses compounds in which the pyrazole nitrogen bears hydrogen and additional compounds in which the same nitrogen bears a methyl substituent, thereby demonstrating that such substitution was within the scope of structural modifications investigated by the references. Accordingly, Gray would have suggested to one of ordinary skill in the art that methyl substation at the pyrazole nitrogen represented a routine medical chemistry modification worthy of investigating in known active compounds.
Applicant relies upon comparisons between compounds 214 and 242 and between compound 216 and 243 to argue that methyl substitution dramatically reduces CDK7 inhibitory activity and therefore teaches away from the presently claimed invention.
In response, Applicant’s argument has been fully considered but is not persuasive. Gray, considered as a whole, does not criticize, discredit, or otherwise discourage methyl substitution at the pyrazole nitrogen. Rather, Gray demonstrates that the effect of such substitution depends upon the overall molecular structure and the surrounding substitution pattern. Instead, Gray also discloses compounds 120 and 241, wherein replacement of the pyrazole hydrogen with a methyl substituent retains CDK7 inhibitory activity. Thus, Gray teaches that methyl substitution can be tolerated in appropriate structural contexts. The existence of examples in which activity decreases following methyl substitution merely demonstrates that biological activity depends upon the overall molecular framework, which is a well-recognized principle in medicinal chemistry. Such structure-activity-variability does not constitute a teaching away. A reference teaches away only when it criticizes, discredits, or otherwise discourages the claimed modification. Gray contains no such teaching. Instead, Gray demonstrates that the success of methyl substitution depends upon the remaining structural feature of the molecule. Accordingly, Gray would not have discouraged one of ordinary skill in the art from exploring methyl substitution in compound 214.
Applicant further relies upon biological data comparing compounds outside the presently claimed scope.
In response, Applicant’s argument is not persuasive. The compounds relied upon by Applicant contain differences beyond the pyrazole methyl substitution, including different substitution patterns on Ring A that are excluded from the presently pending claims. Consequently, the cited comparisons do not establish that the presently claimed compound possess unexpected properties relative to the closest prior art compound. More importantly, Applicant has not submitted experimental evidence comparing the presently claimed compounds with the closest prior art compound, namely compound 214, demonstrating any unexpected improvement attributable to the claimed modification. Instead, Applicant relies upon comparisons involving different compounds having different substitution patterns and molecular framework. Accordingly, the cited data are insufficient to overcome the prima facie case of obviousness established by the prior art.
Conclusion
For the foregoing reasons, Applicant’s arguments have been fully considered but are not persuasive. Gray expressly teaches compound 214 as a potent CDK7 inhibitor suitable for further medicinal chemistry optimization. Gray further demonstrates that methyl substitution at the pyrazole nitrogen was among the structural variations investigated within the disclosed scaffold and does not teach away from such modification. Additionally, Applicant has not provided objective evidence establishing unexpected results for the presently claimed compounds relative to the closest prior art compound. Therefore, the rejection of claims 1, 43, 75, 80, 115, and 124-125 under 35 U.S.C. 103 over Gray is maintained.
Conclusion
Claims 1, 43, 75, 80, 115, and 124-125 are not 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 JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-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, 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.
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/JEAN P CORNET/ Primary Examiner, Art Unit 1628
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