DETAILED ACTION
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 the Claims and Response to Amendments
The amendments filed on March 24, 2026 have been acknowledged and entered. Claims 1-16 and 22-25 are pending. Claims 17-21 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/EP2022/055808, filed on March 8, 2022. This application also claims the benefits of foreign priority to EP21161543.0, filed on March 9, 2021.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this office action has been withdrawn or rendered moot in view of applicant's amendments and/or remarks.
Specification - Abstract
The abstract of the disclosure is objected to because of the following informalities:
The abstract discloses a compound represented by formula (I), but does not provide a structure of formula (I).
Appropriate correction is required.
Specification – Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 15 is objected to because of the following informalities:
Several of the structures in Claim 15 are illegible. A clean copy is recommended which clearly identifies the structures.
For consistency and clarity, in claim 15:
“compound” and the comma that is recited after “wherein the compound is selected from” and before “# STRUCTURE” can be removed.
A period should be added after the structure of compound 547.
Appropriate correction is required.
Examiner’s note on novelty and nonobviousness:
From nonfinal rejection (dated January 22, 2026)
The closest prior art references are the following:
Sava et al. (Sava) (Sava, G. P. et al. Cancer Metastasis Rev 2020, 39, 805-823.)
Liang et al. (Liang) (Liang, H. et al. Expert Opinion on Investigational Drugs 2021, 30, 61-76).
Novelty:
Both prior art references provide overviews of studies and literature concerning cyclin-dependent kinase 7 (CDK7) inhibitors as anticancer agents. Neither of the references disclose a compound falling within the scope of instant formula (I):
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. A further search conducted using STN database also did not identify any prior art disclosing compounds represented by instant formula (I).
Thus, the instant invention is considered novel.
Nonobviousness:
Both prior art references disclose CDK7 inhibitors reported in past studies and literature. However, the disclosed compounds possess core structures that are not structurally similar to the core structure of the instant compounds. In particular, the references mainly describe CDK7 inhibitors containing fused bicyclic ring systems. Neither reference provides a teaching, suggestion, or motivation to modify the disclosed compounds to incorporate the fused tricyclic ring structure recited in the instant claims.
Thus, the instant invention is considered nonobvious.
---------------------------- Maintained Rejections ------------------------------
Claim Rejections - 35 USC § 112(a) - Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 22-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed to make and use the invention based on the content of the disclosure, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims
compounds of formula (I):
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and pharmaceutical compositions comprising said compounds,
processes for the preparation of said compounds
the use of said compounds as inhibitors of CDK7 and
the use of said compounds in the treatment of diseases, e.g., cancer.
State of the prior art
See “Examiner’s note on novelty and nonobviousness” section above.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in medicinal chemistry and organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
The presence or absence of working examples;
the amount of direction or guidance present; and
the quantity of experimentation needed to make and use the invention based on the content of the disclosure
The specification only discloses in vitro biochemical and cellular assay data demonstrating inhibition of CDK7 activity and reduced proliferation in a certain cancer cell line. The in vitro results are listed in Tables A (starts on pg. 491), B (starts on pg. 506), and C (starts on pg. 508) of the instant specification.
However, such data does not establish that the disclosed compounds are effective for treating the broad range of diseases recited in claims 22-24 in subjects (such as animal models), nor does it provide guidance as to how in vitro activity translates to therapeutic efficacy in a subject (such as animal models).
The instant specification fails to provide guidance for selecting compounds for in vivo use (such as in animal models) from among the numerous disclosed candidates. For example, the specification does not identify any structural features or pharmacological properties that correlate with therapeutic efficacy in a subject (such as animal models). The mere identification of compounds with in vitro activity does not direct a POSITA to choose compounds that would be effective in treating the claimed diseases in a subject. Further, a POSITA would require undue experimentation to:
Determine which of the instant compounds can be used to treat any of the disease states or conditions mediated by CDK7 (as encompassed by instant claims 22 and 24) including those listed in instant claim 23 in a subject (such as animal models) and
determine appropriate parameters, such as dosage and frequency of administration, in order to treat a subject for any of the disease states or conditions mediated by CDK7 (as encompassed by instant claims 22 and 24) including those listed in instant claim 23.
The breadth of the claims
The claims are broad insofar as the instant claims recite tricyclic heterocycles of general formula (1) wherein the tricyclic heterocycle can possess a structurally diverse range of chemical groups. Further, the instant claims recite a method of treating a wide variety of disease states or conditions mediated by a CDK7.
Claim Rejections - 35 USC § 112(b)
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.
Claim 15 remains 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
**Note: In Applicant Remarks (dated March 24, 2026), Applicant states, “To advance prosecution, Applicant has amended claim 15 to be an independent claim” (see last page of Remarks).
Claim 15 has not been amended. Thus, the rejections from the Office Action (dated 01/22/2026) is maintained and reproduced below:
Claim 15 recites compounds 190, 244, 285, 333, 346, 379-381, 390, 399, 434, 449, and 450 which all have X = a pyrazolyl ring (i.e., an aromatic ring). However, according to claim 1 (wherein claim 15 is dependent on), if X is a heterocycle, it can only be a 4-7 membered non-aromatic heterocycle, a 4-10 membered non-aromatic bridged heterocycle, pyridine, or pyrimidine. Thus, there is insufficient antecedent basis for the limitation X = pyrazolyl in claim 15.
Claim 15 further recites the following compounds
135 wherein R3 = -C(=O)-NHMe
158 wherein R3 = -C(=O)-NH2
331 and 383 wherein R3 = -P(=O)Me2
However, the R3 of compounds 135, 158, 331, and 383 are not encompassed by claim 1. Thus, there is insufficient antecedent basis for the limitation R3 = -C(=O)-NHMe, -C(=O)-NH2, or -P(=O)Me2 in claim 15.
Claim 15 further recites the following compounds:
301 and 431 wherein R1 is substituted with
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(here, R6 = -C(=O)OMe)
330, 332, and 432 wherein R1 is substituted with
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(here, R6 = -C(=O)OH)
435 wherein R1 is substituted with
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(here, R6 = -C(=O)OEt)
436 wherein R1 is substituted with
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(here, R6 = -C(=O)OiPr).
However, the R6 of compounds 301, 330, 332, 431, 432, 435, and 436 are not encompassed by claim 1. Thus, there is insufficient antecedent basis for these limitations in claim 15.
Claim 15 further recites compound 160 which has X = absent and R1 = phenyl wherein the phenyl is substituted with -NR11-C(=O)-CH=CH-R6 (wherein R11 = R6 = H). However, R11 = H is not encompassed by claim 1. Thus, there is insufficient antecedent basis for this limitation in claim 15.
Claim 15 further recites compounds:
11, wherein R5 is an 8-membered bridged saturated heterocycle
31, wherein R5 is a 9-membered heteroaryl
132, wherein R5 is a 9-membered partially unsaturated heterocycle.
However, the R5 of compounds 11, 31, and 132 are not encompassed by claim 1. Thus, there is insufficient antecedent basis for these limitations in claim 15.
Allowable Subject Matter
Claims 1-14, 16, and 25 are allowed.
Conclusion
Claims 1-14, 16, and 25 are allowed. Claims 15 and 22-24 are rejected.
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 KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624