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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/13/2026 has been entered.
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 Claims 85, 103, 104, and 106 are withdrawn.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
Claim(s) 1, 43, 75, 77 115, and 124-125 are rejected under 35 U.S.C. 103 as being unpatentable over Gray et al (WO2016105528A2), are maintained, but modified and revised in light of the claim amendment.
Claim(s) 1, 43, 75, 77, 80, and 115 rejected under 35 U.S.C. 103 as being unpatentable over Gray et al (WO2016105528A2), are maintained, but modified and revisited in light of the claim amendment.
Claims 1, 43, 75, 80, 115, and 124-125 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. US12168663B2. Although the claims at issue are not identical, they are not patentably distinct from each other, are withdrawn in light of the terminal disclaimer filed on 03/13/2026.
Claims 1, 43, 75, 80, 115, and 124-125 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. US10870651. Although the claims at issue are not identical, they are not patentably distinct from each other, are withdrawn in light of the terminal disclaimer filed on 03/13/2026.
Terminal Disclaimer
The terminal disclaimer filed on 03/13/2026 has been reviewed and is accepted. The terminal disclaimer has been recorded.
New Rejection
Claim Rejections - 35 USC § 112
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 1, 43, 75, 80, 115, and 124-125 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A “representative number of species” means that the species which are adequately
described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63
USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir.
2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a
genus after only describing a limited number of species because there may be unpredictability
in the results obtained from species other than those specifically enumerated.”). “A patentee
will not be deemed to have invented species sufficient to constitute the genus by virtue of
having disclosed a single species when … the evidence indicates ordinary artisans could not
predict the operability in the invention of any species other than the one disclosed.” In re
Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a
microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in
the record showing applicant conveyed that any other coating was suitable for a PTFE dental
floss.)” The Claim recites a compound of the formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof.
For solvate. The specification discloses the concept of solvate and lists solvents such as methanol, or ethanol. However, the specification fails to disclose a specific solvate form of the compound, such as a methanol solvate with defined stoichiometry.
For hydrate. The specification explains what hydrates are and references hydrates in general. However, the specification fails to provide a specific hydrate form of the compound such as monohydrate or dihydrate.
For isotopically labeled derivative. The specification defines isotopically labeled derivatives and mentions isotopes like deuterium or carbon-13. However, the specification fails to describe any particular isotopically labeled form, for example replacing a specific atom with deuterium or carbon-13, and thus does not reflect possession.
In sum, a written description requires more than just general definitions. While the specification explains what solvates, hydrates, and isotopically labeled derivatives are, it does not show that they actually had any specific version of these forms. Without concrete examples, it does not meet the standard of demonstrating possession.
Modified and revisited Rejection
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.
Claim(s) 1, 43, 75, 80, 115, and 124-125 are 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.
Applicant’s argument
Applicant argues that Gray would not motivate the skilled person to select compound 214 as a starting point for modification. Table A1 of Gray (Gray, pages 176-178) reports CDK7 IC50 data for 42 species. Compound 214 of Gray is among 29 species where the IC50 is reported as "A", which corresponds to an IC50 < 100 nM (Gray, page 176, paragraph [00334]). Gray provides no motivation to select compound 214 from among the 29 most potent CDK7 inhibitors. As such, its selection as a starting point for modification was not based on any teaching or suggestion in Gray itself, rather only by its structural proximity to compound I-1 of the present invention. This is impermissible hindsight. ("It is impermissible, however, simply to engage in a hindsight reconstruction of the claimed invention, using the applicant's structure as a template and selecting elements from the references to the fill the gaps." In re Gorman, 983 F.2d 982, 987 (Fed. Cir. 1991)).
Examiner’s response
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 clearly teaches compound 214 exhibits excellent inhibitory activity for CDK7 with IC50 A which corresponds to less than 100 nM. Gray also teaches hydrogen and methyl are interchangeable at that position and in compound 41. Therefore, Gray would motivate the skilled person to select compound 214 as a starting point for modification.
Applicant’s argument
Applicant argues Gray does not teach the equivalence of hydrogen and methyl as a substituent on the pyrazole nitrogen as the Examiner suggests. At best, Gray teaches that replacing the pyrazole hydrogen with a methyl group is highly unpredictable. Specifically, the IC50 of compound 216 of Gray is reported as "A", corresponding to an IC50 < 100 nM. Compounds 243 and 244 are the methylated pyrazole analogs of compound 216, and their reported IC50 is "C", which corresponds to an IC50 > 1µM as illustrated in the table below.
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By comparison, replacing the pyrazole hydrogen of compound 214 with a methyl group provides compound 241 of Gray where the CDK7 activity is retained as illustrated in the following table.
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The clear teaching of Gray is that the skilled person could not possibly predict the result of replacing a pyrazole hydrogen with methyl on CDK7 inhibitory activity. The skilled person,
considering the teaching of Gray as a whole, would in no way be motivated to replace pyrazole
hydrogen with nitrogen with the expectation that the new molecule would retain potent CDK
inhibitory activity. (A prior art reference must be considered in its entirety, including those
portions that teach away from the claimed invention. (M.P.E.P. § 2141.02(VI); W.L. Gore &
Assoc., Inc. V. Garlock, Inc., 721 F.2d 1540 (Fed. Cir. 1983)). Withdrawal of this rejection in
view of the foregoing discussion is respectfully requested
Examiner’s response
In response, Applicant’s argument is not persuasive. Specifically, Applicant’s comparison involves compounds 216 and 243 which possess a methoxy group at the ortho-position of the phenyl ring and compounds 120 and 243 that contain a vinylcarboxamide on the phenyl ring. However, these compounds are excluded from the claim. Thus, any differences or unpredictability they raise in those non-claimed compounds isn’t directly relevant. In the present case, Gray teaches successful substitution at similar position based on compounds 214 and 41 or suggest small changes, like-hydrogen-to-methyl shifts, can be explored for optimizing CDK7 activity, then predicting the outcome is within ordinary skill. Slight variation in known active scaffolds are a predictable path. Thus, such substitution would not rely on hindsight. In short, the compounds that are excluded does not diminish the logic applied to the claimed scope. Lastly, Applicant has not provided a direct comparison between the claimed compound the closest prior art structure, such as compound 214,
Conclusion
Claims 1, 43, 75, 80, 115, and 124-125 are not allowed.
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.
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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