NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/US2021/058014, filed Nov. 4, 2021, which claims benefit of priority to Provisional Application 63/110,303, filed Nov. 5, 2020.
Claims 1-12, 14-16, and 18-22, as amended, are pending.
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 .
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Oct. 23, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Election/Restrictions
Applicant's election without traverse of Group I, drawn to compounds of formula (I), and Compound 50.0 as the compound species, having the structural formula,
PNG
media_image1.png
256
407
media_image1.png
Greyscale
in the reply filed on Nov. 20, 2025 is acknowledged.
The elected compound species reads on claims 1-9, 11, 12, 14, 15, 19, and 20.
Claims 10, 16, 18, 21, and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Nov. 20, 2025.
Claims 1-9, 11, 12, 14, 15, 19, and 20 are currently pending and under consideration.
Claim Rejections - 35 USC § 112 – Indefiniteness
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.
Claims 1-9, 11, 12, 14, 15, 19, and 20 are 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 pre-AIA the applicant regards as the invention.
Claim 1 recites compounds of formula (I), X-L-Y, wherein X is an "E3 ubiquitin ligase binding ligand." However, the ambiguous scope of "X" and "L" render the claims indefinite.
Specifically, claim 1 defines X as an "E3 ubiquitin ligase binding ligand." While the instant specification provides examples of E3 ubiquitin ligase binding ligands (paras. [0073]-[0092]), no limiting definition of "E3 ubiquitin ligase binding ligand" is set forth, which also has no clear-cut, commonly understood definition in the art.
Thus, the exact set of substances encompassed by "E3 ubiquitin ligase binding ligand," and excluded therefrom, is ambiguous. While methods of assaying for E3 ubiquitin ligase binding activity are known in the art, the term includes substances with levels of E3 ubiquitin ligase binding activity which are detectable but too low to have any therapeutic utility, as well as substances which have not yet been identified to have such activity.
As recognized by MPEP § 2173.05(g), a claim term is merely functional descriptive language when it recites a feature "by what it does, rather than by what it is" (e.g., as evidenced by its specific structure or specific ingredients). In re Swinehart, 439 F.2d 210, 212, 169 USPQ 226, 229 (CCPA 1971).
In addition, claim 1 defines L as "a linking group covalently bonded to X and Y." No further structural features are specified, nor are the positions of X and Y at which L is covalently bonded to them. For example, L could be a single carbon atom, a polymer, or a protein, so long as it is covalently bonded, somehow, to both X and Y.
Further, claim 2 provides that "Y is covalently attached to L through R5," but R5 can be any of a multiplicity of functional groups, which can be further optionally substituted. Thus, the unknown structure and scope of L, and how it connects to X and Y, renders the claims indefinite.
In contrast, claim 1 defines Y in definite, limiting terms, as having the structural formula (II). In addition, X and L are set forth in definite, limiting terms in dependent claims:
claims 14 and 15 define X as being selected from one of five discrete structures; and
claim 19 defines L as having the structural formula (III).
Because claim 1 does not define X or L in definite, limiting terms, the scope of formula X-L-Y is unknown. Thus, compounds encompassed by the claims cannot be distinguished from compounds which are excluded, rendering the metes and bounds of the claims indefinite.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 8, 12, 14, 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (WO 2020/035049, cited on PTO-892).
Chen et al. disclose compound C001 (Table I, p. 10), having the structural formula,
PNG
media_image2.png
200
400
media_image2.png
Greyscale
which reads on formula (I), X-L-Y, wherein
Y is a CDK9-binding ligand of formula (II) as recited by claims 1, 2, and 8,
PNG
media_image3.png
131
164
media_image3.png
Greyscale
wherein R1 is NHR8, and R8 is C6-alkyl substituted with NH2; R2, R3, and R6 are hydrogen; R4 is C3-alkyl (isopropyl); and R5 is methyl;
L is a linking group covalently bonded to X and Y at R5 (-phenyl-hexyl-NH-C(O)-CH2-O-); and
X is a cereblon-binding ligand as recited by claim 12, and an E3 ubiquitin ligase binding ligand as recited by claims 14 and 15, having the structural formula,
PNG
media_image4.png
112
205
media_image4.png
Greyscale
.
For the foregoing reasons, Chen et al. anticipates claims 1, 2, 8, 12, 14, and 15.
Claims 1-8, 11, 12, 14, 15, and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Koehler et al. (US 2023/0158159, cited on PTO-892).
Koehler et al. exemplify a compound (p. 9) having the structural formula,
PNG
media_image5.png
200
400
media_image5.png
Greyscale
which reads on formula (I) (X-L-Y) as recited by claims 1-8, 11, 12, 14, 15, wherein
Y is a CDK9-binding ligand of formula (II) as recited by claim 11,
PNG
media_image6.png
158
181
media_image6.png
Greyscale
;
L is a linking group covalently bonded to X and Y; or, alternately,
Y is a CDK9-binding ligand of formula (II) as recited by claims 1-8,
PNG
media_image3.png
131
164
media_image3.png
Greyscale
wherein R1 is C1-6-alkyl (3-pentyl); R2, R3, R4, and R6 are hydrogen; and R5 is
PNG
media_image7.png
100
144
media_image7.png
Greyscale
,
and L is a linker of structural formula (III) as recited by claim 19,
PNG
media_image8.png
99
482
media_image8.png
Greyscale
wherein R10 and R11 are absent; a, b, c, and d are each selected so as to total 9, i.e., -(CH2)9-;
and e is 1; and
X is a cereblon-binding ligand as recited by claim 12, and an E3 ubiquitin ligase binding ligand as recited by claims 14 and 15, having the structural formula,
PNG
media_image4.png
112
205
media_image4.png
Greyscale
.
For the foregoing reasons, Koehler et al. anticipates claims 1-8, 11, 12, 14, 15, and 19.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
Claims 1-9, 11, 12, 14, 15, 19, and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Koehler et al. (US 2023/0158159, cited on PTO-892).
Koehler et al. disclose bifunctional compounds that bind cyclin-dependent kinase 9 (CDK9) and/or promote targeted ubiquitination for the degradation of CDK9. The compounds can bind CDK9, a protein whose dysregulation is implicated in a variety of cancers, and can promote CDK9's degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL). The E3 ubiquitin ligase can ubiquitinate CDK9, marking it for proteasomal degradation.
In particular, Koehler et al. exemplify a compound (p. 9) having the structural formula,
PNG
media_image5.png
200
400
media_image5.png
Greyscale
which reads on formula (I) (X-L-Y) as recited by claims 1-8, 11, 12, 14, 15, wherein
Y is a CDK9-binding ligand of formula (II) as recited by claim 11,
PNG
media_image6.png
158
181
media_image6.png
Greyscale
;
L is a linking group covalently bonded to X and Y; or, alternately,
Y is a CDK9-binding ligand of formula (II) as recited by claims 1-8,
PNG
media_image3.png
131
164
media_image3.png
Greyscale
wherein R1 is C1-6-alkyl (3-pentyl); R2, R3, R4, and R6 are hydrogen; and R5 is
PNG
media_image7.png
100
144
media_image7.png
Greyscale
,
and L is a linker of structural formula (III) as recited by claim 19,
PNG
media_image8.png
99
482
media_image8.png
Greyscale
wherein R10 and R11 are absent; a, b, c, and d are each selected so as to total 9, i.e., -(CH2)9-;
and e is 1; and
X is a cereblon-binding ligand as recited by claim 12, and an E3 ubiquitin ligase binding ligand as recited by claims 14 and 15, having the structural formula,
PNG
media_image4.png
112
205
media_image4.png
Greyscale
.
The compound of Koehler et al. differs from the elected compound in that the compound of Koehler et al.:
lacks a chlorine substituent at R3; and
the linker is -C(O)-(CH2)9-NH-, rather than -CH2-C(O)-piperazine-(CH2)3-NH-,
as shown side-by-side for comparison below:
Compound of Koehler et al.
Elected Compound 50.0
PNG
media_image5.png
200
400
media_image5.png
Greyscale
PNG
media_image1.png
256
407
media_image1.png
Greyscale
However, the compound of Koehler et al. is disclosed as a species of formula (I),
PNG
media_image9.png
200
400
media_image9.png
Greyscale
wherein R3 is selected from, inter alia, hydrogen or halogen, e.g., chlorine (claim 1).
Further, formula (I) of Koehler et al. broadly defines the linker L to include, e.g., substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, substituted or unsubstituted heterocyclylene, C(O), NH, or a combination thereof (claim 1).
Therefore, it would have been predictable to one of ordinary skill in the art as of the effective filing date to modify the compound of Koehler et al. to arrive at elected compound 50.0 with a reasonable expectation of success, because Koehler et al. claim compounds of formula (I) wherein hydrogen and halogen are interchangeable alternatives at R3; the linker of formula (I) of Koehler et al. encompasses the linker of Compound 50.0; both Koehler and the instant specification suggest that the exact structure of the linker isn't critical. Moreover, the closely similar compounds of Koehler et al. are disclosed to have the same mechanism of action, as CDK9 inhibitors, and to be useful for treating the same diseases, e.g., cancer.
As recognized by MPEP § 2144.09, a prima facie case of obviousness may be made when chemical compounds have (1) very close structural similarities and (2) 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).
The closer the chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., In re Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904 (and cases cited therein); and In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995).
Citation of Additional Prior Art
Additional references made of record are considered pertinent to applicant's disclosure:
WO 2020/035049; US Pub. 20230257380; US Pub. 20210323952; and US Pub. 20200339704 (all cited on PTO-892).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://portal.uspto.gov/external/portal. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629