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 .
All previous objections and rejections not reiterated herein were overcome by claim amendments, filed July 30th, 2026, that have been fully considered and found persuasive. As such all objections and rejections not reiterated herein have been withdrawn.
Election/Restrictions
Claims 30 – 31, 34, and 58 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 43 – 44, 49, 51, and 53 – 54, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on September 4th, 2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
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 43 – 44, 49, 51, and 53 – 54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the inducing CDK1/2/4/6 protein degradation and cellular proliferation of human epithelial cell line derived from ovarian cancer OVCAR-3, does not reasonably provide enablement for the prevention of a CDK-associated disease, such as cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The examined claims are drawn to a method for treating or preventing a CDK-associated disease, disorder or condition in a subject in need thereof, comprising administering a therapeutically effective amount of the compound of claim 30 to the subject, such that the CDK- associated disease, disorder or condition is treated or prevented in the subject. The instant specification fails to provide information that would allow a person of skill in the art to practice the prevention of CDK-associated disease, disorder or condition which includes cancer.
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: 1) the quantity of experimentation necessary; 2) the amount of direction or guidance provided; 3) the presence or absence of working examples; 4) the nature of the invention; 5) the state of the prior art; 6) the relative skill of those in the art; 7) the predictability of the art; and 8) the breadth of the claims. All of the Wands factors have been considered and those most relevant to the cited claims are discussed below.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The breadth of the claims
The claims are thus very broad insofar as they recite “a method for treating or preventing a CDK-associated disease, disorder or condition,” which includes cancers. CDK-associated disease, disorder or condition encompasses cancers which contains a number of different disease which divergent causes, physiological processes, and treatments. Thus cancer represents a very broad therapeutic target for prevention given the many causes and physiological processes involved.
The amount of direction or guidance provided and the presence or absence of working examples
The disclosure does not provide representative examples which provide reasonable assurance to one skilled in the art that the instant method is effective in preventing the full scope of conditions related to CDKs as claimed. The specification has provided guidance for the screening of compounds of claim 30 in cell-based assays in OVCAR3 cell lines. See page 247 – 251, Examples 102 – 103. While systems, such as GraphPad, offer qualitative information that can help triage compounds with the highest efficacious impact and lowest risk for adverse concerns, allowing for prioritization of potential therapeutic agents, such systems do not replace the actual testing of compounds in relevant animal models of disease, to determine efficacy in a method of prevention. Thus the specification does not provide guidance for prevention of CDK-assoctaed diseases, disorder, or conditions as broadly claimed with any of the compounds of the examined claims.
The nature of the invention, state and predictability of the art, and relative skill level
The invention relates to a method for treating or preventing a CDK-associated disease, disorder or condition in a subject in need thereof, comprising administering a therapeutically effective amount of the compound of claim 30 to the subject, such that the CDK- associated disease, disorder or condition is treated or prevented in the subject. The relative skill of those in the art is high being that of an MD or PHD. That factor is outweighed; however, by the unpredictable nature of preventing cancer. As illustrative of the state of the art, the examiner cites the fact that while the prior art enables the use of certain CDKs inhibitors for the treatment of specific cancers, the basis of the instant invention relies on prevention through the administration of a compound species claim 30 as a treatment option for a broad variety of conditions that includes cancers.
As taught by the state of the art of Zugazagoitia et. al. ((2016), Current Challenges in Cancer Treatment, Clinical Therapeutics, 38, 1551 – 1566), that there predictive genomic abnormalities are uncommon, diverse in nature, and distributed across many tumor types. See page 1557 column 1 paragraph 3. Furthermore, Zugazagoitia et. al. teach that several lines of evidence indicate that tumor initiation and progression could rely on a relatively minor population of self-renewing cancer stem cells. See page 1559 column 2 paragraph 2. Moreover, Zugazagoitia et. al. teach that tumor progression is accelerated by the progressive genomic instability inherent in cancer cells or exogenous carcinogens (eg, sunburn and smoking), which increase the generation of new mutations, probably exceeding Darwinian selection. See page 1559 column 2 paragraph 2. Thus Zugazagoitia et. al. suggest the unpredictability of trying to prevent all CDK-associated disease which include cancers. Furthermore, there is no way to predict based on the state of the prior art or the teachings in the specification whether or not the claimed compound would be effective for preventing CDKs-associated disease, disorders, or conditions which include cancer as listed in the claim.
The quantity of experimentation necessary
While the treatment of CDK-associated disease, disorder or condition is theoretically possible, as a practical matter not all CDK-associated disease, disorder or condition have the same pathology. And thus, it is nearly impossible to prevent all CDK-associated disease, disorder or condition, with the method as claimed. Moreover, as recited in dependent claims 44, 49, and 51 – 54 it is nearly impossible to prevent all cancers, with the method as claimed.
The amount of experimentation needed to determine how to prevent CDK-associated disease, disorder or condition would be enormous. The types of studies that would be necessary to establish the prevention would include a study of the different individual situations and specific contexts in which CDK-associated disease, disorder or condition occur, and metabolomics studies to identify key pathways involved in the progression of CDK-associated disease, disorder or condition.
Considering the diversity of conditions related to CDK-associated disease, disorder or condition claimed, the complexity of the underlying mechanisms, and the high unpredictability in the art, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in scope with the instant claims. Since the specification does not demonstrate prevention of CDK-associated disease, disorder or condition using any of the compound species of claim 30 the examiner maintains that the examined claims are not enabled for the full scope of claims 43 – 44, 49, 51, and 53 – 54 in light of the entire disclosure.
Accordingly, claims 43 – 44, 49, 51, and 53 – 54 do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Discussion of the Prior Art
The close prior art of US Patent Application US 2019/0248774 A1 to Pham et. al. (herein after Pham’774; cited on the IDS dated 10/13/2023) teach compounds that inhibit cyclin-dependent kinases (CDK) (page 1 paragraph 0002). Specifically, Pham’774 teach one embodiment wherein a compound of chemical structure (I-A)
PNG
media_image1.png
200
400
media_image1.png
Greyscale
(page 8 paragraph 0096). More specifically, Pham’774 teach compound no. 510 of the structure
PNG
media_image2.png
264
562
media_image2.png
Greyscale
(page 162 Table 1 row 2) wherein instant W = formula (Ia); a substituted carbon is C-F; and instant Z =
PNG
media_image3.png
264
8
media_image3.png
Greyscale
wherein instant Z2 =
PNG
media_image3.png
264
8
media_image3.png
Greyscale
and instant Z3 =
PNG
media_image3.png
264
8
media_image3.png
Greyscale
, that is a substituted carbonyl. Moreover, Pham’774 teach that compound no. 510 had an IC50 of 3 nM against CDK4 and 4 nM against CDK6; but, no inhibition against CDK1/B, CDK2/A, CDK2/E, CDK5/p25, CDK7/H, CSK9/K, FMS, nor PI3Kδ (page 406 Table 2 row 45). Additionally, Pham’774 teach that the compounds of this disclosure, which include compound 510, may be used in combination with other anti-cancer agents or immunotherapies (page 231 paragraph 0189).
However, Pham’774 fails to teach any compound species of as recited in claim 30. Moreover, as demonstrated by the applicant, the instant specification demonstrates that subtle structural variations in the linker portion lead to unpredictable changes in the final compound's activity. As shown in Table 5 of the specification as filed, Compound 2 (IC50>10 pM) and Compound 5 (IC50 <100 nM) differ by only a single carbonyl group, yet their activity difference is greater than 100-fold. Similarly, Compound 6 (IC50 1-5 pM) and Compound 5 (IC50s100 nM) have different linkers, yet their activity difference is greater than 20-fold. These data underscore the unpredictability of linker modifications in this field. See Applicant’s response page 16 paragraphs 2 – 3. As such the prior art of Pham’774 fails to anticipate or render obvious any of the compound species of claim 30. Thus claims 30 – 31, 34, and 58 are free of the prior art.
Conclusion
Claims 43 – 44, 49, 51, and 53 – 54 are rejected. Claims 30 – 31, 34, and 58 are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
Prosecution Insights