DETAILED ACTION
Status of Claims
The amendment submitted October 27, 2025 has been entered.
Claims 1-8, 12-14, 18-23, and 25 are pending and under consideration.
Claims 9-11, 15-17, and 24 are/were previously cancelled by Applicant.
Claims 4-7, 12-14, 18-19, and 21-23 are withdrawn.
Claims 1-3, 8, 20, and 25 are under consideration in the instant office action as explained below in the Election/Restriction section
Election/Restrictions
Applicant's election with traverse of Group II, claims 2-3, 20, and 25 directed to Crystal Form A and pharmaceutical formulations comprising the Crystal Form A in the reply filed on October 27, 2025 is acknowledged. The traversal is on the ground(s) that Applicant alleges that the Office has not shown that a serious search burden would be required to examine all of the claims. However, Applicant’s arguments are not found persuasive because the instant application is a 371 national stage application and is not filed under 35 U.S.C. 111(a); therefore, “unity of invention” analysis, not “independent and distinct” analysis is applied. Please refer to MPEP 1893.03 (d).
The examiner respectfully required restriction based on the lack of unity of invention as Applicant’s claims are directed towards more than one product and multiple methods of use.
The requirement is still deemed proper and is therefore made FINAL.
For the purposes of compact prosecution, the Examiner rejoins Group I, claims 1 and 8 drawn to compound of claim I and pharmaceutical formulation comprising the succinate of claim 1.
Claims 4-7, 12-14, 18-19, and 21-23 are/remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 27, 2025.
Consequently, claims 1-3, 8, 20, and 25 are under consideration and the subject of this Office Action.
Information Disclosure Statement
One information disclosure statements (IDS) submitted on May 10, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Priority
This application is a 371 National Phase Application of PCT/AU2021/051325 filed November 10, 2021, which claims the benefit of priority to Chinese Patent Application No. CN202011249267.6, filed on November 10, 2020.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d), and the certified copy has been filed.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the DSC thermogram as described on page 16, paragraph [0076] of the specification must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Abstract Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
Claims 2-3, 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In claim 2, the phrase “The succinate of claim 1 which is Crystal Form A of the succinate,” is unclear as it is ambiguous if Applicant is claiming the salt or polymorph, or if the succinate of claim 1 is by default in Crystal Form A based on the present claim language.
The Examiner suggests amending claim 2 instead read as “Crystal Form A of the succinate according to claim 1,” to remedy this ambiguity.
Claim 3, line 2 contains references to figures. As per MPEP 2173.05(s), “where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Claim 20 depends on claim 2 and does not remedy the deficiency; therefore, it is likewise rejected.
Claim Rejections - 35 USC § 103
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.
Claims 1-3, 8, 20, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Tadesse et al. (Tadesse, S., Yu, M., Mekonnen, L.B., Lam, F., Islam, S., Tomusange, K., Rahaman, M.H., Noll, B., Basnet, S.K., Teo, T. and Albrecht, H., 2017. Highly potent, selective, and orally bioavailable 4-thiazol-N-(pyridin-2-yl) pyrimidin-2-amine cyclin-dependent kinases 4 and 6 inhibitors as anticancer drug candidates: design, synthesis, and evaluation. Journal of Medicinal Chemistry, 60(5), pp.1892-1915, Information Disclosure Statement filed May 10, 2023, Non-patent Literature Document No. 2) in view of Wang et al. (USPN 10,479,785 B2) and further in view of Bastin et al. (Bastin, Richard J., Michael J. Bowker, and Bryan J. Slater. "Salt selection and optimisation procedures for pharmaceutical new chemical entities." Organic Process Research & Development 4, no. 5 (2000): 427-435) and Thorson et al. (Thorson, M.R., Goyal, S., Schudel, B.R., Zukoski, C.F., Zhang, G.G., Gong, Y. and Kenis, P.J., 2011. A microfluidic platform for pharmaceutical salt screening. Lab on a Chip, 11(22), pp.3829-3837) as evidenced by Berge (Berge et al., J. Pharm. Sci. 66:1-19 (1977)).
The applied reference has a common applicant/assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claims 1-3, 8, 20, and 25, Tadesse discloses compound 116 (see below, page 1895, Scheme 3) which is identical to the compound of claim 1, excepting instant claim 1 is the succinate salt form.
PNG
media_image1.png
181
193
media_image1.png
Greyscale
PNG
media_image2.png
72
214
media_image2.png
Greyscale
Tadesse teaches compound 116 demonstrates beneficial properties as a CDK inhibitor and shows anti-proliferative activity (Table 3, page 1898), and teaches pharmaceutical formulations with 116, and notes that “we have identified nine compounds, i.e., 78, 79, 83, 89, 97, 107, 108, 112, and 116, as highly selective CDK4/6 inhibitors, all of which exhibited potent cellular antiproliferative activities in cancer cell lines (page 1898, column 1, last paragraph).”
Tadesse does not explicitly teach the succinate salt and Crystal Form A nor does Tadesse explicitly teach pharmaceutical formulations containing the succinate and Crystal Form A.
Wang teaches the identical compound as instant claim 1 as compound 84, excepting instant claim 1 is the succinate salt form (column 47, last compound). Wang also recites the identical compound as instant claim 1 in claim 28 of Wang and as a pharmaceutical formulation as per claim 29 of Wang excepting instant claim 1 is the succinate salt form.
Wang teaches that “The term “pharmaceutically acceptable salt” as used herein, refers to salts that retain the desired biological activity of the compounds of formula I, and include pharmaceutically acceptable acid addition salts and base addition salts. Suitable pharmaceutically acceptable acid addition salts of the compounds of formula I may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, heterocyclic carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, fumaric, maleic, alkyl sulfonic and arylsulfonic. Additional information on pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 19th Edition, Mack Publishing Co., Easton, Pa. 1995.
In the case of compounds of formula I that are solid, it will be understood by those skilled in the art that the compounds (or pharmaceutically acceptable salts, solvates or prodrugs thereof) may exist in different crystalline or polymorphic forms, all of which are encompassed within the scope of the present invention.
“Prodrug” means a compound that undergoes conversion to a compound of formula I within a biological system, usually by metabolic means (e.g. by hydrolysis, reduction or oxidation). For example, an ester prodrug of a compound of formula I containing a hydroxyl group may be convertible by hydrolysis in vivo to the compound of formula I. Suitable esters of the compounds of formula I containing a hydroxyl group may be, for example, acetates, citrates, lactates, tartrates, malonates, oxalates, salicylates, propionates, succinates, fumarates, maleates, methylene-bis-P-hydroxynaphthoates, gestisates, isethionates, di-p-toluoyltartrates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, cyclohexylsulfamates and quinates (column 6, lines 26-61).”
Consequently, Wang teaches that succinic salts are pharmaceutically acceptable salts for compound 84 and that compound 84 can exist in different crystalline or polymorphic forms as included in the scope of Wang’s invention.
Wang additionally teaches that “The compounds of the present invention may be provided as a pharmaceutically acceptable salt including, for example, suitable acid addition or base salts thereof. A review of suitable pharmaceutical salts may be found in Berge et al., J. Pharm. Sci. 66:1-19 (1977). Salts are formed, for example with strong inorganic acids such as mineral acids (e.g. sulfuric acid, phosphoric acid or hydrohalic acids), with strong organic carboxylic acids, such as alkanecarboxylic acids of 1 to 4 carbon atoms which are unsubstituted or substituted (e.g. by halogen), such as acetic acid, with saturated or unsaturated dicarboxylic acids (e.g. oxalic, malonic, succinic, maleic, fumaric, phthalic or terephthalic acid), with hydroxycarboxylic acids (e.g. ascorbic, glycolic, lactic, malic, tartaric or citric acid), with amino acids (e.g. aspartic or glutamic acid), with benzoic acid, or with organic sulfonic acids (e.g. (C1-C4)-alkyl- or aryl-sulfonic acids which are unsubstituted or substituted by, for example, halogen) such as methane- or p-toluene sulfonic acid).
The compounds of the present invention may be provided in their various crystalline forms, polymorphic forms and (an)hydrous forms. In this regard, it is well known to those skilled in the art that chemical compounds may be isolated in any of such forms by slightly varying the method of purification and or isolation from the solvents used in the synthetic preparation of such compounds (column 63, lines 20-44).”
Consequently, Wang teaches accessing the pharmaceutically acceptable salts and crystalline forms of compound 84 is well-known and facile to access for a person of ordinary skill in the art, which as cited by Wang, Berge further evidences the well-established knowledge of how salts are formed.
Bastin teaches the workflow and process for salt selection and optimization procedures for pharmaceutical new chemical entities (entire article). Specifically, Bastin teaches that succinate salts are common pharmaceutical salts (Table 1, page 428).
Bastin teaches microplate techniques for screening salts, scale-up, and HPLC as a tool to test sample purity, noting specifically that “Knowledge of the approximate purity is important at this stage as the presence of high levels of some impurities can often hinder crystallization or alter the polymorphic form obtained (page 428).”
Bastin also teaches various motivations to prepare salts including solubility, taste masking, and physical stability (column 1, paragraph 2, page 429).
Bastin also teaches common tests employed for evaluating salts during the optimization process, including XRD and DSC.
Thorson teaches that “A key challenge to identify salts of parent compounds (PCs) is screening an extensive number of salt formers (SFs) under a variety of crystallization conditions with limited material. Extensive screens are traditionally conducted at various conditions to identify salts with suitable properties for formulation development because many parameters influence crystallization of salts, including SF identity, PC to SF ratios, solvents employed, pH, and temperature. To carry out high-throughput screens, automated robotic systems have been developed, which improve efficiency and reduce turnaround time… This study presents a microfluidic approach that addresses these challenges by enabling extensive salt screenings with reduced sample requirement and much improved control over the crystallization processes.”
Thorson also teaches “The microfluidic platform reported here can also find its application in salt screening using evaporation and/or antisolvent modes. Other high throughput crystallization applications include the screening for crystal habit, polymorphs or co-crystals covering wide ranges of conditions while using minimal amounts of material. Furthermore, modifications to the microfluidic chips, specifically the mixing zone and chamber geometries, would change the rate of supersaturation, thereby influencing crystallization events. In summary, with simple modifications, this platform could be used to study the nucleation, polymorphism and crystal habit of drugs and other compounds.”
Consequently, Thorson teaches that salt and polymorph screening of pharmaceutical compounds can be achieved with improved efficiency and requiring minimal material via routine optimization using a microfluidic platform and/or automated robotic systems.
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to subject Compound 116 of Tadesse and Compound 84 of Wang to a salt selection and optimization process as disclosed by Bastin using high-throughput approaches taught by Thorson to access the succinic salt and its crystal Form A as in instant invention.
A person of ordinary skill in the art would be motivated to perform Bastin’s salt screening and optimization procedure in combination with high throughput approaches towards salt and polymorph screening as taught by Thorson to access the succinic salt and crystal Form A of instant invention as it is well-known in the art that “selection of an appropriate salt form for a new chemical entity provides the pharmaceutical chemist and formulation scientist with the opportunity to modify the characteristics of the potential drug substance and to permit the development of dosage forms with good bioavailability, stability, manufacturability and patient compliance,” which is further evidenced by the teachings of Berge.
Wang additionally teaches that “The compounds of the present invention may be provided in their various crystalline forms, polymorphic forms and (an)hydrous forms. In this regard, it is well known to those skilled in the art that chemical compounds may be isolated in any of such forms by slightly varying the method of purification and or isolation from the solvents used in the synthetic preparation of such compounds,” and additionally, specifically names succinic acid and succinate as a pharmaceutically acceptable salt, supporting that accessing the succinate salt and crystal Form A would be readily obtained by an ordinarily-skilled artisan as a highly predictable result with a reasonable expectation of success.
It would have been also prima facie obvious to perform standard characterization of Crystal Form A such as XRD and DSC as recited in claims 2-3 and 25 as part of the salt screening and crystallization optimization process as taught by Bastin and Thorson.
Finally, it would have been further prima facie obvious to develop pharmaceutical compositions using succinate salt and crystal form A as a highly predictable result with a reasonable expectation of success as Wang teaches pharmaceutical compositions using the identical compounds and its pharmaceutically acceptable salts and such experimentation would be part of routine optimization in developing new drugs as part of the formulation process.
Therefore, claims 1-3, 8, 20 and 25 are rejected as being obvious based on the beneficial teachings of Tadesse, Wang, Bastin, Thorson and Berge.
Conclusion
Claims 1-3, 8, 20, and 25 are under consideration and are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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, James H. Alstrum-Acevedo can be reached at 571-272-5548. 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.
/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622