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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7 July 2026 has been entered.
Claims 7 and 12 have undergone amendments. Claims 13-15 have been cancelled. Thus, Claims 2, 4, 5, 7, 9-12, 16-19, and 21, submitted on 7 July 2026, represent all claims currently under consideration.
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.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 7 July 2026, is acknowledged and has been considered.
Response to Arguments
The 35 U.S.C. § 112(a) rejection of Claims 7 and 17-19 is withdrawn. Applicant has amended the claims to remove “preventing”, which corrects the lack of enablement.
The 35 U.S.C. § 112(d) rejection of Claims 12-15 is withdrawn. Applicant has cancelled claims 13-15 rendering those rejections moot, and has placed Claim 12 in independent form, correcting the improper dependency.
Claim Objections
Claim 2 is objected to because of the following informalities: The phrasing “wherein the salt crystal form is one or more selected from the group consisting of” should be “wherein the salt crystal form is selected from the group consisting of” as the claim should only be directed towards one salt form. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: The phrasing “wherein the salt is one or more selected from the group consisting of” should read -- wherein the salt is selected from the group consisting of -- since the claim should only be directed towards one salt form. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: The phrasing “wherein the tumor cells are with abnormal CDK4 and/or CDK6 selected from” should read -- wherein the tumor cells with abnormal CDK4 and/or CDK6 are selected from -- to improve clarity. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 4 and 16 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. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing
include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural
chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional
characteristics when coupled with a known or disclosed correlation between function
and structure; (d) Method of making the claimed invention; (e) Level of skill and
knowledge in the art and (f) Predictability in the art. While all of these factors are
considered, a sufficient number for a prima facie case are discussed below:
Claim 4 is directed towards methods for preparing the salt crystal form of Compound I of Claim 2, comprising reacting the free base form of the compound with a solvent selected from ketone solvents, ether solvents, alcohol solvents, ester solvents, anti-solvents, and a mixed solvent of a halogenated alkane and an alcohol solvent. Claim 16 claims the method of preparing the salt crystal form of Claim 2 (the Examiner believes this should be Claim 4, see 112(b) rejection below) wherein the solvents comprise acetone, tetrahydrofuran, methanol, ethyl acetate, dichloromethane/methanol, acetone and toluene. The specification provides acetone as an example of a ketone solvent, tetrahydrofuran as an example of an ether solvent, methanol as an example of an alcohol solvent, ethyl acetate as an ester solvent, acetone and toluene as anti-solvents, and methanol/dichloromethane as a mixed solvent. The specification does not provide support for the breadth of the claims of all ketone, ether, alcohol, ester, anti-solvents, or mixed solvents as these are the only examples of these solvents which are provided. The artisan would not know if these are the only solvents which can be used to synthesize these salt forms. The specification does not provide data demonstrating that other distinct solvents, such as hexanol, methyl ethyl ketone or carbon tetrachloride can be used to practice this invention. There is no reasonable expectation that substituting these solvents in place of what are shown in the specification would result in the same crystal polymorphic forms that are claimed as these solvents introduce different molecular interactions that can result in different crystal states being thermodynamically preferred. Claim 16 also lacks written support in the specification due to the limitation of “comprises” following each solvent group. The use of “comprises” indicates that there are other unrecited solvents which may be used in these methods. However, as described above, there is only support in the specification for the solvents which are explicitly recited within the specification. Therefore, there is no support in the specification that Applicant was in possession of the entire invention as claimed at the time of filing of the invention. This rejection can be overcome by specifying the solvents and anti-solvents which are used in this method and are supported in the specification.
Claims 4 and 16 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 methods of preparing salt crystal forms of Compound I wherein the ketone solvent is acetone, ether solvent is tetrahydrofuran, alcohol solvent is methanol, ester solvent is ethyl acetate, mixed solvent is dichloromethane/methanol, it does not reasonably provide enablement for the preparation of these salt forms using all ketone, ether, alcohol, ester, mixed solvents, or anti-solvents. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth below:
The nature of the invention and breadth of the claims:
The claims are directed towards methods of preparing the salt forms of Compound 1 of Claim 2 utilizing a ketone solvent, ether solvent, alcohol solvent, ester solvent, mixed solvent of a halogenated alkane and an alcohol, or anti-solvent, or wherein the solvents comprise several specific solvents, indicating that unrecited solvents can be used in these methods. Thus, the claims are directed to methods of producing the specific salt forms of Claim 2 using any ketone, ether, alcohol, ester, mixed solvent of halogenated alkane and alcohol, or anti-solvent.
The state of the prior art and the predictability or unpredictability of the art:
Pu (Chemical Engineering Research and Design, 201, 2024, 45-66) provides an overview of pharmaceutical crystallization and how habit modification can occur. Habit represents a critical quality attribute of pharmaceutical crystals. Solvent selection is one of the most widely used in habit modification for pharmaceuticals (Abstract). Solvent selection is of great importance in any solvent-mediated crystallization processes employed in the pharmaceutical industry. Solvent selection influences the rate of nucleation and growth via solvent-surface interactions, which in turn affect the resulting crystal form and habit. The interactions between the functional groups of the solvent and the crystal’s atoms determine the crystal’s affinity towards the solvent. Different levels of solvent-crystal affinity regulate the growth rates of crystal faces, potentially resulting in different crystal habits when different solvents are used. Table 3 provides a list of several pharmaceutical compounds which shows that changes in the solvent results in different crystalline habits being formed, which indicates that these are different crystalline forms of each compound. Thus, in view of the teachings of Pu, the selection of a solvent, even within the same class of solvent such as “ketone” or “ether” would not be expected to result in the same crystalline form being generated as these solvents all possess different hydrogen bonding properties and will be expected to interact with the pharmaceutical ingredient in different manners from one another, resulting in altered crystallization.
The relative skill of those in the art:
The artisan would generally have a degree in medicinal chemistry or pharmaceutical chemistry, with further expertise in the development of pharmaceutical crystal forms. However, their extensive training and experience would not be enough to overcome the lack of evidence from the specification, and within the prior art, that any solvent within the claimed groups of solvents would predictably result in the formation of the crystalline forms as claimed due to each solvent having different physicochemical properties, altering crystallization patterns.
The amount of direction or guidance presented and the presence or absence of working examples:
The specification provides enablement for the use of the specific solvents acetone, tetrahydrofuran, methanol, ethyl acetate, dichloromethane/methanol, and the anti-solvent of acetone and toluene to produce the crystal forms of the compounds of the invention (Table 6, Page 21). However, the specification does not demonstrate that solvents or anti-solvents other than these specific solvents can be used, nor does it demonstrate that mixtures of ketones (“comprising”), for example, can be used to produce these crystalline forms.
The quantity of experimentation necessary:
Considering the state of the art as described above, in particular with regards to the lack of evidence that all solvents of one class can produce the same crystalline form, and the high unpredictability of the art as evidenced therein, 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 with the scope of the claims.
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 4 is 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. Claim 4 is indefinite due to the limitations of “ambient humidity” and “room temperature”. “Ambient humidity” and “room temperature” are not defined terms in the specification, and are relative terms, causing ambiguity as to what exactly constitutes “ambient humidity” or “room temperature” as these can vary broadly. Thus, the metes and bounds of the claim are indefinite, and therefore, undefined.
Claim 12 is 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. Claim 12 recites the limitation "the maleate crystal form A" in line 5. There is insufficient antecedent basis for this limitation in the claim as “the maleate crystal form A” has not been introduced prior to the use of this term.
Claim 16 is 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. Claim 16 recites the limitation "The method of preparing the salt crystal form of Compound I of Claim 2" in Lines 1-2. There is insufficient antecedent basis for this limitation in the claim as Claim 2 does not claim a method of preparing the salt crystal form of Compound 1. The Examiner believes this claim should depend on Claim 4, which claims a method for preparing these crystal forms.
Claim 19 is 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. Claim 19 is indefinite because the of the language “includes breast cancer, central nervous system primary tumor/metastatic tumor”. It is unclear if the language following “includes” is a necessary part of the invention or merely representative. The Examiner suggests amending the claim to read “wherein the advanced solid tumor is selected from breast cancer and central nervous system primary tumor/metastatic tumor” or similar to clearly define the advanced solid tumors which can be treated using this method.
Allowable Subject Matter
Claim 2, 11, and 21 are objected to (see “Claim Objections”, above), but otherwise allowable.
Claims 5, 7, 9, 10, and 17-18 are objected to as dependent on an objected claim, but are otherwise allowable.
Claims 4, 12, 16, and 19 are rejected.
The following is an examiner’s statement of reasons for allowance: There is no prior art which teaches the specific crystalline forms of the compound of Formula I of the examined application (See Updated STN Search, Search Notes). The closest prior art comes from U.S. Patent No. 10,662,186 (Patent Date: 26 May 2020) (‘186). ‘186 claims the same compound as the examined application, as well as pharmaceutically acceptable salts thereof, and methods of inhibiting CDK activity in a subject and the inhibition of tumor cell growth in a subject. However, there is no teaching, suggestion, or motivation provided in ‘186 to select the specific salt forms and further develop them into the specifically claimed crystalline forms of the examined application. As the specific salt forms which are claimed are free of prior art, methods of their use and their compositions are similarly free of prior art.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claim 2, 11, and 21 are objected to (see “Claim Objections”, above), but otherwise allowable.
Claims 5, 7, 9, 10, and 17-18 are objected to as dependent on an objected claim, but are otherwise allowable.
Claims 4, 12, 16, and 19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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