DETAILED ACITION
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 .
Status of the Claims
The status of the claims are as follows:
Claims 1-14 are pending.
Claims 1-4, 7-10, and 12-14 are rejected.
Claims 5-6 and 11 are objected to.
Priority
Acknowledgement is made that Instant Application 18/839,865, filed on 2025, Aug. 20, is a National Stage entry of PCT/CN2023/082140, filed on 2023, Mar. 17., which claims foreign priority to CN 202210268968.7, filed on 2022, Mar. 18.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 2024, Aug. 20 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
Claim Objections
Claims 5-6 and 11 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 5 is directed to the crystal form I of the dihydrochloride salt of the compound of formula (I) according to claim 3, wherein the crystal form has properties as shown in Figs 1-3, and/or possess specific thermogravimetric and/or differential scanning calorimetric properties. The closest prior art teaches the discovery and pharmacological use of the compound of formula (I) in its free base and monohydrochloride salt forms. The art is silent on the crystal form of the dihydrochloride salt of the compound of formula (I), the and therefore is silent on any properties thereof.
Claim 6 is directed to a preparation method for the crystal form I of the dihydrochloride salt of the compound of formula (I) according to claim 3. The closest prior art teaches methods of making and isolating the monohydrochloride salt of the compound of formula (I) in its amorphous form. The art is silent on crystal forms of the dihydrochloride salt of the compound of formula (I), and therefore is free methods of its preparation.
Claims 11 is directed to a pharmaceutical composition comprising the crystal form I of the dihydrochloride salt of the compound of formula (I) according to claim 3. The art is silent on crystal forms of the dihydrochloride salt of the compound of formula (I), and therefore is free on compositions thereof.
Claim Rejections - 35 USC § 112
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 2-4, 7, 9, and 12-14 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.
Regarding claims 2-4 and 7, the claims include the word “preferably”, which is open to multiple interpretations. As a result, the scope of the claim is ambiguous as to whether the preferred limitations are non-limiting preferences or required features. Accordingly, the claim is rejected for lack of clarity and definiteness.
Regarding claims 9 and 12-14, the phrase “a disease associated with the activity or expression of” renders the scope of the claim ambiguous. The phrase “a disease associated with the activity or expression of” does not make clear what diseases are or are not covered by the scope of the claim (e.g., dwarfism, obesity, chronic kidney disease, etc.) Furthermore, a skilled artisan cannot discern to what degree of association is necessary for a disease to be covered by the scope of the claim. Accordingly, the above claims are ambiguous.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei (Design, Synthesis and Biological Evaluation of a Series of Novel 2-benzamide-4-(6-oxy-N-methyl-1-naphthamide)-pyridine Derivatives as Potent Fibroblast Growth Factor Receptor (FGFR) inhibitors. European Journal of Medicinal Chemistry, 154, 2018, 9-28. Doi: 10.1016/j.ejmech.2018.05.005) in view of PubChem (CID 25031915, created 2015, Aug. 11), and evidenced by Guerrieri (Analysis of Relationships Between Solid-State Properties, Counterion, and Developability of Pharmaceutical Salts. AAPS PharmSciTech., 2010, 11, 1212-1222. Doi: 10.1208/s12249-010-9499-4).
Claims 1-2 are directed to a dihydrochloride salt of a compound of formula (I) (Table 1), wherein the dihydrochloride salt is in a solid form, preferably in a crystalline form.
Wei teaches the compound of formula (I) as compound 19a (Table 1) as a potent inhibitor of FGFR1 that is highly effective against FGFR1-positive KG-1 cancer cells (page 16, Table 1). Wei further teaches the lead compound of this study, compound 25a (Table 1) has relatively low plasma exposure after both intravenous and oral administration; however, by making the dihydrochloride salt, it is aqueously soluble and readily used for in vivo study (page 15, left column, paragraph 1). Furthermore, Wei teaches the purpose of the study was to conduct a structure-activity relationship of the phase II clinical FGFR inhibitor lucitanib (Table 1) (abstract).
The difference between Wei and the instant application is that Wei fails to teach the dihydrochloride salt of compound 19a and also fails to teach the crystalline form of compound 19a.
However, the dihydrochloride salt of lucitanib is known in the art under the PubChem CID 25031915. Furthermore, prior to the effective filing date of the current invention, it was known in the art that the crystalline form of active pharmaceutical ingredients is often preferred over the amorphous form due to the enhanced stability, solubility, and hygroscopicity (see Guerrieri). Accordingly, one of ordinary skill in the art would have found it prima facie obvious to form the dihydrochloride salt of lucitanib derivatives, e.g., compound 19a, wherein the dihydrochloride salt is in a crystalline form.
Table 1. Instant formula (I) and related compounds.
Instant formula (I)
Compound 19a
PNG
media_image1.png
682
810
media_image1.png
Greyscale
Compound 25a
PNG
media_image2.png
648
826
media_image2.png
Greyscale
Lucitanib
PNG
media_image3.png
638
820
media_image3.png
Greyscale
Claim(s) 8-10 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wei, in view of PubChem and evidenced by Guerrieri, in further view of Zhang (US 11,834,432 B2, published 2023, Dec. 05; foreign priority claim to CN 201610094401.7, published 2016, Feb. 19).
Claims 8 and 13 is directed to a pharmaceutical composition comprising the dihydrochloride salt of the compound of formula (I) and a pharmaceutically acceptable carrier thereof and a method for preventing and/or treating a disease associated with the activity or expression of FGFR, KDR, and/or CSF-1R, comprising administering to a subject in need a therapeutically effective amount of the pharmaceutical composition.
The teachings of Wei in view of PubMed and evidenced by Guerrieri are discussed above and incorporated herein by reference.
The difference between the combined teachings and claims 8 and 13 is that the combined teachings fail to teach a pharmaceutical composition comprising the dihydrochloride salt of the compound of formula (I) a pharmaceutically acceptable carrier thereof in treating a disease associated with the activity or expression of FGFR, KDR, and/or CSF-1R.
However, Zhang teaches substituted amino six-membered nitric heterocyclic ring compounds and their use as FGFR inhibitors (title; column 3, lines 30-35). Specifically, Zhang teaches compounds the compound of formula (I) as compound S10 (column 15, Table 1). Zhang further teaches pharmaceutical compositions comprising a therapeutically effective amount of the compound, pharmaceutically acceptable salts, prodrugs, hydrates, or solvates thereof, and optionally a pharmaceutically acceptable carrier or excipient (column 5, lines 55-60).
One would be motivated to combine the teachings of Zhang with the teachings of Wei as in view of PubMed and evidenced by Guerrieri because they teach the same compound as an effective inhibitor for the same receptor. Zhang additionally teaches the compound is isolated as the hydrochloride salt (column 43, lines 1-10), while Wei teaches the dihydrochloride salt is superior for in vivo application (page 15, paragraph 1). Accordingly, one of ordinary skill in the art would have found it prima facie obvious to form the dihydrochloride salt of compound S10 as taught by Zhang to arrive at the invention of the instant claim.
Claims 9 and 10 are directed to a method for preventing and/or treating a disease associated with the activity or expression of FGFR, KDR and/or CSF-1R, comprising administering to a subject or patient in need thereof a therapeutically effective amount of the dihydrochloride salt of the compound of formula (I), wherein the associated disease is a tumor-associated disease selected from the provided group.
Zhang teaches the pharmaceutical composition of compound s10 is used for treating a tumor or for treating a disease associated with tyrosine kinase (preferably FGFR, more preferably FGFR1) activity (column 5, lines 60-65). Zhang further teaches the tumor-related diseases treated by the pharmaceutical composition are selected from the group consisting of breast cancer, lung cancer, non-small cell lung cancer, bladder cancer, gastric cancer, pancreatic cancer, prostate cancer, colon cancer, myeloma, liver cancer, melanoma, head and neck cancer, thyroid cancer, renal cell carcinoma, glioblastoma, and testicular cancer (column 6, lines 6-13), all of which read on the provided group of tumor-associated diseases from the instant claim.
Conclusions
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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