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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a compound of formula (I) or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition comprising the compound of formula (I) or pharmaceutically acceptable salt thereof and a therapeutically inert carrier; and (3R)-N-[2,4-difluoro-3-[8-methyl-7-oxo-2-(2-phenylethylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-fluoropyrrolidinel-sulfonamide, which is the compound having the structure of:
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as the elected compound species of formula (I) in the reply filed on December 22, 2025 is acknowledged.
Claims 16 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 22, 2025.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected compound species of formula (I) conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected compound species:
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. In light of this discovery, the search is expanded to the subject matter of the subgenus of the elected compound species, i.e.,
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, and (3R)-N-[3-[2-( cyclopropylmethylamino)-8-methyl-7-oxopyrido[2,3-d]pyrimidin-6-yl]-2,4-difluorophenyl]-3-fluoropyrrolidine-1-sulfonamide having the structure of:
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(see page 62, compound 10 of the instant specification).
Status of the Claims
Claims 1-20 are pending. Claims 16 and 18-20 are withdrawn.
Claims 1-15 and 17 are under examination in accordance with the elected species along with the expanded species sets forth in the Expansion of Election of Species Requirement section above.
Priority
The instant application 18/210,991 filed on June 16, 2023 is a continuation of PCT/EP2021/086050 filed on December 16, 2021, which claims priority to, and the benefits of Foreign Application No. EP20215299.7 filed on December 18, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/14/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: Aryl-pyrido-pyrimidin-one derivatives.
Please note the term “New” should not be included at the beginning of the title of the invention and will be deleted when the Office enters the title into the Office’s computer records, and when any patent issues. See MPEP §606 with regard to Title of Invention.
The disclosure is objected to because of the following informalities:
Page 77, line 4, Example 37: the chemical structure recites in the table is missing covalent bonds in between the sulfur and dioxide groups shown below (see shaded):
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.
Appropriate correction is required.
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 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.
Claims 1-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Ren et al. (Bioorg Med Chem Lett. 2012;22(10):3387-3391; cited in the IDS filed on August 14, 2024), in view of Ding et al. (WO 2005/034869 A2).
Ren et al. teaches B-Raf inhibitor compound 17 having the structure of (see shaded):
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is a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies (see e.g., Table 4; abstract).
Ren et al. does not teach a compound of formula (I).
Ding et al. teaches a compound of Example 2 having the structure of:
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is an exemplary compound of Formula I (see e.g., p. 24, Example 2). Ding et al. further teaches compounds of Formula I:
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useful for modulating the activity of protein tyrosine kinases (see e.g., [0019]), wherein Y is selected from -C(H)= and -N=; R1 is selected from, inter alia, hydrogen and R4; R4 is selected from -XNR5S(O)0-2R6 ; wherein X is a bond; R5 is, inter alia, hydrogen; R6 is selected from, inter alia, C1-6 alkyl and C3-8heterocycloalkyl-C0-4alkyl; wherein any heterocycloalkyl of R4 is optionally substituted by 1 to 3 radicals independently selected from, inter alia, halo (see e.g., [0005]). Ding et al. further teaches the term “halogen” (or halo) preferably represents chloro or fluoro (see e.g., [0013]). Ding et al. further teaches examples of “heterocycloalkyl” includes, inter alia, pyrrolidinyl (see e.g., [0012]). Ding et al. further teaches the compounds of the present invention also inhibit cellular processes involving b-Raf kinase, providing a new therapeutic opportunity for treatment of human cancers, especially for melanoma (see e.g., [0031]). Ding et al. further teaches compounds of the invention can be prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers and recovering the optically pure enantiomers (see e.g., [0063]). Ding et al. further teaches a pharmaceutical composition comprising the compound in free form or in a pharmaceutically acceptable salt form in association with at least one pharmaceutically acceptable carrier or diluent can be manufactured in a conventional manner by mixing, granulating or coating methods (see e.g., [0043]).
In the present case, Ren et al. teaches compound 17 is a B-Raf inhibitor. The difference between the compound 17 of Ren et al. and the claimed compound of formula (I) is that the prior art compound has propyl (-CH2-CH2-CH3) substituted on the sulfur dioxide moiety rather than a pyrrolidine ring shown below (see shaded):
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. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to select the compound 17 of Ren et al., and then modify said compound by substituting the propyl with a pyrrolidine ring in view of the Formula (I) taught by Ding et al. to arrive at the claimed invention. One would have been motivated to do so, because Ding et al. teaches compounds of Formula (I) are also useful for inhibiting cellular processes involving b-Raf kinase; and further teaches a list of R6, including C1-6 alkyl and heterocycloalkyl such as pyrrolidinyl, that can be interchanged to give the -XNR5S(O)0-2R6 moiety at the R4 position of Formula I. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the compound 17 of Ren et al. is structurally similar to compound of Formula (I) taught by Ding et al. with similar utilities (B-Raf inhibitor), and therefore, said compound 17 modified in view of the Formula (I) of Ding et al. by substituting the propyl with a pyrrolidine ring as the heterocycloalkyl would have successfully arrive at a compound that is similarity useful for inhibiting cellular processes involving b-Raf kinase; and one would have reasonably expected that said modified compound can successfully be combined with a pharmaceutically acceptable carrier to arrive at a pharmaceutical composition. Please note the pharmaceutically acceptable carrier taught by Ding et al. is a therapeutically inert carrier. Please note the modified compound 17 of Ren et al. in view of Ding et al. sets forth above is a compound of formula (I)
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instantly claimed, wherein R1 is
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; R2 and R3 are fluorine; R4 is methyl; n is 1; R5 is
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.
Regarding the limitations recites in claims 4-5 and 14-15, the difference between the modified compound 17 of Ren et al. and Ding et al. sets forth above and the claimed compound, (3R)-N-[2,4-difluoro-3-[8-methyl-7-oxo-2-(2-phenylethylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-fluoropyrrolidinel-sulfonamide, is that the claimed compound has a fluorine atom substituted on the pyrrolidine ring shown below (see shaded):
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the modified compound 17 of Ren et al. and Ding et al. sets forth above by substituting the heterocycloalkyl, in this case, the pyrrolidinyl ring with a fluorine atom as the halogen as taught by Ding et al. One would have been motivated to do so, because Ding et al. further teaches the any heterocycloalkyl of R4 can be optionally substituted by 1 to 3 radicals, including halo that is preferably chloro or fluoro, to arrive at the compound of Formula I useful for inhibiting cellular processes involving b-Raf kinase; and further teaches the compound can be prepared as their individual stereoisomers from the racemic mixture of the compound. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the modified compound 17 of Ren et al. and Ding et al. substituted with a fluorine atom on the pyrrolidinyl ring would have successfully arrive at a compound useful for inhibiting cellular processes involving b-Raf kinase. Please note the fact that Ding et al. teaches individual stereoisomers of the compound separate from the racemic mixture of the compound renders obvious the limitation of
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instantly claimed.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628