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 .
DETAILED ACTION
Applicant’s amendment dated 23 July 2026, in which claims 1, 18, 35 have been amended, and claims 21-22, 26-27 have been cancelled, is acknowledged.
Claims 1-3, 5, 8-9, 17-18, 25, 28, 35-37, 39-40 are pending in the instant application.
Claim 40 is withdrawn, as being drawn to a non-elected invention.
Claims 1-3, 5, 8-9, 17-18, 25, 28, 35-37, 39 are examined herein.
Response to arguments of 23 July 2026
In view of Applicant’s amendment of 23 July 2026, all the objections and rejections to claims 21-22, 26-27 are herein withdrawn. Claims 21-22, 26-27 have been cancelled.
On 23 July 2026, Applicant has amended independent claim 1 to recite that R3 is unsubstituted cycloalkyl or unsubstituted heterocyclyl.
The amendment of 23 July 2026 deletes from the claims Applicant’s elected species, over which rejections were made. As previously stated, in the interest of compact prosecution, on 17 June 2025, the examiner has extended the search to a subgenus of compounds of formula (I) encompassing the elected species
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namely compounds of formula (I) where
L is
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wherein Ra = Rb = H; n is 1; and
R3 is piperidinyl (as heterocyclyl) substituted with hydroxy. Claims 1-3, 5, 8-9, 17, 21, 28, 35-37, 39 had been examined to the extent they read on this subgenus, and rejections were made.
In view of Applicant’s amendment of 23 July 2026, the rejection of claims 1-3, 5, 8, 17, 21, 28, 36, 37, 39 under 35 U.S.C. 103 over Bahl; the rejection of claims 1-3, 5, 8, 9, 17, 21, 28, 35, 36, 37, 39 under 35 U.S.C. 103 over Bahl, in view of Patani; and the rejection of claims 1-3, 5, 8-9, 17, 21, 28, 35-37, 39 under 35 U.S.C. 103 over Bondke in view of Bahl, are herein withdrawn.
Applicant’s amendment of 23 July 2026 necessitated the following new rejections.
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.
Claim 35 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 35 depends on claim 1 and recites that the compound is
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Yet, claim 1, as amended, is drawn to a compound of formula (I)
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where R3 is unsubstituted heterocyclyl. As such, there is insufficient antecedent basis for the above compounds of claim 35, in claim 1.
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 1-3, 5, 8, 17-18, 25, 28, 36-37, 39 are rejected under 35 U.S.C. 103 as being unpatentable over Kosugi et al. (J. Med. Chem. 2012, 55. 6700-6715, cited in PTO-892).
Kosugi teaches Table 3) the following pyrazolo-pyrimidines as anti-inflammatory agents:
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(Table 3)
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Kosugi also teaches compositions comprising said compounds.
The compounds above taught by Kosugi differ from compounds of instant formula (I)
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where R2 is phenyl (as in instant claim 5) substituted with fluoro and chloro (as in instant claim 8); L is NH or -NH-CH2- (as in instant claim 28); R3 is unsubstituted cyclohexyl (as in instant claim 25), or unsubstituted piperidinyl (as in instant claims 17, 18)
in that substituent R1 is H, while in the instant compounds
R1 is, for example, -CN, chloro.
Kosugi also teaches (Table 1, compounds 1, 22, 23) that the substituent in the 3-position of the pyrazole[1,5-a]pyrimidines (which corresponds to R1 in instant formula I) can be, for example, H, -CN, or chloro, with retention of anti-inflammatory properties.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Kosugi to arrive at the instant invention.
The person of ordinary skill in the art would have replaced R1 = H in the compounds above specifically disclosed by Kosugi, with chloro, or CN, to arrive at the instant invention, because Kosugi teaches that the substituent in the 3-position of the pyrazole[1,5-a]pyrimidines (which corresponds to R1 in instant formula I) can be, for example, H, -CN, or chloro, with retention of anti-inflammatory properties. Thus, the person of ordinary skill in the art would have replaced R1 = H in the compounds above disclosed by Kosugi, with Cl or CN, with a reasonable expectation that the compounds retain biological activity as anti-inflammatory agents.
Regarding claims 36, 37, 39, the person of ordinary skill in the art would have prepared a salt of such a compound, because preparing salts of therapeutically active compounds, specifically HCl salts which are most commonly used, with the aim of optimizing drug solubility, bioavailability and stability of the formulation, is considered well within the competency of a person of ordinary skill in the art in the field of pharmaceutical research.
As such, claims 1-3, 5, 8, 17-18, 25, 28, 36-37, 39 are rejected as prima facie obvious.
Claims 1-3, 5, 8, 9, 28, 36, 37, 39 are rejected under 35 U.S.C. 103 as being unpatentable over et Parratt al. (US 2007/0179161, cited in PTO-892).
Parratt discloses (page 60) the following compounds as CDK inhibitors useful to treat, for example, cancer:
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which are -SO2NMe2 versus -SO2NH2 homologs of compounds of instant formula (I)
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for which the following definitions apply:
R1 = Cl;
R2 = phenyl substituted with -SO2NH2 (as in instant claims 1, 8);
L is O;
R3 = unsubstituted heterocyclyl.
Parratt teaches pharmaceutically acceptable salts of the compounds of the invention (page 3, [0030]), as in instant claim 36, specifically hydrochloric acid salt (page 3, [0030]), as in instant claim 37, and pharmaceutical compositions thereof, as in instant claim 39.
It would have been obvious to a person of ordinary skill in the art to synthesize a direct homolog phenyl substituted with -SO2NH2 vs. phenyl substituted with -SO2NMe2 in compounds 195, 196 taught by Parratt. The person of ordinary skill in the art would have synthesized a direct homolog of a compound taught by Parratt, with the expectation that said homolog will retain therapeutic effect.
In the absence of unexpected results, stereoisomers are considered obvious variants of each other. "Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties". In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
As such, a compound of instant claims 1-3, 5, 8, 9, 28, 36, 37, 39 or a pharmaceutically acceptable salt thereof, and a composition comprising said compound, are rendered obvious by Parratt.
Claims 1-3, 5, 8, 9, 25, 28, 36, 37, 39 are rejected under 35 U.S.C. 103 as being unpatentable over et Parratt al. (US 2007/0179161, cited in PTO-892).
Parratt discloses (page 16) the following compound as a CDK inhibitor useful to treat, for example, cancer:
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Compound Example 25 taught by Parratt differs from a compound of instant formula (I)
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where R2 is phenyl (as in instant claim 5) substituted with -SO2-Me (as in instant claim 8); L is -O- (as in instant claim 28); R3 is unsubstituted cyclohexyl (as in instant claim 25),
in that substituent R1 is isopropyl, while in the instant compounds
R1 is, for example, cycloalkyl, or chloro.
Parratt teaches [0049] that in the compounds of the invention
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, R (which corresponds to the instant R1) is, for example, isopropyl, chloro, cyclopropyl, cyclopentyl, or cyclohexyl.
Parratt teaches pharmaceutically acceptable salts of the compounds of the invention (page 3, [0030]), as in instant claim 36, specifically hydrochloric acid salt (page 3, [0030]), as in instant claim 37, and pharmaceutical compositions thereof, as in instant claim 39.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Parratt to arrive at the instant invention.
The person of ordinary skill in the art would have replaced R1 = isopropyl in the compound above specifically disclosed by Parratt, with chloro, or cycloalkyl, to arrive at the instant invention, because Parratt teaches that the substituent in the 3-position of the pyrazole[1,5-a]pyrimidines of the invention (which corresponds to R1 in instant formula I) can be, for example, isopropyl, chloro, cyclopropyl, cyclopentyl, or cyclohexyl. Thus, the person of ordinary skill in the art would have replaced R1 = isopropyl in the compound above disclosed by Parratt, with Cl, or cycloalkyl, with a reasonable expectation that the resulting compound retains biological activity as CDK inhibitor useful to treat cancer.
As such, claims 1-3, 5, 8, 9, 25, 28, 36, 37, 39 are rejected as prima facie obvious.
Claims 1-3, 5, 8, 9, 25, 28, 36, 37, 39 are rejected under 35 U.S.C. 103 as being unpatentable over et Guzi al. (US 2006/0041131, cited in PTO-892).
Guzi discloses (page 13, left column, line 4) the following compound as a CDK inhibitor useful to treat, for example, cancer:
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The compound above taught by Guzi differs from a compound of instant formula (I)
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where R2 is phenyl (as in instant claim 5) substituted with -SO2-Me (as in instant claim 8); L is -NH- (as in instant claim 28); R3 is unsubstituted cyclohexyl (as in instant claim 25),
in that substituent R1 is Br, while in the instant compounds
R1 is cycloalkyl, -CN, or chloro.
Guzi teaches ([0010], [0012], [0021]) that in the compounds of the invention
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R2 (which corresponds to the instant R1) is, for example, cycloalkyl or R9, where R9 is, for example, halogen or CN.
Guzi teaches pharmaceutically acceptable salts of the compounds of the invention, as in instant claim 36, specifically hydrochloric acid salt, as in instant claim 37, and pharmaceutical compositions thereof, as in instant claim 39.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Guzi to arrive at the instant invention.
The person of ordinary skill in the art would have replaced R1 = Br in the compound above specifically disclosed by Guzi, with chloro, or CN, or cycloalkyl, to arrive at the instant invention, because Guzi teaches that the substituent in the 3-position of the pyrazole[1,5-a]pyrimidines (which corresponds to R1 in instant formula I) can be, for example, halogen, CN or cycloalkyl. Thus, the person of ordinary skill in the art would have replaced R1 = Br in the compound above disclosed by Guzi, with Cl or CN, or cycloalkyl, with a reasonable expectation that the resulting compound retains biological activity as CDK inhibitor useful to treat cancer.
As such, claims 1-3, 5, 8, 9, 25, 28, 36, 37, 39 are rejected as prima facie obvious.
Claims 1-3, 5, 8-9, 17-18, 28, 35-37, 39 are rejected under 35 U.S.C. 103 as being unpatentable over et Kataoka al. (US 7,557,110 of 7 July 2009, cited in PTO-892).
Kataoka discloses (column 3, lines 30-40) pyrazolo[1,5-a]pyrimidines as kinase inhibitors and compositions thereof, useful to treat, for example, cancer (abstract).
Kataoka teaches pharmaceutically acceptable salts of the compounds of the invention, as in instant claim 36, specifically hydrochloric acid salt, as in instant claim 37, and pharmaceutical compositions thereof, as in instant claim 39.
Kataoka specifically teaches (column 303) the following compound (compound 743):
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which is a -N-Me versus -NH- homolog of a compound of instant formula (I)
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for which the following definitions apply:
R1 = CN;
R2 = phenyl substituted with -Cl;
L is -NH-;
R3 = unsubstituted heterocyclyl.
Kataoka also specifically teaches (column 83) the following compound (compound 169):
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which is a R4 = Et versus H homolog of a compound of instant formula (I)
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for which the following definitions apply:
R1 = Cl;
R2 = phenyl substituted with halogen;
L is -NH-;
R3 = unsubstituted heterocyclyl.
It would have been obvious to a person of ordinary skill in the art to synthesize a direct homolog of a compound disclosed by Kataoka. The person of ordinary skill in the art would have synthesized a direct homolog of a compound taught by Kataoka, with the expectation that said homolog will retain therapeutic effect.
In the absence of unexpected results, stereoisomers are considered obvious variants of each other. "Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties". In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
As such, claims 1-3, 5, 8-9, 17-18, 28, 35-37, 39 are rejected as prima facie obvious.
Claims 1-3, 5, 8-9, 17-18, 28, 35-37, 39 are rejected under 35 U.S.C. 103 as being unpatentable over et Kataoka al. (US7,557,110 of 7 July 2009, cited in PTO-892).
Kataoka discloses (column 3, lines 30-40) pyrazolo[1,5-a]pyrimidines as kinase inhibitors and compositions thereof, useful to treat, for example, cancer (abstract)
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where
R1 is, for example, H (column 3, line 42);
R2 is, for example, halogen, -CN, C3 to C8 cycloalkyl (column 3, lines 51, 54-55);
R3 is, for example, aryl substituted with halogen, -CN, alkyl, optionally substituted (column 4, lines 23-30);
R4 is, for example, H (column 5, line 14, also column 9, lines 14-15);
R5 is, for example, unsubstituted heterocyclyl (column 9, lines 40-41), such as unsubstituted piperidin-3-yl, unsubstituted piperidin-4-yl, or unsubstituted pyrrolidine-3-yl (column 9, lines 48-50);
R6 is for example, H (column 9, lines 63-64).
The genus taught by Kataoka overlaps with compounds of formula (I) of the instant claims
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where
R2 is phenyl or benzyl substituted with, for example, halogen, -CN, alkyl, (as in instant claims 8, 9, 35);
R1 is cycloalkyl (cyclopropyl, or cyclobutyl as in instant claims 2, 3, 35), or Cl, or -CN;
L is
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wherein Ra = Rb = H; n is 1 (as in instant claims 28, 35);
R3 = unsubstituted heterocyclyl such as, for example, piperidinyl, as in instant claims 17, 18, 35.
Kataoka teaches pharmaceutically acceptable salts of the compounds of the invention, as in instant claim 36, specifically hydrochloric acid salt, as in instant claim 37, and pharmaceutical compositions thereof, as in instant claim 39.
Kataoka specifically teaches (column 303, column 83) the following compounds (compound 743, compound 169):
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where R3 is phenyl or benzyl substituted with halogen; and where NR5R6 is
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and R2 is CN or Cl.
Kataoka also specifically teaches (column 47) the following compound (compound 50):
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which differs from a compound of instant formula (I)
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where R2 is phenyl (as in instant claim 5) substituted with fluoro and chloro (as in instant claim 8); L is NH (as in instant claim 28); R3 is unsubstituted piperidinyl (as in instant claims 17, 18)
in that substituent R1 is Br, while in the instant compounds
R1 is, for example, -CN, chloro, or cycloalkyl.
Kataoka discloses compounds 43-45, 89-90, 104-106, 152, 156, 160, 458, where R3 is phenyl or benzyl substituted with one or more halogen, cyano, or alkyl; and where NR5R6 is
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and R2 is H. Kataoka also discloses compound 164, where R2 is cyclopropyl and NR5R6 is
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Kataoka does not disclose the instant compounds.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Kataoka to arrive at the instant invention.
The person of ordinary skill in the art would have replaced R1 = Br in the compound 50 above specifically disclosed by Kataoka, with chloro, or CN, or cycloalkyl, to arrive at the instant invention, because Kataoka teaches that the substituent in the 3-position of the pyrazole[1,5-a]pyrimidines (R2 in Kataoka, which corresponds to R1 in instant formula I) can be, for example, halogen, -CN, C3 to C8 cycloalkyl. Thus, the person of ordinary skill in the art would have replaced R1 = Br in the compound above disclosed by Kataoka, with Cl or CN, or cycloalkyl, with a reasonable expectation that the compounds retain biological activity as kinase inhibitors anti-cancer agents.
Further, the person of ordinary skill in the art would have synthesized a compound from the genus taught by Kataoka, where R3 is phenyl or benzyl substituted with halogen, cyano, alkyl, and would have explored different halogens F, Cl, in different relative positions on the phenyl or benzyl ring, in combination with R2 = cyclopropyl, or cyclobutyl, or Cl, or CN, and where NR5R6 is
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, with a reasonable expectation that the resulting compounds retain biological activity as kinase inhibitors and are effective to treat cancer.
As such, claims 1-3, 5, 8-9, 17-18, 28, 35-37, 39 are rejected as prima facie obvious.
Conclusion
Claims 1-3, 5, 8-9, 17-18, 25, 28, 35-37, 39 are rejected.
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 IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S. LUNDGREN can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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