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
Claims 1 and 6-14 are currently pending.
Election/Restriction
Applicant’s election without traverse of Group I (Claims 1, 6-12, and 14, drawn to compounds of formulae (I) and (II)) and the species of B34 (also labelled B133 in the application) in the reply filed on 9/20/2024 is acknowledged.
Claim 13 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Group II, there being no allowable generic or linking claim. Thus, Claims 1, 6-12, and 14 are being examined on the merits herein.
The requirement is deemed proper and is therefore made final.
The elected compound, B34 (and B133), was searched and found to be free of the art. The search was expanded to compounds specifically listed in Claims 11-12 and 14.
Claim Objections
Claims 1, 11-12, and 14 are objected to because of the following informalities:
Claim 1 reintroduces several comma-separated R and R1 groups without clearly striking out the groups which are to be replaced:
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The groups to be replaced are not entirely struck through and appear to be repeat structures.
Claims 11-12 and 14 specify several compounds which are repeated with different labels; e.g., elected species B34 and B133, and B99 and B159.
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The above examples of repeated structures are not exhaustive. It is applicant’s burden to seek out and strike from the claims all compounds which are depicted more than once.
Appropriate correction is required.
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 1 and 6-10 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 regards as the invention.
Claim 1 uses the variable “X” no less than three times to denote alternate groups in the structures of Formulae (I) and (II). First, X is used to define a member of the bicyclic core structure:
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Second, X is used to define the following group of the R substituent:
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Third, X is depicted as a ring member on the R1 ring substituent:
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.
It is unclear whether the definitions of X are interchangeable and how the groups of the same variable, “X”, are structurally related given each instance describes separate groups within Formulae (I) and (II). Claims 1 and 6-10 are rejected by virtue of dependency.
Claim 1 uses the variable “Q” to define two different ring members on distinct substituents. R1 can be
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wherein
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. Also, R2 can be
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wherein Q in this instance is undefined. The metes and bounds of the variable “Q” are unclear because said variable is used to describe unrelated substituent groups R1 and R2 with potentially different definitions. Therefore variables X and Q have at least two sets of different metes and bounds. Claims 6-10 are rejected by virtue of dependency.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 6-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Reddy (Journal of Medicinal Chemistry, Vol. 57, No. 3, 2014, pp. 578-599, cited in 9/20/2021 and 7/02/2024 IDS).
Reddy teaches Compound 7x (Abstract):
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in which the following examined definitions of Formulae (I) and (II): A is H;
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is CN; X and Y are each N; R is
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; and R1 is
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, wherein X (with respect to R1) is CH and R3 is Me.
Claims 1 and 6-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Temple (US8987267, published 3/24/2015).
Temple teaches Compound 12 (PDF Page 2, Figure 1):
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in which the following examined definitions of Formulae (I) and (II): A is H;
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is CN; X and Y are each N; R is
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; and R1 is
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, wherein X (with respect to R1) is CH and R3 is Me.
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, 6-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Temple (US8987267, published 3/24/2015) in view of Burkhard (Angewandte Chemie International Edition 2010, 49, 3524-3527).
Temple teaches Compound 12 (PDF Page 2, Figure 1):
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in which the following examined definitions of Formulae (I) and (II): A is H;
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is CN; X and Y are each N; R is
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; and R1 is
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, wherein X (with respect to R1) is CH and R3 is Me. The compound is formulated with excipients and carriers into pharmaceutical compositions and exhibits CDK(4/6) inhibitory activity (Col 16, Lines 1-11; Col 27, Table 4). Temple teaches exemplary compounds wherein the 4-methylpiperazinyl group may vary (Col 22-33, Table 1, Compound 13):
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Temple does not teach the modification of the 4-methylpiperazinyl group to a 2-methyl-2,6-diazaspiro[3.3]heptanyl group.
Burkhard teaches “In the process of lead optimization, various structural features are fine-tuned and physicochemical properties” are improved (Page 3524, Para 1). Spiro[3.3]heptanes are taught as isosteres of heterocycles in the process of structural fine-tuning (Page 3524, Figure 1):
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Burkard specifically depicts 4-methylmorpholino and 2-methyl-2,6-diazaspiro[3.3]heptanyl as an isosteric pair (Page 3525, Table 1):
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The spirocyclic group is not merely a substitute for 4-methylpiperazinyl but also offers several pharmacokinetic advantages. “Replacing a six-membered monocyclic unit in a drug candidate by a corresponding spiro[3.3]heptane analogue is worth implementing, as it may significantly improve relevant aspects of the pharmacokinetic profile by increasing the aqueous solubility and reducing both lipophilicity and metabolic degradation” (Page 3526, Para 1; Page 3526, Last Para).
One of skill in the art seeking to improve upon the pharmacokinetic profile of Compound 12 of Temple would replace the 4-methylmorpholino with 2-methyl-2,6-diazaspiro[3.3]heptanyl, motivated by the desire to form a more metabolically stable CDK inhibitor with improved pharmacokinetic properties. The modification would render
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or
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of Claims 11-12 and 14 obvious. The same artisan would expect the modified inhibitor to successfully inhibit CDK as Burkhard also teaches “inhibitory properties may be retained with refinement of pharmacokinetic and -dynamic properties and the overall efficacy may even be improved” (Page 3526, Para 2).
Conclusion
No claim is allowable.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/NOBLE E JARRELL/Primary Examiner, Art Unit 1699