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
Response to Amendment
The amendment filed 6/29/2026 has been entered. Newly amended Claims 111-117, 119-123, 125-144, and 154-162 are pending in the application.
Claim 139 and claims dependent therefrom were found to be free of the prior art. The species election requirement is therefore withdrawn and the previously withdrawn claims 142-143, drawn to unelected species, are rejoined for examination. Further, newly added Claims 154-162, drawn to compounds and compositions of Group I, are examined herein.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Applicant’s Arguments
Applicant’s amendments to the claims render the rejections over 35 USC 102 moot.
Regarding the first rejection over Lindenthal, applicant argues nothing leads one of skill in the art to select compound 145 and that a majority of the compounds are direct toward non-cyclic R2 groups. Applicant states compound 145 was not assessed for biological activity. Further, applicant cites Brumby teaching generally that select R2 groups possessing alkyl yield compounds with lower IC50 values than those containing cycles. Second, applicant argues that selecting O as the alternative X group would require the selection of a single moiety out of hundreds or thousands of other options. Applicant’s arguments are fully considered but not persuasive.
First, the Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound: "Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e. a lead compound) in a particular way to achieve the claimed compound." Eisai, 533 F.3d at 1357, 87 USPQ2d at 1455. There must be some reason for starting with that particular lead compound other than the mere fact that the "lead compound" exists. (See MPEP 2143 I B Example 9.) The reason for having selected said compound for modification was provided by examiner on Pages 5-6 of the nonfinal action; “Lindenthal teaches compound 145 as a CDK inhibitor” and “Lindenthal teach[es] that compounds of the genus of formula I, including a modified Compound 145, are acceptable CDK inhibitors”. Therefore, the compound of Lindenthal referenced herein is indeed a lead compound as defined in the MPEP due to its use as a CDK inhibitor in the prior art.
Applicant, in comparing cyclic and (hetero)alkyl R2 groups, errs in identifying the distinguishing features which yield IC50 values of under 10nM versus those over several hundred nM. All groups in Pages 56-58 on Tables 1-2 of applicant’s Remarks can be categorized as having an instant R1 position of SO2NH2 para with respect to the amino linakge or failing to possess the p-sulfamoyl group altogether. Applicant does not explain why Compound 8 of Table 2—despite having an R2 group containing a cycle—has an IC50 value comparable to those of Table 1. Therefore, Brumby does not in fact teach away from the selection of a cyclic R2 as characterized by applicant.
Regarding “teaching away”, the term may only be applied to a reference teaching insofar as said reference truly teaches away from a compound or practice. A compound does not have to be the “most preferred” or “most potent” compound to be obvious. See In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (a conclusion of obviousness does not require “something in the prior art as a whole to suggest that the combination is the most desirable combination available”). See also In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971) (Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments.). See In re Lamberti, 545 F.2d 747, 750 (CCPA 1976) (explaining that “all disclosures of the prior art, including unpreferred embodiments, must be considered”); cf. In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012) (noting that “just because better alternatives exist in the prior art does not mean that an inferior combination is inapt for obviousness purposes”), In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (stating that “finding that the prior art as a whole suggests the desirability of a particular combination need not be supported by a finding that the prior art suggests that the combination claimed by the patent applicant is the preferred, or most desirable, combination”), Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 1008 (Fed. Cir. 2009). See also Merck & Co., Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976)) (“[I]n a section 103 inquiry, ‘the fact that a specific [embodiment] is taught to be preferred is not controlling, since all disclosures of the prior art, including unpreferred embodiments, must be considered.’”). See also In re Mills, 470 F.2d 649,651 (CCPA 1972) ("All the disclosures in a reference must be evaluated, including nonpreferred embodiments, and a reference is not limited to the disclosure of specific working examples.").
Lastly, applicant argues the selection of oxygen in place of nitrogen at the X position is not obvious due to the several other alternative embodiments which may be employed. However, Lindenthal teaches X may be either O, NH, N(alkyl), or OC3-C10-cycloalkyl. Of these groups, only a single monatomic divalent classical isosteric variant is listed. One of skill in the art recognizing the electronic and steric similarities between NH and O might find the substitution obvious even absent the explicit teaching in Lindenthal. However, Lindenthal does in fact teach such a substitution as acceptable and even deploy said X group in the prior compound depicted on the same Page 35: compound 144. The rejection is reapplied and amended appropriately to account for applicant’s amendments to the claims.
Regarding the second and third rejection over the same concerning compound 144, applicant’s amendments to Claim 111 preclude the following R2 group:
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, which was previously rendered obvious. With respect to independent claims 123 and 132, the required hydroxyl group affixed to R2 is one of several hundred or thousands of embodiments (
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) describing the particular substituent affixed to R2. (It is noted that despite being bolded, even the alkoxy groups are not acceptable groups following amendment.) To choose to 1) substitute the moiety, 2) choose hydroxyl out of thousands of groups, and 3) choose the R2 carbon position adjacent to the ether oxygen would require impermissible hindsight and picking and choosing from the extensive list of embodiments to arrive at a compound encompassed by Formula II(-1). Both the second and third rejections are withdrawn.
Applicant further argues with respect to all rejections over 35 USC 103 over Lindenthal that the compounds of the invention are unexpectedly selective for CDK2 as opposed to those of the prior art. Applicant states Brumby, teaching several select compounds also found in Lindenthal, characterizes the CDK modulators as broadly inhibitory towards several CDKs. Oppositely, applicant characterizes the claimed compounds as selective inhibitors of CDK2 as compared to other CDKs, citing paragraph 437 of the specification. The argument is fully considered but not persuasive. The results are not unexpected because no direct comparison is drawn between data of the Brumby compounds and the instant compounds. Further, several of the instant compounds in the referenced Table 2 below paragraph 437 show excellent inhibitory activity across an array of CDKs:
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Lastly, a showing of unexpected results requires that the closest prior art, Lindenthal compound 145 in the outstanding rejection, be compared to the scope of the compounds claimed. The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See MPEP 716.02(b).
Regarding the double patenting rejections over apps no. 18670469 and 18958484, applicant is correct that said applications are later filed. It is also true that said applications have a later patent term filing date. However, because these rejections are not the only outstanding rejections, both are reissued hereinbelow and amended appropriately.
The rejection over app no. 19431098 is withdrawn. Applicant’s arguments regarding different structural requirements in the amended claims of the copending application are persuasive.
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 § 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 111, 113-117, 119-123, 126, 129-132, 134, 136-138, and 157-158 are rejected under 35 U.S.C. 103 as being unpatentable over Lindenthal (US20060252748).
Lindenthal teaches CDK inhibitors (Abstract). Lindenthal teaches compound 145 as a CDK inhibitor on Page 35:
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, in which the following definitions of examined Formula I apply: X is N; R3 is Br; R4 is H; L1 is
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, wherein n is 0; R1 is SO2NH2; L2 is a NH2 ; L3 is a bond; and R2 is
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. Compounds of the inventions are to be formulated with various excipients in various dosage forms, or pharmaceutical compositions (Para 100-105).
Lindenthal teaches that the instant L2 position—X in formula I of Lindenthal—may instead be an oxygen (Para 16). One of skill in the art seeking to form CDK inhibitors would find it obvious to make the modification to Compound 145 using the alternative embodiment to position X as suggested by Lindenthal before the filing date of the instant application. The same artisan would expect the successful modification of the compound because of the limited acceptable embodiments of X and Lindenthal teaching that compounds of the genus of formula I, including a modified Compound 145, are acceptable CDK inhibitors.
Double Patenting
1. Claims 111-117, 119-123, 125-144, and 154-162 are provisionally rejected on the grounds of anticipatory nonstatutory double patenting as being unpatentable over Claims 17-38 of copending Application No. 18670469 (hereinafter referred to as Allorion).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to the same compounds and pharmaceutical compositions thereof with excipients. For example, both applications teach the elected species:
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Method claims require the existence of the claimed compounds.
Since both applications teach the same species, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Allorion.
This is a provisional nonstatutory double patenting rejection.
2. Claims 111-117, 119-123, 125-140, 144, and 157-159 are provisionally rejected on the grounds of anticipatory nonstatutory double patenting as being unpatentable over Claims 1-41 of copending Application No. 18958484 (hereinafter referred to as Allorion).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to overlapping genera of kinase inhibitors and pharmaceutical compositions thereof. Allorion teaches more narrow genera of Formulae I, II, II-1, and II-2, where R10 in particular is limited to aromatic carbocycles and heterocycles. The same compounds are also taught; e.g.,
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(Claim 34). Methylene homologs are also taught:
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(instant Claim 140) vs.
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(copending Claim 39). Compounds which are 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). See MPEP 2144.09.
Method claims require the existence of the claimed compounds.
Since both applications teach overlapping genera, similar compounds, and the same compounds, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Allorion.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
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 extension fee 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.
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 7:30am - 4:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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