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) in the reply filed on 11/20/2024 is acknowledged.
Applicant’s election without traverse of compound of example 46,
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in the reply filed on 11/20/2024 is acknowledged and maintained.
Expansion of Election of Species Requirement
A reasonable and comprehensive search 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 species
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. In light of this discovery, the search is expanded to compound of example 5
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. This compound reads on the claimed compound of the formula (I)
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wherein
A is unsubstituted heteroaryl (e.g., morpholino);
R is a carbocyclo (cyclobutyl);
W is C(O)NRa, Ra is hydrogen;
R1 and R2 are both hydrogen atoms;
n is 1;
L is hydrogen or
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, Rd is substituted aryl (methyl substituted phenyl).
Priority
This application is a continuation of International Patent Application No. PCT/US2020/035160, filed May 29, 2020, which claims the benefit of priority to U.S. Provisional Patent Application No. 62/854,181, which was filed on May 29, 2019.
Claims status
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on August 03, 2026.
Claims 1-3, 22, 26-31, 37-39, and 43 are pending. Claims 4-21, 23-25, 32-36, and 40-42 are canceled. Claims 2-3, 28-31, 37-49, and 43 are withdrawn. Claims 1, 22, and 26-27 are examined in accordance to the elected and expanded species.
The amendment to claim 43 renders claim 43 withdrawn from consideration under the election of species. As amended, claim 43 recites compounds 31-35 and 43-45, which are outside the elected and expanded species examined here. Its amendment does not place it within the maintained 103 rejection.
Action Summary
The rejection of claims 1, 19-22, 26-27, and 41-42 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn because Applicant’s amendment to claim 1 replace the previously recited broad substituent classes with identified substituents corresponding to disclosed examples.
The rejection of claim 26 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph is withdrawn because Applicant amendment removes Examples 41-42 from claim 26 and amended claim 1 to include the alternatives identified in Examples 36 and 39.
The rejection of claims 1 and 27 under 35 U.S.C. 103 as being unpatentable over Bennett et al (US2010/0093696 A1) in view of Patani et al (Chem. Rev. 1996, 96, 3147-3176), is withdrawn because the rationale set forth in that rejection does not adequately account for L/R3 arrangements encompassed by the amended claim 1.
The rejection of Claims 1, 22, and 26-27 under 35 U.S.C. 103 as being unpatentable over Bennett et al (US2010/0093696 A1) in view of Asif et al (Hindawi Publishing Corporation Journal of Applied Chemistry, Volume 2013, Article ID 247203, pages 1-7) and Zhu et al (The Pharmaceutical Society of Japan, Chem. Pharm. Bull. 60(8) 1037–1045 (2012)) are maintained.
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 non-obviousness.
Claims 1, 22, and 26-27 remain rejected under 35 U.S.C. 103 as being unpatentable over Bennett et al (US2010/0093696 A1) in view of Asif et al (Hindawi Publishing Corporation Journal of Applied Chemistry, Volume 2013, Article ID 247203, pages 1-7) and Zhu et al (The Pharmaceutical Society of Japan, Chem. Pharm. Bull. 60(8) 1037–1045 (2012)).
Bennett teaches a pharmaceutical composition comprising a compound of the formula (I)
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wherein X is a bond, R1 is C3-C12 heterocyclcyl, or a pharmaceutically acceptable salt thereof, and a pharmaceutical acceptable carrier as a medicament for the treatment of cancer. (See claims 1,15, and 16.) Moreover, Bennett teaches the heterocyclyl can be a morpholinyl ring. (See paragraph [0125].) Furthermore, Bennett teaches one of the preferred compounds is compound 42
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. (See page 40].)
Bennett does not teach claimed expanded compound of example 5.
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The difference between the prior art compound and the expanded compound is as follow:
Bennett compound 42 Claimed expanded compound 5
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Asif teaches Hydrazones (–NHN=CH group and R1R2C=NNH2) are present in many of the bioactive compounds with wide interest because of their diverse pharmacological applications and biological activities such as anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiplatelet, antimicrobial, anticancer, antihypertensive, anthelmintic, antidiabetic, antiparasitic, and other anticipated activities. (See Abstract.) Moreover, Asif teaches hydrazine compounds that possess the 4-tolyl or 4-fluorophenyl moiety are more active than 4-bromoephenyl and 4-N, N-dimethyl aminophenyl. (See first paragraph of the right column of page 2.)
Zhu teaches the aryl methylene hydrazine moiety, an attractive active pharmacophore, has been successfully applied to the design of anticancer agents. It is noteworthy that aryl methylene hydrazinyl derivatives CID13401328) (Fig. 1) and benzylidene hydrazinyl derivatives reported by our research group showed potent antitumor activity against several cancer cell lines. (See last paragraph of the right column.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to select the compound 42 of Bennett and modify said compound by replacing the 4-bromo-2-chloro-5-methoxyphenyl with morpholinyl moiety and further replacing one of the hydrogen of the amino group of the 5,7-dihydro-6H-pyroolo[3,4-d] pyrimidine with N'-(3-methyl- benzylidene)-hydrazine to give Applicant’s claimed compound. One would have been motivated to do so, because not only Bennett teaches the morpholinyl and 4-bromo-2-chloro-5-methoxyphenyl are interchangeable and also because Zhu and Asif teach benzylidene hydrazine including N'-(3-methyl- benzylidene)-hydrazine is a moiety that can enhance anticancer activity. One would reasonably expect the modified compound to exhibit excellent anticancer activity that can be used to treat cancer successfully.
Applicant’s arguments and Response to Applicant’s arguments
Acknowledgement is made of the receipt and entry of Applicant’s arguments, filed on August 03, 2026.
Applicant’s argument with respect to the Written description rejection, the 112(d) rejection, and the 103 rejections directed to Bennett in view of Patani has been fully considered and are persuasive in view of the amendment to the claims.
However, Applicant’s arguments directing toward Bennett in view of Asif and Zhu have been full considered and are not persuasive.
Applicant argues that Bennett lacks the L/R3 arrangement and that Asif and Zhu do not provide a reason to make it.
In response, Applicant’s argument is not persuasive. Specifically, the rejection does not rely on Bennett alone for the L/R3 arrangement. Bennett discloses morpholinyl as an R1 alternative within its compound class and the fused pyrimidine scaffold of compound 42 and expressly identifies morpholinyl as a heterocyclyl alternative at R1. Asif and Zhu supply the teaching upon for introducing an arylmethylene hydrazinyl group. Zhu, im particular, describes morpholino-substituted fused pyrimidines bearing that group at the amino-bearing position and reports anticancer activity. Thus, the asserted absence of the L/R3 arrangement from Bennett’s exemplified compound does not address the modification proposed by the combined references.
The amendments narrow claim 1 but leave within its scope the Example 5 embodiment addressed by the rejection. Claim 26 continues to recite Example 5 and claim 27 encompasses a pharmaceutical composition comprising the compound of claim 1. Accordingly, the rejection over Bennett in view of Asif and Zhu is maintained as claims 1, 22, and 26-27.
Conclusion
Claims 1, 22, and 26-27 are not allowed.
THIS ACTION IS MADE FINAL. 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 JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
