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
Status of the Claims
Claims 1-17, 19-25, 28-29 and 31-33 are currently pending. Claims 6-10, 16-17, 19-23, 28-29 and 31-33 are withdrawn. Claims 1-5, 14 and 25 are rejected. Claims 11-13 and 15 are objected to. Claim 24 is allowed.
Information Disclosure Statement
The Information Disclosure Statement (IDS) dated 01/05/2026 has been considered.
Response to Amendment/Arguments
The amendment filed 03/16/2026 is compliant with the requirements of 37 CFR 1.121(c), accordingly the amendment has been entered. Applicant’s arguments have been fully considered and are addressed below:
Objection to the Claims
The objection of the claim 1 for informalities has been overcome by the amendment correcting said informalities. The objection has been withdrawn.
35 USC § 112 Rejections
The rejection of claims 3, 15 and 24 under 35 USC 112 has been overcome by the amendments to said claims. The rejection has been withdrawn.
35 USC § 102 Rejection
The rejection of claims 1-5, 14 and 18 under 35 USC 102 for being anticipated by Zhao, Qing-jie et al. Chinese Journal of Medicinal Chemistry, (2006) 16(3) p. 150-153 has been overcome by the amendments to said claims and cancellation of claim 18. The rejection has been withdrawn.
The rejection of claim 25 under 35 USC 102 for being anticipated by Zhao, Qing-jie et al. Chinese Journal of Medicinal Chemistry, (2006) 16(3) p. 150-153 as evidenced by National Committee for Clinical Laboratory Standards (NCCLS) (1997) has been overcome by the amendments to said claim. The rejection has been withdrawn.
Scope of the Elected Invention
In accordance with the MPEP 803.02, examination of the Markush-type claims has been extended, as necessitated by amendment, to the scope of:
claim 24;
formula (I) of claim 1 wherein R1, n, R2, L1, Q2 and their possible substituents are as defined in the claim and Q1 is Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij or Ik; and
formula (I) of claim 1 wherein R1 is F, n is 2, R2 is H, Q1 is Ia, L1 is -CH2-, and Q2 is substituted phenyl, which was not found allowable over the prior art.
Claims 6-10, 16-17, 19-23, 28-29 and 32-33 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
New 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.
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 1-5, 14 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao, Qing-jie et al. “Synthesis and antifungal activities of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted-piperazine)-1-yl]-2-propanols” Chinese Journal of Medicinal Chemistry, (2006) 16(3) p. 150-153 in view of Jiang, et al. “Design, synthesis and antifungal activity of novel triazole derivatives containing substituted 1,2,3-triazole piperidine side chains,” Eur J Med Chem, Vol. 82, pp. 490-497, June 2, 2014, as cited in the IDS dated 04/14/2023.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Zhao et al. teach compound 4,
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, see page 151, Figure 1. Prior art compound 4 is nearly embraced by instant formula (I) of claim 1 wherein:
R1 is F (see instant claims 3-5),
n is 2 (see instant claims 3-5),
R2 is H (see instant claim 2),
Q1 is
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,
L1 is -CH2-, and
Q2 is phenyl (see instant claims 14 and 18).
Jiang et al. teach compounds of formula 8,
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, and in particular compounds 8t and 8v:
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. See page 492, Scheme 1. Compounds 8t and 8v are nearly embraced by instant formula (I) of claim 1 wherein:
R1 is F (see instant claims 3-5),
n is 2 (see instant claims 3-5),
R2 is H (see instant claim 2),
Q1 is
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,
L1 is a bond, and
R5 is Q3-L3- wherein L3 is a bond and Q3 is phenyl substituted with one R7 wherein R7 is either -C(O)RA2 wherein RA2 is C1 alkyl (per compound 8t) or -ORA1 wherein RA1 is C1 haloalkyl (per compound 8v).
The difference between Jiang’s compounds and the presently claimed invention as that the instant claims require a proviso that when n is 1 or 2, R1 is halo, L1 is a bond and Q1 is Ia, then Q2 is a phenyl or 6-membered heteroaryl substituted with X wherein X is Q3-L3-, whereas Jiang’s compounds have the 5-membered heteroaryl triazolyl as Q2.
Each of these prior art compounds (4, 8t and 8v) have the common core structure of
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. Zhang et al. teach that compound 4 exhibited activity that was “more than 4 times as high as that of fluconazole and itraconazole against Candida albicans in vitro” (see Abstract and Table 2 on page 153). Jiang et al. teach that “compounds 8t and 8v were highly active against Candida albicans and Cryptococcus neoformans with MIC values in the range of 0.125 ug/mL to 0.0125 ug/mL” (see Abstract and Table 1 on page 493).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The difference between Zhao’s compound 4 and the presently claimed invention is that the instant claims require that Q2 is further substituted by R5 wherein R5 is Q3-L3-.
The difference between Jiang’s compounds and the presently claimed invention is that the instant claims require a proviso that when n is 1 or 2, R1 is halo, L1 is a bond and Q1 is Ia, then Q2 is a phenyl or 6-membered heteroaryl substituted with X wherein X is Q3-L3-, whereas Jiang’s compounds have Q2 as the 5-membered heteroaryl triazolyl ring.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2144)
A person having ordinary skill in the art would be motivated to further optimize Zhao’s compound 4 to improve antifungal activity. In doing so, the skilled artisan would seek comparable inhibitors with the same core, such as those taught by Jiang. Jiang’s compounds 8t and 8v are an improvement on compound 8q which is the structure
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wherein R is the unsubstituted phenyl ring. See page 492, Scheme 1. For instance, Jiang teaches that 8q inhibits C. albicans at an MIC80 of 0.125 ug/mL and that 8t and 8v are significantly better inhibitors at 0.0625 and 0.0125, respectively.
In seeking to improve the activity of compound 4, it would have been obvious to a person having ordinary skill in the art to substitute the phenyl ring of Zhao’s compound 4 in the same way that Jiang substituted 8q. There would be a reasonable expectation of success in doing so since Jiang’s compounds 8t and 8v have improved anti-fungal activity over the unsubstituted 8q.
The claims are thus obvious in view of the prior art.
Regarding claim 25, drawn to a pharmaceutical composition comprising a compound of claim 1, Jiang teaches an in vitro antifungal assay wherein compounds 8t and 8v are tested. See page 491, right column, section 4.2 and Table 1 on page 493. A person having ordinary skill in the art would expect that the assay requires dissolution of the compounds in buffer and/or media, which are pharmaceutically acceptable excipients. Thus, claim 25 is obvious in view of the prior art.
Allowable Subject Matter
Claims 11-13 and 15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-5, 14 and 25 are rejected. Claims 11-13 and 15 are objected to. Claim 24 is allowed. Claims 6-10, 16-17, 19-23, 28-29 and 31-33 are withdrawn.
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 date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jalisa H. Ferguson whose telephone number is (703)756-1489. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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/J.H.F./Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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