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 17/633,617
Claims 1, 4-11, and 13-17 are currently pending.
Priority
Instant application 17/633,617, filed 2/8/2022, claims priority as follows:
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Receipt of the foreign priority application is acknowledged.
Information Disclosure Statement
All references from the IDS submitted on 2/8/2022, 4/22/2022, and 12/19/2023 have been considered unless marked with a strikethrough.
Response to Arguments/Amendments
The amendment filed 10/9/2025 has been entered. Claims 1, 4, 6-7, 10, and 13 have been amended. Claims 3 and 12 have been cancelled. No new matter has been added.
In the Non-Final dated 5/12/2025, the abstract was objected to for the unclear term, “LIT-TB”. In response, Applicant has deleted the term to overcome the objection and the objection is withdrawn.
Claims 1, 3-5, 7, 10-13, and 16-17 were rejected under 35 U.S.C. 112(b) in the Non-Final dated 5/12/2025. Upon cancellation of claims 3 and 12, and amendments to claims 1 and 7, the rejections of claims 1, 4-5, 7, 11, 13, and 17 are overcome and withdrawn. However, Applicant did not delete or properly define the term “non fluorescent analogue” recited in claim 10, and thus, the rejection of claims 10 and 16 under 35 U.S.C. 112(b) is maintained.
In the Non-Final dated 5/12/2025, claims 1, 5, 10-12, and 16-17 were rejected under 35 U.S.C. 102(a)(1). In response, Applicant has amended claims 1 and 10 to omit the limitation where X4 is NH to overcome and withdraw the rejection.
Claims 1, 3-7, 11-13, and 17 were rejected under 35 U.S.C. 103 in the Non-Final dated 5/12/2025. After an interview and Applicant’s amendment to claim 1 to recite an “effective amount”, this rejection has been overcome and thus, withdrawn.
Election/Restriction
Applicant’s election of Group I, claims 1, 3-7, 10-13, and 16-17, drawn to compounds and compositions of Formula I, in the reply filed 4/24/2025 is acknowledged. Applicant’s election of compound TB001 (9a):
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in the reply filed 4/24/2025, is also acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
In the Non-Final dated 5/12/2025, the elected species was searched and prior art was identified. However, upon an interview with the attorney of record and the amendment to claim 1, the 103 rejection of claims 1, 3-7, 11-13, and 17 was overcome. Additionally, the rejection under 35 U.S.C. 102(a)(1) of claims 1, 5, 10-12, and 16-17 was overcome by amendment. Thus, the search was expanded to the full scope of formula I, and was found to be free of the prior art. However, Group I contains an outstanding rejection as listed above and thus Group I is not yet directed to an allowable product. The Examiner notes method claims 8-9 and 14-15 contain the same 112(b) rejections as claims 1 and 10, specifically “such as” and “non fluorescent analogue”, recite a broader scope of compounds as X4 of formula I in claims 8 and 9 may be NH, and claim 8 does not provide a structure/function relationship for treatment therefore generating a written description issue.
MAINTAINED REJECTIONS
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, 3-5, 7, 10-13, and 16-17 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites the limitation, “a non-fluorescent analogue thereof”, in reference to the fluorescent group in the definition of variable “fl”. It is unclear what a non-fluorescent analogue of a fluorescent group is, and the limitation is not defined in the disclosure. Thus, the limitation is deemed indefinite. Dependent claim 16 does not resolve this issue by claiming a specific non-fluorescent analogue and are therefore also rejected. Appropriate correction is required.
Close Prior Art Not Cited
The reference Array BioPharma, Inc. (US 2016/0137654 A1, herein after “Array”) was identified as close prior art during the search. Array is drawn to a crystalline form of (S}-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-l-yl)-pyrazolo[ 1,5-a ]pyrimidin-3-yl)-3-hydroxypyrrolidine-l -carboxamide (abstract and para [0022]):
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Which partially maps to a compound of instant formula I:
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When R1 is a substituted aryl, G is a -G1-G2- linker, where G1 is a bond and G2 is heteroalicyclic, X1 is N, X3 is C, X4 is N, X2 is CH, A is an amide, m is 0, m’ is 1, t is 1, T1 is CH2, T2 is CH2, and Z is H, so R2 is null. Array further discloses that the compound inhibits TrkB (page 28, para [0261]), and is able to decrease the growth of tumors (page 37, para [0318]). The compound of Array differs from compounds of instant formula I because it contains an additional nitrogen in the core, does not contain an alkyl linker between the core and variable A, connects to the pyrrolidine via N-connection, not C-connection, and has a hydroxy group substituted on the pyrrolidine, which instant R6 or R2 do not allow. Additionally, though Array discloses the biological activity of the compound against the same target as the instant disclosure and treatment of cancer, it does not explicitly disclose the treatment of neurodegenerative diseases, metabolic disorders, mood disorders, spinal cord injury, brain stroke, or ischemia. There is no motivation, teaching, or suggestion in Array alone or in combination with the prior art to modify the compound therein to arrive at a compounds of the instant claims.
Additional close prior art identified during the search is East China University of Science and Technology (CN109912576A, herein after “East China”), which is drawn to pyrimidine-hydroxamic acid compounds useful in treatment of parasitic infections (abstract). Specifically, East China discloses compound IA-13 (page 9, lines 1-7):
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Which partially maps to instant formula I:
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When R1 is H, G is a bond, X1 is CH, X3 is N, X2 is CH, X4 is N, r is 1, A is an amine, m and m’ are 1, t is 0, T1 and T2 are CH2, Y is CH, and R2 is a 6-membered aromatic heterocycle. Compound IA-13 differs from instant formula 1 because it does not contain Z, where Z is a bond, H, or an optionally branched C1 to C3 alkyl chain and R2 is substituted with hydroxamic acid, which is not a variable listed in the Markush group of instant R7. Further compound IA-13 was found to have biological activity as an anti-malarial (page 25, Table 1.1), which differs from the compounds of the instant invention as they are TrkB modulators. Similar to Array above, there is no motivation, teaching, or suggestion in East China alone or in combination with the prior art to modify the compound therein to arrive at a compounds of the instant claims.
Allowable Subject Matter
Claims 1, 3-7, 11-13, and 17 are allowed.
Conclusion
Claims 1, 3-7, 11-13, and 17 are allowed. Claims 10 and 16 are rejected. Claims 8-9 and 14-15 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 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 Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621