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 1-13 are pending in the instant application.
Claims 2, 6-9, and 12 are amended.
Claims 14-21 are new.
Claims 1-21 are examined herein.
Priority
The instant application claims benefit of priority to U.S. Provisional Application No. 63230942, filed on 07 September 2021, and PCT/US2022/075966, filed on 06 September 2022. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 07 September 2021.
Information Disclosure Statement
The information disclosure statements (IDS), submitted on 29 May 2024, 25 November 2024, 13 January 2025, 02 July 2025, and 16 January 2026 are acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Arguments
The amendment filed on 28 July 2026 has been entered.
In view of applicant amendment to claim 6, the objection of record is withdrawn.
In view of applicant amendment to claim 12, the objection of record is withdrawn.
With respect to the 103 rejection, Applicant amendment has been considered but is not found persuasive for at least the following reasons. Applicant argues that there is no suggestion, teaching, or motivation to amend the compounds of Slaugenhaupt to that of the instant genus. The Examiner respectfully disagrees. Slaugenhaupt teaches that X3 can be CR3, the reference R3 corresponds to the instant R3 and Slaugenhaupt teaches R3 can be C1-6 alkyl, which can be substituted by 1-4 R20 groups, which includes amino moieties. Modification would be obvious because the teaching is present. The instant compound 7 and reference compound 193 are homologs, with an additional methylene group added to the reference compound; these are structurally similar compounds that would be expected to exhibit similar behaviors and are obvious variants. The Applicant points to a comparison of one of Slaugenhaupt’s compounds in Example 2 of the specification to demonstrate that the instant genus produces significant and unexpected results. However, the compound used does not contain a substituent at the reference R3 and is an inadequate comparison to the instant genus. Slaugenhaupt teaches several preferred embodiments with an alkyl substituent at R3 such as compounds 147, 154, 158, 169, 170, 171, or 193. To prove unexpected results the Applicant needs to demonstrate that the addition of one methylene group to the preferred embodiments of Slaugenhaupt with an alkyl group result in an inactive compound. Therefore, the rejection is maintained and amended to include the new claims recited.
All rejections and objections not found below have been withdrawn.
MAINTAINED AND AMENDED REJECTIONS
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 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.
Claim(s) 1-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Slaugenhaupt et al. (WO2016115434A1; cited by applicant on 1449 IDS) in view of Park et al. (BMB Rep. 2016 Aug 31;49(8):405–413).
Regarding claim 1, Slaugenhaupt discloses the method of treating a disease associated with mRNA splicing defects comprising administering compounds of Formula (I) (pictured below) (page 2 line 10) which overlaps with the instant Formula (I) when:
X1 is C
X2 is CR2, wherein R2 is hydrogen, halo, or C1-6 alkyl
X3 is CR3, wherein R3 is C2-6 alkyl
X4 is NR4, wherein R4 is hydrogen, C1-6 alkyl, or C6 aryl
X7 is N
X8 is N
R1 is C6-8 aryl or a 5-6 membered heteroaryl, optionally substituted
R5 is hydrogen, halo, or C1-6 alkyl
R6 is hydrogen
L is C1 alkylene
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Slaugenhaupt does not explicitly teach the method of treating a neurodegenerative disease characterized by the accumulation of aberrant forms of the microtubule associated protein Tau (MAPT).
Park teaches that tau mis-splicing is linked to neurodegenerative disorders (page 409) as the mis-splicing leads to the accumulation of certain tau isoforms.
It would be prima facie obvious to one of ordinary skill in the art that the compounds taught by Slaugenhaupt to treat neurodegenerative diseases associated with mRNA splicing defects could be used in tauopathies, as taught by Park. The skilled artisan would be motivated to use the compounds of Slaugenhaupt for treating neurodegenerative disorders via tauopathies as Park teaches the role of tau mis-splicing in taupathy.
Regarding claim 2, Slaugenhaupt teaches R1 (which corresponds to the instant R1) can be a C6-8 aryl, or 5-6 membered heteroaryl. Exemplary ring structures recited include phenyl (page 190), furyl, 1,2,3-triazolyl, 1,2,4-oxadiazolyl, 1,2,3-thiadiazoly, pyridyl, pyrimidinyl, and pyridazinyl. (page 192)
Regarding claim 3, Slaugenhaupt teaches R1 (which corresponds to the instant R1) can be a 5-6 membered heteroaryl. Exemplary ring structures recited include furyl and pyridyl (page 192).
Regarding claims 4 and 5, Slaugenhaupt teaches R3 can be C2-6 alkyl, optionally substituted with 1-4 substituents, substitution would result in a chiral carbon, this would encompass both the (S) and (R) enantiomer.
Regarding claim 6, Slaugenhaupt does not teach a preferred embodiment of the instant genus.
Slaugenhaupt does teach compound 81 (page 97) (pictured below). Compound 81 can be modified to instant compound 2 (6-(3-aminopropyl)-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine) with the addition of the 3-aminopropyl group at reference R3, which is a recited substituent (claim 1). Slaugenhaupt also teaches compound 193 (page 112) (pictured below). Instant compound 7 (2-chloro-6-[2-(dimethylamino)ethyl]-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine) is a homolog of reference compound 193, with an additional methylene group added at reference R3. As homologs the compound would be considered to be structurally similar and therefore would be expected to exhibit similar properties. See MPEP 2144.09.
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Regarding claim 7, Slaugenhaupt does teach compound 81 (page 97) (pictured below). Compound 81 can be modified to instant compound 10 (6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine) with the addition of the 2-aminopropyl group at reference R3, which is a recited substituent (claim 1).
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Regarding claim 8, Slaugenhaupt teaches administering compound 81 and compound 193 in the method of treating a disease associated with mRNA splicing defects.
Slaugenhaupt does not teach a preferred embodiment of the instant genus.
Slaugenhaupt does teach compound 81 (page 97) (pictured above). Compound 81 can be modified to instant compound 2 (6-(3-aminopropyl)-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine) with the addition of the 3-aminopropyl group at reference R3, which is a recited substituent (claim 1). Slaugenhaupt also teaches compound 193 (page 112) (pictured above). Reference compound 7 (2-chloro-6-[2-(dimethylamino)ethyl]-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine) is a homolog of reference compound 193, with an additional methylene group added at reference R3. As homologs the compound would be considered to be structurally similar and therefore would be expected to exhibit similar properties. See MPEP 2144.09.
Slaugenhaupt does not explicitly teach the method of treating a neurodegenerative disease characterized by the accumulation of aberrant forms of the microtubule associated protein Tau (MAPT).
Park teaches that tau mis-splicing is linked to neurodegenerative disorders (page 409) as the mis-splicing leads to the accumulation of certain tau isoforms.
It would be prima facie obvious to one of ordinary skill in the art that the compounds taught by Slaugenhaupt to treat neurodegenerative diseases associated with mRNA splicing defects could be used in tauopathies, as taught by Park. The skilled artisan would be motivated to use the compounds of Slaugenhaupt for treating neurodegenerative disorders via tauopathies as Park teaches the role of tau mis-splicing in taupathy.
Regarding claim 9, Slaugenhaupt does teach compound 81 (page 97) (pictured above). Compound 81 can be modified to instant compound 10 (6-[(2S)-2-aminopropyl]-2-chloro-5-fluoro-N-[(furan-2-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine) with the addition of the 2-aminopropyl group at reference R3, which is a recited substituent (claim 1).
Regarding claims 10-11, 14-15, and 18-19 Slaugenhaupt teaches the method of administering an effective amount of a compound of Formula (I), which overlaps with the instant formula (I), to a subject defined as any animal (page 196, line 16). As the prior art teaches administering an overlapping genus to the claimed patient population (defined by the instant specification as an animal on page 36, line 12), in an effective amount it would appear that the claimed limitations of inducing exon 10 skipping in MAPTA mRNA and lowering MAPT4R protein in a subject does necessarily occurs. MPEP 2112.01:I states:
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.”
Regarding claims 12, 16, and 20, Slaugenhaupt teaches Alzheimer’s disease and frontotemporal dementia. And Park teaches Alzheimer’s disease, Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease, and frontotemporal dementia.
Regarding claims 13, 17, and 21, Slaugenhaupt teaches the pharmaceutical composition with one or more pharmaceutically acceptable excipients (page 213).
Conclusion
Claims 1-21 are rejected.
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 Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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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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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
