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
Election/Restriction
Applicant elected, without traverse, Group II (claims 6-9), and compound species II-1d, wherein n is 4, R1 is H, R2 is CH3, having following structure (See instant spec [0177]), in the reply filed on 04/02/2026.
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The elected species, compound II-1d is a compound of Formula II-1, wherein n is 4, R1 is H, R2 is CH3. Claim 9 reciting compound II-2 does not read on the elected species. Claim 9 is withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions/species.
The elected species, compound II-1d, (CAS # 2919475-49-1, entered STN on April 06, 2023, see STN search note )
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Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. 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 reconsidered. 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 reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Status of Claims
Claims 6-9 and 11-13 are pending in the instant application.
Claims 9, 11-13 are withdrawn.
Claims 6-8 are currently under examination.
Priority
This instant application 18/689,852 filed 03/06/2024 is 371 of PCT/US2022/042814, filed September 07, 2022 which claims the priority of U.S. provisional application No. 63/241,543, filed September 08, 2021.
Specification
The specification is objected to because, the name of compound II-1d (See [0177]), is NOT consistent with the structure of Formula II-1d, wherein n is 4.
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is a compound of Formula II-1 wherein n is 2 as shown in compound II-1b (See [0167]).
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Instant specification contain compounds having chiral centers, stereochemistry and very lengthy names. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible error for the chemical names and other errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 6 is rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the full-scope of claimed compound of Formula II. This is a written description rejection, rather than an enablement rejection under 35 U.S.C. 112, first paragraph. Applicant is directed to the MPEP 2163 and Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1st "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
MPEP 2163.02 states “ Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, the inventor was in possession of the invention, and that the invention, in that context, is whatever is now claimed.”
Instant claim 6 is directed to compound II genus comprising A, Z and L moieties and combination thereof. Instant specification only disclose working example wherein Z is O. Instant specification does not disclose working examples wherein Z is S or NH. Instant specification does not disclose working examples wherein A is CH2. In absence of sufficient working examples, an ordinary skilled artisan would not know if the Applicant is in possession of full scope of compound II.
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.
Claims 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Ferguson et al. (WO 2021/257650 A1) , in view of Patani et. al. (Chem. Rev., 1996, 96, page 3147–3176, Bioisosterism: A rational approach in drug design) and Amyvid (Florbetapir F18) label (2012).
Ferguson teaches bifunctional compound of formula I, that target at α-synuclein protein degradation for treating neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s disease), wherein the targeting ligand TL represents a group that binds α-synuclein protein, a degron moiety that binds an E3 ubiquitin ligase, and a linker moiety that covalently connects the degron and the targeting ligand (See abstract, [0002]-[0003] , [0087], claims 1-22).
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Ferguson teaches a variety of targeting ligand moiety, e.g. TL-1, TL-2, TL-3, TL-4, TL-5, (See [0003], [0036] , for example,
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Ferguson teaches degron binds the E3 ubiquitin ligase which is cereblon (CRBN), e. g. D1-a to D1-i, etc. (See [0051]-0052]) wherein Y is NH or O.
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Ferguson teaches variety of linker moiety, e. g. polyethylene glycol chain, alkylene chain or a bivalent alkylene chain, etc. at different length (See([0042], [0045], [0047]), for example,
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Ferguson teaches embodiments that are similar to the core structure of instant compound of Formula II-1 except the pyridine ring (See [0041], [0049], [0055], page 24)
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Ferguson teaches compounds species that are similar to instantly claimed compound, except the pyridine ring (See page 80, claim 17).
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Ferguson collectively teaches core structure and compounds species that are similar to instantly claimed compounds.
The main difference of instant compounds and Ferguson compound is pyridine vs benzene ring.
Patani teaches CH2, NH, O are classic bioisosteres based on Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (See p. 3148-3149). Patani also teaches benzene, pyridine and thiophene are classical ring equivalent bioisosteres (See page 3158, left column).
Amyvid (Florbetapir F18) ( CAS# 956103-76-7, PubChem CID 24822371), having following structure comprising styrylpyridin-2-yl ethoxy moiety (See 11 Description), is approved by FDA in 2012 as positron emission tomography (PET) imaging ligand that binds to amyloid aggregates associated with Alzheimer disease and cognitive impair.
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According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
It would have been prima facie obvious to one of ordinary skilled in the art to explore more bifunctional α-synuclein protein degrader based on the collective teachings of Ferguson, together with structure similarity and bioisosteric modification as taught by Patani and general knowledge of neurodegenerative disease, and arrive at instantly claimed invention with reasonable expected success. Florbetapir comprises styryl-pyridin-2-yl ethoxy moiety
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as ligand that binds to amyloid aggregation. A skilled artisan would be motivated to explore more alternative bifunctional compounds comprising
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that are reasonably expected to bind with amyloid aggregates /target at α-synuclein aggregate for treating neurodegenerative disease.
For example, Ferguson compound 12 comprising polyethylene glycol linker moiety (n =2) could have been modified to instant non-elected compound II-1b (n=2), by replacing the benzene ring with pyridine and attaching the linker moiety directly to the degron moiety since Ferguson taught
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(Y= NH) .
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Instant non-elected compound II-1b ( n=2) could have been further modified to instant elected species, compound II-1d ( n= 4) by exploring longer polyethylene glycol linker as Ferguson teaches different length of linker moiety .
Therefore, the invention as a whole is prima facie obvious to one of ordinary skilled in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mukherjee et al.( US 2020/0171016 A1). Mukherjee teaches Αβ plaque targeting agent comprising
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for target removal of amyloid beta plaques for treating Alzheimer’s disease.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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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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/LIYUAN MOU/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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