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
Claim 17 is directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 18-20 and 27-28, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 4 September 2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 17, 18, 22-24, and 27 have undergone amendments. Claims 29-33 are newly added. Thus, Claims 17-33, submitted on 23 July 2026, represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 22 July 2026, is acknowledged and has been considered.
Response to Arguments
The objection to the drawings is withdrawn. Applicant has provided new drawings of higher quality.
The objection to Claims 17 and 22-26 is withdrawn. Applicant argues that the recitation alongside their salts, polymorphs, stereoisomers, solvates, co-crystals, and pro-drugs in a single claim preamble is widely accepted. Applicant has further amended Claim 17 to recite “A compound and pharmaceutically acceptable salts thereof,…”, obviating the objection.
The 35 U.S.C. § 112(a) rejections of Claims 17 and 22-26 over the limitations “intermediates” and “metabolites” is withdrawn. Applicant has amended the claims to remove these limitations.
The 35 U.S.C. § 112(b) rejection of Claims 17 and 22-26 over the lack of providing a corresponding neutralizing anion for compounds (a) and (d) is withdrawn. Applicant argues that the limitation “pharmaceutically acceptable salts” provides the metes and bounds for these two compounds, with the specification stating that “an equivalent of an anion (X-) is associated with the positive charge of the N atom”. The Examiner finds these arguments to be persuasive.
The 35 U.S.C. § 112(b) rejection of Claim 22 is withdrawn. Applicant has amended Claim 22 to depend on Claim 21, which provides antecedent basis for the limitation “wherein the neurodegenerative disease is selected from…”.
The 35 U.S.C. § 112(b) rejection of Claims 23 and 24 is withdrawn. Applicant has amended Claims 23 and 24 to replace “the compounds of Formula (I)” with “the compound”, which has antecedent basis in Claim 17.
All 35 U.S.C. § 102 (a)(1) rejections of the previous office action are withdrawn. Applicant has amended the claims to remove the limitation of “intermediates”, which the compounds cited in the prior office action encompassed.
Claim Rejections - 35 USC § 112(a)- NEW GROUNDS OF REJECTION
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 21, 22, 27 and 28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of neurodegenerative diseases which are mediated by aggregation of Aβ42, tau, or α-syn, it does not reasonably provide enablement for the treatment of all forms of neurodegenerative diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth below:
The nature of the invention and breadth of the claims:
The claims are directed towards a method of a condition mediated by a neurodegenerative disease or by aggregation of Aβ42, tau, or α-syn, comprising administering to a patient in need a therapeutically effective amount of a compound of Claim 17. The specification demonstrates that these compounds are inhibitors of aggregation of protein fibrils such as Aβ42 and tau. Thus, the claims are directed to a method which can be used to treat any form of neurodegenerative disease by using the compounds of the invention to inhibit the aggregation of protein fibrils such as tau, Aβ42, or α-syn.
The state of the prior art and the predictability or unpredictability of the art:
Wu (Neurochemistry International, 180, 2024, 105880) provides an overview of protein aggregation and its relationship to neurodegenerative diseases. Protein aggregation serves as a critical pathological biomarker in a spectrum of neurodegenerative diseases, including the formation of amyloid β and Tau neurofibrillary tangles in Alzheimer’s disease, as well as α-syn aggregates in Parkinson’s disease, Parkinson’s disease related dementia, dementia with Lewy bodies, and multiple system atrophy. Patients with ALS exhibit TDP-43 aggregates (Abstract). Aggregates of TDF-42, Aβ, and α-syn pathology were found in Pick’s disease, corticobasal degeneration, and progressive supranuclear palsy, whereas most Alzheimer’s disease cases showed generalized TDP-43 or α-syn co-pathologies. In frontotemporal dementia and ALS that have TDP-43 inclusion bodies, the co-pathology of α-syn and Aβ were nearly close to the TDP-43 pathology (2.5 Interaction in α-syn, Aβ, tau, and TDP-43). Other disorders which have involvements of protein fibril aggregation include prion diseases as well as Huntington’s disease (Table 1, 5. Familial Mutations).
However, not all neurodegenerative diseases involve protein aggregation or are linked to protein fibril toxicity, and thus cannot be treated using agents that inhibit this aggregation. For example, multiple sclerosis is a neurodegenerative disease caused by the immune system attacking the myelin sheath around neurons, resulting in the loss of the ability of the central nervous system to transmit signals. Alcohol-induced dementia is another neurodegenerative disease caused by excessive alcohol consumption, and the only treatment which is known is complete cessation of alcohol.
The relative skill of those in the art:
The artisan would generally have an advanced degree related to the treatment or study of various neurological and neurodegenerative conditions; however, their high level of training and knowledge would not be sufficient to overcome the lack of understanding of how to use the claimed compounds to treat all forms of neurodegenerative disease, as not all neurodegenerative diseases are the result of protein aggregation or protein fibril toxicity.
The amount of direction or guidance presented and the presence or absence of working examples:
The specification provides data demonstrating that the compounds of the invention are capable of inhibiting aggregation of Aβ-42, α-syn, and tau, as well as demonstrating efficacy in various mouse models of Alzheimer’s disease (Figures 1-25). Thus, the specification enables the treatment of conditions mediated by aggregation of protein or protein fibril toxicity. However, the specification does not demonstrate the treatment of all forms of neurodegenerative disease.
The quantity of experimentation necessary:
Considering the state of the art as described above, in particular with regards to the lack of a panacea for the treatment of all neurodegenerative disease due to the heterogenous nature of the disease, differences in underlying pathology, and the high unpredictability of the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate with the scope of the claims.
Claim 33 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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 claimed invention. Factors to be considered
in making the determination as to whether one skilled in the art would recognize that
applicant was in possession of the claimed invention as a whole at the time of filing
include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural
chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional
characteristics when coupled with a known or disclosed correlation between function
and structure; (d) Method of making the claimed invention; (e) Level of skill and
knowledge in the art and (f) Predictability in the art. While all of these factors are
considered, a sufficient number for a prima facie case are discussed below:
The claim is directed to a compound of Claim 17 wherein the compound is in the form of a prodrug. The specification states that the term prodrug refers to a derivative of a drug molecule as form example, esters, carbonates, carbamates, urea, amides, or phosphates that requires a transformation in the body to release the active drug. Some examples of prodrugs within the scope of this invention include: if the compound contains a hydroxyl group, the hydroxyl group may be modified to form an ester, carbonate or carbamate. The ester may also be derived from amino acids such as glycine, serine or lysine (Paragraph 0057). Example 1.10 (Page 41) of the specification provides an example of the synthesis of a compound of Formula (I) with a peptide (Scheme 6). However, the specification does not demonstrate that this compound is capable of functioning as a prodrug, as it does not demonstrate that the drug moiety is cleaved in vitro or in vivo, and does not demonstrate that an active metabolite is formed as a result of this in vitro or in vivo cleavage. The artisan generally understands how a prodrug functions, but it is not evident from the specification that Applicant is in possession of prodrugs of the compounds claimed as no evidence is provided demonstrating the formation of these prodrugs. Therefore, there is no support in the specification that would lead one of ordinary skill in the art to recognize that applicant was in possession of the claimed invention as a whole at the time of filing.
Claim Rejections - 35 USC § 112(b)- NEW GROUNDS OF REJECTION
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 18-20 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. The method figure of Claim 18 is entirely illegible and cannot be interpreted from what is found in the claim set, causing Claim 18 to be indefinite. Claims 19 and 20 are similarly rejected as indefinite as dependent upon an indefinite claim without resolving the underlying issues of indefiniteness.
Allowable Subject Matter
Claims 17, 23-26, and 29-32 are allowed.
Claims 18-20 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
The following is an examiner’s statement of reasons for allowance: There is no prior art which teaches, suggests or provides motivation for the compounds of examined Claim 17 (See Updated STN Search, Search Notes). As the compounds are free of prior art, the methods of synthesizing these compounds are similarly free of prior art. The closest prior art comes from Jackson (WO 99/11684; Publication Date: 2 September 1998). Jackson discloses the compound
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(Page 64) as an inhibitor of PARP which is useful for the treatment of neurodegenerative diseases. However, this compound does not have the amine, alkylene, or alkoxy modifications of the compounds of the examined application, and there is no motivation provided by Jackson to modify the compounds to arrive at those claimed in this application, nor is there any reasonable expectation that these modifications would result in a compound which is useful for the treatment of neurodegenerative disease.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 17, 23-26, and 29-32 are allowed.
Claims 18-22, 27, 28 and 33 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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