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 .
Priority
This application is a 371 of PCT/US2022/014932 (02/02/2022)
PCT/US2022/014932 has PRO 63/146,148 (02/05/2021).
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). For example, see page 74 of the specification listing primer sequences.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Election/Restrictions
Applicant's election without traverse of Group I, drawn to a method of treating SCA3, in the reply filed on 1/9/26 is acknowledged.
Applicant also elected the species of compound 57 with the following structure:
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stated as reading on claims 1-5, 7-13. A search of the elected species full scope of the claims was performed and prior art not found.
Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement restricting inventions I and II, as set forth in the Office action mailed on 11/20/25, is hereby withdrawn and all pending claims are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, 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.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-13 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are to “[a] method for treating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound of Formula (I) … .” The instant disclosure does not contain sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention upon consideration of the factors set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998), as follows. See also MPEP § 2164.01(a) and § 2164.04.
The breadth of the claims – claim 1 is treating SCA3 by administering a large scope of compounds of Formula (I) - claim 1 is to in excess of millions of compounds, and exemplary claim 7 is to more than 160 species. The specification defines the term “treating” as including “preventing”, “inhibiting”, and “ameliorating” (p. 61-62).
The nature of the invention – the nature of the claimed invention is to affect treating SCA3 by inducing exon 4 skipping in the ATXN3 pre-mRNA during splicing in a patient. To date there are no known disease-modifying therapies for SCA3 (Spec p. 2).
The state of the prior art – the therapeutic approach of treating SCA3 with small molecules to induce exon skipping is unknown as detailed in the Specification (Spec p. 2) and taught by Wang (Neuroscience 371 (2018) 138–154, Table 1).
The level of one of ordinary skill – the level of skill in the art is high as evidenced by Wang – considering numerous therapeutic approaches including altering pathways of mechanisms of disease.
The level of predictability in the art – the art is highly unpredictable due to the complex nature of the disease and the mode of action of the compounds used. The particular art is also unpredictable because there is no known or articulated rationale for how the compounds are alleged to induce exon skipping.
The amount of direction provided by the inventor – the primary guidance provided by the inventor is given in two assays Example 1 (“Endogenous Total ATXN3 (tATXN3) Protein Assay” and Example 2 (“RT-qPCR Assay to Quantify Exon 4 Skipping inATXN3 pre-mRNA in Cells”) where fewer than half of the species of claim 7 were tested in an assay and varied in activity in a range including “inactive” and > 2 mM. There is no apparent correlation between the structure of those compounds that are indicated as “inactive” vs. mM level of activity. Importantly, the assays do not indicate what “Cells” were used in the assays and whether they would be relevant to treating any disease in a subject. The guidance provided by the examples do not clearly describe how the results are correlated with an expectation of any therapeutic effect and are akin to raw data lacking explanation. This lack of analysis and explanation combined with an unclear meaning of “Cells” would cause one of skill in the art to question whether the examples support enablement. Regarding dosing and effective amounts, all of the guidance provided regarding dosing and effective amounts is completely generic without any specificity related to response curves or any experimental data.
The existence of working examples – there are no working examples of the compounds treating disease and as indicated above and stated in the Specification, there are no known treatments for SCA3.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure – given the high level of unpredictability in the art, the lack of working examples, and the unclear and limited guidance provided in the examples, there would be a tremendous amount of experimentation required before one of skill in the art could treat SCA3 disease in a subject.
In view of the specification and evidence of record, one of skill in the art would be required to perform an undue amount of experimentation to test each of the compounds of the claims using an appropriate model germane to treating SCA3 (Applicant’s disclosure does not meet this requirement), select candidates for further development in vivo, perform testing to determine dosing, and finally efficacy testing. The disclosure does not include an appropriate model for activity testing that one of skill in the art could utilize, there are no in vivo studies, and no structure activity correlations. Thus, one of skill in the art would be required to start ab initio and develop any compound within the scope of the claims. Such a level of experimentation is undue. Weighing the above factors by a preponderance of the evidence results in the conclusion that the claims are not enabled for treating SCA3 in a subject with the full scope of Formula (I).
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.
Claims 1-6, 11-13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 has the following language which is unclear with respect to whether “5-8 membered” applies to both mono- and bi-cyclic alternatives, and is also ambiguous with respect to whether “carbon atom ring structure radical” is limited to “5-8 membered” or whether the “1-3 heteroatoms” are included in the counting of the members.
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One of skill in the art would not know how to evaluate the language to unambiguously determine the ring structures that are within the scope of the claims. Thus, the claim and those that depend therefrom are indefinite.
Prior Art
The closest prior art of record relating to pharmaceutical use of compounds to affect mRNA splicing is that of Slaugenhaupt et al. (WO2016115434, cited in 2024-11-26 IDS) wherein compounds such as 373 are taught:
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differing at least by the bicyclic ring structure and the particular method of treatment.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at (571) 270-5293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626