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 .
Priority
The application is a 371 PCT of EP2021/082539 filed 11/22/2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed 05/22/2023 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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.
Specification
The use of the term Thermofisher, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. A cursory review of the specification has revealed these trademarks or names. It would be remedial to check the specification for additional trademarks or names and amend all upon amendment.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 is objected to because of the following informalities: to “abc-DNA” should be spelled out the abbreviation in the first occurrence.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-4, 6-8, 11-13, 19, 22-23, 27, 30, 33 and 37-40 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 1 recites “a compound comprising a first oligomeric compound and a second oligomeric compound”. It is not reasonably certain whether the recited “compound” is intended to be a single molecular entity, a duplex, a conjugate, a non-covalent complex, or merely a composition containing two separate oligomeric compounds. Accordingly, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the claimed subject matter.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
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.
Claim 40 is 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 a method of preventing or treating Duchenne muscular dystrophy, does not reasonably provide enablement for a method of preventing or treating a neuromuscular or musculoskeletal disease in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claim encompasses methods of preventing or treating any neuromuscular or musculoskeletal disease by administering a compound according to Claim 1. The scope of the claim includes a vast number of diseases having distinct etiologies, pathological mechanisms, and molecular targets. The claim further encompasses innumerable oligonucleotide sequences because the first oligonucleotide need only contain at least one abc-DNA nucleoside and be complementary to an unspecified nucleic acid target, while the second oligonucleotide need only be complementary to the first oligonucleotide. The specification does not reasonably teach how to identify suitable targets, design effective compounds, determine appropriate dosing regimens, or achieve therapeutic efficacy across the full breadth of the claimed disease genus without undue experimentation. The art recognizes that different neuromuscular diseases require different therapeutic strategies tailored to the underlying disease mechanism rather than a single universally applicable treatment approach [Dowling et al, 2017 AmJMedGenet.2018;176:804–841]. Given the unpredictability of oligonucleotide therapeutics and the breadth of the claimed subject matter, a person of ordinary skill in the art would be required to engage in extensive research and screening to practice the full scope of the claimed invention. Accordingly, absent guidance identifying which nucleic acid targets should be selected for the numerous diseases encompassed by the claims, the specification would require undue experimentation to practice the full scope of the claimed genus.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: The claims are directed to a duplex oligonucleotide system comprising: a first oligonucleotide containing at least one α-anomeric bicyclo-DNA (ABC-DNA) nucleoside, wherein the first oligonucleotide is complementary to a nucleic acid target, and a second oligonucleotide complementary to the first oligonucleotide. The specification teaches that the first and second oligonucleotides form a duplex structure prior to interaction with the target nucleic acid.
The closest art of the claimed invention is Renner (WO 2019/215333). Renner teaches a method for altering expression of a gene by permitting hybridization of an oligonucleotide-lipid group conjugate, wherein the oligonucleotide comprises at least two alpha anomeric bicyclo-DNA (abc-DNA) residues connected by a phosphodiester bond, and wherein the lipid group is covalently attached to the oligonucleotide, to an RNA expressed from the gene, the oligonucleotide comprising a sequence that is complementary to a portion of the RNA [para 4, last paragraph]. Renner teaches that abc-DNA is useful in antisense oligonucleotides [pg. 21, para 2]. Renner teaches a complex comprising an antisense oligonucleotide consisting of abc-DNA nucleosides linked by phosphorothioate linkages and a complementary unmodified RNA oligonucleotide [example 1; table 1]. Renner teaches the use of the antisense abc-DNA lipid group conjugated oligonucleotide to cause causes exon skipping of the pre-mRNA of a gene of interest [example 7]. Thereby Renner teaches antisense oligonucleotides comprising abc-DNA nucleotides that bind pre-mRNA and induce exon skipping. Renner does not teach a pre-formed duplex oligonucleotide system where a second oligonucleotide is hybridized to the abc-DNA-containing first nucleotide prior to target interaction. Although the teachings of Elbashir (Elbashir et al. Nature. Vol 441. 2001), who teaches double stranded RNA duplexes that facilitates sequence-specific, post-transcriptional gene silencing that comprises two complementary strands (i.e. a first and second oligonucleotide) where one strand comprises a modification (i.e. (2’-deoxy) thymidine [abstract; pg. 494-495; Fig. 1 and 2]; and Guo (US 2020/0190522 A1; published 6/18/2020), who teaches compositions and compounds comprising modified oligonucleotides can be an antisense compounds (i.e. siRNAs) with have chemically modified subunits, such as a bicyclic nucleoside, arranged in patterns, or motifs, to confer to the antisense compounds properties such as enhanced inhibitory activity, increased binding affinity for a target nucleic acid, or resistance to degradation by in vivo nucleases [0167, 0183-0196], provides evidence that duplex systems comprising a bicyclic nucleoside are known, there is no articulated reasoning in the prior art that would have led a person of ordinary skill in the art to incorporate abc-DNA nucleosides into a pre-formed duplex oligonucleotide system with an expectation that such a system would retain functional nucleic acid targeting capability. The prior art does not provide sufficient guidance that such constrained nucleosides would be fully compatible with duplex formation while retaining sequence-specific nucleic acid recognition in a multi-strand system.
Accordingly, while each individual element of the claims is generally known in the art, the specific combination of features recited in the claims—particularly the incorporation of α-anomeric bicyclo-DNA nucleosides within a duplex oligonucleotide system configured for sequence-specific nucleic acid targeting—is not taught or suggested by the prior art of record.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
Prosecution Insights