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
The species election requirement as set forth in the Office action mailed on February 13, 2025, is hereby withdrawn. 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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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 Status
The claim listing filed May 21, 2026 is pending. Claims 1-89 are canceled. Claims 94, 101-103, 105 and 106 are amended. 90-106 are pending and under examination.
Priority
This application is the national stage of international application PCT/US20/47505, filed August 21, 2020, and claims priority to U.S. Provisional Application No. 62/890,364, filed August 22, 2019, and U.S. Provisional Application No. 62/945,062, filed December 6, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted August 12, 2026, complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Response to Arguments: The objection to claims 94 and 106 have been withdrawn in view of the amendments filed May 21, 2026.
Claim Rejections - 35 USC § 112(b)
Response to Arguments: The rejection of claims 101-102, 105 and 106 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph has been withdrawn in view of the amendments filed May 21,2026.
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.
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.
The rejection below is maintained.
Claim 100 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabled for improving comprising administering a lentiviral vector expressing a polypeptide consisting of the amino acid sequence of SEQ ID NOs: 14 or 30 in a human CD34+ hematopoietic stem cell (HSC), does not reasonably provide enablement for the full scope of treating Angelman syndrome as instantly claimed. 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. This is a scope of enablement rejection.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. §112, first paragraph, have been described In re Wands, 8 USPQ2d 1400(1988). The factors include, but are not limited to:
1) The breadth of the claims;
2) The nature of the invention;
3) The state of the prior art;
4) The level of skill in the art;
5) The level of predictability in the art;
6) The amount of direction provided by the inventor;
7) The presence or absence of working examples;
8) The quantity of experimentation necessary to make or use the invention based on the content of the disclosure.
The relevant factors are addressed below on the basis of comparison of the disclosure, the claims, and the state of the prior art in the assessment of undue experimentation.
Nature of the Invention/Breadth of the Claims The instant invention is directed to a method of treating Angelman syndrome in a subject in need thereof where the subject carries a defective Ubiquitin Protein Ligase E3A (Ube3a) allele. The method comprises locally or systemically administering to the subject a recombinant Ube3a polypeptide comprising an amino acid sequence identified as SEQ ID NO: 14 or SEQ ID NO: 30. The specification defines the term “treating” as “obtaining a desired pharmacologic and/or physiologic effect where the effect can be can be prophylactic in terms of completely or partially preventing a disorder or sign or symptom thereof, and/or can be therapeutic in terms of a partial or complete cure for a disorder and/or adverse effect attributable to the disorder”. Therefore, under broadest reasonable interpretation in view of the specification, the claimed method encompasses prevention and/or cure of Angelman syndrome and its signs/symptoms in subjects with a defective Ube3a allele.
State of the Prior Art/Predictability in the Art The incidence of Angelman syndrome (AS) varies from 1 in 20,000 to 1 in 12,000 live births. Many cases may go undiagnosed due to the underreporting of cases and misdiagnosis. Angelman syndrome (AS) is a challenging disorder with complex management. The management of Angelman syndrome is mainly symptomatic as there is no curative treatment. Due to no definitive cure, the management aims to control symptoms and improve the quality of life. See Madaan et al.1 Angelman Syndrome cannot be prevented because it is caused by genetic mutations that occur spontaneously.2
In view of the foregoing, the predictability for achieving prevention or cure of AS across the claim scope is low.
Amount of direction provided by the inventor and presence or absence of working examples The specification does not provide sufficient guidance to practice the full scope of treating AS. Applicant presents mouse models demonstrating improvement in specific AS-related phenotypes (e.g., motor/locomotor assays such as beam walking) in neonatal mouse models after intervention and in adult mouse models presenting AS phenotypes and do not demonstrate cure or prevention of AS, nor do they established that polypeptides comprising SEQ ID NOs: 14 or 30 achieve the full effects as instantly claimed. The examples were performed with humans CD34+ hematopoietic stem cell transplant using a lentivirus that expresses the amino acid sequences consisting of SEQ ID NOs: 14 or 30; synthetic Human Ube3a isoform 1 and synthetic mouse Ube3a isoform 3, respectively.
The level of skill in the art Even assuming a high level of ordinary skill (e.g., advanced training in molecular biology/biotherapeutics and CNS delivery), the combined breadth of the claims and the limited guidance in the specification would require extensive and unpredictable experimentation to achieve prevention or cure of AS across the full scope.
Quantity of experimentation required Based on the state of the prior art and the limited guidance in the specification, a person of ordinary skill in the art would be required to undertake undue experimentation to practice the full scope of the claimed invention
In summary, considering the Wands factors as a whole, the specification does not enable a person of ordinary skill in the art to make and use the full scope of the claimed method without undue experimentation. Accordingly, claim 100 is rejected under 35 USC 112(a).
Response to Arguments: Applicant’s arguments filed May 21, 2026, have been fully considered but are found unpersuasive. Therefore, the rejection of claim 100 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is maintained for reasons set forth below.
Applicant argues claim 100 is enabled for the full claim scope because the specification provides a comprehensive battery of tests demonstrating rescue of Angelman syndrome-related phenotypes. See pages 4-6 in the remarks filed May 21, 2026.
Applicant’s argument is unpersuasive. Angelman syndrome is a rare genetic neurodevelopment disorder that is characterized by motor coordination deficits.3 Rotarod, beam-walking, open field and DigiGait are tests utilized to assess motor skills (e.g., locomotive activity, balance, motor coordination and gait). Applicant’s data demonstrates the administration of the peptides to an Ueb3a deficit mouse results in improvement or rescue of syndrome-associated phenotypes, specifically motor/locomotive behaviors. These results demonstrate that the peptides may ameliorate some of the motor/locomotive phenotypes deficiencies associated with Angelman Syndrome but does not by itself establish that the peptides prevent, cure or even entirely treat Angelman syndrome. Improvement in motor/locomotive skills is not equivalent to preventing or curing the underlying genetic disorder or is a demonstration of treatment of Angelman syndrome as whole. Accordingly, the specification does not enable the full scope of treating Angelman syndrome as presently claimed. Therefore, for the reasons above, the rejection is maintained.
Allowable Subject Matter
Claims 90-93, 95-99 and 101-106 are allowed.
The following is a statement of reasons for the indication of allowable subject matter: An amino acid sequence represented by SEQ ID NOs: 14 and 30 is novel and unobvious. A nucleotide sequence represented by SEQ ID NOs: 13 and 29 is novel and unobvious.
Conclusion
Claims 90-93, 95-99, and 101-106 are allowed. Claims 94 and 106 are objected to. Claim 100 is rejected.
THIS ACTION IS MADE FINAL. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lianko G Garyu whose telephone number is (571)270-7367. The examiner can normally be reached Monday through Friday 8:30 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Michener, can be reached at 571-272-0900. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Lianko G. Garyu, Ph.D.
Supervisory Patent Examiner
Art Unit 1654
1 Madaan M, Mendez MD. Angelman Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560870/
2 Angelman Syndrome | Speech and Health Library https://www.mtavspeechtherapy.com/speech-health-library/angelman-syndrome
3 Petkova et al., “Gait as a quantitative translational outcome measure in Angelman syndrome”, Autism Research, 2022, 821-833
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