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The species election requirement as set forth in the Office action mailed on February 13, 2025, is hereby withdrawn.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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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 September 23, 2025 is pending. Claims 1-89 are canceled. Claims 90-106 are new, 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 March 3, 2026 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 94 is objected to because of the following informalities:
It is suggested to amend claim 94 as follows:
94. (currently amended) A polynucleotide that is a reverse or complement or reverse-complement to the polynucleotide of claim 92.
Appropriate correction is required.
Claim106 is objected to because of the following informalities: It is suggested to amend the phrase “claims 98” to “claim 98”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
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 101-102, 105 and 106 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.
(1) Claim 101 recites the limitation "in the subject in need carrying a defective Ube3a allele" in the preamble. There is insufficient antecedent basis for this limitation in the claim because there is no previously recited subject carrying a defective Ube3a allele previously recited and it is unclear that the limitation is referencing.
Applicant may overcome the rejection with an amendment such as the following:
101. (Currently Amended) A method of ing an Ube3a polypeptide of claim 90 in a the method comprising administering to the subject a polynucleotide of claim 92, thereby expressing the Ube3a polypeptide in the subject
102. (Currently Amended) The method of claim 101, wherein the subject
103. (Currently Amended) The method of claim 101, wherein the subject
(2) Claim 105 recites the limitation “comprising transducing a packaging cell line with the system of claim 104 under conditions suitable to package the viral particle”. The claim is indefinite because the claim and specification do not provide an objective standard that would inform a person of ordinary skill in the with reasonable certainty to distinguish conditions thatare suitable from conditions that are unsuitable. There is no guidance on the “suitable” condition under which any packaging cell line with the system of claim 104 would package a viral particle. Therefore, the metes and bounds of the instant claim are not clearly and precisely defined.
(3) Claim 106 recites the limitation "the secreted Ube3a polypeptide" in the preamble. There is insufficient antecedent basis for this limitation in the claim because there is no previously recited secreted Ube3a polypeptide and it is unclear that the limitation is referencing.
(4) Claim 106 recites the limitation "the recombinant Ube3a polypeptide" in the preamble. There is insufficient antecedent basis for this limitation in the claim because there is no previously recited recombinant Ube3a polypeptide and it is unclear that the limitation is referencing.
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.
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 locomotor ability, balance, motor coordination and gait in subject carrying a loss of function of an Ube3a allele 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 birth. 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 specifications does not enabled 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).
Allowable Subject Matter
Claims 90-93 and 95-99 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 are novel and unobvious. An nucleotide sequence represented by SEQ ID NOs: 13 and 29 are novel and unobvious.
Conclusion
Claims 90-93 and 95-99 are allowed. Claims 94 and 106 are objected to. Claims 100-106 are rejected.
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 571-272-1424. 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