SECRETED UBE3A FOR TREATMENT OF NEUROLOGICAL DISORDERS

§102 §103 §112 §DOUBLEPATENT

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 . Claims 1-20 are pending. Election/Restrictions Applicant's election with traverse of invention Group II, drawn to methods of improving motor function and methods of improving associative learning and memory deficits by administering a secreted UBE3A AAV vector in the reply filed on 04 September 2026 is acknowledged. The traversal is on the ground(s) that there is no search burden because a search for the process of using the claimed product would require searching for the product itself. This is not found persuasive because examination of the product requires examination of all claims directed to the product and searching for the dependent claims requires additional searches (e.g., the limitations of Claim 2). Since Examiners perform a search under time constraints, Examiners are best positioned to determine what is or is not a search burden. In this case, searching for the additional limitations in the dependent claims in the limited time provided for examination is indeed a search burden. Applicant's election with traverse of the species: SEQ ID NO 2 (Claims 6 and 15), SEQ ID NO 3 (Claims 9 and 18), Angelman’s syndrome (Claims 13 and 20), and Motor function (Claim 6) is acknowledged. The traversal is on the ground(s) that a search for the elected limitations “would likely include the other listed items in each group”. This is not found persuasive because searching for a single SEQ ID NO requires sifting through hundreds, thousands, and oftentimes, tens of thousands of results from a single database. At least 8 databases are searched for each SEQ ID NO. The time provided for examination is limited. Regarding Applicant’s statement about “provisional” elections, the elections are provisional in the sense that if one species within one election group is found to be free of the art, the other, nonelected species will be examined. Regarding the elected diseases and improvement of Angelman’s syndrome and motor function, Applicant hasn’t argued why there are not non-prior art issues under 112(a) that apply to one species but not the other and Applicant makes no argument addressing that statement. Determining whether a method of improving different recited outcomes in individuals with different disease status is adequately described and enabled requires analysis of what the art teaches about the claimed invention relative to those outcomes and diseases. That requires different search and consideration. The requirement is still deemed proper and is therefore made FINAL. Claims 1-5 and 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04 September 2026. Claims 6-13 are examined. Information Disclosure Statement The Spec. cites references. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. The IDS(es) has been considered. Some items are struck-through because the copy provided is illegible. Claim Interpretation The claims recite that a sequence [sequence x] is “disposed” downstream of another sequence [sequence y]. That is interpreted as meaning the sequence [sequence x] is located downstream of sequence [sequence y]. The claims recite “a UBE3A deficiency disease”. That is not defined in the Spec. so in the interest of compact prosecution, it’s interpreted as broadly meaning any disease wherein a patient has a lower amount of UBE3A (vs. a healthy individual) or a mutation in UBE3A that reduces its function. Claims 6 and 8-9 recite “…or a homologous sequence”. The Spec. defines (¶62) that term: As used herein, the term "homologous" means a nucleotide sequence possessing at least 80% sequence identity… Therefore, “a homologous sequence” is interpreted to be a sequence that is at least 80% identical to a stated SEQ ID NO. In addition, the recitations SEQ ID NO 1, SEQ ID NO 2… SEQ ID NO 10, or a homologous sequence (and similar in Claim 9) are interpreted as meaning that or a homologous sequence follows each SEQ ID NO: e.g., SEQ ID NO 1 or a homologous sequence, SEQ ID NO 2 or a homologous sequence … SEQ ID NO 10, or a homologous sequence… and (Claim 9) …SEQ ID NO 3 or a homologous sequence… . Claims 6 and 9 recite a secretion sequence. Claims 7 and 8 recite a cell uptake sequence. Those terms are not defined in the Spec. In the interest of compact prosecution, a “secretion sequence” is understood to be synonymous with “a signal peptide” which in the art is a sequence that allows a protein to be placed along the secretory pathway. A “cell uptake sequence” is understood to be synonymous with “a cell penetrating peptide” (CPP) which in the art is a sequence that allows a protein to be taken up by a cell or helps a protein traverse the cell membrane. See Wikipedia (“signal peptide” and “cell-penetrating peptide”. Paged archived May 2021. Available at Wikipedia.com. Accessed on 30 September 2026, “Wikipedia”). Claim 6 recites …to improve the motor function of the patient. That is interpreted as an intended outcome of carrying out the method. Claim 6 recites …the UBE3A sequence is a cDNA of SEQ ID NO 1. That is interpreted as requiring that the UBE3A sequence comprises a nt sequence encoding SEQ ID NO 1. Other Note on Terminology The Spec. refers to (e.g., ¶9, ¶15) UBE3A gene, UBE3A protein, and E6-AP. Those are interpreted as interchangeable names for the same gene/protein. Note about Citations to Page and Paragraph Number The following style is used for citations to page and paragraph number (for documents that don’t have ¶ or L #s): p. # refers to PDF p. #. ¶1 refers to the first complete ¶ on a page. ¶0 refers to a partial ¶ that is the first ¶ on a page. Claim Rejections - 35 USC § 112 Claims 6-13 are 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. This is a written description (WD) rejection. Claim 6 recites a method of improving motor function comprising administering a secreted UBE3A (SUB) AAV vector comprising a UBE3A sequence that is SEQ ID NO 1 or a homologous sequence…. As discussed in §Claim interpretation, the Spec. defines (¶62) “homologous: As used herein, the term "homologous" means a nucleotide sequence possessing at least 80% sequence identity… Therefore, “a homologous sequence” is interpreted to be a sequence that is at least 80% identical to a stated SEQ ID NO. Therefore, the claim broadly encompasses the large genus of sequences that are at least 80% identical to SEQ ID NO 1, and any sequence that is at least 80% identical to SEQ ID NO 1 would be encompassed by the claims as instantly presented. There is a WD problem because the claims broadly encompass sequences whose structure cannot be envisioned. There is a WD problem because Applicant hasn’t disclosed any requisite structure that is less than 100% identical to SEQ ID NO 1 but is sufficiently “homologous” to SEQ ID NO 1 so it still encodes a “UBE3A” sequence. Similarly, Claim 8 recites a cell uptake sequence that is SEQ ID NO 4 or a homologous sequence and Claim 9 recites a secretion sequence that is SEQ ID NO 3 or a homologous sequence. Those claims broadly encompass sequences at least 80% identical to SEQ ID NOs 3 and 4. There is a WD problem because Applicant hasn’t disclosed any requisite structure that encodes a secretion sequence/signal peptide. Applicant hasn’t disclosed any requisite structure that is less than 100% identical to SEQ ID NO 3 but sufficiently homologous to SEQ ID NO 3 so it still encodes a secretion sequence. There is a WD problem because Applicant hasn’t disclosed any requisite structure that encodes a cell uptake sequence/CPP. Applicant hasn’t disclosed any requisite structure that is less than 100% identical to SEQ ID NO 4 but sufficiently homologous to SEQ ID NO 4 so it still encodes a cell uptake sequence. An original claim may lack written description support when a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163. SEQ ID NO 1 is 868 amino acids (AA) so it would be encoded by a nucleotide (nt) sequence that is at least 2604 nt long. A UBE3A sequence… wherein the UBE3A sequence is a cDNA sequence [encoding] SEQ ID NO 1 or a homologous sequence includes a large genus of nt sequences that may be ≤20% different from SEQ ID NO 1. A nt sequence could be or have: up to 20% of the nts removed from SEQ ID NO 1; a single chunk comprising ≤20% of the nts different from SEQ ID NO 1; every 5th nt (starting at any position) different from SEQ ID NO 1; every 5th nt (starting at any position) removed from SEQ ID NO 1; any other combination of nts mutated or removed as long as the total adds up to ≤20% of total nts. That could be as many as 520 nt different or missing. SEQ ID NO 3 is a 57-mer nt sequence. A secretion sequence that is SEQ ID NO 3 or a homologous sequence includes a large genus of nt sequences that may be ≤20% different from SEQ ID NO 3. A nt sequence could be or have: up to 20% of the nts removed from SEQ ID NO 3; a single chunk comprising ≤20% of the nts different from SEQ ID NO 3; every 5th nt (starting at any position) different from SEQ ID NO 3; every 5th nt (starting at any position) removed from SEQ ID NO 3; any other combination of nts mutated or removed as long as the total adds up to ≤20% of total nts. That could be as many as 11 nt different or missing. SEQ ID NO 4 is a 33-mer nt sequence. A cell uptake sequence that is SEQ ID NO 4 or a homologous sequence includes a large genus of nt sequences that may be ≤20% different from SEQ ID NO 4. A nt sequence could be or have: up to 20% of the nts removed from SEQ ID NO 4; a single chunk comprising ≤20% of the nts different from SEQ ID NO 4; every 5th nt (starting at any position) different from SEQ ID NO 4; every 5th nt (starting at any position) removed from SEQ ID NO 4; any other combination of nts mutated or removed as long as the total adds up to ≤20% of total nts. That could be as many as 6 nt different or missing. Each of those categories comprises a broad subgenus with diverse members and different structures that affect their functions. Some of those structures may have altered UBE3A, secretion, or cell uptake activity or other altered function(s). As discussed above, the Spec. defines the term “homologous” at ¶62). That § teaches variations in the nt sequence “can” be conservative mutations, but conservative mutations are not required by the definition of “homologous”. That definition requires only 80% identity. MedlinePlus (2026, access date. Help Me Understand Genetics Variants and Health. Available online at medlineplus.gov. Accessed on 01 October 2026, “Medline”) teaches (§4 What kinds of gene variants are possible?) even a single nt or AA variation can change a nt or protein/peptide’s function. Therefore, the effect of using any sequence “homologous” to the claimed SEQ ID NOs would be unpredictable. The Spec. doesn’t provide any definition for a UBE3A sequence, a secretion sequence/signal peptide, or a cell uptake sequence/CPP, but each of those sequences can reasonably be interpreted to possess a specific function: it encodes a functional UBE3A protein, a signal peptide, or a CPP. But the Spec. hasn’t disclosed any minimal structure that comprises a UBE3A protein, a signal peptide, or a CPP. Nothing in the Spec. discloses what portions of sequences homologous to SEQ ID NOs 3 or 4 or what portions of sequences homologous to a cDNA sequence encoding SEQ ID NO 1 are required for each of those sequences to function as claimed. Although the claims recite a homologous sequence which encompasses 80% identity to the parent sequence, the Spec. hasn’t demonstrated possession of a representative number of those sequences or demonstrated that sequences with less than 100% percent identity function as claimed and are suitable to use in the invention. The Spec. does not teach any core structure that is responsible for the function of encoding a UBE3A protein of SEQ ID NO 1, being a signal peptide, or being a CPP. It does not teach which 20% of nts may or may not be altered for the product of each encoded sequence to function. It does not teach which 80% of nts must be present or must not be altered for the product of each encoded sequence to function. It does not teach the portion of the protein or peptide necessary to carry out a specific recited function. Although the claims recite certain functional characteristics (i.e., encoding a UBE3A protein, signal peptide, or CPP), each functional characteristic is not coupled with a known structure. The specification does not teach any examples of using any sequence(s) that are less than 100% identical to SEQ ID NOs 1, 3, and 4. Therefore, it is not possible to know whether versions of SEQ ID NOs 1, 3, and 4 that are altered any amount up to 20% can meet the terms of the claims. Although the Specification teaches the examples discussed above, it does not identify a core structure or nucleotide sequence (or way to identify such a sequence) of which at least 80% must be preserved and which is common among various members of the claimed genus. No core structure, partial structure, physical or chemical property, or functional characteristic coupled with a known or disclosed structure/function relationship of a cDNA sequence encoding SEQ ID NO 1, a signal peptide/secretion sequence that is SEQ ID NO 3 a cell uptake sequence that is SEQ ID NO 4 an mRNA wherein each nt sequence is at least 80% identical to the stated SEQ ID NO is disclosed in such a way to demonstrate possession of the full invention as claimed at time of filing. The specification teaches only these species within the claimed genus/genera: SEQ ID NOs 1, 3, and 4. But those are only a paltry number compared with the breadth of what is claimed. .Altogether, the number of species disclosed by complete structure is not sufficient to provide the written description support for the huge genera and subgenera that are encompassed by the claims: sequences at least 80% identical to each claimed SEQ ID NO. While none of these elements is specifically required to demonstrate possession, in combination their absence means that one skilled in the art at the time of filing would conclude that the inventors lacked possession of the full breadth of the invention claimed. Claims 6 and 8-9 are rejected for failing to demonstrate possession of the claimed invention. Claims 7-13 are rejected because they depend from Claim(s) 6 and do not remedy the issues. Claims 6-13 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: a method of improving motor function in a patient having Angelman syndrome, the method comprising: administering to the patient a therapeutically effective amount of a Secreted TAT UBE3A (STUB) adeno-associated viral (AAV) vector, the vector comprising: a transcription initiation sequence; a UBE3A sequence disposed downstream of the transcription initiation sequence, wherein the UBE3A sequence is a cDNA encoding SEQ ID NO: 1; a secretion sequence disposed downstream of the transcription initiation sequence and upstream from the UBE3A sequence, wherein the secretion sequence is SEQ ID NO 3; and a cell uptake sequence disposed downstream of the transcription initiation sequence and between the secretion sequence and the UBE3A sequence, wherein the cell uptake sequence is SEQ ID NO 4; wherein the vector is administered via intracerebroventricular (ICV) injection, hippocampal injection, or a combination thereof, does not reasonably provide enablement for the full scope of the claims as written. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection. The factors to be considered in determining whether a disclosure would require undue experimentation include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the specification; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01. The breadth of the claims and the nature of the invention: With respect to claim breadth, the standard under 35 U.S.C. §112(a) entails determining what the claims recite and what the claims mean as a whole. Claim 6 recites: A method of improving motor function in a patient having a UBE3A deficiency disease comprising: administering to the patient a therapeutically effective amount of a secreted UBE3A (SUB) AAV vector, the vector comprising: a transcription initiation sequence; a UBE3A sequence disposed downstream of the transcription initiation sequence, wherein the UBE3A sequence is a cDNA of SEQ ID NO: 1 or a homologous sequence; and a secretion sequence disposed downstream of the transcription initiation sequence and upstream from the UBE3A sequence, wherein the vector is administered via intracerebroventricular (ICV) injection, hippocampal injection, or a combination thereof to improve the motor function of the patient. In addition, Claims 6 and 8-9 recite UBE3A sequences, cell uptake (i.e., CPP) sequences, and secretion sequences (i.e., signal peptides) that are or are encoded by, respectively, SEQ ID NOs 1, 4, and 3 or a sequence homologous to each of those SEQ ID NOs. The issues with the “homologous sequence” are explained in the WD rejection above. The broadest reasonable interpretation (BRI) of Claim 6 is that administering via ICV and/or hippocampal injection an AAV vector that comprises the recited elements of a transcription initiation sequence, a sequence encoding a UBE3A protein, and a secretion sequence will improve motor function in any patient suffering from any UBE3A deficiency disease. The nature of the invention is a method for improving motor function in any subject suffering from any UBE3A deficiency disease. A skilled artisan would not be able to use the method as claimed with a reasonable expectation of success based solely on what is disclosed in the specification. The specific problems are: 1. Successfully improving motor function in any patient suffering from any UBE3A deficiency disease would be unpredictable. 2. Successfully improving motor function in any patient suffering from any UBE3A deficiency disease by administering a vector comprising a secretion sequence and a UBE3A sequence but lacking a cell uptake sequence would be unpredictable. 3. Applicant has not demonstrated that any sequence encompassed by the recitations ...SEQ ID NO [#] or a homologous sequence would properly function in the invention. The state of the art and prior art, the level of one of ordinary skill, and the level of predictability in the art. Regarding point 1: The Spec. (¶13), Maheshwari, and Olabarria (both cited on IDS) teach deficiencies in UBE3A are linked to Huntington’s disease (HD) and Alzheimer’s disease (AD). The art of Ruitenberg (2024. Cognition and movement in neurodegenerative disorders: a dynamic duo. Neural Regen. Res. 19[10]:2101–2102, Ruitenberg) indicates that both of HD and AD are known to cause (see Ruitenberg ¶4-5) motor impairment. Both Maheshwari and Olabarria indicate that genetic pathways other than merely those involving UBE3A are involved in HD and AD. In fact, Maheswari teaches (§Abstract) loss of UBE3A accelerates an HD phenotype that has already occurred. Therefore, the art indicates that there are numerous diseases that can be considered “UBE3A deficiency” diseases and some of them are multifactorial or polygenic diseases. The art of Children’s Health (2023. 3 ways gene therapy is transforming treatment for pediatric neurological diseases. Available online at childrens.com. Accessed on 01 October 2026, “Childrens”) teaches (§Applying lessons learned: Gene therapy for polygenic neurological diseases) polygenic conditions are complicated and can require replacing more than one gene. Based on those teachings, and without demonstration of evidence to the contrary, an artisan would reasonably conclude that successfully improving any motor function in any patient suffering from any UBE3A deficiency disease, including AD and HD (wherein motor function deficits have causes besides for UBE3A deficiency), by using the claimed method would be unpredictable. Regarding point 2: The Spec. describes that (¶177) motor function improvements were observed only in rats injected with the STUB vector (which includes a sequence encoding UBE3A, a secretion sequence, and a CPP) and rescue of motor deficits was not observed in rats who were injected with rAAV-hUBE3A (a construct that lacks the secretion sequence and CPP). That indicates that successfully attaining the claimed outcomes by administering a vector that lacks a CPP would be unpredictable. Regarding point 3: the problems with the claims in terms of the broad genera of claimed sequences “homologous” to SEQ ID NOs have been addressed in the WD rejection. Briefly, MedlinePlus (2026, access date. Help Me Understand Genetics Variants and Health. Available online at medlineplus.gov. Accessed on 01 October 2026, “Medline”) teaches (§4 What kinds of gene variants are possible?) even a single nt or AA variation can change a nt or protein/peptide’s function. Therefore, the effect of using any sequence “homologous” to the claimed SEQ ID NOs would be unpredictable. Altogether, although the skill level of an artisan is high, the art teaches there are numerous “UBE3A deficiency” diseases, those diseases involve many pathways and can involve mutations in various proteins, and treating a polygenic disease is complicated. The art indicates variation in a single nt or AA can alter nt or protein/peptide function. The Spec. teaches the inventors were not able to successfully improve motor function when they administered a vector encoding UBE3A without a secretion sequence/signal peptide and a CPP. Those teachings indicate that successfully using the full breadth of the claimed methods would be unpredictable. The amount of direction provided by the specification and the existence of working examples: What is enabled by the working examples is narrow compared to the breadth of the claims. The Spec. discusses (¶176) others have found reinstating UBE3A at any age and thereby improving motor function is not successful because adult animals showed no improvement. The Spec. also describes that (§Example 3, starts at ¶158) they administered to an Angelman syndrome rodent model via ICV injection an AAV vector encoding STUB which comprises a secretion signal along with a CPP sequence. They then tested the rats for motor function tasks and found (¶171-177, Fig. 15) that while animals treated with human UBE3A (hUBE3A) were indistinguishable from the PBS treated control group… the rAAV-STUB group showed significant improvement and recovery to WT levels. That § describes that (¶176) they used adult rats in their experiments and (¶177) they observed motor function improvements only in rats injected with the STUB vector (which includes a sequence encoding UBE3A, a secretion sequence, and a CPP) and didn’t observe rescue of motor deficits in the rats who were injected with rAAV-hUBE3A (a construct that lacks the secretion sequence and CPP). That indicates that successfully attaining the claimed outcomes in any patient or by administering a vector that lacks a CPP would be unpredictable. Furthermore, none of the Examples describe improving motor function in any disease model other than the one Angelman syndrome model. The Spec. provides no evidence of successfully using the claimed method to improve motor function for any other disease model. Finally, nothing in the Spec. shows success using any sequences “homologous” to the claimed SEQ ID NOs or discloses any requisite structure that should be preserved in the sequences “homologous” to those SEQ ID NOs. For that reason, an artisan wouldn’t know what portion(s) of those recited SEQ ID NOs is required to improve motor function. Therefore, a person of ordinary skill in the art would determine that successfully using the full scope of the method—a vector that lacks a CPP, a vector comprising sequences “homologous” to claimed SEQ ID NOs—to improve motor function in a patient with any UBE3A deficiency disease (such as Prader-Willi syndrome, Alzheimer’s disease, or Huntington’s disease) would be unpredictable. The quantity of experimentation needed to make or use the invention: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given experimental evidence to the contrary (described in the Spec. ¶177), and given the lack of experimental evidence in any other disease model, an artisan of ordinary skill would not be able to use the invention as claimed with a reasonable expectation of success. The amount of experimentation required for enabling guidance commensurate in scope with what is claimed goes beyond what is considered “routine” within the art and constitutes undue further experimentation in order to have any reasonable expectation of successfully using the full scope of the claimed methods of improving any motor function in any patient having any UBE3A deficiency disease. Claims 6 and 8-9 are rejected for those reasons. Claims 7-13 are rejected because they depend from Claim 6 and do not remedy the issues. In conclusion, the specification provides enablement for: A method of improving motor function in a patient having Angelman syndrome, the method comprising: administering to the patient a therapeutically effective amount of a secreted UBE3A (SUB) adeno-associated viral (AAV) vector, the vector comprising: a transcription initiation sequence; a UBE3A sequence disposed downstream of the transcription initiation sequence, wherein the UBE3A sequence is a cDNA encoding SEQ ID NO: 1; and a secretion sequence disposed downstream of the transcription initiation sequence and upstream from the UBE3A sequence, wherein the secretion sequence is SEQ ID NO 3; and a cell uptake sequence disposed downstream of the transcription initiation sequence and between the secretion sequence and the UBE3A sequence, wherein the cell uptake sequence is SEQ ID NO 4; wherein the vector is administered via intracerebroventricular (ICV) injection, hippocampal injection, or a combination thereof. 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 6-13 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. A claim may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173. In the present instance, Claim 6 recites wherein the UBE3A sequence is a cDNA of SEQ ID NO 1… a cDNA of SEQ ID NO 8, a cDNA of SEQ ID NO 10. The claim(s) are considered indefinite because there is a question or doubt as to what are the metes and bounds of the claim. It is not clear what is “a cDNA of a SEQ ID NO” or how much of the AA sequence the cDNA comprises. Claim 6 is rejected for those reasons. Claims 7-13 are rejected because they depend from Claim 6 and do not remedy the issues. In the interest of compact prosecution, the claim is interpreted as reciting: wherein the UBE3A sequence comprises a cDNA encoding SEQ ID NO 1… comprises a cDNA encoding SEQ ID NO 8, comprises a cDNA encoding SEQ ID NO 10… In the present instance, Claim 6 recites improving motor function. The claim(s) are considered indefinite because there is a question or doubt as to what are the metes and bounds of the claim. It is not clear what motor functions are dysfunctional or what counts or doesn’t count as improving motor function. Claim 6 is rejected for those reasons. Claims 7-13 are rejected because they depend from Claim 6 and do not remedy the issues. In the interest of compact prosecution, improving motor function is interpreted as observing improvement (vs. baseline) in any clinical or laboratory test of an individual’s ability to move. Claim Rejections - 35 USC § 102 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim(s) 6-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by International Publication Number WO 2016/179584 (published on 10 November 2016, “WO584”, of record on IDS). Citations to WO p. # refer to the PDF p. #. WO584 discloses (§Abstract) a gene therapy approach for treating Angelman syndrome (AS) that utilizes a UBE3A protein with additional sequences that allow secretion from cells and uptake by neighboring neuronal cells. Regarding Claim 6: WO584 teaches (p. 3 L15-end) AS presents with delayed and reduced developmental advancement, particularly with respect to motor skills. Specifically, that § teaches that movement is jerky and walking is commonly associated with hand flapping and a stiff gait, and afflicted individuals can possess sucking and swallowing problems. That indicates that those forms of motor impairment are symptoms of the disease. WO584 teaches (p. 6 L25-end) the invention provides a functional E6-AP protein and thereby rescues disease pathology. WO584 teaches (p. 13 L29-end) a “therapeutically effective amount” is an amount of therapy (e.g., agent or vector) sufficient to result in amelioration of AS or one or more symptoms thereof. That indicates that WO584’s method of treatment will ameliorate a symptom of AS, including any symptoms of motor impairment. WO584 teaches (p. 9 L15-15; p. 16 L17) using an AAV vector to administer a gene encoding the UBE3A protein and (p. 10 L15-25) administration to the brain via intrahippocampal or ventricular injection. WO584 teaches (pp. 71-72 items #14-16) a method of treating AS (or Prader-Willi syndrome or Huntington’s disease), the method comprising administering via injection to a patient’s hippocampus or ventricle a vector comprising a transcription initiation sequence (TIS), a UBE3A sequence disposed downstream of the TIS, wherein the UBE3A sequence is SEQ ID NO 15 or a cDNA of SEQ ID NO 14, or a sequence homologous to either of those; a secretion sequence disposed downstream of the TIS sequence, wherein the secretion sequence is SEQ ID NO 8; and a cell uptake sequence disposed downstream of the TIS sequence, wherein the cell uptake sequence is SEQ ID NO 4. WO585 specifies (p. 7 L1-20) the secretion sequence is upstream of the UBE3A sequence. Further regarding Claim 6: The following alignments show that WO584’s SEQ ID NO 14 is 95.8% identical to claimed SEQ ID NO 1 and WO584’s SEQ ID NO 15 is a nucleic acid sequence that encodes a sequence that is 95.9% identical to claimed SEQ ID NO 1: BDI57070 ID BDI57070 standard; protein; 875 AA. XX AC BDI57070; XX DT 29-DEC-2016 (first entry) XX DE Human UBE3A variant 2 protein, SEQ ID 14. XX KW UBE3A protein; Ubiquitin ligase E3A; angelman syndrome; anorectic; KW genetic-disease-gen.; growth-disorder-gen.; huntingtons chorea; KW neuroprotective; nootropic; nutrition-disorder-gen.; KW prader-willi syndrome; therapeutic; vector. XX OS Homo sapiens. XX CC PN WO2016179584-A1. XX CC PD 10-NOV-2016. XX CC PF 09-MAY-2016; 2016WO-US031468. XX PR 07-MAY-2015; 2015US-0158269P. XX CC PA (UYSF ) UNIV SOUTH FLORIDA. CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2016-70063D/81. XX CC PT New ubiquitin ligase E3a (UBE3A) vector comprising a transcription CC PT initiation sequence, a UBE3A sequence, a secretion sequence, and a cell CC PT uptake sequence, useful for treating a UBE3A deficiency disease. XX CC PS Disclosure; SEQ ID NO 14; 92pp; English. XX CC The present invention relates to a novel ubiquitin ligase E3a (UBE3A) CC vector, for treating a UBE3A deficiency disease. The vector comprises: a CC transcription initiation sequence; a UBE3A sequence disposed downstream CC of the transcription initiation sequence; a secretion sequence disposed CC downstream of the transcription initiation sequence; and a cell uptake CC sequence disposed downstream of the transcription initiation sequence. CC The invention also provides: (1) a method for synthesizing a UBE3A vector CC ; and (2) a method for treating a UBE3A deficiency disease. The UBE3A CC vector is useful for treating a UBE3A deficiency disease selected from CC Angelman syndrome, Prader-Willi syndrome, and Huntington's disease. The CC present sequence is a human UBE3A variant 2 protein, whose encoding DNA CC is used in the invention for constructing the vector of the invention. XX SQ Sequence 875 AA; ALIGNMENT: Query Match 95.8%; Score 4316.5; Length 875; Best Local Similarity 95.6%; Matches 831; Conservative 20; Mismatches 13; Indels 5; Gaps 2; Qy 5 CKRSSGESQSEDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTFLRMDNN 64 | ||| ||:||||||||||||||||||||||||||||||||||||||||||||||||| Db 7 CYWKSGEPQSDDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTFLRMDNN 66 Qy 65 AAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGASNN--SEIKMNKKE---EFKEVD 119 ||||||||||||||||||||||||||||||||||||| || |||||||| :||:| Db 67 AAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGAPNNSCSEIKMNKKGARIDFKDVT 126 Qy 120 YLTEEKVYEIYEFCREREDYSPLIRVIGRIFSSAEALVQSFRKVKQHTKEELKSLQEKDE 179 |||||||||| | ||||||||||||||||:|||||||||||||||||||||||||| ||| Db 127 YLTEEKVYEILELCREREDYSPLIRVIGRVFSSAEALVQSFRKVKQHTKEELKSLQAKDE 186 Qy 180 DKDEDEKEKAACSAAAMEEDSEASSSRMGDSSQGDNNVQKLGPDDVTVDIDAIRRVYSSL 239 |||||||||||||||||||||||||||:|||||||||:||||||||:||||||||||: | Db 187 DKDEDEKEKAACSAAAMEEDSEASSSRIGDSSQGDNNLQKLGPDDVSVDIDAIRRVYTRL 246 Qy 240 LSDEKIETAFLNALVYLSPNVECDLTYHNVYTRDPNYLNLFIIVMENRNLHSPEYLEMAL 299 ||:||||||||||||||||||||||||||||:|||||||||||||||||||||||||||| Db 247 LSNEKIETAFLNALVYLSPNVECDLTYHNVYSRDPNYLNLFIIVMENRNLHSPEYLEMAL 306 Qy 300 PLFCKAMSKLPLAAQGKLIRLWSKYSADQIRRMMETFQQLITYKVISNEFNSRNLVNDDD 359 |||||||||||||||||||||||||:|||||||||||||||||||||||||||||||||| Db 307 PLFCKAMSKLPLAAQGKLIRLWSKYNADQIRRMMETFQQLITYKVISNEFNSRNLVNDDD 366 Qy 360 AIVAASKCLKMVYYANVVGGDVDTNHNEEDDEEPIPESSELTLQELLGEERRNKKGPRVD 419 ||||||||||||||||||||:||||||||||||||||||||||||||||||||||||||| Db 367 AIVAASKCLKMVYYANVVGGEVDTNHNEEDDEEPIPESSELTLQELLGEERRNKKGPRVD 426 Qy 420 PLETEIGVKTLDCRKPLISFEEFINEPLNDVLEMDKDYTFFKVETENKFSFMTCPFILNA 479 |||||:|||||||||||| ||||||||||:|||||||||||||||||||||||||||||| Db 427 PLETELGVKTLDCRKPLIPFEEFINEPLNEVLEMDKDYTFFKVETENKFSFMTCPFILNA 486 Qy 480 VTKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRLEMIAME 539 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 487 VTKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRLEMIAME 546 Qy 540 NPADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDEATRLFWFNPSSF 599 ||||||||||||||||||||||||||||||||||||||||||||||||:|:||||||||| Db 547 NPADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDESTKLFWFNPSSF 606 Qy 600 ETEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFCDLGDSHPILYQSLKDLL 659 |||||||||||||||||||||||||||||||||||||||||| |||||||:||||||||| Db 607 ETEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFRDLGDSHPVLYQSLKDLL 666 Qy 660 EYEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVSLYSDYILNKSV 719 ||||||||||||||||||||||||||||||||||||||||||||||||:||||||||||| Db 667 EYEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVNLYSDYILNKSV 726 Qy 720 EKQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRESVV 779 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||:||: Db 727 EKQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRDSVL 786 Qy 780 IREFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNV 839 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 787 IREFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNV 846 Qy 840 LLLPEYSSKEKLKERLLKAITYAKGFGML 868 claimed SEQ ID NO 1 ||||||||||||||||||||||||||||| Db 847 LLLPEYSSKEKLKERLLKAITYAKGFGML 875 WO584 SEQ ID NO 14 BDI57071 (NOTE: this sequence has 2 duplicates in the database searched. See complete list at the end of this report) ID BDI57071 standard; DNA; 2970 BP. XX AC BDI57071; XX DT 29-DEC-2016 (first entry) XX DE Mouse ubiquitin ligase E3a gene, SEQ ID 15. XX KW UBE3A gene; Ubiquitin ligase E3A; angelman syndrome; anorectic; KW genetic-disease-gen.; growth-disorder-gen.; huntingtons chorea; KW neuroprotective; nootropic; nutrition-disorder-gen.; KW prader-willi syndrome; ss; therapeutic; vector. XX OS Mus musculus. XX CC PN WO2016179584-A1. XX CC PD 10-NOV-2016. XX CC PF 09-MAY-2016; 2016WO-US031468. XX PR 07-MAY-2015; 2015US-0158269P. XX CC PA (UYSF ) UNIV SOUTH FLORIDA. CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2016-70063D/81. XX CC PT New ubiquitin ligase E3a (UBE3A) vector comprising a transcription CC PT initiation sequence, a UBE3A sequence, a secretion sequence, and a cell CC PT uptake sequence, useful for treating a UBE3A deficiency disease. XX CC PS Claim 1; SEQ ID NO 15; 92pp; English. XX CC The present invention relates to a novel ubiquitin ligase E3a (UBE3A) CC vector, for treating a UBE3A deficiency disease. The vector comprises: a CC transcription initiation sequence; a UBE3A sequence disposed downstream CC of the transcription initiation sequence; a secretion sequence disposed CC downstream of the transcription initiation sequence; and a cell uptake CC sequence disposed downstream of the transcription initiation sequence. CC The invention also provides: (1) a method for synthesizing a UBE3A vector CC ; and (2) a method for treating a UBE3A deficiency disease. The UBE3A CC vector is useful for treating a UBE3A deficiency disease selected from CC Angelman syndrome, Prader-Willi syndrome, and Huntington's disease. The CC present sequence is a mouse ubiquitin ligase E3a gene, which is used in CC the invention for constructing the vector of the invention. XX SQ Sequence 2970 BP; 976 A; 537 C; 679 G; 778 T; 0 U; 0 Other; Alignment Scores: Length: 2970 Score: 4339.00 Matches: 837 Percent Similarity: 98.2% Conservative: 20 Best Local Similarity: 95.9% Mismatches: 10 Query Match: 96.3% Indels: 6 Gaps: 3 US-18-392-696-1 (1-868) x BDI57071 (1-2970) Qy 1 MetAlaThrAlaCysLysArgSerSerGlyGluSerGlnSerGluAspIleGluAlaSer 20 ||||||||||||||||||||| ||||||||| ||||||:::||||||||||||||| Db 315 ATGGCCACAGCTTGTAAAAGA---TCAGGAGAACCTCAGTCTGACGACATTGAAGCTAGC 371 Qy 21 ArgMetLysArgAlaAlaAlaLysHisLeuIleGluArgTyrTyrHisGlnLeuThrGlu 40 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 372 CGAATGAAGCGAGCAGCTGCAAAGCATCTAATAGAACGCTACTACCACCAGTTAACTGAG 431 Qy 41 GlyCysGlyAsnGluAlaCysThrAsnGluPheCysAlaSerCysProThrPheLeuArg 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 432 GGCTGTGGAAATGAAGCCTGCACGAATGAGTTTTGTGCTTCCTGTCCAACTTTTCTTCGT 491 Qy 61 MetAspAsnAsnAlaAlaAlaIleLysAlaLeuGluLeuTyrLysIleAsnAlaLysLeu 80 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 492 ATGGATAATAATGCAGCAGCTATTAAAGCCCTCGAGCTTTATAAGATTAATGCAAAACTC 551 Qy 81 CysAspProHisProSerLysLysGlyAlaSerSerAlaTyrLeuGluAsnSerLysGly 100 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 552 TGTGATCCTCATCCCTCCAAGAAAGGAGCAAGCTCAGCTTACCTTGAGAACTCGAAAGGT 611 Qy 101 AlaSerAsnAsn------SerGluIleLysMetAsnLysLysGlu---------GluPhe 115 ||| |||||| |||||||||||||||||||||||| :::||| Db 612 GCCCCCAACAACTCCTGCTCTGAGATAAAAATGAACAAGAAAGGCGCTAGAATTGATTTT 671 Qy 116 LysGluValAspTyrLeuThrGluGluLysValTyrGluIleTyrGluPheCysArgGlu 135 |||:::||| |||||||||||||||||||||||||||||| ||| ||||||||| Db 672 AAAGATGTGACTTACTTAACAGAAGAGAAGGTATATGAAATTCTTGAATTATGTAGAGAA 731 Qy 136 ArgGluAspTyrSerProLeuIleArgValIleGlyArgIlePheSerSerAlaGluAla 155 |||||||||||||||||||||||||||||||||||||||:::|||||||||||||||||| Db 732 AGAGAGGATTATTCCCCTTTAATCCGTGTTATTGGAAGAGTTTTTTCTAGTGCTGAGGCA 791 Qy 156 LeuValGlnSerPheArgLysValLysGlnHisThrLysGluGluLeuLysSerLeuGln 175 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 792 TTGGTACAGAGCTTCCGGAAAGTTAAACAACACACCAAGGAAGAACTGAAATCTCTTCAA 851 Qy 176 GluLysAspGluAspLysAspGluAspGluLysGluLysAlaAlaCysSerAlaAlaAla 195 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 852 GCAAAAGATGAAGACAAAGATGAAGATGAAAAGGAAAAAGCTGCATGTTCTGCTGCTGCT 911 Qy 196 MetGluGluAspSerGluAlaSerSerSerArgMetGlyAspSerSerGlnGlyAspAsn 215 |||||||||||||||||||||||||||||||||:::|||||||||||||||||||||||| Db 912 ATGGAAGAAGACTCAGAGGCATCTTCCTCAAGGATAGGTGATAGCTCACAGGGAGACAAC 971 Qy 216 AsnValGlnLysLeuGlyProAspAspValThrValAspIleAspAlaIleArgArgVal 235 |||:::||||||||||||||||||||||||:::||||||||||||||||||||||||||| Db 972 AATTTGCAAAAATTAGGCCCTGATGATGTGTCTGTGGATATTGATGCCATTAGAAGGGTC 1031 Qy 236 TyrSerSerLeuLeuSerAspGluLysIleGluThrAlaPheLeuAsnAlaLeuValTyr 255 |||::: |||||||||:::||||||||||||||||||||||||||||||||||||||| Db 1032 TACACCAGATTGCTCTCTAATGAAAAAATTGAAACTGCCTTTCTCAATGCACTTGTATAT 1091 Qy 256 LeuSerProAsnValGluCysAspLeuThrTyrHisAsnValTyrThrArgAspProAsn 275 |||||||||||||||||||||||||||||||||||||||||||||:::|||||||||||| Db 1092 TTGTCACCTAACGTGGAATGTGACTTGACGTATCACAATGTATACTCTCGAGATCCTAAT 1151 Qy 276 TyrLeuAsnLeuPheIleIleValMetGluAsnArgAsnLeuHisSerProGluTyrLeu 295 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1152 TATCTGAATTTGTTCATTATCGTAATGGAGAATAGAAATCTCCACAGTCCTGAATATCTG 1211 Qy 296 GluMetAlaLeuProLeuPheCysLysAlaMetSerLysLeuProLeuAlaAlaGlnGly 315 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1212 GAAATGGCTTTGCCATTATTTTGCAAAGCGATGAGCAAGCTACCCCTTGCAGCCCAAGGA 1271 Qy 316 LysLeuIleArgLeuTrpSerLysTyrSerAlaAspGlnIleArgArgMetMetGluThr 335 |||||||||||||||||||||||||||:::|||||||||||||||||||||||||||||| Db 1272 AAACTGATCAGACTGTGGTCTAAATACAATGCAGACCAGATTCGGAGAATGATGGAGACA 1331 Qy 336 PheGlnGlnLeuIleThrTyrLysValIleSerAsnGluPheAsnSerArgAsnLeuVal 355 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1332 TTTCAGCAACTTATTACTTATAAAGTCATAAGCAATGAATTTAACAGTCGAAATCTAGTG 1391 Qy 356 AsnAspAspAspAlaIleValAlaAlaSerLysCysLeuLysMetValTyrTyrAlaAsn 375 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1392 AATGATGATGATGCCATTGTTGCTGCTTCGAAGTGCTTGAAAATGGTTTACTATGCAAAT 1451 Qy 376 ValValGlyGlyAspValAspThrAsnHisAsnGluGluAspAspGluGluProIlePro 395 ||||||||||||:::||||||||||||||||||||||||||||||||||||||||||||| Db 1452 GTAGTGGGAGGGGAAGTGGACACAAATCACAATGAAGAAGATGATGAAGAGCCCATCCCT 1511 Qy 396 GluSerSerGluLeuThrLeuGlnGluLeuLeuGlyGluGluArgArgAsnLysLysGly 415 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1512 GAGTCCAGCGAGCTGACACTTCAGGAACTTTTGGGAGAAGAAAGAAGAAACAAGAAAGGT 1571 Qy 416 ProArgValAspProLeuGluThrGluIleGlyValLysThrLeuAspCysArgLysPro 435 |||||||||||||||||||||||||||:::|||||||||||||||||||||||||||||| Db 1572 CCTCGAGTGGACCCCCTGGAAACTGAACTTGGTGTTAAAACCCTGGATTGTCGAAAACCA 1631 Qy 436 LeuIleSerPheGluGluPheIleAsnGluProLeuAsnAspValLeuGluMetAspLys 455 |||||| ||||||||||||||||||||||||||||||:::|||||||||||||||||| Db 1632 CTTATCCCTTTTGAAGAGTTTATTAATGAACCACTGAATGAGGTTCTAGAAATGGATAAA 1691 Qy 456 AspTyrThrPhePheLysValGluThrGluAsnLysPheSerPheMetThrCysProPhe 475 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1692 GATTATACTTTTTTCAAAGTAGAAACAGAGAACAAATTCTCTTTTATGACATGTCCCTTT 1751 Qy 476 IleLeuAsnAlaValThrLysAsnLeuGlyLeuTyrTyrAspAsnArgIleArgMetTyr 495 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1752 ATATTGAATGCTGTCACAAAGAATTTGGGATTATATTATGACAATAGAATTCGCATGTAC 1811 Qy 496 SerGluArgArgIleThrValLeuTyrSerLeuValGlnGlyGlnGlnLeuAsnProTyr 515 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1812 AGTGAACGAAGAATCACTGTTCTCTACAGCTTAGTTCAAGGACAGCAGTTGAATCCATAT 1871 Qy 516 LeuArgLeuLysValArgArgAspHisIleIleAspAspAlaLeuValArgLeuGluMet 535 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1872 TTGAGACTCAAAGTTAGACGTGACCATATCATAGATGATGCACTTGTCCGGCTAGAGATG 1931 Qy 536 IleAlaMetGluAsnProAlaAspLeuLysLysGlnLeuTyrValGluPheGluGlyGlu 555 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1932 ATCGCTATGGAAAATCCTGCAGACTTGAAGAAGCAGTTGTATGTGGAATTTGAAGGAGAA 1991 Qy 556 GlnGlyValAspGluGlyGlyValSerLysGluPhePheGlnLeuValValGluGluIle 575 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1992 CAAGGAGTTGATGAGGGAGGTGTTTCCAAAGAATTTTTTCAGCTGGTTGTGGAGGAAATC 2051 Qy 576 PheAsnProAspIleGlyMetPheThrTyrAspGluAlaThrArgLeuPheTrpPheAsn 595 ||||||||||||||||||||||||||||||||||||:::|||:::||||||||||||||| Db 2052 TTCAATCCAGATATTGGTATGTTCACATACGATGAATCTACAAAATTGTTTTGGTTTAAT 2111 Qy 596 ProSerSerPheGluThrGluGlyGlnPheThrLeuIleGlyIleValLeuGlyLeuAla 615 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2112 CCATCTTCTTTTGAAACTGAGGGTCAGTTTACTCTGATTGGCATAGTACTGGGTCTGGCT 2171 Qy 616 IleTyrAsnAsnCysIleLeuAspValHisPheProMetValValTyrArgLysLeuMet 635 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2172 ATTTACAATAACTGTATACTGGATGTACATTTTCCCATGGTTGTCTACAGGAAGCTAATG 2231 Qy 636 GlyLysLysGlyThrPheCysAspLeuGlyAspSerHisProIleLeuTyrGlnSerLeu 655 |||||||||||||||||| |||||||||||||||||||||:::||||||||||||||| Db 2232 GGGAAAAAAGGAACTTTTCGTGACTTGGGAGACTCTCACCCAGTTCTATATCAGAGTTTA 2291 Qy 656 LysAspLeuLeuGluTyrGluGlyAsnValGluAspAspMetMetIleThrPheGlnIle 675 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2292 AAAGATTTATTGGAGTATGAAGGGAATGTGGAAGATGACATGATGATCACTTTCCAGATA 2351 Qy 676 SerGlnThrAspLeuPheGlyAsnProMetMetTyrAspLeuLysGluAsnGlyAspLys 695 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2352 TCACAGACAGATCTTTTTGGTAACCCAATGATGTATGATCTAAAGGAAAATGGTGATAAA 2411 Qy 696 IleProIleThrAsnGluAsnArgLysGluPheValSerLeuTyrSerAspTyrIleLeu 715 ||||||||||||||||||||||||||||||||||||:::||||||||||||||||||||| Db 2412 ATTCCAATTACAAATGAAAACAGGAAGGAATTTGTCAATCTTTATTCTGACTACATTCTC 2471 Qy 716 AsnLysSerValGluLysGlnPheLysAlaPheArgArgGlyPheHisMetValThrAsn 735 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2472 AATAAATCAGTAGAAAAACAGTTCAAGGCTTTTCGGAGAGGTTTTCATATGGTGACCAAT 2531 Qy 736 GluSerProLeuLysTyrLeuPheArgProGluGluIleGluLeuLeuIleCysGlySer 755 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2532 GAATCTCCCTTAAAGTACTTATTCAGACCAGAAGAAATTGAATTGCTTATATGTGGAAGC 2591 Qy 756 ArgAsnLeuAspPheGlnAlaLeuGluGluThrThrGluTyrAspGlyGlyTyrThrArg 775 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2592 CGGAATCTAGATTTCCAAGCACTAGAAGAAACTACAGAATATGACGGTGGCTATACCAGG 2651 Qy 776 GluSerValValIleArgGluPheTrpGluIleValHisSerPheThrAspGluGlnLys 795 :::||||||:::|||||||||||||||||||||||||||||||||||||||||||||||| Db 2652 GACTCTGTTCTGATTAGGGAGTTCTGGGAAATCGTTCATTCATTTACAGATGAACAGAAA 2711 Qy 796 ArgLeuPheLeuGlnPheThrThrGlyThrAspArgAlaProValGlyGlyLeuGlyLys 815 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2712 AGACTCTTCTTGCAGTTTACAACGGGCACAGACAGAGCACCTGTGGGAGGACTAGGAAAA 2771 Qy 816 LeuLysMetIleIleAlaLysAsnGlyProAspThrGluArgLeuProThrSerHisThr 835 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2772 TTAAAGATGATTATAGCCAAAAATGGCCCAGACACAGAAAGGTTACCTACATCTCATACT 2831 Qy 836 CysPheAsnValLeuLeuLeuProGluTyrSerSerLysGluLysLeuLysGluArgLeu 855 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2832 TGCTTTAATGTGCTTTTACTTCCGGAATACTCAAGCAAAGAAAAACTTAAAGAGAGATTG 2891 Qy 856 LeuLysAlaIleThrTyrAlaLysGlyPheGlyMetLeu 868 Claimed SEQ ID NO 1 ||||||||||||||||||||||||||||||||||||||| Db 2892 TTGAAGGCCATCACGTATGCCAAAGGATTTGGCATGCTG 2930 WO584 SEQ # 15/NT encoding SEQ ID NO 1 Note that WO584 teaches (p. 13 L20-30) “homologous” means a nt sequence possessing at least 80% identity. Therefore, sequences homologous to WO584’s SEQ ID NOs 14-15 includes claimed SEQ ID NO 1 and a nt sequence encoding claimed SEQ ID NO 1. As discussed above, WO584 teaches administering UBE3A treats AS and ameliorates a symptom of AS and that motor dysfunction is a symptom of AS. Therefore, WO584 teaches that administering the AAV encoding the UBE3A protein will treat AS, including motor dysfunction. Therefore, WO584 anticipates all the limitations of Claim 6. Regarding Claim 7: As discussed above, WO584 teaches the vector further comprises a cell uptake sequence (i.e., TAT, see WO584 p. 18 L9-12, p. 20 L24-35). Regarding the location of the cell uptake sequence, Fig. 21 shows it is downstream of a TIS (i.e., a promoter) and between the secretion sequence (i.e., a GDNF sequence) and the UBE3A sequence to form a STUB vector. WO584 teaches (p. 16 L5-6) a GDNF sequence is a secretion signal. An annotated version of WO584 Fig. 21 is shown here: PNG media_image1.png 709 904 media_image1.png Greyscale Therefore, WO584 anticipates Claim 7. Regarding the sequences recited in Claims 8-9: WO584’s secretion sequence that is SEQ ID NO 8 is 100% identical to claimed SEQ ID NO 3 and WO584’s SEQ ID NO 4 is 100% identical to claimed SEQ ID NO 4, as shown by the following alignments: BDI57064 (NOTE: this sequence has 3 duplicates in the database searched. See complete list at the end of this report) ID BDI57064 standard; DNA; 57 BP. XX AC BDI57064; XX DT 29-DEC-2016 (first entry) XX DE Human GDNF gene, SEQ ID 8. XX KW GDNF gene; Glial cell neurotrophic factor ligand; angelman syndrome; KW anorectic; ds; genetic-disease-gen.; growth-disorder-gen.; KW huntingtons chorea; neuroprotective; nootropic; nutrition-disorder-gen.; KW prader-willi syndrome; therapeutic; vector. XX OS Homo sapiens. XX CC PN WO2016179584-A1. XX CC PD 10-NOV-2016. XX CC PF 09-MAY-2016; 2016WO-US031468. XX PR 07-MAY-2015; 2015US-0158269P. XX CC PA (UYSF ) UNIV SOUTH FLORIDA. CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2016-70063D/81. XX CC PT New ubiquitin ligase E3a (UBE3A) vector comprising a transcription CC PT initiation sequence, a UBE3A sequence, a secretion sequence, and a cell CC PT uptake sequence, useful for treating a UBE3A deficiency disease. XX CC PS Claim 1; SEQ ID NO 8; 92pp; English. XX CC The present invention relates to a novel ubiquitin ligase E3a (UBE3A) CC vector, for treating a UBE3A deficiency disease. The vector comprises: a CC transcription initiation sequence; a UBE3A sequence disposed downstream CC of the transcription initiation sequence; a secretion sequence disposed CC downstream of the transcription initiation sequence; and a cell uptake CC sequence disposed downstream of the transcription initiation sequence. CC The invention also provides: (1) a method for synthesizing a UBE3A vector CC ; and (2) a method for treating a UBE3A deficiency disease. The UBE3A CC vector is useful for treating a UBE3A deficiency disease selected from CC Angelman syndrome, Prader-Willi syndrome, and Huntington's disease. The CC present sequence is a human GDNF gene, which is used in the invention for CC constructing the vector of the invention. XX SQ Sequence 57 BP; 7 A; 17 C; 18 G; 15 T; 0 U; 0 Other; Query Match 100.0%; Score 57; Length 57; Best Local Similarity 100.0%; Matches 57; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 ATGAAGTTATGGGATGTCGTGGCTGTCTGCCTGGTGCTGCTCCACACCGCGTCCGCC 57 SEQ ID NO 3 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 ATGAAGTTATGGGATGTCGTGGCTGTCTGCCTGGTGCTGCTCCACACCGCGTCCGCC 57 WO584 SEQ ID #8 BDI57060 (NOTE: this sequence has 2 duplicates in the database searched. See complete list at the end of this report) ID BDI57060 standard; DNA; 33 BP. XX AC BDI57060; XX DT 29-DEC-2016 (first entry) XX DE Human immunodeficiency virus TAT gene, SEQ ID 4. XX KW TAT gene; TAT protein; angelman syndrome; anorectic; ds; KW genetic-disease-gen.; growth-disorder-gen.; huntingtons chorea; KW neuroprotective; nootropic; nutrition-disorder-gen.; KW prader-willi syndrome; therapeutic; vector. XX OS Human immunodeficiency virus. XX FH Key Location/Qualifiers FT CDS 1..33 FT /*tag= a FT /partial FT /product= "TAT protein" FT /note= "No start or stop codon shown" XX CC PN WO2016179584-A1. XX CC PD 10-NOV-2016. XX CC PF 09-MAY-2016; 2016WO-US031468. XX PR 07-MAY-2015; 2015US-0158269P. XX CC PA (UYSF ) UNIV SOUTH FLORIDA. CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2016-70063D/81. XX CC PT New ubiquitin ligase E3a (UBE3A) vector comprising a transcription CC PT initiation sequence, a UBE3A sequence, a secretion sequence, and a cell CC PT uptake sequence, useful for treating a UBE3A deficiency disease. XX CC PS Claim 1; SEQ ID NO 4; 92pp; English. XX CC The present invention relates to a novel ubiquitin ligase E3a (UBE3A) CC vector, for treating a UBE3A deficiency disease. The vector comprises: a CC transcription initiation sequence; a UBE3A sequence disposed downstream CC of the transcription initiation sequence; a secretion sequence disposed CC downstream of the transcription initiation sequence; and a cell uptake CC sequence disposed downstream of the transcription initiation sequence. CC The invention also provides: (1) a method for synthesizing a UBE3A vector CC ; and (2) a method for treating a UBE3A deficiency disease. The UBE3A CC vector is useful for treating a UBE3A deficiency disease selected from CC Angelman syndrome, Prader-Willi syndrome, and Huntington's disease. The CC present sequence is a Human immunodeficiency virus TAT gene, which is CC used in the invention for constructing the vector of the invention. XX SQ Sequence 33 BP; 15 A; 3 C; 14 G; 1 T; 0 U; 0 Other; Query Match 100.0%; Score 33; Length 33; Best Local Similarity 100.0%; Matches 33; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 TACGGCAGAAAGAAGAGGAGGCAGAGAAGGAGA 33 SEQ ID NO 4 ||||||||||||||||||||||||||||||||| Db 1 TACGGCAGAAAGAAGAGGAGGCAGAGAAGGAGA 33 WO584 SEQ ID NO 4 Therefore, WO584 anticipates Claims 8-9. Regarding Claim 10: WO584 teaches (p. 9 L1-10) the TIS sequence is a cytomegalovirus chicken beta actin hybrid promoter or a human ubiquitin C promoter, thereby anticipating Claim 10. Regarding Claim 11: WO584 teaches (p. 9 L1-15) the vector can comprise a cytomegalovirus immediate-early enhancer sequence disposed upstream of the TIS, thereby anticipating Claim 11. Regarding Claim 12: WO584 teaches (p. 9 L1-15) the vector can comprise a woodchuck hepatitis post-transcriptional regulatory element, thereby anticipating Claim 12. Regarding Claim 13: as discussed above, WO584 teaches (p. 10 L15-25, pp. 71-72 items #14-16) a method of treating a UBE3A deficiency disease that is AS (or Prader-Willi syndrome or Huntington’s disease), thereby anticipating Claim 13. Claim(s) 6-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by International Publication Number WO 2019/006107 (published on 13 January 2019, “WO107”). Citations to WO p. # refer to the PDF p. #. WO107 discloses (§Abstract) a gene therapy approach for treating Angelman syndrome (AS) that utilizes a UBE3A protein with additional sequences that allow secretion from cells and uptake by neighboring neuronal cells. Regarding Claim 6: WO107 teaches (p. 2 L20-end) AS presents with delayed and reduced developmental advancement, particularly with respect to motor skills. Specifically, that § teaches that movement is jerky and walking is commonly associated with hand flapping and a stiff gait, and afflicted individuals can possess sucking and swallowing problems. That indicates that those forms of motor impairment are symptoms of the disease. WO107 teaches (p. 5 L15-end) the invention provides a functional E6-AP protein and thereby rescues disease pathology. WO107 teaches (p. 13 L14-end) a “therapeutically effective amount” is an amount of therapy (e.g., agent or vector) sufficient to result in amelioration of AS or one or more symptoms thereof. That indicates that WO107’s method of treatment will ameliorate a symptom of AS, including any symptoms of motor impairment. WO107 teaches (p. 5 L15-40; p. 17 39) using an AAV vector to administer a gene encoding the UBE3A protein and (p. 6 L10-15) administration to the brain via intrahippocampal or intraventricular injection. WO107 teaches (pp. 38-39 items #11-16 and p. 15 L10-30) a method of treating a neurodegenerative disorder, the method comprising administering via injection to a patient’s brain a vector comprising a transcription initiation sequence (TIS), a UBE3A sequence disposed downstream of the TIS, wherein the UBE3A sequence is SEQ ID NO 17 or a cDNA of SEQ ID NO 16, or a sequence homologous to either of those; a secretion sequence disposed downstream of the TIS sequence, wherein the secretion sequence is SEQ ID NO 2; and a cell uptake sequence disposed downstream of the TIS sequence, wherein the cell uptake sequence is SEQ ID NO 6 (called SEQ ID NO 7 in alignment data, see below). WO107 specifies (p. 15 L10-30) the secretion sequence is upstream of the UBE3A sequence. WO107 teaches (p. 15 L5-10) exemplary neurodegenerative disorders include AS (or Prader-Willi syndrome or Huntington’s disease) Further regarding Claim 6: The following alignments show that WO107’s SEQ ID NO 16 is 95.8% identical to claimed SEQ ID NO 1 and WO107’s SEQ ID NO 15 is a nucleic acid sequence that encodes a sequence that is 96.3% identical to claimed SEQ ID NO 1: BFZ21866 ID BFZ21866 standard; protein; 875 AA. XX AC BFZ21866; XX DT 21-FEB-2019 (first entry) XX DE Human UBE3A variant 2 polypeptide, SEQ ID 16. XX KW UBE3A protein; Ubiquitin ligase E3A; angelman syndrome; gene therapy; KW growth-disorder-gen.; neurodegenerative disease; neuroprotective; KW therapeutic; ubiquitin-protein ligase E3A; vector. XX OS Homo sapiens. XX CC PN WO2019006107-A1. XX CC PD 03-JAN-2019. XX CC PF 28-JUN-2018; 2018WO-US039980. XX PR 28-JUN-2017; 2017US-0525787P. XX CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. CC PA (UYSF ) UNIV SOUTH FLORIDA. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2019-01723M/05. DR N-PSDB; BFZ21865. XX CC PT New ubiquitin-protein ligase E3A (UBE3A) vector useful in composition for CC PT treating neurodegenerative disorder, preferably Angelman syndrome, CC PT contains transcription initiation sequence, secretion sequence, and cell CC PT uptake sequence. XX CC PS Example 5; SEQ ID NO 16; 63pp; English. XX CC The present invention relates to a novel ubiquitin-protein ligase E3A CC (UBE3A) vector, useful for preparing a composition to treat a CC neurodegenerative disorder such as Angelman syndrome by gene therapy. The CC vector comprises: (i) a transcription initiation sequence; (ii) a UBE3A CC sequence disposed downstream of the transcription initiation sequence, or CC a homologous sequence; (iii) a secretion sequence disposed downstream of CC the transcription initiation sequence, or a homologous sequence; and (iv) CC a cell uptake sequence disposed downstream of the transcription CC initiation sequence, or a homologous sequence. The invention further CC refers to: (1) a method for treating a neurodegenerative disorder by CC administering the UBE3A vector to a patient suffering from a CC neurodegenerative disorder; and (2) a composition for use in treating a CC neurodegenerative disorder characterized by deficient UBE3A, comprising a CC UBE3A vector and a pharmaceutically acceptable carrier. The present CC sequence is a human UBE3A variant 2 polypeptide, used in the CC exemplification of the invention for constructing a human-UBE3A vector in CC order to treat Angelman syndrome by gene therapy. XX SQ Sequence 875 AA; ALIGNMENT: Query Match 95.8%; Score 4316.5; Length 875; Best Local Similarity 95.6%; Matches 831; Conservative 20; Mismatches 13; Indels 5; Gaps 2; Qy 5 CKRSSGESQSEDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTFLRMDNN 64 | ||| ||:||||||||||||||||||||||||||||||||||||||||||||||||| Db 7 CYWKSGEPQSDDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTFLRMDNN 66 Qy 65 AAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGASNN--SEIKMNKKE---EFKEVD 119 ||||||||||||||||||||||||||||||||||||| || |||||||| :||:| Db 67 AAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGAPNNSCSEIKMNKKGARIDFKDVT 126 Qy 120 YLTEEKVYEIYEFCREREDYSPLIRVIGRIFSSAEALVQSFRKVKQHTKEELKSLQEKDE 179 |||||||||| | ||||||||||||||||:|||||||||||||||||||||||||| ||| Db 127 YLTEEKVYEILELCREREDYSPLIRVIGRVFSSAEALVQSFRKVKQHTKEELKSLQAKDE 186 Qy 180 DKDEDEKEKAACSAAAMEEDSEASSSRMGDSSQGDNNVQKLGPDDVTVDIDAIRRVYSSL 239 |||||||||||||||||||||||||||:|||||||||:||||||||:||||||||||: | Db 187 DKDEDEKEKAACSAAAMEEDSEASSSRIGDSSQGDNNLQKLGPDDVSVDIDAIRRVYTRL 246 Qy 240 LSDEKIETAFLNALVYLSPNVECDLTYHNVYTRDPNYLNLFIIVMENRNLHSPEYLEMAL 299 ||:||||||||||||||||||||||||||||:|||||||||||||||||||||||||||| Db 247 LSNEKIETAFLNALVYLSPNVECDLTYHNVYSRDPNYLNLFIIVMENRNLHSPEYLEMAL 306 Qy 300 PLFCKAMSKLPLAAQGKLIRLWSKYSADQIRRMMETFQQLITYKVISNEFNSRNLVNDDD 359 |||||||||||||||||||||||||:|||||||||||||||||||||||||||||||||| Db 307 PLFCKAMSKLPLAAQGKLIRLWSKYNADQIRRMMETFQQLITYKVISNEFNSRNLVNDDD 366 Qy 360 AIVAASKCLKMVYYANVVGGDVDTNHNEEDDEEPIPESSELTLQELLGEERRNKKGPRVD 419 ||||||||||||||||||||:||||||||||||||||||||||||||||||||||||||| Db 367 AIVAASKCLKMVYYANVVGGEVDTNHNEEDDEEPIPESSELTLQELLGEERRNKKGPRVD 426 Qy 420 PLETEIGVKTLDCRKPLISFEEFINEPLNDVLEMDKDYTFFKVETENKFSFMTCPFILNA 479 |||||:|||||||||||| ||||||||||:|||||||||||||||||||||||||||||| Db 427 PLETELGVKTLDCRKPLIPFEEFINEPLNEVLEMDKDYTFFKVETENKFSFMTCPFILNA 486 Qy 480 VTKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRLEMIAME 539 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 487 VTKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRLEMIAME 546 Qy 540 NPADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDEATRLFWFNPSSF 599 ||||||||||||||||||||||||||||||||||||||||||||||||:|:||||||||| Db 547 NPADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDESTKLFWFNPSSF 606 Qy 600 ETEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFCDLGDSHPILYQSLKDLL 659 |||||||||||||||||||||||||||||||||||||||||| |||||||:||||||||| Db 607 ETEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFRDLGDSHPVLYQSLKDLL 666 Qy 660 EYEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVSLYSDYILNKSV 719 ||||||||||||||||||||||||||||||||||||||||||||||||:||||||||||| Db 667 EYEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVNLYSDYILNKSV 726 Qy 720 EKQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRESVV 779 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||:||: Db 727 EKQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRDSVL 786 Qy 780 IREFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNV 839 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 787 IREFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNV 846 Qy 840 LLLPEYSSKEKLKERLLKAITYAKGFGML 868 claimed SEQ ID NO 1 ||||||||||||||||||||||||||||| Db 847 LLLPEYSSKEKLKERLLKAITYAKGFGML 875 WO107 SEQ ID NO 16 BFZ21867 ID BFZ21867 standard; DNA; 2970 BP. XX AC BFZ21867; XX DT 21-FEB-2019 (first entry) XX DE Human UBE3A variant 3 polynucleotide, SEQ ID 17. XX KW UBE3A gene; Ubiquitin ligase E3A; angelman syndrome; ds; gene therapy; KW growth-disorder-gen.; neurodegenerative disease; neuroprotective; KW therapeutic; ubiquitin-protein ligase E3A; vector. XX OS Homo sapiens. XX FH Key Location/Qualifiers FT CDS 1528..1824 FT /*tag= a FT /product= "UBE3A protein" FT /partial FT /note= "No start and stop codon shown" XX CC PN WO2019006107-A1. XX CC PD 03-JAN-2019. XX CC PF 28-JUN-2018; 2018WO-US039980. XX PR 28-JUN-2017; 2017US-0525787P. XX CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. CC PA (UYSF ) UNIV SOUTH FLORIDA. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2019-01723M/05. DR GENBANK; AK292514.1. XX CC PT New ubiquitin-protein ligase E3A (UBE3A) vector useful in composition for CC PT treating neurodegenerative disorder, preferably Angelman syndrome, CC PT contains transcription initiation sequence, secretion sequence, and cell CC PT uptake sequence. XX CC PS Example 5; SEQ ID NO 17; 63pp; English. XX CC The present invention relates to a novel ubiquitin-protein ligase E3A CC (UBE3A) vector, useful for preparing a composition to treat a CC neurodegenerative disorder such as Angelman syndrome by gene therapy. The CC vector comprises: (i) a transcription initiation sequence; (ii) a UBE3A CC sequence disposed downstream of the transcription initiation sequence, or CC a homologous sequence; (iii) a secretion sequence disposed downstream of CC the transcription initiation sequence, or a homologous sequence; and (iv) CC a cell uptake sequence disposed downstream of the transcription CC initiation sequence, or a homologous sequence. The invention further CC refers to: (1) a method for treating a neurodegenerative disorder by CC administering the UBE3A vector to a patient suffering from a CC neurodegenerative disorder; and (2) a composition for use in treating a CC neurodegenerative disorder characterized by deficient UBE3A, comprising a CC UBE3A vector and a pharmaceutically acceptable carrier. The present CC sequence is a human UBE3A variant 3 polynucleotide, whose encoded protein CC is used in the exemplification of the invention for constructing a human- CC UBE3A vector in order to treat Angelman syndrome by gene therapy. XX SQ Sequence 2970 BP; 976 A; 537 C; 679 G; 778 T; 0 U; 0 Other; Length: 2970 Score: 4339.00 Matches: 837 Percent Similarity: 98.2% Conservative: 20 Best Local Similarity: 95.9% Mismatches: 10 Query Match: 96.3% Indels: 6 Gaps: 3 US-18-392-696-1 (1-868) x BDI57071 (1-2970) Qy 1 MetAlaThrAlaCysLysArgSerSerGlyGluSerGlnSerGluAspIleGluAlaSer 20 ||||||||||||||||||||| ||||||||| ||||||:::||||||||||||||| Db 315 ATGGCCACAGCTTGTAAAAGA---TCAGGAGAACCTCAGTCTGACGACATTGAAGCTAGC 371 Qy 21 ArgMetLysArgAlaAlaAlaLysHisLeuIleGluArgTyrTyrHisGlnLeuThrGlu 40 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 372 CGAATGAAGCGAGCAGCTGCAAAGCATCTAATAGAACGCTACTACCACCAGTTAACTGAG 431 Qy 41 GlyCysGlyAsnGluAlaCysThrAsnGluPheCysAlaSerCysProThrPheLeuArg 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 432 GGCTGTGGAAATGAAGCCTGCACGAATGAGTTTTGTGCTTCCTGTCCAACTTTTCTTCGT 491 Qy 61 MetAspAsnAsnAlaAlaAlaIleLysAlaLeuGluLeuTyrLysIleAsnAlaLysLeu 80 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 492 ATGGATAATAATGCAGCAGCTATTAAAGCCCTCGAGCTTTATAAGATTAATGCAAAACTC 551 Qy 81 CysAspProHisProSerLysLysGlyAlaSerSerAlaTyrLeuGluAsnSerLysGly 100 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 552 TGTGATCCTCATCCCTCCAAGAAAGGAGCAAGCTCAGCTTACCTTGAGAACTCGAAAGGT 611 Qy 101 AlaSerAsnAsn------SerGluIleLysMetAsnLysLysGlu---------GluPhe 115 ||| |||||| |||||||||||||||||||||||| :::||| Db 612 GCCCCCAACAACTCCTGCTCTGAGATAAAAATGAACAAGAAAGGCGCTAGAATTGATTTT 671 Qy 116 LysGluValAspTyrLeuThrGluGluLysValTyrGluIleTyrGluPheCysArgGlu 135 |||:::||| |||||||||||||||||||||||||||||| ||| ||||||||| Db 672 AAAGATGTGACTTACTTAACAGAAGAGAAGGTATATGAAATTCTTGAATTATGTAGAGAA 731 Qy 136 ArgGluAspTyrSerProLeuIleArgValIleGlyArgIlePheSerSerAlaGluAla 155 |||||||||||||||||||||||||||||||||||||||:::|||||||||||||||||| Db 732 AGAGAGGATTATTCCCCTTTAATCCGTGTTATTGGAAGAGTTTTTTCTAGTGCTGAGGCA 791 Qy 156 LeuValGlnSerPheArgLysValLysGlnHisThrLysGluGluLeuLysSerLeuGln 175 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 792 TTGGTACAGAGCTTCCGGAAAGTTAAACAACACACCAAGGAAGAACTGAAATCTCTTCAA 851 Qy 176 GluLysAspGluAspLysAspGluAspGluLysGluLysAlaAlaCysSerAlaAlaAla 195 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 852 GCAAAAGATGAAGACAAAGATGAAGATGAAAAGGAAAAAGCTGCATGTTCTGCTGCTGCT 911 Qy 196 MetGluGluAspSerGluAlaSerSerSerArgMetGlyAspSerSerGlnGlyAspAsn 215 |||||||||||||||||||||||||||||||||:::|||||||||||||||||||||||| Db 912 ATGGAAGAAGACTCAGAGGCATCTTCCTCAAGGATAGGTGATAGCTCACAGGGAGACAAC 971 Qy 216 AsnValGlnLysLeuGlyProAspAspValThrValAspIleAspAlaIleArgArgVal 235 |||:::||||||||||||||||||||||||:::||||||||||||||||||||||||||| Db 972 AATTTGCAAAAATTAGGCCCTGATGATGTGTCTGTGGATATTGATGCCATTAGAAGGGTC 1031 Qy 236 TyrSerSerLeuLeuSerAspGluLysIleGluThrAlaPheLeuAsnAlaLeuValTyr 255 |||::: |||||||||:::||||||||||||||||||||||||||||||||||||||| Db 1032 TACACCAGATTGCTCTCTAATGAAAAAATTGAAACTGCCTTTCTCAATGCACTTGTATAT 1091 Qy 256 LeuSerProAsnValGluCysAspLeuThrTyrHisAsnValTyrThrArgAspProAsn 275 |||||||||||||||||||||||||||||||||||||||||||||:::|||||||||||| Db 1092 TTGTCACCTAACGTGGAATGTGACTTGACGTATCACAATGTATACTCTCGAGATCCTAAT 1151 Qy 276 TyrLeuAsnLeuPheIleIleValMetGluAsnArgAsnLeuHisSerProGluTyrLeu 295 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1152 TATCTGAATTTGTTCATTATCGTAATGGAGAATAGAAATCTCCACAGTCCTGAATATCTG 1211 Qy 296 GluMetAlaLeuProLeuPheCysLysAlaMetSerLysLeuProLeuAlaAlaGlnGly 315 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1212 GAAATGGCTTTGCCATTATTTTGCAAAGCGATGAGCAAGCTACCCCTTGCAGCCCAAGGA 1271 Qy 316 LysLeuIleArgLeuTrpSerLysTyrSerAlaAspGlnIleArgArgMetMetGluThr 335 |||||||||||||||||||||||||||:::|||||||||||||||||||||||||||||| Db 1272 AAACTGATCAGACTGTGGTCTAAATACAATGCAGACCAGATTCGGAGAATGATGGAGACA 1331 Qy 336 PheGlnGlnLeuIleThrTyrLysValIleSerAsnGluPheAsnSerArgAsnLeuVal 355 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1332 TTTCAGCAACTTATTACTTATAAAGTCATAAGCAATGAATTTAACAGTCGAAATCTAGTG 1391 Qy 356 AsnAspAspAspAlaIleValAlaAlaSerLysCysLeuLysMetValTyrTyrAlaAsn 375 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1392 AATGATGATGATGCCATTGTTGCTGCTTCGAAGTGCTTGAAAATGGTTTACTATGCAAAT 1451 Qy 376 ValValGlyGlyAspValAspThrAsnHisAsnGluGluAspAspGluGluProIlePro 395 ||||||||||||:::||||||||||||||||||||||||||||||||||||||||||||| Db 1452 GTAGTGGGAGGGGAAGTGGACACAAATCACAATGAAGAAGATGATGAAGAGCCCATCCCT 1511 Qy 396 GluSerSerGluLeuThrLeuGlnGluLeuLeuGlyGluGluArgArgAsnLysLysGly 415 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1512 GAGTCCAGCGAGCTGACACTTCAGGAACTTTTGGGAGAAGAAAGAAGAAACAAGAAAGGT 1571 Qy 416 ProArgValAspProLeuGluThrGluIleGlyValLysThrLeuAspCysArgLysPro 435 |||||||||||||||||||||||||||:::|||||||||||||||||||||||||||||| Db 1572 CCTCGAGTGGACCCCCTGGAAACTGAACTTGGTGTTAAAACCCTGGATTGTCGAAAACCA 1631 Qy 436 LeuIleSerPheGluGluPheIleAsnGluProLeuAsnAspValLeuGluMetAspLys 455 |||||| ||||||||||||||||||||||||||||||:::|||||||||||||||||| Db 1632 CTTATCCCTTTTGAAGAGTTTATTAATGAACCACTGAATGAGGTTCTAGAAATGGATAAA 1691 Qy 456 AspTyrThrPhePheLysValGluThrGluAsnLysPheSerPheMetThrCysProPhe 475 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1692 GATTATACTTTTTTCAAAGTAGAAACAGAGAACAAATTCTCTTTTATGACATGTCCCTTT 1751 Qy 476 IleLeuAsnAlaValThrLysAsnLeuGlyLeuTyrTyrAspAsnArgIleArgMetTyr 495 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1752 ATATTGAATGCTGTCACAAAGAATTTGGGATTATATTATGACAATAGAATTCGCATGTAC 1811 Qy 496 SerGluArgArgIleThrValLeuTyrSerLeuValGlnGlyGlnGlnLeuAsnProTyr 515 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1812 AGTGAACGAAGAATCACTGTTCTCTACAGCTTAGTTCAAGGACAGCAGTTGAATCCATAT 1871 Qy 516 LeuArgLeuLysValArgArgAspHisIleIleAspAspAlaLeuValArgLeuGluMet 535 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1872 TTGAGACTCAAAGTTAGACGTGACCATATCATAGATGATGCACTTGTCCGGCTAGAGATG 1931 Qy 536 IleAlaMetGluAsnProAlaAspLeuLysLysGlnLeuTyrValGluPheGluGlyGlu 555 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1932 ATCGCTATGGAAAATCCTGCAGACTTGAAGAAGCAGTTGTATGTGGAATTTGAAGGAGAA 1991 Qy 556 GlnGlyValAspGluGlyGlyValSerLysGluPhePheGlnLeuValValGluGluIle 575 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1992 CAAGGAGTTGATGAGGGAGGTGTTTCCAAAGAATTTTTTCAGCTGGTTGTGGAGGAAATC 2051 Qy 576 PheAsnProAspIleGlyMetPheThrTyrAspGluAlaThrArgLeuPheTrpPheAsn 595 ||||||||||||||||||||||||||||||||||||:::|||:::||||||||||||||| Db 2052 TTCAATCCAGATATTGGTATGTTCACATACGATGAATCTACAAAATTGTTTTGGTTTAAT 2111 Qy 596 ProSerSerPheGluThrGluGlyGlnPheThrLeuIleGlyIleValLeuGlyLeuAla 615 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2112 CCATCTTCTTTTGAAACTGAGGGTCAGTTTACTCTGATTGGCATAGTACTGGGTCTGGCT 2171 Qy 616 IleTyrAsnAsnCysIleLeuAspValHisPheProMetValValTyrArgLysLeuMet 635 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2172 ATTTACAATAACTGTATACTGGATGTACATTTTCCCATGGTTGTCTACAGGAAGCTAATG 2231 Qy 636 GlyLysLysGlyThrPheCysAspLeuGlyAspSerHisProIleLeuTyrGlnSerLeu 655 |||||||||||||||||| |||||||||||||||||||||:::||||||||||||||| Db 2232 GGGAAAAAAGGAACTTTTCGTGACTTGGGAGACTCTCACCCAGTTCTATATCAGAGTTTA 2291 Qy 656 LysAspLeuLeuGluTyrGluGlyAsnValGluAspAspMetMetIleThrPheGlnIle 675 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2292 AAAGATTTATTGGAGTATGAAGGGAATGTGGAAGATGACATGATGATCACTTTCCAGATA 2351 Qy 676 SerGlnThrAspLeuPheGlyAsnProMetMetTyrAspLeuLysGluAsnGlyAspLys 695 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2352 TCACAGACAGATCTTTTTGGTAACCCAATGATGTATGATCTAAAGGAAAATGGTGATAAA 2411 Qy 696 IleProIleThrAsnGluAsnArgLysGluPheValSerLeuTyrSerAspTyrIleLeu 715 ||||||||||||||||||||||||||||||||||||:::||||||||||||||||||||| Db 2412 ATTCCAATTACAAATGAAAACAGGAAGGAATTTGTCAATCTTTATTCTGACTACATTCTC 2471 Qy 716 AsnLysSerValGluLysGlnPheLysAlaPheArgArgGlyPheHisMetValThrAsn 735 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2472 AATAAATCAGTAGAAAAACAGTTCAAGGCTTTTCGGAGAGGTTTTCATATGGTGACCAAT 2531 Qy 736 GluSerProLeuLysTyrLeuPheArgProGluGluIleGluLeuLeuIleCysGlySer 755 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2532 GAATCTCCCTTAAAGTACTTATTCAGACCAGAAGAAATTGAATTGCTTATATGTGGAAGC 2591 Qy 756 ArgAsnLeuAspPheGlnAlaLeuGluGluThrThrGluTyrAspGlyGlyTyrThrArg 775 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2592 CGGAATCTAGATTTCCAAGCACTAGAAGAAACTACAGAATATGACGGTGGCTATACCAGG 2651 Qy 776 GluSerValValIleArgGluPheTrpGluIleValHisSerPheThrAspGluGlnLys 795 :::||||||:::|||||||||||||||||||||||||||||||||||||||||||||||| Db 2652 GACTCTGTTCTGATTAGGGAGTTCTGGGAAATCGTTCATTCATTTACAGATGAACAGAAA 2711 Qy 796 ArgLeuPheLeuGlnPheThrThrGlyThrAspArgAlaProValGlyGlyLeuGlyLys 815 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2712 AGACTCTTCTTGCAGTTTACAACGGGCACAGACAGAGCACCTGTGGGAGGACTAGGAAAA 2771 Qy 816 LeuLysMetIleIleAlaLysAsnGlyProAspThrGluArgLeuProThrSerHisThr 835 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2772 TTAAAGATGATTATAGCCAAAAATGGCCCAGACACAGAAAGGTTACCTACATCTCATACT 2831 Qy 836 CysPheAsnValLeuLeuLeuProGluTyrSerSerLysGluLysLeuLysGluArgLeu 855 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2832 TGCTTTAATGTGCTTTTACTTCCGGAATACTCAAGCAAAGAAAAACTTAAAGAGAGATTG 2891 Qy 856 LeuLysAlaIleThrTyrAlaLysGlyPheGlyMetLeu 868 Claimed SEQ ID NO 1 ||||||||||||||||||||||||||||||||||||||| Db 2892 TTGAAGGCCATCACGTATGCCAAAGGATTTGGCATGCTG 2930 WO107 SEQ # 17/NT encoding SEQ ID NO 1 Note that WO107 teaches (p. 13 L1-25) “homologous” means a nt sequence possessing at least 80% identity. Therefore, “sequences homologous to WO107’s SEQ ID NOs 16-17” includes claimed SEQ ID NO 1 and a nt sequence encoding claimed SEQ ID NO 1. As discussed above, WO107 teaches administering UBE3A treats AS and ameliorates a symptom of AS and that motor dysfunction is a symptom of AS. In addition, WO107 teaches (p. 37 L7-20) a method of treating AS by administering a therapeutically effective amount of UBE3A vector, and that doing so results in improvements: increased muscle tone, increased coordination of muscle movement and improvement in speech. Therefore, WO107 teaches administering their vector will improve motor function. Therefore, WO107 teaches that administering the AAV encoding the UBE3A protein will treat AS, including motor dysfunction. Therefore, WO107 anticipates all the limitations of Claim 6. Regarding Claim 7: As discussed above, WO107 teaches the vector further comprises a cell uptake sequence (i.e., TAT, see WO107 p. 16 L35-end, p. 21 L35-end). Regarding the location of the cell uptake sequence, Fig. 21 shows it is downstream of a TIS (i.e., a promoter) and between the secretion sequence (i.e., a GDNF sequence) and the UBE3A sequence to form a STUB vector. WO107 teaches (p. 16 L5-6) a GDNF sequence is a secretion signal. An annotated version of WO107 Fig. 21 is shown here: PNG media_image1.png 709 904 media_image1.png Greyscale Therefore, WO107 anticipates Claim 7. Regarding the sequences recited in Claims 8-9: WO107’s secretion sequence that is SEQ ID NO 2 is 100% identical to claimed SEQ ID NO 3 and WO107’s SEQ ID NO 6 (called SEQ ID NO 6 in WO107 text but called SEQ ID NO 7 in SEQ data) is 100% identical to claimed SEQ ID NO 4, as shown by the following alignments. Note that while the text of WO107 (p. 5 L25-35, p. 15 L25-30, pp. 19-20 L38-10) refers to an HIV TAT sequence called SEQ ID NO 6 and the SEQ data call the same thing SEQ ID NO 7, the reference teaches a cell uptake sequence that for HIV TAT and that is the exact same sequence as what is claimed, even if WO107 calls it by two different SEQ ID NOs. BFZ21852 ID BFZ21852 standard; DNA; 57 BP. XX AC BFZ21852; XX DT 21-FEB-2019 (first entry) XX DE Human GDNF coding sequence, SEQ ID 2. XX KW GDNF gene; Glial cell neurotrophic factor ligand; angelman syndrome; KW coding sequence; ds; gene therapy; growth-disorder-gen.; KW neurodegenerative disease; neuroprotective; signal sequence; therapeutic; KW vector. XX OS Homo sapiens. XX FH Key Location/Qualifiers FT CDS 1..57 FT /*tag= a FT /product= "GDNF protein" FT /partial FT /note= "No stop codon shown" XX CC PN WO2019006107-A1. XX CC PD 03-JAN-2019. XX CC PF 28-JUN-2018; 2018WO-US039980. XX PR 28-JUN-2017; 2017US-0525787P. XX CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. CC PA (UYSF ) UNIV SOUTH FLORIDA. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2019-01723M/05. DR P-PSDB; BFZ21853. DR GENBANK; AB675653.1. XX CC PT New ubiquitin-protein ligase E3A (UBE3A) vector useful in composition for CC PT treating neurodegenerative disorder, preferably Angelman syndrome, CC PT contains transcription initiation sequence, secretion sequence, and cell CC PT uptake sequence. XX CC PS Example 1; SEQ ID NO 2; 63pp; English. XX CC The present invention relates to a novel ubiquitin-protein ligase E3A CC (UBE3A) vector, useful for preparing a composition to treat a CC neurodegenerative disorder such as Angelman syndrome by gene therapy. The CC vector comprises: (i) a transcription initiation sequence; (ii) a UBE3A CC sequence disposed downstream of the transcription initiation sequence, or CC a homologous sequence; (iii) a secretion sequence disposed downstream of CC the transcription initiation sequence, or a homologous sequence; and (iv) CC a cell uptake sequence disposed downstream of the transcription CC initiation sequence, or a homologous sequence. The invention further CC refers to: (1) a method for treating a neurodegenerative disorder by CC administering the UBE3A vector to a patient suffering from a CC neurodegenerative disorder; and (2) a composition for use in treating a CC neurodegenerative disorder characterized by deficient UBE3A, comprising a CC UBE3A vector and a pharmaceutically acceptable carrier. The present CC sequence is a human GDNF coding sequence, whose encoded protein is used CC in the exemplification of the invention for testing the efficiency of the CC secretion signal. XX SQ Sequence 57 BP; 7 A; 17 C; 18 G; 15 T; 0 U; 0 Other; Query Match 100.0%; Score 57; Length 57; Best Local Similarity 100.0%; Matches 57; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 ATGAAGTTATGGGATGTCGTGGCTGTCTGCCTGGTGCTGCTCCACACCGCGTCCGCC 57 SEQ ID NO 3 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 ATGAAGTTATGGGATGTCGTGGCTGTCTGCCTGGTGCTGCTCCACACCGCGTCCGCC 57 WO107 SEQ ID #2 BFZ21857 ID BFZ21857 standard; DNA; 33 BP. XX AC BFZ21857; XX DT 21-FEB-2019 (first entry) XX DE HIV TAT coding sequence, SEQ ID 7. XX KW TAT gene; TAT protein; angelman syndrome; coding sequence; ds; KW gene therapy; growth-disorder-gen.; neurodegenerative disease; KW neuroprotective; therapeutic; vector. XX OS Human immunodeficiency virus. XX FH Key Location/Qualifiers FT CDS 1..33 FT /*tag= a FT /product= "HIV TAT protein" FT /partial FT /note= "No start and stop codon shown" XX CC PN WO2019006107-A1. XX CC PD 03-JAN-2019. XX CC PF 28-JUN-2018; 2018WO-US039980. XX PR 28-JUN-2017; 2017US-0525787P. XX CC PA (NASH/) NASH K R. CC PA (WEEB/) WEEBER E J. CC PA (UYSF ) UNIV SOUTH FLORIDA. XX CC PI Nash KR, Weeber EJ; XX DR WPI; 2019-01723M/05. DR P-PSDB; BFZ21858. DR GENBANK; NP032412.3. XX CC PT New ubiquitin-protein ligase E3A (UBE3A) vector useful in composition for CC PT treating neurodegenerative disorder, preferably Angelman syndrome, CC PT contains transcription initiation sequence, secretion sequence, and cell CC PT uptake sequence. XX CC PS Example 2; SEQ ID NO 7; 63pp; English. XX CC The present invention relates to a novel ubiquitin-protein ligase E3A CC (UBE3A) vector, useful for preparing a composition to treat a CC neurodegenerative disorder such as Angelman syndrome by gene therapy. The CC vector comprises: (i) a transcription initiation sequence; (ii) a UBE3A CC sequence disposed downstream of the transcription initiation sequence, or CC a homologous sequence; (iii) a secretion sequence disposed downstream of CC the transcription initiation sequence, or a homologous sequence; and (iv) CC a cell uptake sequence disposed downstream of the transcription CC initiation sequence, or a homologous sequence. The invention further CC refers to: (1) a method for treating a neurodegenerative disorder by CC administering the UBE3A vector to a patient suffering from a CC neurodegenerative disorder; and (2) a composition for use in treating a CC neurodegenerative disorder characterized by deficient UBE3A, comprising a CC UBE3A vector and a pharmaceutically acceptable carrier. The present CC sequence is a HIV TAT coding sequence, whose encoded protein is used in CC the exemplification of the invention for constructing a mouse-UBE3A CC vector. XX SQ Sequence 33 BP; 15 A; 3 C; 14 G; 1 T; 0 U; 0 Other; Query Match 100.0%; Score 33; Length 33; Best Local Similarity 100.0%; Matches 33; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 TACGGCAGAAAGAAGAGGAGGCAGAGAAGGAGA 33 SEQ ID NO 4 ||||||||||||||||||||||||||||||||| Db 1 TACGGCAGAAAGAAGAGGAGGCAGAGAAGGAGA 33 WO107 SEQ ID NO 7 (a.k.a. SEQ ID NO 6) Therefore, WO107 anticipates Claims 8-9. Regarding Claim 10: WO107 teaches (p. 15 L29-end) the TIS sequence is a cytomegalovirus chicken beta actin hybrid promoter or a human ubiquitin C promoter, thereby anticipating Claim 10. Regarding Claim 11: WO107 teaches (p. 15 L29-end) the vector can comprise a cytomegalovirus immediate-early enhancer sequence disposed upstream of the TIS, thereby anticipating Claim 11. Regarding Claim 12: WO107 teaches (p. 15 L29-end) the vector can comprise a woodchuck hepatitis post-transcriptional regulatory element, thereby anticipating Claim 12. Regarding Claim 13: as discussed above, WO107 teaches (pp. 38-39 items #11-16, p. 15 L10-30, and p. 37 L7-20) a method of treating a UBE3A deficiency disease that is AS (or Prader-Willi syndrome or Huntington’s disease), thereby anticipating Claim 13. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claim(s) 6-13 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2016/179584 (published on 10 November 2016, “WO584”, of record on IDS) as applied to claims 6-13 above, and further in view of International Publication Number WO 2018/067608 (published on 12 April 2018, “WO608”). Note that WO608 is the WO version of US Publication No US 2019/0208752 (published on 11 July 2019, “App752”) which is cited on the IDS. Citations to WO p. # refer to the PDF p. #. The teachings of WO584 as applicable to Claim(s) 6-13 have been described in the 102 rejection above. As discussed in the 102 rejection, WO584 teaches all the limitations of Claims 6-13. WO584 teaches using an AAV vector to administer a gene encoding UBE3A, a secretion sequence that allows the protein to be secreted from cells, and a cell uptake sequence that allows the secreted protein to be taken up by neighboring cells. WO584 teaches sequences identical to claimed SEQ ID NOs 3-4 (i.e., WO584 SEQ ID NOs 8 and 4) and sequences homologous to claimed SEQ ID NO 1 (i.e., SEQ ID NO 14) or to a nt sequence encoding claimed SEQ ID NO 1 (i.e., SEQ ID NO 15). WO584 indicates (pp. 61-68 L10-20) SEQ ID NOs 14-15 are sequences encoding human UBE3A. WO584 does not teach a sequence that is exactly claimed SEQ ID NO 1 or a nt sequence encoding an AA sequence that is exactly claimed SEQ ID NO 1. However, WO608 teaches (§Abstract) an animal model of AS that lacks UBE3A. WO608 teaches (pp. 6-7 L29-10) SEQ ID NOs 3 and 4 which are, respectively, an AA sequence of rat UBE3A and a nt sequence encoding rat UBE3A. WO608 teaches (p. 14 L5-15) their animal model can be used to test the efficacy of an agent for treating AS. WO608 teaches (p. 16 L20-23) such agents may be coupled to a cell-penetrating peptide (CPP) such as a TAT protein, to facilitate cellular intake and/or delivery to the brain. WO608’s SEQ ID NO 3 the sequence for rat UBE3A and is 100% identical to claimed SEQ ID NO 1, and WO608’s SEQ ID NO 4 is 100% identical to a nt sequence encoding claimed SEQ ID NO 1, as shown by the following alignments: RESULT 1 BFE56236 (NOTE: this sequence has 1 duplicate in the database searched. See complete list at the end of this report) ID BFE56236 standard; protein; 868 AA. XX AC BFE56236; XX DT 13-MAR-2025 (revised) DT 31-MAY-2018 (first entry) XX DE Rat ubiquitin ligase E3A protein, SEQ ID 3. XX KW CRISPR-Cas9 system; Genome editing; UBE3A protein; Ubiquitin ligase E3A; KW Ubiquitin-protein ligase E3A; angelman syndrome; animal disease model; KW drug screening; transgenic animal. XX OS Rattus norvegicus. XX CC PN WO2018067608-A2. XX CC PD 12-APR-2018. XX CC PF 03-OCT-2017; 2017WO-US054992. XX PR 03-OCT-2016; 2016US-0403463P. XX CC PA (UYSF ) UNIV SOUTH FLORIDA. CC PA (UTAM ) UNIV TEXAS A & M SYSTEM. CC PA (REGC ) UNIV CALIFORNIA. XX CC PI Weeber EJ, Segal DJ, Ogeen H, Pyles B, Dindot SV; XX DR WPI; 2018-28640E/29. DR N-PSDB; BFE56237. DR REFSEQ; NP_001178766, XP_341868. DR NCBI; Gi300797458. XX CC PT Non-human animal for assessing effect of agent on animal model, comprises CC PT cell having genome that lacks entire E3 ubiquitin ligase gene, where CC PT animal exhibits physicological features associated with Angelman CC PT Syndrome. XX CC PS Disclosure; SEQ ID NO 3; 76pp; English. XX CC The present invention relates to a non-human animal, useful for assessing CC the effect of an agent on an animal model. The non-human animal comprises CC a cell having a genome that lacks the entire E3 ubiquitin ligase (Ube3a) CC gene which is produced by a clustered regularly interspaced short CC palindromic repeat (CRISPR) associated 9 (CAS9) system. The invention CC also includes: (1) a cell, a tissue or an organ isolated from the non- CC human animal; and (2) a method for assessing the effect of an agent on an CC animal model. The animal of the invention is useful for exhibiting CC physiological features associated with Angelman Syndrome. The present CC sequence is a rat ubiquitin-protein ligase E3A, whose encoded gene is CC used as a target for assessing the effect of an agent on an animal model. CC CC Revised record issued on 07-MAR-2025 : Correction to comments. XX SQ Sequence 868 AA; Query Match 100.0%; Score 4504; Length 868; Best Local Similarity 100.0%; Matches 868; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MATACKRSSGESQSEDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTFLR 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MATACKRSSGESQSEDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTFLR 60 Qy 61 MDNNAAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGASNNSEIKMNKKEEFKEVDY 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 MDNNAAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGASNNSEIKMNKKEEFKEVDY 120 Qy 121 LTEEKVYEIYEFCREREDYSPLIRVIGRIFSSAEALVQSFRKVKQHTKEELKSLQEKDED 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 LTEEKVYEIYEFCREREDYSPLIRVIGRIFSSAEALVQSFRKVKQHTKEELKSLQEKDED 180 Qy 181 KDEDEKEKAACSAAAMEEDSEASSSRMGDSSQGDNNVQKLGPDDVTVDIDAIRRVYSSLL 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 KDEDEKEKAACSAAAMEEDSEASSSRMGDSSQGDNNVQKLGPDDVTVDIDAIRRVYSSLL 240 Qy 241 SDEKIETAFLNALVYLSPNVECDLTYHNVYTRDPNYLNLFIIVMENRNLHSPEYLEMALP 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 SDEKIETAFLNALVYLSPNVECDLTYHNVYTRDPNYLNLFIIVMENRNLHSPEYLEMALP 300 Qy 301 LFCKAMSKLPLAAQGKLIRLWSKYSADQIRRMMETFQQLITYKVISNEFNSRNLVNDDDA 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 LFCKAMSKLPLAAQGKLIRLWSKYSADQIRRMMETFQQLITYKVISNEFNSRNLVNDDDA 360 Qy 361 IVAASKCLKMVYYANVVGGDVDTNHNEEDDEEPIPESSELTLQELLGEERRNKKGPRVDP 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 IVAASKCLKMVYYANVVGGDVDTNHNEEDDEEPIPESSELTLQELLGEERRNKKGPRVDP 420 Qy 421 LETEIGVKTLDCRKPLISFEEFINEPLNDVLEMDKDYTFFKVETENKFSFMTCPFILNAV 480 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 421 LETEIGVKTLDCRKPLISFEEFINEPLNDVLEMDKDYTFFKVETENKFSFMTCPFILNAV 480 Qy 481 TKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRLEMIAMEN 540 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 481 TKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRLEMIAMEN 540 Qy 541 PADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDEATRLFWFNPSSFE 600 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 541 PADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDEATRLFWFNPSSFE 600 Qy 601 TEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFCDLGDSHPILYQSLKDLLE 660 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 601 TEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFCDLGDSHPILYQSLKDLLE 660 Qy 661 YEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVSLYSDYILNKSVE 720 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 661 YEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVSLYSDYILNKSVE 720 Qy 721 KQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRESVVI 780 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 721 KQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRESVVI 780 Qy 781 REFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNVL 840 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 781 REFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNVL 840 Qy 841 LLPEYSSKEKLKERLLKAITYAKGFGML 868 SEQ ID NO 1 |||||||||||||||||||||||||||| Db 841 LLPEYSSKEKLKERLLKAITYAKGFGML 868 WO608 SEQ ID NO 3 RESULT 1 BFE56237 ID BFE56237 standard; DNA; 5795 BP. XX AC BFE56237; XX DT 13-MAR-2025 (revised) DT 31-MAY-2018 (first entry) XX DE Rat ubiquitin ligase E3A mRNA, SEQ ID 4. XX KW CRISPR-Cas9 system; Genome editing; UBE3A gene; Ubiquitin ligase E3A; KW Ubiquitin-protein ligase E3A; angelman syndrome; animal disease model; KW drug screening; gene; ss; transgenic animal. XX OS Rattus norvegicus. XX FH Key Location/Qualifiers FT CDS 671..3277 FT /*tag= a FT /product= "Ubiquitin ligase E3A" XX CC PN WO2018067608-A2. XX CC PD 12-APR-2018. XX CC PF 03-OCT-2017; 2017WO-US054992. XX PR 03-OCT-2016; 2016US-0403463P. XX CC PA (UYSF ) UNIV SOUTH FLORIDA. CC PA (UTAM ) UNIV TEXAS A & M SYSTEM. CC PA (REGC ) UNIV CALIFORNIA. XX CC PI Weeber EJ, Segal DJ, Ogeen H, Pyles B, Dindot SV; XX DR WPI; 2018-28640E/29. DR P-PSDB; BFE56236. DR REFSEQ; NM_001191837, XM_341867. DR NCBI; Gi394025712. XX CC PT Non-human animal for assessing effect of agent on animal model, comprises CC PT cell having genome that lacks entire E3 ubiquitin ligase gene, where CC PT animal exhibits physicological features associated with Angelman CC PT Syndrome. XX CC PS Disclosure; SEQ ID NO 4; 76pp; English. XX CC The present invention relates to a non-human animal, useful for assessing CC the effect of an agent on an animal model. The non-human animal comprises CC a cell having a genome that lacks the entire E3 ubiquitin ligase (Ube3a) CC gene which is produced by a clustered regularly interspaced short CC palindromic repeat (CRISPR) associated 9 (CAS9) system. The invention CC also includes: (1) a cell, a tissue or an organ isolated from the non- CC human animal; and (2) a method for assessing the effect of an agent on an CC animal model. The animal of the invention is useful for exhibiting CC physiological features associated with Angelman Syndrome. The present CC sequence is a rat ubiquitin-protein ligase E3A mRNA, used as a target for CC assessing the effect of an agent on an animal model. CC CC Revised record issued on 07-MAR-2025 : Correction to comments. XX SQ Sequence 5795 BP; 1799 A; 1038 C; 1221 G; 1737 T; 0 U; 0 Other; Alignment Scores: Length: 5795 Score: 4504.00 Matches: 868 Percent Similarity: 100.0% Conservative: 0 Best Local Similarity: 100.0% Mismatches: 0 Query Match: 100.0% Indels: 0 Gaps: 0 US-18-392-696-1 (1-868) x BFE56237 (1-5795) Qy 1 MetAlaThrAlaCysLysArgSerSerGlyGluSerGlnSerGluAspIleGluAlaSer 20 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 671 ATGGCCACAGCTTGTAAAAGATCATCAGGAGAATCCCAGTCTGAGGACATTGAAGCTAGC 730 Qy 21 ArgMetLysArgAlaAlaAlaLysHisLeuIleGluArgTyrTyrHisGlnLeuThrGlu 40 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 731 CGAATGAAGCGAGCAGCTGCAAAGCATCTAATAGAGCGCTACTACCATCAGTTAACTGAG 790 Qy 41 GlyCysGlyAsnGluAlaCysThrAsnGluPheCysAlaSerCysProThrPheLeuArg 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 791 GGCTGTGGAAATGAGGCCTGCACGAATGAGTTCTGTGCTTCCTGTCCAACTTTTCTTCGT 850 Qy 61 MetAspAsnAsnAlaAlaAlaIleLysAlaLeuGluLeuTyrLysIleAsnAlaLysLeu 80 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 851 ATGGATAACAATGCAGCAGCTATTAAAGCTCTTGAGCTTTATAAAATTAATGCAAAACTC 910 Qy 81 CysAspProHisProSerLysLysGlyAlaSerSerAlaTyrLeuGluAsnSerLysGly 100 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 911 TGTGATCCTCATCCCTCCAAGAAAGGAGCAAGCTCAGCTTACCTTGAGAACTCAAAAGGT 970 Qy 101 AlaSerAsnAsnSerGluIleLysMetAsnLysLysGluGluPheLysGluValAspTyr 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 971 GCATCTAACAACTCAGAGATAAAAATGAACAAGAAGGAAGAGTTTAAAGAGGTGGACTAC 1030 Qy 121 LeuThrGluGluLysValTyrGluIleTyrGluPheCysArgGluArgGluAspTyrSer 140 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1031 CTAACTGAAGAGAAAGTATATGAAATTTATGAATTTTGTAGGGAGAGAGAGGATTACTCC 1090 Qy 141 ProLeuIleArgValIleGlyArgIlePheSerSerAlaGluAlaLeuValGlnSerPhe 160 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1091 CCTTTAATTCGTGTAATTGGAAGAATATTTTCTAGTGCTGAGGCACTGGTTCAGAGCTTT 1150 Qy 161 ArgLysValLysGlnHisThrLysGluGluLeuLysSerLeuGlnGluLysAspGluAsp 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1151 CGGAAAGTCAAACAGCACACTAAGGAGGAATTGAAATCTCTTCAAGAGAAGGATGAAGAC 1210 Qy 181 LysAspGluAspGluLysGluLysAlaAlaCysSerAlaAlaAlaMetGluGluAspSer 200 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1211 AAGGATGAAGATGAAAAGGAAAAAGCTGCGTGTTCTGCTGCTGCTATGGAAGAAGACTCA 1270 Qy 201 GluAlaSerSerSerArgMetGlyAspSerSerGlnGlyAspAsnAsnValGlnLysLeu 220 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1271 GAAGCATCTTCTTCAAGGATGGGTGATAGCTCACAGGGAGACAACAATGTACAAAAATTA 1330 Qy 221 GlyProAspAspValThrValAspIleAspAlaIleArgArgValTyrSerSerLeuLeu 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1331 GGTCCTGATGATGTGACTGTGGATATTGATGCTATAAGAAGGGTCTACAGCAGTTTGCTC 1390 Qy 241 SerAspGluLysIleGluThrAlaPheLeuAsnAlaLeuValTyrLeuSerProAsnVal 260 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1391 TCTGATGAAAAAATAGAAACTGCCTTCCTGAATGCACTTGTATATCTGTCACCTAACGTG 1450 Qy 261 GluCysAspLeuThrTyrHisAsnValTyrThrArgAspProAsnTyrLeuAsnLeuPhe 280 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1451 GAATGTGATTTGACATATCATAATGTGTACACTCGAGACCCTAATTATCTCAATTTGTTC 1510 Qy 281 IleIleValMetGluAsnArgAsnLeuHisSerProGluTyrLeuGluMetAlaLeuPro 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1511 ATTATTGTAATGGAAAATAGGAATCTCCACAGTCCTGAATATCTGGAAATGGCATTGCCG 1570 Qy 301 LeuPheCysLysAlaMetSerLysLeuProLeuAlaAlaGlnGlyLysLeuIleArgLeu 320 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1571 TTATTTTGCAAAGCTATGAGTAAGCTACCCCTTGCAGCTCAAGGAAAACTGATTAGGCTG 1630 Qy 321 TrpSerLysTyrSerAlaAspGlnIleArgArgMetMetGluThrPheGlnGlnLeuIle 340 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1631 TGGTCTAAATACAGTGCTGACCAGATTCGGAGAATGATGGAAACATTTCAGCAACTTATT 1690 Qy 341 ThrTyrLysValIleSerAsnGluPheAsnSerArgAsnLeuValAsnAspAspAspAla 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1691 ACCTACAAAGTCATAAGCAATGAATTTAATAGCCGAAATCTAGTGAATGATGATGATGCC 1750 Qy 361 IleValAlaAlaSerLysCysLeuLysMetValTyrTyrAlaAsnValValGlyGlyAsp 380 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1751 ATTGTTGCTGCTTCAAAGTGTTTGAAAATGGTTTACTATGCAAATGTAGTGGGAGGGGAC 1810 Qy 381 ValAspThrAsnHisAsnGluGluAspAspGluGluProIleProGluSerSerGluLeu 400 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1811 GTGGACACAAATCATAATGAGGAAGATGATGAAGAGCCTATACCTGAGTCCAGTGAATTG 1870 Qy 401 ThrLeuGlnGluLeuLeuGlyGluGluArgArgAsnLysLysGlyProArgValAspPro 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1871 ACACTTCAGGAGCTTCTGGGAGAGGAAAGAAGAAATAAGAAAGGTCCTCGAGTGGATCCA 1930 Qy 421 LeuGluThrGluIleGlyValLysThrLeuAspCysArgLysProLeuIleSerPheGlu 440 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1931 CTAGAAACCGAAATTGGCGTTAAAACTCTAGATTGTCGAAAACCACTTATCTCCTTTGAA 1990 Qy 441 GluPheIleAsnGluProLeuAsnAspValLeuGluMetAspLysAspTyrThrPhePhe 460 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1991 GAATTCATTAATGAACCACTGAATGATGTTCTAGAAATGGACAAAGATTATACTTTTTTC 2050 Qy 461 LysValGluThrGluAsnLysPheSerPheMetThrCysProPheIleLeuAsnAlaVal 480 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2051 AAAGTTGAAACAGAGAACAAATTCTCTTTTATGACATGTCCCTTTATATTGAATGCTGTC 2110 Qy 481 ThrLysAsnLeuGlyLeuTyrTyrAspAsnArgIleArgMetTyrSerGluArgArgIle 500 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2111 ACAAAGAATCTGGGATTGTATTATGACAATAGAATTCGCATGTACAGTGAAAGAAGAATC 2170 Qy 501 ThrValLeuTyrSerLeuValGlnGlyGlnGlnLeuAsnProTyrLeuArgLeuLysVal 520 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2171 ACTGTTCTTTACAGCCTAGTTCAAGGACAGCAGTTGAATCCATATTTGAGACTTAAAGTC 2230 Qy 521 ArgArgAspHisIleIleAspAspAlaLeuValArgLeuGluMetIleAlaMetGluAsn 540 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2231 AGACGTGACCATATTATAGATGATGCACTTGTCCGGCTAGAGATGATCGCTATGGAAAAT 2290 Qy 541 ProAlaAspLeuLysLysGlnLeuTyrValGluPheGluGlyGluGlnGlyValAspGlu 560 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2291 CCTGCAGACTTGAAGAAACAGTTGTATGTGGAATTTGAAGGAGAACAAGGAGTAGATGAG 2350 Qy 561 GlyGlyValSerLysGluPhePheGlnLeuValValGluGluIlePheAsnProAspIle 580 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2351 GGAGGCGTTTCCAAAGAGTTTTTTCAGTTGGTTGTGGAGGAAATCTTTAATCCAGATATT 2410 Qy 581 GlyMetPheThrTyrAspGluAlaThrArgLeuPheTrpPheAsnProSerSerPheGlu 600 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2411 GGTATGTTCACATACGATGAAGCTACAAGATTATTTTGGTTTAATCCATCTTCTTTTGAA 2470 Qy 601 ThrGluGlyGlnPheThrLeuIleGlyIleValLeuGlyLeuAlaIleTyrAsnAsnCys 620 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2471 ACTGAGGGTCAATTTACTCTGATTGGCATAGTCCTGGGTCTGGCTATTTACAATAACTGT 2530 Qy 621 IleLeuAspValHisPheProMetValValTyrArgLysLeuMetGlyLysLysGlyThr 640 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2531 ATACTGGATGTCCATTTTCCCATGGTTGTGTACAGGAAGCTAATGGGGAAAAAAGGAACG 2590 Qy 641 PheCysAspLeuGlyAspSerHisProIleLeuTyrGlnSerLeuLysAspLeuLeuGlu 660 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2591 TTTTGTGACTTGGGAGACTCTCACCCAATCTTATATCAGAGTTTAAAGGATTTATTGGAA 2650 Qy 661 TyrGluGlyAsnValGluAspAspMetMetIleThrPheGlnIleSerGlnThrAspLeu 680 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2651 TATGAAGGGAATGTGGAAGATGATATGATGATCACTTTCCAGATATCACAGACAGATCTT 2710 Qy 681 PheGlyAsnProMetMetTyrAspLeuLysGluAsnGlyAspLysIleProIleThrAsn 700 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2711 TTTGGTAACCCAATGATGTATGATCTAAAAGAAAATGGTGATAAAATTCCAATTACAAAT 2770 Qy 701 GluAsnArgLysGluPheValSerLeuTyrSerAspTyrIleLeuAsnLysSerValGlu 720 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2771 GAAAACAGGAAGGAATTTGTCAGTCTCTATTCAGACTACATTCTCAATAAATCTGTAGAA 2830 Qy 721 LysGlnPheLysAlaPheArgArgGlyPheHisMetValThrAsnGluSerProLeuLys 740 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2831 AAACAATTCAAGGCATTTCGCAGAGGTTTTCATATGGTGACTAATGAATCACCCTTAAAA 2890 Qy 741 TyrLeuPheArgProGluGluIleGluLeuLeuIleCysGlySerArgAsnLeuAspPhe 760 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2891 TACTTATTCAGACCAGAAGAAATTGAATTACTTATATGTGGAAGCCGGAATCTCGATTTC 2950 Qy 761 GlnAlaLeuGluGluThrThrGluTyrAspGlyGlyTyrThrArgGluSerValValIle 780 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 2951 CAGGCACTAGAAGAAACTACAGAGTATGATGGTGGCTATACGAGAGAATCTGTTGTGATT 3010 Qy 781 ArgGluPheTrpGluIleValHisSerPheThrAspGluGlnLysArgLeuPheLeuGln 800 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 3011 AGGGAGTTCTGGGAAATTGTTCATTCGTTTACAGATGAACAGAAAAGACTTTTCCTGCAG 3070 Qy 801 PheThrThrGlyThrAspArgAlaProValGlyGlyLeuGlyLysLeuLysMetIleIle 820 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 3071 TTTACAACAGGCACAGACAGAGCACCTGTTGGAGGACTCGGAAAATTGAAGATGATTATA 3130 Qy 821 AlaLysAsnGlyProAspThrGluArgLeuProThrSerHisThrCysPheAsnValLeu 840 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 3131 GCCAAAAATGGCCCAGACACAGAAAGGTTACCTACATCTCATACTTGCTTTAATGTCCTT 3190 Qy 841 LeuLeuProGluTyrSerSerLysGluLysLeuLysGluArgLeuLeuLysAlaIleThr 860 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 3191 TTACTTCCGGAATATTCAAGCAAAGAAAAACTTAAAGAGAGATTGCTGAAGGCCATCACA 3250 Qy 861 TyrAlaLysGlyPheGlyMetLeu 868 SEQ ID NO 1 |||||||||||||||||||||||| Db 3251 TATGCCAAAGGATTTGGCATGCTG 3274 WO608 SEQ ID NO 4 (nt encoding SEQ ID NO 1) (Note that WO608 is the WO version of US App752 which is cited on the IDS. The cited SEQ ID NOs also occur in App752.) Therefore, both the AA sequence that is claimed SEQ ID NO 1 and a nt sequence encoding that SEQ ID NO were known in the art before the effective filing date of the claimed invention. Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating AS of WO584 with the specific sequences encoding UBE3A of WO608 for the benefit of testing whether a vector encoding a human UBE3A sequence (i.e., SEQ ID NO 15 of WO584) or a vector encoding a rat UBE3A sequence (i.e., SEQ ID NO 4 of WO608) is better for treating AS in a rat model of WO608. One would have been motivated to do so with a reasonable expectation of success because WO608’s animal model lacks a specific UBE3A sequence, namely WO608 SEQ ID NO 4. After producing such animal model, an artisan would have wanted to test whether replacing the missing copy of UBE3A would treat AS. An artisan would have wanted to know whether WO608’s animal model lacking its native UBE3A sequence would exhibit any differences in treatment when administered a vector comprising that exact UBE3A sequence (i.e., WO608’s SEQ ID NO 4)or a UBE3A sequence similar to the UBE3A sequence it’s lacking (i.e., WO584’s SEQ ID NO 15). It would have been a simple matter to swap WO608’s sequence encoding rat UBE3A for the human UBE3A sequence in WO584’s vector. An artisan also would have wanted to test whether administering the vector comprising a UBE3A comprising a secretion sequence and a cell uptake sequence would have improved treatment outcomes in the AS model rats. They would have wanted to do so because WO584 teaches (§Abstract) a secretion sequence and a cell uptake sequence allow secretion from cells and uptake by neighboring cells and an artisan would have understood that could be beneficial because every cell will not necessarily be transduced with AAV, so the secretion/uptake sequence would increase the probability that any particular cell would receive some amount of UBE3A. They would have had a reasonable expectation of success because it would have been a simple matter to include additional sequences along with the rat UBE3A sequence, including because WO608 teaches (cited above) including a CPP sequence. Therefore, all the limitations of Claims 6-13 would have been obvious in view of WO584 and WO608. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 6-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11534500 (“US500”) in view of International Publication Number WO 2016/179584 (published on 10 November 2016, “WO584”, of record on IDS) and International Publication Number WO 2018/067608 (published on 12 April 2018, “WO608”). Although the claims at issue are not identical they are directed to overlapping subject matter because the instant claims are directed to methods of improving motor function in a patient with AS, the method comprising administering to the patient an AAV vector comprising a TIS, a UBE3A sequence downstream of the TIS, the UBE3A sequence comprising a sequence at least 80% identical to SEQ ID NO 1; a secretion sequence disposed downstream of the TIS but upstream of the UBE3A sequence, wherein the secretion sequence can comprise SEQ ID NO 3; and cell uptake sequence that can comprise SEQ ID NO 4. The instant claims recite additional components including a CMV chicken β-actin or human ubiquitin C promoter, a cytomegalovirus immediate-early enhancer sequence, and a woodchuck hepatitis post-transcriptional regulatory element. The patented US500 claims are directed to an AAV vector encoding UBE3A comprising a TIS, an UBE3A sequence, a secretion sequence, and a cell uptake sequence, and methods of using the vector to treat AS by injecting the vector to the brain, specifically the hippocampus or ventricle. The US500 claims recite additional elements including a CMV chicken β-actin or human ubiquitin C promoter, a cytomegalovirus immediate-early enhancer sequence, and a woodchuck hepatitis post-transcriptional regulatory element. The US500 claims recite different SEQ ID NOs than those instantly claimed. Both claim sets encompass AAV vectors that encode UBE3A, a TIS, a secretion sequence, and a cell uptake sequence, and other elements. The US500 claims don’t recite every element of the instant claims, but those would have been obvious in view of the prior art of WO584 (§Abstract, p. 3 L15-end, p. 6 L25-end, p. 13 L29-end, p. 9 L15-15; p. 16 L17, p. 10 L15-25, pp. 71-72 items #14-16, SEQ ID NOs 15 or a cDNA of SEQ ID NO 14, a secretion sequence that is SEQ ID NO 8, and a cell uptake sequence that is SEQ ID NO 4; p. 7 L1-20, p. 13 L20-30, p. 18 L9-12, p. 20 L24-35, Fig. 21, p. 16 L5-6, p. 9 L1-10, p. 9 L1-15, p. 10 L15-25, pp. 71-72 items #14-16) and WO608 (§Abstract, pp. 6-7 L29-10; SEQ ID NOs 3 and 4; p. 14 L5-15, p. 16 L20-23). It would have been obvious before the effective filing date of the claimed invention to modify the vector and methods of the US500 claims with the teachings of WO584 and WO608 for the benefit of using the vector to express rat UBE3A to treat rats of a rat model suffering from AS. One would have been motivated to do so with a reasonable expectation of success because they would have wanted to treat rats by administering AAV encoding rat UBE3A, and it would have been a simple matter to swap the known UBE3A sequence of WO608 for the sequence of the US500 claims. It would have been obvious to test various secretion sequences, including those of WO584, for the benefit of determining which results in the best treatment, and it would have been a simple matter to swap any known secretion sequence into the vector of the US500 claims. Therefore, the instant claims would have been obvious in view of the US500 claims, WO584, and WO608. Claims 6-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12734250 (“US250”) in view of WO584 and WO608. Although the claims at issue are not identical they are directed to overlapping subject matter because the instant claims are directed to methods of improving motor function in a patient with AS, the method comprising administering to the patient an AAV vector comprising a TIS, a UBE3A sequence downstream of the TIS, the UBE3A sequence comprising a sequence at least 80% identical to SEQ ID NO 1; a secretion sequence disposed downstream of the TIS but upstream of the UBE3A sequence, wherein the secretion sequence can comprise SEQ ID NO 3; and cell uptake sequence that can comprise SEQ ID NO 4. The instant claims recite additional components including a CMV chicken β-actin or human ubiquitin C promoter, a cytomegalovirus immediate-early enhancer sequence, and a woodchuck hepatitis post-transcriptional regulatory element. The patented US250 claims are directed to an AAV vector encoding UBE3A comprising a TIS that is a CMV chicken β-actin or human ubiquitin C promoter, an UBE3A sequence that can be SEQ ID NO 7 or 14 and is downstream of the TIS, a secretion sequence that can be SEQ ID NO 8 and is disposed downstream of the TIS and upstream of the UBE3A sequence, and a cell uptake sequence that can be SEQ ID NO 4 and is downstream of the TIS and between the secretion sequence and the UBE3A sequence, and methods of using the vector to treat AS by injecting the vector to the brain, specifically the hippocampus or ventricle. The US250 claims recite additional elements including a cytomegalovirus immediate-early enhancer sequence and a woodchuck hepatitis post-transcriptional regulatory element. US250’s claimed UBE3A SEQ ID NOs 7 and 14 are at least 80% identical to claimed SEQ ID NO 1. US250’s claimed secretion SEQ ID NO 8 is 100% identical to claimed SEQ ID NO 3. US250’s claimed cell uptake sequence SEQ ID NO 4 is 100% identical to claimed SEQ ID NO 4. Both claim sets encompass AAV vectors that encode UBE3A, a TIS, a secretion sequence, and a cell uptake sequence, and other elements. The US250 claims make obvious the instant claims and instantly claimed SEQ ID NOs. Therefore, the instant claims would have been obvious in view of the US250 claims. Although the US250 claims don’t recite a sequence that is exactly claimed SEQ ID NO 1, and don’t explicitly recite improving motor function, those limitations would have been obvious in view of the prior art of WO584 (§Abstract, p. 3 L15-end, p. 6 L25-end, p. 13 L29-end, p. 9 L15-15; p. 16 L17, p. 10 L15-25, pp. 71-72 items #14-16, SEQ ID NOs 15 or a cDNA of SEQ ID NO 14, a secretion sequence that is SEQ ID NO 8, and a cell uptake sequence that is SEQ ID NO 4; p. 7 L1-20, p. 13 L20-30, p. 18 L9-12, p. 20 L24-35, Fig. 21, p. 16 L5-6, p. 9 L1-10, p. 9 L1-15, p. 10 L15-25, pp. 71-72 items #14-16) and WO608 (§Abstract, pp. 6-7 L29-10; SEQ ID NOs 3 and 4; p. 14 L5-15, p. 16 L20-23). It would have been obvious before the effective filing date of the claimed invention to modify the vector and methods of the US250 claims with the teachings of WO584 and WO608 for the benefit of using the vector to express rat UBE3A to treat rats of a rat model suffering from AS and to improve motor function in those rats. One would have been motivated to do so with a reasonable expectation of success because they would have wanted to treat rats by administering AAV encoding rat UBE3A, and it would have been a simple matter to swap the known UBE3A sequence of WO608 for the sequence of the US250 claims. It would have been obvious to use the methods to improve motor function because WO584 teaches motor dysfunction is a symptom of AS. Therefore, the instant claims would have been obvious in view of the US250 claims, WO584, and WO608. Claims 6-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-20 of copending Application No. 17439140 (“App140”) in view of WO584 and WO608. Although the claims at issue are not identical they are directed to overlapping subject matter because the instant claims are directed to methods of improving motor function in a patient with AS, the method comprising administering to the patient an AAV vector comprising a TIS, a UBE3A sequence downstream of the TIS, the UBE3A sequence comprising a sequence at least 80% identical to SEQ ID NO 1; a secretion sequence disposed downstream of the TIS but upstream of the UBE3A sequence, wherein the secretion sequence can comprise SEQ ID NO 3; and cell uptake sequence that can comprise SEQ ID NO 4. The instant claims recite additional components including a CMV chicken β-actin or human ubiquitin C promoter, a cytomegalovirus immediate-early enhancer sequence, and a woodchuck hepatitis post-transcriptional regulatory element. The copending App140 claims are directed to an AAV vector encoding UBE3A comprising a promoter that can be a CMV chicken β-actin or human ubiquitin C promoter, an UBE3A sequence that can be SEQ ID NO 4 and is downstream of the promoter, and methods of using the vector to treat AS by injecting the vector to the brain, specifically the hippocampus or ventricle. The App140 claims recite that the vector lacks a secretion sequence. App140’s claimed UBE3A SEQ ID NO 4 is at least 80% identical to claimed SEQ ID NO 1. Both claim sets encompass AAV vectors that encode UBE3A and other elements. The instant claims recite additional elements and require a secretion sequence. However, all the limitations of the instant claims would have been obvious in view of the prior art of WO584 (§Abstract, p. 3 L15-end, p. 6 L25-end, p. 13 L29-end, p. 9 L15-15; p. 16 L17, p. 10 L15-25, pp. 71-72 items #14-16, SEQ ID NOs 15 or a cDNA of SEQ ID NO 14, a secretion sequence that is SEQ ID NO 8, and a cell uptake sequence that is SEQ ID NO 4; p. 7 L1-20, p. 13 L20-30, p. 18 L9-12, p. 20 L24-35, Fig. 21, p. 16 L5-6, p. 9 L1-10, p. 9 L1-15, p. 10 L15-25, pp. 71-72 items #14-16) and WO608 (§Abstract, pp. 6-7 L29-10; SEQ ID NOs 3 and 4; p. 14 L5-15, p. 16 L20-23). It would have been obvious before the effective filing date of the claimed invention to modify the vector and methods of the App140 claims with the teachings of WO584 and WO608 for the benefits of using the vector to express rat UBE3A to treat rats of a rat model suffering from AS and improving motor function in those rats, and the benefit of testing whether and how much motor function is improved by including the secretion sequence. One would have been motivated to do so with a reasonable expectation of success because they would have wanted to treat rats by administering AAV encoding rat UBE3A, and it would have been a simple matter to swap the known UBE3A sequence of WO608 for the sequence of the App140 claims. It would have been obvious to use the methods to improve motor function because WO584 teaches motor dysfunction is a symptom of AS. One would have wanted to include the secretion sequence and cell uptake sequence because WO584 teaches those elements allow the UBE3A protein to be secreted and taken up by neighboring cells and an artisan would have wanted to test whether or not including those elements would have any bearing on improving motor function in an AS patient. Therefore, the instant claims would have been obvious in view of the App140 claims, WO584, and WO608. This is a provisional nonstatutory double patenting rejection. Claims 6-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 16-20 of copending Application No. 18112879 (“App879”) in view of WO584 and WO608. Although the claims at issue are not identical they are directed to overlapping subject matter because the instant claims are directed to methods of improving motor function in a patient with AS, the method comprising administering to the patient an AAV vector comprising a TIS, a UBE3A sequence downstream of the TIS, the UBE3A sequence comprising a sequence at least 80% identical to SEQ ID NO 1; a secretion sequence disposed downstream of the TIS but upstream of the UBE3A sequence, wherein the secretion sequence can comprise SEQ ID NO 3; and cell uptake sequence that can comprise SEQ ID NO 4. The instant claims recite additional components including a CMV chicken β-actin or human ubiquitin C promoter, a cytomegalovirus immediate-early enhancer sequence, and a woodchuck hepatitis post-transcriptional regulatory element. The copending App879 claims are directed to methods of treating a tauopathy characterized by a UBE3A deficiency, the method comprising administering a vector encoding UBE3A, comprising a TIS that can be a CMV chicken β-actin or human ubiquitin C promoter, an UBE3A sequence that can be SEQ ID NO 17 and is downstream of the TIS, a secretion signal peptide that is disposed downstream of the TIS and upstream of the UBE3A sequence, and a cell penetrating peptide that is downstream of the TIS; wherein the methods include administering the vector to the brain, specifically the hippocampus or ventricle. The App879 claims recite additional elements including a cytomegalovirus immediate-early enhancer sequence and a woodchuck hepatitis post-transcriptional regulatory element. App879’s claimed UBE3A SEQ ID NO 17 is at least 80% identical to claimed SEQ ID NO 1. Both claim sets encompass AAV vectors that encode UBE3A, a TIS, a secretion sequence, and a cell uptake sequence, and other elements. The App879 do not teach every single limitation of the instant claims, including methods of treating AS. However, those limitations would have been obvious in view of the prior art of WO584 (§Abstract, p. 3 L15-end, p. 6 L25-end, p. 13 L29-end, p. 9 L15-15; p. 16 L17, p. 10 L15-25, pp. 71-72 items #14-16, SEQ ID NOs 15 or a cDNA of SEQ ID NO 14, a secretion sequence that is SEQ ID NO 8, and a cell uptake sequence that is SEQ ID NO 4; p. 7 L1-20, p. 13 L20-30, p. 18 L9-12, p. 20 L24-35, Fig. 21, p. 16 L5-6, p. 9 L1-10, p. 9 L1-15, p. 10 L15-25, pp. 71-72 items #14-16) and WO608 (§Abstract, pp. 6-7 L29-10; SEQ ID NOs 3 and 4; p. 14 L5-15, p. 16 L20-23). It would have been obvious before the effective filing date of the claimed invention to modify the methods of the App879 claims with the teachings of WO584 and WO608 for the benefit of using the methods to treat AS. One would have been motivated to do so with a reasonable expectation of success because the prior art teachings administering an AAV vector encoding UBE3A to treat AS, which is known be caused by a UBE3A deficiency. It would have been obvious to use an AAV vector because the cited art teaches doing so is routine. It would have been obvious to use the modified vector to express rat UBE3A to treat rats of a rat model suffering from AS. One would have been motivated to do so with a reasonable expectation of success because they would have wanted to treat rats by administering AAV encoding rat UBE3A, and it would have been a simple matter to swap the known UBE3A sequence of WO608 for the sequence of the App879 claims. It would have been obvious to test various secretion sequences and cell uptake sequences, including those of WO584, for the benefit of determining which results in the best treatment, and it would have been a simple matter to swap any known secretion or uptake sequence into the vector of the App879 claims. Therefore, the instant claims would have been obvious in view of the App879 claims, WO584, and WO608. Claims 6-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 19805965 (“App965”) in view of WO584 and WO608. Although the claims at issue are not identical they are directed to overlapping subject matter because the instant claims are directed to methods of improving motor function in a patient with AS, the method comprising administering to the patient an AAV vector comprising a TIS, a UBE3A sequence downstream of the TIS, the UBE3A sequence comprising a sequence at least 80% identical to SEQ ID NO 1; a secretion sequence disposed downstream of the TIS but upstream of the UBE3A sequence, wherein the secretion sequence can comprise SEQ ID NO 3; and cell uptake sequence that can comprise SEQ ID NO 4. The instant claims recite additional components including a CMV chicken β-actin or human ubiquitin C promoter, a cytomegalovirus immediate-early enhancer sequence, and a woodchuck hepatitis post-transcriptional regulatory element. The copending App965 claims are directed to a method of synthesizing an AAV vector encoding UBE3A comprising a TIS that is a CMV chicken β-actin or human ubiquitin C promoter, an UBE3A sequence that can be SEQ ID NOs 7 or 12-15 (or a sequence possessing at least 90% sequence identity thereto) and is downstream of the TIS, a secretion sequence that can be SEQ ID NO 8 and is disposed downstream of the TIS and upstream of the UBE3A sequence, and a cell uptake sequence that can be SEQ ID NO 4 and is downstream of the TIS and between the secretion sequence and the UBE3A sequence; and to a pharmaceutical composition for treating AS comprising the vector, wherein the composition is formulated for intracerebroventricular delivery. The App965 claims recite additional elements including a cytomegalovirus immediate-early enhancer sequence and a woodchuck hepatitis post-transcriptional regulatory element. App965’s claimed UBE3A SEQ ID NOs 7 and 12-15 are at least 80% identical to claimed SEQ ID NO 1. App965’s claimed secretion SEQ ID NO 8 is 100% identical to claimed SEQ ID NO 3. App965’s claimed cell uptake sequence SEQ ID NO 4 is 100% identical to claimed SEQ ID NO 4. Both claim sets encompass AAV vectors that encode UBE3A, a TIS, a secretion sequence, and a cell uptake sequence, and other elements. It would have been obvious to use the pharmaceutical compositions of App965 to treat AS because the App965 claims recite that is an intended use. The method of producing the vector of the App965 claims is required to use the instantly claimed method. Therefore, the instant claims would have been obvious in view of the App965 claims. Although the App965 claims don’t recite a sequence that is exactly claimed SEQ ID NO 1, and don’t explicitly recite improving motor function, those limitations would have been obvious in view of the prior art of WO584 (§Abstract, p. 3 L15-end, p. 6 L25-end, p. 13 L29-end, p. 9 L15-15; p. 16 L17, p. 10 L15-25, pp. 71-72 items #14-16, SEQ ID NOs 15 or a cDNA of SEQ ID NO 14, a secretion sequence that is SEQ ID NO 8, and a cell uptake sequence that is SEQ ID NO 4; p. 7 L1-20, p. 13 L20-30, p. 18 L9-12, p. 20 L24-35, Fig. 21, p. 16 L5-6, p. 9 L1-10, p. 9 L1-15, p. 10 L15-25, pp. 71-72 items #14-16) and WO608 (§Abstract, pp. 6-7 L29-10; SEQ ID NOs 3 and 4; p. 14 L5-15, p. 16 L20-23). It would have been obvious before the effective filing date of the claimed invention to modify the composition and methods of the App965 claims with the teachings of WO584 and WO608 for the benefit of using the vector to express rat UBE3A to treat rats of a rat model suffering from AS and to improve motor function in those rats. One would have been motivated to do so with a reasonable expectation of success because they would have wanted to treat rats by administering AAV encoding rat UBE3A, and it would have been a simple matter to swap the known UBE3A sequence of WO608 for the sequence of the App965 claims. It would have been obvious to use the methods to improve motor function because WO584 teaches motor dysfunction is a symptom of AS. Therefore, the instant claims would have been obvious in view of the App965 claims, WO584, and WO608. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Mishra (et al. 2019. Nano-LC based proteomic approach identifies that E6AP interacts with ENO1 and targets it for degradation in breast cancer cells. IUBMB Life 71:1896–1905). Mishra teaches that E6AP colocalizes with extracellular protein ENO1 at the cell surface. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUTHIE S ARIETI whose telephone number is (571)272-1293. The examiner can normally be reached M-Th 10AM-6PM, alternate Fridays 9AM-4PM (ET). 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, Ram R Shukla can be reached at (571)272-0735. 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. RUTHIE S ARIETI Examiner Art Unit 1635 /RUTH SOPHIA ARIETI/Examiner, Art Unit 1635 /NANCY J LEITH/Primary Examiner, Art Unit 1636