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 .
This action is in response to the papers filed on 07/17/2026. Claims 1-13, 16-18, 21-24, 35, 36, 39 and 40 are currently pending as per claims filed on 10/04/2024.
Applicant’s election of Group I, without traverse, of claims 1-13, 16, 35, 36, 39, and 40 in the reply filed on 07/17/2026 is acknowledged.
Therefore, claims 17, 18, and 21-24 are withdrawn from further consideration
pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no
allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 1-13, 16, 35, 36, 39, and 40 are subject to examination to which the following grounds of rejection are applicable. Claim 1 is an independent claim.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International
Application No. PCT/US2023/065364 filed on 04/05/2023, which claims priority to US Provisional Application No. 63/327,624 filed on 04/05/2022.
Thus, the earliest possible priority for the instant application is 04/05/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/13/2025 and 07/17/2026 were filed before the mailing date of the current office action. The submission is in compliance with the provisions of 37 CFR 1.97.
Accordingly, the information disclosure statement is being considered by the
examiner.
Claim Objections
Claim 12 is objected to because abbreviations such as SV40, hGH, BGH, rbGlob, CW3SL, and 2xSNRP should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4, 5-6, 13, 16, 35, and 36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 recites “wherein said viral vector comprises a nucleic acid sequence that can targeted by an anti-sense oligonucleotide (ASO).” It is unclear if the claim is intended to recite that the nucleic acid sequence can be targeted by an ASO or if the claim is intended to recite that the nucleic acid sequence can target an ASO. Appropriate correction is required.
Claim 4, 35, and 36 recite “Syngap1-exon14-20”. It is unclear what the meaning of exon14-20 are relative to. For example, it is unclear if exon14-20 means these exons have been removed or are the only exons present in the polypeptide. Appropriate correction is required.
Claims 5 and 6 use of the indefinite article “an” or 'a' in the expressions “amino acid sequence set forth in any one of SEQ ID NOs:7-11” or “a nucleic acid sequence set forth in any one of SEQ ID NOs: 1-6” which creates a lack of clarity. The use of said
indefinite article makes it unclear which portion of the sequence defined by SEQ ID NOS: 7-11 or 1-6 is encompassed by the claimed amino acid or nucleic acid. If the claims are directed to the entirety of the sequences defined by SEQ ID NOS: 7-11 or 1-6 , the definite article 'the' should be used in place of 'a' or “an”. Appropriate correction is requested.
Claim 16 is rejected for the recitation of “a sequence” for the reasons stated above.
Claim Rejections - 35 USC § 112 (a)
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1-13, 16, 35, 36, 39, and 40 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.
M.P.E.P. § 2163 recites, “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 (see i)(A), above), reduction to drawings (see
i)(B), above), 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 i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
Further, the written description inquiry is limited to that which is contained within the four corners of the specification, not the extent to which the skilled artisan, given his or her
knowledge of the art, would have considered it to expand with only routine
experimentation. See Ariad Pharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en banc); see also id. at 1352 (“[I]t is the specification itself that must
demonstrate possession A description that merely renders the invention obvious does
not satisfy the requirement.").
Claim 1 is directed to a large genus of viral vectors comprising a nucleic acid encoding a truncated Syngap1 polypeptide. The specification discloses 6 specific adeno-associated viral (AAV) vectors which comprise specific nucleic acid sequences which encode a Syngap1 polypeptide wherein the nucleic acid sequences are explicitly identified as SEQ ID NO: 1-6 and 22 (Table 2, page 11 of US application). Furthermore, the recited AAV vectors in the specification encode specifically AAV1 and SYNGAP1-B: α1, SYNGAP1-B: α2, SYNGAP1-B: β, and SYNGAP1-B: γ polypeptides (Table 2, page 11 of US application) and the AAV vectors comprised a CaMKIIα promoter (para 0071). Moreover, while the AAV-SYNGAP1 vector additionally comprises optimized ITR/3’ UTR elements, the only UTR disclosed is CW3SL and bGHpA (para 0071 and 0079). In regard to the truncated version of the Syngap1 polypeptide, the specification discloses the truncated versions of Syngap1 were comprised within a self-complementary AAV (scAAV) and the truncated version of Syngap1 is a version where exon 14-20 of SEQ ID NO: 1-6 and 22 are packaged into a scAAV with 3xFlag and two different poly-A signals (i.e UTRs) CW3SL and bGHpA (para 0079). Additionally, the example disclosed in the specification teaches truncated SYNGAP1-B: α1, SYNGAP1-B: α2, SYNGAP1-B: β, and SYNGAP1-B: γ (Table 3).
The specification does not disclose any viral vector comprising any nucleic acid which can encode a truncated Syngap1 polypeptide with the intended use of treating a mammal having or at risk of developing a SYNGAP I-associated neurodevelopmental disorder (NDD). The only viral vector described in the specification is an AAV which comprises a CaMKIIα promoter, CW3SL and bGHpA UTRs, and the nucleic acid sequences set forth in SEQ ID NO: 1-6 and 22 which encode the SYNGAP1 polypeptide set forth by SEQ ID NO: 7-11 and 23-26 (See table 2 and table 3). Similarly, the specification does not disclose that the truncated Syngap1 can be any truncation of Syngap1, rather the only truncation described is a polypeptide sequence which is encoded by a nucleic acid comprising exon 14-20 within the AAV vector (See Table 3). Additionally, claim 13 recites wherein said viral vector comprises a nucleic acid sequence that can targeted by an anti-sense oligonucleotide (ASO), however the specification only discloses 10 ASOs which target the Flag sequence of the SYNGAP1 that is exogenously expressed from the AAV vector, the junction between the Falg and SYNGAP1, and the codon-optimized regions of the SYNGAP1 cDNA (para 0074). These ASOs are structurally described by being encoded by nucleic acid sequences which are set forth in SEQ ID NO: 12-21 (See Table 1). Furthermore, the specification does not disclose that the ASOs are comprised within the AAV vector comprising the truncated SYNGAP1 nucleic acid sequence, or is the ASO is comprised within a separate vector.
Collectively, the disclosure does not indicate what structural features, besides the truncated Syngap 1 polypeptide identified by SEQ ID NOs recited, the CaMKIIα promoter recited, and the CW3SL and bGHpA UTRs, would display the claimed functional properties of the viral vector being able to encode a truncated Syngap1 polypeptide. Together, the disclosure lacks structural description to establish the relationship between a genus of structures and their ability to express encode the truncated Syngap1 polypeptide to treat a mammal having or at risk of developing a SYNGAP I-associated neurodevelopmental disorder (NDD). Furthermore, the disclosure lacks structural description to establish the relationship between the ASOs such that they can target the nucleic acid sequence comprised by the viral vector.
Structural features that could distinguish the viral vectors of the claimed genus from others not encompassed by the genus of polynucleotides are missing from the disclosure. No common structural attributes identify the members of the genus, other than the Syngap1 polypeptide being encoded from a nucleic acid sequence with exon 14-20 of SEQ ID NO: 1-6 and 22, and there is no indication of the relationship of the structure required for its claimed function of encoding a truncated Syngap1 polypeptide and the viral vectors comprising a nucleic acid sequence which can be targeted by an ASO. The broad and generic scope of the viral vectors (and their promoters, UTRs, and ITRs) that is necessary to encode the truncated Sypgap1 polypeptide and the viral vector capable of being targeted by any ASO, renders the viral vectors as being unpredictable. An adequate description of the materials, which provide the means for practicing the invention, i.e. viral vector which encodes a truncated Syngap1 and capable of being targeted by any ASO, is required.
Claim Interpretation
Claim 13 is interpreted as the viral vector comprises a nucleic acid sequence that can be targeted by an ASO.
Claim Rejections - 35 USC § 102
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.
Claim 1, 7, and 13 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Michaud et al (US 20130065238 A1; as cited in IDS).
Regarding claim 1, Michaud teaches vectors, which can be plasmid vectors or viral vectors (para 0068 and 0123) comprising part (i.e. truncated) of the DNA molecule encoding Syngap1 polypeptide (para 0068-0069), hence Michaud anticipates a viral vector comprising a nucleic acid encoding a truncated Syngap1 polypeptide.
Regarding claim 7, Michaud anticipates claim 1. Moreover, Michaud teaches that the viral vectors (para 0068 and 0123) comprising part (i..e truncated) of the DNA molecule encoding Syngap1 polypeptide can comprise regulatory elements required for expression which can include promoters (i.e. operably linked to permit or facilitate expression of the truncated Syngap1 polypeptide as defined in the specification of the instant application). Hence, Michaud anticipates wherein said nucleic acid encoding said truncated Syngap 1 polypeptide is operably linked to a promoter.
Regarding claim 13, wherein said viral vector comprises a nucleic acid sequence that can targeted by an antisense-oligonucleotide (ASO), the recitation of “that can targeted by an anti-sense oligonucleotide (ASO)” is an intended use of said nucleic acid seqeunce, it is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
It is also noted that, if the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d. As such the functional limitations would be present in the identical nucleic acid sequence taught by Michaud et al and would therefore elicit the effect of being targeted by an ASO.
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.
Claims 1-3, 5-11, 39 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Michaud et al (US 20130065238 A1; as cited in IDS) and further in view of Edna Au et al (Frontiers in Medicine, 2022, pages 1-14), Huganir et al (US 6723838 B1; as cited in IDS), and Aznarez et al (US 20220290142 A1).
Regarding claim 1, Michaud teaches vectors, which can be plasmid vectors or viral vectors (para 0068 and 0123) comprising part (i..e truncated) of the DNA molecule encoding Syngap1 polypeptide (para 0068-0069), hence Michaud anticipates a viral vector comprising a nucleic acid encoding a truncated Syngap1 polypeptide.
Regarding claim 2, 3, 39, and 40, the teachings of Michaud teach claim 1. Michaud also teaches that Syngap1 gene is a causal gene for a large fraction of non-syndromic mental retardation (NSMR) and is selectively expressed in the brain (para 0004-0005). Michaud also teaches the genomic, cDNA and protein sequences of SYNGAP1 can be used in a variety of methods for developing therapies for treatment of disease (para 0027) and the nucleic acid encoding the wild-type Syngap1 polypeptide could be used in a method of gene therapy, to treat a human subject who is unable to synthesize the active protein to normal levels, thereby restoring normal Syngap1 function(s) (para 0122).
Michaud does not teach that the viral vector is a species selected from the group recited in claim 2, is an AAV vector (claim 3), is a species selected from the group recited in claim 39 and is a self-complementary AAV vector (scAAV) (claim 40).
However, one of ordinary skill in the art would have considered the teachings of
Edna Au as this reference is analogous prior art pertaining to the use of AAVs, scAAVs, and use of AAV1 for treating neurological diseases.
Edna Au teaches that gene therapies, which can utilize AAV vectors, can be used to add or overexpress a therapeutic gene or synthetic construct (page 1, para 1).
Edna Au teaches that, to overcome the problem of needing to convert the AAV single strand DNA into double strand DNA (dsDNA), one can use scAAV vectors as they contain a dimeric inverted repeat genome that allows folding into dsDNA (page 2, left col, para 1). Edna Au also teaches that AAV1 is most frequently used for neuromuscular disorders (page 5, right col, para 2).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of a viral vector encoding a truncated Syngap1 polypeptide taught by Michaud such that the viral vector was specifically an AAV vector, and more specifically an scAAV and an AAV1 vector. One would be motivated to make this modification since Edna Au taught that AAV vectors are used to introduce expression of genes as a therapeutic, scAAVs have advantages over AAVs, and AAV1 is used for neuromuscular disorders, and Syngap1 is associated with neuromuscular disorders. Thus, the combined teachings would generate an AAV1 vector that could express a truncated Syngap1 polypeptide as a therapeutic and have a reasonable expectation of success since AAVs and vectors which express truncated Syngap1 polypeptides exist in the art.
Regarding claim 5, the teachings of Michaud teach claim 1.
Michaud does not teach wherein said truncated Syngap1 polypeptide comprises an amino acid sequence set forth in any one of SEQ ID NOs: 7-11 or SEQ ID NOs: 23-26.
Huganir teaches the amino acid sequence of SYNGAP (of SEQ ID NO: 21 of 1135 in length with 100% identity to instant application SEQ ID NO: 11 of SYNGAP. See alignment below.
Qy = Instant application SEQ ID NO: 11, Db = Huganir SEQ ID NO: 21
Query Match 100.0%; Score 2862; Length 1135;
Best Local Similarity 100.0%;
Matches 546; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LNSSIDLQSFMARGLNSSMDMARLPSPTKEKPPPPPPGGGKDLFYVSRPPLARSSPAYCT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 590 LNSSIDLQSFMARGLNSSMDMARLPSPTKEKPPPPPPGGGKDLFYVSRPPLARSSPAYCT 649
Qy 61 SSSDITEPEQKMLSVNKSVSMLDLQGDGPGGRLNSSSVSNLAAVGDLLHSSQASLTAALG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 650 SSSDITEPEQKMLSVNKSVSMLDLQGDGPGGRLNSSSVSNLAAVGDLLHSSQASLTAALG 709
Qy 121 LRPAPAGRLSQGSGSSITAAGMRLSQMGVTTDGVPAQQLRIPLSFQNPLFHMAADGPGPP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 710 LRPAPAGRLSQGSGSSITAAGMRLSQMGVTTDGVPAQQLRIPLSFQNPLFHMAADGPGPP 769
Qy 181 AGHGGSSGHGPPSSHHHHHHHHHHRGGEPPGDTFAPFHGYSKSEDLSTGVPKPPAASILH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 770 AGHGGSSGHGPPSSHHHHHHHHHHRGGEPPGDTFAPFHGYSKSEDLSTGVPKPPAASILH 829
Qy 241 SHSYSDEFGPSGTDFTRRQLSLQDNLQHMLSPPQITIGPQRPAPSGPGGGSGGGSGGGGG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 830 SHSYSDEFGPSGTDFTRRQLSLQDNLQHMLSPPQITIGPQRPAPSGPGGGSGGGSGGGGG 889
Qy 301 GQPPPLQRGKSQQLTVSAAQKPRPSSGNLLQSPEPSYGPARPRQQSLSKEGSIGGSGGSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 890 GQPPPLQRGKSQQLTVSAAQKPRPSSGNLLQSPEPSYGPARPRQQSLSKEGSIGGSGGSG 949
Qy 361 GGGGGGLKPSITKQHSQTPSTLNPTMPASERTVAWVSNMPHLSADIESAHIEREEYKLKE 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 950 GGGGGGLKPSITKQHSQTPSTLNPTMPASERTVAWVSNMPHLSADIESAHIEREEYKLKE 1009
Qy 421 YSKSMDESRLDRVKEYEEEIHSLKERLHMSNRKLEEYERRLLSQEEQTSKILMQYQARLE 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1010 YSKSMDESRLDRVKEYEEEIHSLKERLHMSNRKLEEYERRLLSQEEQTSKILMQYQARLE 1069
Qy 481 QSEKRLRQQQVEKDSQIKSIIGRLMLVEEELRRDHPAMAEPLPEPKKRLLDAQRGSFPPW 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1070 QSEKRLRQQQVEKDSQIKSIIGRLMLVEEELRRDHPAMAEPLPEPKKRLLDAQRGSFPPW 1129
Qy 541 VQQTRV 546
||||||
Db 1130 VQQTRV 1135
Regarding claim 6, the teachings of Michaud teach claim 1.
Michaud does not teach wherein said nucleic acid encoding said truncated Syngap1 polypeptide comprises a nucleic acid sequence set forth in any one of SEQ ID NOs: 1-6 or SEQ ID NO: 22.
Aznarez teaches a nucleic acid sequence of SEQ ID NO: 14357 of 4040 nucleotides in length with 100% identity to instant application SEQ ID NO: 1. See alignment below.
Qy = Instant application SEQ ID NO: 1, Db = Aznarez SEQ ID NO: 14357
Query Match 100.0%; Score 3750; Length 4040;
Best Local Similarity 100.0%;
Matches 3750; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGGCCTAAGGCCTCCCACCCCATCCCCCTCAGGGGGCTCCTGCTCAGGTTCCTTGCCC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGGCCTAAGGCCTCCCACCCCATCCCCCTCAGGGGGCTCCTGCTCAGGTTCCTTGCCC 60
Qy 61 CCTCCTTCCCGCTGCCAGCCTCTCCGCCGTCGCTGCTCTTCCTGCTGCTTTCCGGGGGAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CCTCCTTCCCGCTGCCAGCCTCTCCGCCGTCGCTGCTCTTCCTGCTGCTTTCCGGGGGAA 120
Qy 121 TACCACTTGGGTCGCTCGAGGAGGAAGAGTGTCCCAGGGGGGAAGCAGTACAGCATGGAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TACCACTTGGGTCGCTCGAGGAGGAAGAGTGTCCCAGGGGGGAAGCAGTACAGCATGGAG 180
Qy 181 GGTGCCCCTGCTGCGCCCTTCCGGCCCTCGCAAGGCTTCCTGAGCCGACGGCTAAAAAGC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGTGCCCCTGCTGCGCCCTTCCGGCCCTCGCAAGGCTTCCTGAGCCGACGGCTAAAAAGC 240
Qy 241 TCCATCAAACGAACGAAGTCACAACCCAAACTTGACCGGACCAGCAGCTTTCGCCAGATC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TCCATCAAACGAACGAAGTCACAACCCAAACTTGACCGGACCAGCAGCTTTCGCCAGATC 300
Qy 301 CTGCCTCGCTTCCGAAGTGCTGACCATGACCGGGCCCGGCTGATGCAAAGCTTTAAGGAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTGCCTCGCTTCCGAAGTGCTGACCATGACCGGGCCCGGCTGATGCAAAGCTTTAAGGAG 360
Qy 361 TCACACTCTCATGAGTCCTTGCTGAGTCCTAGCAGTGCAGCTGAGGCATTGGAGCTCAAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TCACACTCTCATGAGTCCTTGCTGAGTCCTAGCAGTGCAGCTGAGGCATTGGAGCTCAAC 420
Qy 421 TTGGATGAAGATTCCATTATCAAGCCAGTGCACAGCTCCATCCTGGGCCAGGAGTTCTGT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 TTGGATGAAGATTCCATTATCAAGCCAGTGCACAGCTCCATCCTGGGCCAGGAGTTCTGT 480
Qy 481 TTTGAGGTAACAACTTCATCAGGAACAAAATGCTTTGCCTGTCGGTCTGCGGCCGAAAGA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TTTGAGGTAACAACTTCATCAGGAACAAAATGCTTTGCCTGTCGGTCTGCGGCCGAAAGA 540
Qy 541 GACAAATGGATTGAGAATCTGCAGCGGGCAGTAAAGCCCAACAAGGACAACAGCCGCCGG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GACAAATGGATTGAGAATCTGCAGCGGGCAGTAAAGCCCAACAAGGACAACAGCCGCCGG 600
Qy 601 GTAGACAATGTGCTAAAGCTGTGGATCATAGAGGCCCGGGAGCTGCCCCCCAAGAAGCGG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GTAGACAATGTGCTAAAGCTGTGGATCATAGAGGCCCGGGAGCTGCCCCCCAAGAAGCGG 660
Qy 661 TACTACTGTGAGCTCTGCCTGGATGACATGCTGTATGCACGCACCACCTCCAAGCCCCGC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 TACTACTGTGAGCTCTGCCTGGATGACATGCTGTATGCACGCACCACCTCCAAGCCCCGC 720
Qy 721 TCTGCCTCTGGGGACACCGTCTTCTGGGGCGAGCACTTCGAGTTTAACAACCTGCCGGCT 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 TCTGCCTCTGGGGACACCGTCTTCTGGGGCGAGCACTTCGAGTTTAACAACCTGCCGGCT 780
Qy 781 GTCCGTGCCCTGCGGCTGCATCTGTACCGTGACTCAGACAAAAAGCGCAAGAAGGACAAG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GTCCGTGCCCTGCGGCTGCATCTGTACCGTGACTCAGACAAAAAGCGCAAGAAGGACAAG 840
Qy 841 GCAGGCTATGTCGGCCTGGTGACTGTGCCAGTGGCCACCCTGGCTGGGCGCCACTTCACA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GCAGGCTATGTCGGCCTGGTGACTGTGCCAGTGGCCACCCTGGCTGGGCGCCACTTCACA 900
Qy 901 GAGCAGTGGTACCCTGTAACCCTGCCAACAGGCAGTGGGGGATCTGGGGGCATGGGTTCG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GAGCAGTGGTACCCTGTAACCCTGCCAACAGGCAGTGGGGGATCTGGGGGCATGGGTTCG 960
Qy 961 GGAGGGGGAGGGGGCTCGGGGGGTGGCTCAGGGGGCAAGGGCAAAGGAGGTTGCCCGGCT 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GGAGGGGGAGGGGGCTCGGGGGGTGGCTCAGGGGGCAAGGGCAAAGGAGGTTGCCCGGCT 1020
Qy 1021 GTGCGGCTGAAAGCACGTTACCAGACAATGAGCATCTTGCCCATGGAGCTATATAAAGAG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GTGCGGCTGAAAGCACGTTACCAGACAATGAGCATCTTGCCCATGGAGCTATATAAAGAG 1080
Qy 1081 TTTGCAGAGTATGTCACCAACCATTATCGGATGCTGTGTGCAGTCTTGGAGCCCGCCCTG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 TTTGCAGAGTATGTCACCAACCATTATCGGATGCTGTGTGCAGTCTTGGAGCCCGCCCTG 1140
Qy 1141 AATGTCAAAGGCAAGGAGGAGGTTGCCAGTGCACTAGTTCACATCCTGCAGAGTACAGGC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 AATGTCAAAGGCAAGGAGGAGGTTGCCAGTGCACTAGTTCACATCCTGCAGAGTACAGGC 1200
Qy 1201 AAGGCCAAGGACTTCCTTTCAGACATGGCCATGTCTGAGGTAGACCGGTTCATGGAACGG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 AAGGCCAAGGACTTCCTTTCAGACATGGCCATGTCTGAGGTAGACCGGTTCATGGAACGG 1260
Qy 1261 GAGCACCTCATATTCCGCGAGAACACGCTTGCCACTAAAGCCATAGAAGAGTATATGAGA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GAGCACCTCATATTCCGCGAGAACACGCTTGCCACTAAAGCCATAGAAGAGTATATGAGA 1320
Qy 1321 CTGATTGGTCAGAAATACCTCAAGGATGCCATTGGAGAATTCATCCGTGCTCTGTATGAA 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 CTGATTGGTCAGAAATACCTCAAGGATGCCATTGGAGAATTCATCCGTGCTCTGTATGAA 1380
Qy 1381 TCTGAGGAAAACTGCGAGGTAGACCCTATCAAGTGCACAGCATCCAGTTTGGCAGAGCAC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 TCTGAGGAAAACTGCGAGGTAGACCCTATCAAGTGCACAGCATCCAGTTTGGCAGAGCAC 1440
Qy 1441 CAGGCCAACCTGCGAATGTGCTGTGAGTTGGCCCTGTGCAAGGTGGTCAACTCCCACTGC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 CAGGCCAACCTGCGAATGTGCTGTGAGTTGGCCCTGTGCAAGGTGGTCAACTCCCACTGC 1500
Qy 1501 GTGTTCCCGAGGGAGCTGAAGGAGGTGTTTGCTTCGTGGCGGCTGCGCTGCGCAGAGCGA 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GTGTTCCCGAGGGAGCTGAAGGAGGTGTTTGCTTCGTGGCGGCTGCGCTGCGCAGAGCGA 1560
Qy 1561 GGCCGGGAGGACATCGCAGACAGGCTTATCAGCGCCTCACTCTTCCTGCGCTTCCTCTGC 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 GGCCGGGAGGACATCGCAGACAGGCTTATCAGCGCCTCACTCTTCCTGCGCTTCCTCTGC 1620
Qy 1621 CCAGCGATTATGTCGCCCAGTCTCTTTGGGCTTATGCAGGAGTACCCAGATGAGCAGACC 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 CCAGCGATTATGTCGCCCAGTCTCTTTGGGCTTATGCAGGAGTACCCAGATGAGCAGACC 1680
Qy 1681 TCACGAACCCTCACCCTCATTGCCAAGGTCATCCAGAACCTGGCCAACTTTTCCAAGTTT 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 TCACGAACCCTCACCCTCATTGCCAAGGTCATCCAGAACCTGGCCAACTTTTCCAAGTTT 1740
Qy 1741 ACCTCAAAGGAGGACTTTCTGGGCTTCATGAATGAGTTTCTGGAGCTGGAATGGGGTTCC 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 ACCTCAAAGGAGGACTTTCTGGGCTTCATGAATGAGTTTCTGGAGCTGGAATGGGGTTCC 1800
Qy 1801 ATGCAGCAGTTTTTGTATGAGATCTCCAATCTGGACACGCTAACCAACAGCAGTAGCTTT 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 ATGCAGCAGTTTTTGTATGAGATCTCCAATCTGGACACGCTAACCAACAGCAGTAGCTTT 1860
Qy 1861 GAGGGTTACATCGACTTGGGCCGAGAGCTCTCCACACTGCATGCCCTACTCTGGGAGGTG 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 GAGGGTTACATCGACTTGGGCCGAGAGCTCTCCACACTGCATGCCCTACTCTGGGAGGTG 1920
Qy 1921 CTGCCCCAGCTCAGCAAGGAAGCCCTCCTGAAGCTGGGTCCACTGCCCCGGCTCCTCAAC 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 CTGCCCCAGCTCAGCAAGGAAGCCCTCCTGAAGCTGGGTCCACTGCCCCGGCTCCTCAAC 1980
Qy 1981 GACATCAGCACAGCTCTGAGGAACCCCAACATCCAAAGGCAGCCAAGCCGCCAGAGTGAG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 GACATCAGCACAGCTCTGAGGAACCCCAACATCCAAAGGCAGCCAAGCCGCCAGAGTGAG 2040
Qy 2041 CGGCCCCGGCCTCAGCCTGTGGTACTGCGGGGGCCATCGGCTGAGATGCAGGGCTACATG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 CGGCCCCGGCCTCAGCCTGTGGTACTGCGGGGGCCATCGGCTGAGATGCAGGGCTACATG 2100
Qy 2101 ATGCGGGACCTCAACAGCTCCATCGACCTTCAGTCCTTCATGGCTCGAGGCCTCAACAGC 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 ATGCGGGACCTCAACAGCTCCATCGACCTTCAGTCCTTCATGGCTCGAGGCCTCAACAGC 2160
Qy 2161 TCTATGGACATGGCTCGCCTCCCCTCCCCAACCAAGGAAAAGCCACCCCCACCACCGCCT 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 TCTATGGACATGGCTCGCCTCCCCTCCCCAACCAAGGAAAAGCCACCCCCACCACCGCCT 2220
Qy 2221 GGTGGTGGTAAAGACCTGTTCTATGTAAGCCGTCCACCCCTGGCCCGTTCCTCACCAGCA 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 GGTGGTGGTAAAGACCTGTTCTATGTAAGCCGTCCACCCCTGGCCCGTTCCTCACCAGCA 2280
Qy 2281 TACTGCACGAGCAGCTCGGACATCACAGAGCCAGAGCAGAAGATGCTGAGTGTCAACAAG 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 TACTGCACGAGCAGCTCGGACATCACAGAGCCAGAGCAGAAGATGCTGAGTGTCAACAAG 2340
Qy 2341 AGTGTGTCCATGCTGGACTTACAGGGTGATGGGCCTGGTGGCCGCCTCAACAGCAGCAGT 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 AGTGTGTCCATGCTGGACTTACAGGGTGATGGGCCTGGTGGCCGCCTCAACAGCAGCAGT 2400
Qy 2401 GTTTCGAACCTGGCGGCCGTAGGGGACCTGCTGCACTCAAGCCAGGCCTCGCTGACAGCA 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 GTTTCGAACCTGGCGGCCGTAGGGGACCTGCTGCACTCAAGCCAGGCCTCGCTGACAGCA 2460
Qy 2461 GCCTTGGGGCTACGGCCTGCGCCTGCCGGACGCCTCTCCCAGGGGAGTGGCTCATCCATC 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 GCCTTGGGGCTACGGCCTGCGCCTGCCGGACGCCTCTCCCAGGGGAGTGGCTCATCCATC 2520
Qy 2521 ACGGCGGCTGGCATGCGCCTCAGCCAGATGGGTGTCACCACAGACGGTGTCCCTGCCCAG 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 ACGGCGGCTGGCATGCGCCTCAGCCAGATGGGTGTCACCACAGACGGTGTCCCTGCCCAG 2580
Qy 2581 CAACTGCGAATCCCCCTCTCCTTCCAGAACCCTCTCTTCCACATGGCTGCTGATGGGCCA 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 CAACTGCGAATCCCCCTCTCCTTCCAGAACCCTCTCTTCCACATGGCTGCTGATGGGCCA 2640
Qy 2641 GGTCCCCCAGGCGGCCATGGAGGGGGCGGTGGCCATGGCCCACCTTCCTCCCATCACCAC 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 GGTCCCCCAGGCGGCCATGGAGGGGGCGGTGGCCATGGCCCACCTTCCTCCCATCACCAC 2700
Qy 2701 CACCACCACCATCACCACCACCGAGGTGGAGAGCCCCCTGGGGACACCTTTGCCCCATTC 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 CACCACCACCATCACCACCACCGAGGTGGAGAGCCCCCTGGGGACACCTTTGCCCCATTC 2760
Qy 2761 CATGGCTATAGCAAGAGTGAGGACCTCTCTTCCGGGGTCCCCAAGCCCCCTGCTGCCTCC 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 CATGGCTATAGCAAGAGTGAGGACCTCTCTTCCGGGGTCCCCAAGCCCCCTGCTGCCTCC 2820
Qy 2821 ATCCTTCATAGCCACAGCTACAGTGATGAGTTTGGACCCTCTGGCACTGACTTCACCCGT 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 ATCCTTCATAGCCACAGCTACAGTGATGAGTTTGGACCCTCTGGCACTGACTTCACCCGT 2880
Qy 2881 CGGCAGCTTTCACTCCAGGACAACCTGCAGCACATGCTGTCCCCTCCCCAGATCACCATT 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 CGGCAGCTTTCACTCCAGGACAACCTGCAGCACATGCTGTCCCCTCCCCAGATCACCATT 2940
Qy 2941 GGTCCCCAGAGGCCAGCCCCCTCAGGGCCTGGAGGTGGGAGCGGTGGGGGCAGCGGTGGG 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 GGTCCCCAGAGGCCAGCCCCCTCAGGGCCTGGAGGTGGGAGCGGTGGGGGCAGCGGTGGG 3000
Qy 3001 GGTGGCGGGGGCCAGCCGCCTCCATTGCAGAGGGGCAAGTCTCAGCAGTTGACAGTCAGC 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 GGTGGCGGGGGCCAGCCGCCTCCATTGCAGAGGGGCAAGTCTCAGCAGTTGACAGTCAGC 3060
Qy 3061 GCAGCCCAGAAACCCCGGCCATCCAGCGGGAATCTATTGCAGTCCCCAGAGCCAAGTTAT 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 GCAGCCCAGAAACCCCGGCCATCCAGCGGGAATCTATTGCAGTCCCCAGAGCCAAGTTAT 3120
Qy 3121 GGCCCCGCCCGTCCACGGCAACAGAGCCTCAGCAAGGAGGGCAGCATTGGGGGCAGCGGG 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 GGCCCCGCCCGTCCACGGCAACAGAGCCTCAGCAAGGAGGGCAGCATTGGGGGCAGCGGG 3180
Qy 3181 GGCAGCGGTGGCGGAGGGGGTGGGGGGCTGAAGCCCTCCATCACCAAGCAGCATTCTCAG 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 GGCAGCGGTGGCGGAGGGGGTGGGGGGCTGAAGCCCTCCATCACCAAGCAGCATTCTCAG 3240
Qy 3241 ACACCATCCACATTGAACCCCACAATGCCAGCCTCTGAGCGGACAGTGGCCTGGGTCTCC 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 ACACCATCCACATTGAACCCCACAATGCCAGCCTCTGAGCGGACAGTGGCCTGGGTCTCC 3300
Qy 3301 AACATGCCTCACCTGTCGGCTGACATCGAGAGTGCCCACATCGAGCGGGAAGAGTACAAG 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 AACATGCCTCACCTGTCGGCTGACATCGAGAGTGCCCACATCGAGCGGGAAGAGTACAAG 3360
Qy 3361 CTCAAGGAGTACTCAAAATCGATGGATGAGAGCCGGCTGGATAGGGTGAAGGAGTACGAG 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 CTCAAGGAGTACTCAAAATCGATGGATGAGAGCCGGCTGGATAGGGTGAAGGAGTACGAG 3420
Qy 3421 GAGGAGATTCACTCACTGAAAGAGCGGCTGCACATGTCCAACCGGAAGCTGGAAGAGTAT 3480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3421 GAGGAGATTCACTCACTGAAAGAGCGGCTGCACATGTCCAACCGGAAGCTGGAAGAGTAT 3480
Qy 3481 GAGCGGAGGCTGCTGTCCCAGGAAGAACAAACCAGCAAAATCCTGATGCAGTATCAGGCC 3540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3481 GAGCGGAGGCTGCTGTCCCAGGAAGAACAAACCAGCAAAATCCTGATGCAGTATCAGGCC 3540
Qy 3541 CGACTGGAGCAGAGTGAGAAGAGGCTAAGGCAGCAGCAGGCAGAGAAGGATTCCCAGATC 3600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3541 CGACTGGAGCAGAGTGAGAAGAGGCTAAGGCAGCAGCAGGCAGAGAAGGATTCCCAGATC 3600
Qy 3601 AAGAGCATCATTGGCAGGCTGATGCTGGTGGAGGAGGAGCTGCGCCGGGACCACCCCGCC 3660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3601 AAGAGCATCATTGGCAGGCTGATGCTGGTGGAGGAGGAGCTGCGCCGGGACCACCCCGCC 3660
Qy 3661 ATGGCTGAGCCGCTGCCAGAACCCAAGAAGAGGCTGCTCGACGCTCAGAGAGGCAGCTTC 3720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3661 ATGGCTGAGCCGCTGCCAGAACCCAAGAAGAGGCTGCTCGACGCTCAGAGAGGCAGCTTC 3720
Qy 3721 CCCCCTTGGGTCCAACAAACCCGCGTGTGA 3750
||||||||||||||||||||||||||||||
Db 3721 CCCCCTTGGGTCCAACAAACCCGCGTGTGA 3750
Regarding claims 7-9, the teachings of Michaud teach claim 1.
Moreover, Michaud teaches that the viral vectors (para 0068 and 0123) comprising part (i..e truncated) of the DNA molecule encoding Syngap1 polypeptide can comprise regulatory elements required for expression which can include promoters (i.e. operably linked to permit or facilitate expression of the truncated Syngap1 polypeptide as defined in the specification of the instant application). Hence, Michaud teaches wherein said nucleic acid encoding said truncated Syngap 1 polypeptide is operably linked to a promoter (claim 7).
Michaud does not teach wherein said promoter is a neuron-specific promoter (claim 8), and the promoter is a species selected from the group recited in claim 9.
Edna Au teaches that AAVs (i.e. viral vector) have been engineered to comprise expression cassettes containing a promoter, genes of interest, and a terminator, in order to make them more suitable for clinical applications (page 2, left col, para 1). Edna Au teaches the promoters used frequently for central nervous system expression of AAVs include hSYN (i.e. SYN1 which is neuron-specific).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of a viral vector encoding a truncated Syngap1 polypeptide taught by Michaud to use a neuron-specific promoter that is able to induce expression of Syngap1 polypeptide since Edna Au teaches that inclusion of promoters for the gene of interest (i.e. Syngap1) make AAV vectors more suitable for clinical applications and hSYN is a neuron-specific promoter frequently used for central nervous system-specific expression. One would be motivated to do so to ensure that Syngap1 is exclusively expressed in neurons as a therapeutic for clinical application and one would have a reasonable expectation of success.
Regarding claims 10 and 11, the teachings of Michaud teach claim 1.
Michaud does not teach wherein said viral vector comprises an optimized inverted terminal repeat (ITR) (claim 10) and wherein said viral vector comprises an optimized 3' untranslated region (UTR) (claim 11).
Edna Au teaches that AAVs are a safe and effective delivery vector to deliver genes of interest and that AAVs comprise ITRs and polyadenylation sequences (i.e. 3’untranslated regions) (Introduction, page 1; page 2, left col para 1; Figure 1 showing ITR and PolyA sequence within AAV).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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