DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 05/22/2026 is acknowledged.
Claims 21, 28-31, 39, 43-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/22/2026.
Claims Status
Claims 23-27 is/are cancelled. Claims 1-22, 28-45 is/are currently pending with claims 21, 28-31, 39, 43-45 withdrawn. Claims 1-20, 22, 32-38, 40-42 is/are under examination.
Information Disclosure Statement
The information disclosure statement filed 06/13/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. No copy of NPL12 was provided.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Fig. 2 contains sequences without corresponding SEQ ID NOs.
Claim Rejections - 35 USC § 112
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.
Claims 1, 3-11, 14-17, 19-20, 22, 34-35, 37-38, 40-42 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.
Claims 1 and 11 recite GAT-1 variants comprising one or more mutations relative to SEQ ID NO:18, and do not recite any limitations to the number of mutations allowable.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, variants of SEQ ID NO:18 whose only alterations are selected from those listed on page 6 and Table 3 of the instant specification are the only species whose complete structures are disclosed. While the genus encompasses a large number of variants and molecules that have the same activity as a transporter and the genus encompasses a large number of variants and molecules that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of SLC6A1 variants or functional equivalents thereof. Additionally, the specification does not describe the complete structure of a representative number of species of the large genus of modified SLC6A1 variants.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic is that the variants are able to be classified as GAT-2 transporters with “normal” range of transporter function (see page 3 of the specification; the transduced cell should be capable of restoring GAT-1 transporter function to the normal range). Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of variant SLC6A1 genes or functional equivalent thereof, all members of the claimed genus will have that characteristic. Further, no identifying characteristics of the modified SLC6A1 genes are disclosed.
The inventions of claims 3-10, 14-17, 19-20, 22, 34-35, 37-38, 40-42 require the use of the inventions of claims 1 and 11 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 19-20, 40-42 are rejected under 35 U.S.C. 101 because Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 19-20 and 40-42 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). Claims 19-20 are drawn to a host cell, but do not require that the host cell be an isolated cell or otherwise a cell outside of a human organism. Cells within a human organism are considered to comprise part of a human organism. As the host cell of claims 19-20 encompass (but are not limited to) cells in a human organism, claims 19-20 are considered to encompass a human organism.
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) 1, 5-6, 8-9,11, 14, 16, 19, 22, 32, 35-36 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ramu (WO2021216975A1, EFD 04/23/2020), as evidenced by Addgene (2019).
MPEP §2131.01 provides guidance as to 35 U.S.C. 102 rejections over multiple references. Such rejection has been held to be proper when the extra references are cited to: (C) Show that a characteristic not disclosed in the reference is inherent.
The MPEP states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill.” Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749 (Fed. Cir. 1991) (The court went on to explain that “this modest flexibility in the rule that 'anticipation' requires that every element of the claims appear in a single reference accommodates situations in which the common knowledge of technologists is not recorded in the reference; that is, where technological facts are known to those in the field of the invention, albeit not known to judges.” 948 F.2d at 1268, 20 USPQ at 1749-50.). Note that the critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP §2124.
Regarding claim 1, Ramu teaches a vector encoding a GAT1 protein of SEQ ID NO:28 (SEQ ID NO:28 is 100% identical to instant SEQ ID NO:18, see alignment below) (claims 1, 6; page 33).
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Regarding claim 5, Ramu teaches a viral vector comprising the nucleic acid of claim 1 flanked at the 3’ and 5’ end by 3’ and 5’ ITR sequences (Fig. 2; claim 1).
Regarding claim 6, Ramu teaches that the ITRs are AAV ITRs (claim 1).
Regarding claim 8, Ramu teaches a viral particle comprising the nucleic acid (claim 1; Fig. 1).
Regarding claim 9, Ramu teaches that the capsid is an AAV9 capsid (claim 9). Ramu teaches that the viral capsid comprises Rep and Cap genes (pages 75-76). Addgene (2019) teaches that the Cap genes of AAV are VP1, VP2, and VP3 (page 1).
Regarding claim 11, Ramu teaches a viral vector comprising a transgene encoding SEQ ID NO:28 (100% identical to instant SEQ ID NO:18), wherein the transgene is operably linked to a promoter, and wherein the nucleic acid sequence encoding SEQ ID NO:28 and comprising the promoter is flanked by 3’ and 5’ ITR sequences (claims 1, 6; page 33).
Regarding claim 14, Ramu teaches a viral particle comprising the nucleic acid (claim 1; Fig. 1).
Regarding claim 16, Ramu teaches that the capsid is an AAV9 capsid (claim 9). Ramu teaches that the viral capsid comprises Rep and Cap genes (pages 75-76). Addgene (2019) teaches that the Cap genes of AAV are VP1, VP2, and VP3 (page 1).
Regarding claim 19, Ramu teaches cells for producing the viral particle, which cells comprise the nucleic acid construct (claim 17).
Regarding claim 22, Ramu teaches a pharmaceutical composition comprising the rAAV vector (claims 15-16).
Regarding claims 32 and 36, instant claims 32 and 36 do not require that the transgene be the variant of SEQ ID NO:18, merely that if the variant of SEQ ID NO:18 be elected, then it comprises one or more of the recited mutations. As such, Ramu anticipates claims 32 and 36 in the case where SEQ ID NO:18 is elected.
Regarding claim 35, Ramu teaches a viral particle comprising the viral vector (claim 1; Fig. 1).
Claim Rejections - 35 USC § 103
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 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) 1-2, 5-6, 8-9, 11-14, 16, 19, 22, 32-33, 35-36, 41-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramu (WO2021216975A1, EFD 04/23/2020), in view of NCBI RefSeq NM_003042.4 (2019), as evidenced by Addgene (2019).
Regarding claim 1, Ramu teaches a vector encoding a GAT1 protein of SEQ ID NO:28 (SEQ ID NO:28 is 100% identical to instant SEQ ID NO:18, see alignment below) (claims 1, 6; page 33).
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Regarding claim 5, Ramu teaches a viral vector comprising the nucleic acid of claim 1 flanked at the 3’ and 5’ end by 3’ and 5’ ITR sequences (Fig. 2; claim 1).
Regarding claim 6, Ramu teaches that the ITRs are AAV ITRs (claim 1).
Regarding claim 8, Ramu teaches a viral particle comprising the nucleic acid (claim 1; Fig. 1).
Regarding claim 9, Ramu teaches that the capsid is an AAV9 capsid (claim 9). Ramu teaches that the viral capsid comprises Rep and Cap genes (pages 75-76). Addgene (2019) teaches that the Cap genes of AAV are VP1, VP2, and VP3 (page 1).
Regarding claim 11, Ramu teaches a viral vector comprising a transgene encoding SEQ ID NO:28 (100% identical to instant SEQ ID NO:18), wherein the transgene is operably linked to a promoter, and wherein the nucleic acid sequence encoding SEQ ID NO:28 and comprising the promoter is flanked by 3’ and 5’ ITR sequences (claims 1, 6; page 33).
Regarding claim 14, Ramu teaches a viral particle comprising the nucleic acid (claim 1; Fig. 1).
Regarding claim 16, Ramu teaches that the capsid is an AAV9 capsid (claim 9). Ramu teaches that the viral capsid comprises Rep and Cap genes (pages 75-76). Addgene (2019) teaches that the Cap genes of AAV are VP1, VP2, and VP3 (page 1).
Regarding claim 19, Ramu teaches cells for producing the viral particle, which cells comprise the nucleic acid construct (claim 17).
Regarding claim 22, Ramu teaches a pharmaceutical composition comprising the rAAV vector (claims 15-16).
Regarding claims 32 and 36, instant claims 32 and 36 do not require that the transgene be the variant of SEQ ID NO:18, merely that if the variant of SEQ ID NO:18 be elected, then it comprises one or more of the recited mutations. As such, Ramu anticipates claims 32 and 36 in the case where SEQ ID NO:18 is elected.
Regarding claim 35, Ramu teaches a viral particle comprising the viral vector (claim 1; Fig. 1).
Regarding claims 41-42, Ramu teaches that the cells comprise the viral vector comprising 3’ and 5’ ITR sequences and the coding sequence, a nucleic acid construct comprising viral helper genes, and a nucleic acid construct encoding AAV Rep and Cap genes (pages 75-76).
Regarding claims 2, 12-13, 33, Ramu teaches a nucleic acid vector encoding a GAT1 protein of SEQ ID NO:28 (claims 1, 6; page 33), but does not teach the sequences of instant SEQ ID NOs: 15, 26-29 as required by instant claims 2, 12-13, and 33. However, sequences of the SLC6A1 gene (encoding GAT1 proteins) were known in the art. The human SLC6A1 mRNA sequence, NCBI RefSeq NM_003042.4, is 100% identical to instant SEQ ID NO:15 (see alignment below). It would have been obvious to an artisan at the time of filing that the invention of Ramu may be modified to comprise the coding sequence of instant SEQ ID NO:15—a known SLC6A1 sequence—instead of SEQ ID NO:29 of Ramu, an alternative SLC6A1 coding sequence. Such sequences would code for GAT-1 proteins, just as the vectors of Ramu code for GAT-1 proteins, and so would be obvious alternatives.
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Claim(s) 1, 5-11, 14, 16-17, 19, 22, 32, 35-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramu (WO2021216975A1, EFD 04/23/2020), in view of Paul (WO2017189963A1), as evidenced by Addgene (2019).
Regarding claim 1, Ramu teaches a vector encoding a GAT1 protein of SEQ ID NO:28 (SEQ ID NO:28 is 100% identical to instant SEQ ID NO:18, see alignment below) (claims 1, 6; page 33).
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Regarding claim 5, Ramu teaches a viral vector comprising the nucleic acid of claim 1 flanked at the 3’ and 5’ end by 3’ and 5’ ITR sequences (Fig. 2; claim 1).
Regarding claim 6, Ramu teaches that the ITRs are AAV ITRs (claim 1).
Regarding claim 8, Ramu teaches a viral particle comprising the nucleic acid (claim 1; Fig. 1).
Regarding claim 9, Ramu teaches that the capsid is an AAV9 capsid (claim 9). Ramu teaches that the viral capsid comprises Rep and Cap genes (pages 75-76). Addgene (2019) teaches that the Cap genes of AAV are VP1, VP2, and VP3 (page 1).
Regarding claim 11, Ramu teaches a viral vector comprising a transgene encoding SEQ ID NO:28 (100% identical to instant SEQ ID NO:18), wherein the transgene is operably linked to a promoter, and wherein the nucleic acid sequence encoding SEQ ID NO:28 and comprising the promoter is flanked by 3’ and 5’ ITR sequences (claims 1, 6; page 33).
Regarding claim 14, Ramu teaches a viral particle comprising the nucleic acid (claim 1; Fig. 1).
Regarding claim 16, Ramu teaches that the capsid is an AAV9 capsid (claim 9). Ramu teaches that the viral capsid comprises Rep and Cap genes (pages 75-76). Addgene (2019) teaches that the Cap genes of AAV are VP1, VP2, and VP3 (page 1).
Regarding claim 19, Ramu teaches cells for producing the viral particle, which cells comprise the nucleic acid construct (claim 17).
Regarding claim 22, Ramu teaches a pharmaceutical composition comprising the rAAV vector (claims 15-16).
Regarding claims 32 and 36, instant claims 32 and 36 do not require that the transgene be the variant of SEQ ID NO:18, merely that if the variant of SEQ ID NO:18 be elected, then it comprises one or more of the recited mutations. As such, Ramu anticipates claims 32 and 36 in the case where SEQ ID NO:18 is elected.
Regarding claim 35, Ramu teaches a viral particle comprising the viral vector (claim 1; Fig. 1).
However, Ramu does not teach the viral capsid protein or ITR sequences required to create the rAAV capsids.
Paul teaches the requisite viral capsid protein and ITR sequences required to create an AAV9 viral capsid.
Regarding claim 7, Paul teaches that the ITR sequences used in an expression vector “may be derived from the same serotype as the capsid, selected from any of the serotypes listed in Table 1, or a derivative thereof” (paragraph [0092]), and teaches that one 5’ ITR sequence is SEQ ID NO:4270 (100% identical to instant SEQ ID NO:23, see alignment below) and one 3’ ITR sequence is SEQ ID NO:4274 (100% identical to instant SEQ ID NO:22, see alignment below) (paragraph [00672]).
SEQ ID NO:4270 and instant SEQ ID NO:23:
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SEQ ID NO:4274 and instant SEQ ID NO:22:
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Regarding claims 9 and 16-17, Paul teaches that one of the required AAV9 viral capsid proteins has the sequence SEQ ID NO:123 (SEQ ID NO:123 is 100% identical to instant SEQ ID NO:25 see alignment below) (Table 1; claims 1-2).
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Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramu (WO2021216975A1, EFD 04/23/2020) and Paul (WO2017189963A1), as evidenced by Addgene (2019), as applied to claims 1, 8-9 above, and further in view of Tordo (2018, of record).
The teachings of Ramu, Paul, and Addgene are discussed above and render obvious the limitations of claims 1 and 8-9.
However, Ramu does not teach that ttAAV should be used.
Regarding claim 10, Paul teaches that a true type AAV (ttAAV) may be used to deliver a vector to neurons (paragraphs [0077], [00396]; claims 1, 4). Such a ttAAV vector requires appropriate Rep and Cap proteins, such as that of SEQ ID NO: 530 (100% identical to instant SEQ ID NO:24, see alignment below) (Table 1; claims 1-2).
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Regarding claim 10, Tordo teaches that ttAAV exhibits enhanced neurotropism compared to AAV9 (Abstract).
It would have been obvious to an artisan at the time of filing that AAV serotypes exhibiting high neurotropism should be used in the compositions and methods of Ramu, as Ramu teaches targeting of neurons by AAV vectors (claims 18, 20). While Ramu teaches the use of AAV9 (claims 8-9), Tordo teaches that ttAAV has greater neurotropism than AAV9, rendering obvious that ttAAV would be preferable over AAV9 in the invention of Ramu. Paul further teaches the requisite capsid proteins, rendering obvious the replacement of the AAV9 of Ramu with a ttAAV comprising the capsid proteins taught by Paul.
Claim(s) 3 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramu (WO2021216975A1, EFD 04/23/2020), in view of Paul (WO2017189963A1), as evidenced by Addgene (2019), as applied to claim 1 above, and further in view of Brandt (WO2019070541A1).
The teachings of Ramu, Paul, and Addgene are discussed above and render obvious the limitations of claim 1.
However, Ramu and Paul do not teach that promoter sequences for the expression of a coding sequence, delivered by AAV vector, in neurons comprise SEQ ID NOs:1-12, or 14. Ramu and Paul do teach, however, that the viral vector is delivered to neurons (see Ramu, claims 7, 18-20; Paul, paragraph [0013], claim 4), and the promotors used may be EF1a, CMV, CBA, CAG, UBC (Paul, paragraph [0013]), CAG/CBA, CMV, PGK, NSE, or SLC6A1 (native) (Ramu pages 2-3) promoters (Ramu teaches that the native promoter is optimal, but that CAG/CBA, CMV, PGK, and NSE promoters are conventional promoters for expression in neurons).
Brandt teaches an EF1a promoter sequence.
Regarding claims 3 and 34, Brandt teaches an EF1a promoter sequence of SEQ ID NO:1360 (paragraph [0900]) (SEQ ID NO:1360 comprises, from 5’ to 3’, instant SEQ ID NOs:35 and 6, see alignments below).
Instant SEQ ID NO:35:
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It would have been obvious to an artisan at the time of filing that any known sequence of the promoters taught by Ramu or Paul as useful in promoting gene expression in neurons could be used as a promoter in the invention rendered obvious by the combined teachings of Ramu and Paul. As such, the teachings of Brandt render obvious a promoter sequence for such an application comprising instant SEQ ID NOs:35 and 6 operably linked 5’ to 3’.
Claim(s) 3 and 37-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramu (WO2021216975A1, EFD 04/23/2020), in view of Paul (WO2017189963A1), as evidenced by Addgene (2019), as applied to claims 1 and 11-12 above, and further in view of Hautbergue (WO2017207979A1).
The teachings of Ramu, Paul, and Addgene are discussed above and render obvious the limitations of claim 1.
However, Ramu and Paul do not teach that promoter sequences for the expression of a coding sequence, delivered by AAV vector, in neurons comprise SEQ ID NOs:1-12, or 14. Ramu and Paul do teach, however, that the viral vector is delivered to neurons (see Ramu, claims 7, 18-20; Paul, paragraph [0013], claim 4), and the promotors used may be EF1a, CMV, CBA, CAG, UBC (Paul, paragraph [0013]), CAG/CBA, CMV, PGK, NSE, or SLC6A1 (native) (Ramu pages 2-3) promoters (Ramu teaches that the native promoter is optimal, but that CAG/CBA, CMV, PGK, and NSE promoters are conventional promoters for expression in neurons).
Hautbergue teaches a PGK promoter sequence.
Regarding claims 3 and 37-38, Hautbergue teaches a PGK promoter sequence of SEQ ID NO:148 (comprises a sequence 100% identical to instant SEQ ID NO:4, see below) (Fig. 18).
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It would have been obvious to an artisan at the time of filing that any known sequence of the promoters taught by Ramu or Paul as useful in promoting gene expression in neurons could be used as a promoter in the invention rendered obvious by the combined teachings of Ramu and Paul. As such, the teachings of Hautbergue render obvious a promoter sequence for such an application comprising instant SEQ ID NO:4.
Claim(s) 4, 14, 20, 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramu (WO2021216975A1, EFD 04/23/2020), in view of Paul (WO2017189963A1) and Addgene (2019), as applied to claims 1 and 11 above, and further in view of McDonald (WO2017021359A1).
The teachings of Ramu and Paul are discussed above and render obvious the limitations of claims 1 and 11.
Regarding claims 4 and 14, Ramu teaches that the expression vector comprises a 3’ polyadenylation tail (Fig. 2).
Regarding claim 20, Ramu teaches a neuronal cell comprising the viral vector nucleic acid and a nucleic acid construct encoding AAV Rep and Cap genes (claims 22-23; pages 75-76). Addgene teaches that it is conventional to introduce a packaging plasmid comprising Rep and Cap genes and no ITR sequences (claims 18, 20, 22-23; Figs. 2 and 3).
Regarding claim 40, Ramu teaches that the helper genes must also be introduced into the cell (page 75). Addgene teaches that it is conventional to package helper genes in a third “helper” plasmid (Figs. 2 and 3). It would have been obvious to an artisan to package the AAV system and system components of Ramu according to the conventional methods available and known in the art.
However, Ramu does not teach a polyadenylation signal sequence.
McDonald teaches a polyadenylation signal sequence useful in cellular expression systems.
Regarding claims 4 and 14, McDonald teaches a polyadenylation signal sequence of SEQ ID NO: 21, for use in a cell expression system (claims 68, 86-90).
Ramu does not disclose the polyadenylation sequence used. An artisan would find obvious to use any polyadenylation sequence known to be used in cellular expression systems, including the polyadenylation signal sequence taught by McDonald, as obvious alternatives or variants of the polyadenylation signal taught by Ramu. As such, the limitations of claims 4 and 14 are rendered obvious.
Allowable Subject Matter
Claim 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: Claim 18 requires that the promoter comprise SEQ ID NO:14. Sequence searches for SEQ ID NO:14 did not yield any results. As such, the plasmid comprising SEQ ID NOs:14 and 15 is free of the art.
Conclusion
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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