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 .
DETAILED ACTION
Applicant's preliminary amendment filed on April 9, 2026 is acknowledged. Claims 16-21 have been canceled. Claims 1 and 6 were amended. Claims 1-15, 22, and 23 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-11 and 22) in the reply filed on April 9, 2026 is acknowledged.
Claims 12-15 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 April 9, 2026.
Claims 1-11 and 22 are examined on the merits herein.
Priority
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 3, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Drawings
The drawings were received on August 11, 2023. These drawings are found acceptable by the examiner.
Specification
The disclosure is objected to because of the following informalities:
In the brief description of the drawings section of the specification:
Figure 5 refers to colors; however, the application does not have colored drawings.
There is a description for Figure 8 “D” and “(D)” [page 30].
No description is provided for Figures 8F, 8G, or 10B.
Page 49, line 12 reads in part “containing sjngle-stranded” and should read “containing single-stranded” (emphasis added).
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See e.g., pages 9, 18, 43, and 50.
Claim Objections
Claim 1 is objected to because of the following informality:
It appears that there is an extra space in between the word “wherein” and “the”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 recites the vector according to claim 1 wherein the promoter is a neuron-specific promoter. Claim 1 recites in part wherein the promoter is selected from the group consisting of a human synapsin 1 promoter, a CAG promoter, a CMV promoter, a CAMKII promoter, a beta-actin promoter, and a human EF1-alpha promoter. Therefore, claim 4 is broader than the specific promoters recited in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-11 and 22 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 1-11 and 22 are drawn to the provision of a genus of sequences with at least 70% identity to the nucleotide sequence of SEQ ID NO: 12 and a genus of sequences with at least 80% identity to the amino acid sequence of SEQ ID NO: 13 that encode a functional DAT protein. Thus, the claims encompass a broad genus of sequences that encode a functional DAT protein.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification envisions on pages 15 through 17 that the human SLC6A3 gene has the nucleotide sequence of SEQ ID NO: 12 or has at least 70% sequence identity thereto, and encodes a functional DAT protein. Further, the specification envisions that the nucleotide sequence of the human SLC6A3 gene may be codon optimized to maximize expression of the protein. The specification also envisions that the human SLC6A3 gene encodes a functional DAT protein having the amino acid sequence of SEQ ID NO: 13 or has at least 80% sequence identity thereto. The specification discloses that the human DAT coding sequence (NM_001044.4) and human Synapsin 1 promoter were cloned into a pCCL lentiviral expression vector [page 48, last paragraph].
Even if one accepts that the example described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the example is only representative of the human SLC6A3 gene having the nucleotide sequence of SEQ ID NO: 12. The results are not necessarily predictive of other sequences falling within the broadly claimed genus. Thus, it is impossible for one to extrapolate from the limited example described herein those sequences that would necessarily meet the structural/functional characteristics of the rejected claims.
Cheng et al. (Structure 2015) discloses that the specific mechanism of function of DAT at the atomic scale has been elusive to date due to lack of structural data [page 2171, left column, second paragraph]. In the absence of structural data for DAT, information on the dynamics of hDAT at the atomic scale has been inferred from models or simulations based on the bacterial transporter LeuT [page 2171, left column, last paragraph bridging to right column].
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of sequences with at least 70% identity to the nucleotide sequence of SEQ ID NO: 12 and a set of sequences with at least 80% identity to the amino acid sequence of SEQ ID NO: 13 that encode a functional DAT protein.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-11 and 22.
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.
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.
Claim 22 is 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).
Claim 22 recites a host cell comprising the vector of claim 1. The specification discloses that a host cell may permit the expression of a nucleic acid molecule of the invention and thus may be, for example, a bacterial, yeast, insect, or mammalian cell [page 25, fifth paragraph]. The specification also discloses on page 22, lines 28-30 that the invention also provides a method of treating DTDS comprising administering a therapeutically effective amount of a vector as described above to a patient with DTDS. Preferably, the patient is human.
Thus, in view of the specification, the broadest reasonable interpretation of the claimed cell includes a human being. Therefore, the claim is directed to nonstatutory subject matter.
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.
Claims 1, 10, 11, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Johnson et al. (The Journal of Biological Chemistry, Vol. 280, No. 12, pages 10914-10919, 2005; reference previously cited by the Examiner) as evidenced by NCBI (SLC6A3 solute carrier family 6 member 3 [Homo sapiens (human)], Gene ID: 6531) and Shikama et al. (BMC Molecular Biology 2010; reference previously cited by the Examiner).
Regarding claims 1 and 10, Johnson et al. teaches hDAT cDNA in a pIREShyg2 vector [page 10915, left column, last paragraph]. As evidenced by NCBI, the SLC6A3 gene is also called DAT and thus the human SLC6A3 gene is hDAT. Shikama et al. teaches a pIREShyg2 vector as shown in Figure 1 [reproduced below; page 3] wherein the vector comprises PCMV which is a human cytomegalovirus major immediate early promoter/enhancer.
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Regarding claim 11, Johnson et al. teaches a composition comprising the vector with Lipofectamine Plus reagent in Opti-MEM medium [page 10915, left column, last paragraph bridging to right column].
Regarding claim 22, Johnson et al. teaches a HEK 293 cell comprising the vector [page 10915, left column, last paragraph bridging to right column].
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Johnson et al. (The Journal of Biological Chemistry 2005; reference previously cited by the Examiner) as evidenced by NCBI (SLC6A3 solute carrier family 6 member 3 [Homo sapiens (human)], Gene ID: 6531) and Shikama et al. (BMC Molecular Biology 2010; reference previously cited by the Examiner) as applied to claims 1, 10, 11, and 22 above in view of Yao et al. (US 2020/0347455).
Regarding claim 2, the teachings of Johnson et al. are discussed above.
However, Johnson et al. does not teach that the human SLC6A3 gene has at least 70% sequence identity to the nucleotide sequence of SEQ ID NO: 12 and encodes a functional DAT protein.
Yao et al. teaches SEQ ID NO: 57 (designated as Db) and has a match to instant SEQ ID NO: 12 (designated as Qy) as shown in the alignment below. According to the sequence listing, SEQ ID NO: 57 is SLC6A3 mRNA (NM_001044.4).
Query Match 100.0%; Score 2120; Length 3952;
Best Local Similarity 100.0%;
Matches 2120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGAGTAAGAGCAAATGCTCCGTGGGACTCATGTCTTCCGTGGTGGCCCCGGCTAAGGAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 127 ATGAGTAAGAGCAAATGCTCCGTGGGACTCATGTCTTCCGTGGTGGCCCCGGCTAAGGAG 186
Qy 61 CCCAATGCCGTGGGCCCGAAGGAGGTGGAGCTCATCCTTGTCAAGGAGCAGAACGGAGTG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 187 CCCAATGCCGTGGGCCCGAAGGAGGTGGAGCTCATCCTTGTCAAGGAGCAGAACGGAGTG 246
Qy 121 CAGCTCACCAGCTCCACCCTCACCAACCCGCGGCAGAGCCCCGTGGAGGCCCAGGATCGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 247 CAGCTCACCAGCTCCACCCTCACCAACCCGCGGCAGAGCCCCGTGGAGGCCCAGGATCGG 306
Qy 181 GAGACCTGGGGCAAGAAGATCGACTTTCTCCTGTCCGTCATTGGCTTTGCTGTGGACCTG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 307 GAGACCTGGGGCAAGAAGATCGACTTTCTCCTGTCCGTCATTGGCTTTGCTGTGGACCTG 366
Qy 241 GCCAACGTCTGGCGGTTCCCCTACCTGTGCTACAAAAATGGTGGCGGTGCCTTCCTGGTC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 367 GCCAACGTCTGGCGGTTCCCCTACCTGTGCTACAAAAATGGTGGCGGTGCCTTCCTGGTC 426
Qy 301 CCCTACCTGCTCTTCATGGTCATTGCTGGGATGCCACTTTTCTACATGGAGCTGGCCCTC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 427 CCCTACCTGCTCTTCATGGTCATTGCTGGGATGCCACTTTTCTACATGGAGCTGGCCCTC 486
Qy 361 GGCCAGTTCAACAGGGAAGGGGCCGCTGGTGTCTGGAAGATCTGCCCCATACTGAAAGGT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 487 GGCCAGTTCAACAGGGAAGGGGCCGCTGGTGTCTGGAAGATCTGCCCCATACTGAAAGGT 546
Qy 421 GTGGGCTTCACGGTCATCCTCATCTCACTGTATGTCGGCTTCTTCTACAACGTCATCATC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 547 GTGGGCTTCACGGTCATCCTCATCTCACTGTATGTCGGCTTCTTCTACAACGTCATCATC 606
Qy 481 GCCTGGGCGCTGCACTATCTCTTCTCCTCCTTCACCACGGAGCTCCCCTGGATCCACTGC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 607 GCCTGGGCGCTGCACTATCTCTTCTCCTCCTTCACCACGGAGCTCCCCTGGATCCACTGC 666
Qy 541 AACAACTCCTGGAACAGCCCCAACTGCTCGGATGCCCATCCTGGTGACTCCAGTGGAGAC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 667 AACAACTCCTGGAACAGCCCCAACTGCTCGGATGCCCATCCTGGTGACTCCAGTGGAGAC 726
Qy 601 AGCTCGGGCCTCAACGACACTTTTGGGACCACACCTGCTGCCGAGTACTTTGAACGTGGC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 727 AGCTCGGGCCTCAACGACACTTTTGGGACCACACCTGCTGCCGAGTACTTTGAACGTGGC 786
Qy 661 GTGCTGCACCTCCACCAGAGCCATGGCATCGACGACCTGGGGCCTCCGCGGTGGCAGCTC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 787 GTGCTGCACCTCCACCAGAGCCATGGCATCGACGACCTGGGGCCTCCGCGGTGGCAGCTC 846
Qy 721 ACAGCCTGCCTGGTGCTGGTCATCGTGCTGCTCTACTTCAGCCTCTGGAAGGGCGTGAAG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 847 ACAGCCTGCCTGGTGCTGGTCATCGTGCTGCTCTACTTCAGCCTCTGGAAGGGCGTGAAG 906
Qy 781 ACCTCAGGGAAGGTGGTATGGATCACAGCCACCATGCCATACGTGGTCCTCACTGCCCTG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 907 ACCTCAGGGAAGGTGGTATGGATCACAGCCACCATGCCATACGTGGTCCTCACTGCCCTG 966
Qy 841 CTCCTGCGTGGGGTCACCCTCCCTGGAGCCATAGACGGCATCAGAGCATACCTGAGCGTT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 967 CTCCTGCGTGGGGTCACCCTCCCTGGAGCCATAGACGGCATCAGAGCATACCTGAGCGTT 1026
Qy 901 GACTTCTACCGGCTCTGCGAGGCGTCTGTTTGGATTGACGCGGCCACCCAGGTGTGCTTC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1027 GACTTCTACCGGCTCTGCGAGGCGTCTGTTTGGATTGACGCGGCCACCCAGGTGTGCTTC 1086
Qy 961 TCCCTGGGCGTGGGGTTCGGGGTGCTGATCGCCTTCTCCAGCTACAACAAGTTCACCAAC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1087 TCCCTGGGCGTGGGGTTCGGGGTGCTGATCGCCTTCTCCAGCTACAACAAGTTCACCAAC 1146
Qy 1021 AACTGCTACAGGGACGCGATTGTCACCACCTCCATCAACTCCCTGACGAGCTTCTCCTCC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1147 AACTGCTACAGGGACGCGATTGTCACCACCTCCATCAACTCCCTGACGAGCTTCTCCTCC 1206
Qy 1081 GGCTTCGTCGTCTTCTCCTTCCTGGGGTACATGGCACAGAAGCACAGTGTGCCCATCGGG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1207 GGCTTCGTCGTCTTCTCCTTCCTGGGGTACATGGCACAGAAGCACAGTGTGCCCATCGGG 1266
Qy 1141 GACGTGGCCAAGGACGGGCCAGGGCTGATCTTCATCATCTACCCGGAAGCCATCGCCACG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1267 GACGTGGCCAAGGACGGGCCAGGGCTGATCTTCATCATCTACCCGGAAGCCATCGCCACG 1326
Qy 1201 CTCCCTCTGTCCTCAGCCTGGGCCGTGGTCTTCTTCATCATGCTGCTCACCCTGGGTATC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1327 CTCCCTCTGTCCTCAGCCTGGGCCGTGGTCTTCTTCATCATGCTGCTCACCCTGGGTATC 1386
Qy 1261 GACAGCGCCATGGGTGGTATGGAGTCAGTGATCACCGGGCTCATCGATGAGTTCCAGCTG 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1387 GACAGCGCCATGGGTGGTATGGAGTCAGTGATCACCGGGCTCATCGATGAGTTCCAGCTG 1446
Qy 1321 CTGCACAGACACCGTGAGCTCTTCACGCTCTTCATCGTCCTGGCGACCTTCCTCCTGTCC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1447 CTGCACAGACACCGTGAGCTCTTCACGCTCTTCATCGTCCTGGCGACCTTCCTCCTGTCC 1506
Qy 1381 CTGTTCTGCGTCACCAACGGTGGCATCTACGTCTTCACGCTCCTGGACCATTTTGCAGCC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1507 CTGTTCTGCGTCACCAACGGTGGCATCTACGTCTTCACGCTCCTGGACCATTTTGCAGCC 1566
Qy 1441 GGCACGTCCATCCTCTTTGGAGTGCTCATCGAAGCCATCGGAGTGGCCTGGTTCTATGGT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1567 GGCACGTCCATCCTCTTTGGAGTGCTCATCGAAGCCATCGGAGTGGCCTGGTTCTATGGT 1626
Qy 1501 GTTGGGCAGTTCAGCGACGACATCCAGCAGATGACCGGGCAGCGGCCCAGCCTGTACTGG 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1627 GTTGGGCAGTTCAGCGACGACATCCAGCAGATGACCGGGCAGCGGCCCAGCCTGTACTGG 1686
Qy 1561 CGGCTGTGCTGGAAGCTGGTCAGCCCCTGCTTTCTCCTGTTCGTGGTCGTGGTCAGCATT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1687 CGGCTGTGCTGGAAGCTGGTCAGCCCCTGCTTTCTCCTGTTCGTGGTCGTGGTCAGCATT 1746
Qy 1621 GTGACCTTCAGACCCCCCCACTACGGAGCCTACATCTTCCCCGACTGGGCCAACGCGCTG 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1747 GTGACCTTCAGACCCCCCCACTACGGAGCCTACATCTTCCCCGACTGGGCCAACGCGCTG 1806
Qy 1681 GGCTGGGTCATCGCCACATCCTCCATGGCCATGGTGCCCATCTATGCGGCCTACAAGTTC 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1807 GGCTGGGTCATCGCCACATCCTCCATGGCCATGGTGCCCATCTATGCGGCCTACAAGTTC 1866
Qy 1741 TGCAGCCTGCCTGGGTCCTTTCGAGAGAAACTGGCCTACGCCATTGCACCCGAGAAGGAC 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1867 TGCAGCCTGCCTGGGTCCTTTCGAGAGAAACTGGCCTACGCCATTGCACCCGAGAAGGAC 1926
Qy 1801 CGTGAGCTGGTGGACAGAGGGGAGGTGCGCCAGTTCACGCTCCGCCACTGGCTCAAGGTG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1927 CGTGAGCTGGTGGACAGAGGGGAGGTGCGCCAGTTCACGCTCCGCCACTGGCTCAAGGTG 1986
Qy 1861 TAGAGGGAGCAGAGACGAAGACCCCAGGAAGTCATCCTGCAATGGGAGAGACACGAACAA 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1987 TAGAGGGAGCAGAGACGAAGACCCCAGGAAGTCATCCTGCAATGGGAGAGACACGAACAA 2046
Qy 1921 ACCAAGGAAATCTAAGTTTCGAGAGAAAGGAGGGCAACTTCTACTCTTCAACCTCTACTG 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2047 ACCAAGGAAATCTAAGTTTCGAGAGAAAGGAGGGCAACTTCTACTCTTCAACCTCTACTG 2106
Qy 1981 AAAACACAAACAACAAAGCAGAAGACTCCTCTCTTCTGACTGTTTACACCTTTCCGTGCC 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2107 AAAACACAAACAACAAAGCAGAAGACTCCTCTCTTCTGACTGTTTACACCTTTCCGTGCC 2166
Qy 2041 GGGAGCGCACCTCGCCGTGTCTTGTGTTGCTGTAATAACGACGTAGATCTGTGCAGCGAG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2167 GGGAGCGCACCTCGCCGTGTCTTGTGTTGCTGTAATAACGACGTAGATCTGTGCAGCGAG 2226
Qy 2101 GTCCACCCCGTTGTTGTCCC 2120
||||||||||||||||||||
Db 2227 GTCCACCCCGTTGTTGTCCC 2246
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the vector of Johnson et al. wherein the human SLC6A3 gene has at least 70% sequence identity to SEQ ID NO: 12 and encodes a functional DAT protein because Johnson et al. taught hDAT cDNA in a pIREShyg2 vector and Yao et al. taught SEQ ID NO: 57 which is the SLC6A3 mRNA sequence. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Johnson et al. (The Journal of Biological Chemistry 2005; reference previously cited by the Examiner) as evidenced by NCBI (SLC6A3 solute carrier family 6 member 3 [Homo sapiens (human)], Gene ID: 6531) and Shikama et al. (BMC Molecular Biology 2010; reference previously cited by the Examiner) as applied to claims 1, 10, 11, and 22 above in view of Liu (US 2008/0213271).
Regarding claim 3, the teachings of Johnson et al. are discussed above.
However, Johnson et al. does not teach that the human SLC6A3 gene encodes a functional DAT protein having the amino acid sequence of SEQ ID NO: 13.
Liu teaches SEQ ID NO: 21 (designated as Db) which is identical to instant SEQ ID NO: 13 (designated as Qy) as shown in the alignment below. According to the sequence listing, SEQ ID NO: 21 is a human dopamine transporter protein.
Query Match 100.0%; Score 3266; DB 1; Length 620;
Best Local Similarity 100.0%;
Matches 620; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSKSKCSVGLMSSVVAPAKEPNAVGPKEVELILVKEQNGVQLTSSTLTNPRQSPVEAQDR 60
Qy 61 ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETWGKKIDFLLSVIGFAVDLANVWRFPYLCYKNGGGAFLVPYLLFMVIAGMPLFYMELAL 120
Qy 121 GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GQFNREGAAGVWKICPILKGVGFTVILISLYVGFFYNVIIAWALHYLFSSFTTELPWIHC 180
Qy 181 NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NNSWNSPNCSDAHPGDSSGDSSGLNDTFGTTPAAEYFERGVLHLHQSHGIDDLGPPRWQL 240
Qy 241 TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TACLVLVIVLLYFSLWKGVKTSGKVVWITATMPYVVLTALLLRGVTLPGAIDGIRAYLSV 300
Qy 301 DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DFYRLCEASVWIDAATQVCFSLGVGFGVLIAFSSYNKFTNNCYRDAIVTTSINSLTSFSS 360
Qy 361 GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIA TLPLSSAWAVVFFIMLLTLGI 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GFVVFSFLGYMAQKHSVPIGDVAKDGPGLIFIIYPEAIA TLPLSSAWAVVFFIMLLTLGI 420
Qy 421 DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DSAMGGMESVITGLIDEFQLLHRHRELFTLFIVLATFLLSLFCVTNGGIYVFTLLDHFAA 480
Qy 481 GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GTSILFGVLIEAIGVAWFYGVGQFSDDIQQMTGQRPSLYWRLCWKLVSPCFLLFVVVVSI 540
Qy 541 VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIA PEKD 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 VTFRPPHYGAYIFPDWANALGWVIATSSMAMVPIYAAYKFCSLPGSFREKLAYAIA PEKD 600
Qy 601 RELVDRGEVRQFTLRHWLKV 620
||||||||||||||||||||
Db 601 RELVDRGEVRQFTLRHWLKV 620
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the vector of Johnson et al. wherein the human SLC6A3 gene encodes a functional DAT protein having the amino acid sequence of SEQ ID NO: 13 because Johnson et al. taught hDAT cDNA in a pIREShyg2 vector and Liu taught SEQ ID NO: 21 which is a human dopamine transporter protein sequence. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claims 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over Johnson et al. (The Journal of Biological Chemistry 2005; reference previously cited by the Examiner) as evidenced by NCBI (SLC6A3 solute carrier family 6 member 3 [Homo sapiens (human)], Gene ID: 6531) and Shikama et al. (BMC Molecular Biology 2010; reference previously cited by the Examiner) as applied to claims 1, 10, 11, and 22 above in view of Kügler et al. (Gene Therapy 2003).
Regarding claims 4-7, the teachings of Johnson et al. are discussed above. Johnson et al. also teaches that DAT is a presynaptic protein that belongs to the SLC6 family of Na+/Cl- dependent neurotransmitter transporters. It is the primary regulator of the duration and strength of the dopamine signal in the synapse. DAT binds extracellular dopamine, Na+, and Cl- and transports them intracellularly, clearing dopamine from the synaptic cleft [page 10914, left column, first paragraph].
However, Johnson et al. does not teach that the promoter is a neuron-specific promoter (claim 4) or that the promoter is a human synapsin 1 promoter (claims 5 and 6). Johnson et al. also does not teach that the vector is an AAV vector (claim 7).
Kügler et al. teaches transgene expression from an adenoviral vector was restricted exclusively to neurons by using a small fragment of the human synapsin 1 gene promoter [abstract]. Kügler et al. tested the human synapsin 1 gene promoter, rat NSE gene promoter, human U1 snRNA promoter, and human cytomegalovirus promoter in terms of their expression kinetics but only the synapsin promoter allowed for a virtually exclusive neuronal targeting [column 337, right column, first full paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the vector of Johnson et al. wherein the vector is an AAV vector and the promoter is a human synapsin 1 promoter because Johnson et al. taught hDAT cDNA in a pIREShyg2 vector, Johnson et al. taught that DAT is the primary regulator of the duration and strength of the dopamine signal in the synapse, and Kügler et al. taught that transgene expression from an adenoviral vector was restricted exclusively to neurons by using a small fragment of the human synapsin 1 gene promoter. One of ordinary skill in the art would have made such a modification because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Johnson et al. (The Journal of Biological Chemistry 2005; reference previously cited by the Examiner) as evidenced by NCBI (SLC6A3 solute carrier family 6 member 3 [Homo sapiens (human)], Gene ID: 6531) and Shikama et al. (BMC Molecular Biology 2010; reference previously cited by the Examiner) in view of Kügler et al. (Gene Therapy 2003) as applied to claims 1, 4-7, 10, 11, and 22 above, and further in view of Kügler et al. (Virology 2003).
Regarding claims 8 and 9, the teachings of Johnson et al. and Kügler et al. (Gene Therapy 2003) are discussed above.
However, Johnson et al. and Kügler et al. (Gene Therapy 2003) do not teach that the vector is an AAV2 vector.
Kügler et al. (Virology 2003) demonstrated that the small human synapsin 1 gene promoter is suited for gene transfer applications in the brain using AAV vectors. As well as in adenoviral vectors, the hSYN promoter mediated completely neuron-restricted transgene expression in both the adult brain and cultured embryonic neurons. Because vectors based on the AAV-2 capsid show a high degree of neuronal tropism, the main advantage of using the hSYN promoter in this type of vector is the gain in transgene capacity [page 91, right column, first full paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the vector of Johnson et al. wherein the vector is an AAV2 vector comprising a human synapsin 1 promoter operably linked to the human SLC6A3 gene because Johnson et al. taught hDAT cDNA in a pIREShyg2 vector and Kügler et al. taught that vectors based on the AAV-2 capsid show a high degree of neuronal tropism and the main advantage of using the hSYN promoter in this type of vector is the gain in transgene capacity. One of ordinary skill in the art would have made such a modification because it would have amounted to a simple substitution of one known element for another to obtain predictable results.
Conclusion
No claims are allowed.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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