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 .
1. Claims 4, 7-12, 14, 15, 22, 24-28, 30-32, 34, 38, 40, 42, and 43 have been cancelled. Claims 3, 13, 16-18, 20, 21, 23, 29, 33, 35-37, and 51 have been amended.
Claims 1-3, 5, 6, 13, 16-21, 23, 29, 33, 35-37, 39, and 41 are pending and under examination.
Claim Objections
2. Claim 1 is objected to because of the recitation “a poly A” on line 6. Correction to “a poly A signal sequence” is required.
3. Claims 2, 3, 5, 6, 13, and 17 should recite “The rAAV vector packaged in the AAV capsid having broad tissue tropism” on the preamble.
4. Claim 3 should be amended to recite:
The recombinant rAAV vector of claim 1, wherein the wide-tropism AAV capsid is selected from the AAV1 capsid, AAV2 capsid, AAV3 capsid, AAV4 capsid, AAV5 capsid, AAV6 capsid, AAV7 capsid, AAV8 capsid, and AAV9 capsid.
5. Claim 5 is objected to because of the recitation “or” in line 3. Correction to “and” is required.
6. Claims 16-18, 29, 33, and 36 should recite “the rAAV vector packaged in the AAV capsid having broad tissue tropism of claim 1”.
7. Claim 17 should recite “the rAAV vector packaged in the AAV capsid having broad tissue tropism of claim 1”.
8. Claim 20 should recite “the rAAV vector further comprises”.
9. Claim 21 should be amended to recite:
The method of claim 19, wherein the wide-tropism AAV capsid is selected from the AAV1 capsid, AAV2 capsid, AAV3 capsid, AAV4 capsid, AAV5 capsid, AAV6 capsid, AAV7 capsid, AAV8 capsid, and AAV9 capsid.
10. Claim 23 is objected to because of the recitation “and/or unmodified” in line 2. Codon optimized and engineered polynucleotides are necessarily modified. Correction to “codon optimized and/or engineered, or unmodified” is required.
11. Claim 37 should be amended to recite:
A method of expressing [Symbol font/0x61]-GAL enzyme in a cell, the method comprising administering the rAAV vector packaged in the AAV capsid having broad tissue tropism of claim 1 to the cell.
12. Claim 41 should recite “The rAAV vector packaged in the AAV capsid having broad tissue tropism of claim 39”.
Claim Rejections - 35 USC § 102
15. 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.
16. Claims 1, 3, 6, 13, 16-19, 21, 23, 29, 33, and 35-37 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kirn et al. (US 2021/0332341), as evidenced by both NCBI BLAST Alignment and GenBank: AF334827.1.
Kirn et al. teach an rAAV particle comprising an rAAV vector packaged in an AAV2 capsid; the rAAV vector comprises in order: a 5’ AAV2 ITR; a CAG promoter (a ubiquitous promoter comprising the CMV early enhancer, the chicken β-actin gene promoter, and a splice acceptor from the rabbit the β-globin gene); polynucleotide which is codon optimized for human use and which encodes [Symbol font/0x61]-Gal; a polyadenylation sequence; and a 3’ AAV2 ITR; the rAAV (claims 1, 3, and 13) (see Abstract;[ 0005]-[0006]; [0008]; [0022]-[0023]; [0066]; [0077]-[0079]; [0094] [0102]-[0103]; [0105]; [0109]; Example 4; claims 1-12).
Although Kirn et al. do not specifically teach that the rabbit β-globin gene splice acceptor is provided as an intron (claim 6), Kirn et al. do teach that the CAG promoter is set forth by SEQ ID NO: 5 (see [0008]-[0009]). As evidenced by the attach NCBI BLAST Alignment, SEQ ID NO: 5 is identical to nucleotides 1-1664 of the cloning vector pTurbo-Cre (GenBank: AF334827.1). As evidenced by GenBank: AF334827.1, nucleotides 1-1664 of pTurbo-Cre comprise the CMV early enhancer, the chicken β-actin gene promoter, and an intron from the rabbit the β-globin gene. Thus, the CAG promoter of Kirn et al. comprises the CMV early enhancer, the chicken β-actin gene promoter, and an intron from the rabbit the β-globin gene (claims 6 and 18).
Kirn et al. also teach treating Fabry disease in a subject by intravenously administering the rAAV particle to the subject (i.e., administering a pharmaceutical composition); upon administration, [Symbol font/0x61]-Gal expression is detected in kidney, small intestine, heart, liver, and plasma at 8 weeks post-administration (claims 16, 17, 19, 21, 23, 29, 33, and 35) (see Abstract; [0022]-[0023]; [0098]-[0099]; [0103]; Example 4; claims 21-25). By administering the rAAV particle to the subject, Kirn et al. necessarily transduce and obtain cells within the subject which comprise the rAAV vector (claims 18 and 37).
With respect to claim 36, Kirn et al. teach that the administration of the rAAV particle results in reduced gb3 levels in the heart, small intestine, kidney, and liver (see [0025]; [0094]; [0144]; [0190]; [0197]-[0206]; Fig. 12).
Thus, Kirn et al. teach all claim limitations and anticipate the claimed invention.
17. Claims 1-3, 13, 16-18, and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park et al. (PNAS, 2003, 100: 3450-3454), as evidenced by both Niwa et al. (Gene, 1991, 108: 193-200) and CD Genomics Blog.
Park et al. teach an rAAV2 particle, i.e., comprising an rAAV vector packaged in the AAV2 capsid; the rAAV vector comprises an expression cassette containing a CAG promoter, a polynucleotide encoding [Symbol font/0x61]GAL, WPRE, and a polyadenylation sequence; Park et al. teach treating Fabry disease in a subject by intravenously administering the rAAV particle to the subject (i.e., administering a pharmaceutical composition); upon administration, [Symbol font/0x61]-Gal expression is detected in kidney, heart, small intestine, liver, spleen, and plasma, at 24 weeks post-administration (i.e., CAG is a ubiquitous promoter; claims 1-3, 13, 16, 17, and 37) (see Abstract; p. 3450, column 2, first and second paragraphs; p. 3451, column 1, fifth paragraph and paragraph bridging columns 1 and 2; p. 3452, Table 1; p. 3453-3454). Park et al. teach that the CAG promoter is the modified chicken β-actin promoter disclosed by Niwa et al. (see p. 3451, column 1). As evidenced by Niwa et al., the CAG promoter used by Park et al. consists of the CMV early enhancer connected to the chicken β-actin promoter (see bridging p. 194 and 195).
Although Park et al. do not specifically teach that the AAV2 vector comprises 5’ and 3’ ITRs, as evidenced by CD Genomics Blog, 5’ and 3’ ITRs flanking the expression cassette are inherent to AAV vectors (claim 1) (see p. 7).
By administering the rAAV particle to the subject, Kirn et al. necessarily transduce and obtain cells within the subject which comprise the rAAV vector (claims 18 and 37).
Thus, Park et al. teach all claim limitations and anticipate the claimed invention.
18. Claim 39 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ziegler et al. (Mol. Ther., 2004, 9: 231-240), as evidenced by CD Genomics Blog.
Ziegler et al. teach an rAAV2 particle comprising an rAAV2 vector packaged in an AAV2 capsid. The rAAV vector comprises an expression cassette containing the liver-specific DC190 promoter operably linked to a polynucleotide encoding [Symbol font/0x61]-Gal, and a polyadenylation sequence (claims 39) (see Abstract; p. 234; p. 238, column 2, last two paragraphs). Although Ziegler et al. do not specifically teach that the AAV2 vector comprises 5’ and 3’ ITRs, as evidenced by CD Genomics Blog, 5’ and 3’ ITRs flanking the expression cassette are inherent to AAV vectors (claim 39) (see p. 7).
Thus, Ziegler et al. teach all claim limitations and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
19. 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.
20. Claims 39 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Ziegler et al., in view of Kirn et al.
The teachings of Ziegler et al. are applied as above for claim 39. Ziegler et al. do not teach a codon-optimized [Symbol font/0x61]-Gal (claim 41). Kirn et al. teach a polynucleotide encoding [Symbol font/0x61]-Gal, where the polynucleotide is codon optimized for human use (see [0006]; [0109]). One of skill in the art would have found obvious to modify the rAAV of Ziegler et al. by using the codon optimized polynucleotide of Kirn et al., to achieve the predictable result of obtaining an rAAV vector suitable for human therapy.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
21. Claims 1-3, 6, 13, 16-21, 23, 29, 33, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Kirn et al. as evidenced by both NCBI BLAST Alignment and GenBank: AF334827.1, in view of Park et al. (PNAS, 2003, 100: 3450-3454).
The teachings of Kirn et al. are applied as above for claims 1, 3, 6, 13, 16-19, 21, 23, 29, 33, and 35-37. Kirn et al. do not teach WPRE (claims 2 and 20). Park et al. teach adding WPRE to rAAV-[Symbol font/0x61]GAL vectors, where WPRE enhances the level and stability of the expressed protein (see Abstract; p. 3450, column 2, second paragraph; p. 3451, column 1, fifth paragraph; p. 3453-3454). One of skill in the art would have found obvious to modify the rAAV of Kirn et al. by further including WPRE, to achieve the predictable result of obtaining an efficient therapeutic composition.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
22. Claims 1, 3, 5, 6, 13, 16-19, 21, 23, 29, 33, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Kirn et al. as evidenced by both NCBI BLAST Alignment and GenBank: AF334827.1, in view Teschendorf et al. (Anticancer Res., 2002, 22: 3325-3330; Abstract).
The teachings of Kirn et al. are applied as above for claims 1, 3, 6, 13, 16-19, 21, 23, 29, 33, and 35-37. Kirn et al. do not teach the EF-1[Symbol font/0x61] promoter (claim 5). Teschendorf et al. teach that the EF-1[Symbol font/0x61] promoter drives robust transgene expression in vivo (see Abstract). Based on these teachings, one of skill in the art would have found obvious to modify the rAAV vector if Kirn et al. by replacing the CAG promoter with EF-1[Symbol font/0x61] promoter to achieve the predictable result of obtaining an efficient therapeutic composition.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
23. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633