DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20, of record 1/10/2024 are pending. Prosecution on the merits commences for claims 1-20.
PRIORITY
The instant application, filed 1/10/2024, is a CONTINUATION of US Patent No. 11,905,312, filed 8/09/2019, which is a 371 of PCT/YS2018/018381, filed 02/15/2018, which claims priority to US Provisional Application No. 62/459,286, filed 02/15/2017. Thus, the earliest possible priority for the instant application is 02/15/2017.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, US Provisional Application No. 62/459,286, filed 02/15/2017, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Independent claims 1 and 16 are directed to an AAV vector comprising a capsid comprising an amino acid sequence of SEQ ID NO: 9 or SEQ ID NO:30, or an AAV capsid comprising an amino acid sequence of SEQ ID NO: 9 or SEQ ID NO:30. US Provisional Application No. 62/459,286 only discloses SEQ ID NOs: 1-29 and does not disclose SEQ ID NOs: 30. Thus instant claims 1-20, which all depend from claims 1 and 16, are afforded priority to PCT/US2018/018381, filed 02-15-2018.
CLAIMS
Instant claims 1 and 16 are directed to an AAV vector comprising a capsid comprising an amino acid sequence of SEQ ID NO: 9 or SEQ ID NO:30, or an AAV capsid comprising an amino acid sequence of SEQ ID NO: 9 or SEQ ID NO:30:
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SEQ ID NOs: 9 and 30 encode variants of a AAV1 capsid protein. The broadest reasonable interpretation of an AAV capsid comprising “an” amino acid sequence is any two consecutive amino acids within the disclosed sequences, and does not require the claim encompass the entire full-length sequence. Amendment to wherein the capsid comprises “the” amino acid sequence of SEQ ID NO:9 or SEQ ID NO:30 would require the full-length protein disclosed in the claimed SEQ ID NO.
Alignment of SEQ ID NOs: 1 (AAV1 VP1), 9 and 30 show they differ only between amino acids S262 through H272 relative to SEQ ID NO:1 (AAV1):
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SEQ ID NO: 9 comprises S262N, A263N, S264T, T265S, A267S, S268T mutations, and a G insertion after residue 265.
SEQ ID NO: 9 comprises S262N, A263N, S264T, T265S, A267S, S268T and H272T mutations, and a G insertion after residue 265.
Claim Objections
Claims are objected to because of the following informalities:
Claim 9 is missing the article “a” in front of “nuclease” in line 1.
Clam 20 is objected to for the use of periods within the body of the claim (“a.” and “b.”). While there is no set statutory form for claims, the present Office practice is to insist that each claim begin with a capital letter and end with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). See M.P.E.P. § 608.01(m).
Appropriate correction is required.
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) 1-8, and 11-20 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US Application Publication No. 2015/0238550 to McCown, of record (IDS 1/10/24), as evidenced by Powell, et al. Characterization of a Novel Adeno-Associated Viral Vector with Preferential Oligodendrocyte Tropism. Gene Therapy, 2016. 23:807-814, of record (IDS 1/10/24).
The art is applied in line with the broadest reasonable interpretation, which only requires 2 consecutive amino acids disclosed within the claimed sequences.
With regard to claims 1 and 16, McCown discloses a recombinant chimeric AAV capsid identified as BNP61, also known as Olig001 (Abstract, paragraphs [0061]-[0062], FIG 1). Oligo001 is encoded by SEQ ID NO:2 therein. McCown does not show an alignment of Olig001 with AAV1 VP1.
Powell discloses recombinant chimeric AAV capsid Olig001, which is 100% identical to Olig001 of McCown.
Powell is cited as evidence to show McCown’s SEQ ID NO:2, when aligned with AAV1, comprises a modification at amino acid residues between S262 and H272 according to AAV1. Residues 201-300 of AAV1 compared to olig001 are shown below, from FIG 3 of Powell:
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A larger section of residues 260-277, corresponding to the variable loop region 1 of the aligned sequences is provided below:
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Thus, McCown anticipates claims 1 and 16.
With regard to claims 2-5, McCown discloses wherein the AAV vector comprising the capsid protein encapsidates a nucleic acid, wherein the nucleic acid comprises at least one terminal repeat sequence that is 5’ and 3’ of a heterologous nucleic acid sequence (paragraphs [0054]-[0058], [0066], [0068]).
With regard to claims 6-8, 11-13 McCown discloses vectors encode one or more heterologous nucleic acids (paragraph [0104]), including wherein the heterologous nucleic acids encode therapeutic proteins, immunogenic peptides, therapeutic RNA, untranslated RNA, antisense RNA, a ribozyme, or a guide RNA (paragraphs [0052], [0069]-[0100], [0152]-[0187]).
With regard to claim 14, McCown discloses the viral vector in a pharmaceutically acceptable carrier (paragraphs [0009], and [0188]-[0189]).
With regard to claims 15, and 17-20 McCown discloses the viral vector and AAV capsid comprising Olig001 are encoded on a nucleic acid, and packaged into a viral vector particle in a packaging cell. Particles produced by the packaging cell are isolated, and are used to introduce the heterologous nucleic acids encapsidated within the capsid into cells (paragraphs [0039]-[0040], [0119]-[0143], [0152]-[0187], [0191], [0266], [0230]).
Claim(s) 1-8, 11, and 13-20 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO2015/191508 to Kotin, of record (IDS 1/10/24).
The art is applied in line with the broadest reasonable interpretation, which only requires 2 consecutive amino acids disclosed within the claimed sequences.
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With regard to claims 1 and 16 Kotin discloses generating chimeric AAV virus capsids by swapping out one or more domains from one donor serotype to an acceptor serotype (Abstract, paragraphs [0026]-[0030], [00162], [00163], [00168], [00203]). See FIG 8 of Kotin below:
Kotin discloses the domains that can be swapped include one or more variable domains I-IX (illustrated above in FIG 8), and/or CNS-variable domains (VRI-CNS to VRXII-CNS), as illustrated by FIG 6 of Kotin (paragraphs [00162]- [00163], [00255]-[00260], Examples 4-8, FIGs 4, 5, 7, 8, 9, 10) . Kotin discloses generating the chimeric AAV capsids by alignment of VP1 peptide sequences of different serotypes to align the variable regions between serotypes, identifying a donor variable sequence from one AAV capsid serotype and replacing the corresponding variable sequence in the acceptor AAV capsid (Examples 4-9, [00162]- [00163], [00506], [00507]).
In particular, Kotin discloses generating chimeric AAV capsids by swapping the variable regions from AAV2 (SEQ ID NO: 435) with the corresponding VRI from AAV7 (SEQ ID NO:442), AAV8 (SEQ ID NO:440), AAV9 (SEQ ID NO:436), AAVrh10 (SEQ ID NO:438) (Examples 4-8, FIGs 4, 6, 10). Kotin discloses additional donor and/or acceptor sequences include AAV1 (SEQ ID NO:431), paragraph [0014]).
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Analysis of Kotin’s FIGs 4 and 6 show Variable Region I (VR1) corresponds to amino acids 260-270 of VP1 of AAV1 (translated from Kotin SEQ ID NO:1), which overlaps with CNS variable region V (VRV-CNS), corresponding to amino acids 262-272 of VP1 of AAV1. Alignment of VP1 sequences from AAV1, AAV8 and AAVrh10 corresponding to the VRI/VRV-CNS is provided below:
Exchange of discrete VR1 domain of AAVrh10 (QISNGTSGGSTND) for the corresponding residues into AAV1 of Kotin (QISSASTGASND) of results in a peptide with 100% identity to instantly claimed SEQ ID NO:9:
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In addition, exchange of discrete VRV-CNS domain of AAVrh10 (NGTSGGSTNDNT) for the corresponding residues into AAV1 of Kotin (SASTGASNDNH) of results in a peptide with 100% identity to instantly claimed SEQ ID NO:30:
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As such, Kontin anticipates claims 1 and 16.
With regard to instant claims 2- 5, Kotin discloses the chimeric capsid proteins are assembled into viral vectors comprising AAV capsids, wherein the viral vectors comprise a nucleic acid comprising as least one terminal repeat 5’ and 3’ of an at least one heterologous nucleic acid (paragraphs [0026], [00146]-[0152], [00162], [00246], [00350]).
With regard to claims 6-8, 11, and 13 Kotin discloses the nucleic acid encoded within the viral vector encodes a heterologous nucleic acid encoding a therapeutic peptide, antigens (thus reading on immunogenic), RNA, non-coding RNA, antisense RNA (paragraphs [0024], [00246]-[00251], [00261]-[00275]).
With regard to claim 14, Kotin discloses the viral vectors can be formulated as pharmaceutical compositions (paragraphs [00353], [00414]-[00439]).
With regard to claims 15, and 17-20 Kotic discloses the viral vectors and chimeric capsid are encoded on a nucleic acid, and packaged into a viral vector particle in a packaging cell. Particles produced by the packaging cell are isolated, and which encode a heterologous nucleic acid are used to introduce the heterologous nucleic acids encapsidated within the capsid into cells (paragraphs [00276]-[00323], [00345]-[00413]).
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.
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.
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over US Application Publication No. 2015/0238550 to McCown, of record, as evidenced by Powell, et al. Characterization of a Novel Adeno-Associated Viral Vector with Preferential Oligodendrocyte Tropism. Gene Therapy, 2016. 23:807-814, of record, as applied to claims 1-8, and 11-20 above, and further in view of US Application Publication No. 2016/0340661 to Le Cong.
Claims 9-10 are directed to embodiments wherein the AAV vector encodes a protein, wherein the protein is a Cas9 nuclease.
The disclosures of McCown as evidenced by Powell are applied as in the 102 rejection above, the content of which is incorporated herein in its entirety. McCown as evidenced by Powell disclose an AAV vector comprising a chimeric capsid protein according to claim 1. McCown discloses the vector encodes a heterologous peptide and/or a therapeutic RNA, including a guide RNA.
However, neither McCown nor Powell disclose wherein the AAV vector encodes a cas9 nuclease, as required by instant claims 9-10.
Le Cong discloses recombinant AAV viral vectors can encode a cas9 nuclease and gRNA on single vector (paragraphs [0008], [0141], [0173], [0279]-[0280]. [0288]-[0299]). Le Cong discloses the AAV vector can comprise any combination of hybrid capsids (paragraph [0328]).
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the nucleic acids encoding a ca9 protein for the one or more heterologous therapeutic peptides/RNA of McCown as evidenced by Powell because they are both explicitly taught as being useful for being encoded on AAV vectors comprising chimeric capsids. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Claims 9-10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over WO2015/191508 to Kotin, of record, as applied to claims 1-8, 11, and 13-20 above, and further in view of US Application Publication No. 2016/0340661 to Le Cong.
Claims 9-10 and 12 are directed to embodiments wherein the AAV vector encodes a protein, wherein the protein is a Cas9 nuclease, or an RNA, wherein the RNA is a guide RNA.
The disclosure of Kotin is applied as in the 102 rejection above, the content of which is incorporated herein in its entirety. Kotin discloses an AAV vector comprising a chimeric capsid protein according to claim 1. Kotin discloses the vector encodes a heterologous peptide and/or a therapeutic RNA.
However, Kotin does not disclose wherein the AAV vector encode a cas9 nuclease, as required by instant claims 9-10, or a guide RNA as required by instant claim 12.
Le Cong discloses recombinant AAV viral vectors can encode a cas9 nuclease and gRNA on single vector (paragraphs [0008], [0141], [0173], [0279]-[0280]. [0288]-[0299]). Le Cong discloses the AAV vector can comprise any combination of hybrid capsids (paragraph [0328).
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the nucleic acids encoding a ca9 protein or guide RNA for the one or more heterologous therapeutic peptides/RNA of Kotin because they are both explicitly taught as being useful for being encoded on AAV vectors comprising chimeric capsids. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY A ARON whose telephone number is (571)272-2789. The examiner can normally be reached Monday-Friday 9AM-5PM.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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