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
Election/Restrictions
Applicant's election without traverse of Group II (claims 7-10 and 42-43) in the reply filed on 02/04/2026 is acknowledged.
Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Election of the following species on the reply filed on 02/04/2026 is acknowledged: 1) delivery method: Intravenous
2) Step (a): claim 28
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US21/45945, filed 08/13/2021.
Applicant' s claim for the benefit of a prior-filed parent provisional application 63/109734, filed on 11/04/2020, 63/065616 filed 08/14/2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is 08/14/2020.
Claims Status
Claims 1-6 and 29-41 are canceled, claims 42-43 (drawn to elected group II) are newly added, claims 11-13 and 21-28 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 7-10 and 42-43 have been considered on the merits.
Claim Objections
Claim 9 is objected to because it recites “identity a nucleotide sequence of Seq ID NO: 1 or 3”. This is improper grammar. If the claim were amended to recite “identity with a nucleotide sequence of Seq ID NO: 1 or 3” the objection as written would be overcome.
Claim 42 is objected to because of the following informalities: The claim recites “having an Clade A capsid”. This is improper grammar. If the claim were amended to recite “having a [. Appropriate correction is required.
Nucleotide and/or Amino Acid Sequence Disclosures
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.
The drawings are objected to because Fig 3A-D and Fig 4A do not have sequence identifiers for the disclosed sequences.
Claim Rejections - 35 USC § 112
Claim 9 is 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.
Regarding claim 9: The claim requires a capsid protein produced by expression of a nucleotide sequence sharing at least 90% identity with a nucleotide sequence of Seq ID NOs: 1 or 3.
Seq Id NO: 1 and 3 are nucleic acid sequences comprising 2211 bp. The broadest reasonable interpretation of the claim limitation “at least 90% identity with a nucleotide sequence of Seq ID NOs: 1 or 3” is a nucleic acid sequence that can differ from Seq Id NO: 1 or 3 by up to 10% (~221 residues) compared to Seq ID NO: 1 or 3.
Teachings of the Specification
The specification provides some guidance for the genus of nucleotide sequences which share at least 90% identity with to a nucleotide sequence of Seq ID Nos: 1 or 3.
Seq Id NO 1 and 3 share ~90% sequence identity with sequence changes distributed throughout much of the sequence (Alignment below; Query is Seq Id NO: 1 and Sbjct is Seq ID NO: 3).
Query 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
|||||||| || |||||||||||||||||||||||||||||||| ||||| ||||||||
Sbjct 1 ATGGCTGCTGACGGTTATCTTCCAGATTGGCTCGAGGACAACCTTTCTGAAGGCATTCGT 60
Query 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
||||||||||| ||||||||||||||||| ||||||||||| ||||| ||||||||||||
Sbjct 61 GAGTGGTGGGCTCTGAAACCTGGAGCCCCTAAACCCAAAGCGAACCAACAAAAGCAGGAC 120
Query 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
|||||||||||||| |||||||| || ||||| |||||||||||||||||||||||||||
Sbjct 121 GACGGCCGGGGTCTTGTGCTTCCGGGTTACAAATACCTCGGACCCTTCAACGGACTCGAC 180
Query 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
|| || ||||| ||||||||||||||||| || |||||||| |||||||| || ||||||
Sbjct 181 AAAGGAGAGCCGGTCAACGCGGCGGACGCGGCAGCCCTCGAACACGACAAAGCTTACGAC 240
Query 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
||||||||||| || |||||||| |||||||| ||||| |||||||||||||||||||||
Sbjct 241 CAGCAGCTCAAGGCCGGTGACAACCCGTACCTCCGGTACAACCACGCCGACGCCGAGTTT 300
Query 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
||||||||||| ||||||||||||||||||||||||||||| || ||||||||||||||
Sbjct 301 CAGGAGCGTCTTCAAGAAGATACGTCTTTTGGGGGCAACCTTGGCAGAGCAGTCTTCCAG 360
Query 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
||||| ||| ||||||| || ||||||||||||||||||||||||||||| |||||||||
Sbjct 361 GCCAAAAAGAGGGTTCTTGAGCCTTTTGGTCTGGTTGAGGAAGCAGCTAAAACGGCTCCT 420
Query 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
|||||||| | || ||||||||||| || || ||||| ||||| || || || ||||||
Sbjct 421 GGAAAGAAGAGGCCTGTAGAGCAGTCTCCTCAGGAACCGGACTCATCATCTGGTATTGGC 480
Query 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
||||| ||||||||||| |||||||| ||||| |||||||||||||||||||||||||||
Sbjct 481 AAATCGGGCCAGCAGCCTGCCAAAAAAAGACTAAATTTCGGTCAGACTGGCGACTCAGAG 540
Query 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
Query 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
Query 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
Query 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
Query 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
Query 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
Query 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
Query 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
Query 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
Query 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
||||||||||||||||||||||||||||||||||||||||||||||| || ||||| ||
Sbjct 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTATGGATACCTCACC 1140
Query 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
|| ||||| || || || || || ||||| ||||||||||| |||||||| || |||||
Sbjct 1141 CTGAACAACGGAAGTCAAGCGGTGGGACGCTCATCCTTTTACTGCCTGGAGTACTTCCCT 1200
Query 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
|| || ||||| || || || || ||||| ||||||||||| ||||| || ||||| |||
Sbjct 1201 TCGCAGATGCTAAGGACTGGAAATAACTTCACCTTCAGCTATACCTTCGAGGATGTACCT 1260
Query 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
|| |||||||| ||||| ||||||||||| |||| | | ||||||||||| || ||
Sbjct 1261 TTTCACAGCAGCTACGCTCACAGCCAGAGTTTGGATCGCTTGATGAATCCTCTTATTGAT 1320
Query 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
||||| ||||| ||||| |||||||| || |||||||| |||||||||||||||||||||
Sbjct 1321 CAGTATCTGTACTACCTGAACAGAACGCAAAATCAATCTGGAAGTGCACAAAACAAGGAC 1380
Query 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
|||| ||||||||||||||||| |||||||||||||||||||||||||| ||||||||
Sbjct 1381 CTGCTTTTTAGCCGGGGGTCTCCTGCTGGCATGTCTGTTCAGCCCAAAAATTGGCTACCT 1440
Query 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
|||||||| ||||| || ||| | ||||| || || |||||||||||||||||||| |||
Sbjct 1441 GGGCCCTGCTACCGGCAACAGAGAGTTTCAAAGACTAAAACAGACAACAACAACAGTAAC 1500
Query 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
||||||||||| |||||| |||||| ||||| || || || ||||| |||||||| ||
Sbjct 1501 TTTACCTGGACAGGTGCCAGCAAATATAATCTCAATGGCCGCGAATCGATCATTAATCCA 1560
Query 1561 GGCACCGCTATGGC-ATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGT 1619
|| ||||||||||| | ||||||||||| |||||||||||||| || |||||||| ||
Sbjct 1561 GGAACCGCTATGGCCAGT-CACAAGGACGATGAAGACAAATTTTTCCCTATGAGCGGCGT 1619
Query 1620 TATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGAT 1679
|||||| |||||||||||||||||||||||| |||||||||||||| ||||| |||||
Sbjct 1620 TATGATATTTGGCAAAGAAAATGCAGGAGCAAGTAACACTGCATTAGATAATGTAATGAT 1679
Query 1680 TACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGT 1739
||| |||||||| || |||||||||||||| || ||||| || |||||||||||||||||
Sbjct 1680 TACGGATGAAGAAGAGATTAAAGCTACCAATCCTGTGGCAACAGAGAGATTTGGAACTGT 1739
Query 1740 GGCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGG 1799
||||||||| | || ||| ||||||||||| ||||| |||||||| |||||||||||
Sbjct 1740 GGCAGTCAACTTGCAGAGCTCAAATACAGACCCCGCAACTGGAGACGTCCATGTCATGGG 1799
Query 1800 GGCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGC 1859
||| ||||||||||||||||||||||| | ||||||||||| || || || || |||||
Sbjct 1800 GGCCTTACCTGGCATGGTGTGGCAAGATCGTGACGTGTACCTTCAAGGACCTATCTGGGC 1859
Query 1860 CAAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACT 1919
||||||||||||||||||||||||||||| || |||||||| ||||| |||||||||||
Sbjct 1860 AAAGATTCCTCACACGGATGGACACTTTCATCCTTCTCCTCTGATGGGAGGCTTTGGACT 1919
Query 1920 TAAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGC 1979
|| || ||||||||||| |||||||||||||| || || || || || |||||||||||
Sbjct 1920 GAAACATCCGCCTCCTCAAATCCTCATCAAAAATACTCCGGTACCGGCAAATCCTCCGGC 1979
Query 1980 AGAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAG 2039
|||||| |||||||||||||||||||| ||||| ||||||||||| ||||| || ||
Sbjct 1980 AGAGTTCAGCGCTACAAAGTTTGCTTCATTTATCACTCAGTACTCCACTGGACAGGTCAG 2039
Query 2040 CGTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCA 2099
|||||||||||| |||||||| |||||||||||||| || || |||||||| || |||||
Sbjct 2040 CGTGGAAATTGAGTGGGAGCTACAGAAAGAAAACAGCAAACGTTGGAATCCAGAGGTGCA 2099
Query 2100 GTACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACT 2159
|||||| |||||||||||||| |||||||| || || || ||||| ||||||||||| ||
Sbjct 2100 GTACACTTCCAACTACGCGAAGTCTGCCAATGTGGACTTTACTGTAGACAACAATGGTCT 2159
Query 2160 TTATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCC 2205
||||||||| |||||||| ||||| ||||| || || || || |||
Sbjct 2160 TTATACTGAACCTCGCCCTATTGGAACCCGGTATCTCACACGACCC 2205
The instant specification teach AAVrh91 vp1 proteins are encoded by Seq ID NO:1 or 3 (p2 ln25-30). The instant specification also teaches vp2 proteins are encoded by 412-2208 of Seq ID NO: 1 or 3 (p2 ln 30-34) and vp3 proteins are encoded by nucleotides 607-2208 of Seq ID NO: 1 or 3 (p3 ln 5-10).
The instant specification teaches variable proteins of the capsids encoded by Seq ID NO: 1(AAVrh91: vpl- nt 1 to 2208; vp2- nt 412 to 2208; vp3-nt 607 to 2208 of SEQ ID NO: 1) and Seq ID NO: 3 (AAVrh9leng: vpl- nt 1 to 2208; vp2- nt 412 to 2208; vp3- nt 607 to 2208 of SEQ ID N0:3) (p23 ln 25-30).
Fig 3A-3D shows an alignment of nucleic acid sequences encoding the capsid proteins and the start of the sequence encoding VP1 (1bp) VP2 (~412) and VP3 (~607).
Figure 4A shows the alignment of the amino acid sequences encoding capsid proteins and identify amino acid residues that are conserved among the four AAV vectors AAVrh91eng, AAVrh91, AAV6.2 and AAV1.
The state of the art:
It is well known in the art that the AAV capsid proteins of various serotypes share amino acid homology and that changes in the nucleic acid sequence encoding the capsid protein can cause unpredictable changes capsid function. It is also understood that the degree of amino acid identity varies among serotypes and amino acid homology is not a reliable predictor of capsid protein function. Furthermore, it is well understood in the art that small changes in the amino acid sequence of the VP1 capsid protein can have a large and unpredictable effect on capsid protein function, which can effect overall viral particle function/targeting.
Deverman et al (US 10519198 B2) teach the capsid surface for AAV9 comprises loop regions and regions that are not highly conserved are which can tolerate sequence changes such as insertions (p91 col 16 ln 15-25). Example 2 of Deverman teaches generating libraries of AAV capsid protein by introducing 7 amino acids of randomized sequence into the AAV9 capsid after amino acid position 588 (p98 col 30 ln 17-25).
Van Vliet et al (Journal of Virological Methods (2009)159;167-177) teach there are twelve known serotypes of AAV, each with unique properties, and that AAV serotypes differ in tissue tropism, transduction efficiency and antigenic reactivity (p167 col 2 para 1). Table 1 shows the amino acid identity of AAV serotypes with AAV2 for VP1 ranges from 87%-62% (p170).
Vandenberghe et al (WO 2019/217911) teach the liver-specific tropism of an AAV capsid protein can be altered by changing one residue at position 266 of the capsid; replacing the naturally occurring residue with a glycine enhances liver tropism, while replacing the naturally occurring residue with an alanine reduces liver trophism (p12 ln 20-25).
Conclusion
The instant specification provides guidance on two specific nucleic acid sequences (Seq IN NO: 1 and 3) which comprise 90% sequence identity and encode AAVrh91 capsid proteins.
The prior art teaches changes to the nucleic acid sequence encoding an AAV capsid protein can have unpredictable effects when the changes result in amino acid changes. Capsid function (such as trophism and infectivity) require protein-protein interactions between the viral capsid and the host cell receptor. It is well known in the art that protein function requires a specific structure and that amino acid substitutions and mutations can have unpredictable effects on protein folding and protein-protein interactions and thus on capsid function.
Vandenberghe further teach that a single point mutation can either increase or decrease liver trophism of a capsid protein depending on the specific residue selected, thus small amino acid changes (which can be mediated by small changes in the nucleic acid sequence encoding the protein) can have a large and unpredictable effect on capsid protein function that must be empirically determined.
Nam teach that sequence homology of capsid proteins does not predict function/trophism, thus again, the effect of amino acid changes must be determined experimentally to understand the effect such changes would have on AAV infection.
Therefore, while AAV capsid variants are known in the art one of ordinary skill in the art would not be able to predict, beyond what is taught in the instant specification, whether sequence changes to the nucleotide sequence encoding a capsid protein would generate a functional capsid protein without empirical testing.
Furthermore, the instant specification provides no guidance as how to avoid losing key structural or binding components AAV capsid proteins with nucleic acid changes of up to 221 bp of the nucleic acid sequence encoding the capsid protein and the art does not provide a remedy.
One of ordinary skill in the art would understand that capsid protein function requires binding cell receptors and other capsid proteins for a functional system. One of ordinary skill in the art would also understand that the effect of nucleic acid changes in the nucleotide sequence encoding the capsid protein can have unpredictable effects on the encoded protein structure and thus function
This demonstrates that, while capsid protein variants are known in the art, the effect of changes to the nucleotide sequences encoding a capsid protein must be tested empirically to determine how the sequence change affects protein function.
MPEP states “[a] specification may call for a reasonable amount of experimentation to make and use a patented invention. What is reasonable in any case will depend on the nature of the invention and the underlying art”.
In the case of the instant claim 9, trial and error and/or laborious screening methods are required to identify nucleic acid sequences which encode capsid variants as claimed and the species examples provided in the art are not of a large enough breadth to impart predictability on the genus as claimed.
Claim 9 is rejected as failing to meet the requirement for written description.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 42 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 42: The claim is indefinite because the claim recites “levels of transduction of the liver and/or liver toxicity observed following administration”. While “observed” implies an active step after the deliver step, there is not an explicit active step recited in the claim, apart from “delivering”.
Thus it is unclear if there is an additional active step required by the method, or if there is an optional step required by the method.
For purposes of compact prosecution the claim is examined with the explicit active steps as recited by the claim. In this case “delivering” is the only active step recited by the claim and the claim is examined accordingly.
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)(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) 7 and 42-43 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Hordeaux (US 2023/0304034 A1; priority to 63/023,593 filed 5/12/2020).
The applied reference has a common Inventor and Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Support for the teachings of Hordeaux is found in the priority application 62/023,593.
Regarding claim 7: The intended use phrases “for detargeting the liver and/or reducing liver toxicity following systemic administration of an AAV vector to a subject” does not impart active steps or structure on the claimed method.
The intended result “wherein levels of transduction of the liver and/or liver toxicity observed following administration of the AAV vector are reduced relative to an AAV vector having an AAV1, AAV8, and/or AAV9 capsid” does not impart active steps or structure on the claimed method.
Therefore any method which comprises administration of any AAV vector comprising an AAVrh91 capsid and a vector genome comprising a transgene operably linked to any regulatory sequences that direct expression of the transgene in cells of the liver, which is administered via intravenous injection, is considered to read on the invention as claimed.
Hordeaux teach an AAV vector comprising a capsid, a transgene (gene product) under the control of regulatory sequences that direct expression of the gene product (abstract, claim 1). Hordeaux teach the AAV capsid may be selected from AAFrh91 (p12 [0100]). Hordeaux teach the AAV vector comprises a liver-specific promoter (claim 17) which reads on regulatory sequences that direct expression of a transgene in cells of the liver.
Hordeaux further teach administration of the vector via intravenous injection (p1/2 [0008]).
Regarding claim 42: As discussed above, the intended use phrases “for detargeting the liver and/or reducing liver toxicity following systemic administration of an AAV vector to a subject” does not impart active steps or structure on the claimed method.
The intended result “wherein levels of transduction of the liver and/or liver toxicity observed following administration of the AAV vector are lower than transduction levels of a reference rAAV vector having an Clade A capsid” does not impart active steps or structure on the claimed method.
Therefore, any method comprising delivering via intravenous infusion a recombinant AAV vector comprising a vector genome in an AAVrh91 capsid, wherein the vector genome comprises a transgene operably linked to regulatory sequences is considered to read on the claim as written.
Hordeaux teach an AAV vector comprising a capsid, a transgene (gene product) under the control of regulatory sequences that direct expression of the gene product (abstract, claim 1). Hordeaux teach the AAV capsid may be selected from AAFrh91 (p12 [0100]). Hordeaux teach the AAV vector comprises a liver-specific promoter (claim 17) which reads on regulatory sequences that direct expression of a transgene in cells of the liver.
Hordeaux further teach administration of the vector via intravenous injection (p1/2 [0008]).
Regarding claim 43: The claim is drawn to the reference rAAV as recited in the intended result of claim 43. Because the claim does not impart an active step or structural limitation on the claimed method, a method that reads on the parent claim 42 is also considered to read on the instant claim (see claim 42 above).
Claims 7-10 and 42-43 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nambiar et al (US 2022/0204990 A1; priority to 62/840,184, filed 4/29/2019).
Regarding claim 7: The intended use phrases “for detargeting the liver and/or reducing liver toxicity following systemic administration of an AAV vector to a subject” does not impart active steps or structure on the claimed method.
The intended result “wherein levels of transduction of the liver and/or liver toxicity observed following administration of the AAV vector are reduced relative to an AAV vector having an AAV1, AAV8, and/or AAV9 capsid” does not impart active steps or structure on the claimed method.
Therefore method which comprises administration of any AAV vector comprising an AAVrh91 capsid and a vector genome comprising a transgene operably linked to regulatory sequences that direct expression of the transgene in cells of the liver, which is administered via intravenous injection, is considered to read on the invention as claimed.
Nambiar teach a recombinant AAV vector comprising an AAVrh91 capsid and a genome comprising a transgene operably linked to a regulatory sequence that directs expression of the transgene (p2 [0028]).
Nambiar further teach the promoter is specific for expression of the transgene in liver cells (p16 [0128]).
Finally, Nambiar teach a pharmaceutical composition comprising the AAV vector is administered intravenously ([18/19 [0145]/[0146]).
Regarding claim 8: The teachings of Nambiar are discussed supra. Nambiar further teach an rAAV comprising an AAVrh91 capsid protein comprising the amino acid sequence of Seq ID NO: 2 (p1 [0004]).
Seq ID NO:2 as taught by Nambiar comprises 100% identity with Seq ID NO: 2 of the instant invention (see below, Qy is Seq ID No: 2 of the instant application and Db is Seq ID No: 2 of Nambiar).
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPFGLVEEAAKTAPGKKRPVEQSPQEPDSSSGIGKSGQQPAKKRLNFGQTGDSE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPFGLVEEAAKTAPGKKRPVEQSPQEPDSSSGIGKSGQQPAKKRLNFGQTGDSE 180
Qy 181 SVPDPQPLGEPPETPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPLGEPPETPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
Qy 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
Qy 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVP 420
Qy 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
Qy 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
Qy 541 MIFGKENAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNLQSSNTDPATGDVHVMG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 MIFGKENAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNLQSSNTDPATGDVHVMG 600
Qy 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPA 660
Qy 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
Qy 721 YTEPRPIGTRYLTRPL 736
||||||||||||||||
Db 721 YTEPRPIGTRYLTRPL 736
Regarding claims 9-10: The claim recites “a capsid protein produced by expression of a nucleotide sequence of SEQ ID NO: 1 or 3”.
Claim language such as recited above encompasses nucleic acids that comprise the full-length sequence of SEQ ID NO: 1 or 3 or any portion of SEQ ID NO: 1 or 3.
This claim limitation is anticipated by any nucleic acid comprising any dinucleotide or larger oligonucleotide which is a portion of SEQ ID NO:1 or 3.
If the claim were amended to recite “a capsid protein produced by expression of the nucleotide sequence of SEQ ID NO: 1 or 3” the examiner would interpret the claims to encompass only nucleic acids that comprise the full length of the specified SEQ ID NO:, with or without additional nucleotides at either or both ends.
The teachings of Nambiar are discussed supra. Nambiar also teach Seq ID NO: 1, which comprises 100% sequence identity with Seq ID NO: 1 of the instant invention (see below; Query is Seq Id NO: 1 on the instant disclosure, Sbjct is Seq ID NO:1 of Nambiar).
Query 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
Query 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
Query 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
Query 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
Query 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
Query 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
Query 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
Query 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
Query 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
Query 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
Query 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
Query 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
Query 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
Query 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
Query 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
Query 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
Query 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
Query 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
Query 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
Query 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
Query 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
Query 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
Query 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
Query 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
Query 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
Query 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
Query 1561 GGCACCGCTATGGCATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGTT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1561 GGCACCGCTATGGCATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGTT 1620
Query 1621 ATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGATT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1621 ATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGATT 1680
Query 1681 ACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGTG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1681 ACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGTG 1740
Query 1741 GCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGGG 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1741 GCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGGG 1800
Query 1801 GCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGCC 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1801 GCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGCC 1860
Query 1861 AAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACTT 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1861 AAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACTT 1920
Query 1921 AAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGCA 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1921 AAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGCA 1980
Query 1981 GAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAGC 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1981 GAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAGC 2040
Query 2041 GTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCAG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2041 GTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCAG 2100
Query 2101 TACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACTT 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2101 TACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACTT 2160
Query 2161 TATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCCCTTTAA 2211
|||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2161 TATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCCCTTTAA 2211
Regarding claim 42: The intended use phrases “for detargeting the liver and/or reducing liver toxicity following systemic administration of an AAV vector to a subject” does not impart active steps or structure on the claimed method.
The intended result “wherein levels of transduction of the liver and/or liver toxicity observed following administration of the AAV vector are lower than transduction levels of a reference rAAV vector having an Clade A capsid” does not impart active steps or structure on the claimed method.
Therefore, any method comprising delivering via intravenous infusion a recombinant AAV vector comprising a vector genome in an AAVrh91 capsid, wherein the vector genome comprises a transgene operably linked to regulatory sequences is considered to read on the claim as written.
Nambiar teach a recombinant AAV vector comprising an AAVrh91 capsid and a genome comprising a transgene operably linked to a regulatory sequence that directs expression of the transgene (p2 [0028]).
Nambiar further teach the promoter is specific for expression of the transgene in liver cells (p16 [0128]).
Finally, Nambiar teach a pharmaceutical composition comprising the AAV vector is administered intravenously ([18/19 [0145]/[0146]).
Regarding claim 43: The claim is drawn to the reference rAAV as recited in the intended result of claim 43. Because the claim does not impart an active step or structural limitation on the claimed method, a method that reads on the parent claim 42 is also considered to read on the instant claim (see claim 42 above).
The invention as claimed is anticipated by Nambiar et al.
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.
Claim(s) 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hordeaux as applied to claims 7 and 42-43 above, and further in view of Nambiar et al (US 2022/0204990 A1; priority to 62/840,184, filed 4/29/2019).
Support for the teachings of Nambiar is found in the priority application 62/840,184.
Hordeaux anticipates claims 7 and 42-43 and thus, render them obvious, see above.
Regarding claim 8: The teachings of Hordeaux are discussed supra. Hordeaux do not disclose the amino acid sequence of the AAVrh91 capsid and thus do not teach the capsid comprises the amino acid sequence of Seq ID NO: 2.
Nambiar teach an rAAV comprising an AAVrh91 capsid protein comprising the amino acid sequence of Seq ID NO: 2 (p1 [0004]).
Seq ID NO:2 as taught by Nambiar comprises 100% identity with Seq ID NO: 2 of the instant invention (see below, Qy is Seq ID No: 2 of the instant application and Db is Seq ID No: 2 of Nambiar).
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPFGLVEEAAKTAPGKKRPVEQSPQEPDSSSGIGKSGQQPAKKRLNFGQTGDSE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPFGLVEEAAKTAPGKKRPVEQSPQEPDSSSGIGKSGQQPAKKRLNFGQTGDSE 180
Qy 181 SVPDPQPLGEPPETPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPLGEPPETPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
Qy 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
Qy 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVP 420
Qy 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
Qy 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
Qy 541 MIFGKENAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNLQSSNTDPATGDVHVMG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 MIFGKENAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNLQSSNTDPATGDVHVMG 600
Qy 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPA 660
Qy 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
Qy 721 YTEPRPIGTRYLTRPL 736
||||||||||||||||
Db 721 YTEPRPIGTRYLTRPL 736
It would have been obvious to modify the AAVrh91 capsid as taught by Hordeaux with the teachings of Nambiar, to use a an AAVrh91 capsid protein comprising the amino acid sequence of Seq ID NO: 2 of Nambiar.
One would have been motivated to modify the AAVrh91 capsid taught by Hordeaux by using the amino acid sequence of Seq ID NO: 2 of Nambiar because Hordeaux is silent on a specific amino acid sequence for the capsid protein and Hordeaux discloses a sequence for the same capsid protein.
One would have a reasonable expectation of success because both inventions are drawn to an AArh91 capsid.
Regarding claims 9-10: The claim recites “a capsid protein produced by expression of a nucleotide sequence of SEQ ID NO: 1 or 3”.
Claim language such as recited above encompasses nucleic acids that comprise the full-length sequence of SEQ ID NO: 1 or 3 or any portion of SEQ ID NO: 1 or 3.
This claim limitation is anticipated or rendered obvious by any nucleic acid comprising any dinucleotide or larger oligonucleotide which is a portion of SEQ ID NO:1 or 3.
If the claim were amended to recite “a capsid protein produced by expression of the nucleotide sequence of SEQ ID NO: 1 or 3” the examiner would interpret the claims to encompass only nucleic acids that comprise the full length of the specified SEQ ID NO:, with or without additional nucleotides at either or both ends.
The teachings of Hordeaux are discussed supra. Hordeaux are silent on the nucleic acid sequence encoding the AAV91 capsid and thus do not teach not teach the AAVrh91 is encoded by a nucleotide sequence that comprises at least 90% sequence homology with Seq Id NO: 1 or 3 or is encoded by Seq ID No: 1 or 3.
Nambiar teach Seq ID NO: 1, which comprises 100% sequence identity with Seq ID NO: 1 of the instant invention (see below; Query is Seq Id NO: 1 on the instant disclosure, Sbjct is Seq ID NO:1 of Nambiar).
Query 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
Query 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
Query 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
Query 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
Query 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
Query 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
Query 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
Query 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
Query 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
Query 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
Query 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
Query 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
Query 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
Query 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
Query 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
Query 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
Query 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
Query 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
Query 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
Query 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
Query 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
Query 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
Query 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
Query 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
Query 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
Query 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
Query 1561 GGCACCGCTATGGCATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGTT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1561 GGCACCGCTATGGCATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGTT 1620
Query 1621 ATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGATT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1621 ATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGATT 1680
Query 1681 ACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGTG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1681 ACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGTG 1740
Query 1741 GCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGGG 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1741 GCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGGG 1800
Query 1801 GCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGCC 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1801 GCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGCC 1860
Query 1861 AAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACTT 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1861 AAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACTT 1920
Query 1921 AAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGCA 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1921 AAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGCA 1980
Query 1981 GAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAGC 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1981 GAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAGC 2040
Query 2041 GTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCAG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2041 GTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCAG 2100
Query 2101 TACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACTT 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2101 TACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACTT 2160
Query 2161 TATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCCCTTTAA 2211
|||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2161 TATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCCCTTTAA 2211
It would have been obvious to modify the AAVrh91 capsid as taught by Hordeaux with the teachings of Nambiar, to use an AAVrh91 capsid protein encoded Seq ID NO: 1 as taught by Nambiar.
One would have been motivated to modify the AAVrh91 capsid taught by Hordeaux by using an AAVrh91 capsid protein encoded Seq ID NO: 1 as taught by Nambiar because Hordeaux is silent on a specific nucleic acid sequence to encode the capsid protein and Hordeaux discloses a nucleic acid sequence that encodes the same capsid protein.
One would have a reasonable expectation of success because both inventions are drawn to an AArh91 capsid.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 7-10 and 42-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. US12516351B2 in view of Sands et al (Methods Mol Biol (2011) 807;1-17).
Regarding claim 7: The intended use phrases “for detargeting the liver and/or reducing liver toxicity following systemic administration of an AAV vector to a subject” does not impart active steps or structure on the claimed method.
The intended result “wherein levels of transduction of the liver and/or liver toxicity observed following administration of the AAV vector are reduced relative to an AAV vector having an AAV1, AAV8, and/or AAV9 capsid” does not impart active steps or structure on the claimed method.
Therefore method which comprises administration of any AAV vector comprising an AAVrh91 capsid and a vector genome comprising a transgene operably linked to regulatory sequences that direct expression of the transgene in cells of the liver, which is administered via intravenous injection, is considered to read on the invention as claimed.
Claim 1 of US12516351B2 teach an AAVrh.91 capsid and a vector genome comprising a transgene (heterologous nucleic acid sequence) operably linked to regulatory sequences that direct expression in a target cell (p51).
Claim 1 of US12516351B2 do not teach the regulatory sequences direct expression of the transgene in cells of the liver or that the recombinant AAV vector is administered via intravenous injection.
Sands teach recombinant AAV vectors which can be pseudotyped with different AAV capsid proteins, and the effective use of liver-specific promoters, provides an opportunity to accomplish the goals of an effective liver-directed gene therapy (p4 ¶2). Sands further teach gene therapy with a liver-directed gene transfer AAV using a liver-specific vector/promoter combination can be accomplished with a simple intravenous injection which eliminates the need to use surgical techniques (p5 ¶1). Sand further teach there are numerous liver-specific expression cassettes (p5 ¶1).
It would have been obvious to modify the vector genome as taught by claim 1 US12516351B2 with the teachings of Sands, to administer the vector via intravenous injection and to use regulatory sequences that direct expression of the transgene in cells of the liver (e.g. liver-specific expression cassettes) .
One would have been motivated to modify claim 1 of US12516351B2 to use a method of intravenous administration of an AAV with a genome that comprises a transgene operably linked to regulatory sequences that direct expression of the transgene in cells of the liver because Sands further teach that many inherited diseases could be effectively treated by targeting the liver using gene transfer approaches, and that AAV vectors overcome many of the challenges associated with liver-directed gene therapy (abstract). One would also have been motivated because Sands teach that intravenous injection is simple and eliminates the need to use surgical techniques. One of ordinary skill in the art would understand that a method which avoids surgical techniques would be more efficient and less traumatic to the subject.
One would have had a reasonable expectation of success because Sands teach intravenous injection of AAV2-based gene transfer vectors resulted in transduction of most tissues and mediated a high level of transgene expression in the liver (p2 ¶3).
Regarding claim 8: The teachings of US12516351B2 are discussed supra.
Claim 1 of US12516351B2 also teaches the amino acid sequence of the AAVrh.91 capsid is Seq Id NO: 2 of US12516351B2.
Seq ID NO:2 as taught by US12516351B2 comprises 100% identity with Seq ID NO: 2 of the instant invention (see below, Qy is Seq ID No: 2 of the instant application and Db is Seq ID No: 2 of US12516351B2).
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPFGLVEEAAKTAPGKKRPVEQSPQEPDSSSGIGKSGQQPAKKRLNFGQTGDSE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPFGLVEEAAKTAPGKKRPVEQSPQEPDSSSGIGKSGQQPAKKRLNFGQTGDSE 180
Qy 181 SVPDPQPLGEPPETPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPLGEPPETPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
Qy 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
Qy 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVP 420
Qy 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
Qy 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
Qy 541 MIFGKENAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNLQSSNTDPATGDVHVMG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 MIFGKENAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNLQSSNTDPATGDVHVMG 600
Qy 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKNTPVPANPPA 660
Qy 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
Qy 721 YTEPRPIGTRYLTRPL 736
||||||||||||||||
Db 721 YTEPRPIGTRYLTRPL 736
Regarding claims 9-10: The claim recites “a capsid protein produced by expression of a nucleotide sequence of SEQ ID NO: 1 or 3”.
Claim language such as recited above encompasses nucleic acids that comprise the full-length sequence of SEQ ID NO: 1 or 3 or any portion of SEQ ID NO: 1 or 3.
This claim limitation is anticipated by any nucleic acid comprising any dinucleotide or larger oligonucleotide which is a portion of SEQ ID NO:1 or 3.
If the claim were amended to recite “a capsid protein produced by expression of the nucleotide sequence of SEQ ID NO: 1 or 3” the examiner would interpret the claims to encompass only nucleic acids that comprise the full length of the specified SEQ ID NO:, with or without additional nucleotides at either or both ends.
The teachings of US12516351B2 are discussed supra.
Claim 2 of US12516351B2 teaches the nucleotide sequence encoding the amino acid sequence of the AAVrh91 capsid comprises Seq ID NO: 1 as taught by US12516351B2.
Seq ID NO: 1 as taught by US12516351B2 comprises 100% sequence identity with Seq ID NO: 1 of the instant invention (see below; Query is Seq Id NO: 1 on the instant disclosure, Sbjct is Seq ID NO:1 of US12516351B2).
Query 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 ATGGCTGCCGATGGTTATCTTCCAGATTGGCTCGAGGACAACCTCTCTGAGGGCATTCGC 60
Query 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 GAGTGGTGGGCGCTGAAACCTGGAGCCCCGAAACCCAAAGCCAACCAGCAAAAGCAGGAC 120
Query 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 121 GACGGCCGGGGTCTGGTGCTTCCTGGCTACAAGTACCTCGGACCCTTCAACGGACTCGAC 180
Query 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 181 AAGGGGGAGCCCGTCAACGCGGCGGACGCAGCGGCCCTCGAGCACGACAAGGCCTACGAC 240
Query 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 CAGCAGCTCAAAGCGGGTGACAATCCGTACCTGCGGTATAACCACGCCGACGCCGAGTTT 300
Query 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 CAGGAGCGTCTGCAAGAAGATACGTCTTTTGGGGGCAACCTCGGGCGAGCAGTCTTCCAG 360
Query 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 GCCAAGAAGCGGGTTCTCGAACCTTTTGGTCTGGTTGAGGAAGCAGCTAAGACGGCTCCT 420
Query 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 GGAAAGAAACGTCCGGTAGAGCAGTCGCCCCAAGAACCAGACTCCTCCTCGGGCATTGGC 480
Query 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 AAATCAGGCCAGCAGCCCGCCAAAAAGAGACTCAATTTCGGTCAGACTGGCGACTCAGAG 540
Query 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 TCAGTCCCCGACCCTCAACCTCTCGGAGAACCTCCAGAAACCCCCGCTGCTGTGGGACCT 600
Query 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 ACTACAATGGCTTCAGGCGGTGGCGCACCAATGGCAGACAATAACGAAGGCGCCGACGGA 660
Query 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 661 GTGGGTAATGCCTCAGGAAATTGGCATTGCGATTCCACATGGCTGGGCGACAGAGTCATC 720
Query 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 721 ACCACCAGCACCCGAACCTGGGCCCTTCCTACCTACAACAACCACCTCTACAAGCAAATC 780
Query 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 781 TCCAGCGCTTCAACGGGGGCCAGTAACGACAACCACTACTTTGGCTACAGCACCCCCTGG 840
Query 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 841 GGGTATTTTGATTTCAACAGATTCCACTGCCACTTCTCACCACGTGACTGGCAGCGACTC 900
Query 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 901 ATTAACAACAACTGGGGATTCCGGCCCAAGAGACTCAACTTCAAGCTCTTCAACATCCAG 960
Query 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 961 GTCAAGGAGGTCACGACGAATGATGGCGTCACAACCATCGCTAATAACCTTACCAGCACG 1020
Query 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1021 GTTCAAGTGTTCTCGGACTCGGAGTACCAGCTGCCGTACGTCCTCGGTTCTGCGCACCAG 1080
Query 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1081 GGCTGCCTCCCTCCGTTCCCGGCGGACGTATTCATGATTCCTCAGTACGGCTACCTAACG 1140
Query 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1141 CTCAACAATGGCAGCCAGGCCGTAGGACGTTCATCCTTTTATTGCCTGGAATATTTCCCA 1200
Query 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1201 TCTCAAATGCTGAGAACGGGCAACAACTTTACCTTCAGCTACACCTTTGAAGATGTGCCT 1260
Query 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1261 TTCCACAGCAGTTACGCGCACAGCCAGAGCCTGGACAGGCTAATGAATCCTCTAATCGAC 1320
Query 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1321 CAGTACCTGTATTACCTAAACAGAACTCAGAATCAATCCGGAAGTGCACAAAACAAGGAC 1380
Query 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1381 TTGCTGTTTAGCCGGGGGTCTCCAGCTGGCATGTCTGTTCAGCCCAAAAACTGGCTACCC 1440
Query 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1441 GGGCCCTGTTACCGACAGCAGCGTGTTTCTAAAACAAAAACAGACAACAACAACAGCAAC 1500
Query 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1501 TTTACCTGGACTGGTGCCTCCAAATACAATCTGAACGGACGTGAATCCATCATTAACCCT 1560
Query 1561 GGCACCGCTATGGCATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGTT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1561 GGCACCGCTATGGCATCCCACAAGGACGACGAAGACAAATTTTTTCCCATGAGCGGTGTT 1620
Query 1621 ATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGATT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1621 ATGATTTTTGGCAAAGAAAATGCAGGAGCATCAAACACTGCATTAGACAATGTTATGATT 1680
Query 1681 ACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGTG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1681 ACAGATGAAGAGGAAATTAAAGCTACCAACCCCGTGGCCACCGAGAGATTTGGAACTGTG 1740
Query 1741 GCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGGG 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1741 GCAGTCAATCTCCAAAGCAGCAATACAGACCCTGCAACAGGAGACGTGCATGTCATGGGG 1800
Query 1801 GCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGCC 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1801 GCTTTACCTGGCATGGTGTGGCAAGACAGAGACGTGTACCTGCAGGGTCCCATTTGGGCC 1860
Query 1861 AAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACTT 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1861 AAGATTCCTCACACGGATGGACACTTTCACCCGTCTCCTCTTATGGGCGGCTTTGGACTT 1920
Query 1921 AAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGCA 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1921 AAGCACCCGCCTCCTCAGATCCTCATCAAAAACACGCCTGTTCCTGCGAATCCTCCGGCA 1980
Query 1981 GAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAGC 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1981 GAGTTTTCGGCTACAAAGTTTGCTTCATTCATCACCCAGTACTCCACAGGACAAGTGAGC 2040
Query 2041 GTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCAG 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2041 GTGGAAATTGAATGGGAGCTGCAGAAAGAAAACAGTAAGCGCTGGAATCCTGAAGTGCAG 2100
Query 2101 TACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACTT 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2101 TACACCTCCAACTACGCGAAATCTGCCAACGTTGATTTCACTGTGGACAACAATGGACTT 2160
Query 2161 TATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCCCTTTAA 2211
|||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2161 TATACTGAGCCTCGCCCCATTGGCACCCGTTACCTTACCCGTCCCCTTTAA 2211
Regarding claim 42: The intended use phrases “for detargeting the liver and/or reducing liver toxicity following systemic administration of an AAV vector to a subject” does not impart active steps or structure on the claimed method.
The intended result “wherein levels of transduction of the liver and/or liver toxicity observed following administration of the AAV vector are lower than transduction levels of a reference rAAV vector having an Clade A capsid” does not impart active steps or structure on the claimed method.
Therefore, any method comprising delivering via intravenous infusion a recombinant AAV vector comprising a vector genome in an AAVrh91 capsid, wherein the vector genome comprises a transgene operably linked to regulatory sequences is considered to read on the claim as written.
Claim 1 of US12516351B2 teach a recombinant AAV vector comprising an AAVrh91 capsid and a genome comprising a transgene operably linked to a regulatory sequence that directs expression of the transgene (p2 [0028]).
Claim 1 of US12516351B2 do not teach the regulatory sequences direct expression of the transgene in cells of the liver or that the recombinant AAV vector is administered via intravenous infusion.
Sands teach recombinant AAV vectors which can be pseudotyped with different AAV capsid proteins, and the effective use of liver-specific promoters, provides an opportunity to accomplish the goals of an effective liver-directed gene therapy (p4 ¶2). Sands further teach gene therapy with a liver-directed gene transfer AAV using a liver-specific vector/promoter combination can be accomplished with a simple intravenous injection which eliminates the need to use surgical techniques (p5 ¶1). Sand further teach there are numerous liver-specific expression cassettes (p5 ¶1).
It would have been obvious to modify the vector genome as taught by claim 1 US12516351B2 with the teachings of Sands, to administer the vector via intravenous injection and to use regulatory sequences that direct expression of the transgene in cells of the liver (e.g. liver-specific expression cassettes).
One would have been motivated to modify claim 1 of US12516351B2 to use a method of intravenous administration of an AAV with a genome that comprises a transgene operably linked to regulatory sequences that direct expression of the transgene in cells of the liver because Sands further teach that many inherited diseases could be effectively treated by targeting the liver using gene transfer approaches, and that AAV vectors overcome many of the challenges associated with liver-directed gene therapy (abstract). One would also have been motivated because Sands teach that intravenous injection is simple and eliminates the need to use surgical techniques. One of ordinary skill in the art would understand that a method which avoids surgical techniques would be more efficient and less traumatic to the subject.
One would have had a reasonable expectation of success because Sands teach intravenous injection of AAV2-based gene transfer vectors resulted in transduction of most tissues and mediated a high level of transgene expression in the liver (p2 ¶3).
Regarding claim 43: The claim limitation is drawn to the reference rAAV as recited in the intended result of claim 43. Because the claim does not impart an active step or structural limitation on the claimed method, a method that reads on the parent claim 42 is also considered to read on the instant claim (see claim 42 above).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA LYNNE MORRIS SPENCER whose telephone number is (571)272-3328. The examiner can normally be reached Monday-Friday 9:00-5:00.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631
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