DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group I, presently claims 1, 2, 4, 6, and 8-12, in the reply filed on 5/15/2026 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)).
Claims 5, 13, 14, 16, 18, 19, and 21-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/15/2026.
Claims 1, 2, 4, 6, and 8-12 are under consideration on the merits.
Claim Objections
Claims 5, 13, 14, 16, 18, 19, are 21-25 are withdrawn but were not amended in reply to indicate as such. See 37 C.F.R. § 1.121(c). Appropriate correction is required with the next reply.
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 1, 4, 6, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffer et al. (US 2020/009559; provided in the IDS 9/06/2024) in view of Berezin et al. (US 2007/0116702; provided in the IDS 9/06/2024).
Schaffer teaches recombinant AAV virions with variant AAV capsid protein and having increased ability to infect neural stem cells or neuronal cells (Abstract) and recombinant virion therein (claim 1). Schaffer teaches AAV capsid protein comprising an insertion of 5-20 amino acids in loop IV within amino acids (e.g. residues) 411-650 or amino acids 587-588 ([0141]-[0142]), reading in-part on claim 1 and reading on claim 4. Schaffer teaches AAV capsid protein selected from AAV1, AAV9 or AAVrh10 (Fig. 4 and [0285]), reading on claim 12. Schaffer teaches that AAV utilizes heparin sulfate proteoglycans for cell transduction ([0927]), reading in-part on claims 1, 6, and 8-11.
Regarding claim 1, Schaffer does not teach the embodiment of SEQ ID NO: 15 (i.e. GRILARGEINFK) or SEQ ID NO: 16 (i.e. ASKKPKRNIKA). Regarding claims 6 and 8-11, Schaffer does not teach the functional properties of the modified AAV capsid protein of claim 1.
Berezin teaches peptides comprising at least 5 contiguous amino acid residues of NCAM (Abstract). Berezin teaches a peptide comprising the NCAM Ig2 domain and consisting of the sequence ASKKPKRNIKA ([0075]-[0076], SEQ ID NO: 1) or GRILARGEINFK ([0084]-[0086])), reading on SEQ IDs NO: 16 and 15 respectively. Berezin teaches that ligands of NCAM comprise in-part heparin sulfate proteoglycans ([0004] and [0029]), reading in-part on claims 1, 6, and 8-11. Berezin teaches that NCAM is a cell adhesion molecule abundant in the nervous system, and binds to NCAM, proteins, and glycoconjugates expressed on nerve cells ([0002]), reading in-part on claims 1, 6, and 8-11.
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the peptides comprising the NCAM Ig2 domain of Berezin for loop IV in Schaffer’s AAV capsid protein. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Schaffer teaches insertion of peptides at loop IV of AAV capsid protein, and because Berezin teaches peptides comprising the NCAM Ig2 domain. The skilled artisan would have been motivated to do so because both Schaffer and Berezin are related as Schaffer teaches variant AAV capsid proteins with increased infectivity of neural cells, Schaffer teaches that AAV utilizes heparin sulfate proteoglycans for cell transduction and Berezin teaches that NCAM in-part binds to heparin sulfate proteoglycans on nerve cells. The prior art as a whole suggests that the substitution would be predictably advantageous to improve the binding of Schaffer’s recombinant AAV virion comprising the variant AAV capsid protein to NCAM ligands such as to improve viral transduction of neural cells.
Regarding the functional properties of claims 6 and 9-11, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Also see M.P.E.P. § 2112.01. In this case, the combination of peptides comprising the NCAM Ig2 domain of Berezin inserted into loop IV of the AAV capsid protein of a Schaffer would inherently generate increased binding to glycans for claim 6, polysialic acid attached to NCAM for claim 8, a neuronal cell for claims 9 and 10, and a brain neuronal cell for claim 11 because Berezin teaches that NCAM is a cell adhesion molecule abundant in the nervous system, and binds to NCAM, proteins, and glycoconjugates expressed on nerve cells. Therefore and
absent any showing to the contrary, the functional properties of claims 6 and 8-11 are reasonably presumed to be inherent to the substantially identical AAV capsid protein yielded by the combination of Schaffer and Berezin.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Schaffer and Berezin as applied to claim 1 above, and further in view of Schaffer et al. (WO 2012/0145601; Reference N, and hereafter referred to as “the Schaffer WIPO publication”).
The teachings of Schaffer and Berezin are relied upon as set forth above. Schafer further teaches variant AAV capsid comprising a peptide insert or a peptide replacement ([0102]), reading in-part on claim 2. Schaffer further teaches AAV1 capsid protein as set forth in GenBank Accession No. NP_049542 ([0142]), wherein SEQ ID NO: 1 is 100% identical to NP_049542a and so reading in-part on claim 2.
Regarding claim 2, Schaffer and Berezin do not teach insertion of the embodiment of SEQ ID NO: 15 or 16 between positions 450 and 459 or replacement the amino acids at positions 451-458 in the AAV1 capsid protein of SEQ ID NO: 1.
The Schaffer WIPO publication teaches AAV virions with altered capsid proteins and having greater infectivity of retinal cells (Abstract). The Schaffer WIPO publication teaches inserting peptides at 450-460 in AAV1 capsid protein and which corresponds to loop IV (i.e. variable region IV or VRIV) (Fig. 17, [0078], and [00100]), reading on claim 2.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the peptides comprising the NCAM Ig2 domain of Berezin for either inserted between residues Q450-K459 or replacing residues 451-458 in loop IV of AAV1 in Schaffer’s AAV capsid protein in view of the Schaffer WIPO publication. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Schaffer teaches insertion of peptides and replacement of residues in loop IV of AAV1 capsid protein, because Berezin teaches peptides comprising the NCAM Ig2 domain, and because Schaffer and the Schaffer WIPO publication are both directed towards variant AAV1 capsid protein with improved infectivity of neural cells. The skilled artisan would have been motivated to do so because the Schaffer WIPO teaches that loop IV of the AAV capsid protein is confined to a smaller region of residues, and so it would be predictably advantageous to then confine the insertion of replacement of residues within loop IV of AAV in the AAV1 capsid protein of Schaffer over the broader range of residues 411-650 in view of the Schaffer WIPO publication.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Billman et al. (US 2005/0222041; Reference A) for SEQ ID NO: 17, and Bock et al. (US 2008/0249004; Reference B) for SEQ ID NO: 18-20. See [0198] of Billman, with SEQ ID NO: 1 = instant SEQ ID NO: 17. And, see [0123]-[0125] of Bock, with SEQ ID NO: 19 = instant SEQ ID NO: 18, SEQ ID NO: 20 = instant SEQ ID NO: 19, and SEQ ID NO: 13 = instant SEQ ID NO: 20.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sean C. Barron/Primary Examiner, Art Unit 1653
SEQ ID NO: 1
capsid protein [Adeno-associated virus - 1]
Sequence ID: NP_049542.1Length: 736Number of Matches: 1
Related Information
Gene-associated gene details
Range 1: 1 to 736GenPeptGraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score
Expect
Method
Identities
Positives
Gaps
1531 bits(3963)
0.0
Compositional matrix adjust.
736/736(100%)
736/736(100%)
0/736(0%)
Query 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD
Sbjct 1 MAADGYLPDWLEDNLSEGIREWWDLKPGAPKPKANQQKQDDGRGLVLPGYKYLGPFNGLD 60
Query 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ
Sbjct 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLRYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
Query 121 AKKRVLEPLGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSE 180
AKKRVLEPLGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSE
Sbjct 121 AKKRVLEPLGLVEEGAKTAPGKKRPVEQSPQEPDSSSGIGKTGQQPAKKRLNFGQTGDSE 180
Query 181 SVPDPQPLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
SVPDPQPLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI
Sbjct 181 SVPDPQPLGEPPATPAAVGPTTMASGGGAPMADNNEGADGVGNASGNWHCDSTWLGDRVI 240
Query 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL
Sbjct 241 TTSTRTWALPTYNNHLYKQISSASTGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRL 300
Query 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ
Sbjct 301 INNNWGFRPKRLNFKLFNIQVKEVTTNDGVTTIANNLTSTVQVFSDSEYQLPYVLGSAHQ 360
Query 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEEVP 420
GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEEVP
Sbjct 361 GCLPPFPADVFMIPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEEVP 420
Query 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP
Sbjct 421 FHSSYAHSQSLDRLMNPLIDQYLYYLNRTQNQSGSAQNKDLLFSRGSPAGMSVQPKNWLP 480
Query 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV
Sbjct 481 GPCYRQQRVSKTKTDNNNSNFTWTGASKYNLNGRESIINPGTAMASHKDDEDKFFPMSGV 540
Query 541 MIFGKESAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNFQSSSTDPATGDVHAMG 600
MIFGKESAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNFQSSSTDPATGDVHAMG
Sbjct 541 MIFGKESAGASNTALDNVMITDEEEIKATNPVATERFGTVAVNFQSSSTDPATGDVHAMG 600
Query 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKNPPPQILIKNTPVPANPPA 660
ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKNPPPQILIKNTPVPANPPA
Sbjct 601 ALPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKNPPPQILIKNTPVPANPPA 660
Query 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL
Sbjct 661 EFSATKFASFITQYSTGQVSVEIEWELQKENSKRWNPEVQYTSNYAKSANVDFTVDNNGL 720
Query 721 YTEPRPIGTRYLTRPL 736
YTEPRPIGTRYLTRPL
Sbjct 721 YTEPRPIGTRYLTRPL 736
Prosecution Insights