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 .
Claim Status
Applicant’s submission filed 07/09/2026 has been received and entered. Claim 47 has been cancelled. Claims 23 and 40 have been amended. Claim 88 has been newly added. Claims 1, 4, 6, 9-10, 12, 14-15, 45-46, 53-55, 57-58, 60, 63, 65-68, 70-73, 75-77, 79-80 and 87 remain withdrawn as being directed to non-elected inventions. Accordingly, claims 23-24, 29-31, 39-44 and 88 are pending and under current examination.
Status of Prior Rejections/Response to Arguments
The objection to claim 31 is withdrawn:
Applicant’s amendment to claim 31 obviates the objection on record. The objection is withdrawn.
The rejection to claims 40-44 as improper Markush group is withdrawn:
Applicant’s amendment to claim 44 using the Markush language “the sequence selected from the group consisting of SEQ ID NO:5865-6698, 7700-11444 and 11445” is effective to obviate the rejection on record. The rejection is withdrawn.
The rejection to claims 23-24, 29, 30-31 and 39 under 35 U.S.C. 103 over Esteves in view of Schaffer is withdrawn:
Applicant has amended claim 23, asserting that neither Esteves et al. nor Schaffer et al. teach or suggest the capsid or rAAV having the recited targeting peptides in loop 1 and/or loop 2 (Remarks, p1).
Applicant’s argument is found persuasive. Neither Esteves et al. nor Schaffer et al. teach or suggest the heterologous targeting peptide comprising the sequence selected from the group consisting of SEQ ID NO:5865-6698, 7700-11444 and 11445, as recited in instant claims. The rejection is withdrawn.
The rejection to claims 23-24, 29, 30-31, 39 and 40-44 under 35 U.S.C. 103 over Esteves in view of Schaffer, further in view of Hood et al. is maintained:
Applicant has amended claims 23 and 43, asserting that none Esteves et al., Schaffer et al. and/or Hood et al. teach or suggest the capsid or rAAV having the recited targeting peptides in loop 1 and/or loop 2 (Remarks, p2).
Applicant’s arguments have been fully considered but they are not persuasive. Specifically, instant claims disclose the amino acid sequences of the heterologous targeting peptide in loop 1 and/or loop 2 of the capsid protein, wherein, i.e., SEQ ID NO: 10288 is taught by Hood et al.. Hood et al. teach SEQ ID NO: 66498 (100% identical to SEQ ID NO: 10288 of instant claim) is one of amino acid sequences of peptides identified by mass spectrometry that map to the organ-specific proteins (Col 80, L60-64). Given that Esteves et al. teach the heterologous targeting peptides confer desired cell and/or tissue targeting properties on rAAVs (see i.e., p9, L23-24), and Hood et al. teach the sequence of organ-specific proteins, one of ordinary skill in the art would have substituted Esteves et al.’s sequence of heterologous targeting peptides for Hood et al.’s sequence of organ-specific proteins depends on their research interest. This simple substitution of one known element (Hood et al.’s sequence of organ-specific proteins) for another known element (Esteves et al.’s sequence of heterologous targeting peptides) is likely to be obvious when predictable results are achieved. The rejection is maintained in modified form to address amended limitations.
Modified Rejections
Claim Interpretation
Instant claims 23 and 40 recite “loop 1 and/or loop 2 of the capsid protein”, the phrase is interpreted in light of figure 6A and paragraph [00103] in Specification. Figure 6A shows the structure of loop 1 and loop 2, paragraph [00103] states the amino acid position of “loop 1 and/or loop 2 of the capsid protein”: positions N443 (AAV5-Loop1) and S576 (AAV5-Loop2) were identified for AAV5, and positions Q456 (AAV9-Loop1) and A587 (AAV9-Loop2) were identified for AAV9.
Claims 23 and 40 recite “the heterologous targeting peptide has the sequence selected from the group consisting of SEQ ID NO:5865-6698, 7700-11444 and 11445”, herein the word “has” is interpreted as “comprises”.
Modified Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 23-24, 29, 30-31, 39 and 40-44 stand rejected and claim 88 is newly rejected under 35 U.S.C. 103 as being unpatentable over Esteves et al. (WO 2016/054554 A1, cited in IDS) in view of Schaffer et al. (WO 2012/145601 A2) and Hood et al. (US 8,586,006 B2, patented in 2013). The claims are modified as necessitated by Applicant’s amendment.
Esteves et al. teach recombinant adeno-associated viruses having distinct tissue targeting capabilities (Abstract).
Regarding claim 23, Esteves et al. teach recombinant AAVs (rAAVs) engineered to contain heterologous targeting peptides that target the rAAVs to certain cells and/or tissues (p1, L25-26). In some embodiments, an rAAV comprises a VP1 and/or VP2 and/or VP3 capsid protein comprising a heterologous targeting peptide (p2, L25-27). This teaching reads on an AAV capsid protein comprising a heterologous targeting peptide as recited in instant claim.
Esteves et al. do not specifically teach the heterologous targeting peptide is cloned into loop 1 and/or loop 2 of the capsid protein (i.e., at position N443 (AAV5-Loop 1) or S576 (AAV5-Loop 2), see Specification parag 00103), as well as the heterologous targeting peptide comprises the sequence selected from the group consisting of SEQ ID NO:5865-6698, 7700-11444 and 11445. However, such was disclosed by Schaffer et al. and Hood et al. at the time of instant invention.
Schaffer et al. teach adeno-associated vims (AAV) virions with altered capsid protein (Abstract).
Hood et al. teach methods for identifying and using organ-specific proteins and transcripts (Abstract).
Regarding the limitation “the heterologous targeting peptide cloned into loop 1 and/or loop 2 of the capsid protein”, Schaffer et al. teach the variant AAV capsid protein comprises an insertion of from about 5 amino acids to about 11 amino acids in an insertion site in the capsid protein GH loop or loop IV, relative to a corresponding parental AAV capsid protein (parag 0073). An "insertion of from about 5 amino acids to about 11 amino acids" is also referred to herein as a "peptide insertion" (e.g., a heterologous peptide insertion) (parag 0073). The insertion site can be between amino acids 575 and 576 of AAV5 (parag 0077).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Esteves et al.’s rAAVs having capsid protein comprising heterologous targeting peptides, and insert the heterologous targeting peptides at amino acid 576 of AAV5 as taught by Schaffer et al.. The only difference between instant claim and Esteves et al.’s rAAVs having capsid protein comprising heterologous targeting peptides is instant claim inserting the heterologous targeting peptides into loop 1 and/or loop 2 of the capsid protein (i.e., amino acid 576 of AAV5). Given that Esteves et al. teach using heterologous targeting peptides that confer desired cell and/or tissue targeting properties on rAAVs (p9, L23-24), Schaffer et al. teach AAV with insertion of the heterologous targeting peptides at amino acid 576 of AAV5 exhibit greater infectivity, one of ordinary skill in the art would have substituted Esteves et al.’s rAAVs comprising heterologous targeting peptides in the capsid protein, and insert the heterologous targeting peptides at the position corresponding to at amino acid 576 of AAV5 depends on their research interest or preference, as well as the expectation for obtaining a rAAV targeting to a specific cell and/or tissue with greater infectivity. This simple substitution of one known element (insert the heterologous targeting peptides into loop 1 and/or loop 2 of the capsid protein (i.e., amino acid 576 of AAV5)) for another known element (insert the heterologous targeting peptides into a position in capsid protein) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding the sequence of the heterologous targeting peptide, Hood et al. teach SEQ ID NOs: 65803-72641 are amino acid sequences of peptides identified by mass spectrometry that map to the organ-specific proteins (Col 80, L60-64). Herein the SEQ ID NO: 66498 is 100% identical to SEQ ID NO: 10288 of instant claim.
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Esteves et al.’s rAAVs having capsid protein comprising heterologous targeting peptides, insert the heterologous targeting peptides at amino acid 576 of AAV5 as taught by Schaffer et al., and have the sequence of the heterologous targeting peptide as taught by Hood et al.. The only difference between instant claim and Esteves et al. and Schaffer et al.’s capsid protein comprising heterologous targeting peptides is instant claims having a different heterologous targeting peptide sequence. Given that Esteves et al. teach the heterologous targeting peptides confer desired cell and/or tissue targeting properties on rAAVs (see i.e., p9, L23-24), and Hood et al. teach the sequence of organ-specific proteins, one of ordinary skill in the art would have substitute Esteves et al.’s sequence of heterologous targeting peptides for Hood et al.’s sequence of organ-specific proteins depends on their research interest. This simple substitution of one known element (Hood et al.’s sequence of organ-specific proteins) for another known element (Esteves et al.’s sequence of heterologous targeting peptides) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 24, following the discussion above, Esteves et al. teach recombinant AAVs (rAAVs) engineered to contain heterologous targeting peptides that target the rAAVs to certain cells and/or tissues (p1, L25-26). In some embodiments, an rAAV comprises a VP1 and/or VP2 and/or VP3 capsid protein comprising a heterologous targeting peptide (p2, L25-27).
Regarding claim 29, following the discussion above, Esteves et al. teach in some embodiments, an AAV capsid protein further comprises a linker conjugated to the C-terminus of the heterologous targeting peptide (p2, L28-29).
Regarding claims 30-31, Esteves et al. teach recombinant AAVs (rAAVs) engineered to contain
heterologous targeting peptides that target the rAAVs to certain cells and/or tissues (p1, L25-26). In some embodiments, such heterologous targeting peptides are useful for targeting AAVs to tissues of the central nervous system (CNS) (p2, L2-3), optionally brain (p3, L1), which can target to neuronal in the visual cortex (see i.e., p6, L21, the legend of figure 3). This teaching reads on heterologous targeting peptide targets neuron cells and brain tissue.
Regarding claim 39, following the discussion above, Esteves et al. teach rAAVs engineered to contain heterologous targeting peptides that target the rAAVs to certain cells and/or tissues (p1, L25-26). In some embodiments, an rAAV comprises a VP1 and/or VP2 and/or VP3 capsid protein comprising a heterologous targeting peptide (p2, L25-27). Schaffer et al. teach AAV capsid protein comprises a heterologous peptide insertion in an insertion site in amino acids 576 of AAV5 (see parag 0077), which is loop2 of the capsid protein in AAV5. Hood et al. teach the amino acid sequence of the heterologous targeting peptides. Based on the same reason stated in claim 23, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Esteves et al.’s rAAVs and obtain the rAAVs as recited in instant claim.
Regarding claim 40, as stated above, Hood et al. teach SEQ ID NOS: 65803-72641 are amino acid sequences of peptides identified by mass spectrometry that map to the organ-specific proteins (Col 80, L60-64). Herein the SEQ ID NO: 66498 is 100% identical to SEQ ID NO: 10288 of instant claim.
Regarding claims 41 and 42, following the discussion above, Esteves et al. teach the rAAV-based methods for delivering a transgene to a target tissue in a subject are provided. The transgene delivery methods may be used for gene therapy (e.g., to treat disease)(p9, L27-29). Transgene is a heterologous polynucleotide, and since the transgene is used for gene therapy, it is a therapeutic gene.
Regarding claims 43 and 44, following the discussion above, Esteves et al. teach the rAAVs may be delivered to a subject in compositions (p42, L8). A composition comprising the isolated AAV capsid proteins. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier (p5, L15-17).
Regarding claim 88, following the discussion above, Hood et al. teach SEQ ID NOS: 65803-72641 are amino acid sequences of peptides identified by mass spectrometry that map to the organ-specific proteins (Col 80, L60-64). Herein the SEQ ID NO: 66498 (25 amino acids in length) is 100% identical to SEQ ID NO: 10288 of instant claim.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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