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 .
Priority
The instant application is a national stage entry of PCT application PCT/US2022/023177, filed 09/29/2023 under 35 USC 371. Acknowledgement is made of the applicant’s claim for benefit to prior-filed U.S. provisional patent applications 63/170,100 (filed 04/02/2021).
Election/Restrictions
Applicant's election with traverse of Group II, claims 23-24, 29-31 and 39-44, drawn to an AAV capsid protein comprising a heterologous targeting peptide cloned into loop 1 and/or loop 2 of the capsid protein, in the reply filed on 03/13/2026 is acknowledged. The traversal is on the grounds that Group II (claims 23-24, 29-31 and 39-44) is drawn to an adeno-associated virus capsid protein which can be found in the methods of Group III. Moreover, Group IV claims are directed to nucleic acids that encode the capsid protein of Group II. Accordingly, Examination in a separate Application for the Group III and IV claims would be an undue burden on Applicant and the USPTO (see Remarks, p1). This is not found persuasive because this application is a national stage filing of an international application. Restriction in such applications is based on lack of unity practice. As stated in the Restriction Requirement mailed 01/13/2026, Groups (II, III) and Group IV do not share the same or corresponding technical feature. Specifically, the shared technical feature of the inventions of Groups (II, III) is an adeno-associated virus (AAV) capsid protein comprising a heterologous targeting peptide cloned into loop 1 and/or loop 2 of the capsid protein, wherein the heterologous targeting peptide is about 10-30 amino acids in length; while the shared technical feature of the inventions of Group IV is an isolated nucleic acid encoding an AAV capsid protein, thus Groups (II, III) and IV and lack unity of invention. For the analysis of the unity between Groups II and III, even though the inventions of these groups require the same technical feature, this technical feature is not a special technical feature as it does not make a contribution over the prior art Esteves et al. (WO 2016/054554 A1, cited in IDS) in view of Schaffer et al. (WO 2012/145601 A2) as stated in the Office Action. Therefore Groups II and III lack unity of invention.
The requirement is still deemed proper and is therefore made FINAL. Accordingly, claims 23-24, 29-31 and 39-44 have been considered on the merits. Claims 1, 4, 6, 9-10, 12, 14-15, 45-47, 53-55, 57-58, 60, 63, 65-68, 70-73, 75-77, 79-80 and 87 are withdrawn from consideration pursuant 37 CFR 1.142(b).
Claim Objections
Claim 31 is objected to because of the following informalities: Claim 31 recites “heat tissue” needs to be “heart tissue”. Appropriate correction is required.
Improper Markush Group
Claims 40-44 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping in claim 40 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Claim 40 recites “the targeting peptide is independently selected from SEQ ID Nos: 5865 to 11445”, it is interpreted under the broadest reasonable interpretation (BRI) as the targeting peptide comprises the SEQ ID Nos: 5865 to 11445. That is, ANY amino acid with a fragment comprising said SEQ ID Nos: 5865 to 11445 is considered as one of the alternatives in the Markush group. These amino acids, however, would be extremely broad and not be supposed to direct to a common use. Therefore the claims are rejected as containing an improper Markush grouping.
Claims 41-44 depend from claim 40 directly or indirectly, and thus inherit the deficiency and are rejected on the same basis.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claim 40 recites “the targeting peptide is independently selected from SEQ ID Nos: 5865 to 11445”, it is interpreted under broadest reasonable interpretation (BRI) that the targeting peptide is 10-30 amino acids in length and comprising the amino acid sequence of SEQ ID Nos: 5865 to 11445.
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.
Claims 23-24, 29, 30-31 and 39 are 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).
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. teach in some embodiments, heterologous targeting peptides are provided that are in a range of 11 to 27 amino acids in length (p2, L5-6), which is in the range of 10-30 amino acids in length as recited in instant claim.
Esteves et al. do not specifically teach the heterologous targeting peptide 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). However, this was disclosed by Schaffer et al. at the time of instant invention.
Schaffer et al. teach adeno-associated vims (AAV) virions with altered capsid protein (Abstract).
Regarding claim 23, 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 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. 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. to obtain the recombinant AAV (rAAV). 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.).
Claims 23-24, 29, 30-31, 39 and 40-44 are 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), as applied to claims 23-24, 29, 30-31 and 39 above, further in view of Hood et al. (US 8,586,006 B2, patented in 2013).
The teaching of Esteves et al. and Schaffer et al. is set forth above.
Regarding claim 40, Esteves et al. and Schaffer et al. do not teach the targeting peptide is independently selected from SEQ ID Nos:5865 to 11445. However, this was disclosed by Hood et al. at the time of instant invention.
Hood et al. teach methods for identifying and using organ-specific proteins and transcripts (Abstract).
Regarding claim 40, Hood et al. teach SEQ ID NOS:32935-52639 are amino acid sequences of peptides identified by mass spectrometry that map to the organ-specific proteins (Col 80, L48-50). Herein the SEQ ID NO: 42357 is 100% identical to SEQ ID NO: 6699 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 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).
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699