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
Status of the Claims
Claims 1, 6, 10-13, 16, 18, 23 and 25-30 are pending.
Claims 2-5, 7-9, 14-15, 17, 19-22, and 24 are cancelled,
Claims 16 and 23 are withdrawn pursuant to a restriction requirement.
Claims 1, 6, 10, 16, and 23 are amended,
Claims 25-30 are newly added,
Claims 1, 6, 10-13, 18 and 25-30 have been examined on the merits.
Withdrawn Objections & Rejections
Applicant's response filed 12/01/2025 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 06/03/2025 are hereby withdrawn.
The rejections under 112b, 102, and 103 and the warning over double patenting have been withdrawn in view of the amendments to the claims.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
The species election requirement for an insertion sequence is withdrawn as the elected species Seq ID NO: 13 is found allowable (see below).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 10-13, 18 and 25-30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Michalakis et al (WO 2019/076856 A1).
This is a new rejection due to the amendments to the claims.
Regarding claim 1: Michalakis teach AAV capsids with an insertion of at least 6 amino acids between positions corresponding to positions 87 and 588 (abstract).
Michalakis teach a peptide insertion at position 587 of AAV2 VP1 comprising the amino acid sequence of Seq ID NO: 20 (HAAGLPK; Figure 2 column 2). Michalakis also teach a peptide insertion at position 587 of AAV2 VP1 comprising the amino acid sequence of Seq ID NO: 18 (WHAPTHG; Figure 3 second page col1).
Michalakis do not explicitly teach efficient targeting of hepatic tissue, however MPEP 2173.05(g) states “A claim term is functional when it recites a feature ‘by what it does rather than by what it is’”. MPEP 2173.05(g) further recites “when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear”.
The wherein clause stating “wherein the mutated AAV capsid protein or its homologs being efficient in specifically targeting hepatic tissue, hepatocytes, hepatic cells and cell lines or hepatocellular carcinoma (HCC)” is interpreted as a function of the invention and does not confer structural limitations, therefore it is considered non-limiting to the disclosure. Furthermore, if “targeting heptatic tissue” were considered limiting, because it is a function of the claimed invention a disclosure of the identical structure as the claimed invention would also inherently comprise identical properties. Thus the disclosure of Michalakis would read on “targeting hepatic tissue” if it was considered limiting to the claim.
Regarding claim 10-13, 18, 25: The teachings of Michalakis are described supra. Michalakis also teach a modified pRC99 plasmids are used to produce AAV particles with the novel AAV capsid modification for biological testing (p15 [54]. Michalakis further teach 293 cells were transfected with plasmids to produce the AAV variants (p15 [55]). This reads on a host cell containing the nucleic acid vector.
Regarding claim 26-30: The teachings of Michalakis are described supra. Michalakis also teach pharmaceutical compositions comprising the AAV (abstract, p1 [1]). As discussed supra, the AAV taught by Michalakis comprises AAV particles with the novel capsid modification, plasmids (nucleic acid vectors) comprising a nucleic acid molecule encoding the AAV capsid and host cells comprising the AAV. Thus the pharmaceutical compositions comprising the AAV read on compositions comprising particles, nucleic acid vectors comprising a nucleic acid molecule encoding the AAV, and host cells.
Therefore the disclosure of Michalakis anticipates the invention as claimed.
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 6 is rejected under 35 U.S.C. 103 as being unpatentable over Michalakis et al (WO 2019/076856 A1) as applied to claims 1, 10-13, 18 and 25-30 above, and further in view of Zhong et al (PNAS (2008) 105:22;1-6).
Claims 1, 10-13, 18 and 25-30 are anticipated by Michalakis and are therefore also rendered obvious (see above).
This is a new rejection due to the amendments to the claims.
Regarding claim 6: The teachings of Michalakis are described supra. Mickalakis do not teach the capsid protein comprises a further mutation.
Zhong teach mutagenesis of surface-exposed tyrosine residues of the AAV2 capsid leads to production of vectors that transduce HeLa cells 10 fold more efficiently (abstract). Zhong further teaches that each of 7 surface exposed tyrosines were substituted with phenylalanine residues (p2 col1 ¶1). The reads on a point mutation as required by the instant claim.
It would have been obvious to one of ordinary skill in the art to adapt the AAV capsid of Mickalakis drawn to a capsid with an insertion, by including the Y730F point mutation as taught by Zhong.
One of ordinary skill in the art would have been motivated to modify AAV capsid of Mickalakis with the point mutation taught by Zhong because Zhong teach the Y730F mutation has 11 fold increased transgene expression compared to the wild type vector (Figure 1C).
One would have had a reasonable expectation of success because both inventions are drawn to modifications of AAV2 capsid vectors.
Response to Arguments
The responses are directed to the Arguments filed 12/01/2025.
Regarding Arguments directed to 35 USC § 112a:
Regarding claims 1, 6, 10-13, and 18: The claim amendments overcome the rejections. The specific phrases that were rejected are removed and thus the rejection is withdrawn.
Regarding Arguments directed to 35 USC § 112b:
Regarding claim 5: Claim 5 has been cancelled and Seq ID Nos: 13 to 21 and 276 to 284 are moved into claim 1, thus the Arguments directed to the rejection are relevant sequences recited in claim 1.
Applicant argues sequence differences among alternative nucleic acids are not an adequate basis to sustain a Markush grouping rejection.
The argument is found persuasive and the rejection under 112(a) relating to an improper Markush group is withdrawn.
Regarding Arguments directed to 35 USC § 102:
The rejection under 102 in the action filed 06/03/2025 is withdrawn in view of the claim amendments. Specifically, claim 1 is amended to recite an insert after the amino acid number 587 of SEQ ID No. 2. This overcomes the disclosure of Deverman which is drawn to an insert after amino acid 588.
Regarding Arguments directed to 35 USC § 103:
The rejection under 103 in the action filed 06/03/2025 is withdrawn in view of the claim amendments. Specifically, Deverman and Perbo are no longer relied upon and thus arguments in respect with the teachings are moot. As discussed supra, the amendment to claim 1 overcomes the teachings of Deverman, and the instant claims no longer recite the polylinker for which Perbo was relied.
The new rejection directed to 35 USC § 103 does not rely upon previous art of record and thus the arguments against said art are moot.
Regarding the warning over double patenting:
In view of the claim amendments (cancellation of claims 2 and 8) the double patenting warning is withdrawn.
Allowable Subject Matter
Regarding claim 1: As discussed in the previous action, Perabo (EP 1456383 B1) teach libraries containing modified parvovirus capsid genes useful for the identification of parvovirus capsids able to transduce predefined cell types and methods for the production thereof (p3 ln 1-2).
Perabo disclose an AAV wherein the insert is inserted after a nucleic acid corresponding to multiple amino acid positions, preferably position 447 or 587, wherein the numbering of amino acids relates to the VP1 protein of AAV2 (p4 ln 1-10). Figure 5 of Perabo teaches a model of an AAV2 with a random heptamer following amino acid 587.
Perabo do not teach that the random heptamer is the sequence of Seq ID NO: 13. While Perabo teach multiple 7 sequence amino acid sequences which can be inserted following amino acid residue 587, Perabo do not teach the insertion of Seq ID NO: 13-21 or a 12 residue insertion of Seq ID NOs: 276-284.
Furthermore, a sequence search of Seq ID NO: 2 and an insertion of any one of the sequences from Seq ID NO: 13-17, 19 and 21 or Seq ID NOs: 276-284 at position 587 of Seq ID NO:2 does not produce a result in an alignment of greater than 91% for any of the sequences.
Thus Seq ID NO: 2 comprising the insertion of any one of Seq ID NOs: 13-17, 19, 21 and 276-284 at position 587 of Seq ID NO:2, as recited in claim 1, is considered free of the art.
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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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631
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