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 .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/15/2026 has been entered.
Claims 2, 3, 6-11, 14, and 21-25 have been cancelled. Claims 13 and 15 have been withdrawn. Claims 1, 4, 16, 18, and 19 have been amended.
Claims 1, 4, 5, 12, and 16-20 are under examination.
2. The rejection of claim 12 under 35 U.S.C. 112(b) is withdrawn in response to the amendment to make the claim dependent upon claim 1.
The rejection of claim 12 under 35 U.S.C. 112(d) is withdrawn in response to the amendment to delete the recitation “exon 13 or” from the claim.
Upon further considerations, the rejection of claims 1, 4, 5, 12, and 16-20 under 35 U.S.C. 103 as being unpatentable over Allocca et al. (CA 3084633), in view of both Kaiserman et al. (Arch. Ophthalmol., 2007, 125: 219-224) and Laskowski et al. (Stem Cell Reports, 2016 7: 139-148) is withdrawn. New grounds of rejection are set forth below.
Specification
3. The claim listing is objected to because claims 13 and 15 are identified as “previously presented” and “currently amended’. However, the claims have been withdrawn. Thus, the proper status identifier for claims 13 and 15 is “withdrawn”. Correction to “withdrawn” is required.
Claim Rejections - 35 USC § 103
4. 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.
5. Claims 1, 4, 5, 12, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Allocca et al. (CA 3084633), in view of both Kaiserman et al. (Arch. Ophthalmol., 2007, 125: 219-224) and Mates et al. (Genome Biology, 2007, 8, Suppl. 1, p. SI.1-SI.19).
Allocca et al. teach a method for integrating a donor transgene into the USH2A gene via homology-dependent repair (HDR), where the USHA2A gene comprises a mutation causing retinitis pigmentosa; the method comprises in vivo or ex vivo administering a CRISPR endonuclease, one sgRNA comprising a spacer targeting the CRISPR endonuclease to a target site within the USH2A gene (such as intron 13) to make a single cut within the target site, and the donor transgene to patients or human cells comprising mutations in the USH2A gene. Allocca et al. teach that the donor transgene is delivered via electroporation, AAV, or a liposome. Allocca et al. teach that the donor transgene is flanked by sequences homologous to sequences flanking the targeted site (homology arms) and is operably linked to a promoter, where the promoter increases HDR by three-fold. Allocca et al. teach that in vivo administration is to photoreceptors (claims 1, 4, 5, 12, 16-18, and 20) (see Abstract; [0007]; [0009]-[0011]; [0014]; [0120]; [0150]-[0151]; [0276]; [0337]; [0472]; [0475]; [0487]; [0508]-[0509]; [0523]; [0527]; [0533]; [0535]; [0550]; [0561]).
Allocca et al. do not specifically teach delivering the transgene via lipid nanoparticles (LNPs) (claim 19). However, Allocca et al. teach using LNPs to deliver the CRISPR endonuclease (see [0412]-[0413]). One of skill in the art would have readily concluded that LNPs could also be used to deliver the transgene. Using LNPs to deliver the transgene would have been obvious to one of skill in the art to achieve the predictable result of delivering the transgene to the patients or cells.
Allocca et al. do not teach that the transgene encodes the polypeptide set forth by SEQ ID NO: 13 (claim 1). However, it is noted that there is no evidence of record indicating that specifically using the transgene encoding the polypeptide set forth by SEQ ID NO: 13 leads to unexpected results. Furthermore, Allocca et al. teach using the CRISPR endonuclease to correct for exon mutations by integrating the transgene within intron 13, where the transgene encodes at least a portion of the wild type USH2A gene (see [0112]; [0118]; [0150]-[0151]; [0154]). While Allocca et al. do not specifically teach that the portion consists of exons 2-13, Kaiserman et al. teach that pathogenic mutations also occur in exon 2 (see p. 222, Table 1). Based on these teachings, one of skill in the art would have found obvious to use a transgene encoding the polypeptide produced by exons 2-13 of the wild type USH2A to achieve the predictable result of obtaining a single composition suitable to repair mutations occurring in exon 2 as well as in exon 13. By doing so, one of skill in the art would have used a transgene encoding the polypeptide set forth by SEQ ID NO: 13 (claim 1).
Allocca et al. and Kaiserman et al. do not specifically teach a 3’ splice donor (claim 1). However, Allocca et al. teach that the donor transgene is expressed from an operably linked to a promoter. Mates et al. teach that a splice donor at the 3’ end is needed when integrated transgenes are to be expressed from the operably linked promoters (see p. SI.8, Fig. 2 (c) and (d); the legend for Fig. 2 in SI.9). Based on these teachings, one of skill in the art would have found obvious to include a splice donor at the 3’ end of the donor transgene, to achieve the predictable result of splicing the transgene to the downstream exon and restore the wild type USH2A activity.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
6. The arguments are answered below to the extent that they pertain to the new rejection.
The argument that Allocca’s method always involves two cuts in the genome is not found persuasive because it does not consider the totality of the teachings in Allocca. Patents are relevant as prior art for all they contain and may be relied upon for all that they would have reasonably suggested to one of skill the art; nonpreferred and alternative embodiments constitute prior art. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (see MPEP 2123). As indicated in the rejection, Allocca does teach using only one gRNA to target the CRISPR endonuclease at the targeted site to effect a single cut within the targeted site (see [0508]; [0527]).
The applicant points to Fig. 3 in Allocca. Fig. 3 is not material to the rejection because it only pertains to methods 1-3 described in [0112], which do not use HDR and which are not the basis for rejection.
The applicant also points to [0118]. This paragraph discloses that HR “can involve” two cuts. This teaching is only one HDR embodiment. Allocca also teaches the embodiment where HDR takes place by using a single cut within the targeted site.
For these reasons, the following arguments are not found persuasive: (1) Allocca’s method and the claimed method involve different mechanisms; and (2) change in the principle of operation.
The argument that Allocca’s method would not operate with a single cut is not found persuasive because it is just an argument not supported by any evidence.
7. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633