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 .
Amendments
In the reply filed 6/01/2026, Applicant has amended Claim 181, and canceled claim 182 and 203-204.
Claims 169-180, 186-201 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 181, 185, and 202 are under consideration.
Withdrawn 35 USC § 112
The prior rejection of Claims 181, 185, and 202 under 35 U.S.C. § 112(b) pre-AIA 2nd paragraph as being indefinite is withdrawn in light of Applicant’s amendments of Claim 181 to describe the AAV6 vector.
Maintained 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 181, 185, and 202 are rejected under 35 U.S.C. 103 as being unpatentable over Dion et al., (US 2019/0167814, filed 4/13/2017, published 6/06/2019, prior art of record), in view of Rutledge et al. (J Virol, 1998, (72):309-319, prior art of record), as evidenced by Burns et al. (US2019/0142972, filed 4/21/2017, published 5/16/2019, prior art of record)
With respect to claim 181, Dion claims a composition comprising (a) an AAV vector, and (b) a nucleotide sequence that encodes a Cas9 protein, and a nucleic acid sequence that encodes a sgRNA capable of down-regulating gene expression of a mutant allele of target gene that causes Fuch’s endothelial corneal dystrophy (see Claims 1-12 of Dion). Specifically, in regard to the AAV vector, Dion teaches the AAV vector serotype is AAV6 [0055].
However, Dion is silent to a “wildtype” AAV6 comprising an AAV6 capsid and AAV6 ITRs.
Nevertheless, the “wildtype” AAV6 for gene therapy purposes was well known, and Rutledge provides the sequences and enabling disclosure for making and using a wildtype AAV6 vector comprising at least one AAV6 ITR and capsid encoding a transgene (Figures, 2, 3, 5 and 7).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have prepared the AAV6 composition as suggested by Dion and choose a “wildtype” AAV6 vector comprising the AAV6 ITR and capsid as taught by Rutledge with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so not only because Dion suggests the AAV6 vector and the “wildtype” version comprising the AAV6 ITR and capsid is an obvious member of a limited genus of AAV6 vectors, but also because Rutledge teaches that the “wildtype” AAV6 vector is resistance to neutralizing antibodies against AAV2, and that this could be especially important for gene therapy, as significant immunity against AAV2 exists in human populations (Abstract).
In regard to claims 185 and 202, Dion teaches the target gene that causes Fuchs’ endothelial corneal dystrophy to which the sgRNA binds encodes the transcription factor protein TCF4 ([0058, 0150] see Tables 1 and 8). In regard to claim 185 reciting the wherein clauses directed to the preferential expression of the TCF4 target gene in the anterior portion of the eye, this was a well-known expression pattern for TCF4 and reflects an inherent proper of this particular target gene as evidenced by Burns et al. ([0005, 0175]). Moreover, the phrase “preferentially expressed” is not defined by the claim, nor the specification. Thus, the fact that TCF4 causes Fuchs endothelial corneal dystrophy, by preferentially affecting the corneal endothelium compared to other cells evidences that the TCF4 target gene fulfills this limitation. Furthermore, in regard to the contingent clause of Claim 185 directed to TCF4 gene expression “after intracameral (IC) injection” is an intended use of the claimed composition, and a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Thus, the fact that Dion discloses a sgRNA that down-regulates the TCF4 target gene, and the TCF4 target gene is naturally preferentially expressed in the cornea of the eye, the AAV based composition possesses the structure capable of performing the intended use.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 6/01/2026 are acknowledged.
First, Applicant argues there was no motivation to choose AAV6. Specifically, Applicant argues that the primary reference of Dion is directed to the general field of DNA repair for triplet repeat diseases, and although Dion teaches the type of AAV determines the target tissue tropism, they are silent to AAV6 targeting the cornea. In fact, Dion cites that the AAV6 can be used in culture cells such as iPSCs or ES cells, not the cornea. Furthermore, Applicant argues that neither Rutledge or Burns cure this deficiency. Thus, Applicant argues that there was not motivation to choose an AAV6 vector for targeting a corneal disease, and the Examiner has relied upon and “obvious to try” rationale for choosing the AAV6 vector. Applicant argues the Examiner’s rationale is flawed because the possible targets for gene therapy in body, as well as the possible viral vectors to be used is near infinite.
Second, Applicant argues that AAV6 yielded unexpected results. Specifically, Applicant argues that Applicant’s Fig. 10 had shown that AAV6 exhibited the strongest targeting and expression in the cornea.
Applicant's arguments have been fully considered but they are not persuasive.
In regard to the motivation to choose AAV6 to treat Fuch’s endothelial corneal dystrophy (FECD), as stated in the pending rejection, Dion explicitly claims an AAV vector encoding a Cas9 and sgRNA for the treatment of the DNA triplet repeat disease of FECD. Furthermore, when turning to the specification of Dion, only two AAV vectors are suggested, i.e., AAV6 and AAV9. Thus, as acknowledged by Applicant, an “obvious to try” rationale may support a conclusion that a claim would have been obvious where one skilled in the art is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. In instant case, there was a finite number of only two options of AAV vectors to choose from, which according to Dion were the preferred options due to their “broad tissue specificity and expression levels”, thereby establishing that the AAV6 vector could have been used with a reasonable expectation of success. Applicant is reminded that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.” KSR International Co. v. Teleflex Inc., 550 U.S. 82 USPQ2d 1385, 1397 (2007).
In response to Applicant’s argument that Dion teaches AVV6 can also be used with cultured patient-derived cells, such as with iPSCs or ES cells, MPEP 2141.02 (VI) states that "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). As stated supra, Dion teaches AAV6 was a preferred options due to their “broad tissue specificity and expression levels”. Note that neither Applicant’s claims nor specification require tissue specific expression of the AAV6 vector to treat a corneal disease.
In regard to Applicant’s purported unexpected results, as a first matter, independent claim 181 is extremely broad with respect to targeting any gene in any cell of the cornea, and contrary to Applicant’s assertion, the use of an AAV6 to target cells of the cornea was well known in the prior art. Importantly, in order to rebuke Applicant’s arguments, the prior art of Sharma et al., (Brain Res Bull, 2010, 81:273, prior art of record) evidences that the AAV6 serotype was “safe for corneal gene therapy” (Abstract). Although Sharma uses and AAV2/6 vector, which Applicant had amended instant claims to disqualify, does not change the fact that the tropism of the AAV6 vector as dependent on the AAV6 capsid was fully capable of transducing cells of the cornea. Thus, there was nothing unexpected about using AAV6 to target any gene associated with any diseases/conditions of cornea, and Applicant’s invention simply worked as predicted by the prior art.
Furthermore, in regard to Applicant’s findings that AAV6 targets endothelial cells of the cornea, Applicant’s specification admits that although AAV6 demonstrates targeting to the corneal endothelium, AAV6 also displayed tropism to other corneal and anterior structures, as well as the retina [0041]. Thus, Applicant provides no critical nexus for making and using an AAV6 vector for specifically targeting a disease gene of the corneal endothelium such as TCF4 which contribute to Fuch’s endothelial corneal dystrophy.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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