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 .
Applicant's response to the previous Office action, dated July 21, 2026, has been received. By way of this submission, Applicant has amended claim 24, and cancelled claims 25, 31, and 32.
Claims 24, 26-29, and 33 are pending in the application and under examination before the Office.
The rejections of record can be found in the previous Office action, dated April 22, 2026.
Claim Interpretation
Claim 26 recites an “AldhlL1” promoter. It is assumed that this is meant to refer to an “Aldh1L1” promoter, wherein the fifth character is the numeral 1 and not a lowercase l.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 21, 2026 was filed after the mailing date of the first Office action on the merits on June 18, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant argues that the references to Schon, De Faria, Di Rosa, Ghosh, and Li do not teach every aspect of the claims as amended; specifically, none of the cited references teach an astrocyte-specific promoter operably linked to a nucleic acid encoding a polypeptide comprising beta-A1-crystallin.
Applicant's amendments to the claims have addressed this issue, and the rejection under 35 U.S.C. 103 over Schon in view of De Faria, Di Rosa, and Ghosh is hereby withdrawn.
Applicant's cancellation of claim 32 has rendered the rejection under 35 U.S.C. 103 over Li in view of De Faria, Di Rosa, and Ghosh moot, and it is withdrawn.
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.
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 24, 27-29, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Scaria (US20170096683A1) in view of Zigler (Prog Retin Eye Res. 2014 Nov 13;0:62–85, cited previously). This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
Scaria teaches the use of a recombinant adeno-associated vector (AAV) as a vehicle for gene therapy in the treatment of retinal degenerative diseases (para. 0004).
Scaria further teaches that the disease may be diabetic retinopathy (para. 0013 and 0171).
Scaria further teaches that this method delivers a therapeutic nucleic acid to astrocytes (para. 0007).
Scaria also teaches that this method improves expression of a heterologous nucleic acid following subretinal delivery of AAV particles to the eye of an individual (para. 0015).
Scaria also teaches that glial cells of the retina include astroglia (i.e., astrocytes) (para. 0221).
Scaria further teaches that the nucleic acid is operably linked to a promoter suitable for expression of the therapeutic nucleic acid in one or more retina cell types (para. 0020).
Scaria further teaches that the AAV may be AAV2, which promotes transduction following subretinal injection (para. 0081), which is pertinent to claims 27 and 29.
Scaria further teaches that the subject is human (para. 0013), which is pertinent to claim 33.
However, Scaria does not teach beta-A1-crystallin.
Zigler (Prog Retin Eye Res. 2014 Nov 13;0:62–85) teaches that mutant mice deficient in beta A1-crystallin have abnormal vascularity in the retina (Figure 9H and 9I: "...while the Nuc1 vascular pattern is sparse, appears to be lacking a deep capillary plexus and has an abnormal pattern...").
Zigler further teaches that over-expression of bA3/A1-crystallin is capable of rescue of V-ATPase activity in the above mutant mice (Figure 13).
Zigler further teaches that beta A1-crystallin is expressed in astrocytes, and are required for proper function of lysosomes, and that a vector construct over-expressing beta-A1 crystallin rescues this phenotype (abstract and page 79, left column, first paragraph: "When cultured cKO astrocytes were transfected with a vector construct over-expressing beta A3/A1 crystallin, both of these effects were reversed.").
Zigler further teaches that this model may provide mechanistic insights as to how abnormalities in astrocytes contribute to both neuronal cell death and vascular changes in diabetic retinopathy (page 80, left column, first paragraph).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Scaria and Zigler to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Scaria and Zigler are concerned with gene therapy for the eye. Scalia teaches that AAV vectors are useful to treatment of diabetic retinopathy by delivering a therapeutic gene to cells of the eye, especially in combination with a promoter suitable for expression in specific retinal cell types. Zigler teaches that beta A1-crystallin is one such gene that may be useful to rescue a diabetic retinopathy phenotype. One of ordinary skill could apply the beta A1-crystallin of Zigler to the method of Scaria by simple substitution, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Scaria and Zigler as applied to claim 24 above, and further in view of Mudannayake (Mol Ther Methods Clin Dev. 2016 Nov 30:3:16075). This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
The teachings of Scaria and Zigler have been discussed supra. However, Scaria and Zigler do not teach the astrocyte-specific promoter Aldh1L1.
Mudannayake teaches that Aldh1L1 is homogenously expressed in astrocytes (page 1, right column, first paragraph).
Mudannayake further teaches the use of Aldh1L1 promoters for use in AAV vector mediated gene transfer to astrocytes (page 1, right column, second paragraph).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Scaria, Zigler and Mudannayake to arrive at the claimed invention. Scaria teaches that it is useful to use a cell-specific promoter to target a therapeutic nucleic acid to specific cell types when using an AAV, including astrocytes. Mudannayake teaches that an Aldh1L1 promoter is a suitable astrocyte-specific promoter. One of ordinary skill could apply the Aldh1L1 promoter of Mudannayake to the method of Scaria and Zigler by simple substitution, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 7:00 to 3:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PETER JOHANSEN/Examiner, Art Unit 1644
Prosecution Insights