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
Claim status
Claims 1-20 are pending
Claims 8-9, 11-20 are withdrawn
Claims 1-7 and 10 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 3/30/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-10, drawn to methods of treating, reducing the risk of, preventing, or alleviating at least one symptom of a retinal disease, injury, or condition.
Claims 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of the following species is acknowledged.
Glaucoma is the retinal disease/condition with an increase in intraocular pressure.
Claims 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/22/2023, 11/21/2025, and 4/08/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objections to the Specification
Specific deficiency – Applicant’s specification refers to SEQ ID NOs: 1-4. This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
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 of this title, 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.
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 1-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over O’Reilly et al. (Mol Neurobiol, 2010, 42:124-132), in view of Whitlock et al. (IOVS, 2005, 46:1085-1091) and Kwong et al., (Gene Therapy, 2015, 22:138-145, see IDS file 8/22/2023).
O’Reilly reviews the role of Hsp27 (alias HspB1) in neuroprotection of the retina.
Specifically, in regard to retinal disease of claim 1, O’Reilly teaches that the retinal disease glaucoma is an optic neuropathy, marked by a progressive degeneration of retinal ganglion cells (RGCs) that contributes to the progressive vision loss during glaucoma (p. 125, Introduction, 2nd para., p. 129, Potential as a Clinical Therapeutic). Furthermore, O’Reilly teaches that Hsp27 is induced by elevated intraocular pressure and in glaucoma models (p. 126, Induction of HspB1 by Elevated Pressure or Glaucoma Models), and that the increase of Hsp27 in the retina of the glaucomateous eye suggest that it functions as a defense mechanism of stressed or injured neurons in glaucoma (p. 127, HspB1 Neuroprotection against Elevated Intraocular Pressure and Glaucoma).
In regard to the expression of Hsp27 in RGCs as per claim 1, O’Reilly summarizes that there is a protection of RGCs conferred by Hsp27, which has direct implications for preventing vison loss (p. 129, Potential as a Clinical Therapeutic).
Finally, in regard to administering to a subject a nucleic acid encoding Hsp27 as per claim 1, O’Reilly concludes the use of gene therapy to deliver exogenous Hsp27 to the retina may help treat retinal disease (p. 130, 1st para.).
However in regard to the nucleic acid of claim 1, O’Reilly does not teach a nucleic acid encoding at least one biologically active Hsp27 protein and promoter that is expressed in RGCs. Nevertheless, O’Reilly cites the prior art of Whitlock et al. (2005) for the overexpression of Hsp27 in RGCs (p.128, HspB1 Inhibition of Apoptosis).
In regard to the Hsp27 nucleic acid of claim 1, Whitlock teaches a nucleic acid sequence encoding Hsp27, and a promoter sequence positioned upstream of the nucleic acid sequence, wherein the promoter sequence induces expression of the nucleic acid in RGCs (p. 1085, Stable Overexpression rHsp27 in RGC-5 Cells). Specifically, Whitlock demonstrates that overexpression of Hsp27 protected RGCs in vitro from oxygen-glucose deprivation and calcium overload (p. 1087, Results, para. 1-3, see also Figs. 2-4).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of treating glaucoma by gene therapy with Hsp27 as suggested in the review of O’Reilly, and use a Hsp27 nucleic acid operably linked to a promoter that induces expression in RGCs as taught by Whitlock with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, O’Reilly cites the prior art of Whitlock, and it would have been obvious to turn cited relevant art for an enabling disclosure for nucleic acids of a gene of interest. Second, Whitlock concludes that retinal ischemia plays a central role in ocular diseases such as glaucoma, and that Hsp27 expression can protect retinal cells from ischemic injury (pgs. 1088-1089, Discussion, para. 1 -2). Thus, one of ordinary skill in the art would have been motivated to use the Hsp27 nucleic acid operably linked to a promoter that expresses in RGCs to treat a glaucoma model.
However, O’Reilly and Whitlock are silent to the step of administering the Hsp27 nucleic acid to a subject in vivo in and AAV vector as per claim 1.
In regard to the in vivo gene therapy step of claim 1, Kwon et al. (2014) teaches gene therapy methods for treating the degeneration of RGCs in optic neuropathies, including glaucoma by intravitreally administering to the eye of a subject an AAV2 vector encoding a Hsp70 gene (p. 2, Introduction, 2nd para., pgs. 7-8, Methods, 2nd para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice a method of treating glaucoma by gene therapy with Hsp27 nucleic acid operably linked to a promoter that is expressed in RGCs as suggested by O’Reilly, in view of Whitlock, and to substitute the in vivo step of intravitreally administering an AAV2 vector encoding the heat shock protein as taught by Kwong with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do as taught by Kwong because a single intravitreal injection of the AAV2 vector transfects about 75% of RGCs, indicating a preferential transfection of RGCs with the AAV2 vectors by intravitreous injection (Abstract, p. 3, Results, para. 2). This would have been especially advantageous to the proposed method of O’Reilly because RGCs are the cell type that are affected in glaucoma.
In regard to claims 2, 7, and 10, as stated supra, O’Reilly teaches Hsp27 is neuroprotective against elevated intraocular pressure and in glaucoma animal models.
In regard to claim 3, although Whitlock and Kwong provide the nucleic acids before the retinal insults in vitro or in the in vivo animal models, this is not a realistic scenario for a subject who has been just diagnosed with glaucoma. As stated supra, O’Reilly teaches glaucoma is a progressive degeneration of RGCs, and glaucoma causes RGC pathology and a progressive loss of vision. Accordingly, it would have been obvious to begin Hsp27 gene therapy as soon as possible after diagnosis (i.e., within 24 hours), so as to minimize the progressive degeneration of RGCs and progressive loss of vision.
In regard to claims 4-6, as stated supra, Kwong teaches a single intravitreal injection of the AAV2 vector, which would have been obvious to transfect the majority of RGCs in the subject’s eye with minimal intervention.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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