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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 4/29/2026 has been considered. Claims 133-134 are newly added. Claims 120, 129, 131 and 132 are canceled. Claims 123 and 128 have been amended. Clams 117-121, 123, 127-128, 130 and 133-134 are pending. Claims 117-119, 121 and 133 are currently withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 123, 127-128, 130 and 134 are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/459,102, PRO 63/460,948 and PRO 63/593,085 filed on 4/13/2023, 4/21/2023 and 10/25/2023, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 4/13/2023
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4/29/2026 and 5/22/2026 were received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Withdrawn Rejections
The non-statutory double patenting rejection of claims 123 and 127-130 over US 11,865,148 has been withdrawn in light of applicants claim amendments which define the inactivating mutation as targeting ICP4.
Claim Interpretation
It is emphasized that any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims, see MPEP 2173.05(i).
Maintained 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 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.
Claims 123, 127-128, 130 and 134 are rejected under 35 U.S.C. 103 as being unpatentable over Krishnan et al. US 2021/0189427, published 6/24/2021 (hereinafter Krishnan, reference of record) in view of Robinson et al. US 2021/0147870, published 5/20/2021 (hereinafter Robinson, reference of record) and Spencer et al. "Herpes simplex virus–mediated gene delivery to the rodent visual system." Investigative ophthalmology & visual science 41.6 (2000): 1392-1401 (hereinafter Spencer, reference of record) as evidenced by Manservigi et al. "HSV recombinant vectors for gene therapy." The open virology journal 4 (2010): 123. This rejection is maintained for the same reasons of record as outlined in the office action mailed on 10/29/2025 and newly applied to claim 134. A reply to applicants’ traversal is found below.
Claim 123: Krishnan describes a method for delivering therapeutic recombinant nucleic acids using replication defective recombinant herpes simplex viruses (Krishnan, para 7-9). Krishnan describes generating the replication defective recombinant herpes simplex viruses via inactivating mutations to one or both copies of the ICP4 gene (Krishnan, para 9 and 175). Krishnan provides preferred embodiments to the delivery of therapeutic recombinant nucleic acids including sarcoplasmic/endoplasmic reticulum calcium ATPase 2 polypeptides (Krishnan, para 11, 25, 70, 123). Krishnan describes the use of a pharmaceutically acceptable carrier or excipient for subretinal administration (Krishnan, para 206-207, 234). Subretinal administration indicates that the aforementioned method is applied to an eye condition or disease for therapeutic relief. Krishnan describes alternative embodiments towards a recombinant herpes simplex virus which do not encode the listed polynucleotides in claim 123 (Krishnan, para 232 and examples 1-3). Krishnan does not state that the eye condition is Stargardt disease or that the ATPase is specifically a ABCA4 polypeptide which is expressed in one or more cells (corneal epithelial cell, photoreceptor cell, retinal pigment epithelial cell, retinal ganglion cell, bipolar cell, horizontal cel, muller cell, amacrine cell) of the eye of a subject.
Claim 127: Krishnan describes the use of recombinant herpes simplex viruses including HSV-1 and HSV-2 (Krishnan, para 8).
Claim 128: Krishnan describes generating replication defective recombinant herpes simplex viruses by targeted inactivating mutations to one or more of ICP0, ICP4, ICP22, ICP27, ICP47, thymine kinase, UL41 and UL55 (Krishnan, para 9).
Claim 134: Krishnan describes preferred embodiments wherein “the recombinant herpes simplex virus genome is not oncolytic” (Krishnan, para 175).
Claims 123: Spencer describes expression of a therapeutic transgene using a HSV-1 vector in corneal epithelial cells and retinal pigment epithelium following intracameral and intravitreal ocular injection (Spencer, pg 1399 col 2). Spencer found that attenuated HSV-1 vectors allowed for the efficient transduction of numerous cell types of the eye, including corneal epithelial cells and the retinal pigment epithelium, while offering increased cargo capacity and lower toxicity when compared to AAV based vectors (pg 1392-1393 and 1399 col 2).
Claim 123: Robinson describes gene therapy methods for the treatment of Stargardt disease (Robinson, para 3-6). Robinson discloses viral vector delivery methods including subretinal, direct retinal suprachoroidal or intravitreal injection (Robinson, para 359). Robinson describes the genetic origins of Stargardt disease and how it’s a recessive disorder linked to mutations in the gene encoding the protein ATP Binding Cassette, sub-family A, member 4 (ABCA4). Stargardt disease results from mutations in the ABCA4 gene, leading to a lack of functional ABCA4 protein in retinal cells (Robinson, para 5). Robinson describes delivering a gene therapy vector for expressing an ABCA4 polypeptide (Robinson, para 3).
Claim 130: The ABCA4 protein (SEQ ID NO: 11 as disclosed in Robinson in para 431) comprises the retinal-specific phospholipid-transporting ATPase polypeptide (instant SEQ ID NO: 33) of the claimed invention (see sequence search results below).
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It would have been prima facie obvious to one of ordinary skill in the art to suprachoroidally deliver the retinal-specific phospholipid-transporting ATPase ABCA4 polypeptide encoded by SEQ ID NO: 33 as disclosed by Robinson in the replication defective recombinant herpes simplex viruses disclosed by Krishnan and Spencer as a treatment for Stargardt disease. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Robinson shows that the viral delivery of ABCA4 is an effective treatment for Stargardt disease. Although it is acknowledged that Robinson uses an AAV vector to achieve the viral delivery of ABCA4, Spencer shows that attenuated HSV-1 vectors offer numerous advantages over AAV vectors when delivering therapeutic transgenes to the eye. Therefore, one would have been motivated to make this combination given that replication defective recombinant herpes simplex viruses offer numerous advantages over the AAV vectors used by Robinson including increased cargo capacity and lower toxicity to host cells as described by Spencer. One would have a reasonable expectation of success given that the substitution of one therapeutic transgene for another in viral vector systems is considered routine in the art given that the size constraints of the HSV vector described by Krishnan could readily accommodate the ABCA4 transgene. Furthermore, administration via retinal suprachoroidal injection would result in higher transduction efficiencies while minimize off-target effects. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Response to Traversal
Applicant traverses the rejection by pointing to amendments to claim 123 which specify that the inactivating mutations are in one or more copies of the ICP4 gene and further limitations to expression in specific eye cells. Applicant argues that Spencer teaches a replicant competent HSV vector which therefore does not contain an inactivating mutation in the ICP4 gene. Applicant submits that one of skill in the art would therefore not be motivated to turn towards the teachings of Spencer since the disclosure teaches away from the use of replicant defective HSV. Applicant argues that Spencer disparages the use of replicant defective HSV vectors because Spencer teaches that the two most frequently used HSV-based vectors include replicant defective HSV vectors and amplicon vectors.
These arguments have been fully considered, but were not found persuasive since teaching away requires the prior art to criticize, discredit, or otherwise discourage the claimed solution, see MPEP § 2141.02(VI): “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.” Since the prior art clearly does not do this, this argument is unconvincing. Although it may be true that Spencer teaches a replication competent HSV-1 vector, Krishnan is relied upon to show a replication defective recombinant herpes simplex virus via inactivating mutations to one or both copies of the ICP4 gene (Krishnan, para 9 and 175). Spencer is introduced to merely show that HSV-1 vectors have tropism towards corneal epithelial cells and retinal pigment epithelium following intracameral and intravitreal ocular injection (Spencer, pg 1399 col 2). As evidenced by Manservigi, the glycoproteins present on the viral envelope are responsible for viral tropism (tissue specificity to the corneal epithelium) would not be changed by mutating ICP4 genes (Manservigi, Fig 1 and Herpes simplex virus life cycle). Furthermore, it is emphasized that Spencer is already experimenting with attenuated HSV-1 vectors which already have suppressed replication. Thus, one of ordinary skill would understand from the disclosure of Spencer that HSV-1 vectors have tissue tropism towards corneal epithelium and that this would similarly apply to the replication defective HSV-1 vectors taught by Krishnan given that they share the same extracellular envelope.
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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1633
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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