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/RCE under 37 CFR 1.114
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1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 7/24/2025 has been considered.
Claims 131 and 132 are newly added. Claims 123 and 132 have been amended. Clams 117-121, 123 and 127-132 are pending. Claims 117-121 and 131 are currently withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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, 127-130 and 132 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 statement (IDS) submitted on 1/26/2015 and 7/24/2025 was 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Withdrawn Rejections
The 35 U.S.C. 103 rejection of claims 123 and 127-130 has been withdrawn and newly applied in modified form to address applicants claim amendments which specify that the ABCA4 polypeptide is expressed from the HSV genome in one or more cells of the eye of a subject.
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).
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, 127-130 and 132 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). This rejection is newly applied in modified form to address applicants claim amendments on 7/24/2025. 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 provides preferred embodiments to 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 describe suprachoroidal administration, that the eye condition is Stargardt disease or that the ATPase is specifically a ABCA4 polypeptide which is expressed in one or more cells 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 and 129: Krishnan describes generating replication defective recombinant herpes simplex viruses by targeted inactivating mutations to ICP0, ICP4, ICP22, ICP27, ICP47, thymine kinase, UL41 and UL55 (Krishnan, para 9).
Claims 123 and 132: 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 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 arguing that there would have been no motivation to combine references and that no articulate reasoning was provided by the Examiner to combine the cited art to meet the claim limitations. Applicant states that there is no rationale as to why one of ordinary skill would focus on the teaching of subretinal administration among the many routes of administration listed by Krishnan. Applicant argues that there is no reasonable expectation of success given the AAV vector upper size limit described by Robinson. Applicant argues that the therapeutic transgenes of Robinson are partial ABCA4 coding sequences rather than full length ABCA4.
These arguments have been fully considered, but were not found persuasive. With respect to the administration routes, it is noted that nonpreferred and alternative embodiments constitute prior art. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments, see MPEP 2123. Thus, 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. Furthermore, Robinson discloses viral vector delivery methods including subretinal, direct retinal suprachoroidal or intravitreal injection (Robinson, para 359).
With respect to applicants’ arguments regarding motivation to combine, 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.
Furthermore, the examiner has introduced Spencer as a prior art reference to show the known advantages of using HSV vectors for ocular gene therapy. Specifically, Spencer found that attenuated HSV-1 vectors allowed for the efficient transduction of numerous cell types of the eye while offering increased cargo capacity and lower toxicity when compared to AAV based vectors (pg 1392-1393 and 1399 col 2).
With respect to applicants’ arguments on reasonable expectation of success, 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. 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.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Langi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717 .02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP 706.02(1)(1) - 706.02(1)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 123 and 127-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of US Patent No. 11,865,148 (application number 18/060,515) in view of Robinson (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims would anticipate the instant claims if they were available as prior art. This rejection is maintained for the same reasons as set forth in the office action mailed on 1/28/2025. A response to applicant’s traversal follows the reiterated rejection below.
Claims 123: The patented claims describe a method for delivering a human transgene to an eye of a subject, wherein the subject has an eye disease associated with vision loss (claim 1). The patented claims describe the human transgene broadly enough to encompass any retinal-specific phospholipid-transporting ATPase polypeptide (Claims 1, 11). The patented claims describe the use of a pharmaceutically acceptable carrier (Claim 1). The patented claims describe the use of a replicative deficient herpes simplex virus (claim 1, 7). The patented claims do not describe delivering an ATPase ABCA4 polypeptide and expression in eye cells of a subject, treatments for Stargardt disease or subretinal injection.
Claim 127: The patented claims describe the use of recombinant HSV-1 vectors (Claim 10).
Claims 128 and 129: The patented claims describe inactivating mutations to the ICP4 HSV-1 gene.
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 the patented claims. 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. 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. 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. 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 arguing that the examiner has failed to make a prima facie case of obviousness. Specifically, applicant points to amendments to calm 123 and repeat arguments that there would have not been an expectation of success.
These arguments have been fully considered, but were not found persuasive since the patented claims describe a method for delivering a human transgene to an eye of a subject, wherein the subject has an eye disease associated with vision loss (claim 1). The patented claims describe the human transgene broadly enough to encompass any retinal-specific phospholipid-transporting ATPase polypeptide (Claims 1, 11). The patented claims describe the use of a pharmaceutically acceptable carrier (Claim 1). The patented claims describe the use of a replicative deficient herpes simplex virus (claim 1, 7). Although the patented claims do not describe delivering an ATPase ABCA4 polypeptide and expression in eye cells of a subject, treatments for Stargardt disease or subretinal injection, this would have been obvious in light of the disclosure of Robinson who describes gene therapy methods for the treatment of Stargardt disease (Robinson, para 3-6).
With respect to applicants’ arguments on reasonable expectation of success, 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. 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.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. 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, Maria Leavitt can be reached on (571)272-1085. 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