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 7/21/2026 has been considered. Claim 24 is canceled. Claims 7 and 21 have been amended. Claims 1-5, 7, 10-11, 15-21, 25-30 and 33-34 are pending. Claims 1-5 are currently withdrawn without traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking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 7, 10-11, 15-21, 25-30 and 33-34 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.
The declaration submitted on 7/8/2026 by Dr. Weldon Haw was received and fully considered. Briefly, the declaration argues against the motivation to combine the cited references with a reasonable expectation of success in view of the knowledge that (1) HSV infection of the eye is a major cause of neurotrophic keratitis through a mechanism involving immunogenicity and subsequent pathogenesis resulting in an elevated immune response in neurotrophic keratitis patients and (2) it was unknown ant the time of filing whether a replication defective HSV vector could induce an immune response in neurotrophic keratitis patients. The declaration refers to Exhibit A which shows the unexpected findings that a single HSV-bNGF topical treatment resulted in higher mouse eye NGF levels as compared to six doses of rhNGF.
The declaration submitted on 7/21/2026 by Dr. Trevor Parry was received and fully considered. Briefly, the declaration revies the data presented in Fig 1 of Exhibit A which shows the results of a subject treated with a replication-defective HSV encoding bNGF administered topically to the affected eye twice weekly for eight weeks. The declaration argues unexpected results in a substantial reduction in the corneal epithelial defect which was completely closed by week 8.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/459,102, PRO 63/460,948, PRO 63/593,085 and DIV of 10/634,382 filed on 4/13/2023, 4/21/2023, 10/25/2023 and 4/12/2024, 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 7/21/2026 was received. The submission was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Withdrawn Rejections and Objections
The objections to claims 7 and 21 have been withdrawn in light of applicants’ claim amendments which add the appropriate acronyms.
The 35 U.S.C. 103 rejection of claims 21, 24-30 and 34 over Krishnan in view of Wen as evidenced by DelMonte has been withdrawn in light of applicants claim amendments specifying that the one or more cells are from the corneal epithelium of a subject.
Claim Interpretation
Claim 10 describes a HSV vector “suitable” for delivery into one or more target cells. Under the broadest reasonable interpretation, the claim language does not necessarily require that the HSV vector delivers the bNGF polypeptide only that it is suitable for such an application.
Claims 11 and 21 list out target cell types from a subject with a corneal injury. Absent evidence to the contrary, the corneal epithelium (outermost cell layer of the eye) would be in contact with the HSV vector upon topical administration.
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 7, 10-11, 15-20 and 33 stand 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 Wen et al. US 2022/0339251, published 10/27/2022 (hereinafter Wen, reference of record) and Ferrari et al. "Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial." BioDrugs 28 (2014): 275-283 (hereinafter Ferrari, reference of record). This rejection is repeated for the same reasons as outlined in the office action mailed on 7/8/2026. A response to applicant’s arguments is found below.
Claim 7: Krishnan describes a method for delivering therapeutic recombinant nucleic acids using replication defective recombinant herpes simplex viruses (Krishnan, para 7-9). Krishnan describes the use of a pharmaceutically acceptable carrier or excipient for topical administration (Krishnan, para 14, 206). Krishnan also describes subretinal administration routes, which indicates that the aforementioned method is applied to an eye condition or disease for therapeutic relief (Krishnan, para 14, 206-207, 234). Krishnan provides preferred embodiments to therapeutic recombinant nucleic acids including bone morphogenic protein receptor type-2 polypeptide (BMPR2) among others (Krishnan, para 11, 25, 70, 123 and claim 118). However, Krishnan does not describe the delivery of a polynucleotide encoding a beta nerve growth factor (bNGF) or an express description of administering the pharmaceutical composition topically to the eye as a method of treating neurotrophic keratitis.
Claim 10: Krishnan describes generating replication defective recombinant herpes simplex viruses which for delivering therapeutic transgenes like BMPR2 and would therefore be “suitable” for delivering polynucleotides encoding the bNGF polypeptide to one or more target cells of a subject’s eye (Krishnan, para 11, 25, 70, 123 and claim 118; see claim interpretation above).
Claim 15: Krishnan describes the use of recombinant herpes simplex viruses including HSV-1 and HSV-2 (Krishnan, para 8).
Claims 16-17: Krishnan describes generating replication defective recombinant herpes simplex viruses by targeted inactivating mutations to one or more copies of ICP0, ICP4, ICP22, ICP27, ICP47, thymine kinase, UL41 and UL55 (Krishnan, para 9). Krishnan describes how these inactivating mutations allow for the long-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176).
Claim 19: Krishnan describes human target cells and treating human subjects (Krishnan, para 12 and 18).
Claim 20: Krishnan describes a HSV vector that has reduced cytotoxicity as compared to a corresponding wild-type HSV (Krishnan, para 12).
Claim 33: Krishnan describes administration of the pharmaceutical composition one, two, three four or five times per day to the subject (Krishnan, para 241).
Claims 7 and 11: Wen describes the delivery of beta nerve growth factor (bNGF) using herpes viral vectors (Wen, para 6 and 102). Wen describes ophthalmic formulations, eye ointments and topical solutions (Wen, para 88, 92). Wen describes topical administration such as the use of eye drops (Wen, para 85, 92).
Claims 18: Wen discloses a bNGF polypeptide sequence with 100% sequence similarity to SEQ ID NO: 363 (Sequence search results shown below).
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It would have been prima facie obvious to one of ordinary skill in the art to deliver bNGF as described by Wen in the replication defective recombinant herpes simplex viruses disclosed by Krishnan as a therapeutic eye treatment. It would have been a matter of simple substitution of one known therapeutic polypeptide like BMPR2 disclosed by Krishnan for bNGF as described by Wen to obtain predictable results. One would have been motivated to make this substitution given that Wen states that bNGF would be useful in an ophthalmic formulation for treating optic nerve injuries (Wen, para 92). One would have a reasonable expectation of success given that Wen expressly lists HSV vectors as a possible gene vector to deliver bNGF (Wen, para 102). Furthermore, replication defective recombinant HSV offer numerous advantages over traditional HSV vectors including longer-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176, 188).
However, either Krishnan nor Wen describes treating neurotrophic keratitis as an eye condition.
Claims 7: Ferrari describes a double-masked randomized clinical trial examining the therapeutic applications of NGF towards treating ocular conditions like neurotrophic keratitis (Ferrari, abstract and discussion para 1). Ferrari found that rhNGF eye drops were well tolerated with no detectable clinical evidence of systemic adverse side effects (Ferrari, abstract). Furthermore, Ferrari describes NGF treatment as a promising therapy for a variety of ocular conditions involving damage of the cornea (inclusive of the corneal epithelial cell layer), conjunctiva, retina and optical nerve (Ferrari, discussion para 1).
It would have been prima facie obvious to one of ordinary skill in the art to deliver the replication defective HSV vector encoding bNGF as described by Krishnan in view of Wen as a treatment for neurotrophic keratitis as described by Ferrari. It would have been a matter of combining prior art elements according to known methods to yield predictable results. One would have been motivated to make this combination given that Ferrari demonstrated that bNGF is an effective treatment for ocular conditions like neurotrophic keratitis using rhNGF eye drops (Ferrari, abstract and discussion para 1). Thus, one of ordinary skill would be motivated to express NGF as a HSV based gene therapy rather than directly administering the protein as a treatment for neurotrophic keratitis given that a longer-term or permanent effect may be achieved while reducing the necessity for repeat administration and potential negative immune responses. One would have a reasonable expectation of success given that the replication defective recombinant HSV vectors described by Krishnan offer longer-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176, 188). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 7, 10-11, 15-20 and 33 to have been prima facie obvious to at the time the invention was made.
Response to Traversal
Applicant traverses the rejection by arguing that one of ordinary skill in the art would have no motivation to modify the teachings of Krishnan in view of Wen and Ferrari to arrive at the claimed invention with a reasonable expectation of success. Applicant argues that Wen refers to herpes gene-therapy vectors exactly one time (para 102) in a list of alterative embodiments and does not disclose a replication-defective herpes simplex virus encoding bNGF. Applicant argues that although Wen states that the invention includes gene delivery forms like viral vectors and replication defective retroviruses, this does not cover herpes viruses. Therefore, applicant argues that the Office position requires impermissible picking and choosing and hindsight analysis for one to select a replication defective herpes virus. Applicant argues that a skilled artisan would have to (i) select herpes virus from Wen’s list in preference to retrovirus (ii) read that family-level term as the herpes simplex virus (iii) render it replication-defective (iv) substitute bNGF for Krishnan’s exemplified transgene and (v) direct the therapy to the cornea to treat neurotrophic keratitis.
These arguments have been fully considered but were not found persuasive since one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references, see MPEP 2145. With respect to points (i) - (iii), Krishnan is the primary reference of the rejection and expressly describes methods for delivering therapeutic recombinant nucleic acids using replication defective recombinant herpes simplex viruses (Krishnan, para 7-9). With respect to point (iv), Wen is introduced as a secondary reference to show that it would have been a matter of simple substitution of one known therapeutic polypeptide like BMPR2 disclosed by Krishnan for bNGF as described by Wen. Wen expressly states that bNGF would be useful in an ophthalmic formulation for treating optic nerve injuries and even considers alternative embodiments wherein herpes viruses and topical administration are used to deliver bNGF (Wen, para 88, 92). Thus, the obviousness rejection argues that it would have been prima facie obvious to one of ordinary skill in the art to deliver bNGF as described by Wen in the replication defective recombinant herpes simplex viruses disclosed by Krishnan as a therapeutic eye treatment. Motivation to make this substitution would come from Wens express statement that bNGF would be useful in an ophthalmic formulation for treating optic nerve injuries (Wen, para 92). Furthermore, replication defective recombinant HSV offer numerous advantages over traditional HSV vectors including longer-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176, 188). With respect to point (v), the obviousness rejection introduces an additional reference Ferrari, who describes the therapeutic application of rhNGF eye drops towards treating ocular conditions like neurotrophic keratitis (Ferrari, abstract and discussion para 1). The obviousness rejection makes it clear that it would have been prima facie obvious to one of ordinary skill in the art to deliver the replication defective HSV vector encoding bNGF as described by Krishnan in view of Wen as a treatment for neurotrophic keratitis as described by Ferrari. One of ordinary skill would be motivated to express NGF as a HSV based gene therapy rather than directly administering the protein as a treatment for neurotrophic keratitis given that a longer-term or permanent effect may be achieved while reducing the necessity for repeat administration and potential negative immune responses.
Applicant further argues that a skilled artisan seeking sustained local ocular delivery would have no reason to teach for Wen’s systemic half-life extended fusion protein and Wen provides no direction towards Krishnan’s vector platform. Applicant argues that the references solve different problems in different ways, which undercuts the articulated motivation, see MPEP 2143.01. Applicant argues that substituting bNGF for Krishnan’s exemplified transgene is not a simple substitution since these have different processing, secretion, dosing and mehcnisms of therapeutic action. Applicant argues that the Office position requires impermissible picking and choosing and hindsight analysis.
Although applicant has argued that the Examiner’s conclusion of obviousness is based on improper hindsight reasoning. However, any judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper, see MPEP 2145. Furthermore, the claims recite a recombinant herpes simplex virus genome comprising a polynucleotide encoding bNGF. Although it may be admitted that Wen describes a bNGF fusion protein with an extended systemic half-life, the claims are broad enough to encompass such bNGF fusion protein. Furthermore, discloses a bNGF polypeptide sequence with 100% sequence similarity to SEQ ID NO: 363 as recited in dependent claim 18.
Applicant points to the declaration of Dr. Weldon Haw submitted on 7/8/2026 which is argued to show direct evidence from a qualified expert that the rejection lacks a reasonable expectation of success. The declaration argues against the motivation to combine the cited references with a reasonable expectation of success in view of the knowledge that (1) HSV infection of the eye is a major cause of neurotrophic keratitis through a mechanism involving immunogenicity and subsequent pathogenesis resulting in an elevated immune response in neurotrophic keratitis patients and (2) it was unknown ant the time of filing whether a replication defective HSV vector could induce an immune response in neurotrophic keratitis patients. The declaration refers to Exhibit A which shows the unexpected findings that a single HSV-bNGF topical treatment resulted in higher mouse eye NGF levels as compared to six doses of rhNGF.
These arguments have been fully considered, but were not found persuasive since Krishnan expressly describes the use of a replication defective HSV-1 vector by targeted inactivating mutations to one or more copies of ICP0, ICP4, ICP22, ICP27, ICP47, thymine kinase, UL41 and UL55 (Krishnan, para 9). Krishnan describes how these inactivating mutations allow for the long-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176). Thus, one of ordinary skill would be motivated to express NGF as a replication defective HSV based gene therapy rather than directly administering the protein as a treatment for neurotrophic keratitis given that a longer-term or permanent effect may be achieved while reducing the necessity for repeat administration and potential negative immune responses. One would have a reasonable expectation of success given that the replication defective recombinant HSV vectors described by Krishnan offer longer-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176, 188).
New Claim Rejections - 35 USC § 103
Claims 21, 24-30 and 34 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 Wen et al. US 2022/0339251, published 10/27/2022 (hereinafter Wen, reference of record) as evidenced by DelMonte et al. "Anatomy and physiology of the cornea." Journal of Cataract & Refractive Surgery 37.3 (2011): 588-598 (hereinafter DelMonte, reference of record). This rejection is newly applied to address applicants claim amendments on 7/21/2026.
Claim 21: Krishnan describes a method for delivering therapeutic recombinant nucleic acids using replication defective recombinant herpes simplex viruses (Krishnan, para 7-9). Krishnan describes the use of a pharmaceutically acceptable carrier or excipient for topical administration (Krishnan, para 14, 206). Krishnan also describes subretinal administration routes, which indicates that the aforementioned method is applied to an eye condition or disease for therapeutic relief (Krishnan, para 14, 206-207). Krishnan provides preferred embodiments to therapeutic recombinant nucleic acids including bone morphogenic protein receptor type-2 polypeptide (BMPR2) among others (Krishnan, para 11, 25, 70, 123 and claim 118). However, Krishnan does not describe the delivery of a polynucleotide encoding a beta nerve growth factor (bNGF) or an express description of administering the pharmaceutical composition topically to the eye of a subject with a corneal epithelium injury.
Claim 25: Krishnan describes the use of recombinant herpes simplex viruses including HSV-1 and HSV-2 (Krishnan, para 8).
Claims 26-27: Krishnan describes generating replication defective recombinant herpes simplex viruses by targeted inactivating mutations to one or more copies of ICP0, ICP4, ICP22, ICP27, ICP47, thymine kinase, UL41 and UL55 (Krishnan, para 9). Krishnan describes how these inactivating mutations allow for the long-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176).
Claim 29: Krishnan describes human target cells and treating human subjects (Krishnan, para 12 and 18).
Claim 30: Krishnan describes a HSV vector that has reduced cytotoxicity as compared to a corresponding wild-type HSV (Krishnan, para 12).
Claim 34: Krishnan describes administration of the pharmaceutical composition one, two, three four or five times per day to the subject (Krishnan, para 241).
Claim 21: Wen describes the delivery of beta nerve growth factor (bNGF) using herpes viral vectors (Wen, para 6 and 102). Wen describes ophthalmic formulations, eye ointments and topical solutions (Wen, para 88, 92). Wen describes topical administration such as the use of eye drops (Wen, para 3, 85, 92).
Claim 28: Wen discloses a bNGF polypeptide sequence with 100% sequence similarity to SEQ ID NO: 363 (Sequence search results shown below).
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It would have been prima facie obvious to one of ordinary skill in the art to deliver bNGF as described by Wen in the replication defective recombinant herpes simplex viruses disclosed by Krishnan as a therapeutic eye treatment. It would have been a matter of simple substitution of one known therapeutic polypeptide like BMPR2 disclosed by Krishnan for bNGF as described by Wen to obtain predictable results. One would have been motivated to make this substitution given that Wen states that bNGF would be useful in an ophthalmic formulation for treating optic nerve injuries (Wen, para 92). One would have a reasonable expectation of success given that Wen expressly lists HSV vectors as a possible gene vector to deliver bNGF. Furthermore, replication defective recombinant HSV offer numerous advantages over traditional HSV vectors including longer-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176, 188).
However, neither Krishnan nor Wen describe increasing bNGF to one or more cells in the corneal epithelium of a subject with a wound of the corneal epithelium.
Claim 21: Cuthbertson describes ocular gene therapy treatments for treating specific genetic mutations (Cuthbertson, col 1 and 2). Cuthbertson describes how corneal epithelial cells are particularly susceptible to injury and infection and specifically lists NGF as a protein associated with ocular disease which could be supplemented through gene therapy to alleviate symptoms of an ocular disease (Cuthbertson, col 7 and example 1).
It would have been prima facie obvious to one of ordinary skill in the art to deliver the replication defective HSV vector encoding bNGF as described by Krishnan in view of Wen as a method for supplementing levels of bNGF in the corneal epithelium of a subject as described by Cuthbertson. It would have been a matter of combining prior art elements according to known methods to yield predictable results. One would have been motivated to make this combination given that Cuthbertson describes how corneal epithelial cells are particularly susceptible to injury and infection and specifically lists NGF as a protein associated with ocular disease which could be supplemented through gene therapy (Cuthbertson, col 7 and example 1). One would have a reasonable expectation of success given that Cuthbertson successfully demonstrated the delivery of exogenous nucleic acids to corneal epithelial cells in example 1 and the replication defective recombinant HSV vectors described by Krishnan offer longer-term expression of therapeutic genes without HSV toxicity (Krishnan, para 9, 176, 188). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 21, 25-30 and 34 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 autoprocessed 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 7, 10-11, 15-21, 25-30 and 33-34 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of US Patent No. 11,865,148 published on 1/9/2024 (application number 18/060,515) in view of Wen et al. US 2022/0339251, published 10/27/2022 (hereinafter Wen, reference of record). 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 repeated for the same reasons as outlined in the office action mailed on 7/8/2026. A response to applicant’s arguments is found below.
Claims 7, 10-11, 15-21, 25-30 and 33-34: 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 a replicative deficient herpes simplex virus (HSV-1) encoding one or more polynucleotides to treat a disease of the eye associated with vision loss (claims 1 and 11). It is emphasized that neurotrophic keratitis is considered an eye disease associated with vision loss and is a species which is immediately envisagable and fully embraced within the claimed genus, see MPEP § 2131.02. The patented claims describe topical or injection-based administration of the gene therapy vector into the eye of a subject, which embraces the expression of the encoded transgene in the corneal epithelium which is the outermost cell layer of the eye and would therefore be in direct contact with the composition upon topical administration. The patented claims describe an inactivating mutation in one or both copies of ICP4 HSV-1 (Claim 14). The patented claims describe the HSV-1 having reduced cytotoxicity when compared to its wild-type counterpart (Claim 9). The patented claims do not describe the HSV-1 vector encoding a bNGF polypeptide as described in independent claims 7 and 21.
However, Wen describes the delivery of beta nerve growth factor (bNGF) using herpes viral vectors (Wen, para 6 and 102). Wen describes ophthalmic formulations, eye ointments and solutions (Wen, para 88 and 92). Wen describes applications to the patient’s eye and neurons thereof, which reads on the various neuronal cell types listed (Wen, para 52, 88 and 92). Wen discloses a bNGF polypeptide sequence with 100% sequence similarity to SEQ ID NO: 363 (Sequence search results shown below).
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It would have been prima facie obvious to one of ordinary skill in the art to deliver bNGF as described by Wen in the replication defective recombinant herpes simplex viruses disclosed by the patented claims as a therapeutic eye treatment. It would have been a matter of simple substitution of one known therapeutic polypeptide for another to obtain predictable results. One would have been motivated to make this substitution given that Wen states that bNGF would be useful in an ophthalmic formulation for an eye treatment (Wen, para 92). One would have a reasonable expectation of success given that Wen expressly lists HSV vectors as a possible gene vector to deliver bNGF. Furthermore, replication defective recombinant HSV offer numerous advantages over traditional HSV vectors including lower toxicity to host cells.
Response to Traversal
Applicant traverses the rejection by arguing that the patented claims do not describe treating neurotrophic keratitis and is not described by Wen. Applicant argues that Wen does not describe a method of increasing bNGF levels in the corneal epithelium. Applicant argues that a proper prima facie case of obviousness has not been made.
These arguments have been fully considered but were not found persuasive since the claims clearly recite the treatment of a disease of the eye associated with vision loss (claims 1 and 11) which embraces neurotrophic keratitis. It is emphasized that neurotrophic keratitis is considered an eye disease associated with vision loss and is a species which is immediately envisagable and fully embraced within the claimed genus, see MPEP § 2131.02. Furthermore, the patented claims describe topical or injection-based administration of the gene therapy vector into the eye of a subject, which embraces the expression of the encoded transgene in the corneal epithelium which is the outermost cell layer of the eye and would therefore be in direct contact with the composition upon topical administration.
Conclusion
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 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, 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 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
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