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 .
This action is in response to the amendment, filed 06/12/2023, in which claims 3-4, were amended, and claims 7-8 were added.
Claims 1-8 are under consideration and examined on the merits.
Priority
Applicant’s claim for the benefit of a Provisional Application No 63275351 filed 11/03/2021 is acknowledged.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feinsod M. (“Feinsod”, WO 2017/070491 A1, cited as reference 1 in IDS filed 06/02/2024).
Regarding claims 1, Feinsod teaches methods of treating X-linked retinoschisis by administering an effective amount of an ophthalmic formulations of the present invention (e.g., abstract). Feinsod teaches formulations of the invention have a number of uses in methods of treating ocular diseases or disorders where the back of the eye or retina is the preferred target. Exemplary methods include treating X-linked retinoschisis (XLRS) and treating macular degeneration (e.g., paragraph 5th, page 1). Feinsod teaches delivery to the eye, the therapeutic vector is desirably non-toxic, nonimmunogenic, easy to produce, and efficient in protecting and delivering DNA into the target cells. The viral vector is an adeno-associated virus vector (AAV). The invention provides an ophthalmic formulation for delivery of a gene therapy vector into the eye of a patient in need thereof, wherein the vector comprises the RS1 gene or a fragment thereof (e.g., paragraph 2nd, page 10). Feinsod teaches ophthalmic formulations of the present invention may be delivered by a number of different methods, including intravitreal injection, subretinal injection, or suprachordial injection (e.g., paragraph 3rd, page 18).
Regarding claims 3, Feinsod teaches selection of the promoter to be employed in the rAAV may be made from among a wide number of constitutive or inducible promoters that can express the selected trans gene in the desired an ocular cell (e.g., paragraph 2nd, page 14). Feinsod teaches examples of constitutive promoters including chicken beta actin (CBA) promoter (e.g., paragraph 4th, page 14).
Regarding claims 4, Feinsod teaches the immediate early CMV enhancer coupled with the chicken beta actin (CBA) promoter (e.g., paragraph 4th, page 14).
Regarding claim 5, Feinsod teaches the recombinant adeno-associated virus (rAAV)-based gene therapy vector is AAV2tYF (containing three YF mutations) (SEQ ID 30 NO: 1) (e.g., paragraph 10, page 2). Feinsod teaches the transduction efficiency of AAV vectors (e.g., AAV2tYF-CB-hRS1) formulated in BSS/0.014% Tween 20 with or without 5% dextrose when administered via intravitreal injection in nonhuman primates (e.g., paragraph 2nd, Example 3, Table 4, page 25).
Regarding claim 6, Feinsod teaches methods of treating X-linked retinoschisis by administering an effective amount of an ophthalmic formulations of the present invention (e.g., abstract). Feinsod teaches the recombinant vector AAV2tYF-CB-hRS1 (e.g., paragraph 2nd, Example 3, Table 4, page 25). Feinsod teaches ophthalmic formulation for delivery of a therapeutic, e.g., a gene therapy vector, into the eye of a patient in need thereof, wherein the formulation comprises a density modifying agent the density modifying agent is dextrose. The dextrose is present in a range of about 2% to about 10% (v/v). The density modifying agent is sucrose, present in a range of about 2% to about 10% (v/v). The density modifying agent is polyethylene glycol (PEG), present in a range of about 2% to about 10% (v/v). The density modifying agent is glycerin, present in a range of about 0.05% to about 10% (v/v). The ophthalmic formulation further comprises Tween-20 in a range of about 0.005% to about 0.025% (v/v). The formulation further comprises a balanced salt solution (BSS) (e.g., paragraph 2nd, page 2).
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 (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.
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.
Claims 2, 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Feinsod M. (“Feinsod”, WO 2017/070491 A1, cited as reference 1 in IDS filed 06/02/2024) in view of Markusic et al. (“Markusic”, Molecular Therapy, 2010).
The teachings of Feinsod are discussed above.
Feinsod does not teach the AAV2 with phenylalanine (F) for tyrosine (Y) at positions Y444, Y500 and Y730, as required by claims 2, 7-8. However, this is cured by Markusic.
Markusic teaches that elimination of specific surface-exposed single tyrosine (Y) residues substantially improves hepatic gene transfer
with adeno-associated virus type 2 (AAV2) vectors. A triple-mutant (Y444+500+730F) vector consistently had the highest level of in vivo
gene transfer to murine hepatocytes, approximately threefold more efficient than the best single-mutants, and ~30–80-fold higher compared with the wild-type (WT) AAV2 capsids (e.g., paragraph 1st, column left, page 2048; Figs. 1-2).
It would have obvious to one of ordinary skill in the art before the effective filing day of the claimed invention to combine the teaching of Feinsod – a method of treating XLRS in a patient in need, with an adeno-associated virus vector (AAV) comprising the RS1 gene in an ophthalmic formulation- with the teaching of Markusic – a triple-mutant (Y444+500+730F) adeno-associated virus type 2 (AAV2) vector. For someone skilled in the art would have been obvious to use both teachings to achieve the predictable result of obtaining a method for delivering RS1 gene using a highly transduction efficient mutated AAV2 vector.
One would have been motivated to develop a method to deliver an ophthalmic formulation comprising the RS1 gene in a mutated AAV2 vector for treating XLRS patients.
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 Longi, 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18486941 (reference application).
The following rejection is in view of the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims. The instant claims are to a method of using the product claimed in the issued patent and the instant application is NOT a DIV of the instant patent.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims encompass those of the copending application: A method of treating X-linked juvenile retinoschisis (XLRS) in a human subject, comprising: subretinally delivering to the human subject a therapeutically effective amount of an rAAV vector, the rAAV vector comprising a nucleic acid sequence comprising coding sequence for human RS 1 protein. The method of claim 1, wherein the rAAV vector further comprises a mutated AAV2 VP3 capsid protein comprising phenylalanine (F) for tyrosine (Y) substitutions at each of the positions corresponding to Y444, Y500 and Y730 in a wild type AAV2 VP3 capsid protein. The method of claims 1 or 2, wherein the nucleic acid sequence of the rAAV vector further comprises a chicken beta actin promoter sequence. The method of claims 1 or 2, wherein the nucleic acid sequence of the rAAV vector further comprises a CMV enhancer. The method of any of the foregoing claims, wherein the rAAV vector is rAAV2tYF-CB-hRS 1. A method of treating X-linked juvenile retinoschisis (XLRS) in a human subject, comprising: subretinally delivering to the human subject a pharmaceutical composition comprising rAAV2tYF-CB -hRS 1 and a pharmaceutically-acceptable carrier. The method of claim 2, wherein the nucleic acid sequence of the rAAV vector further comprises a chicken beta actin promoter sequence. The method of claim 2, wherein the nucleic acid sequence of the rAAV vector further comprises a CMV enhancer.
It is noted that “941” represents a species with regard to A method of treating X-linked juvenile retinoschisis (XLRS) in a human subject, comprising: subretinally delivering to the human subject a therapeutically effective amount of an rAAV vector, the rAAV vector comprising a nucleic acid sequence comprising coding sequence for human RS 1 protein, see “941” claim 1. The method of claim 1, wherein the rAAV vector further comprises a mutated AAV2 VP3 capsid protein comprising phenylalanine (F) for tyrosine (Y) substitutions at each of the positions corresponding to Y444, Y500 and Y730 in a wild type AAV2 VP3 capsid protein, see “941” claim 2. The method of claims 1 or 2, wherein the nucleic acid sequence of the rAAV vector further comprises a chicken beta actin promoter sequence, see “941” claim 3. The method of claims 1 or 2, wherein the nucleic acid sequence of the rAAV vector further comprises a CMV enhancer, see “941” claim 4. The method of any of the foregoing claims, wherein the rAAV vector is rAAV2tYF-CB- hRS 1, see “941” claim 5. A method of treating X-linked juvenile retinoschisis (XLRS) in a human subject, comprising: subretinally delivering to the human subject a pharmaceutical composition comprising rAAV2tYF-CB-hRS 1 and a pharmaceutically-acceptable carrier, see “941” claim 6.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/Examiner, Art Unit 1637
/J. E. ANGELL, Ph.D./Primary Examiner, Art Unit 1637