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
This action is in response to the papers filed March 5, 2026.
Amendments
Applicant's response and amendments, filed March 5, 2026, is acknowledged. Applicant has cancelled Claims 3-4, 6-8, 10-26, 28, 38, and 42-50, and amended Claim 1.
The amendment to the claims filed on March 5, 2026 does not comply with the requirements of 37 CFR 1.121(c). Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
The correct status of Claims 33, 35-37, and 39-41 is (Withdrawn).
Claims 1-2, 5, 9, 27, 29-37, and 39-41 are pending.
Election/Restrictions
Applicant has elected without traverse the following species:
i) the alternative additional method step is performing in vivo retinal imaging to evaluate one or more of a longitudinal reflectivity profile (LRP), as recited in Claim 34;
ii) the alternative in vivo retinal imaging assay/step and alternative microarchitecture to be imaged, measured, or evaluated is retinal imaging performed using ultrahigh-resolution optical coherence tomography (OCT) and treatment efficacy indicated by reestablishment of proper apposition between RPE cells and photoreceptor (PR) outer segments (cytoarchitecture of RPE-PR interface), as recited in Claim 34; and
iv) the alternative AAV capsid is AAV2, as recited in Claims 27 and 29.
Claims 1-2, 5, 9, 27, 29-37, and 39-41 are pending.
Claims 33, 35-37, and 39-41 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-2, 5, 9, 27, 29-32, and 34 are under consideration.
Priority
This application is a 371 of PCT/US2021/020169 filed on February 28, 2021. Applicant’s claim for the benefit of prior-filed application provisional application 62/983,052 filed on February 28, 2020 and 62/983,046 filed on February 28, 2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
The Examiner also acknowledges Applicant’s co-pending application 17/904,903, which is a 371 of PCT/US2021/020169 filed on February 28, 2021, which also claims benefit of prior-filed application provisional application 62/983,052 filed on February 28, 2020 and 62/983,046 filed on February 28, 2020.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on April 23, 2026 that has been considered.
The information disclosure statement filed April 23, 2026 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
NPL citations 259-260 have been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
Claim Objections
1. Claim 32 is objected to under 37 CFR 1.75 as being a substantial duplicate of Claim 31. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 31 recites administration to each eye of the subject.
Claim 32 recites administration to both eyes of the subject.
The claims have the same scope because, while worded differently, all said subjects naturally comprise two eyes, and thus “each” and “both” yield the same result.
Instant specification fails to disclose a subject suffering from BVMD, ADVIRC, or AVMD to whom each eye of the subject receiving the viral gene therapy is anatomically and biologically different than a subject suffering from BVMD, ADVIRC, or AVMD to whom both eyes of the subject receive the viral gene therapy.
Claim Rejections - 35 USC § 112
2. The prior rejection of Claims 1-2, 4-6, 9, 27, 29-32, and 34 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of Applicant’s amendment to the independent claim reciting the dose is administered in a volume between 50µl and 500µl, which the Examiner finds persuasive.
The claim is directed to administering via subretinal, intravitreal, or suprachoroidal injection a dose of about 5x10^8, 1x10^9, 5x10^9, 1x10^10, 5x10^11, 5x10^12, 1x10^13, or 1x10^14 rAAV-BEST1 vector genomes per eye of the subject in a volume in a volume between 50µl and 500µl.
3. The prior rejections of Claims 1-2, 4-6, 17, 27, 29, 31-32, and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in light of Applicant’s amendment to the independent claim reciting the rAAV vector encodes a promoter operably linked to the nucleic acid sequence encoding BEST1.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
4. Claim(s) 1-2, 4-6, 17, 27, 29, 31-32, and 34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guziewicz et al (BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure, Proc. Nat’l. Acad. Sci. 115(12): e2839-e2848, available online March 5, 2018; Applicant’s own work; of record in IDS).
With respect to Claim 1, Guziewicz et al is considered relevant prior art for having taught a method of treating a subject suffering from two mutant BEST1 alleles, to wit, canine subjects comprising homozygous or biallelic BEST1 mutations (e.g. pg e2847, col. 2, Methods, canine model) comprising the step of administering to an eye of the subject a dose of at least 1x10^8 to 9x10^9 vector genomes an rAAV vector encoding BEST1 (e.g. human BEST1, pg e2842, col. 2) operably linked to a human VMD2 (syn. BEST1) promoter (Supplementary Methods; pg e2842, col. 2).
Guziewicz et al taught the rAAV-BEST1 viral gene therapy was administered in a volume between 50µl to 180µl. (e.g. Suppl Methods).
Guziewicz et al taught wherein the BEST1 mutations are recognized in the art to be causal of Best Vitelliform Macular Dystrophy (BVMD) (e.g. citations 9, 34, 70-72, 74, and 84).
Guziewicz et al taught wherein the rAAV is administered to the subject’s retina (e.g. pg e2842, col. 2, heading, subretinal).
With respect to Claim 2, Guziewicz et al taught wherein the subject is canine (e.g. pg e2847, col. 2, Methods, canine model).
With respect to Claim 5, Guziewicz et al taught wherein the rAAV is administered to the subject’s retina (e.g. pg e2842, col. 2, heading, subretinal).
With respect to Claim 9, Guziewicz et al taught wherein the rAAV encoding a human BEST1 protein (e.g. human BEST1, pg e2842, col. 2) operably linked to a human VMD2 (syn. BEST1) promoter (Supplementary Methods; pg e2842, col. 2).
With respect to Claims 27 and 29-30, Guziewicz et al taught wherein the rAAV is an AAV2 comprising an AAV2 capsid (syn. AAV2/2; pg e2842, col. 2; Supplemental Methods).
With respect to Claims 31-32, Guziewicz et al taught wherein the rAAV was administered one of the subject’s eyes (e.g. pg e2842, col. 2, “the fellow eye was not injected”), and wherein the rAAV was administered both of the subject’s eyes (e.g. Figure 3, legend, “both eyes were injected”).
With respect to Claim 34, Guziewicz et al taught wherein the gene therapy method further comprises the step of performing in vivo retinal imaging by obtaining longitudinal reflectivity profiles and measuring a re-establishment of proper apposition between RPE cells and photoreceptor (PR) outer segments (cytoarchitecture of RPE-PR interface) (e.g. pg e2840, col. 2; Figures 1, 2B, 3D).
Thus, Guziewicz et al anticipate the claims.
Response to Arguments
Applicant argues that Guziewicz et al do not teach wherein the subject has, e.g. BVMD.
Applicant’s argument(s) has been fully considered, but is not persuasive. Guziewicz et al taught wherein the canine subject comprises biallelic mutations in BEST1 (e.g. pg e2839, col. 2), whereby said BEST1 mutations are recognized in the art to be causal of Best Vitelliform Macular Dystrophy (BVMD) (e.g. citations 9, 34, 70-72, 74, and 84).
To further rebut Applicant’s argument, the Examiner provides National Library of Medicine NM_004183.4(BEST1):c.73C>T (p.Arg25Trp) AND Vitelliform macular dystrophy 2 (January 30, 2021) evidencing that, for example, the (c.73C>T) mutation previously taught by Applicant is recognized to be associated with Best Vitelliform Macular Dystrophy (BVMD).
5. Claim(s) 1-2, 4-6, 17, 27, 29, 31-32, and 34 are rejected under 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) as being anticipated by Maclaren et al (U.S. 2019/0307900; filed April 5, 2019; priority to April 5, 2018).
With respect to Claims 1-2, Maclaren et al is considered relevant prior art for having disclosed an rAAV expression vector whose genome comprises a VMD2 promoter operably linked to a BEST1 cDNA (e.g. Figure 1), and a method of using said rAAV vector to treat a bestrophinopathy in a human subject, wherein the subject has a mutation in one or both BEST1 alleles, e.g. a dominant mutation causing BVMD, retinitis pigmentosa, or a recessive mutation causing ARB (e.g. [0026, 67]).
Maclaren et al disclosed administering about 5x10^10, 1x10^11, 5x10^11, or 1x10^12 vector genomes in a volume of 100 µl to the eye of the human subject (e.g. Figures 30-31), wherein the rAAV may be administered via subretinal, suprachoroidal, or intravitreal route (e.g. [0027]).
With respect to Claim 5, Maclaren et al disclosed the rAAV may be administered via subretinal injection (e.g. [0027]).
With respect to Claims 9 and 30, Maclaren et al disclosed an rAAV expression vector whose genome comprises a VMD2 promoter operably linked to a BEST1 cDNA (e.g. Figure 1; [0005], “human VMD2 promoter”, “human BEST1 protein”).
With respect to Claims 27 and 29, Maclaren et al disclosed the rAAV vector comprises an AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAVS, AAV9, AAV10, or AAV11 capsid serotype (e.g. [0017]).
With respect to Claims 31-32, Maclaren et al disclosed bilateral injection of the rAAV to the eyes of a subject (e.g. Figure 29) or to one eye of the subject (e.g. Figure 15).
Thus, Maclaren et al anticipate the claims.
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.
6. Claims 1-2, 4-6, 17, 27, 29, 31-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 10, 27, 29-32, and 41 of copending Application No. 17/904,903 (reference application) (claim set filed March 5, 2026). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant Claim 1 recites a method of a bestrophinopathy in a subject comprising at least one mutant BEST1 allele.
‘903 recites a method of a bestrophinopathy in a subject comprising two mutant BEST1 alleles.
As a first matter, the term "comprising" is open-ended and allows for additional, unrecited elements in the claims. MPEP 2111.03 specifically sets forth that the transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Instant Claim 1 fails to specifically exclude the presence of a second mutant BEST1 allele.
As a second matter, it would have been obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.”
One of ordinary skill in the art immediately recognizes that mammals, including humans, are diploid, and thus their genomes only comprise two BEST1 alleles, be they mutant or non-mutant. Thus, it is axiomatic that a subject suffering from a bestrophinopathy will necessarily comprise at least one mutant BEST1 allele or two BEST1 alleles, whereby the ordinary artisan could have pursued the known potential options, two wit, one mutant BEST1 allele or two mutant BEST1 alleles, with a reasonable expectation of success, whereby the number of possible mutant BEST1 genotypes from which to choose, 1 or 2 mutant BEST1 alleles, is neither astronomical nor insurmountable.
Thus, instantly claimed method(s) is/are considered to anticipate and/or be obvious variants of the co-pending ‘903 claimed method(s).
Conclusion
7. No claims are allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 KEVIN K. HILL whose telephone number is (571)272-8036. The examiner can normally be reached 12pm-8pm EST.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
Prosecution Insights