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 September 20, 2025.
Amendments
Applicant's response and amendments, filed September 20, 2025, is acknowledged. Applicant has cancelled Claims 3, 7-8, 10-16, 18-26, 28, 38, and 42-50, and amended Claims 32, 34-35, and 40-41.
Claims 1-2, 4-6, 9, 17, 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, 4-6, 9, 17, 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Claims 33, 35-37, and 39-41 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.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, 4-6, 9, 17, 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 Information Disclosure Statements on April 10, 2023 and June 27, 2024 that have been considered.
The signed and initialed PTO Forms 1449 are mailed with this action.
Specification and Drawings
1. The prior objection to the disclosure is withdrawn in light of Applicant’s amendments to the specification and drawings.
Claim Objections
2. The prior objection to Claims 34-35 and 40-41 is withdrawn in light of Applicant’s amendments to the claims to first identify the acronyms by their complete names.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
3. Claims 1-2, 4-6, 9, 27, 29-32, and 34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
Claim 1 recites a method of treating a bestrophinopathy in a subject, the method comprising the step of administering the eye of the subject a dose of an rAAV-BEST1 vector.
Claim 1(a) recites wherein the dose administered is at a concentration of about 1x10^9 to 1.5x10^13 vector genomes/ml.
Claim 1(a) renders the claim indefinite because it is directed to a concentration, which does nothing for “administering… a dose” and “wherein the dose….is”, and specification does not clearly redefine the term “concentration” as it pertains to the dose.
Claim 1(a) fails to recite the volume that is to be administered, from which the dose can be calculated per the recited concentration. See, instead, Claim 17.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
4. 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, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a method of treating a bestrophinopathy in a subject, the method comprising the step of administering the eye of the subject a dose of an rAAV vector whose genome comprises a nucleic acid encoding a human BEST1 protein.
However, the claim fails to recite the nucleic acid encoding a human BEST1 protein is operably linked to a promoter, and thus the breadth of the claim encompasses embodiments whereby the rAAV encodes, but does not express, the human BEST1 protein.
See, instead, Claims 9 and 30 that positively recite the nucleic acid encoding the human BEST1 protein is operably linked to a promoter.
The prior art does not teach, and the specification fails to disclose that administration of an rAAV that encodes, but does not express, the human BEST1 protein will necessarily and predictably achieve a real-world, clinically meaningful therapeutic result of treating a bestrophinopathy in a subject.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
5. 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, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The Examiner incorporates herein the above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description rejection.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
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.
6. 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).
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 4, 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).
With respect to Claims 5-6, 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 Claim 17, Guziewicz et al taught wherein the rAAV was administered in a volume of 50 to 180uL (Supplemental Methods).
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 Claim 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”).
With respect to Claim 31, Guziewicz et al taught 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 reflectiveity 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.
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.
7. Claims 1-2, 4-6, 9, 17, 27, 29-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-6, 10, 17, 27, 29-32, and 41 of copending Application No. 17/904,903 (reference application). 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
8. No claims are allowed.
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