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 .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on October 23, 2025 has been entered. This action is in response to the papers filed October 23, 2025. Claims 1 and 4-13 are currently pending in the application. Claim 1 is amended. No new claims are added. Claims 2-3 and 14-21 are canceled. Claim 1 is independent.
Therefore, claims 1 and 4-13 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US19/68690, filed December 27, 2019.
This application is claiming the benefit under 35 U.S.C. 119(e) of prior-filed provisional application 62/785,739 filing date 12/28/2018 and application 62/833,069 filing date 04/12/2019.
Thus, the earliest possible priority for the instant application is December 28, 2018.
Response to arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112
The rejection of claims 1-21 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn.
Applicant’s arguments and amendments filed 10/23/2025 have been considered and are persuasive.
In particular, the amendments to claim 1 which narrow the scope of BEST WT to SEQ ID NO: 1 & 2 are persuasive.
The rejection of claims 14 and 17-21 under 35 U.S.C. 103 as being unpatentable over Guziewicz (2013. PLoS ONE 8(10): e75666; IDS Reference) in view of Wu (WO2016/176690; Applicant’s own work) is withdrawn.
Applicant’s arguments and amendments filed 10/23/2025 have been considered and are moot in light of the cancelation of claims 14-21.
The rejection of claims 15 under 35 U.S.C. 103 as being unpatentable over Guziewicz (supra) in view of Wu (supra) as applied to claim 14 above, and in further view of Rag (SCORE Results, .rag, SEQ ID NO: 1 accessed 9/17/2024) is withdrawn.
Applicant’s arguments and amendments filed 10/23/2025 have been considered and are moot in light of the cancelation of claims 14-21.
The rejection of claims 16 under 35 U.S.C. 103 as being unpatentable over Guziewicz (supra) in view of Wu (supra) and Rag (supra) as applied to claims 15 above, and in further view of Rge (SCORE Results, .rge, SEQ ID NO: 1 accessed 9/17/2024) is withdrawn.
Applicant’s arguments and amendments filed 10/23/2025 have been considered and are moot in light of the cancelation of claims 14-21.
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112
Claims 1 and 4-13 remain rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for
A recombinant AAV2 vector comprising a nucleic acid sequence comprising the nucleic acid sequence of SEQ ID NO:2 or encoding the WT Best1 polypeptide of SEQ ID NO: 1 and administering a specific dosage of said recombinant vector via subretinal injection to a subject in order to treat a retinal degenerative disorder associated with a BES Tl dominant mutation in a subject in need thereof, wherein expression of the WT Best1 polypeptide of SEQ ID NO: 2 in retinal pigment epithelial cells improves Ca 2+ -dependent Cl − conductance caused by a BEST1 loss-of-function mutation,
does not reasonably provide enablement for
a genus of gene therapy vectors comprising the nucleic acid sequence of SEQ ID NO:2 or encoding the WT Best1 polypeptide of SEQ ID NO: 1 that predictably have the functional property of treating a retinal degenerative disease caused by a BEST1 mutation at any amount by any route of retinal administration and any improvement of visual function and prevention of disease progression.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 10/23/2025.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention. If not, whether an artisan would have required undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make or use the invention based on the content of the disclosure is “undue” (In re Wands, 858 F.2d 731, 737, 8 USPQ2ds 1400, 1404 (Fed. Cir. 1988)). Furthermore, USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
The Breadth of the Claims and The Nature of the Invention
The claims are directed to a method of treating a subject having a retinal degenerative disorder, the method comprising the step of rationally administering an rAAV vector encoding wild type BEST1 encoded by SEQ ID NO: 1 or SEQ ID NO: 2, thereby treating the subject.
The claims are broad for reasonably encompassing administration routes other than the subretinal administration recited in Claim 9.
However, the specification and dependent claims are directed towards the administration route of subretinal injection (p. 11 in the instant specification, Claim 9)
Scaria (US2017/0096683) teaches that delivering gene therapy vectors to the cells of the RPE requires injection into the subretinal space between the retina and RPE because LCA treatment requires local delivery of the vector (para. 0167). The scope encompasses any injection route, which could be systemic or intravenous or intrathecal, etc. Therefore the entire scope of claim 1 is not enabled.
Additionally, Claim 1 recites an “effective amount” which suggests that there is an amount that is not therapeutic of the gene therapy vector and is therefore only enabled for that amount. The specification does not disclose an appropriate dosage but merely states the MOI of the AAV Best1 at day 1 and day 2 (Figure 5E, p. 7).
The State of the Prior Art, The Level of One of Ordinary Skill and The Level of Predictability in the Art
Considering the mode of administration, the specification simply requires administration of the AAV to the subject by any retinal means. The art has demonstrated through numerous publications, delivery of nucleic acid vectors in vivo is highly unpredictable for successful human therapy.
Acland et al (U.S. 2004/0022766) is considered relevant prior art for having disclosed a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid [0023], and a vector genome packaged therein, said vector genome comprising:
(a) an AAV 5' inverted terminal repeat (ITR) sequence;
(b) a promoter;
(c) a coding sequence encoding a human Lebercilin [0031].
Acland et al disclosed [0057] “[T]he use of subretinal injection as the route of delivery is a critical component of this method, as intravitreal administration does not enable the same therapeutic effects. The vector and carrier cannot diffuse across the multiple cell layers in the retina to reach the RPE, when intravitreal injection is used. Similarly, intravenous delivery is unacceptable because the material does not penetrate the blood-brain (blood-retina) barrier. Because the virus does not diffuse well, topical administration is similarly not preferred for this method.”
The Quantity of Any Necessary Experimentation to Make or Use the Invention
Thus, the quantity of necessary experimentation to make or use the invention as claimed, based upon what is known in the art and what has been disclosed in the specification, will create an undue burden for a person of ordinary skill in the art to demonstrate that the broadly claimed genus of rAAV serotypes may be administered at a vast number of amounts by the broadly encompassed administration retinal routes so as to necessarily and predictably achieve a real-world, clinically meaningful therapeutic result treating retinal diseases or disorders with BEST1 thereby restoring visual function.
It is generally recognized in the art that biological compounds often react unpredictably under different circumstances (Nationwide Chem. Corp. v. Wright, 458 F. supp. 828, 839, 192 USPQ95, 105(M.D. Fla. 1976); Affd 584 F.2d 714, 200 USPQ257 (5th Cir. 1978); In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970)). The relative skill of the artisan and the unpredictability of the pharmaceutical art are very high. Where the physiological activity of a chemical or biological compound is considered to be an unpredictable art (Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved" (See In re Fischer, 427 F.2d 833, 839, 166 USPQ 10, 24(CCPA 1970))), the skilled artisan would have not known how to extrapolate the results provided in the instant specification intravitreal or subretinal administering the AAV vector encoding BEST1 to the larger genus of administration routes and rAAV dosages reasonably encompassed by the claims. Neither the specification nor the claims provide the appropriate nucleic acid vector or viral dosage to be administered in the plurality of possible intravenous, intracranial, intraperitoneal, intramuscular, subcutaneous, intramuscular, intrarectal, intravaginal, intrathecal, intratracheal, intradermal, or transdermal injection, by oral or nasal administration means that would reasonably be expected by the ordinary artisan to necessarily and predictably achieve a clinically meaningful, real-world therapeutic result to treat degenerative retinal disease.
The gene therapy art is extremely unpredictable. The unpredictability is manifested in the poor and unpredictable targeting of the gene therapy vectors to target cells (the enormous genus of possible AAV serotypes disclosed), routes of administration (as disclosed, do not even require direct administration to the diseased tissue), the transient and unpredictable expression of the transgenes in target cells (the genus of disclosed possible promoters and/or regulatory sequences), and the unsuitability of many animal models of human diseases, etc…, all critical for the success of a gene therapy method.
The courts have stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in patent application. 27 USPQ2d 1662 Exparte Maizel. In the instant case, in view of the lack of guidance, working examples, breadth of the claims, the level of skill in the art and state of the art at the time of the claimed invention was made, it would have required undue experimentation to make and/or use the invention as claimed.
If little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004) ("Nascent technology, however, must be enabled with a 'specific and useful teaching.' The law requires an enabling disclosure for nascent technology because a person of ordinary skill in the art has little or no knowledge independent from the patentee's instruction. Thus, the public's end of the bargain struck by the patent system is a full enabling disclosure of the claimed technology." (citations omitted)).
As In re Gardner, Roe and Willey, 427 F.2d 786,789 (C.C.P.A. 1970), the skilled artisan might eventually find out how to use the invention after “a great deal of work”. In the case of In re Gardner, Roe and Willey, the invention was a compound which the inventor claimed to have antidepressant activity, but was not enabled because the inventor failed to disclose how to use the invention based on insufficient disclosure of effective drug dosage. The court held that “the law requires that the disclosure in the application shall inform them how to use, not how to find out how to use for themselves”.
Greenberg (Gene Therapy for heart failure, Trends in Cardiovascular Medicine 27: 216-222, 2017) is considered relevant prior art for taught that despite success in experimental animal models, translating gene transfer strategies from the laboratory to the clinic remains at an early stage (Abstract). The success of gene therapy depends on a variety of factors that will ultimately determine the level of transgene expression within the targeted cells. These factors include the vector used for delivery, the method and conditions of delivery of the vector to the [target tissue], the dose that is given and interactions between the host and the vector that alter the efficiency of transfection of [target] cells (e.g. pg 217, col. 1). Failure of therapeutic results may arise because the vector DNA levels were at the lower end of the threshold for dose-response curves in pharmacology studies, and/or only a small proportion of target cells were expressing the therapeutic transgene (e.g. pg 220, col. 1). Although the use of AAVs for gene therapy is appealing, additional information about the best strain of AAVs to use in human patients is needed. Experience indicates that there is a need to carefully consider the dose of the gene therapy vector; however, this has proved to be difficult in early phase developmental studies due to the complexity and cost of such studies (e.g. pg 221, col. 1).
In conclusion, the specification fails to provide any guidance as to how an artisan would have dealt with the art-recognized limitations of the claimed method commensurate with the scope of the claimed invention and therefore, limiting the claimed invention to a gene therapy vector comprising the WT Best1 gene sequence of SEQ ID NO: 2 in an AAV2 vector and administering a specific dosage of said vector via subretinal injection to a subject in order to treat retinal degenerative disease is proper.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Response to Applicants’ Arguments as they apply to rejection of claims 1-21 under 35 USC § 112(a) Enablement,
Applicant’s arguments and amendments filed 10/23/2025 have been considered however they are not persuasive.
Applicant argues that the amendments overcome the 112a rejection and that a reasonable amount of experimentation may be called in by the specification. Applicant solely to advance prosecution amended to narrow the BEST1 WT sequence to SEQ ID NO: 1 & 2.
As previously stated and set forth in the rejection, Examiner disagrees that this fully overcomes the enablement issue. While it addresses part of the enablement rejection regarding the breadth of BEST1 WT, as stated above, subretinal injection is the only administration route disclosed in the specification and as evidenced by references within the rejection, subretinal administration is critical for the delivery of the vector to the target RPE cells. Examiner points to the specification which does not disclose an appropriate dosage but merely states the MOI of the AAV Best1 at day 1 and day 2 (Figure 5E, p. 7). This would not reasonably apprise an artisan to make or use the invention. The range could vary from very little administered to too much administered, causing undue experimentation and loss of supplies and time. Ranges known in the art via Guziewicz, show an effective amount of 1.5x10-6.5x10 vg/ml (Abstract, Figure 6, Figure 7), which is much more narrow a range than the current claims which recite any possible concentration.
Claims 1 and 4-13 remain 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.
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 10/23/2025.
Regarding claim 1 and its dependent claims, Claim 1 recites an “effective amount” which suggests that there is an amount that is not effective of the gene therapy vector and is therefore only enabled for that amount.
The specification does not disclose an appropriate amount but merely states the MOI of different AAV2 vectors encoding for WT BEST1 (Figure 5E, p. 7). However, there is no disclosure which treatment or prevention amount applied is capable of improving visual function and preventing disease progression.
Guziewicz (2013. PLoS ONE 8(10): e75666; IDS Reference) teaches various “effective amounts” of AAV in subretinal administration such as 2.5x10^9, 2.63x10^11, 3.92x10^11, and 4.44x10^11 AAV- wildtype BEST1 vector genomes (Figure 5 legend; Figure 6 legend), yet observed “patchy loss of cone photoreceptors” (Figure 6, legend) and “cone toxicity associated with rAAV2/1 vector serotype” (Figure 7 legend). Figure 7 legend taught “Co-expression of endogenous canine bestrophin1 and human BEST1 transgene was well tolerated when injected with rAAV2/2 serotype and no abnormalities were noted”.
The phrase “an effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. In reFredericksen, 213 F.2d 547, 102 USPQ 35 (CCPA 1954). MPEP 2173.05(c).
The claim also denotes that there is an amount of the pharmaceutical composition that upon administration to the subject is not, in fact, “a therapeutically effective amount”.
The recitation implies a genus of unrecited and undisclosed phenotypes by which the therapeutically effective dose is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The specification discloses what potentially could be a therapeutic result in the treatment of a disease such as reducing the frequency or severity of a symptom or disease experienced (p. 15, lines 28-30). This does not provide a definition for a therapeutic result from the BEST1 administration via an effective amount, but only a subjective or arbitrary determination.
If there are multiple ways to measure “therapeutically effective dose” or “therapeutically effective amount”, to wit, concentration, time after administration, and/or phenotypic result, yet each yields a different result, then the claim is indefinite because it is unclear which phenotypic result is to be achieved in order to determine the metes and bounds of the invention.
Therefore, the metes and bounds of the invention would be unclear to one of ordinary skill in the art.
Claim 1 is indefinite in its recitation of “ to improve visual function and prevent disease progression” as it is unclear as to “the visual function” or visual functions that are intended as being encompassed by the noted phrase. The retina of a subject is known in the prior art to have numerous visual functions, both specific and general. For example, all retina's primary function is to convert light into electrical signals that the brain can interpret as images. It is suggested that applicant clarify the intended meaning of the noted phrase.
Claim 1 is indefinite in its recitation of a polypeptide comprising an amino acid sequence comprising SEO ID NO: 1 or a nucleic acid molecule comprises a nucleic acid sequence of SEQ ID NO: 2. The recitation of the phrase “an amino acid sequence comprising SEO ID NO: 1” or “a nucleic acid sequence of SEQ ID NO: 2” renders the claim indefinite. The phrase “comprising an amino acid sequence comprising SEO ID NO: 1” is broadly interpreted as an amino acid sequence comprising the full length of the amino acid of SEQ ID NO:1 or any domain within that sequence, e.g., two amino acids. Likewise, the recitation of “a nucleic acid sequence of SEQ ID NO: 2” is broadly interpreted as a nucleic acid sequence comprising the full length of the nucleic acid of SEQ ID NO:2 or any domain, e.g., 2 amino acids.
Amending the claim to recite “ a polypeptide comprising the amino acid sequence comprising SEO ID NO: 1, or the nucleic acid molecule comprises the nucleic acid sequence of SEO ID NO: 2.” Would obviate this rejection.
Therefore, claims 1 and 4-13 are rejected as being indefinite.
Response to Applicants’ Arguments as they apply to rejection of claims 1-21 under 35 USC § 112(b),
Applicant argues that one of ordinary skill in the art would not find a ‘therapeutically effective amount’ indefinite as the specification discloses BEST1 mutation symptoms and Applicant determines that treatment such that it relates to
Examiner points to the specification which does not disclose an appropriate dosage but merely states the MOI of the AAV Best1 at day 1 and day 2 (Figure 5E, p. 7). This would not reasonably apprise an artisan to make or use the invention. The range could vary from very little administered to too much administered. Ranges known in the art via Guziewicz, show an effective amount of 1.5x10-6.5x10 vg/ml (Abstract, Figure 6, Figure 7), which is much more narrow a range than the current claims which recite any possible concentration. It is unclear what the metes and bounds of therapeutically effective are as it does not describe the therapeutic administered but rather an end result. It is noted that the case law states ‘in light of the supporting disclosure which provided guidelines to the intended utilities,’ no such guidelines are present in the specification.
New grounds of objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4-7 and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Guziewicz (2013. PLoS ONE 8(10): e75666; IDS Reference) in view of Steuernagel (US20050049212).
Regarding claims 1, 9-12, Guziewicz teaches subretinally injecting (i.e. administering) rAAV2 vectors encoding wild type human BEST1 cDNA (i.e. nucleic acid) into canine (i.e. mammal) eyes in vivo (i.e. to a subject) (p. 10, Supporting Information; p. 7, Animals; p. 8, 1st column). As an effective amount was not specified in the claims, it is interpreted that as their vectors induced overexpression of BEST1, Guziewicz administered an effective amount (1.5x10-6.5x10 vg/ml) (Abstract, Figure 6, Figure 7). The vectors were administered to both wild type and cmr1 carrier retina (i.e. autosomal recessive BEST1 disease) to demonstrate expression of BEST1 in both retina through subretinal delivery methods (Abstract, p. 2). Guziewicz teaches that both autosomal recessive and autosomal dominant bestrophinopathies are caused by mutants to BEST1 (p. 1). As the method does not rely on gene editing with a Cas/crispr system, it is interpreted that the method does not require disruption or suppression of the mutant allele.
However, while Guziewicz teaches treatment of autosomal recessive BEST1 disease, the references does not teach treating autosomal dominant BEST1 mutations in a subject in need thereof or that the wild type BEST1 is encoded by SEQ ID NO: 1 or 2.
Steuernagel teaches a method of providing a composition comprising a nucleic acid molecule for Bestrophin or polypeptide encoded thereby to a subject in need thereof encoded by SEQ ID NO: 1 or 2 in order to treat a condition such as Best vitelliform macular dystrophy (BVMD) which is dominantly inherited (i.e. dominant mutation) (Claim 1-2, Fig 4, para. 0132, 0061). SEQ ID NO: 2 of Steuernagel is identical to SEQ ID NO: 1 of the instant application as shown below.
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Based on such teachings, it would have been obvious to one of ordinary skill in the art to administer a nucleic acid encoding wild type BEST1 according to SEQ ID NO: 1 as taught by Steuernagel in an rAAV vector as taught by Guziewicz in order to treat autosomal dominant diseases associated with BEST1 mutations as described by Steuernagel with a reasonable expectation of success. An artisan would have been motivated to utilize an rAAV vector encoding wild type BEST1 for the purpose of treating autosomal dominant diseases as Guziewicz teaches that mutations cause both autosomal dominant and autosomal recessive types of bestrophinopathies (p. 1) and Steuernagel teaches that administering BEST1 subretinally in a subject can have efficacy in treating autosomal dominant diseases such as Best vitelliform macular dystrophy (para. 0042, 0050).
Regarding claim 10, as the cell having the endogenous mutation would necessarily be in the subject being treated with BEST1 and the BRI does not limit the cells to being isolated and Guziewicz specifically teaches that the BEST1 transgene is localized to the RPE cells (Abstract), it is interpreted that claims 14 and 21 are additionally rejected based on the above rationale. As each and every limitation has been taught by the references, it would be obvious to one of ordinary skill in the art that the same method steps would yield the same predictable results of improving visual function and preventing disease progression.
Regarding claims 4-7, as the claims nor instant specification define what an “recombinant AAV2 promoter” is and the examples utilize a CMV promoter. It is interpreted that any promoter capable of use with AAV2 is an AAV2 promoter. Guziewicz teaches that hVMD2 promoter is utilized in the rAAV2 vector to encode BEST1 (p. 2, 1st column).
Regarding claims 13, Guziewicz and Steuernagel make obvious claims 1 and 12. Moreover, Steuernagel teaches that a method of providing a BEST1 protein for therapy is most preferably for human subjects (para. 0074).
Therefore, the invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 8 is rejected under 35 U.S.C. 103 as being unpatentable over Guziewicz (2013. PLoS ONE 8(10): e75666; IDS Reference) in view of Steuernagel (US20050049212) as applied to claim 1 above, and in further view of Marmorstein (Progress in Retinal and Eye Research 28 (2009) 206-226; previously cited)
Guziewicz and Steuernagel make obvious a method of treating BVMD via administering an rAAV vector encoding wild type BEST1 encoded by SEQ ID NO: 1 as discussed in the above rejection and incorporated herein in its entirety.
However, regarding claim 8, these references do not teach wherein the dominant mutation is selected from the group consisting of p.A10T, p.R218H, p.L234P, p.A243T, p.Q293K and p.D302A.
Marmorstein teaches many mutations in BEST1 which result in various diseases (Figure 1). Particularly, Arg243 Val (p.A243V) causes both AVMD (adult-onset vitelliform macular dystrophy) and BVMD (Best vitelliform macular dystrophy) (p. 213, 2™ column) and mutations in R218 is additionally associated with BVMD (p. 217, 18 column). Mutations at D302, A10, L234 and Q293 are also associated with BVMD (Figure 1B).
Based on such teachings, it would have been obvious to one of ordinary skill in the art for a subject with a dominant mutation in the BEST1 have a mutation at Arg243 or a mutation at R218, D302, A10, L234 and Q293 with a reasonable expectation of success as Arg234Val and other mutations are known to be associated with dominant mutation associated diseases such as BVMD.
Therefore, the invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Conclusion
No claims are allowed.
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/ALEXANDRA F CONNORS/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634