DETAILED ACTION
Claim Status
As of the Non-Final Office Action mailed 9/9/2025, claims 102-117 were pending.
In Applicant's Response filed on 3/9/2026, claim 114 was amended and claims 116-117 were canceled.
As such, claims 102-115 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
Claim Rejections - 35 USC § 112(b) - Maintained
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.
Claim 114 is 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.
Claim 114 recites “wherein the transduction of one or more supporting cells results in expression of anti-VEGF in one or more supporting cells in the inner ear of a mammal.” Claim 102, of which this claim ultimately depends, is a composition and does not recite any transduction step of any cells. Thus, there is no nexus between the composition as claimed and the resulting expression of anti-VEGF as recited in claim 114. For the purposes of compact prosecution, the examiner is interpreting this limitation to be an intended use of the composition. For the purpose of compact prosecution, the examiner is interpreting claim 114 to be an intended use/result of the composition.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to rejections made based on said interpretations. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Response to Arguments
Applicant has not provided any arguments to the 112(b) rejection regarding the wherein clause recited in instant claim 114. Thus, the rejection has been maintained.
Claim Rejections - 35 USC § 103 - Maintained
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.
Claim(s) 102-108 and 111-115 remain rejected under 35 U.S.C. 103 as being unpatentable over Stankovic et al (WO2017100791 A1, 12 Dec 2016; Published 15 June 2017; Ref. B15 of Foreign Patent Documents in IDS filed 1 Oct 2024; previously cited) in view of Limberis et al (Molecular Therapy, May 2012; 20(1):S31; previously cited) as evidenced by Suzuki et al (Sci Rep., 3 April 2017; 7:45524, p. 1-11. Ref. C179 of NPL in IDS filed 8/19/2025).
Stankovic teaches a method of delivering a transgene to one or more cells in the inner ear in a subject, the method comprising administering an adeno-associated virus (AAV) to the inner ear in a subject, wherein the AAV comprises an Anc80 capsid protein and a transgene (see claim 2 of Stankovic). The reference teaches that adeno-associated virus (AAV) containing an Anc80 capsid protein provide highly efficient gene transfer to inner ear cells including both IHCs and OHCs (p. 1, lines 24-30). The one or more cells of the inner ear also include supporting cells (see claim 5 of Stankovic) (“wherein the composition is capable of transducing one or more supporting cells in the inner ear of a mammal” as in instant claim 113). The transgene is under control of a heterologous promoter sequence such as CMV promoter or CBA promoter (p. 3, lines 19-21) (“a composition comprising a recombinant adeno-associated virus vector, wherein the rAAV vector comprises: (i) a nucleotide sequence comprising a coding sequence operably linked to a promoter . . . and (ii) an AAV Anc80 capsid” as in instant claim 102 in-part; “wherein the promoter is a constitutive promoter” as in instant claim 107; “wherein the constitutive promoter is a . . . CBA promoter or a CMV promoter” as in instant claim 108). The reference teaches that nucleic acids can be used to deliver transgenes to the inner ear while suspended in an artificial perilymph solution (p. 21, lines 21-27) (“wherein the composition comprises a synthetic perilymph fluid” as in instant claim 103; “wherein the composition is formulated for intra-cochlear delivery” as in instant claim 104; “wherein the composition is a pharmaceutical composition” as in instant claim 105). It also teaches that the virus particle containing the Anc80 capsid protein has a construct carrying the transgene that is flanked by suitable inverted terminal repeats (ITRs) that allow the transgene to be packaged within the Anc80 capsid (p. 19, lines 8-11) (“wherein the nucleotide sequence further comprises two AAV inverted terminal repeats (ITRs) flanking the coding sequence” as in instant claim 111). The reference also teaches that AAV2 ITRs were used in the vector (“Viral vector generation,” para 2) (“wherein the two AAV ITRs are AAV2 ITRs” as in instant claim 112).
Stankovic differs from the instantly claimed invention in that it does not teach that the transgene is a VEGF binding agent (ranibizumab; see claim interpretation above) (related to instant claim 102 in-part).
Limberis teaches AAV8 mediated expression of ranibizumab (title). The reference teaches that macaques were injected intravitreally or subretinally with 1011 genome copies of AAV8 vector expressing ranibizumab under the transcriptional control of the CMV promoter (“a composition comprising a recombinant adeno-associated virus vector, wherein the rAAV vector comprises (i) a nucleotide sequence comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent” as in instant claim 102 in part). The AAV-8 expressed ranibizumab inhibited VEGF-induced proliferation by ~75% (p. S31, col 2, top para). This shows that ranibizumab is a VEGF binding agent that can be delivered in a vector.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a vector containing Anc80 capsid protein as taught by Stankovic, where the vector contains ranibizumab as taught by Limberis, to arrive at the instantly claimed invention. As Limberis shows that a vector can contain ranibizumab, one of ordinary skill would have been motivated to simply substitute the transgene of Stankovic for the ranibizumab as taught by Limberis with a reasonable expectation of advantageously having a transgene be able to be efficiently inhibit VEGF expression and proliferation as taught by the prior art.
Regarding claim 106, Limberis teaches a vector containing the nucleic acid sequence for ranibizumab. The instant specification states that SEQ ID NO 102 encodes for ranibizumab (para 222 of specification) such that, absent evidence to the contrary, the nucleic acid sequence of Limberis renders obvious on “wherein the coding sequence comprises the nucleic acid sequence of SEQ ID NO: 102” as in instant claim 106.
Instant claim 114 recites, inter alia, “wherein the transduction of one or more supporting cells results in expression of anti-VEGF in one or more supporting cells in the inner ear of a mammal” which raises a question as to its limiting effect (see MPEP 2111.04). Limitations in a claim are not given weight when it simply expresses an intended result or use. Furthermore, the combination of Stankovic and Limberis render obvious the composition of instant claim 102 and shows that the composition can transduce inner ear supporting cells via the Anc80 capsid protein. Thus, absent evidence to the contrary, the vector of Stankovic and Limberis in combination would result in “expression of anti-VEGF in one or more supporting cells of the inner ear of a mammal” as instantly claimed in instant claim 114.
Regarding claim 115, Stankovic teaches that Anc80 containing vectors can transduce supporting cells of the inner ear but does not explicitly state that the vector transduces supporting cells “comprising Hensen’s cells, Claudius cells, Dieter cells, inner and outer pillar cells, inner border cells, inner phalangeal cells, or any combination thereof” as instantly claimed. However, evidentiary reference Suzuki evidences that inner ear gene therapy containing Anc80 capsid protein can be used to transduce inner ear cells (abstract). The reference evidences that injections targets virtually 100% of IHCs throughout the cochlear spiral, as well as a significant fraction of OHCs (Introduction, para 4). The AAV vector transduced virtually all of the supporting cells (“Transduction in the vestibular epithelia” para 1; Fig. 5). This evidences that Anc80 containing vectors can transduce all supporting cells of the inner ear. Thus, absent evidence to the contrary, the vector of Stankovic and Limberis in combination can induce expression in the supporting cells as instantly claimed in instant claim 115.
Response to Arguments
On p. 7-9 of Remarks, Applicant argues that the Office has not provided a reasoned statement for combining previously cited Stankovic and Limberis. Applicant argues that Stankovic teaches efficient delivery of nucleic acids to cochlear and vestibular cells with vectors containing Anc80 vectors and Limberis teaches transgene encoding a VEGF binding agent, ranibizumab, in an AAV vector to treat eye diseases. Applicant argues that nothing in Limberis suggests that any of its teachings can be applied to the ear and that the Office action does not provide a rationale for why one of ordinary skill in the art would modify the teachings of Stankovic to include a VEGF binding agent. Applicant argues that the vectors in Stankovic and Limberis are different and contemplated to address different problems. Applicant argus that the Office action, in sum, fails to establish a motivation to combine the vectors of Stankovic and Limberis. Applicant further argues, in sum, (p. 9-10 of Remarks) that one of ordinary skill would not consider substituting one or more components from an eye optimized vector into an ear optimized vector as in cited references Stankovic and Limberis. Applicant argues that Limberis is not relevant to the claimed Anc80 vector being claimed and cannot provide any guidance to one of ordinary skill in the art. Applicant further argues (p. 11-12 of Remarks), in sum, that the Stankovic reference could not provide the solution to Applicant’s argued problem of an AAV vector encoding a VEGF binding agent to treat inner ear disorders because VEGF binding agents were not contemplated by Stankovic and Limberis teaches use of an AAV vector for delivering ranibizumab to an unrelated organ system.
In response, the examiner disagrees. First, the examiner notes that at least independent claim 1 is drawn to a composition comprising Anc80 capsid and SEQ ID NO 95 (ranibizumab) in an rAAV vector and is not, for example, a method of treating, method of delivering to a particular cell type, etc. How it is used (optimized for eye versus ear) is not commensurate in scope with the instantly claimed invention. Second, in order for a reference to be proper for use in an obviousness rejection under 35 U.S.C. 103, the reference must be analogous art to the claimed invention. In re Bigio, 381 F.3d 1320, 1325, 72 USPQ2d 1209, 1212 (Fed. Cir. 2004). A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). Note that "same field of endeavor" and "reasonably pertinent" are two separate tests for establishing analogous art; it is not necessary for a reference to fulfill both tests in order to qualify as analogous art. See Bigio, 381 F.3d at 1325, 72 USPQ2d at 1212. Even if, arguendo, Applicant’s argued “usefulness in delivery and expressing VEGF binding agent to the inner ear” was commensurate with the scope of the instantly claimed invention, the Stankovic reference is both in the same field of endeavor (gene therapy) and is reasonably pertinent to the instant invention (i.e., related to Applicant’s instantly argued concern of targeting inner ear cells via the use of Anc80). The Limberis reference, while it addresses a different problem from the instant invention, it provides one of ordinary skill ample teachings, suggestions, and motivations to create a vector containing VEGF binding agent (gene therapeutic), such as ranibizumab, for any reason (even not pertinent to Applicant’s instant problem solved, especially considering that the instant invention is a composition and not a method of treating, etc.). Limberis shows that a vector can be created that contains ranibizumab, and Stankovic shows that Anc80 capsids can be used within vectors to specifically target inner ear cells with transgenes. Thus, Applicant’s arguments are not persuasive.
Claim(s) 109-110 remain rejected under 35 U.S.C. 103 as being unpatentable over Stankovic et al (WO2017100791 A1, 12 Dec 2016; Published 15 June 2017; Ref. B15 of Foreign Patent Documents in IDS filed 1 Oct 2024; previously cited) in view of Limberis et al (Molecular Therapy, May 2012; 20(1):S31; previously cited) as applied to claims 102-108 and 111-112, and further in view of Taylor-Parker (AddGene, 31 Mar 2016; Retrieved from the Internet 5/13/2025 from https://blog.addgene.org/plasmids-101-terminators-and-polya-signals; previously cited).
The teachings of Stankovic and Limberis in combination were recited in the above 35 U.S.C. 103 rejection as applied to claim 102 of which claims 109-110 ultimately depend. The teachings will not be repeated here.
The difference between the combined teachings and the invention as instantly claimed is that they do not teach that the nucleotide sequence further comprises a polyadenylation sequence (related to claim 109) or that the polyadenylation sequence comprises a bovine growth hormone polyadenylation sequence, a mouse-beta-globin polyadenylation sequence, a mouse-alpha-globin polyadenylation sequence, a human collagen polyadenylation sequence, a polyoma virus polyadenylation sequence, a herpes simplex virus thymidine kinase polyadenylation sequence, an IgG heavy chain polyadenylation sequence, a human growth hormone polyadenylation sequence, or a SV40 polyadenylation sequence (related to claim 110).
Taylor-Parker describes PolyA signals (title). The reference teaches that mammalian expression plasmids are primarily used to create mRNA and the commonly used mammalian terminators (SV40, hGH, BGH, and rbGlob) include the sequence motif AAUAAA which promotes both polyadenylation and termination. Out of those listed, the SV40 late polyA and rbGlob polyA are thought to be more efficient in terminating transcription due to the presence of additional helper sequences (“Eukaryotic termination and polyadenylation” para 2) (“a polyadenylation sequence” as in instant claim 109; “the polyadenylation sequence comprises a bovine growth hormone polyadenylation sequence . . . a human growth hormone polyadenylation sequence, or SV40 polyadenylation sequence” as in instant claim 110). It also teaches that the addition of the poly(A) tail is important for stability of the mRNA, protection from degradation, and is integral to the nuclear export and translation processes as well (“Eukaryotic termination and polyadenylation” para 3). This shows why one of ordinary skill would include a polyadenylation signal in a vector construct.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a vector containing Anc80 and ranibizumab as taught by Stankovic and Limberis in combination, where the vector contains a polyadenylation signal as taught by Taylor-Parker, to arrive at the instantly claimed invention. As Taylor-Parker shows that polyadenylation is important in termination of transcription of nucleotide sequences, one of ordinary skill would have been motivated to modify the vector of Stankovic and Limberis in combination to include hGH, BGH, or SV40 polyA signal in the nucleotide sequence as taught by Taylor-Parker with a reasonable expectation of advantageously improving mRNA stability, protecting the synthesized RNA from degradation, and being able to have nuclear export as taught by the prior art.
Response to Arguments
Applicant has not presented any arguments related to previously cited reference Taylor-Parker nor has Applicant attempted to distinguish the specific teachings of Taylor-Parker and the portions of the instantly claimed invention rendered prima facie obvious by the reference. Thus, the rejection is maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 GILLIAN C REGLAS whose telephone number is (571)270-0320. The examiner can normally be reached M-F 9-5.
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/G.R./Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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