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 .
Priority
Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application No. 63/339,937 (filed 05/09/2022).
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 12/09/2025 in response to a Restriction requirement is acknowledged.
Claims 8-10, 12-17, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, and 167 read on the elected invention and are examined on the merits herein.
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claim 8: Claim 8 and its dependents are drawn to an expression construct comprising a polynucleotide encoding a polypeptide operably linked to a promoter. The term operably linked is interpreted as a functional relationship between the polynucleotide and promoter element; this is supported by the specification of the instant application (par. 0100), which recites, “Operably linked…refers to a juxtaposition wherein the components described are in a relationship permitting them to function in their intended manner.” The same paragraph recites examples of such a functional relationship, including an example wherein “…a functional linkage may include transcriptional control.”
Par. 0107 of the specification defines the term promoter as “…a nucleic acid sequence that functions to control the transcription of one or more coding sequences…located upstream with respect to the direction of transcription of the transcription initiation site of the coding sequence.” Thus, in light of this definition, and under broadest reasonable interpretation, the term promoter is interpreted as a gene regulatory element which directs transcription of the coding sequence of interest, and includes promoters, enhancers, repressors, and activators. This is supported in par. 0107 of the specification: “In some aspects, the promoter is structurally identified by the presence of a binding site for DNA-dependent RNA polymerase, transcription initiation sites or other DNA sequence (e.g., a transcription factor binding site, a repressor and/or activator protein binding site, or other sequences of nucleotides that act directly or indirectly to regulate the amount of transcription from the promoter).”
Regarding claim 17: Claim 17 recites the limitation, a minimal GJB2 promoter; par. 0093 of the instant specification recites, “the term ‘minimal promoter’…refers to a promoter that includes less than the full naturally occurring promoter sequence, which is still capable of directing transcription…”. Thus, the term minimal GJB2 promoter is interpreted as any GJB2 promoter capable of directing transcription which comprises less nucleotides than the wild-type GJB2 promoter sequence.
Claim Objections
Claims 14, 16 are objected to because of the following informalities:
Claim 14 appears to contain a typographical error; “The expression construct of claim 8 further comprising…” should read “The expression construct of claim 8, further comprising…”.
Claim 16 appears to contain a typographical error; “…miR182…” should read “…miR-182…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
Claims 8-9, 92, 109, 113-114, 117-118, 120, 157, and 167 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Sena-Esteves, et al. (US 2018/0311290).
Sena-Esteves, et al. teaches recombinant adeno-associated viruses comprising artificial genetic regulatory elements that modulate transgene expression (Abstract).
Regarding claims 8-9, 109, 113-114: Sena-Esteves, et al. teaches a recombinant adeno-associated virus (rAAV) containing a nucleic acid comprising a first promoter operably linked to a first transgene and a second promoter operably linked to a second transgene, wherein the second promoter is a GFAP promoter encoded by SEQ ID NO: 14 (par. 0019). Sena-Esteves, et al. teaches the second transgene encodes a CNS disease-associated gene, e.g., protein (par. 0020), such as DRD2 (par. 0120). SEQ ID NO: 14 shares 99% sequence identity with SEQ ID NO: 91; please see end of Office action for all sequence alignments.
Thus, the rAAV comprising the GFAP promoter encoded by SEQ ID NO: 14 and the DRD2 transgene reads on the expression construct comprising a polynucleotide encoding a polypeptide operably linked to a promoter, wherein the promoter comprises a nucleic acid sequence having at least 99% identity to SEQ ID NO: 91 limitation recited in claim 8, the wherein the promoter is heterologous to the polynucleotide limitation recited in claim 9, the viral vector comprising the expression construct of claim 8 limitation recited in claim 109, the wherein the viral vector is an AAV vector limitation recited in claim 113, and the AAV particle comprising the expression construct of claim 8 limitation recited in claim 114.
Regarding claim 92: Following the above discussion, Sena-Esteves, et al. teaches an embodiment wherein the nucleic acid further comprises a polyadenylation sequence (par. 0106); this reads on the further comprising a polyA tail limitation recited in claim 92.
Regarding claims 117-118: Following the above discussion, Sena-Esteves, et al. teaches a composition comprising the rAAV and a pharmaceutically acceptable carrier (par. 0124); this reads on the composition comprising the expression construct of claim 8 limitation recited in claim 117, as well as the wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier limitation recited in claim 118.
Regarding claim 120: Following the above discussion, Sena-Esteves, et al. teaches a host cell comprising a nucleic acid encoding the rAAV (par. 0016); this reads on the ex vivo cell comprising the expression construct of claim 8 limitation recited in claim 120.
Regarding claim 157: Following the above discussion, Sena-Esteves, et al. teaches a kit comprising the components of the rAAV (par. 0146); this reads on the kit comprising the expression construct of claim 8 limitation recited in claim 157.
Regarding claim 167: Following the above discussion, Sena-Esteves, et al. teaches the rAAV comprises 5’ and 3’ ITRs (par. 0096); this reads on the 5' and a 3' inverted terminal repeat (ITR) limitation recited in claim 167.
Claims 8, 10, 12, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, and 167 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Corey, et al. (US 2023/0340038).
Corey, et al. teaches compositions and methods for treating Non-syndromic hearing loss and deafness (DFNB1) by delivering gap junction beta 2 (GJB2) protein to inner ear cells (Abstract).
Regarding claims 8, 10, 12, 106: Corey, et al. teaches an isolated nucleic acid comprising an expression cassette, wherein the cassette comprises a GJB2 gene regulatory element (GRE) and a nucleotide sequence encoding a GJB2 protein (par. 0004), disclosing an embodiment wherein the GRE is a GJB2 enhancer encoded by SEQ ID NO: 12 (par. 0010). SEQ ID NO: 12 shares 100% sequence identity to instant SEQ ID NO: 16; please see end of Office action for all sequence alignments. Corey, et al. teaches the enhancer confers cell-specific gene expression regulation by binding to transcription factors, leading to transcriptional activation (par. 0076); additionally disclosed is an embodiment wherein the nucleic acid expresses GJB2 in pillar cells, Deiter cells, Hensen’s cells, Claudius cells, inner phalangeal cells, and border cells (par. 0015).
Thus, the expression cassette comprising a GJB2 enhancer encoded by SEQ ID NO: 12 and a nucleotide sequence encoding a GJB2 protein taught by Corey, et al. reads on the expression construct comprising a polynucleotide encoding a polypeptide operably linked to a promoter, wherein the promoter comprises a nucleic acid sequence having 100% identity to any one of SEQ ID NO: 16 limitation recited in claim 8, the wherein the promoter is capable of directing transcription of the polynucleotide in an inner ear support cell limitation recited in claim 10, the wherein the inner ear support cell is inner phalangeal cells/border cells (IPhC), inner pillar cells (IPC), outer pillar cells (OPC), Deiters' cells rows 1 and 2 (DC1/2), Deiters' cells row 3 (DC3), Hensen's cells (Hec), Claudius cells/outer sulcus cells (CC/OSC) limitation recited in claim 12, and the wherein the construct is selectively expressed in an inner ear supporting cell limitation recited in claim 106.
Regarding claim 87: Following the above discussion, Corey, et al. teaches the expression cassette as comprising a nucleotide sequence encoding a 5’ UTR (par. 0009), as well as a nucleotide sequence encoding a 3’ UTR (par. 0020). This reads on the wherein the construct further comprises a 5' UTR and a 3' UTR limitation recited in claim 87.
Regarding claim 91: Following the above discussion, Corey, et al. teaches an embodiment wherein the cassette further comprises one or more miRNA binding sites positioned in the 3’ UTR (par. 0021); this reads on the wherein the 3' UTR comprises a miRTS limitation recited in claim 91.
Regarding claim 92: Following the above discussion, Corey, et al. teaches the expression cassette further comprises a poly A signal (par. 0022); this reads on the further comprising a polyA tail limitation recited in claim 92.
Regarding claims 109, 113-114: Following the above discussion, Corey, et al. teaches an AAV vector comprising the isolated nucleic acid (par. 0025); this reads on the viral vector comprising the expression construct of claim 8 limitation recited in claim 109, the wherein the viral vector is an AAV vector limitation recited in claim 113, as well as the AAV particle comprising the expression construct of claim 8 limitation recited in claim 114.
Regarding claims 117-118: Following the above discussion, Corey, et al. teaches a pharmaceutical composition comprising the rAAV and pharmaceutically acceptable carrier (par. 0035); this reads on the composition comprising the expression construct of claim 8 limitation recited in claim 117, and the wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier limitation recited in claim 118.
Regarding claim 120: Following the above discussion, Corey, et al. teaches a host cell comprising the rAAV (par. 0034); this reads on the ex vivo cell comprising the expression construct of claim 8 limitation recited in claim 120.
Regarding claim 157: Following the above discussion, Corey, et al. teaches a kit comprising the rAAV (par. 0204); this reads on the kit comprising the expression construct of claim 8 limitation recited in claim 157.
Regarding claim 167: Following the above discussion, Corey, et al. teaches the rAAV comprises an AAV 5’ ITR and an AAV 3’ ITR (par. 0031); this reads on the 5' and a 3' inverted terminal repeat (ITR) limitation recited in claim 167.
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.
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 8-10, 12, 14-16, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, and 167 are rejected under 35 U.S.C. 103 as being unpatentable over Corey, et al. (US 2023/0340038) in view of Sena-Esteves, et al. (US 2018/0311290), further in view of Boye, et al. (WO 2021/202817).
The teachings of Corey, et al. and Sena-Esteves, et al. are set forth above; claims 8, 10, 12, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, 167 are anticipated by Corey, et al.
Boye, et al. teaches compositions and methods for treating diseases of the mammalian inner ear (Abstract).
Regarding claims 9, 14-16: It is set forth above Corey, et al. anticipates the expression construct of claim 8, additionally disclosing an embodiment wherein the cassette further comprises cochlear hair cell-associated miRNA binding sites miR-182 and miR-183 (par. 0021). Corey, et al. also discloses an embodiment wherein the cassette further comprises a GJB2 promoter (par. 0004). Corey, et al. does not teach the GJB2 promoter as capable of delivering the nucleic acid to hair cells of the inner ear.
However, Sena-Esteves, et al. teaches a GFAP promoter encoded by SEQ ID NO: 14 (par. 0019), which shares 99% sequence identity to instant SEQ ID NO: 91; please see end of Office action for all sequence alignments.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the expression cassette of Corey, et al. by substituting the GJB2 promoter with the GFAP promoter of Sena-Esteves, et al. This conclusion of obviousness is based on the ‘substitution rationale’; the use of the GFAP promoter in place of the GJB2 promoter is a predictable use of prior art elements according to their established functions as gene regulatory elements, leading to the predictable result of transcription modulation. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B). Further, one skilled in the art would have a reasonable expectation of success in doing so, as Boye, et al. teaches the GFAP promoter as an appropriate promoter for delivery of a polynucleotide to hair cells of the inner ear (pg. 40; par. 1).
Thus, the modified expression cassette of Corey, et al. as set forth above renders obvious the wherein the promoter is heterologous to the polynucleotide limitation recited in claim 9, the comprising a miRNA regulatory target site (miRTS) for a microRNA expressed in an inner ear cell limitation recited in claim 14, the wherein the microRNA is expressed in an inner ear hair cell limitation recited in claim 15, as well as the wherein the microRNA is miR-182 and miR-183 limitation recited in claim 16.
Claims 8, 10, 12, 17, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, and 167 are rejected under 35 U.S.C. 103 as being unpatentable over Corey, et al. (US 2023/0340038) in view of Adam and Cyr (Biol Reprod. 2016).
The teachings of Corey, et al. are set forth above; claims 8, 10, 12, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, 167 are anticipated by Corey, et al.
Adam and Cyr (hereinafter Adam) teaches SP1 and TFAP2A regulate GJB2 promoter activity during epididymal differentiation (Abstract).
Regarding claim 17: It is set forth above Corey, et al. anticipates the expression construct of claim 8, additionally disclosing an embodiment wherein the cassette further comprises a GJB2 promoter (par. 0004). Corey, et al. does not teach the GJB2 promoter as a minimal GJB2 promoter.
However, Adam teaches the GJB2 promoter was used to generate a 230-bp fragment, the -230/+133 construct, which showed increased luciferase activity compared to the full-length GJB2 promoter (“Gjb2 Promoter Activity”, pg. 4; Fig. 3; Fig. 4).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the expression cassette of Corey, et al. by substituting the GJB2 promoter with the -230/+133 GJB2 promoter construct of Adam. This conclusion of obviousness is based on the ‘substitution rationale’; the use of the -230/+133 GJB2 promoter construct in place of the GJB2 promoter is a predictable use of prior art elements according to their established functions as GJB2 promoter elements, leading to the predictable result of transcription modulation. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B). One skilled in the art would have a reasonable expectation of success in doing so, as Corey, et al. teaches the inclusion of a GJB2 promoter in the expression cassette. This expectation is further increased as Adam teaches increased transactivation activity with the -230/+133 GJB2 promoter construct (“Gjb2 Promoter Activity”, pg. 4; Fig. 3; Fig. 4).
Thus, the modified expression cassette of Corey, et al. as set forth above renders obvious the further comprising a minimal GJB2 promoter which is operably linked to the nucleic acid sequence encoding the polypeptide limitation recited in claim 17.
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 8-10, 12-17, 87, 91-92, 106, 109, 113-114, 117-118, 120, 157, and 167 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 12, 15, 19-21, 35, 39-40, 43, 58, 61-62, 64, and 102 of copending Application No. 17/998,486 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 8, 13, 106: Copending claim 1 recites a construct comprising a coding sequence operably linked to a promoter, wherein: the coding sequence encodes a connexin 26 protein, and the promoter is a supporting cell selective promoter comprising a nucleic acid sequence with at least 85% identity to any one of SEQ ID NOs: 90, 95, 98, 101, and 104.
Copending SEQ ID NO: 90 shares 100% sequence identity to instant SEQ ID NO: 90; copending SEQ ID NO: 95 shares 100% sequence identity to instant SEQ ID NO: 57; copending SEQ ID NO: 98 shares 100% sequence identity to instant SEQ ID NO: 28; copending SEQ ID NO: 101 shares 100% sequence identity to instant SEQ ID NO: 16; and copending SEQ ID NO: 104 shares 100% sequence identity to instant SEQ ID NO: 40. Please see end of Office action for all sequence alignments.
Thus, copending claim 1 anticipates the limitations recited in instant claim 8, 13, and 106.
Regarding claim 9: Copending claims 2 and 3 further narrow the promoter limitation of copending claim 1, reciting the promoter as comprising a nucleic acid sequence with at least 85% identity to SEQ ID NOs: 90 and 104, respectively. This anticipates the limitation recited in instant claim 9.
Regarding claims 10, 12: Copending claim 15 recites wherein the promoter is capable of expressing the polynucleotide in an inner ear support cell selected from one or more of inner phalangeal cells/border cells (IPhC), inner pillar cells (IPC), outer pillar cells (OPC), Deiters' cells rows 1 and 2 (DC1/2), Deiters' cells row 3 (DC3), Hensen's cells (Hec), Claudius cells/outer sulcus cells (CC/OSC), interdental cells (Idc), inner sulcus cells (ISC), Kölliker's organ cells (KO), fibroblasts and other cells of the lateral wall, greater epithelial ridge cells (GER) (including lateral greater epithelial ridge cells (LGER)), and OC90+ cells (OC90); this anticipates the limitation recited in instant claims 10 and 12.
Regarding claims 14-16: Copending claim 19 recites the construct further comprises a nucleic acid sequence comprising a microRNA regulatory target site (miRTS) for a microRNA expressed in an inner ear cell; copending claim 20 recites wherein the microRNA is one or more of miR-194, miR-140, miR-18a, miR-99a, miR-30b, miR-15a, miR182, or miR-183; copending claim 21 recites wherein the microRNA is expressed in inner ear hair cells. These copending claims anticipate the limitations recited in instant claims 14, 15, and 16.
Regarding claim 17: Copending claim 12 recites the construct further comprises an hGJB2 minimal promoter; this anticipates the limitation recited in instant claim 17.
Regarding claim 87: Copending claim 35 recites wherein the construct further comprises a 5' UTR and a 3' UTR; this anticipates the limitation recited in instant claim 87.
Regarding claim 91: Copending claim 39 recites wherein the 3’ UTR and/or the 5’ UTR comprises the miRTS; this anticipates the limitation recited in instant claim 91.
Regarding claim 92: Copending claim 40 recites the construct further comprises a polyA tail; this anticipates the limitation recited in instant claim 92.
Regarding claims 109, 113-114, 167: Copending claim 58 recites an AAV particle comprising the construct of claim 1; this anticipates the limitations recited in instant claims 109, 113, and 114. Copending claim 43 recites the construct comprises a 5’ and a 3’ inverted terminal repeat (ITR); this anticipates the limitation recited in instant claim 167.
Regarding claims 117-118: Copending claim 61 recites a composition comprising the construct, while copending claim 62 recites the composition is a pharmaceutical composition comprising a pharmaceutically acceptable carrier; this anticipates the limitation recited in instant claims 117 and 118.
Regarding claim 120: Copending claim 64 recites an ex vivo cell comprising the construct; this anticipates the limitation recited in instant claim 120.
Regarding claim 157: Copending claim 102 recites a kit comprising the construct; this anticipates the limitation recited in instant claim 157.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 8-10, 12-13, 17, 87, 92, 106, 109, 113-114, 117-118, 120, 157, and 167 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 15-21, 62, 66, 79, 81, 83-84, 87-88, 90, 111, and 122 of copending Application No. 18/314,661 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 8-9, 13, 106: Copending claim 12 recites an expression construct comprising a coding sequence for a Connexin 26 polypeptide or a functional fragment thereof operably linked to a promoter, wherein the promoter comprises a nucleic acid sequence having at least 85% identity to any one of SEQ ID NO: 96 or 99, wherein the promoter is capable of directing transcription of the coding sequence; copending claims 15 and 16 further narrow the promoter to SEQ ID NOs: 96 and 99, respectively; copending claim 19 recites wherein the promoter comprises a nucleic acid sequence having at least 95% identity to any one of SEQ ID NOs: 90, 40, 96, or 99; copending claim 79 recites wherein the construct is selectively expressed in an inner ear supporting cell.
Copending SEQ ID NO: 40 shares 100% sequence identity to instant SEQ ID NO: 40; copending SEQ ID NO: 90 shares 100% sequence identity to instant SEQ ID NO: 90; copending SEQ ID NO: 96 shares 100% sequence identity to instant SEQ ID NO: 96; and copending SEQ ID NO: 99 shares 100% sequence identity to instant SEQ ID NO: 99. Please see end of Office action for all sequence alignments.
Thus, copending claims 12, 15-16, 19, and 79 anticipate the limitations recited in instant claims 8, 9, 13, and 106.
Regarding claim 10: Copending claim 18 recites wherein the promoter is capable of directing transcription of the coding sequence in an inner ear support cell; this anticipates the limitation recited in instant claim 10.
Regarding claim 12: Copending claim 20 recites wherein the inner ear support cell is selected from one or more of inner phalangeal cells/border cells (IPhC), inner pillar cells (IPC), outer pillar cells (OPC), Deiters' cells rows 1 and 2 (DC1/2), Deiters' cells row 3 (DC3), Hensen's cells (Hec), Claudius cells/outer sulcus cells (CC/OSC), interdental cells (Idc), inner sulcus cells (ISC), Kölliker's organ cells (KO), greater ridge epithelial ridge cells (GER) (including lateral greater epithelial ridge cells (LGER)), and OC90+ cells (OC90), fibroblasts, and other cells of the lateral wall; this anticipates the limitation recited in instant claim 12.
Regarding claim 17: Copending claim 17 recites the expression construct further comprises a second promoter, while copending claim 21 recites wherein the second promoter is a minimal GJB2 promoter; this anticipate the limitation recited in instant claim 17.
Regarding claim 87: Copending claim 62 recites wherein the construct further comprises a 5’ UTR and a 3’ UTR; this anticipates the limitation recited in instant claim 87.
Regarding claim 92: Copending claim 66 recites the expression construct further comprises a polyA tail; this anticipates the limitation recited in instant claim 92.
Regarding claims 109, 113-114, 167: Copending claim 81 recites a viral vector comprising the expression construct; copending claim 83 recites wherein the viral vector is an AAV vector; copending claim 84 recites an AAV particle comprising the expression construct; and copending claim 122 recites the viral vector further comprises a 5’ and a 3’ inverted terminal repeat (ITR). This anticipates the limitations recited in instant claims 109, 113, 114, and 167.
Regarding claims 117-118: Copending claim 87 recites a composition comprising the expression construct, while copending claim 88 recites wherein the composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier; this anticipates the limitations recited in instant claims 117 and 118.
Regarding claim 120: Copending claim 90 recites an ex vivo cell comprising the expression construct; this anticipates the limitation recited in instant claim 120.
Regarding claim 157: Copending claim 111 recites a kit comprising the expression construct; this anticipates the limitation recited in instant claim 157.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 8, 10, 12-14, 17, 87, 92, 106, 109, 113-114, 117-118, 120, 157, and 167 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 19-22, 62, 66, 69, 71, 81, 84-86, 90, 111, 139, 144, 147, 150, and 154 of copending Application No. 18/560,064 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 8-9, 13, 106: Copending claims 1-5, 7, 19, 22, 139, and 150 are drawn to a viral vector comprising a polynucleotide encoding a polypeptide operably linked to a promoter, wherein the promoter is heterologous to the polynucleotide, and wherein the promoter comprises a nucleic acid sequence having at least 85% identity to any one of SEQ ID NOs: 40, 90, 96, or 99.
Copending SEQ ID NO: 40 shares 100% sequence identity to instant SEQ ID NO: 40; copending SEQ ID NO: 90 shares 100% sequence identity to instant SEQ ID NO: 90; copending SEQ ID NO: 96 shares 100% sequence identity to instant SEQ ID NO: 96; and copending SEQ ID NO: 99 shares 100% sequence identity to instant SEQ ID NO: 99. Please see end of Office action for all sequence alignments.
Thus, copending claims 1-5, 7, 19, 22, 139, and 150 anticipate the limitations recited in instant claims 8, 9, 13, and 106.
Regarding claim 10, 12: Copending claims 6-7, 20, 139, 144, 150, and 154 recite the promoter as capable of directing transcription in an inner ear support cell, wherein the inner ear support cell is selected from one or more of inner phalangeal cells/border cells (IPhC), inner pillar cells (IPC), outer pillar cells (OPC), Deiters' cells rows 1 and 2 (DC1/2), Deiters' cells row 3 (DC3), Hensen's cells (Hec), Claudius cells/outer sulcus cells (CC/OSC), interdental cells (Idc), inner sulcus cells (ISC), Kölliker's organ cells (KO), greater ridge epithelial ridge cells (GER) (including lateral greater epithelial ridge cells (LGER)), and OC90+ cells (OC90), fibroblasts, and other cells of the lateral wall; this anticipates the limitations recited in instant claims 10 and 12.
Regarding claim 14: Copending claims 147 and 154 recites the expression construct comprises an miRNA regulatory target site (miRTS) for a microRNA expressed in an inner ear cell; this anticipates the limitation recited in instant claim 14.
Regarding claim 17: Copending claim 21 recites the expression construct further comprises a minimal GJB2 promoter; this anticipates the limitation recited in instant claim 17.
Regarding claim 87: Copending claims 62 and 154 recite the construct comprises a 5’ UTR and a 3’ UTR; this anticipates the limitation recited in instant claim 87.
Regarding claim 92: Copending claim 66 recites the construct further comprises a polyA tail; this anticipates the limitation recited in instant claim 92.
Regarding claims 109, 113-114, 167: Copending claims 69, 71, 81, 84-86, 150, and 154 are drawn to an AAV particle comprising the expression construct, further comprising a 5’ and a 3’ inverted terminal repeat (ITR); this anticipates the limitations recited in instant claims 109, 113, 114, and 167.
Regarding claim 120: Copending claim 90 recites an ex vivo cell comprising the polynucleotide of claim 1; this anticipates the limitation recited in instant claim 120.
Regarding claim 157: Copending claim 111 recites a kit comprising the polynucleotide of claim 1; this anticipates the limitation recited in instant claim 157.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
All claims are rejected. However, in the interest of advancing prosecution, the following is a statement of reasons for the indication of allowable subject matter:
During the course of examination, the promoter sequences of the instant application as set forth in SEQ ID NOs: 28, 40, 57, 90, and 92-99 were found to be non-obvious over the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
SEQUENCE ALIGNMENTS
For Sena-Esteves, et al. (US 2018/0311290):
Query (SEQ ID NO: 91) vs. Subject (SEQ ID NO: 14)
PNG
media_image1.png
209
613
media_image1.png
Greyscale
For Corey, et al. (US 2023/0340038):
Query, ‘Qy’ (SEQ ID NO: 16) vs. Database, ‘Db’ (SEQ ID NO: 12)
PNG
media_image2.png
317
648
media_image2.png
Greyscale
For copending U.S. Application No. 17/998,486
Query, ‘Qy’ (instant SEQ ID NO: 90) vs. Database, ‘Db’ (copending SEQ ID NO: 90)
PNG
media_image3.png
315
640
media_image3.png
Greyscale
SEQUENCE ALIGNMENTS (continued)
For copending U.S. Application No. 17/998,486 (continued):
Query, ‘Qy’ (instant SEQ ID NO: 57) vs. Database, ‘Db’ (copending SEQ ID NO: 95)
PNG
media_image4.png
313
644
media_image4.png
Greyscale
Query, ‘Qy’ (instant SEQ ID NO: 28) vs. Database, ‘Db’ (copending SEQ ID NO: 98)
PNG
media_image5.png
317
642
media_image5.png
Greyscale
Query, ‘Qy’ (instant SEQ ID NO: 16) vs. Database, ‘Db’ (copending SEQ ID NO: 101)
PNG
media_image6.png
318
646
media_image6.png
Greyscale
SEQUENCE ALIGNMENTS (continued)
For copending U.S. Application No. 17/998,486 (continued):
Query, ‘Qy’ (instant SEQ ID NO: 40) vs. Database, ‘Db’ (copending SEQ ID NO: 104)
PNG
media_image7.png
314
641
media_image7.png
Greyscale
For copending U.S. Application No. 18/314,661:
Query, ‘Qy’ (instant SEQ ID NO: 40) vs. Database, ‘Db’ (copending SEQ ID NO: 40)
PNG
media_image8.png
320
646
media_image8.png
Greyscale
Query, ‘Qy’ (instant SEQ ID NO: 90) vs. Database, ‘Db’ (copending SEQ ID NO: 90)
PNG
media_image9.png
316
641
media_image9.png
Greyscale
SEQUENCE ALIGNMENTS (continued)
For copending U.S. Application No. 18/314,661 (continued):
Query, ‘Qy’ (instant SEQ ID NO: 96) vs. Database, ‘Db’ (copending SEQ ID NO: 96)
PNG
media_image10.png
319
647
media_image10.png
Greyscale
Query, ‘Qy’ (instant SEQ ID NO: 99) vs. Database, ‘Db’ (copending SEQ ID NO: 99)
PNG
media_image11.png
317
644
media_image11.png
Greyscale
For copending U.S. Application No. 18/560,064:
Query, ‘Qy’ (instant SEQ ID NO: 40) vs. Database, ‘Db’ (copending SEQ ID NO: 40)
PNG
media_image12.png
319
641
media_image12.png
Greyscale
SEQUENCE ALIGNMENTS (continued)
For copending U.S. Application No. 18/560,064 (continued):
Query, ‘Qy’ (instant SEQ ID NO: 90) vs. Database, ‘Db’ (copending SEQ ID NO: 90)
PNG
media_image13.png
316
642
media_image13.png
Greyscale
Query, ‘Qy’ (instant SEQ ID NO: 96) vs. Database, ‘Db’ (copending SEQ ID NO: 96)
PNG
media_image14.png
315
643
media_image14.png
Greyscale
Query, ‘Qy’ (instant SEQ ID NO: 99) vs. Database, ‘Db’ (copending SEQ ID NO: 99)
PNG
media_image15.png
316
642
media_image15.png
Greyscale