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 .
Claim Status
Claims 4-10, 12-15, 16-18, 20-22, 31-32, 39, 43, 45, 47-49, 56 are cancelled.
Claims 1-3, 11, 16-18, 20-22, 31-32, 39, 43, 47-49, 55-56 are pending.
Claims 1-3, 11, 16-18, 32, 39, 43 and 45 are examined on the merits.
Election/Restrictions
Claims 20-22, 31, 47-49, 55-56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/19/2025.
Applicant’s election without traverse of Group I corresponding to claims 1-3, 11, 16-18, 32, 39, 43 and 45 in the reply filed on 11/19/2025 is acknowledged.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63055413, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The application fails to provide support for the claims under examination, since there is no disclosure regarding SEQ ID NO 8-9, 16-19, 39, 111-115, 120-121. Therefore, the effective filling date of SEQ ID NO 8-9, 16-19, 39, 111-115, 120-121 in claims 3, 11, 18 is deemed to be 07/22, 2021, the filling date of the application PCT/US21/42697.
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.
Claims 1-3, 11, 16-18, 32, 39, 43, 45 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.
The dependent claim 3 is drawn to the composition of (a) wherein the hRedO promoter comprises nucleotides 452-2017 of SEQ ID NO:8 directly linked to nucleotides 4541-5032 of SEQ ID NO:8; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 452-2017 of SEQ ID NO:8 directly linked to nucleotides 4541-5032 of SEQ ID NO:8; (b) wherein the hRedO promoter comprises the nucleotide sequence of SEQ ID NO: 16, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:16; (c) wherein the GNAT2 promoter comprises nucleotides 4873-6872 of SEQ ID NO:9; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 4873-6872 of SEQ ID NO:9; (d) wherein the GNAT2 promoter comprises the nucleotide sequence of SEQ ID NO: 17; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO: 17;(e) wherein the GNAT2 promoter comprises the nucleotide sequence of SEQ ID NO:18;or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:18;(f) wherein the GNAT2 promoter comprises the nucleotide sequence of SEQ ID NO:19;or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:19; or (g) wherein the GNAT2 promoter comprises nucleotides 156-655 of the nucleotide sequence of SEQ ID NO: 39, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 156-655 of the nucleotide sequence of SEQ ID NO: 39.
The dependent claim 11, is drawn to the composition of (a) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 366-1541 of SEQ ID NO:111; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 366- 1541 of SEQ ID NO:111; (b) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 162-1172 of SEQ ID NO:112, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 162-1172 of SEQ ID NO:112; (c) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 280-1473 of SEQ ID NO:113; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 280-1473 of SEQ ID NO:113; (d) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 280-1470 of SEQ ID NO:114, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 280-1470 of SEQ ID NO:114; or (e) wherein the nucleic acid molecule encoding TXNIP comprises SEQ ID NO: 120; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:120.
The dependent claim 18, is drawn to the composition of (a) wherein the nucleic acid molecule encoding TXNIP comprises SEQ ID NO: 115; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:115; and/or (b) wherein the nucleic acid molecule encoding TXNIP comprises SEQ ID NO: 121; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:121.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification envisions tissue-specific promoter for use in the present invention is a photoreceptor-specific (PR-specific) promoter, a promoter that drives expression which is substantially restricted to photoreceptor cells and/or retinal pigment epithelial cells. The PR-specific
promoter may be a rod-specific promoter; a cone-specific promoter; or a rod- and cone-specific promoter. In one embodiment, a tissue-specific promoter for use in the present invention is a cone-specific promoter.
Suitable PR-specific promoters are known in the art and include, for example, a human red opsin, a guanine nucleotide-binding protein G subunit alpha-2 (GNAT2) promoter, a human rhodopsin promoter, a human rhodopsin kinase (RK) promoter, a G protein-coupled receptor kinase 1
(GRKl) promoter (e.g., lane 30, page 23). The specification envisions Suitable RedO promoters for use in the present invention include nucleic acid molecules which include nucleotides 452-2017 of SEQ ID NO:8 directly linked, i.e., containing no intervening sequences, to nucleotides 4541-5032 of SEQ ID NO:8; or a nucleotide sequence having about 85%,
86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 452-2017 of SEQ ID NO:8 directly linked to nucleotides 4541-5032 of SEQ ID NO:8. In one embodiment, the RedO promoter comprises the nucleotide sequence of SEQ ID NO:16, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO: 16 (e.g., lane 13, page 24). The specification envisions suitable GNAT2 promoters for use in the present invention include nucleic acid molecules which include nucleotides 4873-6872 of SEQ ID NO:9; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 4873-6872 of SEQ ID NO:9 (e.g., lane 10, page 25). The specification envisions suitable GNAT2 promoters for use in the present invention comprise the nucleotide sequence of SEQ ID NO: 17; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:17. In one embodiment, suitable GNAT2 promoters for use in the present invention comprise the
nucleotide sequence of SEQ ID NO:18; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:18. In another embodiment, suitable GNAT2 promoters for use in the present invention comprise the nucleotide sequence of SEQ ID NO:19; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence
identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:19. In one embodiment, the GNAT2 promoter comprises nucleotides 156-655 of the nucleotide sequence of SEQ ID NO: 39, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 156-655 of the nucleotide sequence of SEQ ID NO: 39 (e.g., lane 17, page 25).
No description is provided of any modifications of SEQ ID NO: 8, SEQ ID NO: 16, SEQ ID NO: 9, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 39, with at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% homology that retain the ability to perform as a promoter activity.
The working examples disclose AAV vectors comprising different promoters and inserts, such as RedO promoter, Txnip and Txnip variant constructs (e.g., Table 1).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
The examples described in the specification does not meet the limitation of the rejected claims (at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% identity), the examples are only representative of RedO promoter and Txnip and Txnip variant with no indication of any nucleotide modifications in either Rod promoter or Txnip sequences. “At least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% identity” encompasses a very large number of different nucleotide sequences (i.e., every sequence at least 85% identical to SEQ ID NO: 8), but there is insufficient guidance provided indicating any of the elements that are critical to the functioning of the promoter, thus it cannot be determined which nucleotides can be changed without disrupting the function of the promoter; thus further experimentation would be required to determine which variants of e.g., SEQ ID NO: 8 are functional and which are not.
As such, the independent and dependent claims encompasses significantly more than what is disclosed in the specification and does not satisfy the written description requirement under 35 U.S.C 112(a).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-3, 11, 16-18, 32, 39, 43, 45.
The claims listed in the statement of rejection but not otherwise discussed are rejected because they are similarly not limited to particular polynucleotides that are considered to be adequately described by the specification.
Claim Rejections - 35 USC § 103
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.
Claims 1-3, 32, 39, 43, 45 are rejected under 35 U.S.C. 103 as being unpatentable over Chalberg et al. (“Chalberg”, US 2015/0259395 A1, cited as reference 2 on IDS filed 11/19/2025) in view of Neitz et al. (“Neitz”, US 2014/0080900 A1), Patwari et al. (“Patwari”, The J. Biol. Chem., cited as reference 3 on IDS filed 11/19/2025) and Perrone et al. (“Perrone”, Cell Death and Disease, 2010).
Regarding claim 1-2, Chalberg teaches polynucleotide cassettes are provided for the expression of a transgene in cone cells of a mammalian retina. In some embodiments, the expression of the trans gene is enhanced expression (e.g., paragraphs 0010). Chalberg teaches the gene delivery vector is a recombinant adeno-associated virus, wherein the recombinant adeno-associated virus comprises an AAV capsid protein (e.g., paragraph 0018). Chalberg teaches that the promoter specifically promotes expression of the gene in mammalian retinal cone cell; more preferably primate retinal cone cells; more preferably in Catarrhini retinal cone cells; even more preferably in human retinal cone cells (e.g., paragraph 0104). Chalberg teaches that the promoter regions include the promoter region for any cone-specific gene, such as a L-opsin promoter region, an M-opsin promoter, an S-opsin promoter (e.g., paragraph 0105). Chalberg teaches the promoter results in enhanced expression in cone cells compared to other promoters known in the art, e.g., the synthetic promoters pR2.1, pRl.7,pRl.1, and IRBP/GNAT2 (e.g., paragraph 0106).
Regarding claims 32, Chalberg expression cassette comprising a
gene encoding a therapeutic polypeptide operably linked to a promoter is an expression cassette that may include other elements in addition to the gene and promoter, e.g. polyadenylation sequence, enhancer elements, other genes, linker domains (e.g., paragraph 0049; Fig. 1 [see below]).
PNG
media_image2.png
200
400
media_image2.png
Greyscale
Regarding claim 39, Chalberg teaches that AAV includes AAV type 1
(AAV-1), AAV type 2 (AAV-2), AAV type 3 (AAV-3), AAV type 4 (AAV-4), AAV type 5 (AAV-5), AAV type 6 (AAV-6), AAV type 7 (AAV-7), AAV type 8 (AAV-8) (e.g., paragraph 0039); Fig. 5).
Regarding claim 43, Chalberg teaches that pharmaceutical compositions are provided comprising a polynucleotide cassette of the invention and a pharmaceutical excipient. The pharmaceutical composition comprises a gene delivery vector of the invention and a pharmaceutical excipient (e.g., paragraph 0019).
Regarding claim 45, Chalberg teaches subretinal administration, the vector can be delivered in the form of a suspension injected subretinally
under direct observation using an operating microscope. The vitrectomy is advantageously performed because (1) the removal ofits cortex (the posterior hyaloid membrane) facilitates penetration of the retina by the cannula; (2) its removal and replacement with fluid (e.g. saline) creates space to accommodate the intraocular injection of vector, and (3) its controlled removal reduces the possibility of retinal tears and unplanned retinal detachment (e.g., paragraph 0196).
Chalberg does not teach C247S variant thioredoxin-interacting protein (TXNIP) as required by instant claim 1. Chalberg does not teach the RedO promoter as required by instant claim 3. However, this is cured by Patwari, Perrone and Neitz.
Patwari teaches overexpression of wild type and C247S Txnip in mature 3T3-L1 adipocytes by lentiviral transduction and measured glucose uptake by incorporation of 2-[3H] deoxyglucose. Uptake was expressed relative to the mean basal uptake of the cells infected with the empty vector control virus. Wild type Txnip inhibited adipocyte glucose uptake compared with an empty vector control under both basal (e.g., paragraph 2nd, page 2998; Fig. 1). Patwari teaches mutation of Txnip Cys-247 leads to loss of interaction with thioredoxin in cells and that inhibition of glucose uptake by Txnip is not affected by the C247S mutation despite loss of ability to bind to thioredoxin (e.g., paragraph 2nd, page 2999).
Perrone teaches that HBP and TXNIP are increased in diabetic retinas and correlate with retinal inflammation, fibrosis/gliosis and neuronal injury, the distinguishing features of early diabetic retinopathy (e.g., paragraph 1st, page 3, Fig. 1 [see below]).
PNG
media_image3.png
200
400
media_image3.png
Greyscale
Perrone teaches that Knockdown of TXNIP in the diabetic retina leads to a significant decrement of both Cox-2 and FN mRNA. In concert, GFAP upregulation is reduced by TXNIP siRNAs. These data demonstrate that TXNIP is required for inflammatory Cox-2 and fibrotic FN expression and gliosis in early DR (e.g., paragraph 2nd, Fig. 4). Perrone teaches that TXNIP ablation in the retina demonstrate that TXNIP indeed has a critical role in inflammation, gliosis/fibrosis and apoptosis in early stages of diabetes, which will ultimately lead to disease onset and progression of blinding ocular complications (e.g., paragraph 4th, page 4; Fig. 5 [see below]). Perrone teaches that RNAi transcriptional gene silencing of TXNIP abolishes diabetes induced retinal gliosis and ganglion injury. Thus, TXNIP has a critical role in inflammation and retinal injury in early stages of diabetic retinopathy. The successful employment of TXNIP transcriptional gene silencing and amelioration of its pathological effects open the way for novel therapeutic strategies aimed to block disease onset and progression of diabetic retinopathy (e.g., abstract).
PNG
media_image4.png
200
400
media_image4.png
Greyscale
Regarding claim 3, Neitz teaches SEQ ID NO 1 with 100% homology to SEQ ID NO 16 of the instant claim.
PNG
media_image5.png
638
612
media_image5.png
Greyscale
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Chalberg -compositions, e.g., pharmaceutical compositions, which include a recombinant adeno-associated virus (AAV) vector, comprising a human opsin promoter, chimeric intron, a polyadenylation signal and the gene of interest; with the teachings of Patwari - expression of C247S Txnip by lentiviral transduction and that mutation of Txnip Cys-247 leads to loss of interaction with thioredoxin in cells; the teachings of Perrone -TXNIP ablation in the retina demonstrate that TXNIP indeed has a critical role in inflammation, gliosis/fibrosis and apoptosis in early stages of diabetes, which will ultimately lead to disease onset and progression of blinding ocular complications and the SEQ ID NO 1 corresponding to the human Red opsin promoter taught by Neitz; for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of pharmaceutical composition, a recombinant adeno-associated virus (AAV) vector, comprising a human red opsin (RedO) promoter SEQ ID NO 1, intron, a polyadenylation signal and carrying the Txnip C247S gene for targeting cells for retinal gene therapy, therefore blocking the onset and progression of diabetic retinopathy.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a pharmaceutical composition comprising an AAV carrying a variant C247 Txnip gene that leads to loss of interaction with thioredoxin in cells for specifically to target cells for retinal gene therapy such as the photoreceptors (rods and cones) and retinal pigment epithelial (RPE) cells, for degenerative ocular disease, such as inherited retinal diseases and disorders, as a novel therapeutic strategies aimed to block disease onset and progression of diabetic retinopathy.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Chalberg et al. (“Chalberg”, US 2015/0259395 A1, cited as reference 2 on IDS filed 11/19/2025), Neitz et al. (“Neitz”, US 2014/0080900 A1), Patwari et al. (“Patwari”, The J. Biol. Chem., cited as reference 3 on IDS filed 11/19/2025) and Perrone et al. (“Perrone”, Cell Death and Disease, 2010) as applied to claims 1-3, 17, 32, 39, 43 above, and further in view of Kim et al. (“Kim”, US 9,732,126 B2).
Chalberg, Patwari, Perrone and Neitz does not teach SEQ ID NO 111 of the instant claim 11. However, this is cured by Kim.
Kim teaches a modified TXNIP protein, a polynucleotide encoding the protein, an expression vector comprising the polynucleotide, and a transformant introduced with the expression vector (e.g., lane 52, column 2). Kim teaches SEQ ID NO 9 with 99.7% similarity with SEQ ID NO 111 of the instant claim 11 (e.g., column 533, [see below]).
PNG
media_image6.png
1001
570
media_image6.png
Greyscale
PNG
media_image7.png
424
574
media_image7.png
Greyscale
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Chalberg -compositions, e.g., pharmaceutical compositions, which include a recombinant adeno-associated virus (AAV) vector, comprising a human opsin promoter, chimeric intron, a polyadenylation signal and the gene of interest; with the teachings of Patwari - expression of C247S Txnip by lentiviral transduction and that mutation of Txnip Cys-247 leads to loss of interaction with thioredoxin in cells; the teachings of Perrone -TXNIP ablation in the retina demonstrate that TXNIP indeed has a critical role in inflammation, gliosis/fibrosis and apoptosis in early stages of diabetes, which will ultimately lead to disease onset and progression of blinding ocular complications and the SEQ ID NO 1 corresponding to the human Red opsin promoter taught by Neitz; and the teachings of Kim a modified TXNIP protein, a polynucleotide encoding the protein, an expression vector comprising the polynucleotide corresponding to SEQ ID NO 9; for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of pharmaceutical composition, a recombinant adeno-associated virus (AAV) vector, comprising a human red opsin (RedO) promoter SEQ ID NO 1, intron, a polyadenylation signal and carrying the modified Txnip C247S gene (SEQ ID NO 9) for targeting cells for retinal gene therapy, therefore blocking the onset and progression of diabetic retinopathy.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a pharmaceutical composition comprising an AAV carrying a variant C247 Txnip gene that leads to loss of interaction with thioredoxin in cells for specifically to target cells for retinal gene therapy such as the photoreceptors (rods and cones) and retinal pigment epithelial (RPE) cells, for degenerative ocular disease, such as inherited retinal diseases and disorders, as a novel therapeutic strategies aimed to block disease onset and progression of diabetic retinopathy.
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 1-3, 11, 32, 39, 43, 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 26, 33, 35-37 of copending Application No. 17/428670 “670”.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims encompass those of the copending application: A composition, comprising an adeno-associated virus (AAV) expression cassette, the expression cassette comprising a photoreceptor-specific (PR- specific) promoter and a nucleic acid molecule encoding a C247S variant thioredoxin-interacting 5 protein (TXNIP). The composition of claim 1, wherein the PR-specific promoter is a human red opsin (hRedO) promoter, or a human guanine nucleotide-binding protein G subunit alpha-2 (GNAT2) promoter. The composition of The composition of (a) wherein the hRedO promoter comprises nucleotides 452-2017 of SEQ ID NO:8 directly linked to nucleotides 4541-5032 of SEQ ID NO:8; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 452-2017 of SEQ ID NO:8 directly linked to nucleotides 4541-5032 of SEQ ID NO:8; (b) wherein the hRedO promoter comprises the nucleotide sequence of SEQ ID NO: 16, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:16; (c) wherein the GNAT2 promoter comprises nucleotides 4873-6872 of SEQ ID NO:9; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 4873-6872 of SEQ ID NO:9; (d) wherein the GNAT2 promoter comprises the nucleotide sequence of SEQ ID NO: 17; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO: 17;(e) wherein the GNAT2 promoter comprises the nucleotide sequence of SEQ ID NO:18;or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:18; (f) wherein the GNAT2 promoter comprises the nucleotide sequence of SEQ ID NO:19;or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO:19; or (g) wherein the GNAT2 promoter comprises nucleotides 156-655 of the nucleotide sequence of SEQ ID NO: 39, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 156-655 of the nucleotide sequence of SEQ ID NO: 39. The composition of The composition of (a) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 366-1541 of SEQ ID NO:111; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 366- 1541 of SEQ ID NO:111; (b) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 162-1172 of SEQ ID NO:112, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 162-1172 of SEQ ID NO:112; (c) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 280-1473 of SEQ ID NO:113; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 280-1473 of SEQ ID NO:113; (d) wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 280-1470 of SEQ ID NO:114, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 280-1470 of SEQ ID NO:114; or (e) wherein the nucleic acid molecule encoding TXNIP comprises SEQ ID NO: 120; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:120. The composition of The composition of (a) wherein the nucleic acid molecule encoding TXNIP comprises SEQ ID NO: 115; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:115; and/or (b) wherein the nucleic acid molecule encoding TXNIP comprises SEQ ID NO: 121; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of SEQ ID NO:121. The composition of claim 1, wherein the expression cassette further comprises a linker, an intron, a post-transcriptional regulatory region, a Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), and/or a polyadenylation signal. The composition of claim 1, wherein the expression cassette is present in a vector; wherein the vector is an AAV vector selected from the group consisting of AAV2, AAV 8, AAV2/5, and AAV 2/8. A pharmaceutical composition comprising the AAV composition of claim 1.
It is noted that “670” represents a species with regard to: A composition, comprising an adeno-associated virus (AAV) expression cassette, the expression cassette comprising a photoreceptor-specific (PR- specific) promoter and a nucleic acid molecule encoding thioredoxin-interacting protein (TXNIP); wherein the PR-specific promoter is a human red opsin (hRedO) promoter, wherein the hRedO promoter comprises nucleotides 2023-2514 of SEQ ID NO:26, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 2023-2514 of SEQ ID NO:26; or wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 366-1541 of SEQ ID NO:1; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 366-1541 of SEQ TD NO:1; or wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 162-1172 of SEQ ID NO:2, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 162-1172 of SEQ TD NO:2; or wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 280-1473 of SEQ ID NO:3; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 280-1473 of SEQ TD NO:3; or wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 280-1470 of SEQ ID NO:4, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 280-1470 of SEQ TD NO:4; or wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 2521-37 14 of SEQ ID NO:26, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 2521-37 14 of SEQ ID NO:26; or wherein the nucleic acid molecule encoding TXNIP comprises nucleotides 663-1856 of SEQ ID NO: 39, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 663-1856 of SEQ ID NO: 39, see “670” claim 1. The composition of claim 1, wherein the PR- specific promoter is a human guanine nucleotide-binding protein G subunit alpha-2 (GNAT2) promoter, wherein the GNAT 2 promoter comprises nucleotides 4873-6872 of SEQ ID NO:9; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 4873-6872 of SEQ ID NO:9; or wherein the GNAT 2 promoter comprises the nucleotide sequence of SEQ ID NO: 17; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO: 17; or wherein the GNAT 2 promoter comprises the nucleotide sequence of SEQ ID NO: 18; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO: 18; or wherein the GNAT 2 promoter comprises the nucleotide sequence of SEQ ID NO: 19; or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of the nucleotide sequence of SEQ ID NO: 19; or wherein the GNAT 2 promoter comprises nucleotides 156-655 of SEQ ID NO: 39, or a nucleotide sequence having about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or about 99% nucleotide sequence identity to the entire nucleotide sequence of nucleotides 156-655 of SEQ ID NO: 39, see “670” claim 10.The composition of claim 1, wherein the expression cassette further comprises a linker, an intron, a post-transcriptional regulatory region, or a polyadenylation signal; or combinations thereof, see “670” claim 26. The composition of claim 1, wherein the expression cassette is present in an AAV vector, see “670” claim 33. An AAV vector particle comprising the composition of claim 1, see “670” claim 35. A pharmaceutical composition formulated for intraocular administration comprising the AAV composition of claim 1, see “670” claim 37.
It is noted that, SEQ ID NO 1 of copending application 17/428670 has 100% homology with SEQ ID NO 111 of the instant claim 11 (see annealing below).
PNG
media_image8.png
1001
574
media_image8.png
Greyscale
PNG
media_image9.png
1002
594
media_image9.png
Greyscale
It is noted that, SEQ ID NO 26 of copending application 17/428670 has 100% homology with SEQ ID NO 16 of the instant claim 3 (see annealing below).
PNG
media_image10.png
1006
580
media_image10.png
Greyscale
PNG
media_image11.png
1005
608
media_image11.png
Greyscale
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIO GOMEZ RODRIGUEZ whose telephone number is (571)270-0991. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 5712722916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JULIO WASHINGTON GOMEZ Examiner, Art Unit 1637RODRIGUEZ/
/J. E. ANGELL/Primary Examiner, Art Unit 1637