DETAILED ACTION
This action is in reply to papers filed 5/18/2026. Claims 57, 63 and 65 -79 are pending and examined herein.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/18/2026 has been entered.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20180100165A1, Published 4/12/2018.
Maintained Rejection(s)
The nonstatutory double patenting rejection of instant claims over claims 1-7 of U.S. Patent No. U.S. Patent 9816108 is maintained. Applicant’s arguments will be addressed following maintained rejection.
The 35 U.S.C. 103(a) rejection of claims 57, 66 -70 and 72-75 as being unpatentable over Acland et al. in view of Hildinger, Eliasof et al. and Young et al. is maintained. Applicant’s arguments will be addressed following maintained rejection.
The 35 U.S.C. 103(a) rejection of claim 65 as being unpatentable over Acland et al. in view of Hildinger, Eliasof et al. and Young et al.. as applied to claims 57, 63, 65-70 and 72-75 and further in view of Young et al. is maintained. Applicant’s arguments will be addressed following maintained rejection.
The 35 U.S.C. 103(a) rejection of claim 71 as being unpatentable over Acland et al. in view of Acland et al. in view of Hildinger, Eliasof et al. , Young et al. as applied to claims 57, 63, 66 -70 and 72-75 and further in view of Gao is maintained. Applicant’s arguments will be addressed following maintained rejection.
The 35 U.S.C. 103(a) rejection of claim 76-77 as being unpatentable over Acland et al. in view of Acland et al. in view of Hildinger, Eliasof et al. , Young et al. as applied to claims 57, 63, 66 -70 and 72-75 and further in view of Wilson is maintained. Applicant’s arguments will be addressed following maintained rejection.
Claim Rejections - 35 USC § 112
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.
Claims 74-75 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 74-75 depend on canceled claims. See below.
PNG
media_image1.png
156
882
media_image1.png
Greyscale
See canceled claim 62 below.
PNG
media_image2.png
66
924
media_image2.png
Greyscale
Accordingly, the metes and bounds of claims 74-75 are unclear.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 57, 66 -70 and 72-75 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Acland et al. (PgPub US20040022766A1, Published 2/5/2004; Reference in IDS filed 3/9/3022) in view of Hildinger (PgPub US20070042462A1, Published 2/22/2007; Reference in IDS filed 3/9/3022), Eliasof et al. (WO2004065576A2, Published 8/5/2004; Reference in IDS filed 3/9/3022) and Young et al. (Investigative Ophthalmology & Visual Science September 2003, Vol.44, 4076-4085). Although maintained, note that the rejection has been updated to reflect amendments to the claims and/or cancelled claims.
Acland teaches a method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject, wherein said method involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene (as in claim 75, in-part) under the control of a promoter sequence which expresses the product of the gene in the ocular cells (Abstract). To this end, Acland teaches introducing into at a first population of human retinal cells (Pg. 3, Para. 29, Lines 1-5) an rAAV vector (Pg. 3, Para. 25, Lines 1-4), such as an rAAV5 vector (as in claim 63) (Pg. 2, para. 20; Pg. 3, para. 23), comprising a polynucleotide that comprises a promoter operably linked (Pg. 4, Para. 35,Lines 1-9 , Pg. 4, Para. 40, Lines 1-4 and Pg. 5, Para. 41, Lines 1-4) to at a first nucleic acid segment that encodes a biologically-active, retinal-specific human guanylate cyclase polypeptide (GUCY2D) (Pg. 3, Para. 28, Lines 1-8 and Pg. 4, Para. 30, Lines 1-4 and 6-9) (as in claim 57, in-part and as in claim 75).
Regarding claim 66, Acland teaches the rAAV vector further comprises an intron sequence operably linked to the at least a first nucleic segment (Pg. 4, Para. 35, lines 1-4 and Pg. 4, Para. 38), which is operably linked to the promoter. Regarding claim 67, claim 68 and claim 69, Acland teaches the rAAV is comprised within an infectious adeno-associated viral particle, virion, or a plurality of infectious AAV particles (Pg. 3, Para. 24, lines 1-4 and Pg. 7, Col. 2, Para. 65, lines 11-15). Regarding claim 70, Acland teaches a composition comprising an rAAV vector and a pharmaceutically-acceptable buffer, carrier, vehicle (Pg. 6, Para. 56, lines 6-10). Regarding claim 72, claim 73 and claim 74, Acland teaches the human has a defect in at least one eye (Pg. 1, Para. 8, lines 1-4). Furthermore, Acland teaches the human is a child that has Leber congenital amaurosis- 1 (LCA- 1) (Pg. 1, Para. 10, lines 1-10 and Pg. 2, Para. 16, lines 1-7).
However, Acland fails to teach the promoter is a photoreceptor-specific human rhodopsin kinase promoter (as further in claim 57).
Before the effective filing date of the claimed invention, Hildinger taught contrary to many prior-art publications, it was discovered that the effective packaging capacity of AAV is larger than 5.7 kb. Particularly, Hildinger discovered that the capsid of AAV5 seems to be able to accommodate larger genomes, even beyond 6.5 kb and up to 8 kb with high efficacy (Pg. 3, para. 38). To this end, Hildinger teaches said vector comprises a rhodopsin kinase promoter for photoreceptor-directed gene expression (as further in claim 57) (Pg. 12, Para. 152).
And although Hildinger et al. teach a rhodopsin kinase promoter for photoreceptor-directed gene expression, Hildinger fails to teach said promoter comprises SEQ ID NO: 12 (as further in claim 57).
Before the effective filing date of the claimed invention, Young taught the human Rk gene (GenBank Acc. No. AY327580) (Pg. 4078, Col. 2). Young teaches the 2.0-kb region flanking the 5′ end of the human Rk gene was isolated, mapped, and sequenced. The sequence was fused upstream of the luciferase gene and was tested for promoter activity in retinoblastoma cells by transient transfection. SEQ ID NO: 12 is 98% identical to nucleotides 1793-2087 (i.e. a subsequence) of the human Rk gene taught by Young. See below. Note that although not 100% identical, the specification does not teach a patentable distinction between a sequence that is 98% identical and a sequence that is 100% identical (as further in claim 57).
PNG
media_image3.png
520
1038
media_image3.png
Greyscale
However, none of Acland, Hildinger or Young teach a nucleic acid encoding a human guanylate cyclase polypeptide comprising SEQ ID NO: 1 (as further in claim 57).
These deficiencies are cured by Eliasof et al.
Eliasof teaches a retinal-specific human guanylate cyclase protein, that comprises an amino acid sequence that is 100% identical to claimed SEQ ID NO: 1 (as further in claim 57). Eliasof teaches said retinal guanylyl cyclase 1 (retGC or guanylate cyclase 2D) is expressed in DRG followed by brain, prostate and breast (see Eliasof, Pg. 10, Para. 39-40). The alignment between SEQ ID NO: 1 (Qy, query) and the retinal-specific human guanylate cyclase protein taught by Karicheti et al. (Db, database) is provided below.
RESULT 1
ADQ89060
ID ADQ89060 standard; protein; 1103 AA.
XX
AC ADQ89060;
XX
DT 15-JUN-2007 (revised)
DT 21-OCT-2004 (first entry)
XX
DE Human urological disorder related protein 1405 SEQ: 12.
XX
KW urological disorder; uropathic; cytostatic; urinary incontinence;
KW benign prostatic hyperplasia; human; BOND_PC;
KW guanylate cyclase 2D, membrane (retina-specific); unnamed;
KW guanylate cyclase 2D, membrane (retina-specific) [Homo sapiens]; GUCY2D;
KW LCA; CYGD; LCA1; CORD6; GUC2D; retGC; GUC1A4; RETGC-1; ROS-GC1;
KW CORD6, LCA, GUC2D, GUC1A4; cone rod dystrophy 5/6; CORD5;
KW guanylyl cyclase; guanylyl cyclase [Homo sapiens]; GO4383; GO4672;
KW GO4872; GO5524; GO5640; GO5887; GO6182; GO6468; GO7168; GO7242; GO7601;
KW GO16020; GO50896.
XX
OS Homo sapiens.
XX
CC PN WO2004065576-A2.
XX
CC PD 05-AUG-2004.
XX
CC PF 14-JAN-2004; 2004WO-US000750.
XX
Query Match 100.0%; Score 5730; DB 5; Length 1103;
Best Local Similarity 100.0%;
Matches 1103; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MTACARRAGGLPDPGLCGPAWWAPSLPRLPRALPRLPLLLLLLLLQPPALSAVFTVGVLG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTACARRAGGLPDPGLCGPAWWAPSLPRLPRALPRLPLLLLLLLLQPPALSAVFTVGVLG 60
Qy 61 PWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALAR120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PWACDPIFSRARPDLAARLAAARLNRDPGLAGGPRFEVALLPEPCRTPGSLGAVSSALAR120
Qy 121 VSGLVGPVNPAACRPAELLAEEAGIALVPWGCPWTQAEGTTAPAVTPAADALYALLRAFG180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSGLVGPVNPAACRPAELLAEEAGIALVPWGCPWTQAEGTTAPAVTPAADALYALLRAFG180
Qy 181 WARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPLDLSGAREALRKVRDGPRVT240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 WARVALVTAPQDLWVEAGRSLSTALRARGLPVASVTSMEPLDLSGAREALRKVRDGPRVT240
Qy 241 AVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEALAALANSSQ300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AVIMVMHSVLLGGEEQRYLLEAAEELGLTDGSLVFLPFDTIHYALSPGPEALAALANSSQ300
Qy 301 LRRAHDAVLTLTRHCPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLARG360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LRRAHDAVLTLTRHCPSEGSVLDSLRRAQERRELPSDLNLQQVSPLFGTIYDAVFLLARG360
Qy 361 VAEARAAAGGRWVSGAAVARHIRDAQVPGFCGDLGGDEEPPFVLLDTDAAGDRLFATYML420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 VAEARAAAGGRWVSGAAVARHIRDAQVPGFCGDLGGDEEPPFVLLDTDAAGDRLFATYML420
Qy 421 DPARGSFLSAGTRMHFPRGGSAPGPDPSCWFDPNNICGGGLEPGLVFLGFLLVVGMGLAG480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DPARGSFLSAGTRMHFPRGGSAPGPDPSCWFDPNNICGGGLEPGLVFLGFLLVVGMGLAG480
Qy 481 AFLAHYVRHRLLHMQMVSGPNKIILTVDDITFLHPHGGTSRKVAQGSRSSLGARSMSDIR540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AFLAHYVRHRLLHMQMVSGPNKIILTVDDITFLHPHGGTSRKVAQGSRSSLGARSMSDIR540
Qy 541 SGPSQHLDSPNIGVYEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFL600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SGPSQHLDSPNIGVYEGDRVWLKKFPGDQHIAIRPATKTAFSKLQELRHENVALYLGLFL600
Qy 601 ARGAEGPAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHR660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ARGAEGPAALWEGNLAVVSEHCTRGSLQDLLAQREIKLDWMFKSSLLLDLIKGIRYLHHR660
Qy 661 GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDPALE720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GVAHGRLKSRNCIVDGRFVLKITDHGHGRLLEAQKVLPEPPRAEDQLWTAPELLRDPALE720
Qy 721 RRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMDQAPVEC780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 RRGTLAGDVFSLAIIMQEVVCRSAPYAMLELTPEEVVQRVRSPPPLCRPLVSMDQAPVEC780
Qy 781 ILLMKQCWAEQPELRPSMDHTFDLFKNINKGRKTNIIDSMLRMLEQYSSNLEDLIRERTE840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 ILLMKQCWAEQPELRPSMDHTFDLFKNINKGRKTNIIDSMLRMLEQYSSNLEDLIRERTE840
Qy 841 ELELEKQKTDRLLTQMLPPSVAEALKTGTPVEPEYFEQVTLYFSDIVGFTTISAMSEPIE900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ELELEKQKTDRLLTQMLPPSVAEALKTGTPVEPEYFEQVTLYFSDIVGFTTISAMSEPIE900
Qy 901 VVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAV960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 VVDLLNDLYTLFDAIIGSHDVYKVETIGDAYMVASGLPQRNGQRHAAEIANMSLDILSAV960
Qy 961 GTFRMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHV 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GTFRMRHMPEVPVRIRIGLHSGPCVAGVVGLTMPRYCLFGDTVNTASRMESTGLPYRIHV 1020
Qy 1021 NLSTVGILRALDSGYQVELRGRTELKGKGAEDTFWLVGRRGFNKPIPKPPDLQPGSSNHG 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 NLSTVGILRALDSGYQVELRGRTELKGKGAEDTFWLVGRRGFNKPIPKPPDLQPGSSNHG 1080
Qy 1081 ISLQEIPPERRRKLEKARPGQFS 1103
|||||||||||||||||||||||
Db 1081 ISLQEIPPERRRKLEKARPGQFS 1103
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A, E and G are applicable. At the time of invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Acland et al., wherein Acland teaches introducing into human retinal cells an rAAV vector comprising a polynucleotide that comprises a photoreceptor promoter operably linked to a nucleic acid segment that encodes a retinal-specific human guanylate cyclase polypeptide with the teachings of Hildinger, wherein Hildinger teaches an rAAV vector comprising a rhodopsin kinase promoter for photoreceptor-directed gene expression with the teachings of Eliasof et al, wherein Eliasof teaches a retinal-specific human guanylate cyclase polypeptide with 100% sequence identity to claimed SEQ ID NO: 1, with a reasonable expectation of arriving at the claimed invention.
A person of skill in the art would have been motivated to modify the method of Acland in order to determine the efficacy of the retinal-specific human guanylate cyclase polypeptide taught by Eliasof in producing a biologically-active human retGC1 polypeptide in the retinal cells of a human. A reasonable expectation of success is present because Acland achieved an rAAV nearly the same as that claimed and the relevant expression in vivo. The only difference is the nucleic acid sequence encoding human guanylate cyclase polypeptide. Thus, there is every expectation that the claimed vector and methods could be reached given the combined teachings of Acland, Hildinger and Eliasof. Moreover, one of ordinary skill in the art would have found it prima facie obvious to substitute the generic rhodopsin kinase promoter of Hildinger et al. for the rhodopsin kinase promoter due to its’ suitability as Young observed no promoter in non-photoreceptor cells (see Young at Pg. 4080, Col. 1).
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
Prior Art Rejection 2
Claim 65 remains rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Acland et al. (PgPub US20040022766A1, Published 2/5/2004; Reference in IDS filed 3/9/3022) in view of Hildinger (PgPub US20070042462A1, Published 2/22/2007; Reference in IDS filed 3/9/3022), Eliasof et al. (WO2004065576A2, Published 8/5/2004; Reference in IDS filed 3/9/3022) and Young et al. (Investigative Ophthalmology & Visual Science September 2003, Vol.44, 4076-4085) as applied to claims 57, 63, 66 -70 and 72-75 and further in view of Wilson et al. (WO1998009657A2, Published 4/23/1998).
The teachings of Acland et al., Hildinger et al., Eliasof et al., Young et al. are relied upon as detailed above. And although Acland teaches expression control sequences operably linked to the promoter includes an SV40 T intron (Pg. 4,para. 38), none of the aforementioned references teach an SV40 SD-SA sequence(as in claim 65).
Before the effective filing date of the claimed invention, Wilson teaches use of a recombinant adeno-associated virus (rAAV) comprising a heterologous gene operably linked to sequences which control expression thereof in a cell for the manufacture of a medicament. In one embodiment, Wilson teaches the sequence is an intron with functional splice donor and acceptor sites (as in claim 64) (Pg. 13, lines 14-29). A common intron sequence is also derived from SV-40, and is referred to as the SV-40 T intron sequence (Pg. 13, lines 24-25).
When taken with the teachings of Wilson et al., one of ordinary skill in the art would have found it prima facie obvious to select an SV40 T intron, comprising splice donor and acceptor sites, to be operably linked to the rhodopsin kinase promoter of Acland et al., Hildinger et al., Eliasof et al. and Young et al. The skilled artisan would have found it prima facie obvious to do so because Wilson teaches the SV40 T intron operably controls expression in a cell. Thus, for the purposes of regulating expression of SEQ ID NO: 1 in a cell, the combination would have been prima facie obvious.
Prior Art Rejection 3
Claim 71 remains rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Acland et al. (PgPub US20040022766A1, Published 2/5/2004; Reference in IDS filed 3/9/3022) in view of Hildinger (PgPub US20070042462A1, Published 2/22/2007; Reference in IDS filed 3/9/3022), Eliasof et al. (WO2004065576A2, Published 8/5/2004; Reference in IDS filed 3/9/3022) and Young et al. (Investigative Ophthalmology & Visual Science September 2003, Vol.44, 4076-4085) as applied to claims 57, 63, 66 -70 and 72-75 and further in view of Gao et al. (PgPub US20050014262A1, Published 1/20/2005).
The teachings of Acland et al., Hildinger et al. and Eliasof et al. are relied upon as detailed above. However, none of the references teach the composition further comprises a liposome (as in claim 71).
Before the effective filing date of the claimed invention, Gao et al. taught compositions particularly well suited for use in compositions requiring re-administration of rAAV for therapeutic or prophylactic purposes (Pg. 1, para. 4). Gao teaches introduction into the host cell of the vector may be achieved by any means known in the art or as disclosed above, including liposome delivery (as in claim 71) (Pg. 8, para. 82).
When taken with the teachings to Acland et al., Hildinger et al., Eliasof et al. and Young et al., one of ordinary skill in the art would have found it prima facie obvious to use the liposome of Gao et al. to deliver the AAV vector Acland et al., Hildinger et al., Eliasof et al. and Young et al. with a reasonable expectation of success. The skilled artisan would have found it prima facie to do so in order to deliver the AAV vector to the eye of patient having LCA-1.
Thus, the claimed invention would have been prima facie obvious.
Prior Art Rejection 4
Claims 76-77 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Acland et al. (PgPub US20040022766A1, Published 2/5/2004; Reference in IDS filed 3/9/3022,) in view of Hildinger (PgPub US20070042462A1, Published 2/22/2007; Reference in IDS filed 3/9/3022 ), Eliasof et al. (WO2004065576A2, Published 8/5/2004; Reference in IDS filed 3/9/3022 ) and Young et al. (Investigative Ophthalmology & Visual Science September 2003, Vol.44, 4076-4085) as applied to claims 57, 63, 66 -70 and 72-75 and further in view of Wilson et al. (U.S. Patent 6261551B1, Published 7/17/2001).
The teachings of Acland et al., Hildinger et al., Eliasof et al., and Young et al. are relied upon as detailed above. And although (1) Acland teaches the rAAV minigene contains AAV 5′ ITRs and 3′ ITRs located 5′ and 3′ to the heterologous molecule (as in claim 76a and claim 76f) and operably linked expression control sequences, such as promoters and introns that are contiguous with the coding sequences, wherein said vector is administered to the eye of a subject that has Leber congenital amaurosis- 1 (LCA- 1) (Pg. 1, Para. 10, lines 1-10 and Pg. 2, Para. 16, lines 1-7) (as in claim 77) and (2) Young teaches the rhodopsin kinase promoter for photoreceptor-directed gene expression comprising that has 98% sequence identity to SEQ ID NO: 12 (as in claim 76b) and (3) Eliasof teaches SEQ ID NO: 1 (as in claim 76d); None of Acland et al., Hildinger et al., Eliasof et al., and Young et al. teach in a 5' to 3' direction, b) the photoreceptor-specific human rhodopsin kinase promoter comprising SEQ ID NO: 12; c) an SV40 SD-SA sequence; d) the nucleic acid encoding the human guanylate cyclase polypeptide of SEQ ID NO: 1 and e) a polyadenylation site.
Before the effective filing date of the claimed invention, Wilson et al. taught a method for enhancing the efficiency of transduction of a recombinant AAV into a target cell is provided by infecting a target cell with a recombinant AAV comprising a selected transgene under the control of regulatory sequences. Wilson teaches the rAAV comprises AAV ITRs flanking a suitable promoter (as further in claim 76b), SV40 splice donor-splice acceptor (SD/SA) (as in claim 76c), a transgene (as further in claim 76d), and SV40 polyA signal (pA) (as in claim 76e).
When taken with the teachings to Acland et al., Hildinger et al., Eliasof et al. and Young et al., one of ordinary skill in the art would have found it prima facie obvious to arrange the rhodopsin kinase promoter, the SV40 SD-SA, the nucleic acid encoding the human guanylate cyclase polypeptide of SEQ ID NO: 1, and a polyadenylation site in 5’ to 3’ order and flanked by 5’ and 3’ AAV ITRs, respectively, because Wilson this configuration is efficient in transducing a target cell.
Thus, the claimed invention would have been prima facie obvious.
Applicant’s Arguments/Response to Arguments
Applicant argues: None of the cited references describe the claimed promoter of SEQ
ID NO: 12. Young is cited for reciting a sequence where " For reciting a sequence where "SEQ ID NO: 12 is 98% identical to nucleotides 1793-2087 (i.e. a subsequence) of the human Rk gene". See Final Office Action p. 6. Furthermore, although Young mentions a rhodopsin kinase promoter, the promoter of Young differs in that it is half the size of the claimed promoter. Thus, Young does not describe a photoreceptor-specific human rhodopsin kinase promoter comprising SEQ ID NO: 12.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. As noted above, with respect to SEQ ID NO: 12, the specification does not teach a functional difference between a sequence that is 98% or a sequence that is 100% identical. Moreover, the argument that “the promoter of Young differs in that it is half the size of the claimed promoter..” is not found persuasive. At the outset, Young teaches a number of promoters with varying sizes (e.g. .11 kb promoter and 2 kb promoter). Moreover, it must be noted that there is no size requirement for the promoter in the claims. All that is required is that the promoter of the art comprise SEQ ID NO: 12, which Young’s 2 kb promoter does.
Applicant argues: Acland, Hildinger, and Eliasof do not remedy this deficiency, alone or in combination with Young. Regarding Hildinger, while this reference provides a promoter sequence that partially overlaps with the claimed human rhodopsin kinase promoter, Hildinger does not disclose a promoter having of the present claims, nor does it provide a person of skill in the art any reason for arriving at such claimed promoter. Acland and Eliasof are silent as to human rhodopsin kinase promoters entirely. Acland describes promoters such as the rod opsin promoter, the red-green opsin promoter, the blue opsin promoter, the inter photoreceptor binding protein(IRBP promoter) and the cGMP-β-phosphodiesterase promoter.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Note that none of Acland, Hildinger, and Eliasof was cited for teaching a promoter sequence.
Applicant argues: There is no rationale to combine prior art elements according to known elements to yield predictable results. The "obvious to try" rationale requires that there is a finite number of identified, predictable solutions with a reasonable expectation of success. There was further no teaching, suggestion or motivation to lead one of ordinary skill in the art to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. At the time of invention, it would have been prima facie obvious in order to determine the efficacy of the retinal-specific human guanylate cyclase polypeptide taught by Eliasof in producing a biologically-active human retGC1 polypeptide in the retinal cells of a human. A reasonable expectation of success is present because Acland achieved an rAAV nearly the same as that claimed and the relevant expression in vivo. Moreover, one of ordinary skill in the art would have found it prima facie obvious to substitute the generic rhodopsin kinase promoter of Hildinger et al. for the rhodopsin kinase promoter due to its’ suitability as Young observed no promoter in non-photoreceptor cells (see Young at Pg. 4080, Col. 1).
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
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 57, 63 and 65 -77 remain and new claims 78-79 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. U.S. Patent 9816108. Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons expressed in the previous office action.
Instant claim 57 is drawn a recombinant adeno-associated viral (rAAV) vector comprising a photoreceptor-specific human rhodopsin kinase promoter comprising SEQ ID NO: 12 operably linked to a nucleic acid encoding a human guanylate cyclase polypeptide comprising SEQ ID NO: 1. Claim 77 is drawn to a method of treating a subject with Leber congenital amaurosis-1 (LCAl), comprising administering the rAAV vector of claim 76 to an eye of the subject. Claim 76 is drawn to vector according to claim 57, comprising, in a 5' to 3' direction, a) a first inverted terminal repeat; b) the photoreceptor-specific human rhodopsin kinase promoter comprising SEQ ID NO: 12; c) an SV40 SD-SA sequence; d) the nucleic acid encoding the human guanylate cyclase polypeptide of SEQ ID NO: 1; e) a polyadenylation site; and f) a second inverted terminal repeat.
Claim 1 of U.S Patent ‘108 is drawn to a method for treating a human suffering from Leber congenital amaurosis-1 (LCA1), wherein the human has a defect, deficiency, or total absence of biologically-active retGC1 protein in at least one eye, as compared to the level of biologically-active retGC1 protein in an eye of a normal, untreated human, the method comprising: introducing into at least a first population of human photoreceptor cells an rAAV vector comprising at least a first polynucleotide that comprises a photoreceptor-specific human rhodopsin kinase promoter, operably linked to at least a first nucleic acid segment that encodes a first biologically-active, retinal-specific human guanylate cyclase polypeptide that comprises a first contiguous amino acid sequence region that is at least about 95% identical to a first sequence region of at least 80-contiguous-amino-acid sequence from SEQ ID NO:1, wherein the rAAV vector is contained within a AAV5 or AAV8 particle and wherein the rAAV vector is administered subretinally into at least a first site within one or both eyes of the human in an amount effective to produce a biologically-active human retGCI polypeptide in the one or more photoreceptor cells, such that production of the biologically-active human retGCI polypeptide in the one or more photoreceptor cells rescues and provides sustained restoration of photoreceptor function, thereby treating Leber congenital amaurosis-1 (LCA1).
Claim 1 of U.S. Patent ‘108 generically recites a photoreceptor-specific human rhodopsin kinase promoter, whereas the instant claims recite the photoreceptor-specific human rhodopsin kinase promoter comprises SEQ ID NO: 12. The species ‘SEQ ID NO: 12’ falls within the genus of ‘photoreceptor-specific human rhodopsin kinase promote’ recited in the parent claims. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention was made to select the specific promoter of SEQ ID NO: 12, as set forth in instant claims, to carry out the generic promoter element recited in parent claims.
Applicant’s Arguments/Response to Arguments
Applicant’s arguments: Regarding the double patenting rejection, Applicant argues
in view of the amendment requiring a human rhodopsin kinase promoter of SEQ
ID NO: 12, and the remarks with respect to the previous obviousness rejection, Applicant
respectfully submits that the rejection is moot with respect to the amended claims.
In Response: Applicant’s arguments are not found persuasive, as parent claims are drawn to use of a generic photoreceptor-specific human rhodopsin kinase promoter.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Allowable Subject Matter
Claims 78 -79 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TITILAYO MOLOYE whose telephone number is (571)270-1094. The examiner can normally be reached Working Hours: 5:30 a.m-3:00 p.m M-F. Off first friday of biweek..
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, Peter Paras can be reached on 571- 272-4517. 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.
/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632
Prosecution Insights