DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ response to restriction requirement filed on November 12, 2025 have been received and entered. Claims 1-4, 8-21 and 22 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of claims 1-4, 8-21 (group I) in the reply filed on November 12, 2025 is acknowledged.
Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 12, 2025.
Priority
This application is a Continuation of PCT/CN2022/117383 filed on 09/06/2022, which claims priority from foreign application PCTCN2021116781 filed on 09/06/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/12/2025 and 12/12/2022 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claims 1-4, 8-20 and 21 are under consideration.
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 1-4, 8-17, 19-20 and 21 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.
Regarding claims 1, 16, the phrase " e.g. "within parentheses renders the claim indefinite because it is unclear whether the limitation(s) following the phrase within parentheses are part of the claimed invention. See MPEP § 2173.05(d). Parenthesis are used in claims to delineate an abbreviation of a term that is recited just prior to the parentheses and does not further impart limitations to the claim. However, in this instant, the term “RPE65 is recited prior to the parentheses and term within parentheses is an example of a single of specie of RPE65. Likewise, the term “eg 100% identical to SEQ ID NO: 3” within parentheses renders the claim indefinite because it is unclear whether the limitation(s) following the phrase within parentheses are part of the claimed invention. Therefore, the term within parentheses is not given any patentable weight.
Regarding claim 1, line 2, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear the limitation following such as is polynucleotide sequence of vector genome, AAV or entire virus. Claims 2-4, -21 directly or indirectly depends from the rejected base claim 1. Claim 19 is vague and unclear as recitation of a sequence identity of at least 90% fails to recite a reference sequence. It is unclear sequence identity is relative to the reference sequence of amino acid sequence, nucleotide sequence or something else. The metes and bounds of sequence identity could not be ascertained. Appropriate clarification and/or correction is required.
Claims 20 recite, "- VP1 (SEQ ID NO: 20)-". The limitations intended to be captured by placing the term " SEQ ID NO: 20" within parentheses is not apparent. Parenthesis are used in claims to delineate an abbreviation of a term that is recited just prior to the parentheses and does not further impart limitations to the claim. As such, it is not apparent how the parentheses are to be interpreted or if the term in the parenthesis is intended to be further limiting to the claim are not. For art purposes, the term "- VP1 (SEQ ID NO: 20)-" will be interpreted as a structural limitations of amino acid sequence of SEQ ID NO: 20 as if the parentheses were not present. Amending the claim to remove the parentheses and explicitly reciting that AAV9 VP1 consisting of the amino acid sequence of SEQ ID NO: 9 would be remedial.
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.
Claims 1-4, 8, 12-13 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tian (CN108103096, dated 06/01/2018, IDS) as evidenced by Wang (Molecular Therapy, 2018, 9, 234-246).
Claims are directed to a recombinant adeno-associated virus (rAAV) viral particle comprising an AAV9 serotype capsid and a vector genome encoding an RPE65 (e.g., hRPE65) polypeptide. Dependent claims limit the vector genome comprises: a) a 5' inverted terminal repeat (ITR); b) an RPE65 polynucleotide encoding an RPE65 polypeptide, wherein the RPE65 polynucleotide comprises a polynucleotide sequence of SEQ ID NO: 2 or having a sequence identity of at least 90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.4%, 99.6%, or 99.8% to the polynucleotide sequence of SEQ ID NO: 2; c) a promoter operably linked to and drives the transcription of the RPE65 polynucleotide; d) an optional Kozak sequence upstream of the RPE65 polynucleotide and downstream of the promoter; e) a polyA signal sequence.
Claim interpretation: Recitation of phrases followed by term “such as”, “optional “ or “optionally” are not given any patentable weight.
With respect to claim 1, Tian teaches a viral particle comprising an AAV9 serotype comprising cap gene and a vector encoding an hRPE65 polypeptide (see para. 47 and 92). Regarding claims 2-3, 12-13, Tian teaches that vector genome comprises a 5’AAV3 ITR, an RPE polynucleotide encoding RPE65, a CMV early promoter operably linked to the RPE65 nucleotide, a bGH polyA sequence and an AAV2 3’ITR (see para. 55-59, fig. 1-3). It is noted that Tian teaches hRPE encoded by nucleic acid sequence as set forth in SEQ ID NO: 5 that has 99% sequence identity to SEQ ID NO: 2 (see claim 1, SEQ IDNO: 5) (see sequence search result).
Query Match 99.2%; Score 1589.2; Length 1655;
Best Local Similarity 99.8%;
Matches 1591; Conservative 0; Mismatches 3; Indels 0; Gaps
Qy 6 TATCCAGGTTGAGCATCCTGCTGGTGGTTACAAGAAACTGTTTGAAACTGTGGAGGAACT 65
| || ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 TTTCAGGGTTGAGCATCCTGCTGGTGGTTACAAGAAACTGTTTGAAACTGTGGAGGAACT 121
Qy 66 GTCCTCGCCGCTCACAGCTCATGTAACAGGCAGGATCCCCCTCTGGCTCACCGGCAGTCT 125 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 GTCCTCGCCGCTCACAGCTCATGTAACAGGCAGGATCCCCCTCTGGCTCACCGGCAGTCT 181
Qy 126 CCTTCGATGTGGGCCAGGACTCTTTGAAGTTGGATCTGAGCCATTTTACCACCTGTTTGA 185 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 182 CCTTCGATGTGGGCCAGGACTCTTTGAAGTTGGATCTGAGCCATTTTACCACCTGTTTGA 241
Qy 186 TGGGCAAGCCCTCCTGCACAAGTTTGACTTTAAAGAAGGACATGTCACATACCACAGAAG 245 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 242 TGGGCAAGCCCTCCTGCACAAGTTTGACTTTAAAGAAGGACATGTCACATACCACAGAAG 301
Qy 246 GTTCATCCGCACTGATGCTTACGTACGGGCAATGACTGAGAAAAGGATCGTCATAACAGA 305 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 302 GTTCATCCGCACTGATGCTTACGTACGGGCAATGACTGAGAAAAGGATCGTCATAACAGA 361
Qy 306 ATTTGGCACCTGTGCTTTCCCAGATCCCTGCAAGAATATATTTTCCAGGTTTTTTTCTTA 365 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 362 ATTTGGCACCTGTGCTTTCCCAGATCCCTGCAAGAATATATTTTCCAGGTTTTTTTCTTA 421
Qy 366 CTTTCGAGGAGTAGAGGTTACTGACAATGCCCTTGTTAATGTCTACCCAGTGGGGGAAGA 425 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 422 CTTTCGAGGAGTAGAGGTTACTGACAATGCCCTTGTTAATGTCTACCCAGTGGGGGAAGA 481
Qy 426 TTACTACGCTTGCACAGAGACCAACTTTATTACAAAGATTAATCCAGAGACCTTGGAGAC 485 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 482 TTACTACGCTTGCACAGAGACCAACTTTATTACAAAGATTAATCCAGAGACCTTGGAGAC 541
Qy 486 AATTAAGCAGGTTGATCTTTGCAACTATGTCTCTGTCAATGGGGCCACTGCTCACCCCCA 545 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 542 AATTAAGCAGGTTGATCTTTGCAACTATGTCTCTGTCAATGGGGCCACTGCTCACCCCCA 601
Qy 546 CATTGAAAATGATGGAACCGTTTACAATATTGGTAATTGCTTTGGAAAAAATTTTTCAAT 605 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 602 CATTGAAAATGATGGAACCGTTTACAATATTGGTAATTGCTTTGGAAAAAATTTTTCAAT 661
Qy 606 TGCCTACAACATTGTAAAGATCCCACCACTGCAAGCAGACAAGGAAGATCCAATAAGCAA 665 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 662 TGCCTACAACATTGTAAAGATCCCACCACTGCAAGCAGACAAGGAAGATCCAATAAGCAA 721
Qy 666 GTCAGAGATCGTTGTACAATTCCCCTGCAGTGACCGATTCAAGCCATCTTACGTTCATAG 725 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 722 GTCAGAGATCGTTGTACAATTCCCCTGCAGTGACCGATTCAAGCCATCTTACGTTCATAG 781
Qy 726 TTTTGGTCTGACTCCCAACTATATCGTTTTTGTGGAGACACCAGTCAAAATTAACCTGTT 785 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 782 TTTTGGTCTGACTCCCAACTATATCGTTTTTGTGGAGACACCAGTCAAAATTAACCTGTT 841
Qy 786 CAAGTTCCTTTCTTCATGGAGTCTTTGGGGAGCCAACTACATGGATTGTTTTGAGTCCAA 845 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 842 CAAGTTCCTTTCTTCATGGAGTCTTTGGGGAGCCAACTACATGGATTGTTTTGAGTCCAA 901
Qy 846 TGAAACCATGGGGGTTTGGCTTCATATTGCTGACAAAAAAAGGAAAAAGTACCTCAATAA 905 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 902 TGAAACCATGGGGGTTTGGCTTCATATTGCTGACAAAAAAAGGAAAAAGTACCTCAATAA 961
Qy 906 TAAATACAGAACTTCTCCTTTCAACCTCTTCCATCACATCAACACCTATGAAGACAATGG 965 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 962 TAAATACAGAACTTCTCCTTTCAACCTCTTCCATCACATCAACACCTATGAAGACAATGG 1021
Qy 966 GTTTCTGATTGTGGATCTCTGCTGCTGGAAAGGATTTGAGTTTGTTTATAATTACTTATA 1025 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1022 GTTTCTGATTGTGGATCTCTGCTGCTGGAAAGGATTTGAGTTTGTTTATAATTACTTATA 1081
Qy 1026 TTTAGCCAATTTACGTGAGAACTGGGAAGAGGTGAAAAAAAATGCCAGAAAGGCTCCCCA 1085 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1082 TTTAGCCAATTTACGTGAGAACTGGGAAGAGGTGAAAAAAAATGCCAGAAAGGCTCCCCA 1141
Qy 1086 ACCTGAAGTTAGGAGATATGTACTTCCTTTGAATATTGACAAGGCTGACACAGGCAAGAA 1145 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1142 ACCTGAAGTTAGGAGATATGTACTTCCTTTGAATATTGACAAGGCTGACACAGGCAAGAA 1201
Qy 1146 TTTAGTCACGCTCCCCAATACAACTGCCACTGCAATTCTGTGCAGTGACGAGACTATCTG 1205 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1202 TTTAGTCACGCTCCCCAATACAACTGCCACTGCAATTCTGTGCAGTGACGAGACTATCTG 1261
Qy 1206 GCTGGAGCCTGAAGTTCTCTTTTCAGGGCCTCGTCAAGCATTTGAGTTTCCTCAAATCAA 1265 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1262 GCTGGAGCCTGAAGTTCTCTTTTCAGGGCCTCGTCAAGCATTTGAGTTTCCTCAAATCAA 1321
Qy 1266 TTACCAGAAGTATTGTGGGAAACCTTACACATATGCGTATGGACTTGGCTTGAATCACTT 1325 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1322 TTACCAGAAGTATTGTGGGAAACCTTACACATATGCGTATGGACTTGGCTTGAATCACTT 1381
Qy 1326 TGTTCCAGATAGGCTCTGTAAGCTGAATGTCAAAACTAAAGAAACTTGGGTTTGGCAAGA 1385 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1382 TGTTCCAGATAGGCTCTGTAAGCTGAATGTCAAAACTAAAGAAACTTGGGTTTGGCAAGA 1441
Qy 1386 GCCTGATTCATACCCATCAGAACCCATCTTTGTTTCTCACCCAGATGCCTTGGAAGAAGA 1445 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1442 GCCTGATTCATACCCATCAGAACCCATCTTTGTTTCTCACCCAGATGCCTTGGAAGAAGA 1501
Qy 1446 TGATGGTGTAGTTCTGAGTGTGGTGGTGAGCCCAGGAGCAGGACAAAAGCCTGCTTATCT 1505 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1502 TGATGGTGTAGTTCTGAGTGTGGTGGTGAGCCCAGGAGCAGGACAAAAGCCTGCTTATCT 1561
Qy 1506 CCTGATTCTGAATGCCAAGGACTTAAGTGAAGTTGCCCGGGCTGAAGTGGAGATTAACAT 1565 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1562 CCTGATTCTGAATGCCAAGGACTTAAGTGAAGTTGCCCGGGCTGAAGTGGAGATTAACAT 1621
Qy 1566 CCCTGTCACCTTTCATGGACTGTTCAAAAAATCT 1599
||||||||||||||||||||||||||||||||||
Db 1622 CCCTGTCACCTTTCATGGACTGTTCAAAAAATCT 1655
With respect to claims 4, 8, Tian teaches that the promoter is a ubiquitous promoter such as a CMV enhancer and/or promoter (see para. 51, fig. 1-2).
Regarding claim 19, Tian teaches that the AAV9 serotype comprises all the cap gene that would inherently include AAV9 VP1, VP2 and VP3 (para. 47) as evident form the teaching of Wang (see VP1, VP2, and VP3 at 1:1:10 ratio in wild type AAV9 see 235, col. 1, para. 2).
Accordingly, Tian as evidenced by Wang anticipates claims 1-4, 8, 12-13 and 19.
Claims 1-4, 8-9, 12-13, 15, 19 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun (CN111118017, dated 08/05/2020, IDS).
Claims are directed to a recombinant adeno-associated virus (rAAV) viral particle comprising an AAV9 serotype capsid and a vector genome encoding an RPE65 (e.g., hRPE65) polypeptide. Dependent claims limit the vector genome comprises: a) a 5' inverted terminal repeat (ITR); b) an RPE65 polynucleotide encoding an RPE65 polypeptide, wherein the RPE65 polynucleotide comprises a polynucleotide sequence of SEQ ID NO: 2 or having a sequence identity of at least 90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.4%, 99.6%, or 99.8% to the polynucleotide sequence of SEQ ID NO: 2; c) a promoter operably linked to and drives the transcription of the RPE65 polynucleotide; d) an optional Kozak sequence upstream of the RPE65 polynucleotide and downstream of the promoter; e) a polyA signal sequence.
Claim interpretation: Recitation of phrases followed by term “such as”, “optional “ or “optionally” are not given any patentable weight.
With respect to claim 1, Sun teaches a rAAV particle comprising an AAV9 serotype comprising cap gene and a vector encoding an hRPE65 polypeptide (see para. 37, 39, 130 and 90, 92, claim 5).
Regarding claim 2, 4, Sun teaches vector comprises a left ITR sequence; a ubiquitous promoter, an optimized human RPE65 encoded sequence; a human growth hormone (hGH polyA); and a right ITR sequence (see para. 42-47) and wherein the coding sequence of human RPE65 comprises SEQ ID NO: 2 that has 97% sequence identity to SEQ ID NO: 2 (see below).
Query Match 97.4%; Score 1560; DB 1; Length 1560;
Best Local Similarity 100.0%; Matches 1560; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGTCTATCCAGGTTGAGCATCCTGCTGGTGGTTACAAGAAACTGTTTGAAACTGTGGAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGTCTATCCAGGTTGAGCATCCTGCTGGTGGTTACAAGAAACTGTTTGAAACTGTGGAG 60
Qy 61 GAACTGTCCTCGCCGCTCACAGCTCATGTAACAGGCAGGATCCCCCTCTGGCTCACCGGC 120 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GAACTGTCCTCGCCGCTCACAGCTCATGTAACAGGCAGGATCCCCCTCTGGCTCACCGGC 120
Qy 121 AGTCTCCTTCGATGTGGGCCAGGACTCTTTGAAGTTGGATCTGAGCCATTTTACCACCTG 180 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AGTCTCCTTCGATGTGGGCCAGGACTCTTTGAAGTTGGATCTGAGCCATTTTACCACCTG 180
Qy 181 TTTGATGGGCAAGCCCTCCTGCACAAGTTTGACTTTAAAGAAGGACATGTCACATACCAC 240 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TTTGATGGGCAAGCCCTCCTGCACAAGTTTGACTTTAAAGAAGGACATGTCACATACCAC 240
Qy 241 AGAAGGTTCATCCGCACTGATGCTTACGTACGGGCAATGACTGAGAAAAGGATCGTCATA 300 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AGAAGGTTCATCCGCACTGATGCTTACGTACGGGCAATGACTGAGAAAAGGATCGTCATA 300
Qy 301 ACAGAATTTGGCACCTGTGCTTTCCCAGATCCCTGCAAGAATATATTTTCCAGGTTTTTT 360 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ACAGAATTTGGCACCTGTGCTTTCCCAGATCCCTGCAAGAATATATTTTCCAGGTTTTTT 360
Qy 361 TCTTACTTTCGAGGAGTAGAGGTTACTGACAATGCCCTTGTTAATGTCTACCCAGTGGGG 420 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 TCTTACTTTCGAGGAGTAGAGGTTACTGACAATGCCCTTGTTAATGTCTACCCAGTGGGG 420
Qy 421 GAAGATTACTACGCTTGCACAGAGACCAACTTTATTACAAAGATTAATCCAGAGACCTTG 480 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GAAGATTACTACGCTTGCACAGAGACCAACTTTATTACAAAGATTAATCCAGAGACCTTG 480
Qy 481 GAGACAATTAAGCAGGTTGATCTTTGCAACTATGTCTCTGTCAATGGGGCCACTGCTCAC 540 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GAGACAATTAAGCAGGTTGATCTTTGCAACTATGTCTCTGTCAATGGGGCCACTGCTCAC 540
Qy 541 CCCCACATTGAAAATGATGGAACCGTTTACAATATTGGTAATTGCTTTGGAAAAAATTTT 600 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 CCCCACATTGAAAATGATGGAACCGTTTACAATATTGGTAATTGCTTTGGAAAAAATTTT 600
Qy 601 TCAATTGCCTACAACATTGTAAAGATCCCACCACTGCAAGCAGACAAGGAAGATCCAATA 660 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 TCAATTGCCTACAACATTGTAAAGATCCCACCACTGCAAGCAGACAAGGAAGATCCAATA 660
Qy 661 AGCAAGTCAGAGATCGTTGTACAATTCCCCTGCAGTGACCGATTCAAGCCATCTTACGTT 720 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AGCAAGTCAGAGATCGTTGTACAATTCCCCTGCAGTGACCGATTCAAGCCATCTTACGTT 720
Qy 721 CATAGTTTTGGTCTGACTCCCAACTATATCGTTTTTGTGGAGACACCAGTCAAAATTAAC 780 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 CATAGTTTTGGTCTGACTCCCAACTATATCGTTTTTGTGGAGACACCAGTCAAAATTAAC 780
Qy 781 CTGTTCAAGTTCCTTTCTTCATGGAGTCTTTGGGGAGCCAACTACATGGATTGTTTTGAG 840 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 CTGTTCAAGTTCCTTTCTTCATGGAGTCTTTGGGGAGCCAACTACATGGATTGTTTTGAG 840
Qy 841 TCCAATGAAACCATGGGGGTTTGGCTTCATATTGCTGACAAAAAAAGGAAAAAGTACCTC 900 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 TCCAATGAAACCATGGGGGTTTGGCTTCATATTGCTGACAAAAAAAGGAAAAAGTACCTC 900
Qy 901 AATAATAAATACAGAACTTCTCCTTTCAACCTCTTCCATCACATCAACACCTATGAAGAC 960 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 AATAATAAATACAGAACTTCTCCTTTCAACCTCTTCCATCACATCAACACCTATGAAGAC 960
Qy 961 AATGGGTTTCTGATTGTGGATCTCTGCTGCTGGAAAGGATTTGAGTTTGTTTATAATTAC 1020 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 AATGGGTTTCTGATTGTGGATCTCTGCTGCTGGAAAGGATTTGAGTTTGTTTATAATTAC 1020
Qy 1021 TTATATTTAGCCAATTTACGTGAGAACTGGGAAGAGGTGAAAAAAAATGCCAGAAAGGCT 1080 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 TTATATTTAGCCAATTTACGTGAGAACTGGGAAGAGGTGAAAAAAAATGCCAGAAAGGCT 1080
Qy 1081 CCCCAACCTGAAGTTAGGAGATATGTACTTCCTTTGAATATTGACAAGGCTGACACAGGC 1140 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 CCCCAACCTGAAGTTAGGAGATATGTACTTCCTTTGAATATTGACAAGGCTGACACAGGC 1140
Qy 1141 AAGAATTTAGTCACGCTCCCCAATACAACTGCCACTGCAATTCTGTGCAGTGACGAGACT 1200 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 AAGAATTTAGTCACGCTCCCCAATACAACTGCCACTGCAATTCTGTGCAGTGACGAGACT 1200
Qy 1201 ATCTGGCTGGAGCCTGAAGTTCTCTTTTCAGGGCCTCGTCAAGCATTTGAGTTTCCTCAA 1260 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 ATCTGGCTGGAGCCTGAAGTTCTCTTTTCAGGGCCTCGTCAAGCATTTGAGTTTCCTCAA 1260
Qy 1261 ATCAATTACCAGAAGTATTGTGGGAAACCTTACACATATGCGTATGGACTTGGCTTGAAT 1320 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 ATCAATTACCAGAAGTATTGTGGGAAACCTTACACATATGCGTATGGACTTGGCTTGAAT 1320
Qy 1321 CACTTTGTTCCAGATAGGCTCTGTAAGCTGAATGTCAAAACTAAAGAAACTTGGGTTTGG 1380 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 CACTTTGTTCCAGATAGGCTCTGTAAGCTGAATGTCAAAACTAAAGAAACTTGGGTTTGG 1380
Qy 1381 CAAGAGCCTGATTCATACCCATCAGAACCCATCTTTGTTTCTCACCCAGATGCCTTGGAA 1440 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 CAAGAGCCTGATTCATACCCATCAGAACCCATCTTTGTTTCTCACCCAGATGCCTTGGAA 1440
Qy 1441 GAAGATGATGGTGTAGTTCTGAGTGTGGTGGTGAGCCCAGGAGCAGGACAAAAGCCTGCT 1500 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GAAGATGATGGTGTAGTTCTGAGTGTGGTGGTGAGCCCAGGAGCAGGACAAAAGCCTGCT 1500
Qy 1501 TATCTCCTGATTCTGAATGCCAAGGACTTAAGTGAAGTTGCCCGGGCTGAAGTGGAGATT 1560 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 TATCTCCTGATTCTGAATGCCAAGGACTTAAGTGAAGTTGCCCGGGCTGAAGTGGAGATT 1560
Regarding claim 3, Sun teaches SEQ ID NO: 4 that contains nt 1-141 that has 100% sequence identity to SEQ ID NO: 7 and nucleotides 4015 to 4155 that has 100% sequence identity to SEQ ID NO: 8 (see para. 43).
With respect to claims 4, 8-9, Sun teaches the promoter is a CAG promoter (see para. 139).
With respect to claims 12-13, Sun teaches that polyA signal sequence is human GH poly sequence (see para. 29, 46).
With respect to claim 15, Sun teaches that vector genome comprises a kozak sequence from nucleotides 951 to 956 of SEQ ID NO: 4 that has 100% sequence identity to SEQ ID NO: 6 (see para. 143 and 183 and sequence search below).
Query Match 100.0%; Score 6; DB 1; Length 6752;
Best Local Similarity 100.0%;
Matches 6; Conservative 0; Mismatches 0; Indels 0; Gaps
Qy 1 GCCACC 6
||||||
Db 951 GCCACC 956
Regarding claim 21, Sun teaches a pharmaceutical composition comprising a rAAV particle comprising an AAV9 serotype complete cap gene and a vector encoding an hRPE65 polypeptide (see para. 37, 39, 130 and 90, 92, claim 5) and an excipient (see para. 149-152).
Accordingly, Sun anticipates claims 1-4, 8-9, 12-13, 15, 19 and 21.
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.
Claims 1-4, 8-15, 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS). Zhang et al (CN109402244, dated 06/27/2019), Tang et al (US US20090215178, 8/27/2009) and Wang (Molecular Therapy, 2018, 9, 234-246).
Claims are directed to a recombinant adeno-associated virus (rAAV) viral particle comprising an AAV9 serotype capsid and a vector genome encoding an RPE65 (e.g., hRPE65) polypeptide. Dependent claims limit the vector genome comprises: a) a 5' inverted terminal repeat (ITR); b) an RPE65 polynucleotide encoding an RPE65 polypeptide, wherein the RPE65 polynucleotide comprises a polynucleotide sequence of SEQ ID NO: 2 or having a sequence identity of at least 90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.4%, 99.6%, or 99.8% to the polynucleotide sequence of SEQ ID NO: 2; c) a promoter operably linked to and drives the transcription of the RPE65 polynucleotide; d) an optional Kozak sequence upstream of the RPE65 polynucleotide and downstream of the promoter; e) a polyA signal sequence.
Claim interpretation: Recitation of phrases followed by term “such as”, “optional “ or “optionally” are not given any patentable weight.
The teaching of Sun and Tian have been described above and relied in same manner here. While combination of references teach vector genome from 5' ITR to 3' ITR included a human RPE65 10 coding sequence that is at least 99% sequence identity to SEQ ID NO: 2 encoding human RPE65 polypeptide, a CAG promoter operably linked to the human RPE65 coding sequence, a bGH polyA sequence downstream of the human RPE65 coding sequence, flanked by a 5' ITR (SEQ ID NO: 7) and a 3' ITR (SEQ ID NO: 8), which are derived from AAV2, but differs from claimed invention by not disclosing use of CAG ubiquitous promoter as set forth in SEQ ID NO: 4, hGH poly sequence as set forth in SEQ ID NO: 5 and use of a Kozak sequence upstream of and immediately 5' to the human RPE65 coding sequence.
Zhang cure the deficiency by providing requisite sequence of CAG promoter as set forth in nt 801 to 2472 of SEQ ID NO: 2 that has 100% sequence identity to SEQ ID NO: 4 (see SEQ ID NO: 2, claim 5 of ‘244), while Tang teaches SEQ ID NO: 30 that has 100% sequence identity to hGH polyA (see example 3, SEQ ID NO: 30). The combination of references differs from claimed invention by not disclosing use of a Kozak sequence upstream of and immediately 5' to the human RPE65 coding sequence.
Prior to instant invention, Wang teaches AAV capsid consists of 60 copies of viral protein (VP) subunits, with VP1, VP2, and VP3 at 1:1:10 ratio (see 235, col. 1, para. 2). Wang teaches Kozak sequence (GCCACC) is added upstream of the start codon sequence of coding sequence to enhance gene expression (see page 242, col. 2, para. 2).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the AAV comprising AAV9 capsid and vector genome encoding hRPE65 under the control of a CAG promoter and hGH polyA as discussed in Tian and Sun with the CAG and hGH sequences disclosed in Zhang and Tang respectively, as instantly claimed, with a reasonable expectation of success, before the effective filing date of instant application. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because both Sun and Tian contemplated using combination of CAG promoter and hGH polyA together function well. Other limitation of incorporating Kozak sequence (GCCACC) upstream of the start codon sequence of coding sequence would be obvious modification using known method in a given field as per the teaching of Wang for efficient gene expression. One of skill in the art would have been expected to have a reasonable expectation of success in using the claimed sequence of CAG and hGH polyA sequence because the art teaches the successful use of these promoter and polyA sequences for gene expression. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS). Zhang et al (CN109402244, dated 06/27/2019), Tang et al (US US2009215178, 8/27/2009), Wang (Molecular Therapy, 2018, 9, 234-246) as applied above and further in view of Banfi (US10369231, 6/8/2019) and Zhou et al (CN106636409A, 10/5/2017).
The teaching of Sun, Tian , Zhang, Tang and Wang have been described above and relied in same manner here. While combination of references teach vector genome from 5' ITR to 3' ITR included a human RPE65 10 coding sequence that is at least 99% sequence identity to SEQ ID NO: 2 encoding human RPE65 polypeptide, a CAG promoter operably linked to the human RPE65 coding sequence, a bGH polyA sequence downstream of the human RPE65 coding sequence, flanked by a 5' ITR (SEQ ID NO: 7) and a 3' ITR (SEQ ID NO: 8), which are derived from AAV2, but differs from claimed invention by not disclosing RPE65 10 coding sequence of SEQ ID NO: 2 .
Before the effective filing date of instant invention, Banfi teaches coding sequence of human RPE65 as set forth in SEQ ID NO 37 that has 100% sequence identity to SEQ ID NO: 2, while Zhou teaches connection sequence comprises a box sequence including TTAT sequence (see claim 2).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the AAV comprising AAV9 capsid and vector genome encoding human RPE65 as disclosed in Sun/Tian with structurally and functionally equivalent human RPE65 coding sequence as disclosed in Banfi, as instantly claimed, with a reasonable expectation of success, before the effective filing date of instant application. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art explicitly reported using human RPE65 coding sequence for therapeutic purpose in human subject. Other limitation of vector genome having a sequence that is at least 99% to SEQ ID NO: 1 would be obvious modification particularly since combination of prior art teaches the same 5’ITR of SEQ ID NO:7, a CAG promoter of SEQ ID NO:4, a linker box sequence, Kozak sequence, a hRPE sequence as set forth in SEQ ID NO: 2, a hGH polyA of SEQ ID NO: 5 and a3’polyA ITR of SEQ ID NO: 8 similar to one recited in claim 16 and 17 and therefore resulting combined sequence would be at least 99% of SEQ ID NO:1. Absent any unexpected superior results, one of skill in the art would have been expected to have a reasonable expectation of success in using the claimed sequence of CAG, hGH polyA and human RPE65 within the AAV construct because prior art teaches the successful use of these promoter, coding and polyA sequences within AAV vector for enhanced gene expression. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS) as evidenced by Wang (Molecular Therapy, 2018, 9, 234-246) as applied above for claim 1 and further in view of Kay (USPGPUB 20070243526).
The teaching of Sun, Tian, and Wang have been described above and relied in same manner here. While combination of references teaches a rAAV virus particle comprising AAV9 serotype comprising all the cap gene that inherently includes VP1, VP2 and VP3 as evidenced by Wang but differs from claimed invention by not disclosing AAV9 serotype capsid comprises AAV9 VP1 as set forth in SEQ ID NO: 9.
Kay provides the requisite sequence of AAV9 VP1 as set forth in SEQ ID NO: 5 that has 100% sequence identity to SEQ ID NO: 9 (see sequence search result).
Query Match 100.0%; Score 3986; Length 736;
Best Local Similarity 100.0%;
Matches 736; Conservative 0; Mismatches 0; Indels 0; Gaps
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480
Qy 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540
Qy 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600
Qy 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660
Qy 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720
Qy 721 YSEPRPIGTRYLTRNL 736
||||||||||||||||
Db 721 YSEPRPIGTRYLTRNL 736
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to use known AAV9 VP1 as disclosed by Kay in the viral particle disclosed in Sun/Tian, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of skill in the art would have been expected to have a reasonable expectation of success because prior art teaches the relevant sequence of AAV9 VP1. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claim Objections
Claim 18 is 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.
Conclusion
No claims allowed.
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/ANOOP K SINGH/Primary Examiner, Art Unit 1632