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 .
Application Status
This action is written in response to applicant’s correspondence received 08/29/2025. Claims 1 and 3-21 are currently pending. Claims 3 and 9-20 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1, 4-8 and 21 are examined herein. The restriction requirement mailed 03/31/2025 is still deemed proper. Applicant elected the invention of Group I, a construct comprising a nucleic acid sequence encoding an ANRIL RNA (claims 1-2 and 4-8), without traverse in the reply filed 04/29/2025.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance because, upon further search and consideration, a new rejection is found applicable. Please see below.
Drawings
The drawings are objected to because the most recent set of drawings contain at least one color drawings. Applicant needs to file an updated version of their drawings that do not contain color, since
the specification does not indicate drawings were submitted and
there is no Petition for entry of color drawings.
NOTE: the most recent drawings of record control. The most recent set do contain at least one color drawing.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4-5 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang (Yang et al. LncRNA ANRIL promotes multiple myeloma progression and bortezomib resistance by EZH2-mediated epigenetically silencing of PTEN. Neoplasma 2021; 68(4): 788–797.), as evidenced by GenBank Accession No. DQ485453.1 (of record) and System Biosciences (pCDH cDNA Cloning and Expression Lentivectors. User Manual. Version 8-05262020. Public availability date: 05/26/2020.)
Regarding claim 1, Yang teaches a construct comprising a nucleic acid sequence encoding an ANRIL RNA (p. 289 §Plasmid constructs, lentivirus packaging, and infection):
Forced expression of ANRIL was achieved by cloning the full length of ANRIL into the pCDH lentivirus vector (System Biosciences #CD510B-1).
While Yang does not explicitly teach that a heterologous promoter is operably connected to the ANRIL coding sequence, System Biosciences evidences that the vector cited by Yang, #CD510B-1, comprised a heterologous promoter:
PNG
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199
700
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Greyscale
PNG
media_image2.png
71
665
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Greyscale
Additionally, while Yang does not explicitly teach that the sequence of the full length ANRIL is SEQ ID NO: 1, GenBank Accession No. DQ485453.1 evidences that the full length ANRIL transcript, as taught by Yang, comprises a sequence with 99.9% identity to the full length of SEQ ID NO: 1 when limited to a local alignment:
RESULT 1
DQ485453
LOCUS DQ485453 3834 bp RNA linear PRI 18-APR-2007
DEFINITION Homo sapiens antisense noncoding RNA in the INK4 locus large
transcript, complete sequence.
ACCESSION DQ485453
VERSION DQ485453.1
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1 to 3834)
AUTHORS Pasmant,E., Laurendeau,I., Heron,D., Vidaud,M., Vidaud,D. and
Bieche,I.
TITLE Characterization of a Germ-Line Deletion, Including the Entire
INK4/ARF Locus, in a Melanoma-Neural System Tumor Family:
Identification of ANRIL, an Antisense Noncoding RNA Whose
Expression Coclusters with ARF
JOURNAL Cancer Res. 67 (8), 3963-3969 (2007)
PUBMED 17440112
REFERENCE 2 (bases 1 to 3834)
AUTHORS Pasmant,E., Laurendeau,I., Heron,D., Vidaud,M., Vidaud,D. and
Bieche,I.
TITLE Direct Submission
JOURNAL Submitted (07-APR-2006) Laboratoire de Genetique Moleculaire -
INSERM U745, Faculte des Sciences Pharmaceutiques et Biologiques,
Universite Paris V, 4 Avenue de l Observatoire, Paris F-75006,
France
FEATURES Location/Qualifiers
source 1..3834
/organism="Homo sapiens"
/mol_type="transcribed RNA"
/db_xref="taxon:9606"
/chromosome="9"
/map="9p21"
misc_RNA 1..3834
/product="antisense noncoding RNA in the INK4 locus large
transcript"
/note="ANRIL large transcript; contains 19 exons
Query Match 99.6%; Score 3439.4; Length 3834;
Best Local Similarity 99.9%;
Matches 3451; Conservative 0; Mismatches 1; Indels 1; Gaps 1;
Regarding claim 4, Yang further teaches wherein the promoter comprises a CMV IE promoter (see above).
Regarding claim 5, Yang further teaches a lentiviral vector comprising the construct of claim 1 (see above).
Regarding claim 8, Yang teaches a pharmaceutical composition (i.e., cells for in vivo experimentation) comprising the construct and a pharmaceutical carrier:
These results indicated that ANRIL overexpression promoted the proliferation of MM cells in vitro. In order to verify this in vivo, RPMI-8226 cells transduced with ANRIL expression lentiviral or EV control were injected into nude mice and assayed for tumor xenograft growth. We found that enforced ANRIL expression dramatically promoted the growth of RPMI-8226 xenografts in nude mice (Figure 2E).
Please note: it is assumed, absent evidence to the contrary, that a composition suitable for in vivo administration to a subject would necessarily be pharmaceutically acceptable.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 6 and 7 are rejected under 35 U.S.C. 103 as being obvious over Yang, as applied to claims 1, 4-5 and 8, in view of Sanchez (The Long Non-Coding RNA ANRIL in Cancers. Cancers (Basel). 2023 Aug 17;15(16):4160.) and VandenDriessche (“Efficacy and safety of adeno‐associated viral vectors based on serotype 8 and 9 vs. lentiviral vectors for hemophilia B gene therapy”. Journal of Thrombosis and Haemostasis, Volume 5, Issue 1, 2007, Pages 16-24.), as evidenced by NCBI Reference Sequence NR_003529.4 (published 06/06/2023).
Yang, as evidenced by GenBank Accession No. DQ485453.1 and System Biosciences, teaches the construct and viral vector comprising it of claims 1 and 5, from which claims 6 and 7 depend.
Yang does not teach wherein the viral vector is an AAV9.
Sanchez teaches that ANRIL isoform 9, a.k.a. NR_003529, is overexpressed in the context of cardiovascular disease (CVD) (p. 7/32):
the ANRIL isoforms 9 (ENTS0000428597.6 or NR_003529) and 13 (ENTS00000584351.5 or DQ485454) have been recognized as regulators of gene expression with antagonistic roles. This duality in their functions has been observed in human endothelial cell lines in the context of CVD. When the isoform 9 is overexpressed, it leads to the down-regulation of the EZR and CXCL11 genes, as well as the up-regulation of TMEM106B. Conversely, overexpression of the isoform 13 has the opposite effect on these genes. These antagonistic
activities are also evident at the cellular level of physiological processes. The expression of the isoform 9 appears to promote transmigration and cellular adhesion, while the isoform 13 elicits contrasting effects
As evidenced by NR_003529, isoform 9 comprises a sequence with 100% identity to SEQ ID NO: 1:
RESULT 1
NR_003529_4
Query Match 100.0%; Score 3453; DB 1; Length 3453;
Best Local Similarity 100.0%;
Matches 3453; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AGCTACATCCGTCACCTGACACGGCCCTACCAGGAACAGCCGCGCTCCCGCGGATTCTGG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AGCTACATCCGTCACCTGACACGGCCCTACCAGGAACAGCCGCGCTCCCGCGGATTCTGG 60
Qy 61 TGCTGCTCGCGTCCCCGCTCCCCTATTCCCCTTATTTTATTCCTGGCTCCCCTCGTCGAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TGCTGCTCGCGTCCCCGCTCCCCTATTCCCCTTATTTTATTCCTGGCTCCCCTCGTCGAA 120
Qy 121 AGTCTTCCATTCTTCAAACTAGATTATTTAAAAATGAAAAAGGAAGAAAGGAAAGCGAGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AGTCTTCCATTCTTCAAACTAGATTATTTAAAAATGAAAAAGGAAGAAAGGAAAGCGAGG 180
Qy 181 TCATCTCATTGCTCTATCCGCCAATCAGGAGGCTGAATGTCAGTTTTGAACTAAAAGCCG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TCATCTCATTGCTCTATCCGCCAATCAGGAGGCTGAATGTCAGTTTTGAACTAAAAGCCG 240
Qy 241 CTCCGCTCCTCTTCTAGATTTGGAAAACAAGCGAAATTAAACTAAACCGCTGCACGCCTC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CTCCGCTCCTCTTCTAGATTTGGAAAACAAGCGAAATTAAACTAAACCGCTGCACGCCTC 300
Qy 301 TGACGCGACATCTGGACACGGCGCGGCGCTGGCGCTGCCGGAGCTGTCGACCCGGCCTGG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TGACGCGACATCTGGACACGGCGCGGCGCTGGCGCTGCCGGAGCTGTCGACCCGGCCTGG 360
Qy 361 CGCCGGACTAGGACTATTTGCCACGACATTTCAAAGGATTCCAAGAGAGAATATTGGTGT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CGCCGGACTAGGACTATTTGCCACGACATTTCAAAGGATTCCAAGAGAGAATATTGGTGT 420
Qy 421 CCATGCTGTGATGATTCCTCAGCTCCTCTCATCTGATCTCCGTCCTGGCCCCCATGACTT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 CCATGCTGTGATGATTCCTCAGCTCCTCTCATCTGATCTCCGTCCTGGCCCCCATGACTT 480
Qy 481 TCTTTGTGGTAGTTAGGGTGTGGTATGTGCCACTGAGGCCCACACCTATTGCTGCAATTT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TCTTTGTGGTAGTTAGGGTGTGGTATGTGCCACTGAGGCCCACACCTATTGCTGCAATTT 540
Qy 541 ATAGCACTGATCTGTCATCAATACCACTTGCTGTCTTGGATGTGAAGATGATTTTTCCTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 ATAGCACTGATCTGTCATCAATACCACTTGCTGTCTTGGATGTGAAGATGATTTTTCCTG 600
Qy 601 CAGGGATTCCCTCTACAAAATTAAAAACACTGGGCATGTGGAAATAATATTCATGCTTTA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CAGGGATTCCCTCTACAAAATTAAAAACACTGGGCATGTGGAAATAATATTCATGCTTTA 660
Qy 661 AATTGTCTTTTCTCTTCACTACACCAGGGGTCCCCAACCCCTAGGCCACAGACTGTGGCC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AATTGTCTTTTCTCTTCACTACACCAGGGGTCCCCAACCCCTAGGCCACAGACTGTGGCC 720
Qy 721 CTAGTGTAGTGAATAGAAAAGACAATTTAAAGCGTGAATATTATTTCCTCATGCCCAGTG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 CTAGTGTAGTGAATAGAAAAGACAATTTAAAGCGTGAATATTATTTCCTCATGCCCAGTG 780
Qy 781 TTTTTAATTTTGTACTGGTCTGTGGCTTGTTAGAAACCAGGCTGCACAGCAGAAGGTGGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 TTTTTAATTTTGTACTGGTCTGTGGCTTGTTAGAAACCAGGCTGCACAGCAGAAGGTGGG 840
Qy 841 CAGCAGATATTGAGAAACCACAGAAAGAGAGAAGTTAAATAATTTTCCTGTCAAAGACCA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 CAGCAGATATTGAGAAACCACAGAAAGAGAGAAGTTAAATAATTTTCCTGTCAAAGACCA 900
Qy 901 CATCAATGATGAAGCCAGAATTTGAGCTCATGTACTTAACCACTGGACTACCTGCCTGCC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CATCAATGATGAAGCCAGAATTTGAGCTCATGTACTTAACCACTGGACTACCTGCCTGCC 960
Qy 961 CTGTCGAGGAACAGCTAAGTGTCCCTTTTGATGAGAAGAATAAGCCTCATTCTGATTCAA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CTGTCGAGGAACAGCTAAGTGTCCCTTTTGATGAGAAGAATAAGCCTCATTCTGATTCAA 1020
Qy 1021 CAGCAGAGATCAAAGAAAAGACTTCTGTTTTCTGGCCACCAGATATATGTTATCTGTGCT 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 CAGCAGAGATCAAAGAAAAGACTTCTGTTTTCTGGCCACCAGATATATGTTATCTGTGCT 1080
Qy 1081 TAAAGAATTGAAAAACACACATCAAAGGAGAATTTTCTTGGAAAGAGAGGGTTCAAGCAT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 TAAAGAATTGAAAAACACACATCAAAGGAGAATTTTCTTGGAAAGAGAGGGTTCAAGCAT 1140
Qy 1141 CACTGTTAGGTGTGCTGGAATCCTTTCCCGAGTCAGTACTGCTTTCTAGAAGAAAACCGG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 CACTGTTAGGTGTGCTGGAATCCTTTCCCGAGTCAGTACTGCTTTCTAGAAGAAAACCGG 1200
Qy 1201 GGAGATCTATTTGGAATGTATCTAACTCCAAAGAAACCATCAGAGGTAACAGTAGAGACG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GGAGATCTATTTGGAATGTATCTAACTCCAAAGAAACCATCAGAGGTAACAGTAGAGACG 1260
Qy 1261 GGGTTTCACCATGTTGGCCAGACTGGTCTTGAACTCTCGACCTCGTGATTCGCCCGCCTC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GGGTTTCACCATGTTGGCCAGACTGGTCTTGAACTCTCGACCTCGTGATTCGCCCGCCTC 1320
Qy 1321 GGCCTCCCAAAGTGCTGGGATTACAGGTGTGAGACACCACACCCGGCGGATAGAGAGAAT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 GGCCTCCCAAAGTGCTGGGATTACAGGTGTGAGACACCACACCCGGCGGATAGAGAGAAT 1380
Qy 1381 TTTGACAGTCTCTCCAATGAACGCCTTCACTGATATCCAAAGCATGAAGGACACACCAGG 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 TTTGACAGTCTCTCCAATGAACGCCTTCACTGATATCCAAAGCATGAAGGACACACCAGG 1440
Qy 1441 GAAAAACATAGACCTAACACAGGACAAATGGAATTATTAGAAACATTTTCTAGCAGAAGA 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GAAAAACATAGACCTAACACAGGACAAATGGAATTATTAGAAACATTTTCTAGCAGAAGA 1500
Qy 1501 ACACTATTCTGTTGCCATTTGAATCTTTGCTTCTTTCTAGGTTTGACAATGAGCCTATCA 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 ACACTATTCTGTTGCCATTTGAATCTTTGCTTCTTTCTAGGTTTGACAATGAGCCTATCA 1560
Qy 1561 TATAAGCCCAAATGTAAACAGAAAGAGGTTGAATCAGTCACGATAAGCCCAATTATGCTG 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 TATAAGCCCAAATGTAAACAGAAAGAGGTTGAATCAGTCACGATAAGCCCAATTATGCTG 1620
Qy 1621 TGGTAACAAACAACCTCAAAATCTCATTGGCTTAAAATATACAGAATTATTCTTACTCAT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TGGTAACAAACAACCTCAAAATCTCATTGGCTTAAAATATACAGAATTATTCTTACTCAT 1680
Qy 1681 GGCACATATCCATCTATCATCTGCAGGGGATCTGCTCACTGAAGTCACTTAGGAACTTGG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 GGCACATATCCATCTATCATCTGCAGGGGATCTGCTCACTGAAGTCACTTAGGAACTTGG 1740
Qy 1741 ACTGATGGAACGGCCACTTTTTGGTCACTATATGTATTAATCTGTTTTAATCCTGCTGAT 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 ACTGATGGAACGGCCACTTTTTGGTCACTATATGTATTAATCTGTTTTAATCCTGCTGAT 1800
Qy 1801 AAAGACCCAAAATTGGGAACAAAAAGAAGTTTAACTAGACTTACAGTTCCGCATGGCTGA 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 AAAGACCCAAAATTGGGAACAAAAAGAAGTTTAACTAGACTTACAGTTCCGCATGGCTGA 1860
Qy 1861 GGAGGCCTCAGAATCATGGTGGGAGGCGAAAGGCACTTCTTACATGGTGGCAGCAAGAGA 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 GGAGGCCTCAGAATCATGGTGGGAGGCGAAAGGCACTTCTTACATGGTGGCAGCAAGAGA 1920
Qy 1921 AAAATGAGGAAGAAGCAAAAGCGGAAACCTCTGATAAACCCATCAGATCTTATGAGACTT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 AAAATGAGGAAGAAGCAAAAGCGGAAACCTCTGATAAACCCATCAGATCTTATGAGACTT 1980
Qy 1981 ATTCCACTATCAAGAGAATAGCATGGGAAAGACTGGCTCCCATAATTTACCTCCCTCTGG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 ATTCCACTATCAAGAGAATAGCATGGGAAAGACTGGCTCCCATAATTTACCTCCCTCTGG 2040
Qy 2041 GTCCCTCCCTCAACATGTGGGAATTCTGGGAGAAACAATTCAAGATATGACACATTCATA 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 GTCCCTCCCTCAACATGTGGGAATTCTGGGAGAAACAATTCAAGATATGACACATTCATA 2100
Qy 2101 ATTTAAACAGAAGCCTACGAAGAACTCATAAATTAAAAGAAGATAATCTTTTCACAAGGT 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 ATTTAAACAGAAGCCTACGAAGAACTCATAAATTAAAAGAAGATAATCTTTTCACAAGGT 2160
Qy 2161 GATGGAGGCTTTTTATTTTGCCACAAAACCACTGGTGACGTTGCCTGTGGCCACCTTGGA 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 GATGGAGGCTTTTTATTTTGCCACAAAACCACTGGTGACGTTGCCTGTGGCCACCTTGGA 2220
Qy 2221 GAAGACACTGGAGGCCTGGGACATGGAGACTGCTTTTCTGCAGAAACCACATCCCTTGGA 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 GAAGACACTGGAGGCCTGGGACATGGAGACTGCTTTTCTGCAGAAACCACATCCCTTGGA 2280
Qy 2281 GTAATGAGCTACACCTACCTCAATTATTCAGTGCAGTACAACACTCCAGACAGGGTCTCA 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 GTAATGAGCTACACCTACCTCAATTATTCAGTGCAGTACAACACTCCAGACAGGGTCTCA 2340
Qy 2341 CTCTGTCACCCAGGCTGGAGTGTATTGGCATGATTACAGCTCACTGCAACCTTGAACTCC 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 CTCTGTCACCCAGGCTGGAGTGTATTGGCATGATTACAGCTCACTGCAACCTTGAACTCC 2400
Qy 2401 CAGGCTCAAACCTGAGCAGCTGGGACTACAGATGCACCACCATGCATGGTACCAGAGATA 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 CAGGCTCAAACCTGAGCAGCTGGGACTACAGATGCACCACCATGCATGGTACCAGAGATA 2460
Qy 2461 TAATAATGAGAAACAGACATGCTCCCTCCCCTCATTGAGGTTACAGCTTAGTGTGGAGAC 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 TAATAATGAGAAACAGACATGCTCCCTCCCCTCATTGAGGTTACAGCTTAGTGTGGAGAC 2520
Qy 2521 ACACAGATGCCTAACGCACTATGGTATGGAAGGTGCTATGGACACAGTGCTCAAATCCAT 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 ACACAGATGCCTAACGCACTATGGTATGGAAGGTGCTATGGACACAGTGCTCAAATCCAT 2580
Qy 2581 GATCTACATAGGTGGAGAACTTCAGTAGAGGAAGTGGCAGGAATTTGGGAATGAGGAGCA 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 GATCTACATAGGTGGAGAACTTCAGTAGAGGAAGTGGCAGGAATTTGGGAATGAGGAGCA 2640
Qy 2641 CAGTGATTAAACTGGGGCCATTCATATGAGAGTTTAAGAACTCAGACCAGTGACTTAGAT 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 CAGTGATTAAACTGGGGCCATTCATATGAGAGTTTAAGAACTCAGACCAGTGACTTAGAT 2700
Qy 2701 TGGCTTCTCTCACATGGCAAGAAACATTGCTGCTAGCACTTCCCGAGTTCTACGTTCTAC 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 TGGCTTCTCTCACATGGCAAGAAACATTGCTGCTAGCACTTCCCGAGTTCTACGTTCTAC 2760
Qy 2761 AACATCCACCACTGGATCTTAACATAGACGTAAGATCAAATGCAATAGCATGTCAAACAA 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 AACATCCACCACTGGATCTTAACATAGACGTAAGATCAAATGCAATAGCATGTCAAACAA 2820
Qy 2821 TGTGTAACTCCAGTTATACAAACATTACTGTATCTCATTGGGGATACGAAGCTCTACACA 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 TGTGTAACTCCAGTTATACAAACATTACTGTATCTCATTGGGGATACGAAGCTCTACACA 2880
Qy 2881 CTTGAAGATGGTGAAGGAATATAAAAATCTATGTCTCACAGTCCAGACTTGGAGTACAAG 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 CTTGAAGATGGTGAAGGAATATAAAAATCTATGTCTCACAGTCCAGACTTGGAGTACAAG 2940
Qy 2941 TAATAAGAAGAATAAAACTTAATCCCTTAAGTAGATTCACCATAAGTTAGCTCAGAGCAA 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 TAATAAGAAGAATAAAACTTAATCCCTTAAGTAGATTCACCATAAGTTAGCTCAGAGCAA 3000
Qy 3001 TTCCAGTGCAAGTATGGTCTGTGATCCAGTAGTATCTTACAGACAGCAAGTTGAACATTG 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 TTCCAGTGCAAGTATGGTCTGTGATCCAGTAGTATCTTACAGACAGCAAGTTGAACATTG 3060
Qy 3061 TGGGATGCATGAGCTATTGAGGCCTTTGCAGCTTTCTGCTACATGGAGGCTAGGGCCAGA 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 TGGGATGCATGAGCTATTGAGGCCTTTGCAGCTTTCTGCTACATGGAGGCTAGGGCCAGA 3120
Qy 3121 GTCAAGATTTATGCTTTGCAGCACACTGGTCAGCTGTTTTTGCAAATCAGATTAAATGAT 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 GTCAAGATTTATGCTTTGCAGCACACTGGTCAGCTGTTTTTGCAAATCAGATTAAATGAT 3180
Qy 3181 TTTTAAATGAGGCTGAGAGCATGGGAGATACTAATGTGTGTTTCCTTGTGAGCTACTGCA 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 TTTTAAATGAGGCTGAGAGCATGGGAGATACTAATGTGTGTTTCCTTGTGAGCTACTGCA 3240
Qy 3241 TAAGTTAGGAAATTGAAATACAGAAAGATGAAAAGTGATTTGCCCAAGCATATAGATCAA 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 TAAGTTAGGAAATTGAAATACAGAAAGATGAAAAGTGATTTGCCCAAGCATATAGATCAA 3300
Qy 3301 AGCTGTGGCAGAACCAGGACTGGAACCTATATCTCTCTACTAATGGTTTTTTTAAAAAAA 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 AGCTGTGGCAGAACCAGGACTGGAACCTATATCTCTCTACTAATGGTTTTTTTAAAAAAA 3360
Qy 3361 TAACCTTGTTTCAAAAATATTAAAAAGTCACAAGAAAGGTAAACATGTGGATAAACAAAA 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 TAACCTTGTTTCAAAAATATTAAAAAGTCACAAGAAAGGTAAACATGTGGATAAACAAAA 3420
Qy 3421 TGAAGAAAATAAAAATTATCCAGTAATAACATA 3453
|||||||||||||||||||||||||||||||||
Db 3421 TGAAGAAAATAAAAATTATCCAGTAATAACATA 3453
Therefore, Sanchez teaches overexpression of ANRIL isoforms to study the isoforms’ effects on cardiovascular disease.
VandenDriessche compared the performance of different AAV serotypes (AAV8 and AAV9) to that of lentiviral vectors, concluding that AAV9 not only yielded higher expression levels and reduced proinflammatory risk relative to lentiviral vectors, but also resulted in widespread cardiac gene transfer relative to the lentiviral and AAV8 vectors (§ Summary).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the ANRIL RNA construct, as taught by Yang, by modifying the lentiviral vector comprising the construct by encoding the construct in an AAV9, as taught by VandenDriessche. Based on VandenDriessche’s teachings, the skilled artisan would have had a reasonable expectation that this would have resulted in an AAV gene transfer vector with higher expression, reduced inflammatory risk, and widespread cardiac gene transfer compared to either lentiviral or AAV8 vectors.
Claim 21 is rejected under 35 U.S.C. 103 as being obvious over Yang, as applied to claims 1, 4-5 and 8, in view of Sanchez (The Long Non-Coding RNA ANRIL in Cancers. Cancers (Basel). 2023 Aug 17;15(16):4160.), as evidenced by NCBI Reference Sequence NR_003529.4 (published 06/06/2023).
Yang, as evidenced by GenBank Accession No. DQ485453.1 and System Biosciences, teaches the construct of claim 1, from which claim 21 depends.
Yang does not teach the construct consisting of SEQ ID NO: 1.
Sanchez teaches that ANRIL isoform 9, a.k.a. NR_003529, is overexpressed in the context of cardiovascular disease (CVD) (p. 7/32):
the ANRIL isoforms 9 (ENTS0000428597.6 or NR_003529) and 13 (ENTS00000584351.5 or DQ485454) have been recognized as regulators of gene expression with antagonistic roles. This duality in their functions has been observed in human endothelial cell lines in the context of CVD. When the isoform 9 is overexpressed, it leads to the down-regulation of the EZR and CXCL11 genes, as well as the up-regulation of TMEM106B. Conversely, overexpression of the isoform 13 has the opposite effect on these genes. These antagonistic
activities are also evident at the cellular level of physiological processes. The expression of the isoform 9 appears to promote transmigration and cellular adhesion, while the isoform 13 elicits contrasting effects
As evidenced by NR_003529, isoform 9 is 3453 nucleotides long and has 100% identity to the full length of SEQ ID NO: 1:
RESULT 1
NR_003529_4
Query Match 100.0%; Score 3453; DB 1; Length 3453;
Best Local Similarity 100.0%;
Matches 3453; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AGCTACATCCGTCACCTGACACGGCCCTACCAGGAACAGCCGCGCTCCCGCGGATTCTGG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AGCTACATCCGTCACCTGACACGGCCCTACCAGGAACAGCCGCGCTCCCGCGGATTCTGG 60
Qy 61 TGCTGCTCGCGTCCCCGCTCCCCTATTCCCCTTATTTTATTCCTGGCTCCCCTCGTCGAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TGCTGCTCGCGTCCCCGCTCCCCTATTCCCCTTATTTTATTCCTGGCTCCCCTCGTCGAA 120
Qy 121 AGTCTTCCATTCTTCAAACTAGATTATTTAAAAATGAAAAAGGAAGAAAGGAAAGCGAGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AGTCTTCCATTCTTCAAACTAGATTATTTAAAAATGAAAAAGGAAGAAAGGAAAGCGAGG 180
Qy 181 TCATCTCATTGCTCTATCCGCCAATCAGGAGGCTGAATGTCAGTTTTGAACTAAAAGCCG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TCATCTCATTGCTCTATCCGCCAATCAGGAGGCTGAATGTCAGTTTTGAACTAAAAGCCG 240
Qy 241 CTCCGCTCCTCTTCTAGATTTGGAAAACAAGCGAAATTAAACTAAACCGCTGCACGCCTC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CTCCGCTCCTCTTCTAGATTTGGAAAACAAGCGAAATTAAACTAAACCGCTGCACGCCTC 300
Qy 301 TGACGCGACATCTGGACACGGCGCGGCGCTGGCGCTGCCGGAGCTGTCGACCCGGCCTGG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TGACGCGACATCTGGACACGGCGCGGCGCTGGCGCTGCCGGAGCTGTCGACCCGGCCTGG 360
Qy 361 CGCCGGACTAGGACTATTTGCCACGACATTTCAAAGGATTCCAAGAGAGAATATTGGTGT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CGCCGGACTAGGACTATTTGCCACGACATTTCAAAGGATTCCAAGAGAGAATATTGGTGT 420
Qy 421 CCATGCTGTGATGATTCCTCAGCTCCTCTCATCTGATCTCCGTCCTGGCCCCCATGACTT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 CCATGCTGTGATGATTCCTCAGCTCCTCTCATCTGATCTCCGTCCTGGCCCCCATGACTT 480
Qy 481 TCTTTGTGGTAGTTAGGGTGTGGTATGTGCCACTGAGGCCCACACCTATTGCTGCAATTT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TCTTTGTGGTAGTTAGGGTGTGGTATGTGCCACTGAGGCCCACACCTATTGCTGCAATTT 540
Qy 541 ATAGCACTGATCTGTCATCAATACCACTTGCTGTCTTGGATGTGAAGATGATTTTTCCTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 ATAGCACTGATCTGTCATCAATACCACTTGCTGTCTTGGATGTGAAGATGATTTTTCCTG 600
Qy 601 CAGGGATTCCCTCTACAAAATTAAAAACACTGGGCATGTGGAAATAATATTCATGCTTTA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CAGGGATTCCCTCTACAAAATTAAAAACACTGGGCATGTGGAAATAATATTCATGCTTTA 660
Qy 661 AATTGTCTTTTCTCTTCACTACACCAGGGGTCCCCAACCCCTAGGCCACAGACTGTGGCC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AATTGTCTTTTCTCTTCACTACACCAGGGGTCCCCAACCCCTAGGCCACAGACTGTGGCC 720
Qy 721 CTAGTGTAGTGAATAGAAAAGACAATTTAAAGCGTGAATATTATTTCCTCATGCCCAGTG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 CTAGTGTAGTGAATAGAAAAGACAATTTAAAGCGTGAATATTATTTCCTCATGCCCAGTG 780
Qy 781 TTTTTAATTTTGTACTGGTCTGTGGCTTGTTAGAAACCAGGCTGCACAGCAGAAGGTGGG 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 TTTTTAATTTTGTACTGGTCTGTGGCTTGTTAGAAACCAGGCTGCACAGCAGAAGGTGGG 840
Qy 841 CAGCAGATATTGAGAAACCACAGAAAGAGAGAAGTTAAATAATTTTCCTGTCAAAGACCA 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 CAGCAGATATTGAGAAACCACAGAAAGAGAGAAGTTAAATAATTTTCCTGTCAAAGACCA 900
Qy 901 CATCAATGATGAAGCCAGAATTTGAGCTCATGTACTTAACCACTGGACTACCTGCCTGCC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 CATCAATGATGAAGCCAGAATTTGAGCTCATGTACTTAACCACTGGACTACCTGCCTGCC 960
Qy 961 CTGTCGAGGAACAGCTAAGTGTCCCTTTTGATGAGAAGAATAAGCCTCATTCTGATTCAA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CTGTCGAGGAACAGCTAAGTGTCCCTTTTGATGAGAAGAATAAGCCTCATTCTGATTCAA 1020
Qy 1021 CAGCAGAGATCAAAGAAAAGACTTCTGTTTTCTGGCCACCAGATATATGTTATCTGTGCT 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 CAGCAGAGATCAAAGAAAAGACTTCTGTTTTCTGGCCACCAGATATATGTTATCTGTGCT 1080
Qy 1081 TAAAGAATTGAAAAACACACATCAAAGGAGAATTTTCTTGGAAAGAGAGGGTTCAAGCAT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 TAAAGAATTGAAAAACACACATCAAAGGAGAATTTTCTTGGAAAGAGAGGGTTCAAGCAT 1140
Qy 1141 CACTGTTAGGTGTGCTGGAATCCTTTCCCGAGTCAGTACTGCTTTCTAGAAGAAAACCGG 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 CACTGTTAGGTGTGCTGGAATCCTTTCCCGAGTCAGTACTGCTTTCTAGAAGAAAACCGG 1200
Qy 1201 GGAGATCTATTTGGAATGTATCTAACTCCAAAGAAACCATCAGAGGTAACAGTAGAGACG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GGAGATCTATTTGGAATGTATCTAACTCCAAAGAAACCATCAGAGGTAACAGTAGAGACG 1260
Qy 1261 GGGTTTCACCATGTTGGCCAGACTGGTCTTGAACTCTCGACCTCGTGATTCGCCCGCCTC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GGGTTTCACCATGTTGGCCAGACTGGTCTTGAACTCTCGACCTCGTGATTCGCCCGCCTC 1320
Qy 1321 GGCCTCCCAAAGTGCTGGGATTACAGGTGTGAGACACCACACCCGGCGGATAGAGAGAAT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 GGCCTCCCAAAGTGCTGGGATTACAGGTGTGAGACACCACACCCGGCGGATAGAGAGAAT 1380
Qy 1381 TTTGACAGTCTCTCCAATGAACGCCTTCACTGATATCCAAAGCATGAAGGACACACCAGG 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 TTTGACAGTCTCTCCAATGAACGCCTTCACTGATATCCAAAGCATGAAGGACACACCAGG 1440
Qy 1441 GAAAAACATAGACCTAACACAGGACAAATGGAATTATTAGAAACATTTTCTAGCAGAAGA 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GAAAAACATAGACCTAACACAGGACAAATGGAATTATTAGAAACATTTTCTAGCAGAAGA 1500
Qy 1501 ACACTATTCTGTTGCCATTTGAATCTTTGCTTCTTTCTAGGTTTGACAATGAGCCTATCA 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 ACACTATTCTGTTGCCATTTGAATCTTTGCTTCTTTCTAGGTTTGACAATGAGCCTATCA 1560
Qy 1561 TATAAGCCCAAATGTAAACAGAAAGAGGTTGAATCAGTCACGATAAGCCCAATTATGCTG 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 TATAAGCCCAAATGTAAACAGAAAGAGGTTGAATCAGTCACGATAAGCCCAATTATGCTG 1620
Qy 1621 TGGTAACAAACAACCTCAAAATCTCATTGGCTTAAAATATACAGAATTATTCTTACTCAT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TGGTAACAAACAACCTCAAAATCTCATTGGCTTAAAATATACAGAATTATTCTTACTCAT 1680
Qy 1681 GGCACATATCCATCTATCATCTGCAGGGGATCTGCTCACTGAAGTCACTTAGGAACTTGG 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 GGCACATATCCATCTATCATCTGCAGGGGATCTGCTCACTGAAGTCACTTAGGAACTTGG 1740
Qy 1741 ACTGATGGAACGGCCACTTTTTGGTCACTATATGTATTAATCTGTTTTAATCCTGCTGAT 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 ACTGATGGAACGGCCACTTTTTGGTCACTATATGTATTAATCTGTTTTAATCCTGCTGAT 1800
Qy 1801 AAAGACCCAAAATTGGGAACAAAAAGAAGTTTAACTAGACTTACAGTTCCGCATGGCTGA 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 AAAGACCCAAAATTGGGAACAAAAAGAAGTTTAACTAGACTTACAGTTCCGCATGGCTGA 1860
Qy 1861 GGAGGCCTCAGAATCATGGTGGGAGGCGAAAGGCACTTCTTACATGGTGGCAGCAAGAGA 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1861 GGAGGCCTCAGAATCATGGTGGGAGGCGAAAGGCACTTCTTACATGGTGGCAGCAAGAGA 1920
Qy 1921 AAAATGAGGAAGAAGCAAAAGCGGAAACCTCTGATAAACCCATCAGATCTTATGAGACTT 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1921 AAAATGAGGAAGAAGCAAAAGCGGAAACCTCTGATAAACCCATCAGATCTTATGAGACTT 1980
Qy 1981 ATTCCACTATCAAGAGAATAGCATGGGAAAGACTGGCTCCCATAATTTACCTCCCTCTGG 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1981 ATTCCACTATCAAGAGAATAGCATGGGAAAGACTGGCTCCCATAATTTACCTCCCTCTGG 2040
Qy 2041 GTCCCTCCCTCAACATGTGGGAATTCTGGGAGAAACAATTCAAGATATGACACATTCATA 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2041 GTCCCTCCCTCAACATGTGGGAATTCTGGGAGAAACAATTCAAGATATGACACATTCATA 2100
Qy 2101 ATTTAAACAGAAGCCTACGAAGAACTCATAAATTAAAAGAAGATAATCTTTTCACAAGGT 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2101 ATTTAAACAGAAGCCTACGAAGAACTCATAAATTAAAAGAAGATAATCTTTTCACAAGGT 2160
Qy 2161 GATGGAGGCTTTTTATTTTGCCACAAAACCACTGGTGACGTTGCCTGTGGCCACCTTGGA 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2161 GATGGAGGCTTTTTATTTTGCCACAAAACCACTGGTGACGTTGCCTGTGGCCACCTTGGA 2220
Qy 2221 GAAGACACTGGAGGCCTGGGACATGGAGACTGCTTTTCTGCAGAAACCACATCCCTTGGA 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2221 GAAGACACTGGAGGCCTGGGACATGGAGACTGCTTTTCTGCAGAAACCACATCCCTTGGA 2280
Qy 2281 GTAATGAGCTACACCTACCTCAATTATTCAGTGCAGTACAACACTCCAGACAGGGTCTCA 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2281 GTAATGAGCTACACCTACCTCAATTATTCAGTGCAGTACAACACTCCAGACAGGGTCTCA 2340
Qy 2341 CTCTGTCACCCAGGCTGGAGTGTATTGGCATGATTACAGCTCACTGCAACCTTGAACTCC 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2341 CTCTGTCACCCAGGCTGGAGTGTATTGGCATGATTACAGCTCACTGCAACCTTGAACTCC 2400
Qy 2401 CAGGCTCAAACCTGAGCAGCTGGGACTACAGATGCACCACCATGCATGGTACCAGAGATA 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2401 CAGGCTCAAACCTGAGCAGCTGGGACTACAGATGCACCACCATGCATGGTACCAGAGATA 2460
Qy 2461 TAATAATGAGAAACAGACATGCTCCCTCCCCTCATTGAGGTTACAGCTTAGTGTGGAGAC 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2461 TAATAATGAGAAACAGACATGCTCCCTCCCCTCATTGAGGTTACAGCTTAGTGTGGAGAC 2520
Qy 2521 ACACAGATGCCTAACGCACTATGGTATGGAAGGTGCTATGGACACAGTGCTCAAATCCAT 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2521 ACACAGATGCCTAACGCACTATGGTATGGAAGGTGCTATGGACACAGTGCTCAAATCCAT 2580
Qy 2581 GATCTACATAGGTGGAGAACTTCAGTAGAGGAAGTGGCAGGAATTTGGGAATGAGGAGCA 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2581 GATCTACATAGGTGGAGAACTTCAGTAGAGGAAGTGGCAGGAATTTGGGAATGAGGAGCA 2640
Qy 2641 CAGTGATTAAACTGGGGCCATTCATATGAGAGTTTAAGAACTCAGACCAGTGACTTAGAT 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2641 CAGTGATTAAACTGGGGCCATTCATATGAGAGTTTAAGAACTCAGACCAGTGACTTAGAT 2700
Qy 2701 TGGCTTCTCTCACATGGCAAGAAACATTGCTGCTAGCACTTCCCGAGTTCTACGTTCTAC 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2701 TGGCTTCTCTCACATGGCAAGAAACATTGCTGCTAGCACTTCCCGAGTTCTACGTTCTAC 2760
Qy 2761 AACATCCACCACTGGATCTTAACATAGACGTAAGATCAAATGCAATAGCATGTCAAACAA 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2761 AACATCCACCACTGGATCTTAACATAGACGTAAGATCAAATGCAATAGCATGTCAAACAA 2820
Qy 2821 TGTGTAACTCCAGTTATACAAACATTACTGTATCTCATTGGGGATACGAAGCTCTACACA 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2821 TGTGTAACTCCAGTTATACAAACATTACTGTATCTCATTGGGGATACGAAGCTCTACACA 2880
Qy 2881 CTTGAAGATGGTGAAGGAATATAAAAATCTATGTCTCACAGTCCAGACTTGGAGTACAAG 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2881 CTTGAAGATGGTGAAGGAATATAAAAATCTATGTCTCACAGTCCAGACTTGGAGTACAAG 2940
Qy 2941 TAATAAGAAGAATAAAACTTAATCCCTTAAGTAGATTCACCATAAGTTAGCTCAGAGCAA 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2941 TAATAAGAAGAATAAAACTTAATCCCTTAAGTAGATTCACCATAAGTTAGCTCAGAGCAA 3000
Qy 3001 TTCCAGTGCAAGTATGGTCTGTGATCCAGTAGTATCTTACAGACAGCAAGTTGAACATTG 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3001 TTCCAGTGCAAGTATGGTCTGTGATCCAGTAGTATCTTACAGACAGCAAGTTGAACATTG 3060
Qy 3061 TGGGATGCATGAGCTATTGAGGCCTTTGCAGCTTTCTGCTACATGGAGGCTAGGGCCAGA 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3061 TGGGATGCATGAGCTATTGAGGCCTTTGCAGCTTTCTGCTACATGGAGGCTAGGGCCAGA 3120
Qy 3121 GTCAAGATTTATGCTTTGCAGCACACTGGTCAGCTGTTTTTGCAAATCAGATTAAATGAT 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3121 GTCAAGATTTATGCTTTGCAGCACACTGGTCAGCTGTTTTTGCAAATCAGATTAAATGAT 3180
Qy 3181 TTTTAAATGAGGCTGAGAGCATGGGAGATACTAATGTGTGTTTCCTTGTGAGCTACTGCA 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3181 TTTTAAATGAGGCTGAGAGCATGGGAGATACTAATGTGTGTTTCCTTGTGAGCTACTGCA 3240
Qy 3241 TAAGTTAGGAAATTGAAATACAGAAAGATGAAAAGTGATTTGCCCAAGCATATAGATCAA 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3241 TAAGTTAGGAAATTGAAATACAGAAAGATGAAAAGTGATTTGCCCAAGCATATAGATCAA 3300
Qy 3301 AGCTGTGGCAGAACCAGGACTGGAACCTATATCTCTCTACTAATGGTTTTTTTAAAAAAA 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3301 AGCTGTGGCAGAACCAGGACTGGAACCTATATCTCTCTACTAATGGTTTTTTTAAAAAAA 3360
Qy 3361 TAACCTTGTTTCAAAAATATTAAAAAGTCACAAGAAAGGTAAACATGTGGATAAACAAAA 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3361 TAACCTTGTTTCAAAAATATTAAAAAGTCACAAGAAAGGTAAACATGTGGATAAACAAAA 3420
Qy 3421 TGAAGAAAATAAAAATTATCCAGTAATAACATA 3453
|||||||||||||||||||||||||||||||||
Db 3421 TGAAGAAAATAAAAATTATCCAGTAATAACATA 3453
Therefore, Sanchez teaches overexpression of an ANRIL coding sequence consisting of SEQ ID NO: 1 to study the isoform’s effects on cardiovascular disease.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the ANRIL RNA expression vector, as taught by Yang, by encoding ANRIL isoform 9 to further investigate the role of the isoform in CVD. The skilled artisan would have been motivated to do so based on Sanchez’s teachings that various ANRIL isoforms, including isoform 9, play various roles in CVD.
Conclusion
No claim is allowed.
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/A.M.Z./ Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636