Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application 18/037,598 filed on 05/18/2023 is a national phase application under 35 U.S.C. § 371 that claims priority to International Application No. PCT/CN2021/131951 field on 11/19/2021, and claims priority of foreign application CN 202011302953.5 filed on 11/19/2020.
A certified copy of foreign application CN 202011302953.5 filed on 11/19/2020 has been submitted of the record by Applicants on 05/18/2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
No English translation of foreign application CN 202011302953.5 filed on 11/19/2020 has been provided. The priority date of claim set filed on 01/05/2026 is determined to be 11/19/2021, the filing date of PCT/CN2021/131951.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)- (d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Restriction/Election
Applicant’s election without traverse of Group I invention, claims 1-2, in the reply filed on 01/14/2026 is acknowledged.
Regarding Species election (I) of siRNA, Applicants elected the sense strand has a nucleotide sequence of 5'- CUGAGUCUUGGAAGUGGAUCCUUTT-3' (SEQ ID NO.5), and the antisense strand has a nucleotide sequence of 5'- AAGGAUCCACUUCCAAGACUCAGTT-3' (SEQ ID NO.6);
Regarding Species election (II) of siRNA modification, Applicants elected the 2'-O-ribose methylation
Claims 1-11 are pending.
Claims 3-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 01/14/2026.
Claims 1-2 are currently under examination.
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 1-2 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.
Amended claim 1 filed on 01/14/2026 reads as follows: A small interfering RNA that inhibits the expression of target gene NOX1, consisting of a sense strand and an antisense strand reversely complementary thereto, wherein sequences of the sense strand and the antisense strand are (3) sequences of No. 3 small interfering RNA the sense strand has a nucleotide sequence of 5'- CUGAGUCUUGGAAGUGGAUCCUUTT-3' (SEQ ID NO.5), the antisense strand has a nucleotide sequence of 5'- AAGGAUCCACUUCCAAGACUCAGTT-3' (SEQ ID NO.6); wherein, the antisense strand is reversely complementary to a fragment of the target gene.”
The limitation “(3) sequences of No. 3 small interfering RNA” along with limitations “the sense strand has a nucleotide sequence of 5'- CUGAGUCUUGGAAGUGGAUCCUUTT-3' (SEQ ID NO.5), the antisense strand has a nucleotide sequence of 5'- AAGGAUCCACUUCCAAGACUCAGTT-3'(SEQ ID NO.6)” is unclear regarding whether SEQ ID NO: 3 of instant application is encompassed by the limitation “sequences of No. 3”.
Additionally, it is unclear whether “5'- CUGAGUCUUGGAAGUGGAUCCUUTT-3'” is SEQ ID NO. 5 (i.e. a DNA molecule with both nucleotide T and nucleotide U) and whether “5'- AAGGAUCCACUUCCAAGACUCAGTT-3'” is SEQ ID NO. 6 (i.e. a DNA molecule with both nucleotide T and nucleotide U).
<210> SEQ ID NO 5
<211> LENGTH: 25
<212> TYPE: DNA
<213> ORGANISM: Artificial Sequence
<220> FEATURE:
<223> OTHER INFORMATION: sense strand
<400> SEQUENCE:5
cugagucuug gaaguggauc cuutt 25
<210> SEQ ID NO 6
<211> LENGTH: 25
<212> TYPE: DNA
<213> ORGANISM: Artificial Sequence
<220> FEATURE:
<223> OTHER INFORMATION: antisense strand
<400> SEQUENCE: 6
aaggauccac uuccaagacu cagtt 25
Claim 2 depends from claim 1.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Goyal et al. (2004) (Goyal et al., Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species, Free Radic. Biol. Med. 36 (10), 1279-1288 (2004)) in view of GenBank: AK313678.1 (2008), Juhasz et al. (US 2008/0039420 A1, which is the publication of US application No. 11/785, 419), Lisowiec-Wachnicka et al. (2019) (Lisowiec-Wachnicka et al., Contribution of 3′ T and 3′TT overhangs to the thermodynamic stability of model siRNA duplexes, Biophys Chem., 2019 Mar:246:35-39. doi: 10.1016/j.bpc.2018.12.006. Epub 2019 Jan 7.), and Tafer (2014) (Tafer, Bioinformatics of siRNA design, Methods Mol Biol. 2014;1097:477-90. doi: 10.1007/978-1-62703-709-9_22).
Claims 1 is directed to “A small interfering RNA that inhibits the expression of target gene NOX1, consisting of a sense strand and an antisense strand reversely complementary thereto, wherein sequences of the sense strand and the antisense strand are (3) sequences of No. 3 small interfering RNA, the sense strand has a nucleotide sequence of 5'- CUGAGUCUUGGAAGUGGAUCCUUTT-3'(SEQ ID NO. 5), the antisense strand has a nucleotide sequence of 5'- AAGGAUCCACUUCCAAGACUCAGTT-3'(SEQ ID NO. 6); wherein, the antisense strand is reversely complementary to a fragment of the target gene.”
Claim 2 is directed to “The small interfering RNA according to claim 1, wherein the sense strand and the antisense strand are optionally modified with 2'-O-ribose modification on the first 21 nucleotides from the 5' end, and the 2'-O-ribose modification is 2'-O-ribose methylation modification”.
Claim interpretations: Regarding claim 2, the optional 2'-O-ribose methylation modification encompass the absence of 2'-O-ribose methylation.
Goyal et al. (2004) teaches “Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species” (See Title). SEQ ID NO:5 (sense, nucleotides 1-23) and SEQ ID NO:6 (antisense, nucleotides 1-23) of instant application are nucleotide sequences 800-822 of Homo sapiens mRNA for nox1 NAD(P)H-oxidase subunit (NOX1 gene) (See alignments copied below with the Queries (Qy) being SEQID NO: 5 and SEQ ID NO: 6 of instant application).
Instant SEQID NO: 5 being Query (Qy)
Title: US-18-037-598-5
Perfect score: 25
Sequence: 1 cugagucuuggaaguggauccuutt 25
Scoring table: IDENTITY_NUC
Gapop 10.0 , Gapext 1.0
Searched: 62410436 unique seqs, 5372279581277 residues
Total number of hits satisfying chosen parameters: 124820872
Minimum DB seq length: 0
Maximum DB seq length: 2000000000
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 45 summaries
Database : GenEmbl:*
RESULT 2
AJ438989
LOCUS AJ438989 1548 bp mRNA linear PRI 07-OCT-2008
DEFINITION Homo sapiens mRNA for nox1 NAD(P)H-oxidase subunit (NOX1 gene).
ACCESSION AJ438989
VERSION AJ438989.1
KEYWORDS NOX1 gene; nox1 NAD(P)H-oxidase.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1
AUTHORS Goyal,P., Weissmann,N., Grimminger,F., Hegel,C., Bader,L., Rose,F.,
Fink,L., Ghofrani,H.A., Schermuly,R.T., Schmidt,H.H., Seeger,W. and
Hanze,J.
TITLE Upregulation of NAD(P)H oxidase 1 in hypoxia activates
hypoxia-inducible factor 1 via increase in reactive oxygen species
JOURNAL Free Radic. Biol. Med. 36 (10), 1279-1288 (2004)
PUBMED 15110393
REFERENCE 2 (bases 1 to 1548)
AUTHORS Haenze,J.
TITLE Direct Submission
JOURNAL Submitted (13-MAR-2002) Haenze J., Internal Medicine II /
Biochemistry, University of Giessen, Friedrichstr. 24, 35392,
GERMANY
FEATURES Location/Qualifiers
source 1..1548
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
gene 1..1548
/gene="NOX1"
CDS 1..1548
/gene="NOX1"
/function="low output NAD(P)H-oxidase subunit"
/codon_start=1
/product="nox1 NAD(P)H-oxidase subunit"
/protein_id="CAD27735.1"
/db_xref="GOA:Q8TCT3"
/db_xref="HGNC:HGNC:7889"
/db_xref="InterPro:IPR000778"
/db_xref="InterPro:IPR013112"
/db_xref="InterPro:IPR013121"
/db_xref="InterPro:IPR013130"
/db_xref="InterPro:IPR017927"
/db_xref="InterPro:IPR017938"
/db_xref="UniProtKB/TrEMBL:Q8TCT3"
/translation="MGNWVVNHWFSVLFLVVWLGLNVFLFVDAFLKYEKADKYYYTRK
ILGSTLACARASALCLNFNSTLILLPVCRNLLSFLRGTCSFCSRTLRKQLDHNLTFHK
LVAYMICLHTAIHIIAHLFNFDCYSRSRQATDGSLASILSSLSHDEKKGGSWLNPIQS
RNTTVEYVTFTSIAGLTGVIMTIALILMVTSATEFIRRSYFEVFWYTHHLFIFYILGL
GIHGIGGIVRGQTEESMNESHPRKCAESFEMWDDRDSHCRRPKFEGHPPESWKWILAS
VILYICERILRFYRSQQKVVITKVVMHPSKVLELQMNKRGFSMEVGQYIFVNCPSISL
LEWHPFTLTSAPEEDFFSIHIRAAGDWTENLIRAFEQQYSPIPRIEVDGPFGTASEDV
FQYEVAVLVGAGIGVTPFASILKSIWYKFQCADHNLKTKKVGHAALNFDKATDIVTGL
KQKTSFGRPMWDNEFSTIATSHPKSVVGVFLCGPRTLAKSLRKCCHRYSSLDPRKVQF
YFNKENF
Query Match 92.0%; Score 23; Length 1548;
Best Local Similarity 65.2%;
Matches 15; Conservative 8; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CUGAGUCUUGGAAGUGGAUCCUU 23
|:|||:|::|||||:|||:||::
Db 800 CTGAGTCTTGGAAGTGGATCCTT 822
Instant SEQID NO: 6 being Query (Qy)
Title: US-18-037-598-6
Perfect score: 25
Sequence: 1 aaggauccacuuccaagacucagtt 25
Scoring table: IDENTITY_NUC
Gapop 10.0 , Gapext 1.0
Searched: 62410436 unique seqs, 5372279581277 residues
Total number of hits satisfying chosen parameters: 124820872
Minimum DB seq length: 0
Maximum DB seq length: 2000000000
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 45 summaries
Database : GenEmbl:*
RESULT 2
AJ438989/c
LOCUS AJ438989 1548 bp mRNA linear PRI 07-OCT-2008
DEFINITION Homo sapiens mRNA for nox1 NAD(P)H-oxidase subunit (NOX1 gene).
ACCESSION AJ438989
VERSION AJ438989.1
KEYWORDS NOX1 gene; nox1 NAD(P)H-oxidase.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1
AUTHORS Goyal,P., Weissmann,N., Grimminger,F., Hegel,C., Bader,L., Rose,F.,
Fink,L., Ghofrani,H.A., Schermuly,R.T., Schmidt,H.H., Seeger,W. and
Hanze,J.
TITLE Upregulation of NAD(P)H oxidase 1 in hypoxia activates
hypoxia-inducible factor 1 via increase in reactive oxygen species
JOURNAL Free Radic. Biol. Med. 36 (10), 1279-1288 (2004)
PUBMED 15110393
REFERENCE 2 (bases 1 to 1548)
AUTHORS Haenze,J.
TITLE Direct Submission
JOURNAL Submitted (13-MAR-2002) Haenze J., Internal Medicine II /
Biochemistry, University of Giessen, Friedrichstr. 24, 35392,
GERMANY
FEATURES Location/Qualifiers
source 1..1548
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
gene 1..1548
/gene="NOX1"
CDS 1..1548
/gene="NOX1"
/function="low output NAD(P)H-oxidase subunit"
/codon_start=1
/product="nox1 NAD(P)H-oxidase subunit"
/protein_id="CAD27735.1"
/db_xref="GOA:Q8TCT3"
/db_xref="HGNC:HGNC:7889"
/db_xref="InterPro:IPR000778"
/db_xref="InterPro:IPR013112"
/db_xref="InterPro:IPR013121"
/db_xref="InterPro:IPR013130"
/db_xref="InterPro:IPR017927"
/db_xref="InterPro:IPR017938"
/db_xref="UniProtKB/TrEMBL:Q8TCT3"
/translation="MGNWVVNHWFSVLFLVVWLGLNVFLFVDAFLKYEKADKYYYTRK
ILGSTLACARASALCLNFNSTLILLPVCRNLLSFLRGTCSFCSRTLRKQLDHNLTFHK
LVAYMICLHTAIHIIAHLFNFDCYSRSRQATDGSLASILSSLSHDEKKGGSWLNPIQS
RNTTVEYVTFTSIAGLTGVIMTIALILMVTSATEFIRRSYFEVFWYTHHLFIFYILGL
GIHGIGGIVRGQTEESMNESHPRKCAESFEMWDDRDSHCRRPKFEGHPPESWKWILAS
VILYICERILRFYRSQQKVVITKVVMHPSKVLELQMNKRGFSMEVGQYIFVNCPSISL
LEWHPFTLTSAPEEDFFSIHIRAAGDWTENLIRAFEQQYSPIPRIEVDGPFGTASEDV
FQYEVAVLVGAGIGVTPFASILKSIWYKFQCADHNLKTKKVGHAALNFDKATDIVTGL
KQKTSFGRPMWDNEFSTIATSHPKSVVGVFLCGPRTLAKSLRKCCHRYSSLDPRKVQF
YFNKENF
Query Match 92.0%; Score 23; Length 1548;
Best Local Similarity 82.6%;
Matches 19; Conservative 4; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AAGGAUCCACUUCCAAGACUCAG 23
|||||:||||::|||||||:|||
Db 822 AAGGATCCACTTCCAAGACTCAG 800
It is noted that the cDNA sequences correspond to mRNA of Homo sapiens mRNA for nox1 NAD(P)H-oxidase subunit (NOX1 gene) taught by Goyal et al. (2004) are disclosed in GenBank: AK313678.1 (2008). Nucleotides sequences 1-23 of SEQ ID NO: 5 of instant application are the nucleotides sequence 915-937 of cDNA (ctgagt cttggaagtg gatcctt)
disclosed in GenBank: AK313678.1 (2008).
Homo sapiens cDNA, FLJ94265
GenBank: AK313678.1
FASTA Graphics
Go to:
LOCUS AK313678 1810 bp mRNA linear HTC 12-JAN-2008
DEFINITION Homo sapiens cDNA, FLJ94265.
ACCESSION AK313678
VERSION AK313678.1
KEYWORDS HTC; HTC_FLI; oligo capping.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1
AUTHORS Wakamatsu,A., Yamamoto,J., Kimura,K., Kaida,T., Tsuchiya,K.,
Iida,Y., Takayama,Y., Murakawa,K., Kanehori,K., Andoh,T.,
Kagawa,N., Sato,R., Kawamura,Y., Tanaka,S., Kisu,Y., Sugano,S.,
Goshima,N., Nomura,N. and Isogai,T.
TITLE NEDO functional analysis of protein and research application
project
JOURNAL Unpublished
REFERENCE 2 (bases 1 to 1810)
AUTHORS Isogai,T. and Yamamoto,J.
TITLE Direct Submission
JOURNAL Submitted (11-JAN-2008) Contact:Takao Isogai Reverse Proteomics
Research Institute; 1-9-11 Kaji-cho, Chiyoda-ku, Tokyo 101-0044,
Japan E-mail :flj-cdna@nifty.com
COMMENT Human cDNA sequencing project focused on splicing variants of mRNA
in NEDO functional analysis of protein and research application
project supported by Ministry of Economy, Trade and Industry,
Japan; cDNA selection for complete cds sequencing: Reverse
Proteomics Research Institute (REPRORI), Hitachi, Ltd., Japan
(Hitachi) and Japan Biological Informatics Consortium, Japan
(JBIC); cDNA complete cds sequencing: JBIC and Biological
Information Research Center (BIRC), AIST; cDNA library
construction: Helix Research Institute supported by Japan Key
Technology Center, Japan (HRI); cDNA 5'- & 3'-end sequencing:
Research Association for Biotechnology, Japan, Biotechnology
Center, National Institute of Technology and Evaluation, Japan and
HRI; cDNA mapping to human genome: Central Research Laboratory,
Hitachi; evaluation and annotation: REPRORI.
FEATURES Location/Qualifiers
source 1..1810
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
/clone="COLON2003845"
/tissue_type="colon"
/clone_lib="COLON2"
/note="cloning vector: pME18SFL3"
ORIGIN
1 aaaaggctca cagaccctgc gctggacaaa tgttccattc ctgaaggacc tctccagaat
61 ccggattgct gaatcttccc tgttgcctag aagggctcca aaccacctct tgacaatggg
121 aaactgggtg gttaaccact ggttttcagt tttgtttctg gttgtttggt tagggctgaa
181 tgttttcctg tttgtggatg ccttcctgaa atatgagaag gccgacaaat actactacac
241 aagaaaaatc cttgggtcaa cattggcctg tgcccgagcg tctgctctct gcttgaattt
301 taacagcacg ctgatcctgc ttcctgtgtg tcgcaatctg ctgtccttcc tgaggggcac
361 ctgctcattt tgcagccgca cactgagaaa gcaattggat cacaacctca ccttccacaa
421 gctggtggcc tatatgatct gcctacatac agctattcac atcattgcac acctgtttaa
481 ctttgactgc tatagcagaa gccgacaggc cacagatggc tcccttgcct ccattctctc
541 cagcctatct catgatgaga aaaagggggg ttcttggcta aatcccatcc agtcccgaaa
601 cacgacagtg gagtatgtga cattcaccag cattgctggt ctcactggag tgatcatgac
661 aatagccttg attctcatgg taacttcagc tactgagttc atccggagga gttattttga
721 agtcttctgg tatactcacc acctttttat cttctatatc cttggcttag ggattcacgg
781 cattggtgga attgtccggg gtcaaacaga ggagagcatg aatgagagtc atcctcgcaa
841 gtgtgcagag tcttttgaga tgtgggatga tcgtgactcc cactgtaggc gccctaagtt
901 tgaagggcat ccccctgagt cttggaagtg gatccttgca ccggtcattc tttatatctg
961 tgaaaggatc ctccggtttt accgctccca gcagaaggtt gtgattacca aggttgttat
1021 gcacccatcc aaagttttgg aattgcagat gaacaagcgt ggcttcagca tggaagtggg
1081 gcagtatatc tttgttaatt gcccctcaat ctctctcctg gaatggcatc cttttacttt
1141 gacctctgct ccagaggaag atttcttctc cattcatatc cgagcagcag gggactggac
1201 agaaaatctc ataagggctt tcgaacaaca atattcacca attcccagga ttgaagtgga
1261 tggtcccttt ggcacagcca gtgaggatgt tttccagtat gaagtggctg tgctggttgg
1321 agcaggaatt ggggtcaccc cctttgcttc tatcttgaaa tccatctggt acaaattcca
1381 gtgtgcagac cacaacctca aaacaaaaaa gatctatttc tactggatct gcagggagac
1441 aggtgccttt tcctggttca acaacctgtt gacttccctg gaacaggaga tggaggaatt
1501 aggcaaagtg ggttttctaa actaccgtct cttcctcacc ggatgggaca gcaatattgt
1561 tggtcatgca gcattaaact ttgacaaggc cactgacatc gtgacaggtc tgaaacagaa
1621 aacctccttt gggagaccaa tgtgggacaa tgagttttct acaatagcta cctcccaccc
1681 caagtctgta gtgggagttt tcttatgtgg ccctcggact ttggcaaaga gcctgcgcaa
1741 atgctgtcac cgatattcca gtctggatcc tagaaaggtt caattctact tcaacaaaga
1801 aaatttttga
//
The teachings of Goyal et al. (2004) and GenBank: AK313678.1 (2008) do not explicitly teach utilization of siRNA for inhibition of upregulated expression of target gene NOX1.
Juhasz et al. (US 2008/0039420 A1, which is the publication of US application No. 11/785, 419) teaches that “The present invention relates to compositions and methods for gene-specific inhibition of gene expression by short interfering ribonucleic acid (siRNA) effector molecules. The compositions and methods are particularly useful in modulating gene expression of the NOX1 gene in colon cancer cells” (See Abstract).
SEQ ID NO: 1 (sense strand) of instant application matches 100% to SEQ ID No: 7 (DNA construct encoding shRNA, short hairpin RNA) of US application No. 11/785, 419 (See alignment below).
RESULT 2
US-11-785-419-7
Sequence 7, US/11785419
Publication No. US20080039420A1
GENERAL INFORMATION
APPLICANT: Juhasz, Agnes
APPLICANT: Doroshow, James H.
APPLICANT: Markel, Susan
APPLICANT: Gaur, Shikha
TITLE OF INVENTION: Method for Inhibiting Nox1 Gene Expression
FILE REFERENCE: 1954-476
CURRENT APPLICATION NUMBER: US/11/785,419
CURRENT FILING DATE: 2007-05-21
PRIOR APPLICATION NUMBER: 60/793,242
PRIOR FILING DATE: 2006-04-20
NUMBER OF SEQ ID NOS: 8
SEQ ID NO 7
LENGTH: 326
TYPE: DNA
ORGANISM: Artificial
FEATURE:
OTHER INFORMATION: DNA construct encoding shRNA
Query Match 100.0%; Score 23; Length 326;
Best Local Similarity 78.3%;
Matches 18; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAGAUGUGGGAUGAUCGUGACTT 23
||||:|:||||:||:||:|||||
Db 300 GAGATGTGGGATGATCGTGACTT 322
SEQ ID No: 2 (antisense strand) of instant application matches 100% to SEQ ID No: 7 (DNA construct encoding shRNA, short hairpin RNA) of US application No. 11/785, 419 (See alignment below).
RESULT 2
US-11-785-419-7
Sequence 7, US/11785419
Publication No. US20080039420A1
GENERAL INFORMATION
APPLICANT: Juhasz, Agnes
APPLICANT: Doroshow, James H.
APPLICANT: Markel, Susan
APPLICANT: Gaur, Shikha
TITLE OF INVENTION: Method for Inhibiting Nox1 Gene Expression
FILE REFERENCE: 1954-476
CURRENT APPLICATION NUMBER: US/11/785,419
CURRENT FILING DATE: 2007-05-21
PRIOR APPLICATION NUMBER: 60/793,242
PRIOR FILING DATE: 2006-04-20
NUMBER OF SEQ ID NOS: 8
SEQ ID NO 7
LENGTH: 326
TYPE: DNA
ORGANISM: Artificial
FEATURE:
OTHER INFORMATION: DNA construct encoding shRNA
Query Match 100.0%; Score 23; Length 326;
Best Local Similarity 78.3%;
Matches 18; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GUCACGAUCAUCCCACAUCUCTT 23
|:|||||:||:||||||:|:|||
Db 271 GTCACGATCATCCCACATCTCTT 293
Relevant to utilization of siRNA for inhibition of NOX1 gene expression, the nucleotides sequences 1-21 of SEQ ID NO: 1 of instant application are the nucleotides sequence 857-877 of cDNA (gaga tgtgggatga tcgtgac) disclosed in GenBank: AK313678.1 (2008); and the nucleotides sequences 22-23 of SEQ ID NO: 1 (TT at 3’ end) of instant application are disclosed in SEQ ID NO: 7 of Juhasz et al. (US 2008/0039420).
Furthermore, relevant to utilization of siRNA for inhibition of NOX1 gene expression, nucleotides sequences 1-21 of SEQ ID NO: 3 of instant application are the nucleotides sequence 418-428 of cDNA (caa gctggtggcc tatatgat) disclosed in GenBank: AK313678.1 (2008); and the nucleotides sequences 22-23 of SEQ ID NO: 3 (TT at 3’ end) of instant application are similarly designed as in SEQ ID NO: 7 of Juhasz et al. (US 2008/0039420).
The combined teachings of Goyal et al. (2004), GenBank: AK313678.1 (2008), and Juhasz et al. (US 2008/0039420 A1) do not explicitly teach addition of TT di-nucleotides that are added in 5'- CUGAGUCUUGGAAGUGGAUCCUUTT-3' (SEQ ID NO. 5) and in 5'- AAGGAUCCACUUCCAAGACUCAGTT-3' (SEQ ID NO. 6).
Lisowiec-Wachnicka et al. (2019) teaches “Contribution of 3′ T and 3′TT overhangs to the thermodynamic stability of model siRNA duplexes” See Title). Lisowiec-Wachnicka et al. (2019) teaches that “Herein, we report comprehensive thermodynamic studies on 36 RNA/DNA duplexes designed as siRNA mimics to determine the energetic contribution of 3′T and 3′TT dangling ends. The thermodynamic effect induced by the presence of 3′T overhangs on the stability of RNA duplexes ranges from −0.28 to −0.92 kcal/mol and strongly depends on the type and orientation of the adjacent base pair. Further extension of the 3′-dangling end length, by
a second T residue, results in additional stabilization of 0.14 to 0.21 kcal/mol. The results revealed that the thermodynamic contribution of 3′-dangling T and TT on RNA duplexes differs from the influence of 3′-dangling U and UU on RNA duplexes and 3′-dangling T and TT on DNA duplexes. This data suggests that using the contribution of 3′-dangling T values for RNA duplexes, instead of 3′-dangling T values for DNA duplexes or 3′- dangling U values for RNA duplexes, would improve the prediction of the stability of siRNA duplexes (See Abstract).”
PNG
media_image1.png
430
790
media_image1.png
Greyscale
Furthermore, Tafer (2014) teaches “Bioinformatics of siRNA design” (See Title), and “Sequence-Based siRNA Design” (See pages 479-484, Fig. 2 copied below).
PNG
media_image2.png
410
876
media_image2.png
Greyscale
Fig. 2 Top: Weblogo representation of the highest scoring siRNA target sequence for the algorithm from Reynolds, Hsieh, Takasaki, Dsir, Amarzguioui, Katoh, and iScore. The sequence asymmetry is clearly seen, as well as the presence of a T at position 10. Bottom: Heatmap representation of the sum of the normalized coefficients of the models from Reynolds, Hsieh, Takasaki, Dsir, Amarzguioui, Katoh, and iScore for each nucleotide and position along the siRNA target sequence. Dark squares represent preferred nucleotide/position combination while light ones stand for unfavorable nucleotide/position. Here also the sequence asymmetry is
clearly seen, with A/T being highly preferred at the target 3_ end, while G/C being overrepresented at the target 5’ end.
It would have been prima facie obvious for a skilled artisan to incorporate the disclosure of “Contribution of 3′ T and 3′ TT overhangs to the thermodynamic stability of model siRNA duplexes” taught by Lisowiec-Wachnicka et al. (2019) and “Sequence-Based siRNA Design” taught by Tafer (2014) into the combined teachings of modulating gene expression of the NOX1 gene in lung pathology (Goyal et al.) and colon cancer cells (Juhasz et al.) in light of known cDNA, mRNA, and protein sequences of human NOX1 taught by Goyal et al. (2004) and GenBank: AK313678.1 (2008), along with the teachings of Juhasz et al. (US 2008/0039420 A1) regarding “compositions and methods for gene-specific inhibition of gene expression by short interfering ribonucleic acid (siRNA) effector molecules” to arrive at instant claims 1 and 2 because cDNA, mRNA, and protein sequences of human NOX1 are clearly known to a skilled artisan, and siRNA design and application of siRNA in inhibition of gene inhibition are well established in the field of siRNA medicated inhibition of gene expression.
A skilled artisan would be motivated to combine the teachings Lisowiec-Wachnicka et al. (2019) and “Sequence-Based siRNA Design” taught by Tafer (2014) into the combined teachings of Goyal et al. (2004), GenBank: AK313678.1 (2008), and Juhasz et al. (US 2008) with reasonable expectation of success because (i) the three references Lisowiec-Wachnicka et al. (2019), Tafer (2014), and Juhasz et al. (2008) are analogous arts in the same field of endeavor pertaining to compositions for gene-specific inhibition of gene expression by short interfering ribonucleic acid (siRNA) effector molecules, (ii) the teachings of SEQ ID NO. 7 by Juhasz et al. (2008), which includes addition of TT dinucleotide at 3’ end, correspond to SEQ ID NO: 1 (sense) and SEQ ID NO: 2 (antisense) of instant application, and (iii) cDNA, mRNA, and protein sequences of human NOX1 taught by Goyal et al. (2004) and GenBank: AK313678.1 (2008).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Goyal et al. (2004) (Goyal et al., Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species, Free Radic. Biol. Med. 36 (10), 1279-1288 (2004)) in view of GenBank: AK313678.1 (2008), Juhasz et al. (US 2008/0039420 A1, which is the publication of US application No. 11/785, 419), Lisowiec-Wachnicka et al. (2019) (Lisowiec-Wachnicka et al., Contribution of 3′ T and 3′TT overhangs to the thermodynamic stability of model siRNA duplexes, Biophys Chem., 2019 Mar:246:35-39. doi: 10.1016/j.bpc.2018.12.006. Epub 2019 Jan 7.), and Tafer (2014) (Tafer, Bioinformatics of siRNA design, Methods Mol Biol. 2014;1097:477-90. doi: 10.1007/978-1-62703-709-9_22) as applied to claim 1 above, and further in view of Yokata et al. (US 2010/0234282 A1).
Claim 2 is directed to “The small interfering RNA according to claim 1, wherein the sense strand and the antisense strand are optionally modified with 2'-O-ribose modification on the first 21 nucleotides from the 5' end, and the 2'-O-ribose modification is 2'-O-ribose methylation modification”.
Claim interpretations: Regarding claim 2, the optional 2'-O-ribose methylation modification encompass the presence of 2'-O-ribose methylation.
The teachings of Goyal et al. (2004), GenBank: AK313678.1 (2008), Juhasz et al. (US 2008/0039420), Lisowiec-Wachnicka et al. (2019) and Tafer (2014) have been documented above in the rejection of claim 1.
The combined teachings of Goyal et al. (2004), GenBank: AK313678.1 (2008), Juhasz et al. (US 2008/0039420), Lisowiec-Wachnicka et al. (2019) and Tafer (2014) do not explicitly teach the optional 2'-O-ribose methylation modification of nucleotide
Yokata et al. (US 2010/0234282 A1) teaches “System for delivering nucleic acid for suppressing target gene expression (See Title); and “The object of present invention is to provide a system that can deliver in vivo nucleic acids such as an siRNA for suppressing a target gene expression in vivo more safely and efficiently, and to provide an expression-suppressing agent and a pharmaceutical composition utilizing the system. An introduction substance into chylomiclon, particularly nucleic acids to which an alpha-tocopherol is bound for suppressing a target gene expression, can be delivered more safely and efficiently into hepatic cells in vivo by administering the nucleic aids under the condition where the production of chylomicron is induced in the body. Alternatively, alpha-tocopherol-bound nucleic acids are mixed with extracted chylomiclon, and then they are administered. Consequently, a target gene expression is suppressed, thereby a disease caused by an elevated expression of the target gene can be treated more safely and efficiently (See Abstract).
Yokata et al. (US 2010/0234282 A1) further teaches “Subsequently, these nucleotide sequences were modified for an improved stability to in vivo RNases. More specifically, the nucleotides of nucleotide numbers 2, 5, 11, 15, 21, 24, and 25 of the siRNA sense strand (SEQ ID NO: 1) and the nucleotides of nucleotide numbers of 1, 2, 5, 12, 14, 21, 24, 25, and 26 of the antisense strand (SEQ ID NO: 2) were subjected to 2’-O ribose methylation; the skeletal bond of the nucleotide of nucleotide number 26 of the sense strand (SEQ ID NO: 1) was subjected to thiophosphorylation; and further, the nucleotides of nucleotide numbers 3, 4, 6, 27, and 28 of the antisense strand (SEQ ID NO: 2) were subjected to 2'-ribose methylation as well as thiophosphorylation of their skeletal bond” (See [0094]).
It would have been prima facie obvious for a skilled artisan to incorporate the disclosure of “2’-O ribose methylation” to various positions of the nucleotides of siRNA molecules taught by Yokata et al. (US 2010/0234282 A1) into the combined teachings of Goyal et al. (2004), GenBank: AK313678.1 (2008), Juhasz et al. (US 2008/0039420), Lisowiec-Wachnicka et al. (2019) and Tafer (2014) to “provide a system that can deliver in vivo nucleic acids such as an siRNA for suppressing a target gene expression in vivo more safely and efficiently”.
A skilled artisan would be motivated to combine the teachings of Yokata et al. (US 2010/0234282 A1) with the collective teachings of Goyal et al. (2004), GenBank: AK313678.1 (2008), Juhasz et al. (US 2008/0039420), Lisowiec-Wachnicka et al. (2019) and Tafer (2014) with reasonable expectation of success because (i) the three references Lisowiec-Wachnicka et al. (2019), Tafer (2014), and Juhasz et al. (2008) are analogous arts in the same field of endeavor pertaining to compositions for gene-specific inhibition of gene expression by short interfering ribonucleic acid (siRNA) effector molecules, (ii) the teachings of SEQ ID NO. 7 by Juhasz et al. (2008), which includes addition of TT dinucleotide at 3’ end, correspond to SEQ ID NO: 1 (sense) and SEQ ID NO: 2 (antisense) of instant application, and (iii) cDNA, mRNA, and protein sequences of human NOX1 taught by Goyal et al. (2004) and GenBank: AK313678.1 (2008), and (iv) “2’-O ribose methylation” to various positions of the nucleotides of siRNA molecules “provide a system that can deliver in vivo nucleic acids such as an siRNA for suppressing a target gene expression in vivo more safely and efficiently” taught by Yokata et al. (US 2010/0234282 A1)
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Wu-Cheng Winston Shen whose telephone number is (571)272-3157. The examiner can normally be reached Mon. to Fri. 8:00 AM-5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights