Source: https://patents.google.com/patent/US7910566B2/en
Timestamp: 2019-06-25 23:12:58
Document Index: 569215317

Matched Legal Cases: ['application No. 2004', 'Application No. 00914455', 'Application No. 00914455', 'Application No. 00914455', 'Application No. 00914455', 'Application No. 00914455', 'Application No. 00914455', 'Application No. 553987', 'Application No. 2007116168', 'Application No. 00914455', 'Application No. 0702035']

US7910566B2 - Prevention and treatment of acute renal failure and other kidney diseases by inhibition of p53 by siRNA - Google Patents
Prevention and treatment of acute renal failure and other kidney diseases by inhibition of p53 by siRNA Download PDF
US7910566B2
US7910566B2 US12/006,722 US672208A US7910566B2 US 7910566 B2 US7910566 B2 US 7910566B2 US 672208 A US672208 A US 672208A US 7910566 B2 US7910566 B2 US 7910566B2
US12/006,722
US20090105173A1 (en
2006-03-09 Priority to US78103706P priority Critical
2006-10-25 Priority to US85450306P priority
2007-01-18 Priority to US11/655,610 priority patent/US7825099B2/en
2008-01-04 Application filed by Quark Biotech Inc filed Critical Quark Biotech Inc
2008-01-04 Priority to US12/006,722 priority patent/US7910566B2/en
2008-12-29 Assigned to QUARK PHARMACEUTICALS, INC. reassignment QUARK PHARMACEUTICALS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FEINSTEIN, ELENA
2009-04-23 Publication of US20090105173A1 publication Critical patent/US20090105173A1/en
2011-03-22 Publication of US7910566B2 publication Critical patent/US7910566B2/en
5′ (N) 3′ antisense strand
3′ (N′) 5′ sense strand
5′ (N)x 3′ antisense strand
3′ (N′)y 5′ sense strand
In an embodiment the first stretch and for the second stretch comprises from about 14 to 40 nucleotides, preferably about 18 to 30 nucleotides, more preferably from about 19 to 27 nucleotides and most preferably from about 19 to 23 nucleotides, in particular from about 19 to 21 or from about 19 to 23 nucleotides. In such an embodiment the oligonucleotide may be 17-40 nucleotides in length.
Delivery systems aimed specifically at the enhanced and improved delivery of siRNA into mammalian cells have been developed, see, for example, Shen et al (FEBS letters 539: 111-114 (2003)). Xia et al., Nature Biotechnology 20: 1006-1010 (2002), Reich et al., Molecular Vision 9: 210-216 (2003), Sorensen et al. (J. Mol. Biol. 327: 761-766 (2003), Lewis et al., Nature Genetics 32: 107-108 (2002) and Simeoni et al., Nucleic Acids Research 31, 11: 2717-2724 (2003). siRNA has recently been successfully used for inhibition in primates; for further details see Tolentino et al., Retina 24(1) February 2004 I 132-138. Respiratory formulations for siRNA are described in U.S. patent application No. 2004/0063654 of Davis et al. Cholesterol-conjugated siRNAs (and other steroid and lipid conjugated siRNAs) can been used for delivery see Soutschek et al Nature 432: 173-177(2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs; and Lorenz et al. Bioorg. Med. Chemistry. Lett. 14:4975-4977 (2004) Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells.
11 QM4 GGACAGCCAAGUCUGUUAU AUAACAGACUUGCCUGUCC mouse, rat 2 mis 877-895 527-545
13 A17 CUGGGACAGCCAAGUCUGU ACAGACUUGGCUGUCCCAG hum, mus 598-616 874-892 2-mis
16 B1 GCGCCAUGGCCAUCUACAA UUGUAGAUGGCCAUGGCGC hum 724-742 1000-1018 652-668(17)
17 B2 CGCCAUGGCCAUCUACAAG CUUGUAGAUGGCCAUGGCG hum, 725-743 1001-1019 652-669(18)
21 G1 GACAGAAACACUUUUCGAC GUCGAAAAGUGUUUCUGUC 873-891 No No
gi2689466 gi53575emb gi499622
gi13097806 gbU48957.1 X01237. 9dbjAB02
gbBC003596.1 U48957 1MMP53R 0761.1
(Homo (Macaca (Mouse (Canis
No. Source Sense AntiSense sapiens) fascicularis) mRNA) familiaris)
1 Human GUACCACCAUCCACUACAA UUGUAGUGGAUGGUGGUAC [806-824] [835-852]
2 Human GGAAACUACUUCCUGAAAA UUUUCAGGAAGUAGUUUCC [188-206] [234-247]
3 Human AGACUCCAGUGGUAAUCUA UAGAUUACCACUGGAGUCU [894-912] [922-933]
4 Human CCAUCCACUACAACUACAU AUGUAGUUGUAGUGGAUGG [812-830] [840-858]
5 Human CCACCAUCCACUACAACUA UAGUUGUAGUGGAUGGUGG [809-827] [837-852]
6 Human AAACACUUUUCGACAUAGU ACUAUGUCGAAAAGUGUUU [747-765] —
7 Human CAUGAGCGCUGCUCAGAUA UAUCUGAGCAGCGCUCAUG [655-673] [683-696]
8 Human CCAUGGCCAUCUACAAGCA UGCUUGUAGAUGGCCAUGG [596-614] [624-640]
9 Human CCAAGUCUGUGACUUGCAC GUGCAAGUCACAGACUUGG [476-494] —
10 Human AAACUUUGCUGCCAAAAAA UUUUUUGGCAGCAAAGUUU [2476-2494] —
11 Human CCCUCCUUCUCCCUUUUUA UAAAAAGGGAGAAGGAGGG [2421-2439] —
12 Human GCAAGCACAUCUGCAUUUU AAAAUGCAGAUGUGCUUGC [2389-2407] —
13 Human GGGUCAACAUCUUUUACAU AUGUAAAAGAUGUUGACCC [2367-2385] —
14 Human GAAGGGUCAACAUCUUUUA UAAAAGAUGUUGACCCUUC [2364-2382] —
15 Human CUGGAAGGGUCAACAUCUU AAGAUGUUGACCCUUCCAG [2361-2379] —
16 Human CCAGAGUGCUGGGAUUACA UGUAAUCCCAGCACUCUGG [2321-2339] —
17 Human GAUGGGGUCUCACAGUGUU AACACUGUGAGACCCCAUC [2249-2267] —
18 Human GCCAACUUUUGCAUGUUUU AAAACAUGCAAAAGUUGGC [2225-2243] —
19 Human CCAUGGCCAGCCAACUUUU AAAAGUUGGCUGGCCAUGG [2216-2234] —
20 Human AGACCCAGGUCCAGAUGAA UUCAUCUGGACCUGGGUCU [288-306] —
21 Human, CCAUCAUCACACUGGAAGA UCUUCCAGUGUGAUGAUGG [878-896] [906-924]
22 Human, CAUCACACUGGAAGACUCC GGAGUCUUCCAGUGUGAUG [882-900] [910-928]
23 Human, CAUCAUCACACUGGAAGAC GUCUUCCAGUGUGAUGAUG [879-897] [907-925]
24 Human, ACCAUCAUCACACUGGAAG CUUCCAGUGUGAUGAUGGU [877-895] [905-923]
25 Human, AUCAUCACACUGGAAGACU AGUCUUCCAGUGUGAUGAU [880-898] [908-926]
26 Human, CACUGGAAGACUCCAGUGG CCACUGGAGUCUUCCAGUG [887-905] [915-933]
27 Human, ACACUGGAAGACUCCAGUG CACUGGAGUCUUCCAGUGU [886-904] [766-784] [914-932]
28 Human, UCACACUGGAAGACUCCAG CUGGAGUCUUCCAGUGUGA [884-902] [764-782] [912-930]
29 Human, AUCACACUGGAAGACUCCA UGGAGUCUUCCAGUGUGAU [883-901] [763-781] [911-929]
30 Human, CACAGCACAUGACGGAGGU ACCUCCGUCAUGUGCUGUG [617-635] [497-515] [645-663]
31 Human, CACUGGAAGACUCCAGUGG CCACUGGAGUCUUCCAGUG [887-905] [767-785] [915-933]
32 Human, UCACAGCACAUGACGGAGG CCUCCGUCAUGUGCUGUGA [616-634] [496-514] [644-662]
33 Human, GUCACAGCACAUGACGGAG CUCCGUCAUGUGCUGUGAC [615-633] [495-513] [643-661]
34 Human, CCAUCCACUACAACUACAU AUGUAGUUGUAGUGGAUGG [812-830] [692-710] [702-720]
35 Human, CCACCAUCCACUACAACUA UAGUUGUAGUGGAUGGUGG [809-827] [689-707] [699-717]
36 Human, GAAUAUUUCACCCUUCAGA UCUGAAGGGUGAAAUAUUC [1096-1114] [976-994] [986-1004]
37 Human, CGAGUGGAAGGAAAUUUGC GCAAAUUUCCUUCCACUCG [706-724] [586-604] [596-614]
38 Human, GAGAAUAUUUCACCCUUCA UGAAGGGUGAAAUAUUCUC [1094-1112] [974-992] [984-1002]
39 Human, CUACAUGUGUAACAGUUCC GGAACUGUUACACAUGUAG [825-843] [705-723] [715-733]
40 Human, AACUACAUGUGUAACAGUU AACUGUUACACAUGUAGUU [823-841] [703-721] [713-731]
41 Human, CAACUACAUGUGUAACAGU ACUGUUACACAUGUAGUUG [822-840] [702-720] [712-730]
42 Human, CACUACAACUACAUGUGUA UACACAUGUAGUUGUAGUG [817-835] [697-715] [707-725]
43 Human, CCACUACAACUACAUGUGU ACACAUGUAGUUGUAGUGG [816-834] [696-714] [706-724]
44 Human, GACAGAAACACUUUUCGAC GUCGAAAAGUGUUUCUGUC [742-760] [622-640] [632-650]
45 Human, GGAGAAUAUUUCACCCUUC GAAGGGUGAAAUAUUCUCC [1093-1111] [973-991] [983-1001]
46 Human, GUGUAACAGUUCCUGCAUG CAUGCAGGAACUGUUACAC [831-849] [711-729] [721-739]
47 Human, ACAACUACAUGUGUAACAG CUGUUACACAUGUAGUUGU [821-839] [701-719] ]711-729]
48 Human, ACUACAACUACAUGUGUAA UUACACAUGUAGUUGUAGU [818-836] [698-716] [708-726]
49 Human, ACCAUCCACUACAACUACA UGUAGUUGUAGUGGAUGGU [811-829] [691-709] [701-719]
50 Human, ACCACCAUCCACUACAACU AGUUGUAGUGGAUGGUGGU [808-826] [688-706] [698-716]
51 Human, UACCACCAUCCACUACAAC GUUGUAGUGGAUGGUGGUA [807-825] [687-705] [697-715]
52 Human, ACAGAAACACUUUUCGACA UGUCGAAAAGUGUUUCUGU [743-761] [623-641] [633-651]
53 Human, GAGUGGAAGGAAAUUUGCG CGCAAAUUUCCUUCCACUC [707-725] [587-605] [597-615]
54 Human, AUAUUUCACCCUUCAGAUC GAUCUGAAGGGUGAAAUAU [1098-1116] [978-996] [988-1006]
55 Human, AAUAUUUCACCCUUCAGAU AUCUGAAGGGUGAAAUAUU [1097-1115] [977-995] [987-1005]
56 Human, AGAAUAUUUCACCCUUCAG CUGAAGGGUGAAAUAUUCU [1095-1113] [975-993] [985-1003]
57 Human, UGGAGAAUAUUUCACCCUU AAGGGUGAAAUAUUCUCCA [1092-1110] [972-990] [982-1000]
58 Human, ACAUGUGUAACAGUUCCUG CAGGAACUGUUACACAUGU [827-845] [707-725] [717-735]
59 Human, UACAACUACAUGUGUAACA UGUUACACAUGUAGUUGUA [820-838] [700-718] [710-728]
60 Human, CUACAACUACAUGUGUAAC GUUACACAUGUAGUUGUAG [819-837] [699-717] [709-727]
61 Human, UCCACUACAACUACAUGUG CACAUGUAGUUGUAGUGGA [815-833] [695-713] [705-723]
62 Human, AUCCACUACAACUACAUGU ACAUGUAGUUGUAGUGGAU [814-832] [694-712] [704-722]
63 Human, CAUCCACUACAACUACAUG CAUGUAGUUGUAGUGGAUG [813-831] [693-711] [703-721]
64 Human, CACCAUCCACUACAACUAC GUAGUUGUAGUGGAUGGUG [810-828] [690-708] [700-718]
65 Human, UGUGUAACAGUUCCUGCAU AUGCAGGAACUGUUACACA [830-848] [710-728] [720-738]
66 Human, CAUGUGUAACAGUUCCUGC GCAGGAACUGUUACACAUG [828-846] [708-726] [718-736]
67 Human, UACAUGUGUAACAGUUCCU AGGAACUGUUACACAUGUA [826-844] [706-724] [716-734]
68 Human, ACUACAUGUGUAACAGUUC GAACUGUUACACAUGUAGU [824-842] [704-722] [714-732]
69 Human, AUCCGAGUGGAAGGAAAUU AAUUUCCUUCCACUCGGAU [703-721] [583-601] [593-611]
70 Human, UCACUCCAGCCACCUGAAG CUUCAGGUGGCUGGAGUGA [1212-1230] [1092-1110] [1102-1120]
71 Human, CUCACUCCAGCCACCUGAA UUCAGGUGGCUGGAGUGAG [1211-1229] [1091-1109] [1101-1119]
gi13097806 gbU48957.1 gi53575emb gi4996229
gbBC00359 U48957 X01237.1M dbj
6.1 (Macaca MP53R AB020761.1
(Homo fasci- (Mouse (Canis
No. Source Sense SIRNA AntiSense SiRNA sapiens) cularis) mRNA) familiaris)
1 Human GGAAGAGAAUCUCCGCAAGAA UUCUUGCGGAGAUUCUCUUCC [975-995] — — —
2 Human GUACCACCAUCCACUACAACU AGUUGUAGUGGAUGGUGGUAC [806-826] [686-706] [835-852] [697-716]
3 Human GGACGAUAUUGAACAAUGGUU AACCAUUGUUCAAUAUCGUCC [261-281] — — —
4 Human CCAGCCACCUGAAGUCCAAAA UUUUGGACUUCAGGUGGCUGG [1217-1237] [1097-1115] — [1107-1120]
5 Human GAGAAUAUUUCACCCUUCAGA UCUGAAGGGUGAAAUAUUCUC [1094-1114] [974-994] [1122-1137] [984-1004]
6 Human AGAAACCACUGGAUGGAGAAU AUUCUCCAUCCAGUGGUUUCU [1079-1099] [959-979] — —
7 Human CUACUGGGACGOAACAGCUUU AAAGCUGUUCCGUCCCAGUAG [910-930] [790-810] — —
8 Human AGACUCCAGUGGUAAUCUACU AGUAGAUUACCACUGGAGUCU [894-914] [774-794] [922-933] [784-795]
9 Human CUGGAAGACUCCAGUGGUAAU AUUACCACUGGAGUCUUCCAG [889-909] [769-789] [917-933] [779-795]
10 Human GAAACUACUUCCUGAAAACAA UUGUUUUCAGGAAGUAGUUUC [189-209] [69-87] [235-247] [122-135]
11 Human GGAAACUACUUCCUGAAAACA UGUUUUCAGGAAGUAGUUUCC [188-208] [68-87] [234-247] [122-134]
12 Human AAACACUUUUCGACAUAGUGU ACACUAUGUCGAAAAGUGUUU [747-767] [627-647] — [637-657]
13 Human GGAGUAUUUGGAUGACAGAAA UUUCUGUCAUCCAAAUACUCC [729-749] [609-629] — —
14 Human UCAGACCUAUGGAAACUACUU AAGUAGUUUCCAUAGGUCUGA [178-198] [58-78] [231-244] —
15 Human CCAUGGCCAUCUACAAGCAGU ACUGCUUGUAGAUGCCCAUGG [596-616] [476-496] [624-640] [485-495]
16 Human CCAAGUCUGUGACUUGCACGU ACGUGCAAGUCACAGACUUGG [476-496] [356-376] — —
17 Human GGACAGCCAAGUCUGUGACUU AAGUCACAGACUUGGCUGUCC [470-490] [352-370] [498-513] [357-377]
18 Human CCCUCCUUCUCCCUUUUUAUA UAUAAAAAGGGAGAAGGAGGG [2421-2441] — [1721-1731] —
19 Human, CCAUCCACUACAACUACAUGU ACAUGUAGUUGUAGUGGAUGG [812-832] [692-712] [840-860] [702-722]
20 Human, CCACCAUCCACUACAACUACA UGUAGUUGUAGUGGAUGGUGG [809-829] [689-709] [837-857] [699-719]
21 Human, GAGAAUAUUUCACCCUUCAGA UCUGAAGGGUGAAAUAUUCUC [1094-1114] [974-994] [984-1004]
22 Human, GGAGAAUAUUUCACCCUUCAG CUGAAGGGUGAAAUAUUCUCC [1093-1113] [973-993] [983-1003]
23 Human, CUACAUGUGUAACAGUUCCUG CAGGAACUGUUACACAUGUAG [825-845] [705-725] [715-735]
24 Human, ACAACUACAUGUGUAACAGUU AACUGUUACACAUGUAGUUGU [821-841] [701-721] [711-731]
25 Human, CCACUACAACUACAUGUGUAA UUACACAUGUAGUUGUAGUGG [8 16-836] [696-716] [706-726]
26 Human, CACCAUCCACUACAACUACAU AUGUAGUUGUAGUGGAUGGUG [810-830] [690-710] [700-720]
27 Human, GAAUAUUUCACCCUUCAGAUC GAUCUGAAGGGUGAAAUAUUC [1096-11161 [976-996] [986-1006]
28 Human, AGAAUAUUUCACCCUUCAGAU AUCUGAAGGGUGAAAUAUUCU [1095-1115] [975-995] [985-1005]
29 Human, UACCACCAUCCACUACAACUA UAGUUGUAGUGGAUGGUGGUA [807-827] [687-707] [697-717]
30 Human, GAUGGAGAAUAUUUCACCCUU AAGGGUGAAAUAUUCUCCAUC [1090-1110] [970-990] [980-1000]
31 Human, CCGAGUGGAAGGAAAUUUGCG CGCAAAUUUCCUUCCAGUCGG [705-725] [585-605] [595-615]
32 Human, AACUACAUGUGUAACAGUUCC GGAACUGUUACACAUGUAGUU [823-843] [703-723] [713-733]
33 Human, CAACUACAUGUGUAACAGUUC GAACUGUUACACAUGUAGUUG [822-842] [702-722] [712-732]
34 Human, ACUACAACUACAUGUGUAACA UGUUACACAUGUAGUUGUAGU [8 18-838] [698-718] [708-728]
35 Human, CACUACAACUACAUGUGUAAC GUUACACAUGUAGUUGUAGUG [817-8371 [697-717] [707-727]
36 Human, UCCACUACAACUACAUGUGUA UACACAUGUAGUUGUAGUGGA [815-835] [695-715] [705-725]
37 Human, CAUCCACUACAACUACAUGUG CACAUGUAGUUGUAGUGGAUG [813-833] [693-713] [703-723]
38 Human, ACCAUCCACUACAACUACAUG CAUGUAGUUGUAGUGGAUGGU [811-831] [691-711] [701-721]
39 Human, UGGAGAAUAUUUCACCCUUCA UGAAGGGUGAAAUAUUCUCCA [1092-1112] [972-992] [982-1002]
40 Human, AUGUGUAACAGUUCCUGCAUG CAUGCAGGAACUGUUACACAU [829-849] [709-729] [719-739]
41 Human, CAUGUGUAACAGUUCCUGCAU AUGCAGGAACUGUUACACAUG [828-848] [708-728] [718-738]
42 Human, UACAACUACAUGUGUAACAGU ACUGUUACACAUGUAGUUGUA [820-840] [700-720] [710-730]
43 Human, CUACAACUACAUGUGUAACAG CUGUUACACAUGUAGUUGUAG [819-839] [699-719] [709-729]
44 Human, AUCCACUACAACUACAUGUGU ACACAUGUAGUUGUAGUGGAU [814-834] [694-714] [704-724]
45 Human, ACCACCAUCCACUACAACUAC GUAGUUGUAGUGGAUGGUGGU [808-828] [688-708] [698-718]
46 Human, AAUAUUUCACCCUUCAGAUCC GGAUCUGAAGGGUGAAAUAUU [1097-1117] [977-997] [987-1007]
47 Human, ACUACAUGUGUAACAGUUCCU AGGAACUGUUACACAUGUAGU [824-844] [704-724] [714-734]
48 Human, AUGGAGAAUAUUUCACCCUUC GAAGGGUGAAAUAUUCUCCAU [1091-1111] [971-991] [981-1001]
49 Human, UGUGUAACAGUUCCUGCAUGG CCAUGCAGGAACUGUUACACA [830-850] [710-730] [720-740]
50 Human, UCCGAGUGGAAGGAAAUUUGC GCAAAUUUCCUUCCACUCGGA [704-724] [584-604] [594-614]
51 Human, AUCCGAGUGGAAGGAAAUUUG CAAAUUUCCUUCCACUCGGAU [703-723] [583-603] [593-613]
52 Human, UCACACUGGAAGACUCCAGUG CACUGGAGUCUUCCAGUGUGA [884-904] [764-784] [912-932]
53 Human, AUCACACUGGAAGACUCCAGU ACUGGAGUCUUCCAGUGUGAU [883-903] [763-783] [911-931]
54 Human, CACACUGGAAGACUCCAGUGG CCACUGGAGUCUUCCAGUGUG [885-905] [765-785] [913-933]
55 Human, UCAUCACACUGGAAGACUCCA UGGAGUCUUCCAGUGUGAUGA [881-901] [909-929]
56 Human, CCAUCAUCACACUGGAAGACU AGUCUUCCAGUGUGAUGAUGG [878-898] [906-926]
57 Human, CAUCACACUGGAAGACUCCAG CUGGAGUCUUCCAGUGUGAUG [882-902] [910-930]
58 Human, CAUCAUCACACUGGAAGACUC GAGUCUUCCAGUGUGAUGAUG [879-899] [907-927]
59 Human, ACCAUCAUCACACUGGAAGAC GUCUUCCAGUGUGAUGAUGGU [877-897] [905-925]
60 Human, UCACACUGGAAGACUCCAGUG CACUGGAGUCUUCCAGUGUGA [8 84-904] [912-932]
61 Human, AUCACACUGGAAGACUCCAGU ACUGGAGUCUUCCAGUGUGAU [883-903] [911-931]
62 Human, AUCAUCACACUGGAAGACUCC GGAGUCUUCCAGUGUGAUGAU [880-900] [908-928]
63 Human, CACACUGGAAGACUCCAGUGG CCACUGGAGUCUUCCAGUGUG [885-905] [913-933]
Human- Human-
siRNA 120407067; 8400737;
name Sense strand AS strand Other Species ORF:252-1433 ORF:252-1433
1 GGAGAAUAUUUCACCCUUCACAU AUCUGAAGGGUGAAAUAUUCUCC MF, CF 1224-1246 1224-1246
2 UGGAGAAUAUUUCACCCUUCAGA UCUGAAGGGUGAAAUAUUCUCCA MF, CF 1223-1245 1223-1245
3 AUGGAGAAUAUUUCACCCUUCAG CUGAAGGGUGAAAUAUUCUCCAU MF, CF 1222-1244 1222-1244
4 GAUGGAGAAUAUUUCACCCUUCA UGAAGGGUGAAAUAUUCUCCAUC MF, CF 1221-1243 1221-1243
5 GAGAAUAUUUCACCCUUCAGAUC GAUCUGAAGGGUGAAAUAUUCUC MF, CF 1225-1247 1225-1247
6 AGUGUGGUGGUGCCCUAUGAGCC GGCUCAUAGGGCACCACCACACU MF 894-916 894-916
7 UAGUGUGGUGGUGCCCUAUGAGC GCUCAUAGGGCACCACCACACUA MF 893-915 893-915
8 AUAGUGUGGUGGUGCCCUAUGAG CUCAUAGGGCACCACCACACUAU MF 892-914 892-914
9 CAUAGUGUGGUGGUGCCCUAUGA UCAUAGGGCACCACCACACUAUG MF 891-913 891-913
10 GUGUGGUGGUGCCCUAUGAGCCG CGGCUCAUAGGGCACCACCACAC MF 895-917 895-917
11 UGACAGAAACACUUUUCGACAUA UAUGUCGAAAAGUGUUUCUGUCA MF, CF, Sus scrofa 872-894 872-894
12 AUGACAGAAACACUUUUCGACAU AUGUCGAAAAGUGUUUCUGUCAU MF, CF, Sus scrofa 871-893 871-893
13 GAUGACAGAAACACUUUUCGACA UGUCGAAAAGUGUUUCUGUCAUC MF, CF, Sus scrofa 870-892 870-892
14 GGAUGACAGAAACACUUUUCGAC GUCGAAAAGUGUUUCUGUCAUCC MF, CF, Sus scrofa 869-891 869-891
15 GACAGAAACACUUUUCGACAUAG CUAUGUCGAAAAGUGUUUCUGUC MF, CF, Sus scrofa 873-895 873-895
16 UCCGAGUGGAAGGAAAUUUGCGU ACGCAAAUUUCCUUCCACUCGGA MF, CF 835-857 835-857
17 AUCCGAGUGGAAGGAAAUUUGCG CGCAAAUUUCCUUCCACUCGGAU MF, CF 834-856 834-856
18 UAUCCGAGUGGAAGGAAAUUUGC GCAAAUUUCCUUCCACUCGGAUA MF, CF 833-855 833-855
19 UUAUCCGAGUGGAAGGAAAUUUG CAAAUUUCCUUCCACUCGGAUAA MF, CF 832-854 832-854
20 CCGAGUGGAAGGAAAUUUGCGUG CACGCAAAUUUCCUUCCACUCGG MF, CF 836-858 836-858
21 AUCAUCACACUGGAAGACUCCAG CUGGAGUCUUCCAGUGUGAUGAU Mus musculus, 1011-1033 1011-1033
22 CAUCAUCACACUGGAAGACUCCA UGGAGUCUUCCAGUGUGAUGAUG Mus musculus, 1010-1032 1010-1032
23 CCAUCAUCACACUGGAAGACUCC GGAGUCUUCCAGUGUGAUGAUGG Mus musculus, 1009-1032 1009-1032
24 ACCAUCAUCACACUGGAAGACUC GAGUCUUCCAGUGUGAUGAUGGU Mus musculus, 1008-1031 1008-1031
25 UCAUCACACUGGAAGACUCCAGU ACUGGAGUCUUCCAGUGUGAUGA Mus musculus, 1012-1034 1012-1034
26 UCCCAAGCAAUGGAUGAUUUGAU AUCAAAUCAUCCAUUGCUUGGGA 360-382 360-382
27 GUCCCAAGCAAUGGAUGAUUUGA UCAAAUCAUCCAUUGCUUGGGAC 359-381 359-381
28 CGUCCCAAGCAAUGGAUGAUUUG CAAAUCAUCCAUUGCUUGGGACG 358-380 358-380
29 CCGUCCCAAGCAAUGGAUGAUUU AAAUCAUCCAUUGCUUGGGACGG 357-379 357-379
30 CCCAAGCAAUGGAUGAUUUGAUG CAUCAAAUCAUCCAUUGCUUGGG 361-383 361-383
31 UCAGACCUAUGGAAACUACUUCC GGAAGUAGUUUCCAUAGGUCUGA MF 309-331 309-331
32 UUCAGACCUAUGGAAACUACUUC GAAGUAGUUUCCAUAGGUCUGAA MF 308-330 30 8-330
33 UUUCAGACCUAUGGAAACUACUU AAGUAGUUUCCAUAGGUCUGAAA MF 307-329 307-329
34 UUUUCAGACCUAUGGAAACUACU AGUAGUUUCCAUAGGUCUGAAAA MF 306-328 306-328
35 CAGACCUAUGGAAACUACUUCCU AGGAACUAGUUUCCAUAGGUCUG MF 310-332 310-332
Example 2 Testing the siRNA Compounds for Anti-p53 Activity
2. In a sterile, plastic tube, Lipofectamine2000 reagent (the amount is calculated according to 5 ul per well) was added to 250 ul serum-free medium, and incubated for 5 min at room temperature.
4. Lipofectamine2000 complex was combined with the p53 oligonucleotide solution and incubated for 20 min at room temperature.
40 h after transfection, 5 Fu (Sigma) was added to cells to produce a final concentration of 25 ug/ml. 48 h after cells transfection (8 h after 5 Fu treatment), the cells were harvested and proteins were extracted using RIPA buffer.
2. In sterile, plastic tube, Lipofectamine2000 reagent (5 ul per well) was added to 250 ul serum-free medium, and incubated for 5 min at room temperature.
3. In another tube 4 ug DNA (p53 gene:GFP gene, 10:1) and human p53 oligonucleotides were added to 250 ul serum free medium.
4. Lipofectamine2000 complex was combined with p53 oligonucleotides solution and incubated for 20 min at room temperature.
6. 48 h alter transfection, cells were harvested and proteins were extracted using RIPA buffer.
Number oligo species source SW480 HCT116
14 E2 human, mouse, rat Proprietary (+) Not tested
15 E6 human, mouse, rat Proprietary (−) Not tested
16 B1 human, mouse, rat Proprietary (−) Not tested
17 B2 human, mouse, rat Proprietary (−) Not tested
18 C1 human, monkey, mouse Proprietary (−) Not tested
19 F2 human, monkey, dog Proprietary (−) Not tested
20 F3 human, monkey, dog Proprietary (+++) (+++)
21 G1 human, monkey, dog Proprietary (+++) Not tested
22 H2 human, monkey, dog Proprietary (+) Not tested
23 I5 human, monkey, dog Proprietary (+++) Not tested
SIRNA TREATED CONTROL EAR
SiRNA-treated Control
(left ear (right ear)
Outer hair Auditory brainstem
cell (OHC) response (Threshold
Treatment loss shift at 32 KHz)
QC/R PBS 100%  30 dB
QJ/R 801 siRNA (REDD14) 20% 17.5 dB
QJ/L GFP 100%  27.5 dB
QN/L 801 siRNA (REDD14) 0% 10 dB
QN/R PBS 100%  17.5 dB
Example 7 Model Systems of Acute Renal Failure (ARF)
Dosage of siRNA Timing of siRNA
single injection administration Creatinin levels in mg/dl
Clamp only 3.8 mg/dl
12 mg/kg 2 h pre-clamp 2.3 mg/dl
12 mg/kg 0.5 h pre-clamp 2.8 mg/dl
12 mg/kg 4 h post-clamp 1.3 mg/dl
12 mg/kg 8 h post-clamp 2.5 mg/dl
12 mg/kg 12 h post-clamp 3.3 mg/dl
12 mg/kg 16 h post-clamp 3.4 mg/dl
6 mg/kg 4 h post-clamp 2.2 mg/dl
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US20060069056A1 (en) * 2004-09-28 2006-03-30 Elena Feinstein Oligoribonucleotides and methods of use thereof for treatment of alopecia, acute renal failure and other diseases
US20100029746A1 (en) * 2006-01-20 2010-02-04 Quark Pharmaceuticals, Inc. Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
US20110028532A1 (en) * 2004-08-06 2011-02-03 Quark Pharmaceuticals, Inc. Methods of treating eye diseases in diabetic patients
US20110142917A1 (en) * 2008-06-06 2011-06-16 Egvenia Alpert Compositions and methods for treatment of ear disorders
US20150329918A1 (en) * 2011-02-02 2015-11-19 The Trustees Of Princeton University Jagged1 as a marker and therapeutic target for breast cancer bone metastasis
KR20140110683A (en) * 2013-03-05 2014-09-17 경북대학교 산학협력단 Kit for diagnosing renal disease
US4497817A (en) 1979-08-21 1985-02-05 Yamanouchi Pharmaceutical Co., Ltd. 2-Phenylimidazo [2,1-b]benzothiazole derivatives
EP0430334A1 (en) 1989-11-24 1991-06-05 Janssen Pharmaceutica N.V. Immunostimulating 6-aryl-5,6-dihydroimidazo[2,1-b]thiazole derivatives
US20020019425A1 (en) 1999-01-29 2002-02-14 The Board Of Trustees Of The University Of Illinois p53 Inhibitors and therapeutic use of the same
US20050080246A1 (en) 2002-11-05 2005-04-14 Charles Allerson Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
US20060069056A1 (en) 2004-09-28 2006-03-30 Elena Feinstein Oligoribonucleotides and methods of use thereof for treatment of alopecia, acute renal failure and other diseases
US20060217329A1 (en) 2004-08-16 2006-09-28 Elena Feinstein Therapeutic uses of inhibitors of RTP801
US20070185047A1 (en) 2004-06-03 2007-08-09 Balkrishen Bhat Double strand compositions comprising differentially modified strands for use in gene modulation
US20080108583A1 (en) 2006-01-20 2008-05-08 Elena Feinstein Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
2008-01-04 US US12/006,722 patent/US7910566B2/en active Active
US20050222224A1 (en) 1999-01-29 2005-10-06 The Board Of Trustees Of The University Of Illinois p53 Inhibitors and therapeutic use of the same
US7012087B2 (en) 1999-01-29 2006-03-14 The Board Of Trustees Of The University Of Illinois p53 inhibitors and therapeutic use of the same
US6593353B1 (en) 1999-01-29 2003-07-15 Board Of Trustees Of The University Of Illinois p53 inhibitors and therapeutic use of the same
US7008956B2 (en) 1999-01-29 2006-03-07 The Board Of Trustees Of The University Of Illinois p53 inhibitors and therapeutic use of the same
US6982277B2 (en) 1999-01-29 2006-01-03 The Board Of Trutees Of The University Of Illinois P53 inhibitors and therapeutic use of the same
US20080287382A1 (en) 2004-09-28 2008-11-20 Quark Pharmaceuticals, Inc. Oligoribonucleotides and methods of use thereof for treatment of alopecia, acute renal failure and other diseases
US20090082291A1 (en) 2004-09-28 2009-03-26 Quark Biotech, Inc. Methods of treatment of acute renal failure
US20100029746A1 (en) 2006-01-20 2010-02-04 Quark Pharmaceuticals, Inc. Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
Advisory Action issued on Jun. 2, 2008 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Amarzguioui et al. (2003), "Tolerance for mutations and chemical modifications in a siRNA," Nucleic Acids Research, 31(2): 589-595, 2003.
Amendment after notice of allowance filed on Sep. 22, 2010 in connection with Elena Feinstein et al., U.S. Appl. No. 11/655,610, filed Jan. 18, 2007.
Barik, Sailen (2005). "Silence of the Transcripts; RNA Interference In Medicine," J. Mol. Med. 83:764-773.
Bartel, David P. et al. (2004). "MicroRNAs: Genomics Biogenesis, Mechanism, and Function," Cell, 116:281-297.
Bernstein, Emily et al. (2001). "Role For a Bidentate Ribonuclease in the Initiation Step of RNA Interference," Nature, 409:363-366.
Bertrand et al. (2002). "Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo," Biochemical and Biophysical Research Communications, 296:1000-1004.
Bitko, Vira et al. (2004). "Inhibition of Respiratory Viruses By Nasally Administered siRNA," Nature Medicine, 11(1):50-55.
Botchkarev, V.A., et al., (2000). "p53 Is Essential for Chemotherapy-induced Hair Loss," Cancer Res. 60:5002-5006.
Brummelkamp, Thijn R. et al. (2002). "A System For Stable Expression of Short Interfering RNAs in Mammalian Cells," Science, 296: 550-553.
Caplen, Natasha J. et al. (2001). "Specific Inhibition of Gene Expression By Small Double-Stranded RNAs in Invertebrate Vertebrate Systems," PNAS, 98(17):9742-9747.
Chakraborty, Chiranjib (2007). "Potentiality of Small Interfering RNAs (siRNA) as Recent Therapeutic Targets for Gene-Silencing," Current Drug Targets, 8:469-482.
Chalk, Alistair M. et al., (2004). "Improved and Automated Prediction of Effective siRNA," Biochemical and Biophysical Research Communications, 319:264-274.
Cheng, Qing-Li et al. (2000), "Effects of ICAM-1 antisense oligonucleotide on the tubulointerstitium in mice with unilateral ureteral obstruction," Kidney International, vol. 57: 183-190.
Chernov, M.V. and Stark, G.R., (1997). "The p53 activation and apoptosis induced by DNA damage are reversibly inhibited by salicylate," Oncogene 14:2503-2510.
Communication pursuant to Article 96(2) EPC issued by the European Patent Office on Aug. 19, 2004 in connection with European Patent Application No. 00914455.1.
Communication pursuant to Article 96(2) EPC issued by the European Patent Office on Feb. 12, 2004 in connection with European Patent Application No. 00914455.1.
Communication pursuant to Article 96(2) EPC issued by the European Patent Office on Mar. 10, 2006 in connection with European Patent Application No. 00914455.1.
Communication pursuant to Article 96(2) EPC issued by the European Patent Office on May 13, 2005 in connection with European Patent Application No. 00914455.1.
Communication pursuant to Article 96(2) EPC issued by the European Patent Office on Oct. 24, 2006 in connection with European Patent Application No. 00914455.1.
Communication under Rule 112 EPC issued by the European Patent Office on Dec. 16, 2003 in connection with European Patent Application No. 00914455.1.
Cotsarelis, G. and Millar, S.E., (2001). "Towards a molecular understanding of hair loss and its treatment," Trends Mol. Med. 7(7):293-301.
Czauderna F, Fechtner M, Dames S, Aygün H, Klippel A, Pronk GJ, Giese K, Kaufmann J. (2003). "Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells," Nucleic Acids Res. 31(11):2705-16.
Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T. (2001). "Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embroyo lysate," EMBO J. 20(23):6877-88.
Elbashir, Sayda M. et al. (2001). "Duplexes of 21-nucleotide RNAs mediated RNA interference in cultured mammalian cells," Nature, 411:494-498.
Elbashir, Sayda M. et al. (2001). "RNA Interference is Mediated by 21- and 22-nucleotide RNAs," Genes & Development, 15:188-200.
Examination Report issued by the Australian Patent Office on Dec. 22, 2008 in connection with New Zealand Patent Application No. 553987.
Final Office Action issued on Aug. 19, 2009 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Fire, Andrew et al., (1998). "Potent and Specific Genetic Interference by Double-stranded RNA in Caenorhabditis elegans," Nature, 391:806-811.
Gottlieb, T.M., et al., (1996). "p53 in growth control and neoplasia," Biochim Biophys Acta 1287:77-102.
Holen et al., (2002). Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor, Nucleic Acids Research, 30(8):1757-1766.
International Preliminary Report on Patentability issued by the International Searching Authority (ISA/US) on Apr. 2, 2009 in connection with International Application No. PCT/IL05/01035.
International Search Report issued by the International Searching Authority (ISA/US) on Dec. 3, 2007 in connection with International Application No. PCT/IL05/01035.
Komarov, P.G., et al., (1999). "A Chemical Inhibitor of p53 That Protects Mice from the Side Effects of Cancer Therapy," Science 285:1733-1737.
Komarova, E.A., et al., (1997). 'Transgenic mice with p53-responsive lacZ: p53 activity varies dramatically during normal development and determines radiation and drug sensitivity in vivo, EMBO J. 16(6):1391-1400.
Lee, Youngtae et al., (2003). "The nuclear RNase III Drosha initiates microRNA processing," Nature, 425:415-419.
Levenkova, Natasha et al., (2004). "Gene specific siRNA selector," Bioinformatics, 20(3):430-432.
Mahato et al. (2005). "Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA", Expert Opinion on Drug Delivery, 2(1):3-28.
McManus, Michael T. and Sharp, Phillip A., (2002). "Gene Silencing in Mammals by Small Interfering RNAs," Genetics, 3:737-747.
Molitoris et al (2009). "siRNA Targeted to p53 Attenuates Ischemic and Cisplatin-Induced Acute Kidney Injury". J. Am. Soc. Nephrol, published online May 21, 2009.
Non-final Office Action issued on May 1, 2008 in connection with U.S. Appl. No. 11/655,610, filed Jan. 18, 2007.
Non-final Office Action issued on Oct. 2, 2008 in connection with U.S. Appl. No. 11/655,610, filed Jan. 18, 2007.
Non-final Office Action issued on Oct. 28, 2008 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Non-final Official Action issued on May 10, 2010, in connection with Elena Feinstein et al., U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Non-final Official Action issued on May 27, 2010, in connection with Elena Feinstein et al., U.S. Appl. No. 12/459,617, filed Jul. 1, 2009.
Non-final Official Action issued on Oct. 4, 2010, in connection with Elena Feinstein et al., U.S. Appl. No. 12/008,578, filed Jan. 11, 2008.
Notice of Allowance issued on Nov. 18, 2009 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Notice of Allowance mailed on Apr. 7, 2009 in connection with U.S. Appl. No. 11/655,610, filed Jan. 18, 2007.
Notice of Allowance mailed on Jul. 22, 2010 in connection with Elena Feinstein et al., U.S. Appl. No. 11/827,199, filed Jul. 10, 2007 and allowed claims.
Notice of Allowance mailed on Nov. 18, 2009 in connection with Elena Feinstein et al., U.S. Appl. No. 11/237,598, filed Sep. 27, 2005 and allowed claims.
Office Action issued by the Russian Patent Office on Jul. 20, 2009 in connection with Russian Patent Application No. 2007116168.
Office Action issued on Apr. 21, 2005 in connection with U.S. Appl. No. 10/352,597, filed Jan. 28, 2003.
Office Action issued on Apr. 6, 2004 in connection with U.S. Appl. No. 10/350,560, filed Jan. 24, 2003.
Office Action issued on Aug. 19, 2009 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Office Action issued on Dec. 28, 2001 in connection with U.S. Appl. No. 09/947,757, filed Sep. 6, 2001.
Office Action issued on Dec. 3, 2007 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Office Action issued on Feb. 12, 2003 in connection with U.S. Appl. No. 09/880,417, filed Jun. 13, 2001.
Office Action issued on Jan. 3, 2005 in connection with U.S. Appl. No. 10/350,560, filed Jan. 24, 2003.
Office Action issued on Jul. 13, 2004 in connection with U.S. Appl. No. 09/947,757, filed Sep. 6, 2001.
Office Action issued on Jul. 15, 2003 in connection with U.S. Appl. No. 09/947,757, filed Sep. 6, 2001.
Office Action issued on Jul. 2, 2001 in connection with U.S. Appl. No. 09/493,527, filed Jan. 28, 2000.
Office Action issued on Jul. 9, 2004 in connection with U.S. Appl. No. 09/880,417, filed Jun. 13, 2001.
Office Action issued on Jun. 6, 2002 in connection with U.S. Appl. No. 09/493,527, filed Jan. 28, 2000.
Office Action issued on Mar. 14, 2007 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Office Action issued on Mar. 23, 2001 in connection with U.S. Appl. No. 09/493,527, filed Jan. 28, 2000.
Office Action issued on Mar. 26, 2003 in connection with U.S. Appl. No. 09/947,757, filed Sep. 6, 2001.
Office Action issued on Nov. 19, 2003 in connection with U.S. Appl. No. 09/947,757, filed Sep. 6, 2001.
Office Action issued on Nov. 26, 2004 in connection with U.S. Appl. No. 09/947,757, filed Sep. 6, 2001.
Office Action issued on Nov. 9, 2006 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Office Action issued on Oct. 28, 2008 in connection with U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Office Action issued on Oct. 30, 2007 in connection with U.S. Appl. No. 11/136,231, filed May 24, 2005.
Office Action issued on Oct. 9, 2003 in connection with U.S. Appl. No. 09/880,417, filed Jun. 13, 2001.
Office Action issued on Sep. 9, 2004 in connection with U.S. Appl. No. 10/352,597, filed Jan. 28, 2003.
Pending claims in Elena Feinstein et al., U.S. Appl. No. 12/008,578, filed Jan. 11, 2008.
Pending claims in Elena Feinstein, et al., U.S. Appl. No. 11/827,199, filed Jul. 10, 2007.
Pending claims in U.S. Appl. No. 12/459,617, filed Jul. 1, 2009.
Prakash TP, Allerson CR, Dande P, Vickers TA, Sioufi N, Jarres R, Baker BF, Swayze EE, Griffey RH, Bhat B. (2005). "Positional effect of chemical modifications on short interference RNA activity in mammalian cells," J Med Chem. 48(13):4247-53.
Preliminary amendment to the claims filed on Sep. 10, 2010 in connection with Elena Feinstein et al., U.S. Appl. No. 12/008,578, filed Jan. 11, 2008.
Request for Continued Examination filed on Mar. 11, 2010, in connection with Elena Feinstein et al., U.S. Appl. No. 11/237,598, filed Sep. 27, 2005.
Response to Office Action issued on Mar. 14, 2007 in connection with U.S. Appl. No. 11/237,598, filed Sep. 14, 2007.
Response to Office Action issued on Nov. 9, 2006 in connection with U.S. Appl. No. 11/237,598, filed Dec. 8, 2006.
Result of consultation issued by the European Patent Office on Oct. 25, 2005 in connection with European Patent Application No. 00914455.1.
Scherer et al. (2003). "Approaches for the sequence-specific knockdown of mRNA," Nat. Biotechnol., 21 (12):1457-1465.
Schomber et al. (2004). "Gene silencing by lentivirus-mediated delivery of siRNA in human CD34+ cells," Blood, 103(12):4511-4513.
Search Report issued by the Australian Patent Office on May 14, 2008 in connection with Singaporean Application/Patent No. 0702035-7.
Second Written Opinion issued by the Australian Patent Office on May 26, 2009 in connection with Singaporean Application No. 0702035-7.
Sioud, Moudly and Leirdal, Marianne, (2004). "Potential Design Rules and Enzymatic Synthesis of siRNAs," Methods in Molecular Biology, 252:457-468.
Steele, R.J.C., et al., (1998). "The p53 tumour suppressor gene," Br. J. Surg. 85:1460-1467.
Supavekin, S., et al., (2003). "Differential gene expression following early renal ischemia/reperfusion," Kidney Int. 63:1714-1724.
Tekippe, M., et al., (2003). "Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice," Exp. Hematol. 31:521-527.
Tolentino, Michael J. et al., (2004). "Intravitreal Injection of Vascular Endothelial Growth Factor Small Interfering RNA Inhibits Growth and Leakage in a Nonhuman Primate, Laser-induced Model of Choroidal Neovascularization," Retina, The Journal of Retinal and Vitreous Diseases, 24(1):132-138.
Ui-Tei, Kumiko et al., (2004). "Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference," Nucleic Acids Research, 32(3):936-948.
Van de Water, Femke M. et al. (2006). "Intravenously administered short interfering RNA accumulates in the Kidney and selectively suppresses gene function in renal proximal tubules," Drug Metabolism and Disposition. 34:1393-1397.
Wang, J. et al., (2003). "A Peptide Inhibitor of c-Jun N-Terminal Kinase Protects against Both Aminoglycoside and Acoustic Trauma-Induced Auditory Hair Cell Death and Hearing Loss," The J. of Neuroscience, 23(24):8596-8607.
Wlodarski, P., et al., (1998). "Role of p53 in Hematopoietic Recovery After Cytotoxic Treatment9," Blood 91(8):2998-3006.
Written Opinion issued by the Australian patent Office on May 14, 2008 in connection with Singaporean Application/Patent No. 0702035-7.
Written Opinion of the International Searching Authority (ISA/US) issued on Dec. 3,2007 in connection with International Application No. PCT/IL05/01035.
Zhang et al. (2004). "Targeted Gene Silencing by Small Interfering RNA-Based Knock-Down Technology", Current Pharmaceutical Biotechnology, vol. 5:1-7.
Zhang, M. et al., (2003). "Pifithrin-alpha Supresses p53 and Protects Cochlear and Vestibular Hair Cells From Cisplatin-Induced Apoptosis," Neuroscience, 120:191-205.
Zhang, M. et al., (2003). "Pifithrin-α Supresses p53 and Protects Cochlear and Vestibular Hair Cells From Cisplatin-Induced Apoptosis," Neuroscience, 120:191-205.
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US8168607B2 (en) 2004-08-06 2012-05-01 Quark Pharmaceuticals Inc. Methods of treating eye diseases in diabetic patients
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