HRP20120598T1 - Stanično permeabilni peptidni inhibitori jnk signalnog transdukcijskog puta - Google Patents
Stanično permeabilni peptidni inhibitori jnk signalnog transdukcijskog puta Download PDFInfo
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- HRP20120598T1 HRP20120598T1 HRP20120598TT HRP20120598T HRP20120598T1 HR P20120598 T1 HRP20120598 T1 HR P20120598T1 HR P20120598T T HRP20120598T T HR P20120598TT HR P20120598 T HRP20120598 T HR P20120598T HR P20120598 T1 HRP20120598 T1 HR P20120598T1
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims 38
- 239000003112 inhibitor Substances 0.000 title claims 2
- 230000019491 signal transduction Effects 0.000 title claims 2
- 230000002401 inhibitory effect Effects 0.000 claims abstract 15
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims abstract 2
- 125000000539 amino acid group Chemical group 0.000 claims 23
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 claims 22
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 8
- 239000004473 Threonine Substances 0.000 claims 8
- 150000001413 amino acids Chemical group 0.000 claims 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 4
- 108091006116 chimeric peptides Proteins 0.000 claims 4
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 claims 2
- 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 claims 2
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 claims 2
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 claims 2
- 108091023040 Transcription factor Proteins 0.000 claims 2
- 102000040945 Transcription factor Human genes 0.000 claims 2
- 102100023132 Transcription factor Jun Human genes 0.000 claims 2
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- 208000011580 syndromic disease Diseases 0.000 claims 2
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims 1
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- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
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Abstract
JNK inhibicijska sekvenca, naznačena time, da se sastoji od D retro inverzo amino kiselinske sekvence u skladu sa SEQ ID NO: 2. Patent sadrži još 15 patentnih zahtjeva.
Claims (16)
1. JNK inhibicijska sekvenca, naznačena time, da se sastoji od D retro inverzo amino kiselinske sekvence u skladu sa SEQ ID NO: 2.
2. JNK inhibicijska sekvenca prema zahtjevu 1, naznačena time, da JNK inhibicijska sekvenca veže c-jun amino terminalnu kinazu (JNK).
3. JNK inhibicijska sekvenca prema bilo kojem zahtjevu od 1 do 2, naznačena time, da JNK inhibicijska sekvenca inhibira aktivaciju barem jednog JNK ciljanog transkripcijskog faktora kada je navedena JNK inhibicijska sekvenca prisutna u stanici koja eksprimira JNK.
4. JNK inhibicijska sekvenca prema bilo kojem zahtjevu od 1 do 3, naznačena time, da je navedeni JNK ciljani transkripcijski faktor odabran iz skupine koja se sastoji od c-Jun, ATF2 i Elkl.
5. JNK inhibicijska sekvenca prema bilo kojem zahtjevu od 1 do 4, naznačena time, da JNK inhibicijska sekvenca mijenja učinak JNK kada je navedeni peptid prisutan u stanici koja eksprimira JNK.
6. Kimerni peptid, naznačen time, da se sastoji od prve domene i druge domene koje su povezane kovalentnom vezom, pri čemu prva domena sadrži transportnu sekvencu, a druga sadrži JNK inhibicijsku sekvencu prema bilo kojim od zahtjeva od 1-5, gdje je prva domena vezana na C-terminalni kraj druge domene.
7. Peptid prema zahtjevu 6, naznačen time, da transportna sekvenca sadrži amino kiselinsku sekvencu iz TAT polipeptida iz humanog virusa imunodeficijencije.
8. Peptid prema bilo kojem zahtjevu od 6 do 7, naznačen time, da transportna sekvenca sadrži L amino kiselinsku sekvencu iz SEQ ID NO: 5 ili 7 ili D retro-inverzo sekvencu u skladu sa SEQ ID NO: 6 ili 8.
9. Peptid prema bilo kojem zahtjevu od 6 do 8, naznačen time, da transportna sekvenca povećava staničnu absorpciju peptida.
10. Peptid prema bilo kojem zahtjevu od 6 do 9, naznačen time, da transportna sekvenca usmjerava nuklearnu lokalizaciju peptida.
11. Peptid prema bilo kojem zahtjevu od 6 do 10, naznačen time, da JNK inhibicijska sekvenca sadrži D retro-inverzo amino kiselinsku sekvencu u skladu sa SEQ ID NO: 11.
12. Peptid prema bilo kojem zahtjevu od 6 do 11, naznačen time, da peptid sadrži ili se sastoji od D retro-inverzo amino kiselinske sekvence u skladu sa SEQ ID NO: 11.
13. Farmaceutski pripravak, naznačen time, da sadrži JNK inhibicijsku sekvencu koja se sastoji od sekvence prema bilo kojem od zahtjeva od 1 do 5 ili kimerni peptid prema bilo kojem od zahtjeva 6 do 12 i od farmaceutski prihvatljivog nosača.
14. Upotreba JNK inhibicijske sekvence prema bilo kojem od zahtjeva od 1 do 5 ili kimernog peptida prema bilo kojem od zahtjeva 6 do 12, naznačena time, da se koristi za dobivanje farmaceutskog pripravka za liječenje patofiziologije koja je odabrana iz skupine koja sadrži maligne bolesti pluća, dojki, limfnog, gastrointestinalnog i genito-urinarnog trakta kao i adenokarcinoma, uključujući maligna stanja poput raka debelog crijeva, karcinoma renalnih stanica, raka prostate, karcinoma velikih stanica pluća, raka tankog crijeva i raka ezofagusa, kao i leukemije, karcinome sa Bcr-Abl onkogenim transformacijama, psorijazu, pemphigus vulgaris, Behcetov sindrom, akutni respiratorni stresni sindrom (ARDS), ishemijske bolesti srca, post-dijalizni sindroma, reumatoidni artritis, sindrom stečene imuno deficijencije, vaskulitis, septički šok, restenozu, gubitak sluha, ozljedu uha, ishemiju, kap; ozljedu zbog reperfuzije, hipoksiju, sekundarne učinke zbog liječenja s proinflatornim citokinima, dijabetičku, srčanu i kardijalnu hipertrofiju i arteriosklerotske lezije, patološka stanja zbog ionizacijskog zračenja tijekom radioterapije i zračenja sa ultraljubičastim svijetlom (UV svijetlo), patološka stanja prouzročena sredstvima koja oštećuju DNK, uključujući lijekove za kemoterapiju, hipo- i hipertermiju, upalne bolesti, auto-upalne, imune i auto-imune bolesti, degenerativne bolesti, miopatije, kardiomiopatije i odbacivanje transplantata.
15. Uporaba prema zahtjevu 19, naznačena time, da je farmaceutski pripravak namijenjen za davanje putem za davanje koji je odabran iz skupine koja sadrži intraperitonealno, nazalno, intravenozno, oralno davanje i davanje putem flastera.
16. Komplet kemikalija (kit), naznačen time, da sadrži JNK inhibicijsku sekvencu koja se sastoji od sekvence prema bilo kojem od zahtjeva od 1 do 5 i/ili kimernog peptida prema bilo kojem od zahtjeva od 8 do 16.
POPIS SEKVENCI
[0121]
<110> XIGEN S.A.
<120> Peptidni inhibitori JNK signalnog transdukcijskog puta koji mogu ulaziti u stanicu
<130> UO01P006WO1
<150> PCT/EP2005/009782
<151> 2005-09-12
<160> 27
<170> PatentIn verzija 3.3
<210> 1
<211> 19
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-IB1(s) (vidjeti tablicu 1)
<400> 1
[image]
<210> 2
<211> 19
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-IB1(s) (vidjeti tablicu 1)
<400> 2
[image]
<210> 3
<211> 18
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-IB (generički) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(18)
<223> Opća formula: NH2-Xnb-Xna-RPTTLXLXXXXXXXQD-Xnb-COOH, gdje X je bilo koji (nativni) amino kiselinski ostatak, Xna je bilo koji amino kiselinski ostatak osim serina i treonina, a Xnb može biti bilo koji amino kiselinski ostatak;
<220>
<221> ponavljanje
<222> (1)...(1)
<223> Xaa je Xna-Xnb kako je definirano u općoj formuli, gdje n je 0 ili 1 za Xna i 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (18)...(18)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<400> 3
[image]
<210> 4
<211> 18
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-IB (generički) (s) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(18)
<223> Opća formula: NH2-Xnb-DQXXXXXXXLXLTTPR-Xna-Xnb-COOH, gdje X je bilo koji (nativni) amino kiselinski ostatak, Xna je bilo koji amino kiselinski ostatak osim serina i treonina, a Xnb može biti bilo koji amino kiselinski ostatak;
<220>
<221> ponavljanje
<222> (1)...(1)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (18)...(18)
<223> Xaa je Xna-Xnb kako je definirano u općoj formuli, gdje n je 0 ili 1 za Xna, a 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<400> 4
[image]
<210> 5
<211> 10
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-TAT (vidjeti tablicu 1)
<400> 5
[image]
<210> 6
<211> 10
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-TAT (vidjeti tablicu 1)
<400> 6
[image]
<210> 7
<211> 17
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-generički-TAT (s) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(17)
<223> Opća formula: NH2-Xnb-RKKRRQRRR-Xnb-COOH, gdje Xnb može biti bilo koji amino kiselinski ostatak;
<220>
<221> ponavljanje
<222> (1)...(4)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (14)...(17)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<400> 7
[image]
<210> 8
<211> 17
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-generički-TAT (s) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(17)
<223> Opća formula: NH2-Xnb-RRRQRRKKR-Xnb-COOH, gdje Xnb može biti bilo koji amino kiselinski ostatak;
<220>
<221> ponavljanje
<222> (1)...(4)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (14)...(17)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<400> 8
[image]
<210> 9
<211> 31
<212> PRT
<213> Umjetna
<220>
<223> L-TAT-IB1 (s) (vidjeti tablicu 1)
<400> 9
[image]
<210> 10
<211> 38
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-TAT (generički) (s) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(38)
<223> Opća formula: NH2-Xnb-RKKRRQRRR-Xnb-Xna-RPTTLXLXXXXXXXQD-Xnb-COOH, gdje X je bilo koji (nativni) amino kiselinski ostatak, Xna je bilo koji amino kiselinski ostatak osim serina i treonina, a Xnb može biti bilo koji amino kiselinski ostatak;
<220>
<221> ponavljanje
<222> (1)...(7)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (17)...(21)
<223> Xaa je Xna-Xnb kako je definirano u općoj formuli, gdje n je 0 ili 1 za Xna, a 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (38)...(38)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<400> 10
[image]
<210> 11
<211> 31
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-TAT-IB1 (s) (vidjeti tablicu 1)
<400> 11
[image]
<210> 12
<211> 38
<212> PRT
<213> Umjetna
<220>
<223> Peptid: D-TAT (generički) (s) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(38)
<223> Opća formula: NH2-Xnb-DQXXXXXXXLXLTTPR-Xna-Xnb-RRRQRRKKR-Xnb-COOH, gdje X je bilo koji (nativni) amino kiselinski ostatak, Xna je bilo koji amino kiselinski ostatak osim serina i treonina, a Xnb može biti bilo koja amino kiselina;
<220>
<221> ponavljanje
<222> (1)...(7)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (18)...(22)
<223> Xaa je Xna-Xnb kako je definirano u općoj formuli, gdje n je 0 ili 1 za Xna, a 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<220>
<221> ponavljanje
<222> (38)...(38)
<223> Xaa je Xnb kako je definirano u općoj formuli, gdje n je 0-5, 5-10, 10-15, 15-20, 20-30 ili više za Xnb
<400> 12
[image]
<210> 13
<211> 29
<212> PRT
<213> Umjetna
<220>
<223> peptid IB1-dugi (vidjeti tablicu 1)
<400> 13
[image]
[image]
<210> 14
<211> 27
<212> PRT
<213> Umjetna
<220>
<223> Peptid IB2-dugi (vidjeti tablicu 1)
<400> 14
[image]
<210> 15
<211> 29
<212> PRT
<213> Umjetna
<220>
<223> Peptid izveden iz c-Jun (vidjeti tablicu 1)
<400> 15
[image]
<210> 16
<211> 29
<212> PRT
<213> Umjetna
<220>
<223> Peptid izveden iz ATF2 (vidjeti tablicu 1)
<400> 16
[image]
<210> 17
<211> 23
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-IB1 (vidjeti tablicu 1)
<400> 17
[image]
<210> 18
<211> 23
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-IB1 (vidjeti tablicu 1)
<400> 18
[image]
<210> 19
<211> 19
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-IB (generički) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1) .. (17)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<220>
<221> različita_značajka
<222> (18) .. (18)
<223> X je odabran iz serina ili treonina
<220>
<221> različita_značajka
<222> (19) .. (19)
223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<400> 19
[image]
<210> 20
<211> 19
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-IB (generički) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1) .. (1)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<220>
<221> misc feature
<222> (2)..(2)
<223> X je odabran iz serina ili treonina
<220>
<221> različita_značajka
<222> (3) .. (19)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<400> 20
[image]
<210> 21
<211> 17
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-generički-TAT (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1)..(17)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<400> 21
[image]
<210> 22
<211> 17
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-generički-TAT (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1) .. (17)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<400> 22
[image]
<210> 23
<211> 35
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-TAT-IB1 (vidjeti tablicu 1)
<400> 23
[image]
<210> 24
<211> 42
<212> PRT
<213> Umjetna
<220>
<223> Peptid L-TAT (generički) (vidjeti tablicu 1)
<220>
<221> misc feature
<222> (1) .. (40)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<220>
<221> različita_značajka
<222> (41) .. (41)
<223> X je odabran iz serina ili treonina
<220>
<221> različita_značajka
<222> (42) .. (42)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<400> 24
[image]
<210> 25
<211> 35
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-TAT-IB1 (vidjeti tablicu 1)
<400> 25
[image]
<210> 26
<211> 42
<212> PRT
<213> Umjetna
<220>
<223> Peptid D-TAT (generički) (vidjeti tablicu 1)
<220>
<221> različita_značajka
<222> (1) .. (1)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<220>
<221> različita_značajka
<222> (2) .. (2)
<223> X je odabran iz serina ili treonina;
<220>
<221> različita_značajka
<222> (3) .. (42)
<223> X je odabran iz bilo kojeg (nativnog) amino kiselinskog ostatka,
<400> 26
[image]
<210> 27
<211> 21
<212> DNA
<213> Umjetna
<220>
<223> Proba za test retardacije gela (vidjeti Primjer 13)
<400> 27
CGCTTGATGA GTCAGCCGGA A 21
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| PCT/EP2005/009782 WO2007031098A1 (en) | 2005-09-12 | 2005-09-12 | Cell-permeable peptide inhibitors of the jnk signal transduction pathway |
| PCT/EP2006/008882 WO2007031280A2 (en) | 2005-09-12 | 2006-09-12 | Cell-permeable peptide inhibitors of the jnk signal transduction pathway |
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| HRP20160379TT HRP20160379T1 (hr) | 2005-09-12 | 2016-04-12 | Stanično permeabilni peptidni inhibitori jnk signalnog transdukcijskog puta |
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| WO2007031098A1 (en) | 2005-09-12 | 2007-03-22 | Xigen S.A. | Cell-permeable peptide inhibitors of the jnk signal transduction pathway |
| US8080517B2 (en) | 2005-09-12 | 2011-12-20 | Xigen Sa | Cell-permeable peptide inhibitors of the JNK signal transduction pathway |
| WO2008034161A1 (en) | 2006-09-19 | 2008-03-27 | Phylogica Limited | Neuroprotective peptide inhibitors of ap-1 signaling and uses therefor |
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| US11969501B2 (en) | 2008-04-21 | 2024-04-30 | Dompé Farmaceutici S.P.A. | Auris formulations for treating otic diseases and conditions |
| RU2499592C2 (ru) | 2008-04-21 | 2013-11-27 | Отономи, Инк. | Фармацевтическая композиция для лечения ушных заболеваний |
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| US8648119B2 (en) | 2008-05-23 | 2014-02-11 | Otonomy, Inc. | Controlled release immunomodulator compositions and methods for the treatment of otic disorders |
| WO2009143864A1 (en) * | 2008-05-30 | 2009-12-03 | Xigen S.A. | Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of chronic or non-chronic inflammatory digestive diseases |
| WO2009143865A1 (en) * | 2008-05-30 | 2009-12-03 | Xigen S.A. | Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases |
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| WO2010011466A2 (en) | 2008-06-27 | 2010-01-28 | Otonomy, Inc. | Controlled-release cns modulating compositions and methods for the treatment of otic disorders |
| US8349353B2 (en) | 2008-06-27 | 2013-01-08 | Otonomy, Inc. | Controlled release cytotoxic agent compositions and methods for the treatment of otic disorders |
| GB2461961A (en) * | 2008-07-14 | 2010-01-27 | Otonomy Inc | Sterile anti-apoptotic agent for treatment of ear diseases |
| US8399018B2 (en) | 2008-07-21 | 2013-03-19 | Otonomy, Inc. | Controlled release ion channel modulator compositions and methods for the treatment of otic disorders |
| US8496957B2 (en) | 2008-07-21 | 2013-07-30 | Otonomy, Inc | Controlled release auris sensory cell modulator compositions and methods for the treatment of otic disorders |
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| US8784870B2 (en) | 2008-07-21 | 2014-07-22 | Otonomy, Inc. | Controlled release compositions for modulating free-radical induced damage and methods of use thereof |
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2006
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