AU2011218243A1 - Fibronectin based scaffold domain proteins that bind IL-23 - Google Patents
Fibronectin based scaffold domain proteins that bind IL-23 Download PDFInfo
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- AU2011218243A1 AU2011218243A1 AU2011218243A AU2011218243A AU2011218243A1 AU 2011218243 A1 AU2011218243 A1 AU 2011218243A1 AU 2011218243 A AU2011218243 A AU 2011218243A AU 2011218243 A AU2011218243 A AU 2011218243A AU 2011218243 A1 AU2011218243 A1 AU 2011218243A1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
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| JO3244B1 (ar) | 2009-10-26 | 2018-03-08 | Amgen Inc | بروتينات ربط مستضادات il – 23 البشرية |
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| US20140187488A1 (en) | 2011-05-17 | 2014-07-03 | Bristol-Myers Squibb Company | Methods for maintaining pegylation of polypeptides |
| ES2848531T3 (es) | 2011-05-17 | 2021-08-10 | Bristol Myers Squibb Co | Métodos mejorados para la selección de proteínas de unión |
| US9522951B2 (en) | 2011-10-31 | 2016-12-20 | Bristol-Myers Squibb Company | Fibronectin binding domains with reduced immunogenicity |
| WO2013067322A1 (en) * | 2011-11-03 | 2013-05-10 | Stc Biologics, Inc. | Method for determination of pharmacological properties of recombinant proteins |
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| PL3835310T3 (pl) | 2012-09-13 | 2024-06-03 | Bristol-Myers Squibb Company | Białka domeny rusztowania oparte na fibronektynie wiążące się z miostatyną |
| CZ304514B6 (cs) | 2012-11-23 | 2014-06-11 | Biotechnologický Ústav Av Čr, V.V.I. | Polypeptidy pro léčbu autoimunitních chorob založenou na blokaci receptoru pro lidský cytokin IL-23 |
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| ES2870802T3 (es) | 2013-02-12 | 2021-10-27 | Bristol Myers Squibb Co | Métodos de replegado de proteínas a elevado pH |
| KR20150062352A (ko) * | 2013-11-29 | 2015-06-08 | 일진엘이디(주) | 유전체층을 가진 발광 다이오드 |
| EA202090216A3 (ru) | 2014-03-20 | 2020-07-31 | Бристол-Майерс Сквибб Компани | Связывающие сывороточный альбумин домены фибронектина iii типа |
| EP3172339A1 (en) | 2014-07-24 | 2017-05-31 | Boehringer Ingelheim International GmbH | Biomarkers useful in the treatment of il-23a related diseases |
| US10059763B2 (en) | 2014-09-03 | 2018-08-28 | Boehringer Ingelheim International Gmbh | Compound targeting IL-23A and TNF-alpha and uses thereof |
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| JP6872797B2 (ja) * | 2015-12-29 | 2021-05-19 | 国立大学法人東京工業大学 | 標的結合ペプチドの安定化方法 |
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Family Cites Families (34)
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- 2011-02-16 CA CA2790329A patent/CA2790329A1/en not_active Abandoned
- 2011-02-16 JP JP2012553974A patent/JP2013520426A/ja active Pending
- 2011-02-18 TW TW100105496A patent/TWI508736B/zh not_active IP Right Cessation
- 2011-02-18 AR ARP110100518A patent/AR080229A1/es unknown
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2012
- 2012-07-23 TN TNP2012000372A patent/TN2012000372A1/en unknown
- 2012-08-17 CL CL2012002296A patent/CL2012002296A1/es unknown
- 2012-09-17 ZA ZA2012/06969A patent/ZA201206969B/en unknown
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2014
- 2014-11-25 US US14/553,379 patent/US9714281B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP2536757B1 (en) | 2015-03-25 |
| AR080229A1 (es) | 2012-03-21 |
| EA201270713A1 (ru) | 2013-01-30 |
| PE20130041A1 (es) | 2013-01-28 |
| MX2012009050A (es) | 2012-09-07 |
| HK1179276A1 (en) | 2013-09-27 |
| US20150274806A1 (en) | 2015-10-01 |
| WO2011103105A1 (en) | 2011-08-25 |
| US9714281B2 (en) | 2017-07-25 |
| TN2012000372A1 (en) | 2014-01-30 |
| US8927693B2 (en) | 2015-01-06 |
| ZA201206969B (en) | 2015-06-24 |
| KR20130010461A (ko) | 2013-01-28 |
| SG183215A1 (en) | 2012-09-27 |
| TWI508736B (zh) | 2015-11-21 |
| TW201130501A (en) | 2011-09-16 |
| JP2013520426A (ja) | 2013-06-06 |
| EP2536757A1 (en) | 2012-12-26 |
| US20130012436A1 (en) | 2013-01-10 |
| BR112012019881A2 (pt) | 2017-06-27 |
| CL2012002296A1 (es) | 2013-01-11 |
| CA2790329A1 (en) | 2011-08-25 |
| CN102762591A (zh) | 2012-10-31 |
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