CN1234073A - 环状变更的促红细胞生成素受体激动剂 - Google Patents
环状变更的促红细胞生成素受体激动剂 Download PDFInfo
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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| CN97198973A Pending CN1234073A (zh) | 1996-10-25 | 1997-10-23 | 环状变更的促红细胞生成素受体激动剂 |
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| KR (1) | KR20000052807A (enExample) |
| CN (1) | CN1234073A (enExample) |
| AU (1) | AU721196B2 (enExample) |
| BR (1) | BR9712675A (enExample) |
| CA (1) | CA2268001A1 (enExample) |
| CZ (1) | CZ130199A3 (enExample) |
| NO (1) | NO991906D0 (enExample) |
| NZ (1) | NZ334546A (enExample) |
| PL (1) | PL189756B1 (enExample) |
| WO (1) | WO1998018926A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110144010A (zh) * | 2018-02-14 | 2019-08-20 | 上海洛启生物医药技术有限公司 | 阻断型pd-l1驼源单域抗体及其用途 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7309687B1 (en) | 1999-04-13 | 2007-12-18 | The Kenneth S. Warren Institute, Inc. | Methods for treatment and prevention of neuromuscular and muscular conditions by peripherally administered erythropoietin |
| US7345019B1 (en) | 1999-04-13 | 2008-03-18 | The Kenneth S. Warren Institute, Inc. | Modulation of excitable tissue function by peripherally administered erythropoietin |
| US7604960B2 (en) | 1999-04-15 | 2009-10-20 | Crucell Holland B.V. | Transient protein expression methods |
| US8236561B2 (en) | 1999-04-15 | 2012-08-07 | Crucell Holland B.V. | Efficient production of IgA in recombinant mammalian cells |
| US6855544B1 (en) | 1999-04-15 | 2005-02-15 | Crucell Holland B.V. | Recombinant protein production in a human cell |
| US7297680B2 (en) | 1999-04-15 | 2007-11-20 | Crucell Holland B.V. | Compositions of erythropoietin isoforms comprising Lewis-X structures and high sialic acid content |
| US7527961B2 (en) | 1999-11-26 | 2009-05-05 | Crucell Holland B.V. | Production of vaccines |
| US7521220B2 (en) | 1999-11-26 | 2009-04-21 | Crucell Holland B.V. | Production of vaccines |
| US7192759B1 (en) | 1999-11-26 | 2007-03-20 | Crucell Holland B.V. | Production of vaccines |
| US6531121B2 (en) | 2000-12-29 | 2003-03-11 | The Kenneth S. Warren Institute, Inc. | Protection and enhancement of erythropoietin-responsive cells, tissues and organs |
| PA8536201A1 (es) | 2000-12-29 | 2002-08-29 | Kenneth S Warren Inst Inc | Protección y mejoramiento de células, tejidos y órganos que responden a la eritropoyetina |
| KR100979025B1 (ko) | 2001-12-07 | 2010-08-30 | 크루셀 홀란드 비.브이. | 바이러스, 바이러스 단리물 및 백신의 생산 |
| ATE414144T1 (de) | 2003-05-09 | 2008-11-15 | Crucell Holland Bv | Kulturen von e1-immortalisierten zellen und verfahren zu deren kultivierung zur erhöhung der produktausbeuten davon |
| AU2005325768A1 (en) * | 2005-01-25 | 2006-08-03 | Apollo Life Sciences Limited | Molecules and chimeric molecules thereof |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| EA201692543A1 (ru) | 2005-11-23 | 2017-08-31 | Акселерон Фарма Инк. | Антагонисты активина-actriia и их применение для стимулирования роста кости |
| EP1966237A2 (en) * | 2005-11-24 | 2008-09-10 | Laboratoires Serono SA | Erythropoietin polypeptides and uses thereof |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| CA2677007A1 (en) | 2007-02-01 | 2008-08-07 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for treating or preventing breast cancer |
| TWI782836B (zh) | 2007-02-02 | 2022-11-01 | 美商艾瑟勒朗法瑪公司 | 衍生自ActRIIB的變體與其用途 |
| CA3039330C (en) | 2007-02-09 | 2021-11-09 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for promoting bone growth in cancer patients |
| CN103877564A (zh) | 2007-09-18 | 2014-06-25 | 阿塞勒隆制药公司 | 活化素-actriia拮抗剂和减少或抑制fsh分泌的用途 |
| JP5922928B2 (ja) | 2008-08-14 | 2016-05-24 | アクセルロン ファーマ, インコーポレイテッド | 赤血球レベルを高めるためのgdfトラップの使用 |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| CN102482339B (zh) | 2009-06-08 | 2015-06-17 | 阿塞勒隆制药公司 | 用于增加产热脂肪细胞的方法 |
| EP2440577A4 (en) | 2009-06-12 | 2013-01-23 | Acceleron Pharma Inc | SHORTEN ACTRIIB FC FUSION PROTEINS |
| ES2658292T3 (es) | 2009-11-17 | 2018-03-09 | Acceleron Pharma, Inc. | Proteínas ActRIIB y variantes y usos de las mismas con respecto a la inducción de la utrofina para el tratamiento de la distrofia muscular |
| CN103298832A (zh) | 2010-11-08 | 2013-09-11 | 阿塞勒隆制药公司 | Actriia结合剂及其用途 |
| WO2013184938A2 (en) | 2012-06-08 | 2013-12-12 | Alkermes. Inc. | Fusion polypeptides comprising mucin-domain polypeptide linkers |
| MX366336B (es) | 2012-11-02 | 2019-07-05 | Celgene Corp | Antagonistas de activina - actrii y usos para el tratar trastornos oseos y otros. |
| AU2015274277B2 (en) | 2014-06-13 | 2021-03-18 | Acceleron Pharma, Inc. | Methods and compositions for treating ulcers |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| SMT202300166T1 (it) | 2014-12-03 | 2023-07-20 | Celgene Corp | Antagonisti di attivina- actrii e usi per il trattamento di sindrome mielodisplastica |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4751180A (en) * | 1985-03-28 | 1988-06-14 | Chiron Corporation | Expression using fused genes providing for protein product |
| AU8735991A (en) * | 1990-09-28 | 1992-04-28 | Ortho Pharmaceutical Corporation | Hybrid growth factors |
| US5738849A (en) * | 1992-11-24 | 1998-04-14 | G. D. Searle & Co. | Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them |
| US5635599A (en) * | 1994-04-08 | 1997-06-03 | The United States Of America As Represented By The Department Of Health And Human Services | Fusion proteins comprising circularly permuted ligands |
-
1997
- 1997-10-23 EP EP97913680A patent/EP0939816A1/en not_active Withdrawn
- 1997-10-23 WO PCT/US1997/018703 patent/WO1998018926A1/en not_active Ceased
- 1997-10-23 AU AU50810/98A patent/AU721196B2/en not_active Ceased
- 1997-10-23 CA CA002268001A patent/CA2268001A1/en not_active Abandoned
- 1997-10-23 BR BR9712675-6A patent/BR9712675A/pt not_active Application Discontinuation
- 1997-10-23 PL PL97332960A patent/PL189756B1/pl not_active IP Right Cessation
- 1997-10-23 CN CN97198973A patent/CN1234073A/zh active Pending
- 1997-10-23 CZ CZ991301A patent/CZ130199A3/cs unknown
- 1997-10-23 JP JP52052898A patent/JP2001503266A/ja not_active Abandoned
- 1997-10-23 KR KR1019990703627A patent/KR20000052807A/ko not_active Ceased
- 1997-10-23 NZ NZ334546A patent/NZ334546A/xx unknown
-
1999
- 1999-04-21 NO NO991906A patent/NO991906D0/no not_active Application Discontinuation
-
2004
- 2004-10-25 US US10/972,962 patent/US20060172932A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110144010A (zh) * | 2018-02-14 | 2019-08-20 | 上海洛启生物医药技术有限公司 | 阻断型pd-l1驼源单域抗体及其用途 |
| WO2019158113A1 (zh) * | 2018-02-14 | 2019-08-22 | 上海洛启生物医药技术有限公司 | 阻断型pd-l1驼源单域抗体及其用途 |
| US11912770B2 (en) | 2018-02-14 | 2024-02-27 | Shanghai Novamab Biopharmaceuticals Co., Ltd. | Blocking type PD-L1 single-domain camel antibody and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| US20060172932A1 (en) | 2006-08-03 |
| EP0939816A1 (en) | 1999-09-08 |
| NZ334546A (en) | 2000-12-22 |
| PL332960A1 (en) | 1999-10-25 |
| KR20000052807A (ko) | 2000-08-25 |
| NO991906L (no) | 1999-04-21 |
| BR9712675A (pt) | 1999-10-19 |
| CZ130199A3 (cs) | 1999-07-14 |
| CA2268001A1 (en) | 1998-05-07 |
| AU5081098A (en) | 1998-05-22 |
| NO991906D0 (no) | 1999-04-21 |
| WO1998018926A1 (en) | 1998-05-07 |
| JP2001503266A (ja) | 2001-03-13 |
| PL189756B1 (pl) | 2005-09-30 |
| AU721196B2 (en) | 2000-06-29 |
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