DE3587597T2 - Lymphotoxin, dafür kodierende Nukleinsäure, die Nukleinsäure enthaltenden Vektoren und damit transformierte Zellen, Verfahren zum Erhalten von Lymphotoxin und Lymphotoxin neutralisierender Antikörper. - Google Patents
Lymphotoxin, dafür kodierende Nukleinsäure, die Nukleinsäure enthaltenden Vektoren und damit transformierte Zellen, Verfahren zum Erhalten von Lymphotoxin und Lymphotoxin neutralisierender Antikörper.Info
- Publication number
- DE3587597T2 DE3587597T2 DE3587597T DE3587597T DE3587597T2 DE 3587597 T2 DE3587597 T2 DE 3587597T2 DE 3587597 T DE3587597 T DE 3587597T DE 3587597 T DE3587597 T DE 3587597T DE 3587597 T2 DE3587597 T2 DE 3587597T2
- Authority
- DE
- Germany
- Prior art keywords
- lymphotoxin
- nucleic acid
- recombinant nucleic
- substituted
- acid construct
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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Landscapes
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61650384A | 1984-05-31 | 1984-05-31 | |
| US06/616,502 US4959457A (en) | 1984-05-31 | 1984-05-31 | Anti-lymphotoxin |
| US73231285A | 1985-05-09 | 1985-05-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3587597D1 DE3587597D1 (de) | 1993-11-04 |
| DE3587597T2 true DE3587597T2 (de) | 1994-06-01 |
Family
ID=27417179
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3587597T Expired - Lifetime DE3587597T2 (de) | 1984-05-31 | 1985-05-30 | Lymphotoxin, dafür kodierende Nukleinsäure, die Nukleinsäure enthaltenden Vektoren und damit transformierte Zellen, Verfahren zum Erhalten von Lymphotoxin und Lymphotoxin neutralisierender Antikörper. |
| DE3588225T Expired - Lifetime DE3588225T2 (de) | 1984-05-31 | 1985-05-30 | Anti-Lymphotoxin-Antikörper, Herstellung und Verwendung |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3588225T Expired - Lifetime DE3588225T2 (de) | 1984-05-31 | 1985-05-30 | Anti-Lymphotoxin-Antikörper, Herstellung und Verwendung |
Country Status (23)
| Country | Link |
|---|---|
| EP (2) | EP0164965B1 (enExample) |
| JP (3) | JP2521703B2 (enExample) |
| AR (1) | AR245219A1 (enExample) |
| AT (2) | ATE195323T1 (enExample) |
| AU (1) | AU599303B2 (enExample) |
| BG (1) | BG60256B2 (enExample) |
| CA (1) | CA1340641C (enExample) |
| CZ (1) | CZ283148B6 (enExample) |
| DE (2) | DE3587597T2 (enExample) |
| DK (1) | DK171531B1 (enExample) |
| ES (1) | ES8802182A1 (enExample) |
| FI (1) | FI93025C (enExample) |
| GR (1) | GR851317B (enExample) |
| HU (1) | HU204085B (enExample) |
| IE (1) | IE63487B1 (enExample) |
| IL (1) | IL75318A (enExample) |
| NO (1) | NO179075C (enExample) |
| NZ (1) | NZ212207A (enExample) |
| PL (1) | PL155410B1 (enExample) |
| PT (1) | PT80573B (enExample) |
| RO (1) | RO100383A2 (enExample) |
| SK (1) | SK278333B6 (enExample) |
| YU (1) | YU47735B (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU564690B2 (en) | 1980-04-03 | 1987-08-20 | Biogen Idec Ma Inc. | Process for producing human fibroblast interferon-like polypeptides using recombinant dna |
| IL75318A (en) | 1984-05-31 | 1994-08-26 | Genentech Inc | Recombinant human memotoxin and methods for its recombinant production |
| US5683688A (en) | 1984-05-31 | 1997-11-04 | Genentech, Inc. | Unglycosylated recombinant human lymphotoxin polypeptides and compositions |
| IL73883A (en) * | 1984-12-20 | 1990-12-23 | Yeda Res & Dev | Monoclonal antibodies against tnf-alpha,hybridomas producing them and method for the purification of tnf-alpha |
| ATE73856T1 (de) * | 1984-12-21 | 1992-04-15 | Biogen Inc | Reinigung, herstellung und verwendung von tumor- nekrosisfaktoren. |
| JPS62111928A (ja) * | 1985-10-15 | 1987-05-22 | Kanegafuchi Chem Ind Co Ltd | 新規リンホトキシン |
| JPS62195285A (ja) * | 1986-02-19 | 1987-08-28 | Kanegafuchi Chem Ind Co Ltd | リンホトキシン発現ベクタ−及びそれを用いるリンホトキシンの製造方法 |
| AU603768B2 (en) * | 1985-07-04 | 1990-11-29 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Lymphotoxin dna, lymphotoxin expression vector, lymphotoxin resistant cell, transformant with lymphotoxin expression vector and process for preparing lymphotoxin |
| US5403725A (en) * | 1985-12-24 | 1995-04-04 | Denki Kagaku Kogyo Kabushiki Kaisha | Method for production of lymphotoxin (TNFB) in cell line A-C5-8 |
| EP0230781B1 (en) * | 1985-12-24 | 1992-07-22 | Denki Kagaku Kogyo Kabushiki Kaisha | Lymphotoxin gene, method for its production, and lymphotoxin |
| JP2548204B2 (ja) * | 1987-06-27 | 1996-10-30 | 電気化学工業株式会社 | 新生理活性ポリペプチド |
| EP0230574A3 (en) * | 1986-01-31 | 1989-03-22 | Yale University | Pharmaceutical compositions against infections caused by lav/htlv iii virus and the use thereof |
| JPS62181298A (ja) * | 1986-02-05 | 1987-08-08 | Kyowa Hakko Kogyo Co Ltd | ヒトリンホトキシンポリペプチド誘導体 |
| DE3620656A1 (de) * | 1986-06-20 | 1987-12-23 | Basf Ag | Polypeptide mit lymphotoxin-aktivitaet oder lymphotoxin-aehnlicher aktivitaet, ihre herstellung und verwendung |
| JPS63105680A (ja) * | 1986-10-22 | 1988-05-10 | Kanegafuchi Chem Ind Co Ltd | ヒト・リンホトキシン発現ベクタ−、該発現ベクタ−による形質転換細胞および該細胞を用いるリンホトキシンの製造方法 |
| JP2636862B2 (ja) * | 1986-12-24 | 1997-07-30 | 武田薬品工業株式会社 | 組み換え型ヒトリンホトキシン |
| US5175268A (en) * | 1986-12-24 | 1992-12-29 | Takeda Chemical Industries, Ltd. | DNA encoding recombinant human lymphotoxin |
| FI884798A7 (fi) * | 1987-10-28 | 1989-04-29 | Eisai Co Ltd | Rekombinantlymfotoxin. |
| DE3837012A1 (de) * | 1988-01-15 | 1989-07-27 | Knoll Ag | Verwendung von tnf und lt zur herstellung von arzneimitteln |
| GB2217326B (en) * | 1988-04-08 | 1991-11-20 | British Bio Technology | Synthetic gene encoding human tumour necrosis factor beta. |
| EP0338497A3 (en) * | 1988-04-22 | 1990-05-16 | Takeda Chemical Industries, Ltd. | Bispecific hybrid monoclonal antibody |
| JPH023698A (ja) * | 1988-06-20 | 1990-01-09 | Denki Kagaku Kogyo Kk | ヒトリンホトキシンに対するモノクローナル抗体及びそれら抗体を産生するハイブリドーマ、並びにそれら抗体を用いたヒトリンホトキシンの精製方法、測定方法及び測定試薬 |
| CA2001756A1 (en) * | 1988-10-31 | 1991-04-30 | Seiichi Uesugi | New human lymphotoxin n-end deletion mutant |
| JPH03106821A (ja) * | 1989-09-20 | 1991-05-07 | Denki Kagaku Kogyo Kk | 抗腫瘍剤 |
| US5370870A (en) * | 1989-10-06 | 1994-12-06 | Genentech, Inc. | Method for protection against reactive oxygen species |
| US5200176A (en) * | 1989-10-06 | 1993-04-06 | Genentech, Inc. | Method for protection of ischemic tissues using tumor nerosis factor |
| IL97779A (en) * | 1990-04-10 | 2000-01-31 | Genentech Inc | Compositions for cytoprotection against radiation and chemotherapy injury or risk thereof |
| US5747023A (en) * | 1994-07-01 | 1998-05-05 | Genentech, Inc. | Cancer therapy using lymphotoxin |
| JP4231106B2 (ja) * | 1995-01-23 | 2009-02-25 | ゼノテック インコーポレイティッド | 骨溶解および転移を改善する方法 |
| US5925351A (en) | 1995-07-21 | 1999-07-20 | Biogen, Inc. | Soluble lymphotoxin-β receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological disease |
| US6998116B1 (en) | 1996-01-09 | 2006-02-14 | Genentech, Inc. | Apo-2 ligand |
| WO1999036535A1 (en) | 1998-01-15 | 1999-07-22 | Genentech, Inc. | Apo-2 ligand |
| EP2311870A1 (en) * | 2002-11-26 | 2011-04-20 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
| US20050163782A1 (en) | 2003-06-27 | 2005-07-28 | Biogen Idec Ma Inc. | Modified binding molecules comprising connecting peptides |
| WO2005067477A2 (en) * | 2003-12-08 | 2005-07-28 | Centocor, Inc. | Anti-human lymphotoxin alpha antibodies, compositions, methods and uses |
| CN1980957A (zh) | 2004-03-23 | 2007-06-13 | 比奥根艾迪克Ma公司 | 受体偶联剂及其治疗用途 |
| WO2006074399A2 (en) | 2005-01-05 | 2006-07-13 | Biogen Idec Ma Inc. | Multispecific binding molecules comprising connecting peptides |
| UA94484C2 (uk) * | 2006-10-12 | 2011-05-10 | Дженентек, Інк. | Антитіла до лімфотоксину-альфа |
| CA2666934A1 (en) | 2006-10-20 | 2008-04-24 | Biogen Idec Ma Inc. | Treatment of demyelinating disorders with soluble lymphotoxin-beta-receptor |
| US8338376B2 (en) | 2006-10-20 | 2012-12-25 | Biogen Idec Ma Inc. | Compositions comprising variant LT-B-R-IG fusion proteins |
| CN112716890A (zh) * | 2014-04-25 | 2021-04-30 | 诺雷克斯股份有限公司 | 神经活性肽的稳定组合物 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK171727B1 (da) * | 1978-12-22 | 1997-04-14 | Biogen Inc | Rekombinante hepatitis B virus DNA-molekyler, værtsorganismer transformeret hermed, HBV-antigenspecifikke polypeptider, DNA-sekvenser kodende for HBV-antigenspecifikke polypeptider, metoder til påvisning af hepatitis B virus-antistoffer, metoder til fremstilling af nævnte DNA-molekyler, fremgangsmåder til fremstilling af nævnte polypeptider og midler til påvisning af HBV-infektion |
| NZ201918A (en) | 1981-09-18 | 1987-04-30 | Genentech Inc | N-terminal methionyl analogues of bovine growth hormone |
| ZA834976B (en) * | 1982-07-30 | 1984-08-29 | Genentech Inc | Human lymphotoxin |
| FI82266C (fi) * | 1982-10-19 | 1991-02-11 | Cetus Corp | Foerfarande foer framstaellning av il-2 -mutein. |
| EP0135797A3 (de) * | 1983-08-30 | 1987-11-11 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Verfahren zur Herstellung von Lymphotoxin und von Lymphotoxin-mRNA |
| DE3331108A1 (de) * | 1983-08-30 | 1985-05-02 | Boehringer Ingelheim International GmbH, 6507 Ingelheim | Verfahren zur herstellung von lymphotoxin und von lymphotoxin-mrna |
| IL75318A (en) | 1984-05-31 | 1994-08-26 | Genentech Inc | Recombinant human memotoxin and methods for its recombinant production |
-
1985
- 1985-05-27 IL IL7531885A patent/IL75318A/en unknown
- 1985-05-27 NZ NZ212207A patent/NZ212207A/en unknown
- 1985-05-28 IE IE132185A patent/IE63487B1/en not_active IP Right Cessation
- 1985-05-29 FI FI852143A patent/FI93025C/fi not_active IP Right Cessation
- 1985-05-29 GR GR851317A patent/GR851317B/el unknown
- 1985-05-30 DK DK241385A patent/DK171531B1/da not_active IP Right Cessation
- 1985-05-30 AT AT92110196T patent/ATE195323T1/de not_active IP Right Cessation
- 1985-05-30 HU HU852076A patent/HU204085B/hu unknown
- 1985-05-30 DE DE3587597T patent/DE3587597T2/de not_active Expired - Lifetime
- 1985-05-30 AT AT85303818T patent/ATE95243T1/de not_active IP Right Cessation
- 1985-05-30 ES ES543695A patent/ES8802182A1/es not_active Expired
- 1985-05-30 NO NO852173A patent/NO179075C/no unknown
- 1985-05-30 BG BG70460A patent/BG60256B2/bg unknown
- 1985-05-30 EP EP85303818A patent/EP0164965B1/en not_active Expired - Lifetime
- 1985-05-30 DE DE3588225T patent/DE3588225T2/de not_active Expired - Lifetime
- 1985-05-30 EP EP92110196A patent/EP0509553B1/en not_active Expired - Lifetime
- 1985-05-31 YU YU91985A patent/YU47735B/sh unknown
- 1985-05-31 CZ CS853930A patent/CZ283148B6/cs not_active IP Right Cessation
- 1985-05-31 PT PT80573A patent/PT80573B/pt unknown
- 1985-05-31 CA CA000482995A patent/CA1340641C/en not_active Expired - Lifetime
- 1985-05-31 AU AU43203/85A patent/AU599303B2/en not_active Expired
- 1985-05-31 PL PL1985253739A patent/PL155410B1/pl unknown
- 1985-05-31 JP JP60119648A patent/JP2521703B2/ja not_active Expired - Lifetime
- 1985-05-31 SK SK3930-85A patent/SK278333B6/sk unknown
-
1986
- 1986-10-14 AR AR86305572A patent/AR245219A1/es active
-
1988
- 1988-01-19 RO RO131846A patent/RO100383A2/ro unknown
-
1995
- 1995-01-19 JP JP7006657A patent/JPH07291995A/ja active Pending
- 1995-01-19 JP JP7006665A patent/JP2804237B2/ja not_active Expired - Lifetime
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