WO1999036535A9 - Apo-2 ligand - Google Patents
Apo-2 ligandInfo
- Publication number
- WO1999036535A9 WO1999036535A9 PCT/US1999/001039 US9901039W WO9936535A9 WO 1999036535 A9 WO1999036535 A9 WO 1999036535A9 US 9901039 W US9901039 W US 9901039W WO 9936535 A9 WO9936535 A9 WO 9936535A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- apo
- ligand
- polypeptide
- cells
- sequence
- Prior art date
Links
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- 239000004474 valine Substances 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000540237A JP2002508962A (en) | 1998-01-15 | 1999-01-15 | Apo-2 ligand |
EP99903166A EP1045906B1 (en) | 1998-01-15 | 1999-01-15 | Apo-2 ligand |
CA002318029A CA2318029C (en) | 1998-01-15 | 1999-01-15 | Apo-2 ligand |
US09/582,450 US6740739B1 (en) | 1998-01-15 | 1999-01-15 | Substitutional variants of APO-2 ligand |
DK99903166T DK1045906T3 (en) | 1998-01-15 | 1999-01-15 | APO-2 ligand |
AU23251/99A AU2325199A (en) | 1998-01-15 | 1999-01-15 | Apo-2 ligand |
DE69939732T DE69939732D1 (en) | 1998-01-15 | 1999-01-15 | APO-2 LIGAND |
HK01102353.6A HK1032603A1 (en) | 1998-01-15 | 2001-03-31 | Apo-2 ligand |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US788698A | 1998-01-15 | 1998-01-15 | |
US09/007,886 | 1998-01-15 | ||
US6053398A | 1998-04-15 | 1998-04-15 | |
US09/060,533 | 1998-04-15 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1999036535A1 WO1999036535A1 (en) | 1999-07-22 |
WO1999036535A9 true WO1999036535A9 (en) | 2000-03-02 |
Family
ID=26677483
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/001039 WO1999036535A1 (en) | 1998-01-15 | 1999-01-15 | Apo-2 ligand |
Country Status (13)
Country | Link |
---|---|
US (1) | US6740739B1 (en) |
EP (2) | EP1045906B1 (en) |
JP (2) | JP2002508962A (en) |
AT (1) | ATE411385T1 (en) |
AU (1) | AU2325199A (en) |
CA (1) | CA2318029C (en) |
CY (1) | CY1108681T1 (en) |
DE (1) | DE69939732D1 (en) |
DK (1) | DK1045906T3 (en) |
ES (1) | ES2316182T3 (en) |
HK (1) | HK1032603A1 (en) |
PT (1) | PT1045906E (en) |
WO (1) | WO1999036535A1 (en) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6284236B1 (en) | 1995-06-29 | 2001-09-04 | Immunex Corporation | Cytokine that induces apoptosis |
US20040048340A1 (en) * | 1996-03-14 | 2004-03-11 | Human Genome Sciences, Inc. | Apoptosis inducing molecule I |
EP1873244A3 (en) * | 1999-06-02 | 2008-04-02 | Genentech, Inc. | Methods and compositions for inhibiting neoplastic cell growth |
IL147029A0 (en) * | 1999-06-28 | 2002-08-14 | Genentech Inc | Method for making apo-2 ligand using divalent metal ions |
EP2348043A1 (en) * | 2001-10-02 | 2011-07-27 | Genentech, Inc. | APO-2 ligand variants and uses thereof |
JP2005521640A (en) * | 2001-11-13 | 2005-07-21 | ジェネンテック・インコーポレーテッド | Apo-2 ligand / TRAIL formulation |
US7741285B2 (en) | 2001-11-13 | 2010-06-22 | Genentech, Inc. | APO-2 ligand/trail formulations |
CN1313611C (en) * | 2002-02-22 | 2007-05-02 | 中国人民解放军第二军医大学 | Novel tumor wilting matter 2 ligand gene, its expressed tumor wilting matter and its preparation method |
CA2489348A1 (en) * | 2002-06-24 | 2003-12-31 | Genentech, Inc. | Apo-2 ligand/trail variants and uses thereof |
GB0328261D0 (en) * | 2003-12-05 | 2004-01-07 | Univ Groningen | Improved cytokine design |
WO2005082934A2 (en) * | 2004-02-20 | 2005-09-09 | Five Prime Therapeutics, Inc. | Novel apo2l and il-24 polypeptides, polynucleotides, and methods of their use |
JP5237638B2 (en) * | 2004-08-06 | 2013-07-17 | ジェネンテック, インコーポレイテッド | Assays and methods using biomarkers |
AU2012200601B2 (en) * | 2004-08-06 | 2012-10-11 | Genentech, Inc. | Assays and methods using biomarkers |
JO3000B1 (en) | 2004-10-20 | 2016-09-05 | Genentech Inc | Antibody Formulations. |
US8029783B2 (en) | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
US20100150931A1 (en) * | 2006-11-22 | 2010-06-17 | Centre Hospitalier De L'universite De Montreal | Novel receptor for cd40l and uses thereof |
GB0724532D0 (en) * | 2007-12-17 | 2008-01-30 | Nat Univ Ireland | Trail variants for treating cancer |
US20110086770A1 (en) * | 2009-10-09 | 2011-04-14 | Anaphore, Inc. | Combinatorial Libraries Based on C-type Lectin-like Domain |
US9388230B2 (en) | 2010-09-28 | 2016-07-12 | Kahr Medical(2005) Ltd | Compositions and methods for treatment of hematological malignancies |
WO2012151317A1 (en) | 2011-05-03 | 2012-11-08 | Genentech, Inc. | Vascular disruption agents and uses thereof |
JP5956580B2 (en) | 2011-09-16 | 2016-07-27 | 北京沙▲東▼生物技▲術▼有限公司Beijing Sunbio Biotech Co., Ltd. | Fusion proteins comprising circularly permuted variants of TRAIL / APO2L, coding genes and uses thereof |
EP2684896A1 (en) | 2012-07-09 | 2014-01-15 | International-Drug-Development-Biotech | Anti-DR5 family antibodies, bispecific or multivalent anti-DR5 family antibodies and methods of use thereof |
LT2970473T (en) | 2013-03-14 | 2017-10-25 | Bristol-Myers Squibb Company | Combination of dr5 agonist and anti-pd-1 antagonist and methods of use |
US9914761B2 (en) | 2014-07-10 | 2018-03-13 | Washington University | Oligomers for TNF superfamily inhibition |
CN109476737A (en) | 2015-12-01 | 2019-03-15 | 根马布有限公司 | Anti-DR5 antibody and its application method |
ES2916217T3 (en) | 2017-01-05 | 2022-06-29 | Kahr Medical Ltd | A SIRP1 ALPHA-41BBL fusion protein and methods of using the same |
AU2018205888B2 (en) | 2017-01-05 | 2021-09-02 | Kahr Medical Ltd. | A PD1-41BBL fusion protein and methods of use thereof |
US11566060B2 (en) | 2017-01-05 | 2023-01-31 | Kahr Medical Ltd. | PD1-CD70 fusion protein and methods of use thereof |
WO2018127918A1 (en) | 2017-01-05 | 2018-07-12 | Kahr Medical Ltd. | A sirp alpha-cd70 fusion protein and methods of use thereof |
Family Cites Families (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3691016A (en) | 1970-04-17 | 1972-09-12 | Monsanto Co | Process for the preparation of insoluble enzymes |
CA1023287A (en) | 1972-12-08 | 1977-12-27 | Boehringer Mannheim G.M.B.H. | Process for the preparation of carrier-bound proteins |
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US4195128A (en) | 1976-05-03 | 1980-03-25 | Bayer Aktiengesellschaft | Polymeric carrier bound ligands |
US4330440A (en) | 1977-02-08 | 1982-05-18 | Development Finance Corporation Of New Zealand | Activated matrix and method of activation |
CA1093991A (en) | 1977-02-17 | 1981-01-20 | Hideo Hirohara | Enzyme immobilization with pullulan gel |
FR2413974A1 (en) | 1978-01-06 | 1979-08-03 | David Bernard | DRYER FOR SCREEN-PRINTED SHEETS |
US4229537A (en) | 1978-02-09 | 1980-10-21 | New York University | Preparation of trichloro-s-triazine activated supports for coupling ligands |
JPS6023084B2 (en) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | blood substitute |
US4342566A (en) | 1980-02-22 | 1982-08-03 | Scripps Clinic & Research Foundation | Solid phase anti-C3 assay for detection of immune complexes |
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
ZA811368B (en) | 1980-03-24 | 1982-04-28 | Genentech Inc | Bacterial polypedtide expression employing tryptophan promoter-operator |
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
NZ201705A (en) | 1981-08-31 | 1986-03-14 | Genentech Inc | Recombinant dna method for production of hepatitis b surface antigen in yeast |
US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
US4713339A (en) | 1983-01-19 | 1987-12-15 | Genentech, Inc. | Polycistronic expression vector construction |
AU2353384A (en) | 1983-01-19 | 1984-07-26 | Genentech Inc. | Amplification in eukaryotic host cells |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
DD266710A3 (en) | 1983-06-06 | 1989-04-12 | Ve Forschungszentrum Biotechnologie | Process for the biotechnical production of alkaline phosphatase |
US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
NZ212207A (en) | 1984-05-31 | 1991-07-26 | Genentech Inc | Recombinant lymphotoxin |
US4736866A (en) | 1984-06-22 | 1988-04-12 | President And Fellows Of Harvard College | Transgenic non-human mammals |
EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | Method for enhancing glycoprotein stability. |
US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
US5010182A (en) | 1987-07-28 | 1991-04-23 | Chiron Corporation | DNA constructs containing a Kluyveromyces alpha factor leader sequence for directing secretion of heterologous polypeptides |
IL87737A (en) | 1987-09-11 | 1993-08-18 | Genentech Inc | Method for culturing polypeptide factor dependent vertebrate recombinant cells |
EP0308936B1 (en) | 1987-09-23 | 1994-07-06 | Bristol-Myers Squibb Company | Antibody heteroconjugates for the killing of HIV-infected cells |
GB8724885D0 (en) | 1987-10-23 | 1987-11-25 | Binns M M | Fowlpox virus promotors |
EP0321196A3 (en) | 1987-12-18 | 1990-07-18 | Mycogen Plant Science, Inc. | 780 t-dna gene transcription activator |
WO1989005859A1 (en) | 1987-12-21 | 1989-06-29 | The Upjohn Company | Agrobacterium mediated transformation of germinating plant seeds |
AU4005289A (en) | 1988-08-25 | 1990-03-01 | Smithkline Beecham Corporation | Recombinant saccharomyces |
FR2646437B1 (en) | 1989-04-28 | 1991-08-30 | Transgene Sa | NOVEL DNA SEQUENCES, THEIR APPLICATION AS A SEQUENCE ENCODING A SIGNAL PEPTIDE FOR THE SECRETION OF MATURE PROTEINS BY RECOMBINANT YEASTS, EXPRESSION CASSETTES, PROCESSED YEASTS AND PROCESS FOR PREPARING THE SAME |
EP0479909B1 (en) | 1989-06-29 | 1996-10-30 | Medarex, Inc. | Bispecific reagents for aids therapy |
DK168302B1 (en) | 1989-06-29 | 1994-03-07 | Danisco | Method of introducing molecules, especially genetic material into plant cells |
ATE194384T1 (en) | 1989-09-12 | 2000-07-15 | Hoffmann La Roche | TNF-BINDING PROTEINS |
ES2083469T3 (en) | 1989-11-22 | 1996-04-16 | Genentech Inc | PEPTIDO ASSOCIATED WITH A LATENCY AND USES OF THE SAME. |
US5206161A (en) | 1991-02-01 | 1993-04-27 | Genentech, Inc. | Human plasma carboxypeptidase B |
EP0586505A1 (en) | 1991-05-14 | 1994-03-16 | Repligen Corporation | Heteroconjugate antibodies for treatment of hiv infection |
WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
CA2140280A1 (en) | 1992-08-17 | 1994-03-03 | Avi J. Ashkenazi | Bispecific immunoadhesins |
WO1994029347A1 (en) | 1993-06-03 | 1994-12-22 | Therapeutic Antibodies Inc. | Antibody fragments in therapy |
JPH09503672A (en) | 1993-10-14 | 1997-04-15 | イミュネックス・コーポレーション | Fas antagonist and its use |
WO1995011301A1 (en) | 1993-10-19 | 1995-04-27 | The Regents Of The University Of Michigan | P53-mediated apoptosis |
IL111125A0 (en) | 1994-05-11 | 1994-12-29 | Yeda Res & Dev | Soluble oligomeric tnf/ngf super family ligand receptors and their use |
US6284236B1 (en) * | 1995-06-29 | 2001-09-04 | Immunex Corporation | Cytokine that induces apoptosis |
WO1997001633A1 (en) | 1995-06-29 | 1997-01-16 | Immunex Corporation | Cytokine that induces apoptosis |
US6030945A (en) | 1996-01-09 | 2000-02-29 | Genentech, Inc. | Apo-2 ligand |
WO1997033899A1 (en) | 1996-03-14 | 1997-09-18 | Human Genome Sciences, Inc. | Apoptosis inducing molecule i |
WO1997046686A2 (en) | 1996-06-07 | 1997-12-11 | Amgen Inc. | Tumor necrosis factor-related polypeptide |
KR20020056565A (en) | 2000-12-29 | 2002-07-10 | 황규언 | Three-dimensional structure of human derived apoptotic factor and receptor thereof by X-ray chrystallography and TRAIL deletion mutant protein |
US20020115613A1 (en) | 2001-02-16 | 2002-08-22 | Kumar M. Vijay | Treatment of prostate cancer |
-
1999
- 1999-01-15 DE DE69939732T patent/DE69939732D1/en not_active Expired - Lifetime
- 1999-01-15 EP EP99903166A patent/EP1045906B1/en not_active Expired - Lifetime
- 1999-01-15 JP JP2000540237A patent/JP2002508962A/en not_active Withdrawn
- 1999-01-15 CA CA002318029A patent/CA2318029C/en not_active Expired - Lifetime
- 1999-01-15 PT PT99903166T patent/PT1045906E/en unknown
- 1999-01-15 EP EP08012755A patent/EP2017341A3/en not_active Withdrawn
- 1999-01-15 DK DK99903166T patent/DK1045906T3/en active
- 1999-01-15 US US09/582,450 patent/US6740739B1/en not_active Expired - Lifetime
- 1999-01-15 AT AT99903166T patent/ATE411385T1/en active
- 1999-01-15 AU AU23251/99A patent/AU2325199A/en not_active Abandoned
- 1999-01-15 ES ES99903166T patent/ES2316182T3/en not_active Expired - Lifetime
- 1999-01-15 WO PCT/US1999/001039 patent/WO1999036535A1/en active Application Filing
-
2001
- 2001-03-31 HK HK01102353.6A patent/HK1032603A1/en not_active IP Right Cessation
-
2008
- 2008-12-17 CY CY20081101467T patent/CY1108681T1/en unknown
-
2010
- 2010-07-02 JP JP2010151519A patent/JP2010246560A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
EP2017341A2 (en) | 2009-01-21 |
JP2010246560A (en) | 2010-11-04 |
AU2325199A (en) | 1999-08-02 |
EP1045906A1 (en) | 2000-10-25 |
EP2017341A3 (en) | 2009-04-08 |
ATE411385T1 (en) | 2008-10-15 |
WO1999036535A1 (en) | 1999-07-22 |
DK1045906T3 (en) | 2009-02-16 |
DE69939732D1 (en) | 2008-11-27 |
EP1045906B1 (en) | 2008-10-15 |
US6740739B1 (en) | 2004-05-25 |
JP2002508962A (en) | 2002-03-26 |
PT1045906E (en) | 2009-01-27 |
CA2318029C (en) | 2009-05-19 |
CA2318029A1 (en) | 1999-07-22 |
HK1032603A1 (en) | 2001-07-27 |
CY1108681T1 (en) | 2014-04-09 |
ES2316182T3 (en) | 2009-04-01 |
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