CA2361181A1 - Her-2 binding antagonists - Google Patents

Her-2 binding antagonists Download PDF

Info

Publication number
CA2361181A1
CA2361181A1 CA002361181A CA2361181A CA2361181A1 CA 2361181 A1 CA2361181 A1 CA 2361181A1 CA 002361181 A CA002361181 A CA 002361181A CA 2361181 A CA2361181 A CA 2361181A CA 2361181 A1 CA2361181 A1 CA 2361181A1
Authority
CA
Canada
Prior art keywords
amino acids
polypeptide
isolated
sequence
ecd
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.)
Granted
Application number
CA002361181A
Other languages
French (fr)
Other versions
CA2361181C (en
Inventor
Joni Kristin Doherty
Gail M. Clinton
John P. Adelman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Oregon Health Science University
Original Assignee
Oregon Health Sciences University
Joni Kristin Doherty
Gail M. Clinton
John P. Adelman
Oregon Health And Science University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Oregon Health Sciences University, Joni Kristin Doherty, Gail M. Clinton, John P. Adelman, Oregon Health And Science University filed Critical Oregon Health Sciences University
Publication of CA2361181A1 publication Critical patent/CA2361181A1/en
Application granted granted Critical
Publication of CA2361181C publication Critical patent/CA2361181C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

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
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

There is disclosed a pharmaceutical composition for treating solid tumors th at overexpress HER-2, comprising an agent selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken fro m the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 108, (b) an isolated and glycosylated polypeptide having from about 300 to 419 amino aci ds taken from the sequence of SEQ ID NO. 2, wherein the C terminal 79 amino aci ds are present, and wherein at least three N-linked glycosylation sites are present, (c) a monoclonal antibody that binds to the ECD of HER-2, and (d) combinations thereof, with the proviso that the agent cannot be the monoclon al antibody alone, and pharmaceutically acceptable carrier.

Claims (27)

1. An isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 10 8.
2. The isolated polypeptide of claim 1, wherein the isolated polypeptide is from about 69 to 79 amino acids in length.
3. The isolated polypeptide of claim 1, wherein the isolated polypeptide binds to a site on the ECD of HER-2 that is different from the site of binding of Herceptin (a marketed humanized monoclonal antibody that is used for the treatment of cancer and that binds to the ECD or HER-2).
4. An isolated DNA sequence that codes on expression for a polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 10 8.
5. The isolated DNA sequence that codes on expression for a polypeptide of claim 4 wherein the isolated polypeptide is from about 69 to 79 amino acids in length.
6. The isolated DNA sequence of claim 4, wherein the isolated polypeptide binds to a site on the ECD of HER-2 that is different from the site of binding of Herceptin ®.
7. A transfected cell comprising an expression vector having a DNA sequence that codes on expression for a polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 10 8.
8. An isolated and glycosylated polypeptide having from about 300 to 419 amino acids taken from the sequence of SEQ ID NO. 2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present.
9. The isolated and glycosylated polypeptide of claim 6, wherein the isolated polypeptide is from about 350 to 419 amino acids in length and four N-linked glycosylation are present.
10. The isolated and glycosylated polypeptide of claim 6, wherein the isolated polypeptide binds to a site on the ECD of HER-2 that is different from the site of binding of Herceptin®.
11. An isolated DNA sequence that codes on expression for a polypeptide having from about 800 to 419 amino acids taken from the sequence of SEQ ID NO. 2, wherein the C
terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present.
12. The isolated DNA sequence that codes on expression for a polypeptide of claim 11. wherein the isolated polypeptide is from about 350 to 419 amino acids in length and four N-linked glycosylation sites are present.
13. A transfected cell comprising an expression vector having a DNA sequence that codes on expression for a polypeptide having from about 80 to 419 amino acids taken from the sequence of SEQ ID NO. 2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present.
14. A method for treating a solid tumor characterized by overexpression of HER-2, comprising administering an agent that binds to the extracellular domain (ECD) of HER-2, wherein the agent is selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 10 8, (b) an isolated and glycosylated polypeptide having from about 80 to 419 amino acids taken from the sequence of SEQ ID NO. 2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present, (c) a monoclonal antibody that binds to the ECD of HER-2, and (d) combinations thereof, with the proviso that the agent cannot be the monoclonal antibody alone.
15. The method of claim 14, wherein the solid tumor that overexpresses HER-2 is selected from the group consisting of breast cancer, small cell lung carcinoma, ovarian cancer and colon cancer.
16. The method of claim 14, wherein the agent is the isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1.
17. The method of claim 16, wherein the agent is a combination of the isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO.
and the monoclonal antibody that binds to the ECD of HER-2.
18. A pharmaceutical composition for treating solid tumors that overexpress HER-2, comprising an agent selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 at an affinity of at least 10 8, (b) an isolated and glycosylated polypeptide having from about 80 to 419 amino acids taken from the sequence of SEQ ID NO. 2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present, (c) a monoclonal antibody that binds to the ECD of HER-2, and (d) combinations thereof, with the proviso that the agent cannot be the monoclonal antibody alone, and pharmaceutically acceptable carrier.
19. The pharmaceutical composition for treating solid tumors that overexpress HER-2 of claim 18, wherein the agent is the isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1.
20. The pharmaceutical composition for treating solid tumors that overexpress HER-2 of claim 19, wherein the agent is a combination of the isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1 and the monoclonal antibody that binds to the ECD of HER-2.
21. A method for targeting a therapeutic agent to solid tumor tissue, wherein the solid tumor tissue is characterized by overexpression of HER-2, comprising attaching the therapeutic agent to an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD
of HER-2 at an affinity of at least 10 8.
22. The method for targeting a therapeutic agent to solid tumor tissue of claim 21, wherein the isolated polypeptide is from about 69 to 79 amino acids in length.
23. The method for targeting a therapeutic agent to solid tumor tissue of claim 221, wherein the isolated polypeptide binds to a site on the ECD of HER-2 that is different from the site of binding of Herceptin ®.
24. A method for determining the prognosis of tumor treatment for a tumor that overexpresses HER-2, comprising: (a) obtaining a bodily fluid, wherein the bodily fluid is selected from the group consisting of blood, serum, urine, lymph, saliva, tumor tissue, and combinations thereof; and (b) measuring the amount of p68HER-2 expressed using an anti-p68HER-2 antibody-based assay, wherein the assay is selected from the group consisting of ELISA, immunoprecipitation, immunohistocytochemistry, and Western analysis.
25. The method for determining the prognosis of tumor treatment for a tumor that overexpresses HER-2 of claim 24, further comprising measuring the amount of p ECD in the bodily fluid.
26. The method for determining the prognosis of tumor treatment for a tumor that overexpresses HER-2 of claim 24, further comprising determining a ratio between the amount of p68HER-2 and p185HER-2, whereby the higher the p68HER-2 to p 185HER-2 ratio, the better the prognosis of the patient.
27
CA2361181A 1999-01-20 2000-01-20 Her-2 binding antagonists Expired - Fee Related CA2361181C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/234,208 1999-01-20
US09/234,208 US7393823B1 (en) 1999-01-20 1999-01-20 HER-2 binding antagonists
PCT/US2000/001484 WO2000044403A1 (en) 1999-01-20 2000-01-20 Her-2 binding antagonists

Publications (2)

Publication Number Publication Date
CA2361181A1 true CA2361181A1 (en) 2000-08-03
CA2361181C CA2361181C (en) 2011-01-04

Family

ID=22880399

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2361181A Expired - Fee Related CA2361181C (en) 1999-01-20 2000-01-20 Her-2 binding antagonists

Country Status (6)

Country Link
US (4) US7393823B1 (en)
EP (1) EP1144004A4 (en)
JP (1) JP2002534995A (en)
AU (1) AU777422B2 (en)
CA (1) CA2361181C (en)
WO (1) WO2000044403A1 (en)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6541214B1 (en) 1998-11-13 2003-04-01 Oregon Heath Science University N-terminally truncated HER-2/neu protein as a cancer prognostic indicator
US7625859B1 (en) 2000-02-16 2009-12-01 Oregon Health & Science University HER-2 binding antagonists
US7396810B1 (en) 2000-08-14 2008-07-08 Oregon Health Sciences University Compositions and methods for treating cancer by modulating HER-2 and EGF receptors
US7393823B1 (en) 1999-01-20 2008-07-01 Oregon Health And Science University HER-2 binding antagonists
US6294349B1 (en) 1999-03-01 2001-09-25 University Of Mississippi Medical Ctr. Method of diagnosing and monitoring malignant breast carcinomas
EP1189931B1 (en) 1999-07-02 2006-06-21 Genentech, Inc. Peptide compounds that bind her2
US6435873B1 (en) 2000-10-10 2002-08-20 3M Innovative Properties Company Medication delivery devices
JP2005508887A (en) * 2001-08-03 2005-04-07 コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼイション Screening method based on crystal structure of EGF receptor
US7585509B2 (en) * 2002-07-03 2009-09-08 The Curators Of The University Of Missouri Erb-2 receptor targeting peptide
JP4841429B2 (en) * 2003-04-24 2011-12-21 インサイト・コーポレイション Azaspiroalkane derivatives as inhibitors of metalloproteases
JP2007525187A (en) * 2003-05-16 2007-09-06 レセプター・バイオロジクス・インコーポレイテッド Intron fusion proteins and methods for identifying and using the same
WO2005113596A2 (en) * 2004-05-14 2005-12-01 Receptor Biologix, Inc. Cell surface receptor isoforms and methods of identifying and using the same
EP1807106A2 (en) * 2004-10-05 2007-07-18 Oregon Health and Science University Compositions and methods for treating disease
WO2006119510A2 (en) * 2005-05-04 2006-11-09 Receptor Biologix, Inc. Isoforms of receptor for advanced glycation end products (rage) and methods of identifying and using same
US20090170769A1 (en) * 2005-05-13 2009-07-02 Pei Jin Cell surface receptor isoforms and methods of identifying and using the same
KR20080082629A (en) * 2005-11-10 2008-09-11 리셉터 바이오로직스 인크 Hepatocyte growth factor intron fusion proteins
WO2007143600A2 (en) * 2006-06-05 2007-12-13 Incyte Corporation Sheddase inhibitors combined with cd30-binding immunotherapeutics for the treatment of cd30 positive diseases
KR20090031897A (en) * 2006-06-12 2009-03-30 리셉터 바이오로직스 인크 Pan-cell surface receptor-specific therapeutics
WO2008005983A2 (en) * 2006-07-06 2008-01-10 Molecular Logix, Inc. Pan-her antagonists and methods of use
KR20100082775A (en) * 2007-10-16 2010-07-19 심포젠 에이/에스 Compositions comprising optimized herl and her3 multimers and methods of use thereof
CA2761777A1 (en) * 2009-05-14 2010-11-18 Prometheus Laboratories Inc. Biomarkers for determining sensitivity of breast cancer cells to her2-targeted therapy
US20160213777A1 (en) * 2013-09-12 2016-07-28 Thomas Jefferson University Novel Delivery Compositions and Methods of Using Same
US11484505B2 (en) 2016-10-13 2022-11-01 Thomas Jefferson University Delivery compositions, and methods of making and using same
WO2023168426A1 (en) 2022-03-03 2023-09-07 Enosi Therapeutics Corporation Compositions and cells containing mixtures of oligo-trap fusion proteins (ofps) and uses thereof

Family Cites Families (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4376110A (en) 1980-08-04 1983-03-08 Hybritech, Incorporated Immunometric assays using monoclonal antibodies
EP0119528B1 (en) 1983-03-11 1992-05-13 Sloan-Kettering Institute For Cancer Research Monoclonal antibodies to human renal cancer antigens and method
IL74201A0 (en) 1984-01-30 1985-04-30 Icrf Patents Limited Polypeptides for the detection and control of mammalian cell growth
US6054561A (en) 1984-02-08 2000-04-25 Chiron Corporation Antigen-binding sites of antibody molecules specific for cancer antigens
US4959314A (en) 1984-11-09 1990-09-25 Cetus Corporation Cysteine-depleted muteins of biologically active proteins
US4777127A (en) 1985-09-30 1988-10-11 Labsystems Oy Human retrovirus-related products and methods of diagnosing and treating conditions associated with said retrovirus
US7838216B1 (en) 1986-03-05 2010-11-23 The United States Of America, As Represented By The Department Of Health And Human Services Human gene related to but distinct from EGF receptor gene
US5401638A (en) 1986-06-04 1995-03-28 Oncogene Science, Inc. Detection and quantification of neu related proteins in the biological fluids of humans
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
GB8702816D0 (en) 1987-02-07 1987-03-11 Al Sumidaie A M K Obtaining retrovirus-containing fraction
US5219740A (en) 1987-02-13 1993-06-15 Fred Hutchinson Cancer Research Center Retroviral gene transfer into diploid fibroblasts for gene therapy
US5720937A (en) 1988-01-12 1998-02-24 Genentech, Inc. In vivo tumor detection assay
WO1989006692A1 (en) 1988-01-12 1989-07-27 Genentech, Inc. Method of treating tumor cells by inhibiting growth factor receptor function
US5206152A (en) 1988-04-08 1993-04-27 Arch Development Corporation Cloning and expression of early growth regulatory protein genes
WO1989010412A1 (en) 1988-04-18 1989-11-02 Applied Biotechnology, Inc. Detection of neu gene expression and products
US5422120A (en) 1988-05-30 1995-06-06 Depotech Corporation Heterovesicular liposomes
AP129A (en) 1988-06-03 1991-04-17 Smithkline Biologicals S A Expression of retrovirus gag protein eukaryotic cells
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
DK0474727T3 (en) 1989-05-19 1998-01-12 Genentech Inc HER2 extracellular domain
US5705157A (en) 1989-07-27 1998-01-06 The Trustees Of The University Of Pennsylvania Methods of treating cancerous cells with anti-receptor antibodies
JP3859695B2 (en) 1989-08-04 2006-12-20 バーレックス ラボラトリーズ インコーポレイテッド C-erbB-2 foreign domain: GP75
WO1991005264A1 (en) 1989-09-29 1991-04-18 Oncogenetics Partners Detection and quantification of neu related proteins in the biological fluids of humans
ZA911974B (en) 1990-03-21 1994-08-22 Res Dev Foundation Heterovesicular liposomes
EP0527802B1 (en) 1990-04-06 1997-06-04 The Trustees Of The University Of Pennsylvania Ligand for the neu gene product
US5874528A (en) 1990-05-25 1999-02-23 Georgetown University Binding peptides which interact with ligand growth factors of the epidermal growth factor receptor and erbB-2 receptor
US5578482A (en) 1990-05-25 1996-11-26 Georgetown University Ligand growth factors that bind to the erbB-2 receptor protein and induce cellular responses
US5149655A (en) 1990-06-21 1992-09-22 Agracetus, Inc. Apparatus for genetic transformation
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
WO1992014748A1 (en) 1991-02-22 1992-09-03 American Cyanamid Company Identification of a novel human receptor tyrosine kinase gene
IL101943A0 (en) 1991-05-24 1992-12-30 Genentech Inc Structure,production and use of heregulin
CA2111006C (en) 1991-06-21 2008-04-08 Andrew D. Boyd A novel receptor-type tyrosine kinase and use thereof
DE69228300T2 (en) 1991-08-22 1999-09-23 Becton Dickinson Co METHODS AND COMPOSITIONS FOR CANCER THERAPY AND FOR THE PREDICTABILITY OF REACTIONS TO THIS TREATMENT
WO1993014124A1 (en) 1992-01-09 1993-07-22 Helsinki University Holding, Ltd. Tie, a novel endothelial cell receptor tyrosine kinase
US6331302B1 (en) 1992-01-22 2001-12-18 Genentech, Inc. Protein tyrosine kinase agonist antibodies
US5861301A (en) 1992-02-20 1999-01-19 American Cayanamid Company Recombinant kinase insert domain containing receptor and gene encoding same
US5811098A (en) 1992-11-24 1998-09-22 Bristol-Myers Squibb Company Antibodies to HER4, human receptor tyrosine kinase
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
US5801005A (en) 1993-03-17 1998-09-01 University Of Washington Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated
US6340674B1 (en) 1993-03-26 2002-01-22 Thomas Jefferson University Method of inhibiting the proliferation and causing the differentiation of cells with IGF-1 receptor antisense oligonucleotides
CA2158347A1 (en) 1993-03-26 1994-10-13 Renato Baserga Method of inhibiting the proliferation and causing the differentiation of cells with igf-1 receptor antisense oligonucleotides
US6015686A (en) 1993-09-15 2000-01-18 Chiron Viagene, Inc. Eukaryotic layered vector initiation systems
US6696548B2 (en) 1993-12-03 2004-02-24 St. Jude Children's Research Hospital Antibodies for recognition of alk protein tyrosine/kinase receptor
AU2096895A (en) 1994-03-07 1995-09-25 Sugen, Incorporated Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof
CA2187781A1 (en) 1994-03-14 1995-09-21 Ben Lewis Margolis Methods for treatment or diagnosis of diseases or conditions associated with abnormal signal transduction
US6045797A (en) 1994-03-14 2000-04-04 New York University Medical Center Treatment or diagnosis of diseases or conditions associated with a BLM domain
EP0758196A4 (en) 1994-05-05 1999-05-06 Univ Pennsylvania Compositions and methods of treating tumors
US5770567A (en) 1994-11-14 1998-06-23 Genentech, Inc. Sensory and motor neuron derived factor (SMDF)
HRP950558A2 (en) 1994-11-15 1997-12-31 Scott M. Wilhelm Substituted 4-biarylbutric or biarylpentanoic acids and derivatives as matrix metalloprotease inhibitors
US5783404A (en) 1995-04-13 1998-07-21 Amgen Inc. Methods and compositions for determining HER-2/neu expression using monoclonal antibodies
US5663144A (en) 1995-05-03 1997-09-02 The Trustees Of The University Of Pennsylvania Compounds that bind to p185 and methods of using the same
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
US6685940B2 (en) 1995-07-27 2004-02-03 Genentech, Inc. Protein formulation
US5783186A (en) 1995-12-05 1998-07-21 Amgen Inc. Antibody-induced apoptosis
CA2259157A1 (en) 1996-07-05 1998-01-15 Mount Sinai Hospital Corporation Oligomerized receptors which affect pathways regulated by transmembrane ligands for elk-related receptor tyrosine kinases
HRP970371A2 (en) 1996-07-13 1998-08-31 Kathryn Jane Smith Heterocyclic compounds
ATE343400T1 (en) 1996-09-24 2006-11-15 Merck & Co Inc COMPOUNDS FOR INHIBITING ANGIOGENESIS BY GENE THERAPY
US5910583A (en) 1996-11-04 1999-06-08 Duke University Antisense oligonucleotides against ERBB-2
US7125969B1 (en) 1996-11-27 2006-10-24 The Regents Of The University Of California ETS-related gene overexpressed in human breast and epithelial cancers
US20020137890A1 (en) 1997-03-31 2002-09-26 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
DE69838334T2 (en) 1997-06-18 2008-06-12 Merck & Co., Inc. (A New Jersey Corp.) KDR, A HUMAN TYROSINE KINASE RECEPTOR
CA2306451A1 (en) 1997-10-15 1999-04-22 Abbott Laboratories Methods and compositions for detecting hepatitis e virus
JP4485051B2 (en) 1998-02-04 2010-06-16 ジェネンテック， インコーポレイテッド Heregulin as an epidermal growth factor
US6417168B1 (en) 1998-03-04 2002-07-09 The Trustees Of The University Of Pennsylvania Compositions and methods of treating tumors
EP1308456B1 (en) 1998-05-06 2007-08-22 Genentech, Inc. Antibody purification by ion exchange chromatography
US20030032061A1 (en) 1998-05-15 2003-02-13 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
JP2002517241A (en) 1998-06-11 2002-06-18 アストラゼネカ アクチボラグ Human receptor tyrosine kinase
US7173005B2 (en) 1998-09-02 2007-02-06 Antyra Inc. Insulin and IGF-1 receptor agonists and antagonists
EP1126873A1 (en) 1998-11-07 2001-08-29 Genentech, Inc. Method for enhancing proliferation of inner ear hair cells using ligands for her2 and/or her3 receptors
US6541214B1 (en) 1998-11-13 2003-04-01 Oregon Heath Science University N-terminally truncated HER-2/neu protein as a cancer prognostic indicator
WO2000035455A1 (en) 1998-12-15 2000-06-22 Telik, Inc. Heteroaryl-aryl ureas as igf-1 receptor antagonists
US7393823B1 (en) 1999-01-20 2008-07-01 Oregon Health And Science University HER-2 binding antagonists
US7625859B1 (en) 2000-02-16 2009-12-01 Oregon Health & Science University HER-2 binding antagonists
US7396810B1 (en) 2000-08-14 2008-07-08 Oregon Health Sciences University Compositions and methods for treating cancer by modulating HER-2 and EGF receptors
US6399743B1 (en) 1999-05-14 2002-06-04 Dept. Of Veterans Affairs Isolation and characterization of a rat epidermal growth factor related protein
EP1189931B1 (en) 1999-07-02 2006-06-21 Genentech, Inc. Peptide compounds that bind her2
JP2003512044A (en) 1999-10-15 2003-04-02 ヒューマン ジノーム サイエンシーズ， インコーポレイテッド Protein tyrosine kinase receptor polynucleotides, polypeptides, and antibodies
PL400669A1 (en) 2000-05-19 2012-11-05 Genentech, Inc. Genetic probe for detecting a response to ErbB antagonist for improving the likelihood and efficiency of cancer treatment
TWI317285B (en) 2000-07-28 2009-11-21 Dainippon Sumitomo Pharma Co New use and kit for remedies for cancer
EP1311291A4 (en) 2000-08-09 2007-07-25 Imclone Systems Inc Treatment of hyperproliferative diseases with epidermal growth factor receptor antagonists
EP1228766A1 (en) 2001-01-31 2002-08-07 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. PYK2 phosphorylation by HER3 induces tumor invasion
US6780912B2 (en) 2001-02-26 2004-08-24 Hewlett-Packard Development Company L.P. Addition of metal ions to improve lightfastness of inkjet inks
WO2002090991A2 (en) 2001-05-03 2002-11-14 Oxford Glycosciences (Uk) Ltd Proteins and genes for diagnosis and treatment of erbb2-related cancer
WO2002097114A2 (en) 2001-05-29 2002-12-05 Sirna Therapeutics, Inc. Nucleic acid treatment of diseases or conditions related to levels of ras, her2 and hiv
WO2003011897A1 (en) 2001-07-27 2003-02-13 The Regents Of The University Of California Modulation of heregulin and her3 interaction
JP2005532780A (en) 2001-09-19 2005-11-04 インタージェネティックス インコーポレイテッド Genetic analysis for stratification of cancer risk
US20050123896A1 (en) 2001-10-25 2005-06-09 Benz Christopher C. Screening system for modulators of her2 mediated transcription and her2 modulators identified thereby
EP1463751B1 (en) 2001-12-21 2013-05-22 Human Genome Sciences, Inc. Albumin fusion proteins
JP2005525317A (en) 2002-01-18 2005-08-25 カイロン コーポレイション Combined IL-2 / anti-HER2 antibody therapy for cancer characterized by overexpression of HER2 receptor protein
AU2003224916B2 (en) 2002-04-10 2009-01-08 Genentech, Inc. Anti-HER2 antibody variants
JP5069843B2 (en) 2002-07-15 2012-11-07 ジェネンテック， インコーポレイテッド Method for identifying tumors responsive to treatment with anti-ErbB2 antibodies
TW200420565A (en) 2002-12-13 2004-10-16 Bristol Myers Squibb Co C-6 modified indazolylpyrrolotriazines
JP2007525187A (en) 2003-05-16 2007-09-06 レセプター・バイオロジクス・インコーポレイテッド Intron fusion proteins and methods for identifying and using the same
CN100392074C (en) 2003-10-15 2008-06-04 上海海欣生物技术有限公司 Dendritic cell tumor vaccine and its preparation and use

Also Published As

Publication number Publication date
EP1144004A1 (en) 2001-10-17
JP2002534995A (en) 2002-10-22
US20090270316A1 (en) 2009-10-29
WO2000044403A1 (en) 2000-08-03
US7393823B1 (en) 2008-07-01
US20120088255A1 (en) 2012-04-12
EP1144004A4 (en) 2002-09-04
US7939080B2 (en) 2011-05-10
US6414130B1 (en) 2002-07-02
CA2361181C (en) 2011-01-04
AU777422B2 (en) 2004-10-14
AU4795100A (en) 2000-08-18

Similar Documents

Publication Publication Date Title
CA2361181A1 (en) Her-2 binding antagonists
Kuan et al. Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme
Tokunaga et al. Clinical significance of epidermal growth factor (EGF), EGF receptor, and c‐erbB‐2 in human gastric cancer
Yoshida et al. EGF and TGF‐α, the ligands of hyperproduced EGFR in human esophageal carcinoma cells, act as autocrine growth factors
Winkler et al. Epidermal growth factor and transforming growth factor. alpha. bind differently to the epidermal growth factor receptor
Tse et al. CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma.
US6040290A (en) Ligand growth factor gp30 that binds to the erbB-2 receptor protein and induces cellular responses
Poulsom et al. Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co‐expressed in normal, hyperplastic, and neoplastic human breast epithelium
Yoshida et al. Expression of epidermal growth factor, transforming growth factor‐α and their receptor genes in human gastric carcinomas; implication for autocrine growth
Kitazawa et al. Immunohistologic evaluation of parathyroid hormone‐related protein in human lung cancer and normal tissue with newly developed monoclonal antibody
JP2002534995A5 (en)
Jeffers et al. Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis
NZ296638A (en) Ligands which bind to tie-2 (tyrosine kinase with ig and egf homology domains) receptors
Normanno et al. Expression of amphiregulin, cripto-1, and heregulin-alpha in human breast-cancer cells
JP2003521931A (en) Heterologous polypeptides of the TNF family
CN103951752A (en) Novel anti-IGF-IR antibodies and uses thereof
Culouscou et al. Biochemical analysis of the epithelin receptor
EP1956032B1 (en) Monoclonal antibody directed against cd166 and method for production thereof
Guan et al. Herceptin down-regulates HER-2/neu and vascular endothelial growth factor expression and enhances taxol-induced cytotoxicity of human Ewing's sarcoma cells in vitro and in vivo
JPH07224089A (en) Irritancy factor of neu receptor
CA2319715A1 (en) Breast cancer resistance protein (bcrp) and the dna which encodes it
PL330705A1 (en) Tie-2 receptor ligands (ligand-3 tie; ligand-4 tie) and their application
Furger et al. Granulosa cell tumors express erbB4 and are sensitive to the cytotoxic action of heregulin-β2/PE40
ATE542138T1 (en) HER-2 BINDING ANTAGONISTS
JP2004501605A5 (en)

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20140121