Oncogen

Bristol-Myers Squibb Compnay

Oncogen Limited Partnership

Pacific Northwest Research Institute

Other

University of Washington

Ingegerd Hellstrom

Karl E. Hellstrom

George J. Schreiber

Kim F. Bruce

Karl E Hellstrom

Ingegerd E Hellstrom

Joseph P Brown

Peter S Linsley

Hans Marquardt

Diane Horn

Nathalie Scholler

Kim Folger Bruce

George J Schreiber

Gregory D Plowman

Mary L Disis

Clay B Siegall

Anthony F Purchio

Timothy M Rose

Maria S Kahn

Shiu-Lok Hu

Stephen McAndrew

Charles D Estin

Sridhar Pennathur

Efraim Lavie

Alejandro A Aruffo

Mohammed Shoyab

Randy R Robinson

Alvin Y Liu

Gary L Schieven

Ingegerd E Hellestrom

Yoshitaka Yoneyama

Ingegred Hellstrom

Janet Johnston

Gary E Goodman

Donna F Beaton

John Marken

Ursula Garrigues

Jean-Michel Culouscou

Victor K Lee

Ingegerg Hellstrom

The invention is directed to compositions and methods for the detection of a malignant condition, and relates to the discovery of soluble forms of mesothelin polypeptides, including mesothelin related antigen (MRA). In particular the invention provides a nucleic acid sequence encoding MRA and an MRA variant. The invention also provides a method of screening for the presence of a malignant condition in a subject by detecting reactivity of an antibody specific for a mesothelin polypeptide with a molecule naturally occurring in soluble form in a sample from such a subject, and by hybridization screening using an MRA nucleotide sequence, as well as other related advantages.

Methods and compositions for diagnosing carcinomas

The invention provides compositions and methods directed to cell surface receptor antigen specific vaccines. More specifically, vaccines are provided that induce or enhance host antibody titers specific for cell surface receptor antigens and that include recombinant expression constructs containing nucleic acids encoding a target cell surface receptor antigen and one or more immune response altering molecules, or the expressed products themselves.

Surface receptor antigen vaccines

The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab').sub.2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab').sub.2 -LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

Methods for determining the presence of carcinoma using the antigen

Antibodies reactive with human carcinomas

Antibody conjugates reactive with human carcinomas

The present invention provides internalizing ligands (i.e., BR110 ligands) which specifically recognize and bind the BR110 antigen. After binding the antigen, the ligand and antigen form a complex. As a complex, the antigen can be detected using well known and developed methods and commercial systems.

Monoclonal antibody BR110 and uses thereof

The molecular cloning, expression, and biological characteristics of a novel receptor tyrosine kinase related to the epidermal growth factor receptor, termed HER4/p180.sup.erbB4, are described. Antibodies to HER4 are disclosed. A HER4 ligand capable of inducing cellular differentiation of breast cancer cells is also disclosed. In view of the expression of HER4 in several human cancers and in certain tissues of neuronal and muscular origin, various diagnostic and therapeutic uses of HER4-derived and HER4-related biological compositions are provided.

Antibodies to HER4, human receptor tyrosine kinase

The present invention relates to methods which utilize anti-idiotypic antibodies, or fragments thereof, for tumor immunotherapy or immunoprophylaxis. Monoclonal anti-idiotypic antibodies which recognize an idiotype present on a second antibody or on a T lymphocyte or on an immune suppressor factor which is directed against a defined tumor antigen, can be used for immunization against a tumor, for immune anti-tumor activation or inhibition of suppression, or for in vitro activation of lymphocytes to be used in adoptive immunotherapy. The anti-idiotypic antibodies, or fragments thereof, can also be used to monitor anti-antibody induction in patients undergoing passive immunization to a tumor antigen by administration of anti-tumor antibody. In another embodiment, administration of T lymphocytes which express an idiotype directed against a defined tumor antigen can be used to transfer delayed-type hypersensitivity to the tumor. In another method of the invention, the induction of anti-idiotypic antibodies in vivo by administration of anti-tumor antibody or immune cells or factors exhibiting an anti-tumor idiotype can be therapeutically valuable.

Tumor immunotherapy using anti-idiotypic antibodies

The present invention definitively identifies and characterizes the tumor-associated antigen immunologically recognized by the murine monoclonal antibody L6. Further, the present invention provides the nucleotide sequence which encodes the L6 antigen. Various diagnostic, prophylactic and therapeutic methods comprising the L6 antigen and the nucleotide sequence which encodes the L6 antigen are also provided.

Tumor associated antigen recognized by the murine monoclonal antibody

The present invention relates to novel antibodies reactive with human carcinoma cells. More particularly, the antibodies of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; and a F(ab').sub.2 fragment of BR96. These antibodies are reactive with a cell membrane antigen on the surface of human carcinomas. The antibodies display a high degree of selectivity for carcinoma cells and possess the ability to mediate ADCC and CDC activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

Monoclonal antibody BR 96 and chimeric monoclonal antibodies having the

The present invention is concerned with novel monoclonal antibody L53 which binds strongly to a glycoprotein antigen associated with human tumors, including carcinomas of the colon, breast, and lung, as well as melanomas. The antibody binds to normal human cells to a much lesser degree than to tumor cells. The antibody finds use in diagnostic methods for as the detection of malignant cells associated with tumors. Also disclosed is a novel 70,000-75,000 dalton glycoprotein antigen recognized by MAb L53. The L53 antigen is found on the cell surface of human tumor cells. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

Monoclonal antibody L53 which recognizes a human tumor-associated antigen

A chimeric antibody with human constant region and murine variable region, having specificity to a human tumor antigen, methods of production, and uses. In particular, the present invention relates to a chimeric antibody specific for a human tumor antigen L6 and which mediates a potent antibody dependent cellular cytotoxicity against the tumor target cells.

Chimeric antibody with specificity to human tumor antigen

Growing community of inventors

Seattle, WA, United States of America

Karl E Hellstrom