Seattle Genetics, Inc.

Bristol-myers Squibb Compnay

Bristol-myers Squibb

Clay B Siegall

Alan F Wahl

Joseph A Francisco

Henry Perry Fell, Jr

Ingegerd E Hellstrom

Karl E Hellstrom

Dana Chace

Gregory D Plowman

Mohammed Shoyab

Hans Marquardt

Kim Folger Bruce

George J Schreiber

Grant Risdon

Stephen McAndrew

Susan L Gawlak

Jean-Michel Culouscou

Henry P Fell

The present invention relates to methods and compositions for the prevention and treatment of cancer, inflammatory diseases and disorders or deficiencies of the immune system. The methods of the invention comprise administering a CD40 binding protein that potentiates the binding of CD40 to CD40 ligand.

Methods for augmenting an immune response using anti-CD40 antibodies

Methods for the treatment of cancer using anti-CD40 antibodies

Methods for treating immune disorders or cancer with anti-CD40 antibodies

The present invention relates to methods and compositions for the treatment of Hodgkin's Disease, comprising administering proteins characterized by their ability to bind to CD30, or compete with monoclonal antibodies AC10 or HeFi-1 for binding to CD30, and exert a cytostatic or cytotoxic effect on Hodgkin's Disease cells. Such proteins include derivatives of monoclonal antibodies AC10 and HeFi-1. The proteins of the invention can be human, humanized, or chimeric antibodies; further, they can be conjugated to cytotoxic agents such as chemotherapeutic drugs. The invention further relates to nucleic acids encoding the proteins of the invention. The invention yet further relates to a method for identifying an anti-CD30 antibody useful for the treatment or prevention of Hodgkin's Disease.

Recombinant anti-CD30 antibodies and uses thereof

Recombinant anti-CD40 antibody and uses thereof

Methods for the treatment and prevention of cancer using anti-CD40 antibodies

Nucleic acids encoding anti-CD40 proteins and methods of producing recombinant anti-CD40 proteins

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.

Antibodies reactive with human carcinomas

The molecular cloning and expression of biologically active ribosome-inactivating protein bryodin 1 are described. A complete amino acid and oligonucleotide sequence encoding bryodin 1 are also described. Further, plasmids, expression vectors comprising a nucleotide sequence encoding bryodin 1 and transformed host cells are described. Isolation and characterization of the nucleotide sequence for bryodin 1 enables the recombinant production of large amount of bryodin 1 for use in vitro or in vivo directly or as ligand/toxin conjugates or fusion proteins. These compositions can be used to selectively kill undesired cells such as cancer cells, infected cells, bacteria and the like.

Cloning and expression of a gene encoding bryodin 1 from Bryonia dioica

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

A novel method for preventing, stabilizing or causing regression of vascular leak syndrome is disclosed. The method comprises administering to a patient in need thereof a compound selected from the group consisting of a corticosteroid, a non-steroidal anti-inflammatory agent, 15-deoxyspergualin and related compounds, and phospholipase A.sub.2 inhibitors.

Method for treating vascular leak syndrome

The present invention discloses a new ribosome-inactivating protein, bryodin 2, isolated from the plant Bryonia dioica. This ribosome-inactivating protein (RIP) is a type IRIP having a single polypeptide chain and no cellular receptor domain. Like many type I RIPs, bryodin 2 has a molecular weight of about 27,000 daltons and a pI of 9.5. Bryodin 2 differs from previously identified ribosome-inactivating protein in its amino acid composition, amino acid sequence, and toxicity in vitro and in vivo. Bryodin 2 is useful, as are other type I ribosome-inactivating proteins, as an abortifacient, immunomodulator, anti-tumor or anti-viral agent. Compositions comprising bryodin 2 as an immunoconjugate or fusion molecule are particularly useful to kill cells of a target population.

Bryodin 2 a ribosome-inactivating protein isolated from the plant

The molecular cloning and expression of biologically active ribosome-inactivating protein bryodin 1 are described. A complete amino acid and oligonucleotide sequence encoding bryodin 1 are also described. Further, plasmids, expression vectors comprising a nucleotide sequence encoding bryodin 1 and transformed host cells are described. Isolation and characterization of the nucleotide sequence for bryodin 1 enables the recombinant production of large amount of bryodin 1 for use in vitro or in vivo directly or as ligand/toxin conjugates or fusion proteins. These compositions can be used to selectively kill undesired cells such as cancer cells, infected cells, bacteria.

Growing community of inventors

Edmonds, WA, United States of America

Clay B Siegall