Chiron Corporation

Cetus Corporation

Creative Biomolecules, Inc.

Creative Biomoelcules, Inc.

L L Houston

Hermann Oppermann

David B Ring

James S Huston

Kirston E Koths

Paul Stevens

Brian Issell

David Y Liu

James W Larrick

Danute E Nitecki

Lois Aldwin

Robert Zimmerman

Michael Piatak, Jr

Anne W Emerick

Zehra Kaymakcalan

Eric S Groves

Disclosed is DNA encoding a single-chain Fv (sFv) polypeptide defining a binding site which exhibits the immunological binding properties of an immunoglobulin molecule which binds c-erbB-2 or a c-erbB-2-related tumor antigen, the sFv includes at least two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each of the polypeptide domains includes a set of complementarity determining regions (CDRs) interposed between a set of framework regions (FRs), the CDRs conferring immunological binding to the c-erbB-2 or c-erbB-2-related tumor antigen.

DNA encoding biosynthetic binding protein for cancer marker

Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Biosynthetic binding proteins for immuno-targeting

Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a preselected antigen by the binding site of each polypeptide chain when administered to a mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Biosynthetic binding proteins for immunotargeting

A method for controlling the overgrowth of hyperproliferating cells in the presence of non-proliferating cells by exposing the hyperproliferating cells to a toxin conjugate that has a binding region that binds to an internalizable element of the hyperproliferating cell and a toxic moiety bound thereto is provided. The toxin conjugate may be a monoclonal antibody to transferrin receptor. Such toxin conjugates will have use in controlling hyperproliferative diseases of the integument and the eye.

Method for controlling hyperproliferative diseases

Proteins are described that affect adhesion of white blood cells (WBCs) to endothelial cells (ECs). The proteins include inter-.alpha.-trypsin inhibitor, .alpha..sub.1 -M, and HI-30. When administered in therapeutically effective amounts, these proteins can alter adhesion between WBCs and ECs to ultimately prevent inflammatory-type diseases.

Method for inhibing adhesion of white blood cells to endothelial cells

Ricin B muteins, ricin and ricin precursors having at least one amino acid of at least one galactoside binding site altered to decrease the binding of ricin B to galactosides are claimed. DNA sequences encoding the ricin B muteins, ricin and ricin precursor in which the B chain thereof is the ricin B mutein are claimed. Recombinant expression vectors effective in expressing the DNA sequences of the ricin B muteins, ricin and ricin precursors are claimed. Host cells transformed with the foregoing expression vectors are also claimed. Conjugates comprising binding moieties such as antibodies, hormones, and lymphokines bound to the ricin B mutein and ricin wherein the B chain thereof is the mutein is also claimed.

Recombinant ricin toxin fragments

Heterobifunctional crosslinkers up to about 34 .ANG. in length consisting of a sulfhydryl reactive group linked to a spacer group, which in turn is linked to an activated carboxylate group, that are useful for making efficacious anticancer immunotoxin conjugates as shown preferably by reacting an antibody associated amino group with the activated carboxylate group to form an antibody crosslinker complex and reacting the antibody crosslinker complex with a cytotoxin having a reactive sulfhydryl group with the sulfhydryl reactive group of the crosslinker, and using the conjugates so produced to treat cancer patients.

Thioether linked immunotoxin conjugates

Anti-tumor activity in humans can be augmented by administering to the mammalian host a pharmacologically effective amount of mammalian IL-2 and at least one immunotoxin that binds selectively to human tumor cells. The IL-2 and immunotoxin are preferably administered separately to the host. The composition is useful for prophylactic or therapeutic treatment of such cancers as ovarian and breast cancer.

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Oakland, CA, United States of America

L L Houston