Chiron Corporation

Cetus Corporation

Creative Biomolecules, Inc.

Cetus Oncology Corporation

Other

Novartis Vaccines & Diagnostics, Gmbh

Creative Biomoelcules, Inc.

David B Ring

Stephen David Harrison

Arthur E Frankel

John M Nuss

Hermann Oppermann

Savithri Ramurthy

Kirk William Johnson

Keith Bruce Pfister

Allan S Wagman

James S Huston

Rustum S Boyce

L L Houston

Lynn Seely

Michael J Bjorn

Dane A Goff

Walter J Laird

Xiaohui A Zhou

Tian-Xiang Shi

Peter G Schultz

Manoj C Desai

Paul A Renhowe

Sharadha Subramanian

Barry Haskell Levine

Andrew Malcolm Bray

Sean P Brown

Ira H Pastan

Peter S Linsley

Wayne A Marasco

Kirston E Koths

Robert F Halenbeck

Peter Ralph

David J FitzGerald

Joseph P Brown

Mark C Willingham

Robert Zimmerman

Diane Horn

Kong T Chong

Jeffrey L Winkelhake

Abner Mhashilkar

James Devlin

Jeffrey L Windelhake

Lou L Houston

Sylvia Hsieh Ma

Sharon Lea Aukerman

Vincent W Ochs

Julie Porter-Brooks

Urban Ramstedt

Bridget Eberhardt

Joyce Lavecchio

LL Houston

New pyridine-based compounds of Formula I, compositions, and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3-mediated disorders in vivo are provided. The methods, compounds, and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer. 

Inhibitors of glycogen synthase kinase 3

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

Inhibitors of glycogen synthase 3 kinase

New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

A humanized antibody framework motif is described. Preferably, the motif is encoded by the V gene of K5B8 and the V gene of TR1.6. This humanized antibody preferably contains the variable region of a tat antibody.

Humanized antibody and uses thereof

Novel pyridine and pyrimidine derivatives which selectively inhibit glycogen synthase kinase 3 are provided and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions which may be mediated by glycogen synthase kinase 3.

Compounds of formula 1: ##STR1## wherein R.sub.1 is alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, substituted with 0-3 substituents selected from lower alkyl, halo, hydroxy, lower alkoxy, amino, lower alkyl-amino, and nitro; R.sub.2 is hydroxy, amino, or lower alkoxy; R.sub.3 is H, lower alkyl, lower acyl, lower alkoxy-acyl, or amnino-acyl; R.sub.4 is H or lower alkyl; and pharmaceutically acceptable salts and esters thereof; are effective inhibitors of GSK3.

This invention relates generally to the field of immunology, in particular that of antibodies and antibody productions. More specifically, this invention relates to bispecific antibodies, the hybrid hybridomas which produce them, the parent hybridomas, the production and selection of the hybridomas and hybrid hybridomas, and the purification of the bispecific antibodies. Specific examples relate to bispecific monoclonal antibodies which recognize both the human multi-drug resistance antigen, P-glycoprotein and human Fc.gamma. receptor III (hFc.gamma.RIII. These bispecific antibodies are useful in killing cancer cells.

Monoclonal anti-multiple drug resistance antibody, methods of production

This invention relates generally to the field of immunology, in particular that of antibodies and antibody productions. More specifically, this invention relates to bispecific antibodies, the hybrid hybridomas which produce them, the parent hybridomas, the production and selection of the hybridomas and hybrid hybridomas, and the purification of the bispecific antibodies. Specific examples relate to bispecific monoclonal antibodies which recognize both the human multi-drug resistance antigen, P-glycoprotein and human Fc.gamma. receptor III (hFc.gamma.RIII). These bispecific antibodies are useful in killing cancer cells.

Bispecific antibodies, methods of production and use thereof

The invention provides for use of selective inhibitors of GSK3 for treatment of diseases that are mediated by GSK3 activity, including non-insulin dependent diabetes mellitus (NIDDM) and Alzheimer's disease. Also described are methods of identifying inhibitors of GSK3 activity. The selective GSK3 inhibitor can be a peptide, peptoid, small organic molecule, or polynucleotide.

Identification and use of selective inhibitors of glycogen synthase

Novel compositions are provided that are derived from antigen-binding sites of immunoglobulins having affinity for cancer antigens. The compositions exhibit immunological binding properties of antibody molecules capable of binding specifically to a human tumor cell expressing an antigen selected from the group consisting of high molecular weight mucins bound by 2G3 and 369F10, c-erbB-2 tumor antigen, an approximately 42 kD glycoprotein, an approximately 55 kD glycoprotein, and the approximately 40, 60, 100 and 200 kD antigens bound by 113F1. A number of synthetic molecules are provided that include CDR and FR regions derived from same or different immunoglobulin moieties. Also provided are single chain polypeptides wherein V.sub.H and V.sub.L domains are attached by a single polypeptide linker. The sFv molecules can include ancillary polypeptide moieties which can be bioactive, or which provide a site of attachment for other useful moieties. The compositions are useful in specific binding assays, affinity purification schemes, drug or toxin targeting, imaging, and genetic or immunological therapeutics for various cancers. The invention thus provides novel polypeptides, the DNAs encoding those polypeptides, expression cassettes comprising those DNAs, and methods of inducing the production of the polypeptides.

Antigen-binding sites of antibody molecules specific for cancer antigens

Bispecific antibodies, methods of production and uses thereof

Novel compositions are provided that are derived from antigen-binding sites of immunoglobulins having affinity for cancer antigens. The compositions exhibit immunological binding properties of antibody molecules capable of binding specifically to a human tumor cell displaying a MDR phenotype. A number of synthetic molecules are provided that include CDR and FR regions derived from same or different immunoglobulin moieties. Also provided are single chain polypeptides wherein V.sub.H and V.sub.L domains are attached by a single polypeptide linker. The sFv molecules can include ancillary polypeptide moieties which can be bioactive, or which provide a site of attachment for other useful moieties. The compositions are useful in specific binding assays, affinity purification schemes, drug or toxin targeting, imaging, and genetic or immunological therapeutics for various cancers. The invention thus provides novel polypeptides, the DNAs encoding those polypeptides, expression cassettes comprising those DNAs, and methods of inducing the production of the polypeptides.

Nucleic acids encoding antigen-binding sites specific for cancer antigens

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Palo Alto, CA, United States of America

David B Ring