Bristol-Myers Squibb Compnay

Peter A Kiener

Jeffrey A Ledbetter

Peter S Linsley

Nitin Krishnaji Damle

William Brady

Takushi Kaneko

Robert S Greenfield

Gary R Braslawsky

Guchen Yang

Lee J Olech

Xiaorong Chen

Patricia M Davis

Isolated novel cDNA sequences encoding a human C-type lectin and three homologues are provided. They are referred to herein as &ldquo;CLAX&rdquo; (C-type Lectin, Activation Expressed) proteins. The invention also includes methods of using the nucleic acid sequences, polypeptides encoded by the nucleic acid sequences disclosed herein, fusion proteins having all or a portion (e.g., an extracellular region) of the CLAX proteins, antibodies specific for the novel CLAXs, ligands and inhibitors for the novel CLAXs. The genes of CLAX are specifically expressed in lymphoid tissues and activated T lymphocytes but not resting T lymphocytes. The invention concerns the utility in pharmaceutical compositions for the prevention and treatment of infectious, inflammatory and allergic diseases.

DNA molecules encoding human CLAX proteins and their soluble fusion proteins

The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

CTLA4 receptor and uses thereof

Soluble CTLA4 molecules and uses thereof

The invention relates to anthracycline conjugates comprising at least one anthracycline molecule linked to a molecule that is reactive with a cell population to be eliminated such as antibody, bombesin, EGF and transferrin. Each anthracycline molecule, having a keto group at the C-13 position, is conjugated to the antibody via a linker arm and is bound to that linker arm via an acid-sensitive acylhydrazone bond at the 13-keto position of the anthracycline. The linker additionally contains a disulfide or thioether linkage as part of the antibody or ligand attachment to the immunoconjugate. The novel anthracycline acylhydrazone derivatives are useful in the preparation of the conjugates of this invention. The acid-sensitive hydrazone bond of the conjugates of this invention allows the release of free anthracycline from the conjugates in the acidic external or internal environment of the target cell. The conjugates and methods of the invention are therefore useful in antibody- or ligand-mediated drug delivery systems for the preferential killing of a selected cell population in the treatment of diseases such as cancers and other tumors, non-cytocidal viral or other pathogenic infections, and autoimmune disorders.

Anthracycline conjugates having a novel linker and methods for their

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Edmonds, WA, United States of America

Peter A Kiener