Zymogenetics, Inc.

Andrzej Z Sledziewski

Wayne R Kindsvogel

Lillian Anne Bell

Paul O Sheppard

Frederick S Hagen

Anur A Kumar

Ligand-binding, dimerized polypeptide fusions comprising two polypeptide chains are disclosed. Each of the polypeptide chains comprises a ligand-binding domain of either a growth factor receptor or a hormone receptor joined to an immunoglobulin constant region polypeptide. Dimerization of the polypeptide fusion results in enhancement of biological activity. The immunoglobulin constant region polypeptide may comprise an immunoglobulin heavy chain constant region domain and hinge region.

Ligand-binding, dimerized polypeptide fusions

Methods for producing secreted receptor analogs and biologically active peptide dimers are disclosed. The methods for producing secreted receptor analogs and biologically active peptide dimers utilize a DNA sequence encoding a receptor analog or a peptide requiring dimerization for biological activity joined to a dimerizing protein. The receptor analog includes a ligand-binding domain. Polypeptides comprising essentially the extracellular domain of a human PDGF receptor fused to dimerizing proteins, the portion being capable of binding human PDGF or an isoform thereof, are also disclosed. The polypeptides may be used within methods for determining the presence of and for purifying human PDGF or isoforms thereof.

Methods for producing secreted ligand-binding fusion proteins

DNA constructs encoding ligand-binding fusion proteins

Dimerized polypeptide fusions

Biologically active dimerized and multimerized polypeptide fusions

Methods of producing secreted receptor analogs and biologically active

Methods are disclosed for producing hybrid G protein-coupled receptors. DNA sequences encoding hybrid G protein-coupled receptors are provided, wherein the receptors comprise mammalian G protein-coupled receptors having at least one domain other than the ligand-binding domain replaced with a corresponding domain of a yeast G protein-coupled receptor. DNA constructs comprising the following operatively linked elements: a transcriptional promoter, a DNA sequence encoding a hybrid G protein-coupled receptor, wherein the receptor comprises a mammalian G protein-coupled receptor having at least one domain other than the ligand-binding domain replaced with a corresponding domain of a yeast G protein-coupled receptor, and a transcriptional terminator. Host cells transformed with the DNA constructs and methods utilizing the transformed cells are also provided.

Mammalian/yeast hybrid G protein-coupled receptors

Methods of using biologically active dimerized polypeptide fusions to

Methods of producing hybrid G protein-coupled receptors

Methods for purifying factor VIII:C, von Willebrand factor (vWF) or complexes thereof from heterogeneous biological fluids are disclosed. The methods utilize a binding peptide, specific to either factor VIII:C or vWF, bound to an insoluble matrix. Peptides suitable for use within the methods are also disclosed.

Method for purifying factor VIII:C, von Willebrand factor and complexes

Method of producing secreted receptor analogs and biologically active

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Seattle, WA, United States of America

Andrzej Z Sledziewski