The State University of New York

Jonathan L Miller

Vicki A Lyle

David Cunningham

Clara N Finch

Matthew R Pincus

The present invention is directed to an isolated peptide that functionally mimics a binding site for a monoclonal antibody, the monoclonal antibody recognizing an epitope within the human platelet glycoprotein Ib/IX complex. This peptide is called a mimotope. The invention also provides an isolated molecule capable of binding to the peptide, or the mimotope, which molecule can be an antibody, a second peptide, a carbohydrate, a DNA molecule, an RNA molecule, or other naturally or chemically synthesized molecules. This isolated molecule is called an anti-mimotope. Mimotopes mimicking the binding site for monoclonal antibody C-34 and SZ-2, as well as anti-mimotopes to the C-34 mimotopes, are specifically provided.

Mimotopes and anti-mimotopes of human platelet glycoprotein Ib/IX

The present invention is directed to a method of selecting a clone that binds to human platelet glycoprotein Ib alpha using a human variable heavy chain and variable light chain immunoglobulin library. The invention is further directed to isolated nucleic acid molecules encoding a variable heavy chain or variable light chain region of an antibody, wherein the antibody binds to human platelet glycoprotein Ib alpha and inhibits aggregation of platelets. Expression vectors and host cells comprising the nucleic acid molecules are also provided, as well as methods for producing the variable heavy chain or the variable light chain region. An isolated variable heavy chain or variable light chain region of an antibody, wherein the antibody binds to human platelet glycoprotein Ib alpha and inhibits aggregation of platelets, is also provided. An antibody comprising the variable heavy chain or variable light chain regions is provided, as is a composition comprising the antibody and a carrier. The subject invention further provides a method of inhibiting aggregation of platelets, as well as a method of binding human platelet glycoprotein Ib alpha. A method of selecting a variable heavy chain or variable light chain region of an antibody is also provided.

Variable heavy chain and variable light chain regions of antibodies to human platelet glycoprotein Ib alpha

The present invention is directed to an isolated peptide that functionally mimics a binding site for a monoclonal antibody, the monoclonal antibody recognizing an epitope within the human glycoprotein Ib/IX complex. This peptide is called a mimotope. The invention also provides an isolated molecule capable of binding to the peptide, or the mimotope, which molecule can be an antibody, a second peptide, a carbohydrate, a DNA molecule, an RNA molecule, or other naturally or chemically synthesized molecules. This isolated molecule is called an anti-mimotope. Mimotopes mimicking the binding site for monoclonal antibody C-34 are specifically provided.

Mimotopes of human Platelet glycoprotein Ib/IX

The subject invention provides purified polypeptides encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide more reactive with yon Willebrand factor. Preferably, the mutation is in the hinge region of GP Ib.alpha., such as the substitution of valine for glycine at residue 233. These mutations alter the three-dimensional structure of the mutant polypeptide from a beta bend conformation to an alpha helix formation, and also create an amphipathic region within the mutant polypeptide. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

Mutations in the gene encoding the alpha chain of platelet glycoprotein

The subject invention provides purified polypeptides encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide more reactive with von Willebrand factor. Preferably, the mutation is in the hinge region of GP Ib.alpha., such as the substitution of valine for glycine at residue 233. These mutations alter the three-dimensional structure of the mutant polypeptide from a beta bend conformation to an alpha helix formation, and also create an amphipathic region within the mutant polypeptide. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

The subject invention provides purified polypeptides encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide less reactive with von Willebrand factor. Preferably, the mutation is in the leucine rich region of GPIb.alpha., such as the substitution of phenylalanine for leucine at residue 57. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

Mutations rendering platelet glycoprotein Ib-.alpha. less reactive

Mutations in the gene encoding the .alpha. chain on platelet

The subject invention provides purified polypeptide encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide less reactive with von Willebrand factor. Preferably, the mutation is in the leucine rich region of GPIb.alpha., such as the substitution of phenylalanine for leucine at residue 57. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

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Syracuse, NY, United States of America

Jonathan L Miller