The Scripps Research Institute

Scripps Clinic and Research Foundation

Edward F. Plow

Mark H. Ginsberg

Andrew L, Iii Frelinger

Edward F Plow

Mark H Ginsberg

Andrew L Frelinger, Iii

Ronald D Bowditch

Stanley E D'Souza

Thomas S Edgington

Robert McMillan

Dario C Altieri

Timothy E O'Toole

Concepcion Zamarron

Iii Frelinger Andrew L

Diagnostic systems, methods, polypeptides and antibodies for detecting the presence of C-terminal hGPIIb fragment of the platelet receptor GPIIb-IIIa in a body fluid sample are disclosed.

Vitro methods for determining in vivo thrombotic events

In vitro methods for determining in vivo thrombotic events

Test kits for detecting the presence of C-terminal hGPIIb fragments

Novel polypeptides derived from human fibronectin are described which bind to integrin receptors expressed by cells. The receptor binding site of human fibronectin begins at amino acid residue,and ends at residue,of fibronectin. The polypeptides facilitate attachment of cells to substrates either alone or in conjunction with RGD-containing peptides. Vectors, fusion proteins and antibodies are also described. Methods for promoting cell attachment and for inhibiting cell adhesion are also described.

Polypeptides for promoting cell attachment

Antibodies for detecting the presence of C-terminal hGPIIb fragment of the platelet receptor GPIIb-IIIa in a body fluid sample are disclosed.

Novel polypeptides derived from human fibronectin are described which bind to integrin receptors expressed by cells. The receptor binding site of human fibronectin begins at amino acid residue 1394 and ends at residue 1400 of fibronectin. The polypeptides facilitate attachment of cells to substrates either alone or in conjunction with RGD-containing peptides. Vectors, fusion proteins and antibodies are also described. Methods for promoting cell attachment and for inhibiting cell adhesion are also described.

Novel polypeptides derived from human fibronectin, and fusion proteins containing those peptide sequences are described which define a receptor binding site on fibronectin that binds to the platelet receptor glycoprotein GPIIb-IIIa expressed by cells. The receptor binding site of human fibronectin includes at least fibronectin amino acid residues 1410-1436. The polypeptides facilitate attachment of cells to substrates either alone or in conjunction with RGD-containing peptides. Vectors preparing the fusion proteins and antibodies are also described. Methods for promoting cell attachment and for inhibiting cell adhesion are also described.

The present invention contemplates therapeutic compositions containing a D.sub.30 homolog capable of binding to the Mac-1 receptor D.sub.30 binding site and inhibiting fibrinogen binding to the Mac-1 receptor via the D.sub.30 binding site, Methods of inhibiting Mac-1 receptor binding to any Mac-1 ligand and methods of inhibiting Mac-1 receptor mediated inflammation within a patient by administering a D.sub.30 homolog are also contemplated,

Inhibition of Mac-1 receptor binding to fibrinogen using D.sub.30

An antibody that immunoreacts with a ligand-induced binding site (LIBS) on GPIIIa, and particularly, a LIBS induced in a platelet-associated GPIIb-IIIa/fibrinogen complex is disclosed. Further disclosed are diagnostic systems and methods for assaying LIBS-containing platelets in a vascular fluid sample using the antibodies of the invention.

Antibodies that bind to a ligand-induced binding site on GPIIIa

The present invention discloses polypeptides consisting essentially of an amino acid residue sequence corresponding to a formula selected from the group consisting of: Tyr-His-Asp-Arg-Lys-Glu-Phe-Ala-Lys-Phe-Glu-Glu-Glu-Arg-Ala-Arg-Ala-Lys-Tr p-Asp-Thr-Ala-Asn-Asn (SEQ ID NO 1); Ala-Asn-Asn-Pro-Leu-Tyr-Lys-Glu-Ala-Thr-Ser-Thr-Phe-Thr-Asn-Ile-Thr-Tyr-Ar g-Gly-Thr (SEQ ID NO 2); Ile-His-Asp-Arg-Lys-Glu-Phe-Ala-Lys-Phe-Glu-Glu-Glu-Arg-Ala-Arg-Ala-Lys-Tr p-Asp-Thr-Ala-Asn-Asn-Pro-Leu-Tyr-Lys-Glu-Ala-Thr-Ser-Thr-Phe-Thr-Asn-Ile-T hr-Tyr-Arg-Gly-Thr (SEQ ID NO 4); and Gly-Pro-Asp-Ile-Leu-Val-Val-Leu-Leu-Ser-Val-Met-Gly-Ala-Ile-Leu-Leu-Thr-Gl y-Leu-Ala-Ala-Leu-Leu-Ile-Trp-Lys-Leu-Leu-Ile-Thr-Ile-His-Asp-Arg-Lys-Glu-P he-Ala-Lys-Phe-Glu-Glu-Glu-Arg-Ala-Arg-Ala-Lys-Trp-Asp-Thr-Ala-Asn-Asn-Pro- Leu-Tyr-Lys-Glu-Ala-Thr-Ser-Thr-Phe-Thr-Asn-Ile-Thr-Tyr-Arg-Gly-Thr (SEQ ID NO 5), as well as diagnostic kits including same. The present invention also discloses methods for determining the presence of anti-GPIIIa autoantibodies in a vascular fluid sample, which autoantibodies are indicative of chronic immune thrombocytopenic purpura in a patient.

Methods and compositions for diagnosing chronic immune thrombocytopenic

A polypeptide consisting essentially of an amino acid residue sequence corresponding to a formula selected from the group consisting of:

Receptor-induced binding sites (RIBS) expressed in a ligand when that ligand is bound in a complex with a receptor are disclosed, as are polypeptides that correspond in amino acid residue sequence with a RIBS expressed by a receptor-ligand complex. Particularly-preferred polypeptides correspond to a RIBS amino acid sequence of the gamma chain of human fibrinogen. Monoclonal antibodies that immunoreact with a RIBS but do not substantially immunoreact with either the ligand or the receptor when free in solution are also disclosed, as are hybridomas secreting those antibodies, and methods of making and using such antibodies.

Polypeptides that mimic receptor-induced binding sites, and methods of

An integrin-activating antibody is disclosed that immunoreacts with an integrin and when immunoreacted increases the binding affinity of the integrin for binding to ligands specific for the integrin. The antibody also immunoreacts with a ligand-induced binding site (LIBS) on the integrin when the integrin is specifically bound to its ligand. Further disclosed are therapeutic compositions and methods for promoting cell adhesion using the disclosed integrin-activating antibodies.

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San Diego, CA, United States of America

Edward F Plow