30 results about "GPVI" patented technology

The present disclosure relates to agents which interfere with the binding of GPVI to various components. Agents which interfere with GPVI interaction with one or both of fibronectin and vitronectin or sequences thereof are also disclosed. Methods of treating disorders or diseases which involve pathological, dysfunctional or non-pathological interaction of GPVI with fibronectin and / or vitronectin are included in the present disclosure. The invention also relates to uses of agents for the prevention or treatment of disorders arising from blood platelet adhesion and aggregation.

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

The present invention relates, in general, to glycoprotein VI (GPVI) and, in particular, to aptamers to GPVI and to compositions comprising same. The invention also relates to methods of inhibiting platelet aggregation using an aptamer that binds to and inhibits the activity of GPVI. The invention further relates to antidotes to GPVI aptamers and to methods of using such antidotes to reverse aptamer-induced platelet inhibition. The invention also relates to aptamers that bind to and enhance the activity of GPVI.

The present invention discloses novel antibodies that specifically bind to the human platelet membrane protein Glycoprotein VI (GPVI) and their monovalent fragments or derivatives. The antibodies of the invention are antibodies from hybridoma clone 390 and fragment antibodies thereof able to induce a GPVI depletion phenotype. These antibodies and Fab fragments are able to block collagen binding and thus preventing platelet activation by collagen. The invention also relates to hybridoma clones and expression plasmids for the production of disclosed antibodies and Fab fragments. The present invention further refers to the uses of monovalent antibody fragments to manufacture research, diagnostic and immunotherapeutic agents for the treatment of thrombosis and other vascular diseases. The invention also concerns a Fab bearing a molecule at the C-terminal extremity, as well as method for prevention of recognition of Fab by antibodies using such modified Fab. The invention concerns a method for prevention of platelet activation when an anti-GP VI Fab is used.

The present invention relates to Glycoprotein VI (GPVI) fusion proteins (GPVI-fusion proteins) comprising a tag like myc, GST, HA, FLAG, STREP but preferably a Immunoglobulin molecule (Ig), more preferably a Fc portion of said Ig and a protein or oligopeptide having the biological activity of GPVI (GPVI-like protein) which is binding to collagen and their use in methods and kits for the screening of potential agonists or antagonists for GPVI-colagen and / or platelet-collagen interaction is disclosed. Further, pharmaaceutical compositions and therapeutic methods are provided comprising such GPVI-fusion proteins for the treatment of thrombotic and cardiovascular events and disorders related to GPVI-collagen and / or platelet-collagen interactions.

The present invention relates to humanized anti-human GPVI antibodies and uses thereof.

The present invention relates to a fusion protein comprising a) a first polypeptide selected from among SDF-1 (stromal cell derived factor-1) or peptidase / protease-resistant variants or fragments thereof which have the CXCR4- / CXCR7- binding function of SDF-1; and b) a second polypeptide which is selected from among GPVI (glycoprotein VI), or the extracellular domain of GPVI, or fragments or variants of the extracellular domain of GPVI which contain the collagen binding function of GPVI, wherein the first polypeptide and the second peptide are linked to one another directly or via a linker molecule. The invention furthermore relates to the use of the fusion protein for treating diseases.

The present invention relates to Glycoprotein VI (GPVI) fusion proteins (GPVI-fusion proteins) comprising a tag like myc, GST, HA, FLAG, STREP but preferably a Immunoglobulin molecule (Ig), more preferably a Fc portion of said Ig and a protein or oligopeptide having the biological activity of GPVI (GPVI-like protein) which is binding to collagen and their use in methods and kits for the screening of potential agonists or antagonists for GPVI-collagen and / or platelet-collagen interaction is disclosed.Further, pharmaceutical compositions and therapeutic methods are provided comprising such GPVI-fusion proteins for the treatment of thrombotic and cardiovascular events and disorders related to GPVI-collagen and / or platelet-collagen interactions.

The present invention provides a convenient and highly sensitive method of determining sGPVI present in plasma; this is accomplished by establishing a plurality of mouse hybridomas that produce antibody against GPVI and combining the antibodies produced therefrom. Provided thereby are a novel platelet activation marker, a reagent and method for determining this novel platelet activation marker, and novel applications of this marker in, for example, the diagnosis of diseases associated with platelet activation / vascular endothelial injury.

The present invention relates, in general, to glycoprotein VI (GPVI) and, in particular, to aptamers to GPVI and to compositions comprising same. The invention also relates to methods of inhibiting platelet aggregation using an aptamer that binds to and inhibits the activity of GPVI. The invention further relates to antidotes to GPVI aptamers and to methods of using such antidotes to reverse aptamer-induced platelet inhibition. The invention also relates to aptamers that bind to and enhance the activity of GPVI.

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

The present invention describes a method for reducing reperfusion injury and / or infarction by using an inhibitor of platelet GPVI. This method may be used to treat patients during or after a heart attack or elective cardiac surgery.

The present invention relates to methods and pharmaceutical compositions for the prophylactic treatment of metastases. The inventors showed in vivo that lung metastasis in GPVI deficient mice are reduced compared to controls. They demonstrated that GPVI is involved in platetet interaction with tumor cells and this interaction is mediated by EMMPRIN.). Using an anti-EMMPRIN antibody, they showed that the adhesion of platelets to tumors cells is decreased. In particular, the present invention relates to a method for the prophylactic treatment of metastases in a patient suffering from cancer comprising administering to the subject a therapeutically effective amount of an agent which inhibits the interaction between GPVI and EMMPRIN.

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

A crystal comprising the collagen binding domain of human GPVI is provided and defined by structural atomic coordinates. Employing computer modeling based on the crystal structure, including methods for identifying inhibitors of GPVI collagen binding activity, methods for screening libraries of compounds for potential to bind to the GPVI collagen binding domain, and methods of identifying a compound useful for the treatment of a GPVI-mediated disorder, are also provided.

The invention relates to methods and kits for determining platelet susceptibility to activation in a patient. More particularly, the present invention relates to a method for determining platelet susceptibility to activation in a patient, comprising a step consisting of measuring the level of GPVI dimers at the platelet surface in a blood sample obtained from said patient.

The invention relates to the technical field of medicines, in particular to application of a compound in preparation of antithrombotic drugs. At present, in the preclinical research of new anti-platelet drugs, hemostasis is more and more emphasized while thrombus formation is inhibited. In tMCAO, a receptor GPIb or GPVI which plays a role in the early stage of platelet activation can relieve ischemic brain injury of a mouse, and bleeding complications cannot be increased, so that intervention in the early stage of platelet activation is effective and safer. The compound Col003 is obtained by degrading a natural compound molecule AK778 in a culture medium or a buffer solution, can play an anti-platelet role in the early stage of platelet activation, can inhibit the formation of thrombus, does not affect the blood coagulation function, is relatively weak in cytotoxicity, and is expected to become an effective and safe therapeutic drug for cerebral arterial thrombosis.

The invention relates to the technical field of biology, also relates to the bio-pharmaceutical technology, and particularly relates to a human platelet collagen receptor ''Glycoprotein VI'' (or GPVI) resistant human-derived monoclonal antibody fragment and application thereof in medicines. The monoclonal antibody fragment is human derived, and comprises polypeptide amino acid sequences comprising three heavy chain variable region HV sequences and three light chain variable region LV sequences, antibody fragment scFv(single chain fragment variable) or other polypeptides recombined by the monoclonal antibody fragment can be used as a blocking agent of collagen receptor ''Glycoprotein VI'' for application in preparation of medicines for treatment or prevention of thrombotic cardio cerebrovascular diseases, the monoclonal antibody fragment can be used in the preparation of antithrombotic medicines resisting collagen to activate platelet, or in the preparation of detection reagents and the like for detecting whether free ''Glycoprotein VI'' exists. In the preparation of the medicines, a very complex humanized reconstruction process is omitted.

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

The present disclosure provides antibodies or antibody fragments specific for GPVI. In particular, it relates to antibodies or antibody fragments that have combined beneficial properties and are therefore useful for the treatment or prophylaxis of GPVI related disorders or conditions, such as for example thrombotic or vascular disorders.

The invention discloses a primer for detecting methylation level of a GPVI gene promoter region and a detection method of the primer. The primer comprises an amplification primer pair of the GPVI genepromoter region after bisulfite conversion and a sequencing primer GPVI-S, the sequence of the upstream primer GPVI-F is 5'-ATTAGGGAGTTTATGGGAGTACGG-3', and the sequence of the downstream primer GPVI-R is 5'-Biotin-ATTCCTCAACCCTATCCTAAACTCTAT-3'; the sequence of the sequencing primer GPVI-S is 5'-AATATAGATTAGGTTTTAGTAGG-3'. A pyrosequencing method is adopted for sequencing, the methylation and non-methylation proportions of a CpG island in a target region are efficiently detected, the methylation level of the GPVI promoter region is evaluated, and the methylation level can be used as an earlyindex for myocardial infarction.

Provided are an agent for noninvasively and easily diagnosing Alzheimer's disease, a method for diagnosing Alzheimer's disease through the measurement, and a measurement kit therefor. The present invention relates to a reagent for measuring soluble GPVI (sGPVI) in a human body fluid; an agent for specifically diagnosing Alzheimer's disease, said agent comprising a reagent for measuring the activation of platelets or coagulation-fibrinolysis system in said human body fluid; and a method for specifically diagnosing Alzheimer's disease, said method comprising a step for measuring the concentration of sGPVI in a collected human body fluid and a step for measuring the activation of platelets or coagulation-fibrinolysis system in said human body fluid.

The present invention relates to an isolated humanized protein binding to human Glycoprotein VI (hGPVI) for treating a GPVI-related condition in a subject in need thereof, wherein said isolated humanized protein is to be administered during at least 2 hours to the subject, preferably during at least 4 to 6 hours.

The present invention relates to an isolated humanized protein binding to human Glycoprotein VI (hGPVI ) for treating a GPVI-related condition in a subject in need thereof, wherein said isolated humanized protein is to be administered during at least 2 hours to the subject, preferably during at least 4 to 6 hours.

The present invention discloses novel antibodies that specifically bind to the human platelet membrane protein Glycoprotein VI (GPVI) and their monovalent fragments or derivatives. The antibodies of the invention are antibodies from hybridoma clone 390 and fragment antibodies thereof able to induce a GPVI depletion pheno-type. These antibodies and Fab fragments are able to block collagen binding and thus preventing platelet activation by collagen. The invention also relates to hybridoma clones and expression plasmids for the production of disclosed antibodies and Fab fragments. The present invention further refers to the uses of monovalent antibody fragments to manufacture research, diagnostic and immunotherapeutic agents for the treatment of thrombosis and other vascular diseases. The invention also concerns a Fab bearing a molecule at the C-terminal extremity, as well as method for prevention of recognition of Fab by antibodies using such modified Fab. The invention concerns a method for prevention of platelet activation when an anti-GP VI Fab is used.

The invention relates to methods and kits for determining platelet susceptibility to activation in a patient. More particularly, the present invention relates to a method for determining platelet susceptibility to activation in a patient, comprising a step consisting of measuring the level of GPVI dimers at the platelet surface in a blood sample obtained from said patient.

The present disclosure provides antibodies or antibody fragments specific for GPVI. In particular, it relates to antibodies or antibody fragments that have combined beneficial properties and are therefore useful for the treatment or prophylaxis of GPVI related disorders or conditions, such as for example thrombotic or vascular disorders.