Peter Sims - Del Mar CA, US Therese Wiedmer - Del Mar CA, US Robert Silverman - Beachwood OH, US
International Classification:
C07H021/02 C07H021/04 A61K038/46 C12N009/16
US Classification:
536/023100, 435/196000, 424/094600
Abstract:
The present invention is based on a family of membrane proteins, Phospholipid Scramblases (PLSCR), that mediate accelerated trans-bilayer movement of plasma membrane phospholipids in response to elevated cytoplasmic calcium. At least one Phospholipid Scramblase gene is highly inducible by interferon. Interferon-induced expression of Phospholipid Scramblase 1 (and/or related genes) alters the physical and functional properties of the cell surface so as to (1) inhibit tumor cell proliferation and survival; (2) inhibit maturation and release of membrane-enveloped viruses; and/or (3) promote clearance of virus-infected cells and cancer cells through the reticuloendothelial system. The present invention provides Phospholipid Scramblase polypeptides, polynucleotide sequences that encode Phospholipid Scramblase polypeptides, and antibodies that are immunoreactive with the polypeptides. The finding that human Phospholipid Scramblase 1 polypeptides are induced by interferons, indicates a role for the Scramblase polypeptides in treating and preventing cancer and viral infection.
Inhibition Of Complement Mediated Inflammatory Response
Peter J. Sims - Oklahoma City OK Therese Wiedmer - Oklahoma City OK
Assignee:
Oklahoma Medical Research - Oklahoma City OK
International Classification:
C12Q 100 C12Q 102 G01N 3353 G01N 33567
US Classification:
435 4
Abstract:
A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, a 37 kDa protein found on the surface of human platelets, a 37 kDa protein found on the surface of human endothelial cells, active derivatives or fragments thereof which act to inhibit the activity of C5b-9, anti-idiotypic antibodies mimicking the action of the inhibitor proteins or antibodies against C7 or C9 which block the formation of the C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and vascular endothelium of perfused organs and tissues, thereby preventing the C5b-9 initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage. Further, immune disease states can be treated by administering an effective amount of a C5b-9 inhibitor to suppress C5b-9 mediated platelet activation in vivo.
Inhibition Of Complement Mediated Inflammatory Response Using Monoclonal Antibodies Specific For A Component Forming The C56-9 Complex Which Inhibit The Platelet Or Endothelial Cell Activating Function Of The C56-9 Complex
Peter J. Sims - Oklahoma City OK Therese Wiedmer - Oklahoma City OK
Assignee:
Oklahoma Medical Research Foundation - Oklahoma City OK
International Classification:
A61K 39395 C07K 1618
US Classification:
4241451
Abstract:
Compositions and methods for use thereof relating to monoclonal antibodies, and fragments thereof, having inhibitory activity towards the cell-activating function of the complement C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and/or endothelial cells, thereby preventing C5b-9-initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage. Further, disease states can be treated by administering to platelets and/or endothelial cells in vivo an effective amount of a monoclonal antibody, or fragment thereof, which has inhibitory activity towards the cell-activating function of the C5b-9 complex, in a pharmaceutically acceptable carrier.
Method Of Inhibition Of Complement Mediated Inflammatory Response
Peter J. Sims - Oklahoma City OK Therese Wiedmer - Oklahoma City OK
Assignee:
Oklahoma Medical Research Foundation - Oklahoma City OK
International Classification:
A61K 39395 A61K 3800 C07K 1600
US Classification:
4241301
Abstract:
A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, a 37 kDa protein found on the surface of human platelets, a 37 kDa protein found on the surface of human endothelial cells, active derivatives or fragments thereof which act to inhibit the activity of C5b-9, anti-idiotypic antibodies mimicking the action of the inhibitor proteins or antibodies against C7 or C9 which block the formation of the C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and vascular endothelium of perfused organs and tissues, thereby preventing the C5b-9 initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage. Further, immune disease states can be treated by administering an effective amount of a C5b-9 inhibitor to suppress C5b-9 mediated platelet activation in vivo.
Inhibition Of Complement Mediated Inflammatory Response
Peter J. Sims - Oklahoma City OK Therese Wiedmer - Oklahoma City OK
Assignee:
Oklahoma Medical Research Foundation - Oklahoma City OK
International Classification:
C07K 1500 A61K 3702 A61K 3764
US Classification:
514 21
Abstract:
A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, a 37 kDa protei The U. S. Government has rights in this invention by virtue of certain government grants.
Inhibition Of Complement Mediated Inflammatory Response
Peter J. Sims - Oklahoma City OK Therese Wiedmer - Oklahoma City OK
Assignee:
Oklahoma Medical Research Foundation - Oklahoma City OK
International Classification:
C07K 1500 A61K 3702 A61K 3764
US Classification:
514 21
Abstract:
A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, active derivatives or fragments thereof which act to inhibit the activity of C5b-9, anti-idiotypic antibodies mimicking the action of the inhibitor proteins or antibodies against C7 or C9 which block the formation of the C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and vascular endothelium of perfused organs and tissues, thereby preventing the C5b-9 initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage. Further, immune disease states can be treated by administering an effective amount of a C5b-9 inhibitor to suppress C5b-9 mediated platelet activation in vivo.