Bayer Corporation

Talecris Biotherapeutics, Inc.

Other

Miles Inc.

Bayer Pharmaceuticals Corporation

Gary J Jesmok

Grace C Tsay

Kyle A Landskroner

Jeffrey M Greve

Thomas P Zimmerman

Valery Novokhatny

Armen B Shanafelt

Gayle D Wetzel

Kathryn K Taylor

Kenneth Lembach

The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

IL-2 selective agonists and antagonists

Methods of thrombolysis that allow the use of a fibrinolytic composition comprising reversibly inactivated acidified plasmin and the localized delivery of the plasmin to a vascular thrombotic occlusion are disclosed. Further disclosed is a method for administering a therapeutic dose of a fibrinolytic composition substantially free of plasminogen activator to a human or animal having a vascular thrombotic occlusion. The fibrinolytic composition includes a reversibly inactivated acidified plasmin substantially free of plasminogen activator. Intravascular catheter delivery of the fibrinolytic composition directly into or in the immediate vicinity of the thrombus is disclosed to minimize the systemic degradation of fibrin while retaining the maximum plasmin activity against the thrombus. The method is applicable to the dissolution of thrombi in artificial devices, e.g., hemodialysis grafts.

Method of thrombolysis by local delivery of reversibly inactivated acidified plasmin

Methods of thrombolysis that allow the use of a fibrinolytic composition comprising reversibly inactivated acidified plasmin and the localized delivery of the plasmin to a vascular thrombotic occlusion are disclosed. Further disclosed is a method for administering a therapeutic dose of a fibrinolytic composition substantially free of plasminogen activator to a human or animal having a vascular thrombotic occlusion. The fibrinolytic composition includes a reversibly inactivated acidified plasmin substantially free of plasminogen activator. Intravascular catheter delivery of the fibrinolytic composition directly into or in the immediate vicinity of the thrombus is disclosed to minimize the systemic degradation of fibrin while retaining the maximum plasmin activity against the thrombus.

The invention provides an improved method of thrombolytic therapy by the direct admiistration of active plasmin to a clot site via catheter. An active, stable preparation of plasmin is provided, as is a process for activation and isolation of active plasmin.

Method of thrombolysis by local delivery of active plasmin

Mild heat-treatment of IgM antibody concentrates diminishes the potential to induce non-specific complement activation without significant loss of normal immunologic effector functions. These IgM immunoglobulin concentrates retain specific antigen binding properties and activate complement when bound to antigen. Preferred product includes at least 20% by weight IgM in an IgM/IgG antibody mixture. Heating is done at a temperature within the range of about 40.degree. C. to 62.degree. C., preferably about 45.degree. to 55.degree. C., in a solution having an acid pH (preferably 4.0 to 5.0) for at least about 10 minutes.

Methods of treatment using heat-treated IGM antibody preparations

Heat-treated IgM antibody preparations

Mild heat-treatment of IgM antibody concentrates diminishes the potential to induce non-specific complement activation without significant loss of normal immunologic effector functions. These IgM immunoglobulin concentrates retain specific antigen binding properties and activate complement specific antigen binding properties and activate complement when bound to antigen. Preferred product includes at least 20% by weight IgM in an IgM/IgG antibody mixture. Heating is done at a temperature within the range of about 40.degree. C. to 62 .degree. C., preferably about 45.degree. to 55.degree. C., in a solution having an acid pH (preferably 4.0 to 5.0) for at least about 10 minutes.

Growing community of inventors

Raleigh, NC, United States of America

Gary J Jesmok