Eli Lilly and Company

Indiana University

Brian W Grinnell

David Thompson Berg

Mark Alan Richardson

George J Cullinan

Bryan Edward Jones

Sau-Chi Betty Yan

Bruce Edward Gerlitz

Daniel Lawrence Hartman

Charles V Jackson

David S Calnek

Daniel C Howey

Nils U Bang

Lawrence Mark Gelbert

Hartmut Ehrlich

Angelina Vucic Ciaccia

David Eugene Joyce

Joseph A Jakubowski

Bruce Molitoris

S Richard Jaskunas

S Betty Yan

The present invention provides a method for preventing and/or treating subjects with acute renal failure caused by a variety of conditions. The method comprises administering to the subject soluble thrombomodulin which does not activate Protein C. In conjunction with standard of care, soluble thrombomodulin that does not activate Protein C will prevent or reduce acute kidney injury and subsequent morbidity and mortality.

Treating acute renal failure with soluble thrombomodulin variants

Method of treating a disease or pathological condition with activated protein C or a compound having activated protein C activity by direct regulation of the expression of specific genes associated with the disease or pathological condition.

Methods of treating diseases with activated protein C

Novel human protein C derivatives are described. These derivatives have increased anti-coagulation activity, resistance to serpin inactivation, and increased sensitivity to thrombin activation compared to wild-type protein C and retain the biological activity of the wild-type human protein C. These derivatives will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of acute coronary syndromes, vascular occlusive disorders, hypercoagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Protein C derivatives

Methods of modulating NF-kB transcription factor

A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, , meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Method of reducing mortality in severe sepsis

A method of treatment for patients with vascular occlusion and thromboembolic disorders including the acquired disease state of thrombotic stroke, by administering activated protein C. The administration of aPC provides a highly selective therapeutic agent with a low potential for causing bleeding complications. The administration of aPC is beneficial in preventing the local extension of the microvascular and macrovascular occluding arterial thrombus, thereby reducing the neurological deficit resulting from the stroke.

Methods for treating vascular disorders

A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Methods for treating hypercoagulable states or acquired protein C deficiency

Methods for treating vascular disorders using activated protein C

The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells. Additionally, the invention further comprises the recombinant human protein C molecule produced in 293 cells which comprises novel glycosylation patterns.

Method of using eukaryotic expression vectors comprising the bk virus enhancer

Methods for treating hypercoagulable states or acquired protein C

The present invention provides a method of treatment for patients with a variety of thrombotic disorders including, but not limited to, stroke, venous thrombosis, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, and thrombosis as a result of peripheral vascular surgery. Said treatment is a combination therapy with human aPC and antiplatelet agents including, but not limited to, aspirin (ASA), clopidogrel, ReoPro.RTM. (abciximab), dipyridamole, ticlopidine and IIb/IIIa receptor antagonists. The synergy will result in the ability to reduce the dosages of the agents used in the combination therapy.

Methods for treating thrombotic disorders

Method of using eukaryotic expression vectors comprising the BK virus

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Indianapolis, IN, United States of America

Brian W Grinnell