Catalyst Biosciences, Inc.

Dendreon Corporation

Vertex Pharmaceuticals, Inc.

Corvas International, Inc.

The Scripps Research Institute

Torrey Pines Institute for Molecular Studies

Dyax Corporation

Amgen Fremont Inc.

Deadreon Corporation

Dendreon San Diego LLC

Wilex Ag

Gc Biopharma Corp.

Edwin L Madison

Christopher D Thanos

Mikhail Popkov

Vanessa Soros

Edgar Ong

Joseph Edward Semple

Jiunn-chern Yeh

Terence Kevin Brunck

Grant Ellsworth Blouse

Eric Steven Furfine

Jeffrey Charles Way

Marguerita S Lim-Wilby

Kent Pryor

Matthew John Traylor

Kimberly Tipton

Ian Nevin Foltz

Chadwick Terence King

Bruce Alan Keyt

Jaspal Singh Kang

Odile Esther Levy

Gian Luca Araldi

Andrew Nixon

Francine Zhifen Chen

Susan Yoshiko Tamura

Michael I Weinhouse

Sandra Waugh Ruggles

David Duncan

Kathy Manchulenko

John Eugene Reiner

Jack Nguyen

Jennifer Hope Richardson

Amir P Tamiz

Gary Samuel Coombs

Ronald D Lewis, Ii

Caroline Darne Scatena

C Maxwell Lawrence

Stanislaw K Morkowski

Wayne R Godfrey

Peter Koon Bong Ling

Edgar O Ong

Jennifer H Richardson

Peter Koon Ling

Sandra Ruggles

Shaun Coughlin

Provided are nucleic acid molecules, including vectors and plasmids, encoding modified u-PA polypeptides and fusion proteins containing the modified u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The nucleic acids and encoded modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

Modified urokinase-type plasminogen activator polypeptides and methods of use

Provided are MTSP-1 polypeptides modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to inhibit its activity and thereby inhibit complement activation. The modified MTSP-1 polypeptides that inhibit complement activation can be used for treatment of diseases and conditions in which complement activation plays a role. Such diseases and conditions include inflammatory diseases and diseases with an inflammatory component. Exemplary of these disorders are ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, ophthalmic disorders, such as diabetic retinopathies and macular degeneration, including age-related macular degeneration (AMD), and transplanted organ rejection, such as renal delayed graft function (DGF).

Nucleic acid encoding modified membrane type serine protease 1 (MTSP-1) polypeptides and methods of use

Modified membrane type serine protease 1 (MTSP-1) polypeptides and methods of use

Provided are u-PA polypeptides and fusion proteins containing the u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

Nucleic acids encoding modified factor VII polypeptides, vectors and cells containing the nucleic acids, uses of the nucleic acids, methods of making the encoded polypeptides, and methods of treatment are provided. The encoded modified FVII polypeptides include Factor VIIa and other forms of Factor VII. Among the encoded modified FVII polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities.

Factor VII polypeptides that are modified and uses thereof

Nucleic acid molecules encoding modified factor IX (FIX) polypeptides and uses thereof are provided. Such modified FIX polypeptides include FIXa and other forms of FIX. Among the modified FIX polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Modified factor IX polypeptides and uses thereof

Nucleic acid encoding modified factor VII polypeptides, vectors and cells containing the nucleic acid, uses of the nucleic acids, methods of making the encoded polypeptides, and methods of treatment are provided. The encoded modified FVII polypeptides include Factor VIIa and other forms of Factor VII. Among the encoded modified FVII polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities.

Modified therapeutic proteins are provided. In particular modified Factor X polypeptides, which includes the Factor X zymogen, Factor Xa and other forms of Factor X, and uses thereof are provided.

Modified factor X polypeptides and uses thereof

Provided are methods for and compounds for modulating the complement system. In particular, compounds are provided that inhibit complement activation and compounds are provided that promote complement activation. The compounds are therapeutics by virtue of their effects on the complement system. Hence, the compounds that inhibit complement activation can be used for treatment of ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, inflammatory diseases and diseases with an inflammatory component, including Alzheimer's Disease and other neurodegenerative disorders.

Modified MT-SP1 proteases that inhibit complement activation

Modified factor VII polypeptides and uses thereof are provided. Such modified FVII polypeptides include Factor VIIa and other forms of Factor VII. Among modified FVII polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Modified Factor IX (FIX) polypeptides and uses thereof are provided. Such modified FIX polypeptides include FIXa and other forms of FIX. Among the modified FIX polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Methods for identifying modified proteases with modified substrate specificity or other properties are provided. The methods screen candidate and modified proteases by contacting them with a substrate, such as a serpin, an alpha macroglobulins or a p35 family protein or modified serpins and modified p35 family members or modified alpha macroglobulins, that, upon cleavage of the substrate, traps the protease by forming a stable complex. Also provided are modified proteases.

Protease screening methods and proteases identified thereby

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Edwin L Madison