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.

This disclosure relates to nanoparticles coated with fusion proteins comprising a domain that binds a cancer marker and a domain comprising a toxic polypeptide. In certain embodiments, the targeted cancer marker is urokinase plasminogen activator receptor (uPAR) insulin-like growth factor 1 receptor (IGF1R), EGFR, HER2, and/or other member of the ErbB family of receptors. In certain embodiments, the molecule that binds a cancer marker is an amino terminal fragment of uPA or variant capable of binding uPAR and/or IGF1 or variant capable of binding IGF1R. In certain embodiments, the toxic polypeptide is a bacterial exotoxin.

The present application relates to protease substrates, peptide sequences cleavable by a protease, polypeptides comprising a protease cleavage sequence and methods for production thereof, pharmaceutical compositions comprising a polypeptide comprising a protease cleavage sequence, and methods for releasing an antigen-binding domain or a ligand by the cleavage of a protease cleavage sequence included in a polypeptide.

The present invention is directed to methods of treatment of airway obstruction associated with fibrin-containing cast formation by administering a fibrinolytic agent.

This disclosure relates to nanoparticles coated with fusion proteins comprising a domain that binds a cancer marker and a domain comprising a toxic polypeptide. In certain embodiments, the targeted cancer marker is urokinase plasminogen activator receptor (uPAR) insulin-like growth factor 1 receptor (IGF1R), EGFR, HER2, and/or other member of the ErbB family of receptors. In certain embodiments, the molecule that binds a cancer marker is an amino terminal fragment of uPA or variant capable of binding uPAR and/or IGF1 or variant capable of binding IGF1R. In certain embodiments, the toxic polypeptide is a bacterial exotoxin.

Methods and compositions for treating acute kidney injury in a subject are provided. The methods include measuring or having measured a level of soluble urokinase plasminogen activator receptor (suPAR) in a biological sample from the subject, determining or having determined the level of suPAR in the sample compared to a control suPAR level, and administering a therapeutically effective amount of an agent that antagonizes soluble urokinase plasminogen activator receptor (suPAR) to the subject having an elevated level of suPAR relative to the control suPAR level.

This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

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.

The present invention is directed to methods of treatment of airway obstruction associated with fibrin-containing cast formation by administering a fibrinolytic agent.

This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.