The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

Provided herein are engineered proteases of the S1A family that are specific for, and capable of, cleaving Factor B. Also provided herein are methods of making and using such engineered proteases. The engineered proteases provided herein may be useful for treating a disease or condition associated with dysregulation of the complement system by reducing complement activation through cleavage and inactivation of Factor B.

The present invention provides a fusion protein suitable for dissolving a fibrin clot and a pharmaceutical composition containing the fusion protein. According to the present invention, there is provided a fusion protein of an antibody that binds to insoluble fibrin or an antigen-binding fragment thereof and a prourokinase mutant, in which amino acid sequence of a plasmin in a kringle domain is modified so as to be less cleavable with a plasmin, and a pharmaceutical composition containing the fusion protein.

The present invention relates to recombinant proteins having serine protease polypeptides that have serine protease activity in the presence of a serine protease inhibitor and that are able to completely or partially reverse a serine protease inhibitor effect, for example in a subject treated with a serine protease inhibitor. More specifically, described herein are recombinant proteins and methods for completely or partially reversing an anti-coagulant effect of a coagulation inhibitor.

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.

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.

Methods and composition for delivery of enzymes to a subject's airway. In some aspects, nebulized composition of enzymes, such as plasminogen activators are provided. In further aspects perfluorocarbon compositions comprising enzymes, such as plasminogen activators are provided. Compositions may, in some aspects, be used for the treatment of lung infections or acute lung injury, such as inhalational smoke induced acute lung injury (ISALI).

Disclosed is an enzymatic composition including:at least one enzyme, termed plasminogenase, for converting, into plasmin, plasminogen from a blood plasma medium including plasminogen;a solid support that is insoluble in aqueous solution, the solid support having dimensions suitable for being able to be retained on a filter having a cut-off threshold of less than or equal to 0.22 m. The plasminogenase is bound to the solid support and remains bound to this support on contact with a blood plasma medium. The composition is in the dry state. Also disclosed is a process for preparing such an enzymatic composition, to the use thereof and to a device (20) for preparing a blood plasma medium ex vivo rich in sterile plasmin and free of enzymatic composition.

The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.