The present invention relates to methods of producing recombinant plasminogen in a mammalian expression system. A method for producing plasminogen, the method comprising (i) providing a host cell comprising a first recombinant polynucleotide encoding plasminogen and a second recombinant polynucleotide encoding a plasminogen activation inhibitor; (ii) culturing said host cell in a suitable culture medium under conditions to effect expression of plasminogen from the first polynucleotide and plasminogen activation inhibitor from the second polynucleotide.

A method of treating or preventing a disorder, or a complication of a disorder, of an eye of a subject comprising contacting a vitreous and/or aqueous humor with a composition comprising a truncated form of plasmin comprising a catalytic domain of plasmin (TPCD). TPCDs include, but are not limited to, miniplasmin, microplasmin and derivatives and variants thereof. The methods of the invention can be used to reduce the viscosity of the vitreous, liquefy the vitreous, induce posterior vitreous detachment, reduce hemorrhagic blood from the eye, clear or reduce materials toxic to the eye, clear or reduce intraocular foreign substances from the eye, increase diffusion of a composition administered to an eye, reduce extraretinal neovascularization and any combinations thereof. The method can be used in the absence of, or as an adjunct to, vitrectomy.

Compositions and methods for therapeutic delivery are disclosed. More particularly, the present disclosure relates to nanoparticle compositions that sequester the activity of a target molecule while leaving other domains accessible to bind targeted tissues of interest. Methods for thrombus dissolution include administering a nanoparticle reversibly coupled to a target molecule that can dissolve a blood clot. Compositions and methods for inducing blood clotting are also disclosed. Methods for inducing blood clotting include administering a nanoparticle reversibly coupled to a target molecule that can induce the formation of a blood clot. Methods for sequestering a target molecule are also disclosed. The method includes reversibly coupling a target molecule to a nanoparticle having an affinity ligand that reversibly couples the target molecule, and thus, sequesters the target molecule activity until the target molecule interacts with its substrate resulting in the release of the target molecule.

The present invention relates to a method for preventing and/or treating overweight/obesity and their related conditions, comprising administering an effective amount of plasminogen to a subject susceptible to or suffering from obesity and its related conditions, to reduce an abnormal/excessive fat deposition at various sites of the body. The present invention further relates to a medicament for preventing and/or treating obesity, and its use in the preparation of a medicament.

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.

The present invention relates to a method for restoring a balance between glucagon and insulin to normal, comprising administering an effective amount of plasminogen to a subject; furthermore, the present invention relates to a medicament for restoring a balance between glucagon and insulin to normal.

The present invention provides a method for treating a tumor in a subject, maintaining or improving body organ function under tumor conditions, and prolonging the survival period of the subject, comprising administering to the subject a prophylactically and/or therapeutically effective amount of components such as plasminogen of a plasminogen activation pathway. The present invention also provides a medicament comprising plasminogen, a pharmaceutical composition, a formulation and a kit for treating a tumor in a subject.

The present invention relates to a method for isolating Glu-plasminogen, said method comprising the anion exchange chromatography of blood plasma or a plasma fraction comprising Glu-plasminogen. Furthermore, the present invention relates to Glu-plasminogen obtainable from the method of the present invention and its use in a method for treating a patient suffering from or being at risk of developing a disorder selected from the group consisting of organ failure, a thrombotic event, arterial obstructive disease, microcirculation, disseminated intravascular coagulation (DIC), and a combination of two or more thereof.

The present invention relates to a method for preventing and treating hepatic fibrosis, comprising administering an effective amount of plasminogen to a subject.

Some embodiments provide a system for external manipulation of magnetic nanoparticles in vasculature using a remotely placed magnetic field-generating stator. In one aspect, the systems and methods relate to the control of magnetic nanoparticles in a fluid medium using permanent magnet-based or electromagnetic field-generating stator sources. Such a system can be useful for increasing the diffusion of therapeutic agents in a fluid medium, such as a human circulatory system, which can result in substantial clearance of fluid obstructions, such as vascular occlusions, in a circulatory system resulting in increased blood flow.