Subjects of the invention are a method of plasminogen supplementation in a plasminogen-deficient subject, and method for the treatment of plasminogen-deficiency in a plasminogen-deficient subject. These methods comprise administering to the plasminogen-deficient subject a dose of plasminogen, and more particularly Glu-plasminogen, for increasing the subject plasminogen activity level by at least about 1%, and more particularly by at least 10%, of the normal plasminogen activity and for maintaining the plasminogen activity level over a supplementation period or a treatment period. The plasminogen-deficient subject of the present invention may suffer from Type-I, Type-II plasminogen-deficiency or an acquired deficiency.

The present invention discloses modified forms of plasmin with advantageous properties. As compared to their natural unmodified form, these variants exhibit significantly modulated kinetics in terms of delayed inhibition characteristics in the presence of specific inhibitors, such as α.sub.2-antiplasmin (α.sub.2-AP). These include PEG-conjugated thiol derivatives of truncated plasmin with potential clinical applications in various regimens of thrombolytic therapies.

The present invention relates to plasminogen for use in a method for preventing or treating a thrombotic event in a patient, wherein the patient is at risk of developing or is suffering from microthrombi.

Provided are methods for producing biologically active mutant recombinant plasminogen polypeptides with desired pharmaceutical properties. The refolded polypeptides may be treated with a plasminogen activator, such as tPA, urokinase, or streptokinase to generate biologically active mutant plasmin polypeptide for pharmaceutical use. Methods are also provided to producing biologically active fusion recombinant mutant plasminogen/plasmin polypeptides that can cross the BBB through receptor mediated transcytosis. The fusion partner may carry the mutant plasminogen/plasmin polypeptides into the brain for increased therapeutic efficiency.

A system for the physical manipulation of free magnetic rotors in a circulatory system using a remotely placed magnetic field-generating stator is provided. In one embodiment, the invention relates to the control of magnetic particles 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. Examples of vascular occlusions targeted by the system include, but are not limited to, atherosclerotic plaques, including fibrous caps, fatty buildup, coronary occlusions, arterial stenosis, restenosis, vein thrombi, arterial thrombi, cerebral thrombi, embolisms, hemorrhages, other blood clots, and very small vessels.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

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.

The present invention relates to a method and a drug for preventing or treating osteoarthritis by plasminogen. Specifically, the present invention involves administering an effective amount of plasminogen to an osteoarthritis subject for treating the osteoarthritis. In addition, the present invention further relates to an osteoarthritis treatment drug comprising plasminogen, a product, and a kit.

Pharmaceutical compositions comprising plasminogen or a biologically active variant thereof are disclosed. In an embodiment, the composition comprises a tonicity modifier, a bulking agent, and a stabilising agent and has a pH of about 3.0 to about 10.0. In another embodiment, the composition contains an amount of particles in suspension equal to or greater than 10 μm which is lower than 6000 particles per 100 ml, and preferably lower than 2000 particles per 100 ml. Uses of these compositions as a medicament is contemplated. Various therapeutic uses of these pharmaceutical compositions is also contemplated.

The present invention relates to methods for treating or preventing atherosclerotic cardiovascular disease and other conditions associated with elevated levels of lipoprotein (a) (Lp(a)) using RNAi constructs targeting the LPA gene, which encodes apolipoprotein(a), a component of Lp(a) particles. In particular, the present invention relates to methods for reducing serum Lp(a) levels and reducing the risk of cardiovascular events in patients with elevated levels of Lp(a) comprising administering an LPA-targeted RNAi construct according to specific dosage regimens. Pharmaceutical compositions comprising the LPA-targeted RNAi constructs for use in the methods are also disclosed.