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.

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 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.

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

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 invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

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 m 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.

A method is provided for characterising and/or prognosing prostate cancer in a subject comprising measuring the level of at least one protein from a panel or at least one peptide thereof in a sample from the subject. The method may be used to determine the grade and stage of the prostate cancer. Also disclosed is a method for selecting a treatment for prostate cancer, together with corresponding methods of treatment. Systems and computing devices for performing the methods are also provided.