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.

The present invention provides a process for the production of human plasminogen starting from human plasma or a fractionation intermediate thereof. The main stages of the process are: a step of virus inactivation, in which human plasma is contacted with a solvent/detergent mixture, a single affinity chromatographic step and a virus removal nanofiltration step. This process is scalable up to industrial level and it provides, without adding any protease inhibitor, a functional and intact finished product suitable to be administered for the treatment of human diseases due to genetic plasminogen deficiency.

The present invention provides therapeutic products with decreased fibrinolytic activity of t-PA-deficient and/or plasminogen-deficient blood products, as well as compositions, kits and methods using the same in treating bleeding associated with hereditary or acquired bleeding disorders. The invention further provides extracorporeal apparatus for blood or blood products Plasmapheresis aimed to prevent or treat bleeding disorders.

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 plasminogen for use in a method for treating or preventing lung dysfunction associated with the formation of hyaline membranes in a patient, wherein the patient is preferably further administered with at least one plasminogen activator.

The present invention relates to: a fusion peptide comprising a thrombus-targeting peptide, ferritin fragment and a thrombolytic peptide; and a use thereof and, more specifically, to: a fusion peptide in which a thrombus-targeting peptide, ferritin fragment and a thrombolytic peptide are sequentially linked; a composition for preventing or treating thrombotic disorders, containing the same as an active ingredient; a method for treating thrombotic disorders; and a therapeutic use. According to the present invention, CLT-sFt-μPn DCNC as a novel plasmin-based thrombolytic nanocage has: an effect of targeting a site at which thrombus is present; a low sensitivity to inhibitors present in the circulatory system; pharmacological activity strongly destroying both arterial and venous thrombi; and no side effects of bleeding, and thus can be very useful in developing an agent for preventing or treating thrombotic disorders.

It is disclosed a method for determining the biological activity of defibrotide, which comprises the steps of: a) bringing into contact defibrotide, mammalian euglobulin and a substrate specific for the plasmin which, by reaction with the plasmin, provides a measurable product; and b) measuring the amount of product formed at successive times, to thereby determine the biological activity of the defibrotide. Liquid defibrotide formulations are also disclosed, preferably water solutions, having a defined biological activity and, in particular, having an activity of 25 to 35 IU/mg of defibrotide, preferably from 27 to 32 IU/mg and, more preferably, from 28 to 32 IU/mg.

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.

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.