70 results about "PLG - Plasminogen" patented technology

The present disclosure relates to methods for determining concentration of a lysine analog antifibrinolytic agent in a sample. Also provided are kits comprising (a) a composition comprising a fluorescently labeled inactive plasminogen variant and a fluorescence quencher labeled fibrin-degradation product (FDP) and (b) a lysine analog antifibrinolytic agent standard and methods of use thereof.

The present invention includes a method of treating a subject having relapsing-remitting multiple sclerosis (RRMS) that is undergoing relapse, comprising: determining a level of expression for two or more biomarkers selected from urokinase plasminogen activator (uPA), kallikrein-8 (hK8), kallikrein-11 (hK11), or desmoglein-3 (DSG3) in a biological sample of a subject when compared to the same type of sample from a subject or a population of subjects that do not have RRMS; diagnosing that the subject in undergoing relapse if the level of expression of the two or more biomarkers has decreased in the subject; and administering a therapeutically effective amount of treatment for RRMS to the subject.

Provided herein are compositions, systems, kits, and methods for treating a patient with a thromboembolism by administering nanoconjugates comprising nanoparticles encapsulating and / or conjugated to: i) tissue-type plasminogen activator (tPA), and ii) at least one antioxidant enzyme selected from the group consisting of: superoxide dismutase, glutathione peroxidase, glutathione reductase, and a catalase.

There is provided a positron-emitting radionuclide labelled peptide for non-invasive PET imaging of the Urokinase-type Plasminogen Activator Receptor (uPAR) in humans. More specifically the invention relates to human uPAR PET imaging of any solid cancer disease for diagnosis, staging, treatment monitoring and especially as an imaging biomarker for predicting prognosis, progression and recurrence.

To provide methods of identifying new substrates for proteases and methods of using these substrates in a variety of therapeutic, diagnostic and prophylactic indications.SOLUTION: The invention relates generally to: polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator (uPA); activatable antibodies and other large molecules that include the cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator; and methods of making these polypeptides that include the cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator, and methods of use in a variety of therapeutic, diagnostic and prophylactic indications.SELECTED DRAWING: Figure 4A

The present application relates to a method for promoting the degradation of pathological TDP-43 protein, comprising administering to a subject a therapeutically effective amount of one or more compounds selected from components of the plasminogen activation pathway, compounds that can activate plasminogen directly or indirectly by activating upstream components of the plasminogen activation pathway, compounds that mimic the activity of plasminogen or plasmin, compounds that can upregulate the expression of plasminogen or plasminogen activators, plasminogen analogs, plasmin analogs, tPA or uPA analogs, and antagonists of fibrinolysis inhibitors. The present application also relates to agents that promote the degradation of pathological TDP-43 protein and uses thereof.

The invention relates to the technical field of electrochemical sensing, in particular to a multi-channel electrochemical aptamer sensor and a preparation method and application thereof.The multi-channel electrochemical aptamer sensor adopts a commercial silk-screen printing electrode and is combined with a polymer substrate material for amplifying electrochemical signals, and the electrochemical aptamer sensor is prepared. According to the present invention, the corresponding aptamer is fixed by using the gold nanoparticle through the chemical bond so as to specifically detect the three hemorrhage conversion biomarkers after acute cerebral infarction, such as human matrix metalloproteinase (MMP-9), fibrinogen (FN) and plasminogen activation inhibitor (PAI-1); wherein the FN and the PAI-1 are detected through an electrochemical aptamer sensor method for the first time, and simultaneous detection of the three biomarkers is realized through integration with commercial multi-channel micro electrochemical equipment.

The current invention relates to a polypeptide comprising an immunoglobulin single variable domain and an urokinase-type plasminogen activator (uPA) domain wherein the immunoglobulin single variable domain is able to bind to fibrin via a fibrin-binding domain.

The present invention provides methods for modifying a donor organ, e.g., liver, or a portion thereof. The methods comprise contacting the donor liver with lipid nanoparticles comprising RNA. Compositions of lipid nanoparticles comprising RNA are also provided. The disclosed LNPs may comprise an siRNA, e.g., targeting tissue plasminogen activator (tPA) or plasminogen activator inhibitor 1 (PAI-1). The LNPs may comprise an mRNA encoding a protein, e.g., Nuclear Factor-erythroid factor 2-related factor 2 (NRF2) or thrombomodulin.

The present invention relates to double stranded ribonucleic acid (dsRNA) compositions targeting the plasminogen (PLG) gene, as well as methods of inhibiting PLG expression, and methods of using such dsRNA compositions to treat subjects that would benefit from reduced PLG expression, such as subjects having a PLG-related disease, disorder or condition.

The present technology relates to recombinant polypeptides comprising tissue-type plasminogen activator (tPA) fragments or nucleotides encoding said recombinant polypeptides and their use for the treatment of cardiovascular diseases. In some embodiments, the tPA fragment comprises a kringle 2 domain of the tPA.

The invention discloses a PAI-1 protein targeting peptide compound (called P peptide for short) with a thrombus dissolving effect and application thereof, and belongs to the field of biological medicine. The PAI-1 targeted thrombolytic polypeptide compound comprises P1, P2, P3 and P4, and is characterized in that the compound is derived from a core structure 'X-Asp-Glu-Leu-Cys-X-Tyr-Tyr-X-X-Cys-X' (cyclization is performed through a disulfide bond between Cys, and X represents any type of amino acid), and the compound can be specifically bound with a key binding site of PAI-1. The polypeptide can significantly reduce the inhibitory effect of PAI-1 on plasminogen activators (tPA, uPA), enhance the activity of a fibrinolytic system, and generate in-vivo and in-vitro thrombolysis effects. The polypeptide compounds P1, P2, P3 and P4 not only have a thrombolysis effect, but also can reduce the expression level of pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6 and the like), which shows that the polypeptide compounds also have an anti-inflammatory effect. In conclusion, the polypeptide compound can be used for preparing a PAI-1 antagonist, a thrombolytic agent and an anti-inflammatory agent related to thrombus.

Provided herein are plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The disclosure includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

Disclosed herein is the de novo synthesis of phosphorylated polyethylene glycol compounds with three defined ABA (hy-drophilic / -phobic / -philic) structures: ABA-PEG10k-Pi10, ABA-PEG16k-Pi14, and ABA-PEG20k-Pi20 and linear polymer PEG20k-Pi20 absent of hydrophobic block. The disclosure also provides materials and methods for treating or reducing the risk or likelihood of developing, anastomotic leak or other microbe-mediated disorders by administering a therapeutically effective amount of a plasminogen inhibitor such as tranexamic acid and / or a phosphate-loaded polymer.

This invention relates to the field of biological detection, and more particularly to the preparation method and application of the t-PAI·C detection kit. The invention provides a detection reagent comprising: antibody-coated magnetic microparticles and enzyme-labeled antibodies; the antibodies include: tissue plasminogen activator-plasminogen activator inhibitor-1 complex antibody. In the detection reagent provided by this invention, when the sample contains the tissue plasminogen activator-plasminogen activator inhibitor-1 complex, the antibody coated with the magnetic microparticles and the enzyme-labeled antibody undergo an immune reaction with the complex, forming a sandwich-like immune complex consisting of the antibody coated with the magnetic microparticles, the complex, and the enzyme-labeled antibody; the enzyme on this complex acts on a luminescent substrate and emits light, and the concentration of the complex in the sample is calculated by detecting the luminescence signal.

A method comprising the steps of: (a) assessing an expression level of at least one protein, selected from Table 1, 2 or 3 in a sample from a subject, where in the at least one protein may be selected from the list comprising: Beta-Ala-His dipeptidase, Apolipoprotein L1, Methanethiol oxidase, Vitamin K-dependent protein S, von Willebrand factor, Plasminogen, Selenoprotein P, Protein disulfide-isomerase A6 and Inter-alpha-trypsin inhibitor heavy chain H3, and (b) using the expression level to determine whether the subject has endometriosis.

Provided are modified u-PA polypeptides and fusion proteins containing the modified u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and / or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

To provide compositions and methods for modulating the plasmin system for treating and / or preventing various pathological conditions.SOLUTION: The present invention relates to antigen binding proteins comprising an antigen binding domain that binds to plasminogen, wherein the antigen binding protein reduces the activation of plasminogen, pharmaceutical compositions comprising the same, and methods and uses thereof.SELECTED DRAWING: None

This invention belongs to the field of biomedical technology, specifically relating to a recombinant human plasminogen mutant, its preparation method, and its application. A recombinant human plasminogen mutant, the amino acid sequence of which is shown in SEQ ID NO.3. The recombinant human plasminogen mutant of this invention, compared to wild-type mPLG, can be directly expressed solublely in the supernatant of *E. coli* fermentation broth. Soluble expression allows for direct chromatography of the fermentation broth to obtain the target protein, which has significant advantages over inclusion body renaturation treatment in terms of process simplification, activity loss, time cost, and production cost. Furthermore, the activity of the mutant protein was tested using the fibrin plate method and kit method. The results showed that the titer of the target protein was approximately 8 UI / mg, which is similar to the titer of mPLG obtained by renaturation before mutation and PLG obtained from human blood. In summary, compared to the wild type, the mutant strain exhibits significantly improved solubility while maintaining high protein activity.

A product, composition, suspension and / or method to dissolve vaso-occlusive clots in vivo in a sickle diseased subject utilizing Target-specific Thrombolytic Urokinase Spheres (TTUS). The TTUS can target vaso-occlusive clots in vivo and then lyse the obstructive blood clots with high efficiency can be intravenously administered to a subject in need thereof. The TTUS are configured to dissolve vaso-occlusive clots by converting plasminogen in blood of the subject into plasmin molecules that dissolves the clot. The nanospheres can encapsulate an enzymatically active bioreactive agent, such as urokinase. Since the active enzyme is targeting and binding essentially only to obstructive clots, there is minimal risk of side-effects to the subject. The nanospheres are less than one micron in diameter, resulting in a size much smaller than red blood cells.

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.

Novel urokinase-type plasminogen activator receptor (uPAR) binding molecules and soluble urokinase-type plasminogen activator receptor (suPAR) binding molecules and methods of their use are disclosed.

The present invention relates to humanized antibodies and molecular conjugates targeting Urokinase type plasminogen activator receptor associated protein (uPARAP), in particular antibody-drug conjugates (ADCs) comprising humanized antibodies directed against uPARAP and their use in delivery of active agents to cells and tissues expressing uPARAP. The invention further relates to the use of said ADCs in the treatment of diseases involving uPARAP expressing cells, such as certain cancers.

The present disclosure provides humanized anti-GluN1 receptor antibodies and antigen-binding fragments or derivatives thereof, which are effective in inhibiting the deleterious effects of tissue-type plasminogen activator (t-PA) mediated by N-methyl-D- aspartate (NMDA) receptors, as well as pharmaceutical compositions and medical uses thereof, particularly for the treatment of neurological, neurovascular or neurodegenerative disorders, such as stroke, multiple sclerosis, Parkinson' s disease, and others.

The present invention relates to a method for detecting active soluble urokinase receptor and a detection kit, the active soluble urokinase receptor is also called active soluble urokinase-type plasminogen activator receptor (suPAR). The method comprises the following steps: contacting a capture reagent with a sample to be tested to form a complex of the capture reagent and active suPAR; combining the formed complex with a reagent that specifically binds to the captured active suPAR, and detecting the captured active suPAR by detecting the reagent that specifically binds to the captured active suPAR, wherein the capture reagent is a fusion protein containing ATF. The present invention also relates to a kit used in the above detection method. The method of the present invention presents excellent technical effects as described in the specification.

The invention discloses a urokinase affinity chromatography filler, which is characterized in that the amino acid sequence of plasminogen is subjected to mutation design, so that urokinase loses corresponding catalytic activity to a plasminogen mutant, and the plasminogen mutant on the affinity chromatography filler does not generate peptide fragment shedding due to the activity of the urokinase. The affinity of the plasminogen mutant and urokinase is superior to that of wild plasminogen. The initial static loading capacity of the affinity chromatography filler prepared from the plasminogen mutant to urokinase is superior to that of the affinity chromatography filler prepared from wild plasminogen, and the initial static loading capacity is 30 mg / mg or above. The acid resistance of the affinity chromatography filler prepared from the plasminogen mutant is superior to that of the affinity chromatography filler prepared from wild plasminogen. And the residual static loading capacity is at least 80% of the initial static loading capacity after being soaked in a 0.1 M acetic acid solution at 22 + / -2 DEG C for 24 hours.

The present disclosure provides a duplex or single-stranded siRNA molecule against plasminogen, the siRNA molecule containing modified or unmodified nucleotides and wherein at least one strand of the duplex or the single-stranded siRNA has a sequence that has at least 80% sequence identity to any one of SEQ NOs: 1 to 28. Further provided is a duplex or single-stranded siRNA molecule against plasminogen, the siRNA molecule containing modified or unmodified nucleotides and is between 25 and 35 nucleotides in length. The siRNA molecule may be formulated in a lipid nanoparticle as described herein.