96 results about "PLG - Plasminogen" patented technology

The invention relates to the field of nano medicines, in particular to a targeted medicine as well as a preparation method and application thereof. The invention provides a targeted drug. The targeted drug comprises a tissue-type plasminogen activator and a targeted peptide. Thrombus targeting modification is directly carried out on a thrombolytic drug rtPA which is most widely applied clinically by utilizing a chemical method, the defects of narrow treatment time window, high dosage and high bleeding risk of the rtPA are remarkably improved, the preparation process is simple and controllable, materials required for preparation are easy to obtain, the cost is low, and the application prospect is wide. The toxic effect and degradation problems of materials such as compounds are eliminated, other instruments and equipment are not needed in the treatment process, and clinical transformation application of thrombus targeted rtPA becomes possible.

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.

Provided are a targeted drug and a preparation method therefor and the use thereof. The targeted drug comprises a tissue-type plasminogen activator and a targeting peptide. Thrombus-targeting modification is directly performed on thrombolytic drug rtPA, which has the widest clinical application, by means of a chemical method. The defects of rtPA in terms of a narrow therapeutic time window, a high medication dosage and a high hemorrhage risk are significantly improved. The preparation process is simple and controllable, and the materials required for the preparation are readily available and cost-effective. The toxic effects and degradation problems of materials such as compounds are eliminated. In addition, the treatment process does not require other instruments and devices, which makes the clinical transformation and use of the thrombus-targeting rtPA possible.

The invention discloses a t-PA and PAI-1 pseudo compound based on a bispecific functional antibody skeleton, a construction method and a determination kit, the pseudo compound takes a bifunctional antibody as the skeleton, a tissue-type plasminogen activator t-PA and a tissue-type plasminogen activator inhibitor PAI-1 are used for replacing two variable region arms in a natural antibody structure, and the t-PA and PAI-1 pseudo compound is prepared by using the bifunctional antibody as the skeleton. The protein takes an antibody constant region as a support skeleton, and a tissue type plasminogen activator t-PA and a tissue type plasminogen activator inhibitor PAI-1 are respectively arranged at the Y-type top of the antibody. The tissue-type plasminogen activator t-PA and the tissue-type plasminogen activator inhibitor PAI-1 are constructed into the pseudo-complex in a ratio of 1: 1, and a kit using the pseudo-complex as a freeze-drying calibrator or reference has the characteristics of high sensitivity, good stability and difficulty in interference.

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.

The invention relates to a method (500) and a device (100) for unmasking biological cells, in particular circulating tumor cells, by means of plasmin, wherein a reactant (10) is added to a sample containing plasminogen and biological cells, in particular a blood sample, in order to convert plasminogen to plasmin.

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.

To provide pharmaceutical compositions for treating blood pressure abnormalities and complications thereof.SOLUTION: Provided is a drug for preventing or treating hypertension, comprising one or more compounds selected from components of a plasminogen activation pathway, compounds capable of directly activating plasminogen or indirectly activating plasminogen by activating upstream components of the plasminogen activation pathway, compounds for mimicking the activity of plasminogen or plasmin, compounds capable of upregulating the expression of plasminogen or plasminogen activators, plasminogen analogs, plasmin analogs, tPA or uPA analogs, and antagonists of fibrinolysis inhibitors and the like.SELECTED DRAWING: None

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.

To provide a method and a drug for treating viral pneumonia.SOLUTION: A pharmaceutical composition comprises a therapeutically effective amount of one or more compounds selected from the group consisting of a component of plasminogen activation pathway, a compound capable of activating plasminogen, a compound mimicking the activity of plasminogen or plasmin, a compound capable of upregulating the expression of plasminogen or an activator of plasminogen, an analog of plasminogen, an analog of plasmin, an analog of tPA or uPA, and an antagonist of fibrinolysis inhibitor.SELECTED DRAWING: None

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.

The present invention relates to a positron emitting imaging agent for prognostic use in patients with neuroendocrine tumors (NENs) undergoing PET imaging for cancer, said imaging agent comprising a uPAR binding peptide linked to the radionuclide 68Ga or 64Cu via the chelators NOTA or DOTA. The present invention also relates to a composition comprising a radiopharmaceutical for use in treating or alleviating neuroendocrine tumors (NENs) in a subject, said radiopharmaceutical comprising a radionuclide and a uPAR binding peptide. Figure 4A will be published together with the abstract.

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.

The invention discloses an immune biosensor of a human tissue plasminogen activator antigen, and designs a compound for modifying the immune sensor, a compound solution is dropwise added on the surface of an electrode of the immune biosensor by adopting a dispensing method to form a compound film, and then an aldehyde group is introduced into the solution to modify the surface of the film, so that the immune biosensor is obtained. An aldehyde group is introduced to be combined with a to-be-detected object antibody. NPC, MWCNTs and AuNP are dispersed in a chitosan solution, the electroactivity of an electrode interface is improved, the effective area of electrochemical reaction is increased, the sensitivity of the electrode is improved, and large-range active sites are provided while electrochemical signals are increased; the linear range of the immunosensor is relatively large, and human tissue plasminogen activator antigen detection in a normal concentration range can be realized.

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.