22 results about "Plasminogen activator" patented technology

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 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.

This invention relates to a pharmaceutical composition and its application for treating acute ischemic stroke. The pharmaceutical composition for treating acute ischemic stroke comprises separately packaged tissue-type plasminogen activator citPA5 and a platelet aggregation inhibitor. Its beneficial effects include significantly improving cerebral blood flow recovery, shortening thrombolysis time, reducing infarct volume, and improving neurological function without increasing the risk of bleeding, demonstrating a good synergistic thrombolytic effect.

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.

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.

Provided herein are methods for safe and effective thrombolysis in therapy for human subjects with symptoms of a potential stroke or acute myocardial infarction (“AMI”) using a sequential administration of a low dose bolus of human tissue plasminogen activator (“tPA”) followed by an infusion of a mutant form of human pro-urokinase (“proUK”).

The application discloses screening of hemostatic active components in Euphorbiaceae plants and application thereof, and based on ultrafiltration mass spectrometry technology and taking urokinase-type plasminogen activator as a key target enzyme, a hemostatic active component, breynol, of cyclopentanone isocoumarins in Euphorbiaceae plants is screened for the first time. The breynol shows strong specific binding to urokinase plasminogen activator, and the activity inhibition (IC 50 ) of the breynol to the urokinase plasminogen activator is 0.187±0.000 mM, which is superior to that of the positive control tranexamic acid (IC 50 =2.425±0.001 mM). The breynol is reported for the first time in the research of hemostatic activity of Euphorbiaceae plants, and can be used for preparation of daily or clinical hemostatic drugs.

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.

To provide a fusion protein for targeted delivery of a plasminogen activator in a fibrin-independent manner to a platelet-VWF complex or a site where the platelet-VWF complex is located.SOLUTION: A pharmaceutical composition for preventing or treating microvascular thrombosis is provided, comprising a fusion protein, wherein the fusion protein comprises a plasminogen activator and a targeting agent for targeting the plasminogen activator to a site of a thrombus comprising VWF and platelets, wherein the targeting agent comprises an antibody variable domain that specifically binds to VWF, and wherein the antibody variable domain comprises a CDR3 domain having the amino acid sequence of SAGLYVGDGPDDAMDDY.SELECTED DRAWING: None

The invention discloses a transcription template DNA (Deoxyribose Nucleic Acid) of an LMP1 (Lipoprotein Protein 1) antigen mRNA (Messenger Ribonucleic Acid) and the LMP1 antigen mRNA obtained by transcription of the transcription template DNA. The transcription template DNA is formed by sequentially connecting a promoter, a 5'end non-coding region, a human tissue plasminogen activator gene secretion signal peptide, an LMP1 antigen coding region, a main histocompatibility complex I-type transport signal, a 3 'end non-coding region, a poly (adenylic acid) tail and a terminal sequence; the human tissue plasminogen activator gene secretion signal peptide, the LMP1 antigen coding region and the main histocompatibility complex type I transport signal are connected through a GS flexible linker. The LMP1 antigen mRNA disclosed by the invention efficiently expresses the LMP1 antigen and induces specific immune response in a body. The invention also discloses an application of the LMP1 antigen mRNA in preparation of drugs for preventing and / or treating EBV-related tumors.

The present invention provides means and methods for treating MVT and associated and / or similar conditions. The invention therefore provides hybrid proteins for targeted delivery of plasminogen activators to platelet-VWF complexes, or alternatively to the site where these are located, in a fibrin-independent manner. The invention further provides therapeutic methods for conditions that can be prevented or treated by local delivery / stimulation of plasminogen activation to sites of microvascular occlusion.

The present invention relates to novel affinity ligands that bind to human tissue plasminogen activator (tPA). The novel affinity ligands of the present invention are powerful tools because they allow efficient purification methods for human tPA via affinity chromatography. In particular, the affinity ligands are powerful in the purification of recombinant human tPA that was produced in Chinese hamster ovary cells because the affinity ligands of the invention do not detectably bind to hamster tPA. Accordingly, the present invention also relates to a novel process of isolating and purifying tPA, specifically tPA from CHO cells.

The invention discloses application of CREKA modified nanoparticles in treatment of retinal vascular thrombosis, and relates to the technical field of nanoparticles. The nanoparticle contains a polylactic acid-glycolic acid copolymer as a carrier and entraps a recombinant tissue type plasminogen activator and perfluoropentane, the surface of the PLGA is modified with CREKA peptide, the CREKA peptide is used for targeting thrombus fibrin, the rtPA is used for thrombolysis, and the PFP is used for phase change under the ultrasonic effect to promote drug release. According to the invention, thrombus fibrin is specifically targeted through CREKA peptide, high-efficiency enrichment of a drug at a focus part is realized, low-intensity ultrasound is combined to trigger PFP phase change blasting and promote rtPA release, the thrombolysis effect is obviously superior to that of a traditional method, in-vitro experiments show that a thrombus structure is loose after thrombolysis of a PPrC group, and change of absorbance of supernate proves that the thrombolysis rate is the highest.

The present invention provides fusion proteins for targeted delivery of plasminogen activators to platelet-VWF complexes, or alternatively to the site where these are located, in a fibrin-independent manner. The fusion protein of the invention are for use in methods for the prevention or treatment of diseases or conditions associated with such platelet-VWF complexes, which may cause microvascular thrombosis in diseases such as e.g. thrombotic thrombocytopenic purpura. Preferred targeting agents for incorporation into the fusion proteins are e.g. nanobodies against VWF or platelets. Preferred plasminogen activators for use in the fusion proteins comprise the protease domains of uPA or tPA. The invention further pertains to nucleic acid molecule encoding the fusion proteins of the invention, e.g. a gene therapy vector, and to pharmaceutical compositions comprising the fusion proteins of the invention or such gene therapy vectors.

The invention discloses an arteplase mutant for cardiovascular thrombolysis and a preparation method thereof, and relates to the technical field of biological medicines, and the amino acid sequence of the mutant is obtained by modifying the amino acid sequence (SEQ ID NO: 1) of a wild human tissue plasminogen activator (tPA) as follows: 85th phenylalanine is replaced with tryptophan, and 85th phenylalanine is replaced with tryptophan; and / or the tyrosine at the 92nd position is replaced by histidine; the threonine at the 103th site is replaced by asparagine, and / or the threonine at the 105th site is replaced by serine; the amino acids at the 178th site and the 180th site are replaced with cysteine, so that a disulfide bond can be formed between the amino acids, and at least one histidine residue is contained in an adjacent region of the 178th site and / or the 180th site, so that a pH response element sensitive to an acidic environment is formed; the amino acid sequence of the mutant simultaneously contains F85W, Y92H, T103N and T105S, and cysteine is arranged at the 178th site and the 180th site.

This invention relates to the field of biomimetic materials, and particularly to a blood contact material, a biomimetic coating, its construction method, and its applications. The active ingredient in the blood contact material is formed by polymerizing vinyl lysine, oligoethylene glycol methyl ether methacrylate, and vinyl dopamine. The blood contact material is dissolved in a first buffer solution with a pH value of 7.5-9 to obtain a coating solution. The substrate is immersed in the coating solution for a first time and then removed, allowing the substrate surface to be covered with an intermediate coating. The polymerized poly(oligoethylene glycol methyl ether methacrylate) segments can form a dense hydration layer providing antifouling functionality. The polylysine segments can specifically bind plasminogen and tissue-type plasminogen activator, dissolving primary thrombi. The polydopamine segments have adhesive properties, improving the substrate's versatility and facilitating coating formation. The blood contact material can mimic the antifouling and fibrinolytic functions of the vascular endothelium, contributing to a comprehensive antithrombotic effect.

To provide a method for identifying a new substrate for a protease, and a method for using the substrate in various therapeutic, diagnostic and preventive applications.SOLUTION: The present invention relates generally to polypeptides comprising 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 comprising a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator, and methods of making and using these polypeptides comprising a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator in a variety of therapeutic, diagnostic, and prophylactic indications.SELECTED DRAWING: Figure 4A

The application discloses a thrombolytic nano-complex, a preparation method and application thereof, and belongs to the technical field of biological medicines, and provides a thrombolytic nano-complex, wherein the thrombolytic nano-complex is a fluorescently modified ROS-responsive dendritic mesoporous silica, the pores of the dendritic mesoporous silica are loaded with ferroferric oxide and tissue-type plasminogen activator, and the surface of the dendritic mesoporous silica is connected with a CREKA polypeptide. The thrombolytic nano-complex is a fluorescently modified ROS-responsive dendritic mesoporous silica, the pores of the dendritic mesoporous silica are loaded with ferroferric oxide and tissue-type plasminogen activator, and the surface of the dendritic mesoporous silica is connected with a CREKA polypeptide, so that the side effects of the existing thrombolytic method, such as poor targeting, low specificity and high risk of causing bleeding, are solved, the drug aggregation and permeability are improved, it is a biological-targeting intelligent thrombolytic system, and a new thrombolytic direction integrating chemistry and biology is provided.