182 results about "Annexin" patented technology

A modified annexin protein, preferably annexin V, is used to prevent thrombosis without increasing hemorrhage. Annexin binds to phosphatidylserine on the outer surface of cell membranes, thereby preventing binding of the prothrombinase complex necessary for thrombus formation. It does not, however, affect platelet aggregation necessary for hemostasis. The modified annexin molecule can be a homodimer of annexin, an annexin molecule coupled to one or more polyethylene glycol chains, or an annexin molecule coupled to another protein. By increasing the molecular weight of annexin, the modified annexin is made to remain in circulation for sufficient time to provide a sustained therapeutic effect.

One aspect of the invention is an infrared fluorescent reagent that may be useful to provide images of regions of cell death. The reagent may comprise a fluorescent substance, preferably an infrared fluorescent substance, conjugated to a targeting moiety that selectively localizes or binds to cells or tissue undergoing cell death, such as annexin V. The reagent may also comprise an infrared fluorescent substance associated with an antibody, antibody fragment, or ligant that accumulates within a region of diagnostic significance, such as a region characterized by necrosis or apoptosis. In one embodiment, the reagent comprises annexin V covalently conjugated to IRDye 78. In another embodiment, the reagent comprises annexin V covalently conjugated to a quantum dot. More broadly, the reagents described herein may be used in detecting cell death.

The present invention provides methods and compositions for the treatment, diagnosis, and prevention of diseases, such as neoplastic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and inflammatory diseases. The methods include the administration of pharmaceutical complexes comprising annexins coupled to pharmaceutical compounds or carriers to subjects. The present invention also provides methods and compositions for delivering therapeutic compounds into the diseased cells of a subject either to kill them, such as tumor cells, or to rescue them, such as cardiomyocytes and neurons. The compositions include annexins, annexin variants, derivatives thereof, and complexes thereof.

Conjugate molecules comprising a ligand bonded to a polymer are disclosed. One such conjugate molecule comprises a ligand bonded to a polymer, a chelating agent bonded to the polymer, and a radioisotope chelated to the chelating agent. The conjugate molecules may be useful in detecting and / or treating tumors or biological receptors. These conjugate molecules may be synthesized without the necessity of preactivation of the ligand using an SCN-polymer-chelating agent precursor. Conjugate molecules incorporating an annexin V ligand are particularly useful for visualizing apoptotic cells. Conjugate molecules incorporating a C225 ligand are particularly useful for targeting tumors expressing EGFR.

The present invention provides compositions and methods that involve the 36 kDa annexin II monomer, which has been identified as having immunostimulatory properties. Accordingly, in one aspect, the invention provides compositions that include at least one 36 kDa annexin II monomer or an immunomodulatory fragment thereof. In another aspect, the invention provides methods that include administering to a subject a composition that includes at least one 36 kDa annexin II monomer or an immunomodulatory fragment thereof. In another aspect, the invention provides methods that induce an in situ increase in the 36 kDa annexin II monomer by administering to a subject an amount of composition effective to induce localized hypoxia sufficient to cause a localized increase in annexin II.

The invention relates to protein-protein interactions and methods for identifying interacting proteins and the amino acid sequence at the site of interaction. Using overlapping hexapeptides that encode for the entire amino acid sequences of the linker domains of human P-glycoprotein gene 1 and 3 (HP-gp1 and HP-gp3), a direct and specific binding between HP-gp1 and 3 linker domains and intracellular proteins was demonstrated. Three different stretches (617EKGIYFKLVTM627, (SEQ ID NO: 1) 658SRSSLIRKRSTRRSVRGSQA677 (SEQ ID NO: 2) and 694PVSFWRIMKLNLT706 (SEQ ID NO: 3) for HP-gp1 and 618LMKKEGVYFKLVNM631 (SEQ ID NO: 4), 648KAATRMAPNGWKSRLFRHSTQKNLKNS674 (SEQ ID NO: 5), and 695PVSFLKVLKLNKT707 (SEQ ID NO: 6) for HP-gp3) in linker domains bound to proteins with apparent molecular masses of ˜80 kDa, 57 kDa and 30 kDa. The binding of the 57 kDa protein was further characterized. Purification and partial N-terminal amino acid sequencing of the 57 kDa protein showed that it encodes the N-terminal amino acids of alpha and beta-tubulins. The method of the present invention was further validated with Annexin. The present invention thus demonstrates a novel concept whereby the interactions between two proteins are mediated by strings of few amino acids with high and repulsive binding energies, enabling the identification of high affinity binding sites between any interacting proteins.

A modified annexin protein, preferably annexin V, is used to prevent thrombosis without increasing hemorrhage. Annexin binds to phosphatidylserine on the outer surface of cell membranes, thereby preventing binding of the prothrombinase complex necessary for thrombus formation. It does not, however, affect platelet aggregation necessary for hemostasis. The modified annexin molecule can be a homodimer of annexin, an annexin molecule coupled to one or more polyethylene glycol chains, or an annexin molecule coupled to another protein. By increasing the molecular weight of annexin, the modified annexin is made to remain in circulation for sufficient time to provide a sustained therapeutic effect.

The present invention pertains to a device for binding a target entity onto a bait entity that is immobilized on said device, comprising: a) a lipid layer having a negative net charge in an aqueous solution at a neutral pH; b) a two-dimensional matrix of anchoring complexes that are bound to said lipid layer, wherein each of said anchoring complexes comprises: (i) a fusion complex comprising an Annexin protein fused to a partner molecule; and (ii) a bait entity. It also concerns various uses of said device, including for detection and pharmaceutical purposes.

Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage.

The present invention is drawn to immunotherapeutic methods to treat tumors / cancers that produce progastrin ectopically or are dependent on progastrin for their growth. Disclosed herein are immunogenic compositions comprising agents that target progastrin, agents that target the progastrin receptor, annexin II, or both. Such a composition may be administered in combination with chemotherapy or to an individual who had been previously subjected to chemotherapy or radiation therapy. The cancers that may be treated using such a composition may include but are not limited to colon cancer, breast cancer, lung cancer or pancreatic cancer.

Disclosed are Lipids, Annexin, and Lipid-Annexin Complexes for Use in the Prevention and / or Treatment of Ischemia-Reperfusion injury and reperfusion injury associated with a variety of diseases and conditions. Also disclosed are therapeutic targets and compositions for the prevention and treatment of ischemia-reperfusion injury and diseases and conditions associated with ischemia-reperfusion injury.

The invention pertains to a method of reducing scar formation during wound healing by administering a phosphatidylserine-binding compound, in particular an annexin, to a subject in need thereof. The healing wound may be a skin damage, but it may also be a myocardium e.g. which is at risk of suffering or is recovering from a heart failure.

Novel recombinant anticoagulation proteins, methods of their use and methods of their production are described. In particular, recombinant fusions of annexin V (ANV) and Kunitz protease inhibitors (KPI) that possess potent anticoagulant activity are provided. The fusions, abbreviated ANV:KPI, utilize ANV having high affinity for phosphatidyl-L-serine with various KPI's to target serine proteases in membrane-associated coagulation complexes in the blood coagulation cascade. ANV:KPIs are potentially useful antithrombotic drugs permitting localized passivation of thrombogenic vessel walls and associated thrombi.

The present invention provides methods and compositions for imaging cell death in vivo, as well as methods and compositions for tumor radiotherapy.

Here, we present a photodegradable microparticle system that can be employed to entrap and deliver bioactive proteins to cells during culture. By using a photosensitive delivery system, experimenters can achieve a wide variety of spatiotemporally regulated release profiles with a single microparticle formulation, thereby enabling one to probe many questions as to how protein presentation can be manipulated to regulate cell function. Photodegradable microparticles were synthesized via inverse suspension polymerization with a mean diameter of 22 μm, and degradation was demonstrated upon exposure to several irradiation conditions. The protein-loaded depots were incorporated into cell cultures and release of bioactive protein was quantified during the photodegradation process. This phototriggered release allowed for the delivery of TGF-β1 to stimulate PE25 cells and for the delivery of fluorescently labeled Annexin V to assay apoptotic 3T3 fibroblasts during culture. By incorporating these photoresponsive protein delivery depots into cell culture, new types of experiments are now possible to test hypotheses about how individual or multiple soluble factors might affect cell function when presented in a uniform, temporally varying, or gradient manner.

A method for identifying, diagnosing, and monitoring cancerous lung tissues in a subject may include measuring the expression of at least one biomarker in a biological sample in the subject, and comparing the expression against a normal value. When a differential expression of the at least one biomarker between the biological sample and the normal value is more than 1.5-fold, the lung tissue sample is cancerous. The at least one biomarker is selected from the group consisting of peroxiredoxin I, peroxiredoxin II, peroxiredoxin III, peroxiredoxin IV, peroxiredoxin VI, chaperonin, amyloid-P-component, annexin V, dihydropyrimidinase-like 2 protein, glutamate carboxypeptidase, 2,3-bisphosphoglycerate mutase, thymidine phosphorylase, prolyl-4 hydroxylase, selenium binding protein 1, β-mitochondrial ATP synthase H+ transporting F1 complex, laminin-binding protein, minichromosome maintenance deficient protein 5 variant, keratin 9, keratin 10, napsin A aspartic peptidase, M2-type pyruvate kinase, and apolipoprotein A-I.

Modified annexin proteins, including a homodimer of human annexin V, are provided. Methods for their use, such as to prevent thrombosis without increasing hemorrhage, enhancing the survivability of platelets during storage or transfusion and to attenuate ischemia-reperfusion injury (IPI), are also provided. The modified annexins bind phosphatidylserine (PS) on cell surfaces, thereby preventing the assembly of the prothromkinase complex. The modified annexin decreases the binding of leukocytes and platelets during post-ischemic reperfusion, thereby restoring microvascular blood flow and decreasing organ damage. In addition, the modified annexin prevents lipid loss from platelets during storage.

The present invention provides methods and compositions for the treatment and diagnosis of diseases such as neoplastic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and inflammatory diseases. The methods are based on the concept of pretargeting and include the administration of complexes comprising a recognizable compound A coupled to annexins, and the administration of complexes comprising of pharmaceutical or diagnostic compounds coupled to a compound B recognizing and binding to compound A to subjects. The compositions include annexins, annexin variants, that are not internalized by the target cells, derivatives thereof, and complexes thereof.

The present invention provides nucleic acid molecules encoding annexin 1 (ANX1) and annexin 4 (ANX4) that belong to a multigene family of calcium-dependent membrane binding proteins. ANX1 and ANX4 are inducible by abscisic acid (ABA), salt and other various stress treatments. The anx1 and anx4 mutant plants are characterized by their hypersensitivity to salt and ABA during seed germination and early seedling growth. The invention can be utilized to generate transgenic plants that are tolerant to environmental stress.

The invention aims to provide a reagent capable of detecting the expression condition of a target protein in a paraffin-embedded tissue, and particularly provides a kit used for evaluating the prognosis information of a patient suffering from the esophageal squamous cell carcinoma. The kit comprises antibodies of the three target proteins, namely Annexin II, Kindlin-2 and Myosin-9, and further comprises goat serum, 0.01 M citrate repair liquid, 3% H2O2, a Polymer reinforcing agent, a Polymer, a DAB color reagent and a PBS solution. The kit can be used for evaluating the prognosis of the patient; compared with the international TNM staging, the kit is simpler and easier to use, and higher in both sensitivity and specificity, and is more suitable for the prognosis evaluation of Chinese suffering from the esophageal squamous cell carcinoma.

The invention discloses a lotus annexin and an expression vector and application thereof, and belongs to the technical field of plant gene engineering. The lotus annexin has an amino acid sequence shown as SEQ ID NO.1, and the nucleotide sequence of the coded gene of the lotus annexin is shown as SEQ ID NO.2. The invention also discloses the expression vector of the lotus annexin. The expression vector is formed by inserting the coded gene of the lotus annexin into a prokaryotic or eukaryotic expression vector. The lotus annexin can effectively improve the heat resistance of plant seeds and enhance the germinating activity of the seeds, and has wide application prospect in the fields of plant variety breeding and agricultural production.

The present invention relates to the field of reproduction (e.g., human reproduction). In particular, the present invention provides markers (e.g., pentraxin 3 and Annexin A6), and methods of using the same to determine oocyte development potential. The present invention also provides compositions and methods for modifying oocyte development potential and assays (e.g., using markers of the present invention) for detecting gene expression associated with oocyte development potential. Such compositions and methods find use in diagnostic, research and therapeutic applications.

The invention provides protein cross-linking nano silicon as well as a preparation method and an exosome separation and purification method and application. The protein cross-linking nano silicon is prepared from carboxylated nanometer silicon spheres modified with an Annexin V protein or Tim 4 protein. The protein cross-linking nano silicon provided by the invention is applied to separation and purification of cell exosome, stem cell exosome in a sample can be rapidly separated on a large scale, high purity can be ensured for the separated stem cell exosome, and the silicon has great significances in the field of preparation of the stem cell exosome. Due to application of the exosome prepared by using the exosome separation and purification method provided by the invention in preparing medicines related to the exosome, such as application in preparing medicines for nerve injury and heart repairing, a great deal of time can be saved, a lot of cost can be reduced, the quality of the medicines can be ensured, and the application values are great.

Chimeric proteins comprising soluble Tissue Factor (sTF) and another subunit (e.g., annexin V) are described. The proteins promote blood clotting and / or inhibit cancer by targeting sTF to specific receptors such as phosphatidyl serine (PS) on activated cells. These chimeric proteins are useful in treating patients with excessive bleeding due to inborn problems, drug therapy, trauma or surgery and / or as an anti-cancer therapy, for example by causing blood vessels feeding cancers to become clotted, thereby preventing adequate flow of blood to a tumor, which in turn will lead to tumor inhibition and death or may be used in a therapy to cause clotting within blood vessels that pose a threat in the subject in non-cancerous conditions.

The present invention generally provides methods for the site-specific modification of peptides, polypeptides, and proteins, e.g., granulocyte macrophage colony-stimulating factor, human superoxide dismutase, annexin, leptin, antibodies and the like, cytokines and chemokines, at their N-termini and at sites at which unnatural aminoacids have been introduced along the protein framework. The modifications described herein can be used for the synthesis and application of the adducts in radio-labeling, molecular imaging and protein therapeutic applications, and the treatment of disorders such as rheumatoid arthritis, lupus erythematosus, psoriasis, multiple sclerosis, type-1 diabetes, Crohn's disease, and systemic sclerosis, Alzheimer disease, cancer, liver disease (e.g., alcoholic liver disease), and cachexia.