77results about "Lipocortins" 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.

Provided by the invention are novel methods, vectors and cells for the recombinant production of desired gene products. In particular, the invention relates to increased production of desired gene products by inducibly arresting cell proliferation. The invention also provides novel multicistronic expression vectors that are useful not only for recombinant gene expression, but also for other applications such as gene therapy, tissue engineering and metabolic engineering.

The present invention relates generally to the production of recombinant human uteroglobin (rhUG) for use as a therapeutic in the treatment of inflammation and fibrotic diseases. More particularly, the invention provides processes, including broadly the steps of bacterial expression and protein purification, for the scaled-up production of rhUG according to current Good Manufacturing Practices (cGMP). The invention further provides analytical assays for evaluating the relative strength of in vivo biological activity of rhUG produced via the scaled-up cGMP processes.

The present invention provides compositions and methods for targeting an extracellular matrix derived (EMD) peptide predominantly to an injured tissue, as opposed to an uninjured tissue in vivo. The targeted EMD peptide facilitates the repair and / or regeneration of the injured tissue by providing a surface for cells to attach and grow, thereby facilitating the repair and / or regeneration of the injured tissue.

The present invention provides methods and compositions to treat fibrotic conditions, to increase lymphocyte production in vivo, and to improve and / or normalize lung function, pulmonary compliance, blood oxygenation, and blood pH to inhibit inflammatory processes to stimulate or inhibit pro-inflammatory and immune cells, and to inhibit migration of vascular endothelial cells. The invention contemplates the administration of human uteroglobin, native or recombinant, as a means of achieving these ends. Specifically, it has been found that uteroglobin inhibits cell adhesion to fibronectin, increases lymphocyte production in vivo, and improves and / or normalizes lung function, pulmonary compliance, blood oxygenation, and blood pH, and inhibits inflammatory process. In addition it has been found that uteroglobin can stimulate or inhibit pro-inflammatory and immune cells and inhibitor migration of vascular endothelial cells.

The present invention provides methods and compositions to treat fibrotic conditions, to increase lymphocyte production in vivo, and to improve and / or normalize lung function, pulmonary compliance, blood oxygenation, and blood pH to inhibit inflammatory processes to stimulate or inhibit pro-inflammatory and immune cells, and to inhibit migration of vascular endothelial cells. The invention contemplates the administration of human uteroglobin, native or recombinant, as a means of achieving these ends. Specifically, it has been found that uteroglobin inhibits cell adhesion to fibronectin, increases lymphocyte production in vivo, and improves and / or normalizes lung function, pulmonary compliance, blood oxygenation, and blood pH, and inhibits inflammatory process. In addition it has been found that uteroglobin can stimulate or inhibit pro-inflammatory and immune cells and inhibitor migration of vascular endothelial cells.

The present invention provides compositions and methods for targeting an extracellular matrix derived (EMD) peptide predominantly to an injured tissue, as opposed to an uninjured tissue in vivo. The targeted EMD peptide facilitates the repair and / or regeneration of the injured tissue by providing a surface for cells to attach and grow, thereby facilitating the repair and / or regeneration of the injured tissue.

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 provides compositions and methods for targeting an extracellular matrix derived (EMD) peptide predominantly to an injured tissue, as opposed to an uninjured tissue in vivo. The targeted EMD peptide facilitates the repair and / or regeneration of the injured tissue by providing a surface for cells to attach and grow, thereby facilitating the repair and / or regeneration of the injured tissue.

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.

Compositions and methods for preventing or treating primary cancer cell growth and tumor metastasis, as well as stimulation of hematopoiesis are described and claimed. The present invention also relates to methods of treating cancer and uteroglobin receptor-related conditions by targeting a uteroglobin receptor with recombinant human uteroglobin (rhUG). Also disclosed and claimed are methods of purifying a uteroglobin receptor and methods of using such receptor(s) to identify uteroglobin structural analogs and UG-receptor ligands.

The present invention provides methods and compositions to treat fibrotic conditions, to increase lymphocyte production in vivo, and to improve and / or normalize lung function, pulmonary compliance, blood oxygenation, and blood pH to inhibit inflammatory processes to stimulate or inhibit pro-inflammatory and immune cells, and to inhibit migration of vascular endothelial cells. The invention contemplates the administration of human uteroglobin, native or recombinant, as a means of achieving these ends. Specifically, it has been found that uteroglobin inhibits cell adhesion to fibronectin, increases lymphocyte production in vivo, and improves and / or normalizes lung function, pulmonary compliance, blood oxygenation, and blood pH, and inhibits inflammatory process. In addition it has been found that uteroglobin can stimulate or inhibit pro-inflammatory and immune cells and inhibitor migration of vascular endothelial cells.

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 methods and compositions for the treatment of fibrotic conditions, to increase lymphocyte production in vivo, and to improve and / or normalize lung function, pulmonary compliance, blood oxygenation, and blood pH. The invention contemplates the administration of human uteroglobin, native or recombinant, as a means of achieving these ends. Specifically, it has been found that uteroglobin inhibits cell adhesion to fibronectin, increases lymphocyte production in vivo, and improves and / or normalizes lung function, pulmonary compliance, blood oxygenation, and blood pH.

Provided herein are compositions, including pharmaceutical compositions, and methods for modulating, i.e., stimulating or inhibiting, activity of the alternative complement pathway, and methods of identifying factor H-binding proteins.

The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety bound to the targeting moiety; the biological conjugate having a covalent bond between the thiol group of SEQ ID NO:2 and a functional group in the binding moiety. The present invention is directed to a biological conjugate, comprising: (a) a targeting moiety comprising a polypeptide having an amino acid sequence comprising the polypeptide sequence of SEQ ID NO:2 and the polypeptide sequence of a selected targeting protein; and (b) a binding moiety that comprises an adapter protein, the adapter protein having a thiol group; the biological conjugate having a disulfide bond between the thiol group of SEQ ID NO:2 and the thiol group of the adapter protein. The present invention is also directed to biological sequences employed in the above biological conjugates, as well as pharmaceutical preparations and methods using the above biological conjugates.

This invention relates to the use of two or more breast specific markers for the detection of breast cancer in a patient.

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.

Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Uteroglobin has been discovered to prevent IgA mediated diseases, such as IgA nephropathy, by preventing the deposition of IgA-Fibronectin immunocomplexes in tissues such as the renal glomeruli. The invention therefore includes methods of treating such diseases by administering therapeutically effective amounts of uteroglobin (and variants or mimetics) to prevent or improve the IgA mediated condition. Transgenic uteroglobin knockout animals, and animals in which uteroglobin-protein expression is reduced by antisense technology, also provide systems for studying IgA mediated diseases, and screening for appropriate treatments.

The present invention relates to a method for purifying a calcium ion-binding protein by cation exchange chromatography. The present invention provide a method for isolating and purifying a calcium ion-binding protein in a simple and efficient manner from a liquid sample containing a calcium ion-binding protein and contaminants without any pretreatment such as addition of a chelating agent. More specifically, the present invention relates to a method for purifying a calcium ion-binding protein which comprises contacting said protein with a cation exchange carrier in the presence of calcium ions to let the said protein be adsorbed to the carrier, and after washing, eluting said protein, and to a calcium ion-binding protein having substantially no contaminants obtained by the method of the present invention.

Radiolabeled annexin and modified annexin conjugates useful for imaging vascular thrombi are described. Methods for making and using such radiolabeled annexin conjugates are also provided.

This invention provides methods, including a method of assessing the prognosis of a breast cancer patient, comprising assaying for loss of heterozygosity at the 10q21 region of the genome of the patient, a method of identifying a probability that a patient with breast cancer has metastasized breast cancer, a method of determining a survival probability of a patient with breast cancer, and a method of identifying a probability that a patient with prostate cancer has a severe form of prostate cancer. This invention also provides assay complexes, including assay complexes which comprise at least one prostate tissue sample or tissue sample extract, an antibody that specifically binds ANX7, and a label, or which comprise at least one breast tissue sample or tissue sample extract, an antibody that specifically binds ANX7, and a label.

The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of lung cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of lung tumor cells and methods of using the same to prevent or inhibit metastasis of lung tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic lung cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic lung cancer by assaying for the presence of an aberrant form of uteroglobin.

The invention relates to a composition for the treatment of various cancers. The composition is a vaccine containing sequences of EDB, EDA, annexin A1, endosialin, C domain of tenascin C or magic roundabout (MR) or fragments thereof as single or in a combination coupled to one or several heterologous foreign carrier molecules. The vaccine will produce antibodies that are directed against self proteins which are preferentially expressed in and around tumor vessels. The vaccine is preferably administrated together with an adjuvant.

Provided herein are compositions, including pharmaceutical compositions, and methods for modulating, i.e., stimulating or inhibiting, activity of the alternative complement pathway, and methods of identifying factor H-binding proteins.

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 relates to a method for the purification of divalent cation binding proteins with high purity on an anion exchange resin material, to divalent cation binding proteins obtainable by said method, and to a kit comprising means for carrying out said method.