120 results about "Disintegrin" patented technology

The present invention provides methods and compositions for inhibiting the biological activity of integrins, for inhibiting endothelial cell migration. and for inhibiting angiogenesis. In particular, the invention provides compositions comprising ADAM disintegrin domains and methods for using said compositions. In preferred embodiments the methods and compositions of the invention are used to inhibit angiogenesis and to treat diseases or conditions mediated by angiogenesis.

This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, whereinX is carbon or nitrogen;R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl;R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; andR5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl;with the provisos:when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy;when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen;when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula: wherein, Y is —CH2—NH2 or —NH—CH3; andwhen X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.

This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl; R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; and R5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy; when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen; when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula: wherein, Y is —CH2—NH2 or —NH—CH3; and when X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.

Provided herein are methods for purifying recombinant A Disintegrin-like and Metallopeptidase with Thrombospondin Type 1 Motif 13 (ADAMTS13) protein from a sample. The method comprises enriching for ADAMTS13 protein by chromatographically contacting the sample with hydroxyapatite under conditions that allow ADAMTS13 protein to appear in the eluate or supernatant from the hydroxylapatite. The methods may further comprise tandem chromatography with a mixed mode cation exchange / hydrophobic interaction resin that binds ADAMTS13 protein. Additional optional steps involve ultrafiltration / diafiltration, anion exchange chromatography, cation exchange chromatography, and viral inactivation. Also provided herein are methods for inactivating virus contaminants in protein samples, where the protein is immobilized on a support. Also provided herein are compositions of ADAMTS13 prepared according to said methods.

The present invention provides liquid formulations of antibodies or antibody fragments that immunospecifically bind to integrin alphaVbeta3, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention provides liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin alphaVbeta3, which formulations are substantially free of surfactant, inorganic salts, and / or other common excipients. Furthermore, the invention provides methods of preventing, treating or ameliorating an inflammatory disorder, an autoimmune disorder, a disorder associated with aberrant expression and / or activity of integrin alphaVbeta3, a disorder associated with abnormal bone metabolism, a disorder associated with aberrant angiogenesis or cancer utilizing the liquid formulations of the present invention.

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αllbβ3 and / or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αllbβ3 and / or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and / or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.

The present invention provides a monoclonal antibody or a fragment thereof binding to the extracellular I-domain of integrin alpha10beta1 and a hybridoma cell line deposited at the Deutsche Sammlung von Microorganismen und Zellkulturen GmbH under the accession number DSM ACC2583. Furthermore, the present invention also provides a monoclonal antibody or a fragment thereof binding to the extracellular I-domain of integrin alpha10beta1 produced by the hybridoma cell line deposited. Method and uses of the antibody or a fragment thereof in identifying and selecting cells of a chondrogenic nature for treatment purposes, in particular for the identification and isolation of chondrocytes, mesenchymal progenitor cells and embryonic stem cells for tissue engineering of cartilage, or for identifying diagnostic and therapeutic tools in studying the biological role and the structural / functional relationships of the integrin alpha10beta1 with its various extracellular matrix ligands are also included.

This invention relates to methods of expressing eukaryotic proteins in prokaryotic hosts, particularly eukaryotic proteins that require formation of disulfide bridges for biological activity. Various approaches are used including fusion to thioredoxin, cytoplasmic expression of disulfide isomerases, deficiencies in thioredoxin and / or glutathione reductases, deficiencies in proteases, and the like. The method is applicable to express monomeric and dimeric forms of the eukaryotic protein with biological activity such as monomeric and dimeric forms of a disintegrin or a disintegrin domain. Included are the vectors, host cells expressing the proteins, the expressed proteins and methods of using the proteins.

The invention belongs to the field of pharmacology, and relates to stapled-RGD polypeptide, and applications thereof in tumor targeting delivery. Multifunctional targeting polypeptide molecule stapled-RGD with high combination activity with integrin and biological membrane barrier penetration capacity is designed and prepared based on binding peptide cyclization technology; and preparation of fluorescein, drugs, and high molecule carriers modified by the multifunctional targeting polypeptide molecule stapled-RGD, and applications of the fluorescein, the drugs, and the high molecule carriers in tumor imaging and construction of targeted therapy targeted drug delivery systems are disclosed. It is shown by results that specific uptaking of model drugs carried by stapled-RGD by positive cells, tumor mimicry vessels, and tumor ball tissues of expressed integrin is realized, higher tumor targeting capacity, imaging functions, and membrane barrier cell penetration capacity are achieved; nano targeted drug delivery systems constructed by the high molecule carriers modified by stapled-RGD can be used for delivering carried model drugs to target tissues, antitumor drug effect is improved obviously; and stapled-RGD possesses a promising application prospect in mediating drugs, nano targeted drug delivery system membrane barrier penetration, active target searching, tumor diagnosis, and targeted therapy.

The gene clone and expression of Japonese lampreyí»s oral gland model proteins RGD with antineoplastic action are disclosed. Three cDNA sequences with said model proteins RGD and their clones, the protein sequence and its expression in engineered bacteria, and the action of proteins RGD in closing the signal transfer channel to suppress the vascular neogenesis and tumor cell reproduction for antineoplastic purpose are also disclosed.

Integrin-linked kinase (ILK) and Akt / protein kinase B (PKB) are important mediators of signaling in cardiomyocytes and can both prevent damage and promote healing associated with ischemic injury to the heart. Thus, the present invention provides for methods of screening for agents that increase the expression of ILK and / or Akt / PKB. Methods of treatment based on such agents are also provided.

A transgenic carrier with deal targets (fibroblast growth factor receptor and integrant) is composed of the polypeptide CR16 specifically linked with alkaline fibroblast growth factor receptor, the polypeptide CP9 specifically linked with integrant, and the transgenic non-virus carrier system of CR16 / CP9 / cationic polymer PEI / exogenous DNA. Said carrier can effectively introduce the exogenous DNA to the tumor cell line and tumor tissue with high expression of FGFRs, so suppressing the growth of tumor. It can be used to preparation of the medicine for treating tumor and other diseases.

Modified ADAM (A Disintegrin and Metalloproteinase) Polypeptides (MAPs) are provided. Methods are provided for administering MAPs for anti-angiogenesis and anti-tumor growth activity. Compositions of the invention are also useful for treating endothelial cell dysfunction and for diagnosis of integrin-related conditions.

The invention relates to a novel human derived monoclonal antibody for identifying activated integrin alpha 4 beta 7. The monoclonal antibody for specifically identifying activated integrin alpha 4 beta 7 is obtained by screening by an inventor. Based on the identification specificity, the monoclonal antibody can be used as a carrier for targeting transportation to take a medicament to positions of pathological tissues so as to fulfill an aim of treating diseases; and the monoclonal antibody also can be used as a tool for researching the activation status of the integrin alpha 4 beta 7.

The invention provides a tumor dual target liposome mediated by integrin and a preparation method thereof. The composition of the invention comprises the components of an antitumor medicament, polypeptide with tumor new vessel target function and tumor cell target function, polyethylene glycol and derivates thereof and a vector for preparing liposome medicaments.

The present invention relates to polynucleotide and polypeptide molecules, and variants thereof, for ZSNK10, ZSNK11, and ZSNK12, novel members of the Disintegrin Proteases. The polypeptides, and polynucleotides encoding them, are cell-cell interaction modulating and may be used for delivery and therapeutics. The present invention also includes antibodies to the ZSNK10, ZSNK11, and ZSNK12 polypeptides.

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αllbβ3 and / or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αllbβ3 and / or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and / or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.

We show that urinary metalloproteinases (MMP's) (e.g. MMP 9) and a disintegrin and metalloprotease 12 (ADAM 12) are significantly elevated in women at high risk for developing breast cancer and that monitoring for the absence or presence of both MMP 9 and ADAM 12 represents a new means for breast cancer risk assessment. In addition, we show that levels of MMP 9 and ADAM 12 serve as independent predictors of breast cancer risk. Furthermore, we have determined that elevated levels of urinary ADAM 12 predict an increased risk for breast cancer in subjects predicted not to be at risk for breast cancer by the Gail 5 -year risk model<66'67>. Accordingly, methods for assessing breast cancer risk and methods for directing medical care are provided.

The invention relates to the technical field of medicine, in particular to an exosome carrier of a target integrin alpha v beta 3 and a preparation method and application of the exosome carrier. Mononuclear suspension cells THP-1 are adopted and stimulated by PMA of the certain concentration to obtain the exosome carrier, the surface of an exosome after separating contains an RGD target molecule metalloprotease disintegrin family 15, and the target integrin receptor alpha v beta 3 can be obtained. The in-vitro releasing experiment shows that the prepared exosome can slowly release loaded chemotherapeutic medicine, and the better capacity of jointly loading genes and the chemotherapeutic medicine is achieved. In the tumor treatment process, the exosome can enhance the effects of cells of aspecificity target overexpression integrin alpha v beta 3 on tumor cells through the chemotherapeutic medicine or gene medicine, apoptosis of tumor cells is promoted, and therefore the exosome carrierforms a targeted and efficient low-toxicity bionic nanoscale delivery system of tumor treatment.

The invention relates to compositions and methods for treating diseases. In particular aspects, the invention relates to administering a combination of a disintegrin with a microtubule stabilizing agent useful for treatment of cancer.

The invention discloses an Fc-FF-RGD composite. The Fc-FF-RGD composite is characterized in that the composite is a polypeptide analogue sequence composed of ferrocenecarboxylic acid, biphenyl alanine and arginine-glycine-aspartic acid. Compared with the prior art, the Fc-FF-RGD composite has the following advantages that an RGD ligand on hydrogel can be combined with alpha5beta1 integrin on the surfaces of cells so that adhesion and multiplication of the cells are promoted and a good biological nano material application potential is shown; and furthermore, self-assembled nano small balls can identify the alpha5beta1 integrin on the surfaces of cells, so that the Fc-FF-RGD composite can be used as a drug transportation carrier to realize the aim of enhancing the anti-tumor effect.

The invention generally relates to methods of measuring cleaved von Willebrand factor (VWF) fragments. More specifically, the invention relates to methods of measuring the ability of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) to cleave VWF in vivo. The invention also relates to methods of using various animal models which demonstrate ADAMTS13 activity similar to that of a human. The invention further relates to methods of measuring the cleavage products of rVWF in mammals, particularly in humans and in human plasma.

Proteins comprising the amino acid sequence of human disintegrin and DNA sequences encoding the human disintegrin protein are identified. Also described are methods for determining the activity of the disintegrin and for identifying compounds capable of binding to and inhibiting the disintegrin protein. Recombinant expression vectors comprising the DNA sequences encoding the disintegrin, host cells comprising the recombinant expression vector, and antibodies to the disintegrin protein and screening methods for detecting levels of disintegrin protein are exemplified.

Provided is a cell culture vessel characterized in that a surface to be in contact with cells is coated with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in a dry state,the laminin fragment being derived from at least one kind selected from laminin α5β1γ1 and laminin α5β2γ1,the cell culture vessel being any of the following:(1) a cell culture vessel of which a surface to be in contact with cells is coated only with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in a dry state;(2) a cell culture vessel of which a surface to be in contact with cells is coated with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in combination with a laminin fragment having no integrin α6β1 binding activity in a dry state; and(3) a cell culture vessel of which a surface to be in contact with cells is coated with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in combination with a protein that is neither a laminin nor a laminin fragment, in a dry state.

The invention discloses a siRNA for inhibiting ADAM17 (a disintegrin and metalloprotease 17) genes and an application of the siRNA. The invention discloses a chemically-modified dual-chain siRNA molecule, and particularly relates to a dual-chain siRNA molecule which is formed by chemically modifying and supplementing (as shown in (1) to (13)) at least one chain in the siRNA molecule indicated by A. The siRNA can be used as a treatment drug for arthritis and relevant inflammations, and the siRNA and preparations of the siRNA can be locally injected through a bone joint cavity to inhibit the inflammation factor expression so as to realize the treatment for the arthritis.

Radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).