79results about "Thrombopoietin" patented technology

Antibodies or fragments thereof having CDR regions replaced or fused with biologically active peptides are described. Flanking sequences may optionally be attached at one or both the carboxy-terminal and amino-terminal ends of the peptide in covalent association with adjacent framework regions. Compositions containing such antibodies or fragments thereof are useful in therapeutic and diagnostic modalities.

Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and / or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and / or practicing the subject methods.

Antibodies or fragments thereof having at least two CDR regions replaced or fused with biologically active peptides are described. Compositions containing such antibodies or fragments thereof are useful in therapeutic and diagnostic modalities.

The present invention relates to a compound comprising a peptide moiety, a spacer moiety and a water-soluble polymer moiety such as a poly(ethylene glycol) moiety. The spacer moiety is between the peptide moiety and the water-soluble polymer moiety. The spacer moiety has the structure: —NH—(CH2)α—[O—(CH2)β]γ—Oδ—(CH2)ε—Y—wherein α, β, γ, δ, and ε are each integers whose values are independently selected.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

Antibodies or fragments thereof having CDR regions replaced or fused with biologically active peptides are described. Flanking sequences may optionally be attached at one or both the carboxy-terminal and amino-terminal ends of the peptide in covalent association with adjacent framework regions. Compositions containing such antibodies or fragments thereof are useful in therapeutic and diagnostic modalities.

Peptide compounds that bind to and activate the thrombopoietin receptor (c-mpl or TPO-R) or otherwise act as a TPO agonist are disclosed.

This invention provides an agonist antibody to a human thrombopoietin receptor (alias: human c-Mpl). More particularly, this invention provides an agonist antibody to a human thrombopoietin receptor, wherein the agonist antibody comprises: antibody constant regions comprising (1) amino acid sequences in a heavy chain constant region and a light chain constant region of a human antibody, (2) an amino acid sequence of a heavy chain constant region with a domain substituted between human antibody subclasses, and an amino acid sequence of a light chain constant region of a human antibody, or (3) amino acid sequences comprising a deletion(s), substitution(s), addition(s), or insertion(s) of one or several amino acid residues in the amino acid sequences of (1) or (2) above; and antibody variable regions capable of binding to and activating a human thrombopoietin receptor; and wherein the agonist antibody has the properties: (a) that the antibody induces colony formation at a concentration of 10,000 ng / ml or lower as determined by the CFU-MK colony formation assay using human umbilical-cord-blood-derived CD34+ cells; and (b) that the antibody has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less in the cell proliferation assay using UT7 / TPO cell. Also provided is a pharmaceutical composition for treating thrombocytopenia comprising said antibody.

Disclosed is a composition of matter involving a recombinant fusion protein comprising a a pharmacologically active protein partner, and a small pharmacologically inactive protein domain partner of human origin, such as but not limited to, a 10th fibronectin III domain, a SH3 domain, a SH2 domain, a CH2 domain of IgG1, a PDZ domain, a thrombospondin repeat domain, an ubiquitin domain, a leucine-rich repeat domain, a villin headpiece HP35 domain, a villin headpiece HP76 domain, or a fragment or modification of any of these. Also disclosed are nucleic acids (e.g., DNA constructs) encoding the fusion protein, expression vectors and recombinant host cells for expression of the fusion protein, and pharmaceutical compositions containing the recombinant fusion protein and a pharmaceutically acceptable carrier, and method of producing a pharmacologically active recombinant fusion protein.

Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and / or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and / or practicing the subject methods.

Described are peptides and peptide mimetics that bind to and activate the thrombopoietin receptor. Such peptides and peptide mimetics are useful in methods for treating hematological disorders and particularly, thrombocytopenia resulting from chemotherapy, radiation therapy, or bone marrow transfusions as well as in diagnostic methods employing labeled peptides and peptide mimetics.

Peptide compounds that bind to and activate the thrombopoietin receptor (c-mpl or TPO-R) or otherwise act as a TPO agonist are disclosed.

The invention discloses preparation and application of a dimerized thrombopoietin (TPO) mimic peptide TMP diad-human serum albumin fusion protein. The fusion protein contains an HAS and two TPO mimic peptides which are connected through a linkage oligopeptide and a dimerization domain so as to ensure the fusion protein is dimerized correctly when expression. The two TPO mimic peptides can be connected with N terminal or C terminal of HAS. The dimerized HAS protein carrier and the TPO mimic peptide fusion protein provided by the invention have a significant activity of promoting thrombopoiesis in vivo and can be applied in preparation of drugs for treating primary and secondary thrombocytopenia diseases.

The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of human thrombopoietin (TPO) to result in TPO proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

The present invention relates to a method for producing a chimeric non-human animal expressing a desired protein, and a chimeric non-human animal or an offspring thereof expressing a desired protein.The present invention also relates to a method for analyzing the functions of a desired protein or a gene encoding the protein by comparing the phenotype of the above chimeric non-human animal with that of a corresponding wild-type animal.

A fusion protein (I), where a carboxy terminal peptide (CTP) of thrombopoietin (TPO) is fused with the carboxy terminal of human erythropoietin (EPO), is new. Independent claims are also included for the following: (1) nucleic acid (II) encoding (I); and (2) preparing (I). - ACTIVITY : Antianemic. No biological data is given. - MECHANISM OF ACTION : Stimulator of production and differentiation of red blood cells.