461 results about "Erythropoietin" patented technology

The present invention provides conjugates between erythropoietin and PEG moieties. The conjugates are linked via an intact glycosyl linking group interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto a glycosyl residue on the peptide. Also provided are methods for preparing the conjugates, methods for treating various disease conditions with the conjugates, and pharmaceutical formulations including the conjugates.

The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

The present invention provides Fc-erythropoietin (“Fc-EPO”) fusion proteins with improved pharmacokinetics. Nucleic acids, cells, and methods relating to the production and practice of the invention are also provided.

The present invention provides conjugates between erythropoietin and PEG moieties. The conjugates are linked via an intact glycosyl linking group interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto a glycosyl residue on the peptide. Also provided are methods for preparing the conjugates, methods for treating various disease conditions with the conjugates, and pharmaceutical formulations including the conjugates.

Erythropoietin analogs having at least one additional site for glycosylation, or a rearrangement of at least one site for glycosylation are disclosed. The invention also relates to DNA sequences encoding said erythropoietin analogs, and recombinant plasmids and host cells for analog expression.

The present invention provides Fc-erythropoietin (“Fc-EPO”) fusion proteins with improved pharmacokinetics. Nucleic acids, cells, and methods relating to the production and practice of the invention are also provided.

Disclosed are immortalized human embryonic retina cells, having a nucleic acid sequence encoding an adenoviral E1A protein integrated into the genome of the cells, and further comprising a nucleic acid sequence encoding an enzyme involved in post-translational modification of proteins, such as a sialyltransferase, wherein said nucleic acid sequence encoding the enzyme involved in post-translational modification of proteins is under control of a heterologous promoter. Methods for producing recombinant proteins from such cells and obtaining such recombinant proteins having increased sialylation are provided as are novel compositions of isoforms of erythropoietin .

The present invention provides a process for the production of erythropoietin (EPO) with high purity and with a desired profile of EPO glycol-isoforms by using a combination of specific chromatographic steps in such a manner that the starting EPO glycol-isoform profile is changed or modified. The applied chromatographic steps includes at least (a) dye affinity chromatography, and (b) hydrophobic chromatography and/or (c) anion-exchange chromatography. In a preferred embodiment, the process further includes (d) gel filtration chromatography. The present invention also provides a process for the determination of erythropoietin (EPO) glycol-isoform profile in an EPO containing composition.

The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula:

(M)_n-X-A-cys-EPO   (I)

where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position −1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of −1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.

The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.

Methods and compositions are provided for protecting or enhancing excitable tissue function in mammals by systemic administration of an erythropoietin receptor activity modulator, such as erythropoietin, which signals via an EPO-activated receptor to modulate the function of excitable tissue. Excitable tissues include central neuronal tissues, such as the brain, peripheral neuronal tissues, retina, and heart tissue. Protection of excitable tissues provides treatment of hypoxia, seizure disorders, neurodegenerative diseases, hypoglycemia, and neurotoxin poisoning. Enhancement of function is useful in learning and memory. The invention is also directed to compositions and methods for facilitating the transport of molecules across endothelial cell tight junction barriers, such as the blood-brain barrier, by association of molecules with an erythropoietin receptor activity modulator, such as an erythropoietin.

Methods of treating mitochondrial disorders that are not respiratory chain disorders using compositions comprising EPO mimetic compounds or compounds capable of increasing endogenous EPO levels or stimulating erythropoiesis are disclosed. Methods of treating Friedreich's ataxia, Leigh's syndrome, or other disorders by increasing the expression of frataxin with an EPO mimetic compound or a compound capable of increasing endogenous EPO levels or stimulating erythropoiesis are also disclosed.

The invention relates to methods of using compositions comprising EPO-mimetic peptides to treat anemia. The invention relates to methods of treating disorders characterized by the insufficient amounts of erythrocytes and hemoglobulin in the blood due to myelodysplastic syndrome (MDS) or by hemoglobinopathies, such as alpha- or beta-thalessemia or sickle cell disease.

The present invention refers to conjugates of erythropoietin with poly(ethylene glycol) comprising an erythropoietin glycoprotein having an N-terminal α-amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have the sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to one poly(ethylene glycol) group of the formula

—CO—(CH₂)_x—(OCH₂CH₂)_m—OR

wherein the —CO of the poly(ethylene glycol) group forms an amide bond with said N-terminal α-amino group; and wherein R is lower alkyl; x is 2 or 3; and m is from about 450 to about 1350.

The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent of HMG-CoA reductase inhibitors or erythropoietin. The nanoparticles are characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

Co-therapy for the treatment of neurological dysfunctions comprising administration of one or more fructopyranose sulfamates and erythropoietin.

The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor. The invention is further directed to the consensus sequences for use in engineering a synthetic tissue protective peptide. These tissue protective peptides also include fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO. The invention further encompasses methods for treating or preventing a disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.

Methods for increasing and maintaining hematocrit in a mammal comprising administering a hyperglycosylated analog of erythropoietin are disclosed. An analog may be administered less frequently than an equivalent molar amount of recombinant human erythropoietin to obtain a comparable target hematocrit and treat anemia. Alternatively, a lower molar amount of a hyperglycosylated analog may be administered to obtain a comparable target hematocrit and treat anemia. Also disclosed are new hyperglycosylated erythopoietin analogs, methods of production of the analogs, and compositions comprising the analogs.

The present invention relates to a fusion protein in which a carboxy terminal of human erythropoietin (EPO) is fused with a carboxy terminal peptide fragment of β subunit of human chorionic gonadotropin (HCG), to DNA encoding the fusion protein, and to a method for preparation of the fusion protein. The fusion protein has the enhanced in vivo activity of erythropoietin.

The present invention provides conjugates between erythropoietin and PEG moieties. The conjugates are linked via an intact glycosyl linking group interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto a glycosyl residue on the peptide. Also provided are methods for preparing the conjugates, methods for treating various disease conditions with the conjugates, and pharmaceutical formulations including the conjugates.

The invention provides compositions, methods, and kits for increasing transport of a neurotrophin (e.g., erythropoietin (EPO)) across the blood brain barrier while allowing its activity to remain substantially intact. The neurotrophin (e.g., EPO) is transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems.