Hasylated polypeptides
AssigneeFresenius Kabi Deutschland GmbH
InventorsHarald S. Conradt, Eckart Grabenhorst, Manfred Nimtz, Norbert Zander, Ronald Frank, Wolfram Eichner
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Abstract
The present invention relates to hydroxyalkylstarch (HAS)-polypeptide-conjugate (HAS-polypeptide) comprising one or more HAS molecules, wherein each HAS is conjugated to the polypeptide via a carbohydrate moiety or a thioether as well as to methods for the production thereof. In a preferred embodiment, the polypeptide is erythropoietin (EPO).
Claims52
A hydroxyalkylstarch (HAS)-erythropoietin (EPO)-conjugate (HAS-EPO), comprising one or more HAS molecules, wherein the EPO comprises one or more carbohydrate side chains attached to the EPO via N-linked, O-linked, or N-linked and O-linked glycosylation, wherein each HAS is conjugated to the EPO via a carbohydrate moiety that is part of the carbohydrate side chains, wherein the HAS is conjugated to the EPO via O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine, and wherein the reaction between the HAS and the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine takes place at the non-oxidized reducing end of the HAS.
A method for the production of a HAS-EPO, comprising the steps of:
- a) providing EPO being capable of reacting with modified HAS, wherein the EPO comprises one or more carbohydrate side chains attached to the EPO via N-linked, O-linked, or N-linked and O-linked glycosylation,
- b) providing modified HAS being capable of reacting with the EPO of step a), and
- c) reacting the EPO of step a) with the HAS of step b), whereby a HAS-EPO is produced comprising one or more HAS molecules, wherein each HAS is conjugated to the EPO via a carbohydrate moiety that is part of the carbohydrate side chains, wherein the HAS is conjugated to the EPO via O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine, and wherein the reaction between the HAS and the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine takes place at the non-oxidized reducing end of the HAS.
A HAS-EPO, obtainable by a method comprising the steps of:
- a) providing EPO being capable of reacting with modified HAS, wherein the EPO comprises one or more carbohydrate side chains attached to the EPO via N-linked, O-linked, or N-linked and O-linked glycosylation,
- b) providing modified HAS being capable of reacting with the EPO of step a), and
- c) reacting the EPO of step a) with the HAS of step b), whereby an HAS-EPO is produced comprising one or more HAS molecules, wherein each HAS is conjugated to the EPO via a carbohydrate moiety that is part of the carbohydrate side chains, wherein the HAS is conjugated to the EPO via O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine, and wherein the reaction between the HAS and the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine takes place at the non-oxidized reducing end of the HAS.
A HAS-polypeptide-conjugate (HAS-polypeptide), comprising one or more HAS molecules, wherein the polypeptide comprises one or more carbohydrate side chains attached to the polypeptide via N-linked, O-linked, or N-linked and O-linked glycosylation, wherein each HAS is conjugated to the polypeptide via a carbohydrate moiety that is part of the carbohydrate side chains, wherein the HAS is conjugated to the polypeptide via O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine, and wherein the reaction between the HAS and the crosslinking compound takes place at the non-oxidized reducing end of the HAS.
A method for the production of a HAS-polypeptide, comprising the steps of:
- a) providing a polypeptide being capable of reacting with modified HAS, wherein the polypeptide comprises one or more carbohydrate side chains attached to the polypeptide via N-linked, O-linked, or N-linked and O-linked glycosylation,
- b) providing modified HAS being capable of reacting with the polypeptide of step a), and
- c) reacting the polypeptide of step a) with the HAS of step b), whereby HAS-polypeptide is produced comprising one or more HAS molecules, wherein each HAS is conjugated to the polypeptide via a carbohydrate moiety that is part of the carbohydrate side chains, wherein the HAS is conjugated to the polypeptide via O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine, and wherein the reaction between the HAS and the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine takes place at the non-oxidized reducing end of the HAS.
A HAS-polypeptide, obtainable by a method comprising the steps of:
- a) providing a polypeptide being capable of reacting with modified HAS, wherein the polypeptide comprises one or more carbohydrate side chains attached to the polypeptide via N-linked, O-linked, or N-linked and O-linked glycosylation,
- b) providing modified HAS being capable of reacting with the polypeptide of step a), and
- c) reacting the polypeptide of step a) with the HAS of step b), whereby HAS-polypeptide is produced comprising one or more HAS molecules, wherein each HAS is conjugated to the polypeptide via a carbohydrate moiety that is part of the carbohydrate side chains, wherein the HAS is conjugated to the polypeptide via O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine, and wherein the reaction between the HAS and the O-[2-(2-aminooxy-ethoxy)-ethyl]-hydroxylamine takes place at the non-oxidized reducing end of the HAS.
Dependencies are inferred from the claim text.