N-terminal derivatisation of proteins with polysaccharides
First Claim
1. A composition comprising a population of polysialic acid derivatives of a DNase protein, wherein the derivatives comprise between 2 and 200 sialic acid units and wherein the population consists substantially only of N-terminal derivatives of the protein.
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Abstract
The present invention relates to methods for producing N-terminal derivatives of proteins in which a polysaccharide, preferably having at least terminal sialic units and preferably consisting essentially only of sialic acid units, is reacted at the N-terminus of a protein or peptide under controlled conditions to produce an N-terminal derivative. The controlled conditions include use of acidic pH for the derivatization step and a higher pH for purification. The derivatives are useful for improving pharmacokinetics and pharmacodynamics of proteins and peptides.
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Citations
19 Claims
- 1. A composition comprising a population of polysialic acid derivatives of a DNase protein, wherein the derivatives comprise between 2 and 200 sialic acid units and wherein the population consists substantially only of N-terminal derivatives of the protein.
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5. A method for producing a purified N-terminal derivative of a DNase protein in which (i) a Polysialic acid (PSA) is reacted at the amine group of the N-terminus of the DNase in aqueous acidic solution to produce an N-terminal derivative;
- and (ii) the resultant N-terminal derivative is purified in aqueous solution of higher pH than in step (i).
- View Dependent Claims (6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
Specification