N-Terminal Derivatisation of Proteins With Polysaccharides
AssigneeLipoxen Technologies Limited
InventorsSanjay Jain, Peter Laing, Gregory Gregoriadis
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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 derivatisation step and a higher pH for purification. The derivatives are useful for improving pharmacokinetics and pharmacodynamics of proteins and peptides.
Claims21
1-29. (canceled)
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 at least 85% of the population is derivatised with polysialic acid at the N-Terminal amine only.
A polysialic acid derivative according to formula (I)
- wherein m is 2-200;
- HNB is derived from B—NH2 which is the N-terminal amine of a DNase protein;
- L is a bond, a linking group, or comprises a polypeptide or a synthetic oligomer;
- GlyO is a sialic acid unit;
- wherein the linking group, if present, is of general formula —Y—C(O)—R1—C(O)—
- wherein Y is NR2 or NR2—NR2 and R1 is selected from the group consisting of alkanediyl, arylene, alkarylene, heteroarylene and alkylheteroarylene, any of which may be substituted and/or interrupted by carbonyl, ester, sulfide, ether, amide and/or amine linkages;
- and R2 is H or C1-6 alkyl.
Dependencies are inferred from the claim text.