Derivatisation of erythropoietin (EPO)
The present invention relates to a compound which is a polysaccharide derivative of EPO, or of an EPO like protein, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units. The present invention also relates to pharmaceutical compositions comprising the novel compounds, and methods for making the novel compounds.
1. A compound which is an amino-terminal polysaccharide derivative of erythropoietin (EPO), wherein a polysaccharide is attached to the amino-terminus of the EPO, wherein the polysaccharide is anionic and comprises between 2 and 125 saccharide units.
2. A compound according to claim 1 wherein the polysaccharide is polysialic acid.
3. A compound according to claim 2 wherein the polysaccharide consists of sialic acid units.
4. A compound according to claim 1 wherein the EPO is derivatised by the polysaccharide at the reducing terminal unit of the polysaccharide.
5. A compound of formula (I)
wherein m is at least one;
XB is derived from B—XH which is EPO wherein XH is NH 2 and is the amino terminus of the protein, wherein the polysaccharide is attached to the amino terminus of the EPO;
L is a bond or a linking group,
GlyO is an anionic saccharide unit,
wherein the linking group, if present, is of the formula
—Y—C(O) —R 1 —C(O)—;
wherein R 1 is a difunctional organic radical selected from the group consisting of alkanediyl, arylene, alkarylene, heteroarylene and alkylheteroarylene, any of which is optionally substituted and/or interrupted by carbonyl, ester, sulfide, ether, amide and/or amine linkages; and
wherein Y is NR 2 or NR 2 —NR 2 and R 2 is H or C 1-6 alkyl.
6. A compound according to claim 5 wherein L is a bond or is
7. A compound according to claim 1 wherein the EPO is glycosylated and comprises 2-100 saccharide units.
8. A compound according to claim 1 wherein the EPO is non-glycosylated and comprises 80-180 saccharide units.
9. A pharmaceutical composition comprising a compound according to claim 1 and one or more phaimaceutically acceptable excipients.
10. A compound which is an amino-terminal polysaccharide derivative of EPO, wherein the polysaccharide is attached to the amino-terminus of the EPO, wherein the polysaccharide is anionic and comprises between 2 and 200 saccharide units.
11. A pharmaceutical composition comprising a compound according to claim 10 and one or more pharmaceutically acceptable excipients.