Pegylation reagents and compounds formed therewith
AssigneeAmgen Inc.
InventorsRobert C. Thompson, Michael T. Brewer, Tadahiko Kohno
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Abstract
Biologically active conjugates are disclosed which are formed by reaction of a thiol moiety of a biologically active molecule with a non-peptidic polymer having an active sulfone moiety. Also disclosed are compounds having the formula R1—X—R2 wherein at least one of R1 and R2 is a biologically active molecule having a reactive thiol moiety which forms a covalent bond with X, a Michael acceptor-activated non-peptidic polymer. Further disclosed are methods of making the conjugates and compounds of the present invention as well as pharmaceutical compositions containing them. In addition, activated polymers suitable for attachment to a variety of molecules and surfaces are disclosed.
Claims44
A biologically-active conjugate comprising a biologically-active molecule having a reactive thiol moiety and a non-peptidic polymer having an active sulfone moiety forming a linkage with said thiol moiety.
A method of preparing a biologically-active conjugate, comprising the steps of:
- (a) reacting a biologically-active molecule having a reactive thiol moiety with a non-peptidic polymer having an active sulfone moiety to form said conjugate;
- and
- (b) optionally, isolating said conjugate.
A substantially purified compound of the formula R1—X—R2, wherein:
- X comprises a non-peptidic polymer having a first reactive group and a second reactive group, wherein said first reactive group is a Michael acceptor;
- R1 comprises a biologically-active molecule having a reactive thiol moiety, said biologically-active molecule is covalently bonded to said non-peptidic polymer by reaction of said thiol moiety with said Michael acceptor, and said biologically-active molecule retains its biological activity after said reaction;
- and
- R2 comprises a biologically-active molecule or a nonbiologically-active group bonded to said non-peptidic polymer by reaction with said second reactive group.
A water-soluble polymer having a reactive NHS-ester and a reactive Michael acceptor.
Dependencies are inferred from the claim text.