Branched Polymers
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Abstract
The present invention is directed to branched reactive water-soluble polymers comprising at least two polymer arms, such as poly(ethylene glycol), attached to a central aliphatic hydrocarbon core molecule through heteroatom linkages. The branched polymers bear at least one functional group for reacting with a biologically active agent to form a biologically active conjugate. The functional group of the branched polymer can be directly attached to the aliphatic hydrocarbon core or via an intervening linkage, such as a heteroatom, -alkylene-, —O-alkylene-O—, -alkylene-O-alkylene-, -aryl-O—, —O-aryl-, (—O-alkylene-)m, or (-alkylene-O—)m linkage, wherein m is 1-10.
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Citations
54 Claims
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1-36. -36. (canceled)
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37. A biologically active conjugate comprising a branched polymer covalently attached to a biologically active molecule, wherein the conjugate has the structure:
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D-L1-(X)p—
R(—
X′
-POLY)qwherein; D is the biologically active molecule; R is an aliphatic hydrocarbon having a length of at least three carbon atoms; L1 is a linkage resulting from the reaction of a functional group on the linker (X), when present, or on the aliphatic hydrocarbon having a length of at least three carbon atoms (R) of the branched polymer and a functional group of the biologically active molecule; each POLY is a water soluble and non-peptidic polymer that terminates with a hydroxyl or methoxy group; X′
is —
O—
, —
NH—
, or —
S—
;X is a linker of 1 to 10 atoms in length; p is 0 or 1; and q is 2, and further wherein the branched polymer has a molecular weight of about 12,000 Da to about 100,000 Da. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54)
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Specification