Non-antigenic branched polymer conjugates

DETAILED DESCRIPTION OF THE INVENTION 1.
POLYMER SUBSTITUENTS AND FORMULA (I) DEFINED The activated branched polymers of the present invention are preferably prepared from poly(alkylene oxides) (PAO's) that are water soluble at room temperatures.
Within this group are alpha-substituted polyalkylene oxide derivatives such as methoxypoly (ethylene glycols) (mPEG) or other suitable alkyl substituted PAO derivatives such as those containing mono or bis terminal C.
sub.
1 -C.
sub.
4 groups.
Straight-chained non-antigenic polymers such as monomethyl PEG homopolymers including ##STR2## and mPEG--O--CH.
sub.
2 --CH.
sub.
2 -- are preferred.
Alternative polyalkylene oxides such as other poly(ethylene glycol) homopolymers, other alkyl-poly(ethylene oxide) block copolymers, and copolymers of block copolymers of poly(alkylene oxides) are also useful.
The polymers of the present invention are represented by Formula (I): (R).
sub.
n L--A (I) wherein: (R) includes a water-soluble, substantially non-antigenic polymer; (n)=2 or 3; (L) is an aliphatic linking moiety covalently linked to each (R); and (A) represents an activating functional group capable of undergoing nucleophilic substitution.
Each (R) can be a water-soluble, substantially non-antigenic polymer chain.
When the polymer chains are PEG or mPEG, it is preferred that each chain have a molecular weight of between about 200 and about 80,000 daltons and preferably between about 2,000 and about 42,000 daltons.
Molecular weights of about 5,000 to about 20,000 daltons are most preferred.
Alternative polymeric substances include materials such as dextrans, polyvinyl pyrrolidones, polyacrylamides or other similar non-immunogenic polymers.
Such polymers are also capable of being functionalized or activated for inclusion in the invention.
The foregoing is merely illustrative and not intended to restrict the type of non-antigenic polymers suitable for use herein.
In another embodiment of the invention, (R) is a branched polymer for secondary and tertiary branching from a bioactive material