Non-antigenic amine derived polymers and polymer conjugates

DETAILED DESCRIPTION In one aspect of the invention, there are provided amine-based polymer intermediates having the formula: R--B (I) wherein (R) is a water-soluble, substantially non-antigenic polymer residue and (B) is preferably a secondary amine or a tertiary amine.
Suitable secondary amines are of the formula: --NH(CH.
sub.
2).
sub.
n X (II) wherein: (n) is an integer from 1-12, inclusive; and X is selected from the group consisting of H; OH; CO.
sub.
2 R.
sub.
1, where R.
sub.
1 is H or a C.
sub.
1-6 alkyl; halogen, atyl moieties and heteroaromatic moieties.
Suitable tertiary amines can be selected from: ##STR1## wherein (m) is an integer from 0-12, inclusive; (X) is selected from the group consisting of H, OH, CO.
sub.
2 R.
sub.
1, where R.
sub.
1 is H or a C.
sub.
1-6 alkyl, halogen, aryl moieties and heteroaromatic moieties; (Y) is N or CH; and (Z) is a C.
sub.
1-6 alkyl.
The polymer is preferably a poly(alkylene oxide) residue such as a poly(ethylene glycol) having a molecular weight between about 200 and about 100,000.
In addition, the polymer is preferably capped with a C.
sub.
1-4 alkyl group on the end opposite (i.
e.
distal to) the B moiety.
In another aspect of the invention, there are provided substantially non-antigenic polymers of the formula: R--B'--W--L (VII) wherein (R) is as defined above; (B') is NY, where Y is H i.
e.
, a secondary amine or a C.
sub.
1-6 alkyl or cycloalky i.
e.
, a tertiary amine, (W) is a spacer group, such as a C.
sub.
1-6 alkyl and (L) is a functional group capable of bonding with nucleophdies.
Other aspects of the invention include polymer conjugates containing biologically-active materials, described as nucleophiles herein as well as methods of conjugate preparation.
In these aspects of the invention, the conjugates are of the formula: [R--B'--W--L.
sup.
1 ].
sub.
z -(nucleophile) wherein: (R), (B') and (W) are as described above; (L.
sup.
1) represents a covalent linkage between (R--B'--W) and a nucleophile; and (z) represents the number of polymers attached to the nucleophile