Biodegradable high molecular weight polymeric linkers and their conjugates

DETAILED DESCRIPTION The present invention includes compounds of the formula: (D).
sub.
n --M--(R.
sub.
1).
sub.
m (I) wherein (m) and (n) independently selected positive integers, preferably from about 1 to about 6 each; D is a residue of a biologically active moiety: M is a multifunctional linker/spacer moiety; and R.
sub.
1 is a polymer residue.
Methods of preparing the same and methods of treatment using the same are also included as part of the present invention.
With respect to the linking of the polymer strands, the artisan is provided with higher total molecular weight polymers which are useful in providing therapeutic conjugates with relatively long T.
sub.
1/2 's.
There are several advantages associated with these types of polymers.
For example, depending upon the linkages used to attach the polymer strands to the multifunctional spacer groups, the artisan can design relatively high molecular weight polymeric transport systems which will predictably biodegrade into polymers of relatively low molecular weight which are more readily eliminated from the body than the singular polymer of higher molecular weight.
Secondly, because relatively small molecular weight polymers are used to build the biodegradable transport form, the polydispersity associated with some single strand high moleulcar weight polymers such as when PEG has a molecular weight of over 40 kDa is substantially avoided.
Additional advantages associated with using the multifunctional spacers in the polymers of the present invention is that there is a large number of multifunctional moieties readily available.
Thus, the artisan can prepare polymeric prodrug systems having high degrees of loading, i.
e.
3-6 or more molecules of active drug per transport system.
A still further advantage of the multifunctional spacers of polymeric systems of the present invention is that the artisan can form prodrugs of almost any therapeutic molecule.
For example, the multifunctional spacer can be designed to include the capability of accommodating a linker for attaching to hydroxyl residues, amine residues, sulfhydryl residues, etc