Replies to post #9934 on GTC Biotherapeutics (fka GTCB)

[Lewis R Goudy]

It purported to address a means of extending half-life
and specifically mentioned FVII. Your post to which I
responded concerned the activity and half-life of FVII
modifications obtained by various approaches, and I thought
that polymerization might qualify as another.

I find further interest in the prospect of combining
independently optimized targeting and functional moieties
in mabs and perhaps other proteins in potential prospect
of development by GTC, as suggested by the following excerpt:

[0003] Targeting and drug delivery of therapeutics is becoming increasingly important especially with the use of cytotoxics in the treatment of cancer. A number of methods have been used to selectively target tumors with therapeutic agents to treat cancers in humans and other animals. Targeting moieties such as monoclonal antibodies (mAb) or their fragments have been conjugated to linear polymers via their side chain functional groups. However, this approach usually results in reduced receptor binding affinity either due to changes in the chemical properties of the antibodies or due to folded configuration of polymers that imbed the targeting moiety in the random coiled structure. Ideally, a new conjugate would encompass both a targeting functionality as well as a therapeutic value.

[0004] Recently, heterobifunctional polymeric conjugates having a targeting functional group on one end and a therapeutic moiety (e.g. a chemotherapeutic drug) on the opposite end has been disclosed, see US Patent Application 2002/0197261A1. The polymer conjugates employed have a polymeric spacer bonded to a polymeric carrier containing multiple side-chain functional groups that allow the attachment of multiple drug, molecules (e.g. poly(1-glutamic acid)) on one end, with the other end of the polymeric spacer bonded to a targeting moiety.