Protein-polymer-drug conjugates

A therapeutic anti-5T4 drug targeting conjugate useful in anti-neoplastic therapies comprising an anti-5T4 ligand and a polymeric scaffold comprising a poly(1-hydroxymethylethylene hydroxymethyl-formal) (PHF) having a molecular weight from about 2 kDa to about 40 kDa, wherein the conjugate is of the following structure:

• wherein m5 is 1 to 10;
• m is an integer from 1 to about 300;
• m1 is an integer from 1 to about 140;
• m2 is an integer from 1 to about 40;
• m3a is an integer from 0 to about 17;
• m3b is an integer from 1 to about 8;
• provided that the sum of m3a and m3b is an integer from 1 to about 18;
• and the sum of m, m1, m2 and m3 ranges from about 15 to about 300,
• X is NH;
• one of Xa or Xb is H and the other is a water-soluble maleimido blocking moiety;
• and where each occurrence of D independently is a therapeutic agent having a molecular weight of ≤5 kDa, and the
• between D and the carbonyl group denotes direct or indirect attachment of D to the carbonyl group;
• wherein the ANTI-5T4 is an anti-5T4 ligand comprising an immunoglobulin or a functional fragment thereof which is selective for human oncofetal antigen 5T4;
• and
• wherein the sulfur atom is part of the ligand.

A therapeutic drug and targeting conjugate useful in anti-neoplastic therapies comprising an anti-5T4 ligand and a poly(1-hydroxymethylethylene hydroxymethyl-formal) (PHF) polymeric scaffold comprising the units shown below which may be randomly connected to each other,

• wherein:
• ANTI-5T4 is a single chain antibody construct comprising the amino sequence designated as SEQ ID NO:
• 7;
• the sulfur atom is part of the single chain antibody construct;
• the PHF has a molecular weight ranging from about 2 kDa to about 40 kDa;
• the average polymeric scaffold to anti-5T4 single chain antibody ratio is about 2:1 to about 4:1;
• and
• the auristatin F HPA to anti-5T4 antibody ratio is about 12:1 to about 18:1.