Modified antibodies and related compounds, compositions and methods of use
Provided herein are modified antibodies, compounds used to make them, and intermediates in their synthesis; compositions; formulations and methods, including methods of treating diseases, disorders or conditions, for example, cancer, in humans.
1. A modified antibody represented by the following formula (IIa):
wherein:
A is an antibody or antibody fragment;
the two depicted cysteine residues are from at least one reduced interchain cysteine-cysteine disulfide bond in A;
n is an integer from 1 to 13;
the bond represents a single or a double bond; and
each R and R′ is independently hydrogen or C 1-6 alkyl, wherein one or more carbons in the C 1-6 alkyl are optionally substituted by a group selected from an oxo, a thio, an imine, and a substituted imine.
2. The modified antibody of claim 1 , wherein the modified antibody is represented by the following formula (IId):
wherein:
each R a and R a ′ is independently hydrogen, C 1-3 alkyl, or absent.
3. The modified antibody of claim 1 , wherein the bond represents a single bond.
4. The modified antibody of claim 1 , wherein n is 4.
5. The modified antibody of claim 1 , wherein A is an antibody that is specific to a cancer antigen.
6. The modified antibody of claim 1 , wherein A is selected from the group consisting of alemtuzumab, anitumumab, bevacizumab, brentuximab, cetuximab, gemtuzumab, glembatumumab, inotuzumab, ipilimumab, lovortumumab, milatuzumab, ofatumumab, rituximab, tositumomab, and trastuzumab.