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US 12,612,468 B2Granted
Engineering the hinge region to drive antibody dimerization
AssigneeAmgen Inc.
InventorsFernando Garces, Zhulun Wang
Life of this patent
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AssigneeAmgen Inc.
InventorsFernando Garces, Zhulun Wang
Estimating the term…
The clinical potential of multispecific antibodies like bispecific and trispecific antibodies shows great promise for targeting complex diseases. However, the generation of those molecules presents great challenges as in many cases it is desired to specifically drive the specific pairing of multiple polypeptide chains that are present in solutions. In the case of the heavy chains, there are two main regions that form a dimer interface. One of them is the CH3 region, which has been widely exploited by inserting either charge-pair mutations (CPMs) to steer the dimer interface or inserting large bulky residues into cavities (Knob in Hole) to physically favor and disfavor the dimer formation. However, each of these strategies may not be applied to every molecule and therefore there is the need for more tools. Here, we describe the engineering of the Hinge region with a small number of mutations that are capable to alone successfully drive the heavy chain dimerization.
An isolated heteromultimer comprising a heterodimeric immunoglobulin hinge domain comprising a first immunoglobulin hinge domain polypeptide and a second immunoglobulin hinge domain polypeptide, wherein:
An isolated heteromultimer comprising a heterodimeric immunoglobulin hinge domain comprising a first immunoglobulin hinge domain polypeptide and a second immunoglobulin hinge domain polypeptide, wherein:
An isolated heteromultimer comprising a heterodimeric immunoglobulin hinge domain comprising a first immunoglobulin hinge domain polypeptide and a second immunoglobulin hinge domain polypeptide, wherein:
Dependencies are inferred from the claim text.