Increasing antibody affinity by altering glycosylation of immunoglobulin variable region
First Claim
1. A mutant antibody that comprises a mutant immunoglobulin chain, the mutant antibody having higher affinity for an antigen than a parent antibody that comprises a parent immunoglobulin chain, wherein the mutant immunoglobulin chain comprises an amino acid substitution that eliminates a variable region glycosylation site of the parent immunoglobulin chain, said elimination having the effect of increasing the affinity of the mutant antibody relative to the parent antibody.
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Abstract
The present invention provides methods for producing mutationally-altered immunoglobulins and compositions containing such mutationally-altered immunoglobulins, wherein the mutationally-altered immunoglobulins have at least one mutation that alters the pattern of glycosylation in a variable region and thereby modifies the affinity of the immunoglobulin for a preselected antigen. The methods and compositions of the invention provide immunoglobulins that possess increased affinity for antigen. Such glycosylation-altered immunoglobulins are suitable for diagnostic and therapeutic applications.
193 Citations
20 Claims
- 1. A mutant antibody that comprises a mutant immunoglobulin chain, the mutant antibody having higher affinity for an antigen than a parent antibody that comprises a parent immunoglobulin chain, wherein the mutant immunoglobulin chain comprises an amino acid substitution that eliminates a variable region glycosylation site of the parent immunoglobulin chain, said elimination having the effect of increasing the affinity of the mutant antibody relative to the parent antibody.
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18. A method for producing a mutant antibody having higher affinity for an antigen relative to a parent antibody, the method comprising
introducing a mutation into a polynucleotide sequence encoding a chain of the parent antibody, whereby the polynucleotide encodes a mutant immunoglobulin chain comprising an amino acid substitution that eliminates a variable region glycosylation site of the parent immunoglobulin chain, expressing said mutant sequence in a cell; - and
determining that said elimination has the effect of increasing the affinity of the mutant antibody relative to the parent antibody. - View Dependent Claims (19, 20)
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Specification