Modification of antibody FcRn binding
AssigneeHoffmann-La Roche Inc.
InventorsThomas Emrich, Hubert Kettenberger, Thomas Kraft, Wolfgang Richter, Tilman Schlothauer
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Abstract
Herein is reported a method for providing a modified antibody with improved in vivo half-live, comprising the modification of the Fc-region of the antibody by introducing one or more mutations that change the binding of the Fc-region to human FcRn until the (relative) retention time of the modified antibody in an FcRn affinity chromatography is increased for more than 1 minute but not more than 5 minutes compared to the parent antibody.
Claims7
A method for producing an antibody with improved in vivo half-life, comprising the following steps:
- a) determining retention time of an antibody in an FcRn affinity chromatography, thereby defining an antibody retention time
- b) modifying the Fc-region of the antibody by introducing mutations that increase the binding of the Fc-region to human FcRn to obtain a modified antibody,
- c) determining retention time of the modified antibody in an FcRn affinity chromatography, thereby defining a modified antibody retention time,
- d) thereby producing the modified antibody with improved in vivo half-life when a relative retention time between the antibody retention time and the modified antibody retention time is more than about 3 minutes and less than about 4 minutes.
A method for producing an antibody with improved in vivo half-life, comprising the following steps:
- a) determining a retention time of a reference antibody in an FcRn affinity chromatography, thereby defining a reference antibody retention time, wherein the reference antibody is an anti-Her3;
- b) modifying the Fc-region of the reference antibody by introducing mutations that increase the binding of the Fc-region to human FcRn to obtain a modified antibody;
- c) determining a retention time of the modified antibody in an FcRn affinity chromatography, thereby defining a modified antibody retention time;
- and
- d) thereby producing the modified antibody with improved in vivo half-life when a relative retention time between the reference antibody retention time and the modified antibody retention time is more than about 3 minutes and less than about 4 minutes.
Dependencies are inferred from the claim text.