Stabilized polypeptide compositions
AssigneeBiogen Idec MA Inc.
InventorsScott Glaser, Stephen Demarest, Brian Robert Miller, William B. Snyder, Xiufeng Wu, Norman Wang, Lisa J. Croner, Alexey Alexandrovich Lugovsky
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Abstract
The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized scFv and methods for making such stabilized molecules.
Claims28
1-60. (canceled)
A method for designing a stabilized antibody or antigen binding fragment thereof, which comprises a stabilized VH domain and a stabilized VL domain derived from a VH domain and a VL domain of a candidate antibody, wherein said method comprises:
- (a) providing a curated reference set amino acid sequences which belong to immunoglobulin superfamily polypeptides;
- (b) aligning said reference set of amino acid sequences to generate an aligned set;
- (c) calculating covariation between two or more amino acid positions in the aligned set to generate a covariation dataset;
- (d) identifying non-covarying amino acids in said candidate antibody VH domain or said candidate antibody VL domain, wherein said non-covarying amino acids fail to satisfy one or more covariations in the covariation dataset;
- and
- (e) substituting one or more of said non-covarying amino acids in the candidate antibody VH domain or candidate antibody VL domain with amino acids found at the corresponding amino acid positions in the aligned set which satisfy covariations in the covariation dataset, thereby making a stabilized antibody and antigen binding fragment thereof with an improved biophysical property.
An antibody or antigen binding fragment thereof, which is designed by the method of claim 1.
Dependencies are inferred from the claim text.