Fibronectin binding domains with reduced immunogenicity
AssigneeBristol-Myers Squibb Company
InventorsJonathan Davis, Dasa Lipovsek, Ray Camphausen
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Abstract
Fibronectin type III (10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative 10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes 10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are 10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.
Claims45
A polypeptide comprising a human fibronectin type 3 tenth (10Fn3) domain, which comprises AB, BC, CD, DE, EF, and FG loops and β-strands A, B, C, D, E, F, and G, wherein the 10Fn3 domain comprises modifications only in the amino acid sequence of the FG loop relative to the FG loop of the wild-type human 10Fn3 domain as set forth in SEQ ID NO:
- 6, and in the amino acid sequence of the CD loop relative to the corresponding loop of the wild-type human 10Fn3 domain as set forth in SEQ ID NO:
- 6, wherein the modifications contribute to binding a target.
Dependencies are inferred from the claim text.