Reducing the immunogenicity of fusion proteins
First Claim
Patent Images
1. A modified fusion protein produced by:
- (i) identifying a candidate T-cell epitope within a junction region spanning a fusion junction of a fusion protein comprising an IgG region; and
, (ii) changing an amino acid within the junction region to reduce the ability of the candidate T-cell epitope to interact with a T-cell receptor wherein the junction region comprises an IgG region comprising an ATAT amino acid sequence (amino acids 3-6 of SEQ ID NO;
6) instead of an LSLS amino acid sequence (amino acids 3-6 of SEQ ID NO;
5).
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Abstract
Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.
218 Citations
2 Claims
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1. A modified fusion protein produced by:
-
(i) identifying a candidate T-cell epitope within a junction region spanning a fusion junction of a fusion protein comprising an IgG region; and
,(ii) changing an amino acid within the junction region to reduce the ability of the candidate T-cell epitope to interact with a T-cell receptor wherein the junction region comprises an IgG region comprising an ATAT amino acid sequence (amino acids 3-6 of SEQ ID NO;
6) instead of an LSLS amino acid sequence (amino acids 3-6 of SEQ ID NO;
5).
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2. A modified fusion protein produced by changing a candidae T-cell epitope within a junction region spanning a fusion junction of a fusion protein comprising an IgG region to reduce the ability of the candidate T-cell epitope to interact with a T-cell receptor, wherein the junction region comprises an IgG region comprising an ATAT amino acid sequence (amino acids 3-6 of SEQ ID NO:
- 6) instead of an LSLS amino acid sequence (amino acids 3-6 of SEQ ID NO;
5).
- 6) instead of an LSLS amino acid sequence (amino acids 3-6 of SEQ ID NO;
Specification