Reducing the immunogenicity of fusion proteins
First Claim
1. A method for reducing the immunogenicity of a fusion protein, the method comprising:
- i. identifying a candidate T-cell epitope within a junction region spanning a fusion junction of a fusion protein, the fusion protein comprising an immunoglobulin moiety fused to a non-immunoglobulin moiety; and
ii. making one or more amino acid substitutions or deletions within the junction region to reduce the ability of the candidate T-cell epitope to interact with a T cell receptor.
3 Assignments
0 Petitions
Accused Products
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.
-
Citations
39 Claims
-
1. A method for reducing the immunogenicity of a fusion protein, the method comprising:
-
i. identifying a candidate T-cell epitope within a junction region spanning a fusion junction of a fusion protein, the fusion protein comprising an immunoglobulin moiety fused to a non-immunoglobulin moiety; and
ii. making one or more amino acid substitutions or deletions within the junction region to reduce the ability of the candidate T-cell epitope to interact with a T cell receptor. - View Dependent Claims (2, 14, 15, 16, 36, 39)
-
-
3-8. -8. (canceled)
-
9. A method for reducing the immunogenicity of a fusion protein, the method comprising the steps of:
-
i. providing a fusion protein with a junction region comprising a substituted amino acid, the fusion protein comprising an immunoglobulin moiety fused to a non-immunoglobulin moiety; and
ii. assaying said fusion protein in an immunogenicity assay. - View Dependent Claims (10, 13)
-
-
11-12. -12. (canceled)
-
17. (canceled)
-
18. A fusion protein with reduced immunogenicity comprising:
-
a non-immunoglobulin protein and an immunoglobulin protein fused to said non-immunoglobulin protein via a fusion junction, wherein the amino acid sequence of a junction region surrounding the fusion junction is modified by substitution or deletion of one or more amino acids to remove a non-self T-cell epitope. - View Dependent Claims (26, 27, 31, 32, 33, 38)
-
-
19-25. -25. (canceled)
-
28-30. -30. (canceled)
-
34-35. -35. (canceled)
-
37. (canceled)
Specification