Reducing the immunogenicity of fusion proteins
AssigneeLexigen Pharmaceuticals Corp.
InventorsStephen D. Gillies, Jeffrey Way, Anita A. Hamilton
Life of this patent
Estimating the term…
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.
Claims37
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;
- 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.
A method for reducing the immunogenicity of a fusion protein, the method comprising changing a candidate T-cell epitope within a junction region spanning a fusion junction of a fusion protein to reduce the ability of the candidate T-cell epitope to interact with a T cell receptor:
- i. T-cell epitope
A method for reducing the immunogenicity of a fusion protein, the method comprising introducing a glycosylation site within the junction region spanning the fusion junction.
A method for reducing the immunogenicity of a fusion protein, the method comprising introducing a glycosylation site within 10 amino acids of the fusion junction.
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;
- and
- ii. assaying said fusion protein in an immunogenicity assay.
A fusion protein with reduced immunogenicity comprising
- a first protein;
- and,
- a second protein linked to said first protein via a fusion junction,
- wherein the amino acid sequence of a junction region surrounding the fusion junction is modified to remove a non-self T-cell epitope.
A method of reducing the immunogenicity of a fusion protein, the method comprising:
- i. identifying an amino acid in a peptide in a junction region, wherein the amino acid is selected from the group consisting of a leucine, a valine, an isoleucine, a methionine, a phenylalanine, a tryptophan and a tyrosine;
- and
- ii. changing the amino acid in the peptide, such that the ability of the peptide to bind to MHC Class II is reduced.
A nucleic acid encoding a fusion protein with reduced immunogenicity, the fusion protein comprising:
- i. a first protein;
- ii. a second protein linked to the first protein via a fusion junction, wherein the amino acid sequence of a junction region spanning the fusion junction is modified to remove a non-self T-cell epitope.
- iii.
Dependencies are inferred from the claim text.