Modified human brain-derived neutrophic factor (bdnf) with reduced immunogenicity

A method for manufacturing a modified molecule having the biological activity of human brain-derived neutrophic factor (BDNF) as defined in any of the claims of the above-cited claims comprising the following steps:

• (i) determining the amino acid sequence of the polypeptide or part thereof.
• (ii) identifying one or more potential T-cell epitopes within the amino acid sequence of the protein by any method including determination of the binding of the peptides to MHC molecules using in vitro or in silico techniques or biological assays;
• (iii) designing new sequence variants with one or more amino acids within the identified potential T-cell epitopes modified in such a way to substantially reduce or eliminate the activity of the T-cell epitope as determined by the binding of the peptides to MHC molecules using in vitro or in silico techniques or biological assays, or by binding of peptide-MHC complexes to T-cells;
• (iv) constructing such sequence variants by recombinant DNA techniques and testing said variants in order to identify one or more variants with desirable properties;
• and
• (v) optionally repeating steps (ii)-(iv).