Modified hirudin proteins and t-cell epitopes in hirudin
AssigneeMerck Patent GmbH
InventorsMatthew Baker, John Watkins
Life of this patent
Estimating the term…
Abstract
The invention concerns hirudin and in particular modified forms of hirudin with improved properties. The improved proteins contain amino acid substitutions at specific positions. The invention provides modified hirudin with improved biological activity concomitant with reduced immunogenic potential in the protein. The improved proteins are intended for therapeutic use in the treatment of diseases in humans.
Claims16
A modified hirudin molecule being substantially non-immunogenic or less immunogenic than non-modified wild-type hirudin and having the amino acid residue sequence of SEQ ID NO:
- 2:
- VVYTDCTESGQNX1CX2CEGSVX3CGQGNKCX4X5GSDGEKNQCX6TGEGTPX7X8ESHNX9GDX10EEIPEEYLQ
- wherein;
- X1=T or L
- X2=T or A or H or Q or T or L;
- X3=A or G or H or K or N or P or Q or R or V;
- X4=A or D or E or G or H or K or N or Q or R or S or T or I;
- X5=A or D or E or G or H or K or N or P or Q or R or S or T or L;
- X6=A or T or V;
- X7=T or K;
- X8=A or T or P;
- X9=E or N or R or D;
- X10=H or F
- and wherein the wild-type sequence of hirudin (in which X1=L, X2=L, X3=V, X4=I, X5=L, X6=V, X7=K, X8=P, X9=D and X10=F) is excluded.
A modified hirudin molecule having an amino acid residue sequence selected from the group consisting of SEQ ID NO:
- 4 through SEQ ID NO:
- 84, inclusive.
A peptide having the amino acid residue sequence CILGSDGEKNQCVTGEGTPKPESHNDGDFE (SEQ ID NO:
- 1) or a sequence consisting of at least 9 consecutive amino acid residues of SEQ ID NO:
- 1 having a potential MHC class II binding activity, wherein said peptide has a stimulation index of >1.8 in a biological assay of cellular proliferation and said index is taken as the value of cellular proliferation scored following stimulation by the peptide and divided by the value of cellular proliferation scored in control cells not in receipt of the peptide.
(canceled)
Dependencies are inferred from the claim text.