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US 2008/0075715 A1Published application
Modified anti-cd52 antibody
AssigneeMerck Patent GmbH
InventorsFRANCIS CARR, Anita Hamilton
Life of this patent
Estimating the term…
Abstract
The present invention provides for modified forms of anti-CD52 antibodies with reduced numbers of potential T-cell epitopes that are expected to display decreased immunogenicity.
Claims14
An anti-CD52 antibody comprising a heavy chain comprising a V-region heavy chain comprising a substituted variant of SEQ ID NO:
- 1 with one or more of the following substitutions wherein the numbering of amino acid residues relates to those of SEQ ID NO:
- 1:
- substitution of Lys at amino acid residue 3 with Gln;
- Leu at amino acid residue 5 with Ala, Cys, Asn, Asp, Gln, Glu, Gly, His, Lys, Pro, Arg, Ser, or Thr;
- Val at amino acid residue 12 with Asn, Asp, Glu, His, Lys, Pro, Gln, Arg, Ser, or Thr;
- Gln at amino acid residue 13 with Ala, Phe, His, Lys, Asn, Pro, Gln, Arg, Ser, Thr;
- Gly at amino acid residue 15 with Asp, His, Pro, Gln, Arg, Ser, Thr;
- Ser at amino acid residue 17 with Gly, Met, Pro or Trp;
- Met at amino acid residue 18 with Arg, Gly, Pro, Leu;
- Arg at amino acid residue 19 with Ala, Cys, Phe, Gly, Ile, Leu, Met, Pro, Val, Trp, or Tyr;
- Leu at amino acid residue 20 with Ala, Cys, Phe, Gly, His, Ile, Lys, Asn, Asp, Met, Gln, Glu, Pro, Arg, Ser, Thr, Val Trp, or Tyr;
- Ser at amino acid residue 21 with Pro;
- Ala at amino acid residue 23 with Asp, Asn, Glu, Gln, Gly, His, Lys, Pro, Arg, Ser, Thr;
- Ser at amino acid residue 25 with Phe, Gly, Leu, Pro, Trp or Tyr;
- Gly at amino acid residue 26 with Asp, Asn, Glu, Gln, His, Lys, Pro, Arg, Ser, Thr, Trp or Tyr;
- Asp at amino acid residue 31 with Ala, Phe, Gly, Ile, Met, Pro, Val, Trp, or Tyr;
- Tyr at amino acid residue 33 with Ala, Gly, Met, or Pro;
- Asn at amino acid residue 35 with Pro;
- Trp at amino acid residue 36 with Ala, Asp, Glu, Gly, His, Lys, Asn, Pro, Gln, Arg, Ser, or The;
- Ile at amino acid residue 37 with Val;
- Arg at amino acid residue 38 with Phe, His, Pro, or Tyr;
- Pro at amino acid residue 40 with Ala;
- Ala at amino acid residue 41 with Asp, Asn, Glu, Gln, His, Lys, Pro, Arg, Ser, The or Trp;
- Gly at amino acid residue 42 with Ile, Pro, Thr, Tyr;
- Ala at amino acid residue 44 with Gly, His, Asn, Pro, Gln, Ser, Thr, Trp, Tyr;
- Pro at amino acid residue 45 with Leu;
- Leu at amino acid residue 48 with Ile or Val;
- Thr at amino acid residue 71 with Phe, Leu, Pro, Trp, or Tyr;
- Ile at amino acid residue 72 with Asp, Glu, His, Lys, Asn, Pro, Gln, Arg, Ser, or Thr;
- Ser at amino acid residue 73 with Ala, Gly, or Pro;
- Arg at amino acid residue 74 with Ala, Phe, Gly, Ile, Met, Pro, Trp, or Tyr;
- Asn at amino acid residue 76 with Ala, Gly, Met, Pro, Trp or Tyr;
- Thr at amino acid residue 77 with Ala, His, Ile, Pro or Ser;
- Gln at amino acid residue 78 with Lys;
- Asn at amino acid residue 79 with Ala, Phe, Gly, Ile, Met, Pro, Val, Trp or Tyr;
- Met at amino acid residue 80 with Ala, Asp, Glu, Gly, His, Lys, Asn, Pro, Gln, Arg, Thr, or Ser;
- Tyr at amino acid residue 82 with Ala, Asp, Glu, Gly, His, Lys, Asn, Pro, Gln, Arg, Ser or Thr;
- Gln at amino acid residue 84 with Ala, Phe, Gly, Ile, Leu, Met, Pro, Val, Trp or Tyr;
- Met at amino acid residue 85 with Ala, Asp, Glu, Gly, His, Lys, Asn, Pro, Gln, Arg, Ser or Thr;
- Thr at amino acid residue 87 with Ser;
- Leu at amino acid residue 88 with Asp, Glu, Gly, His, Lys, Asn, Pro, Gln, Arg, Ser, Thr;
- Arg at amino acid residue 89 with Phe, Pro, Trp, Tyr;
- Ala at amino acid residue 90 with Asn, Asp, Glu, Gln, His, Lys, Pro, Arg, Ser, Thr, Trp or Tyr;
- Glu at amino acid residue 91 with Pro;
- Asp at amino acid residue 92 with Ala, Phe, Gly, Ile, Leu, Met, Pro, Val, Trp, Tyr;
- Thr at amino acid residue 95 with Val;
- Asp at amino acid residue 109 with Ala, Phe, Gly, Ile, Leu, Met, Pro, Val, Trp or Tyr;
- Trp at amino acid residue 111 with Ala, Asp, Glu, Gly, His, Lys, Asn, Pro, Gln, Arg, Ser, or Thr;
- Gly at amino acid residue 114 with His, Pro, Ser, or Thr;
- Val at amino acid residue 115 with Thr;
- Met at amino acid residue 116 with Thr, Phe, Ile, Leu, Pro, Val, Trp or Tyr;
- Val at amino acid residue 117 with Ala, Phe, Gly, Ile, Met, Pro, Trp or Tyr;
- and comprising a V-region light chain comprising a light chain comprising a substituted variant of SEQ ID NO:
- 2 with one or more of the following substitutions wherein the numbering of amino acid residues relates to those of SEQ ID NO:
- 2:
- substitution of Lys at amino acid residue 3 with Gln Phe at amino acid residue 10 with Ala, Asp, Asn, Glu, Gln, Gly, His, Lys, Pro, Arg, Ser or Thr;
- Val at amino acid residue 15 with Ala, Gly, His or Pro;
- Asp at amino acid residue 17 with Pro;
- Val at amino acid residue 19 with Pro or Trp;
- Leu at amino acid residue 21 with Pro or Ile;
- Asn at amino acid residue 22 with Thr;
- Lys at amino acid residue 24 with Arg;
- Leu at amino acid residue 33 with Ala, Asp, Asn, Gln, Glu, Gly, His, Lys, Pro, Arg, Ser or Thr;
- Leu at amino acid residue 40 with Asp, Asn, Gln, Glu, Gly, His, Lys, Pro, Arg, Ser or Thr;
- Glu at amino acid residue 42 with Lys;
- Ser at amino acid residue 43 with Ala;
- Leu at amino acid residue 46 with Ser;
- Thr at amino acid residue 56 with Ala, Phe, Gly, Ile, Met, Pro, Ser, Trp or Tyr;
- Ile at amino acid residue 58 with Ala;
- Gly, Met, Pro or Val;
- Ser at amino acid residue 60 with Ala, Phe;
- Gly, Ile, Met, Pro;
- Trp or Tyr;
- Arg at amino acid residue with Pro;
- Ser at amino acid residue 63 with Phe, Leu, Pro, Trp or Tyr;
- Gly at amino acid residue 64 with Asp, Asn, Gln, Glu, His, Lys, Pro, Arg, Ser or Thr;
- Leu at amino acid residue 78 with Asp, Asn, Gln, Glu, Gly, His, Lys, Pro, Arg, Ser, Thr;
- Val at amino acid residue 83 with Ala, Asp, Asn, Glu, Gln, Gly, His, Ile, Lys, Pro, Arg, Ser, Thr;
- Phe at amino acid residue 87 with Tyr.
76 more elements
14-34. (canceled)
Dependencies are inferred from the claim text.