Patent ID: 6107465
Filing Date: 2000-08-22
Classification: A61K,C07K,Y10S

Abstract:
An interleukin-1.beta. mutant, wherein said mutant contains a mutation in the amino acid sequence of interleukin-1.beta. represented by Formula (A), and wherein said mutation is selected from the group consisting of a), b), c) and d) as defined below,Formula (A) 5 10 Ala-Pro-Val-Arg-Ser-Leu-Asn-Cys-Thr-Leu- 15 20 Arg-Asp-Ser-Gln-Gln-Lys-Ser-Leu-Val-Met- 25 30 Ser-Gly-Pro-Tyr-Glu-Leu-Lys-Ala-Leu-His- 35 40 Leu-Gln-Gly-Gln-Asp-Met-Glu-Gln-Gln-Val- 45 50 Val-Phe-Ser-Met-Ser-Phe-Val-Gln-Gly-Glu- 55 60 Glu-Ser-Asn-Asp-Lys-Ile-Pro-Val-Ala-Leu- 65 70 Gly-Leu-Lys-Glu-Lys-Asn-Leu-Tyr-Leu-Ser- 75 80 Cys-Val-Leu-Lys-Asp-Asp-Lys-Pro-Thr-Leu- 85 90 Gln-Leu-Glu-Ser-Val-Asp-Pro-Lys-Asn-Tyr- 95 100 Pro-Lys-Lys-Lys-Met-Glu-Lys-Arg-Phe-Val- 105 110 Phe-Asn-Lys-Ile-Glu-Ile-Asn-Asn-Lys-Leu- 115 120 Glu-Phe-Glu-Ser-Ala-Gln-Phe-Pro-Asn-Trp- 125 130 Tyr-Ile-Ser-Thr-Ser-Gln-Ala-Glu-Asn-Met- 135 140 Pro-Val-Phe-Leu-Gly-Gly-Thr-Lys-Gly-Gly- 145 150 Gln-Asp-Ile-Thr-Asp-Phe-Thr-Met-Gln-Phe- Val-Ser-Ser a) at least one amino acid residue selected from the group consisting of Ala at the 1-position, Val at the 3-position, Arg at the 4-position, Ser at the 5-position, Cys at the 8-position, Arg at the 11-position, His at the 30-position, Cys at the 71-position, Lys at the 93-position, Lys at the 97-position, Arg at the 98-position, Phe at the 99-position, Lys at the 103-position, Trp at the 120-position, Tyr at the 121-position and Ser at the 153-position is deficient or replaced by another amino acid;b) the amino acid sequence of Ala at the 1-position to Thr at the 9-position or at least one amino acid residue in the 1-position through 9-position sequence is deficient, with the proviso that at least one amino acid residue selected from the group consisting of Ala at the 1-position, Val at the 3-position, Arg at the 4-position, Ser at the 5-position and Cys at the 8-position is deficient;c) the amino acid sequence of Lys at the 103-position to Ser at the 153-position or at least one amino acid residue in the 103-position through 153-position sequence is deficient, with the proviso that at least one amino acid residue selected from the group consisting of Lys at the 103-position, Trp at the 120-position, Tyr at the 121-position and Ser at the 153-position is deficient;d) Met, or the amino acid sequence of Met at the 1'-position to Asp at the 116'-position represented by the following formula (B), or a portion of the sequence of formula (B) toward its C terminal, is attached to the N terminal of the sequence of formula (A)Formula (B) 5' 10' Met-Ala-Glu-Val-Pro-Glu-Leu-Ala-Ser-Glu- 15' 20' Met-Met-Ala-Tyr-Tyr-Ser-Gly-Asn-Glu-Asp- 25' 30' Asp-Leu-Phe-Phe-Glu-Ala-Asp-Gly-Pro-Lys- 35' 40' Gln-Met-Lys-Cys-Ser-Phe-Gln-Asp-Leu-Asp- 45' 50' Leu-Cys-Pro-Leu-Asp-Gly-Gly-Ile-Gln-Leu- 55' 60' Arg-Ile-Ser-Asp-His-His-Tyr-Ser-Lys-Gly- 65' 70' Phe-Arg-Gln-Ala-Ala-Ser-Val-Val-Val-Ala- 75' 80' Met-Asp-Lys-Leu-Arg-Lys-Met-Leu-Val-Pro- 85' 90' Cys-Pro-Gln-Thr-Phe-Gln-Glu-Asn-Asp-Leu- 95' 100' Ser-Thr-Phe-Phe-Pro-Phe-Ile-Phe-Glu-Glu- 105' 110' Glu-Pro-Ile-Phe-Phe-Asp-Thr-Trp-Asp-Asn- 115' Glu-Ala-Tyr-Val-His-Asp