Claims
- 1. A mutant human interleukin-3 (hIL-3) polypeptide comprising a modified (15-125)hIL-3 amino acid sequence selected from the group consisting of:
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 88];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 89];
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 90];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 91];
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 92];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 117S, 120H and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 93];
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 117S, 120H and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 94];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 95];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 117S, 120H and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 96];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 264];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 265];
- (18I, 25H, 29R, 32N, 37P, 42S, 45V, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 266];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45V, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 267];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45V, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 268];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 49I, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 269];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 49L, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 270];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 49D, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 271];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45V, 49I, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 272];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45V, 49I, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 273];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45V, 49L, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 274];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45V, 49L, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 275];
- (18I, 23A, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 280];
- (18I, 25H, 29R, 32A, 37P, 42N, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 281];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 282];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 283];
- (18I, 25H, 29R, 32A, 37P, 42A, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 284];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 285];
- (18I, 25H, 29R, 32A, 37P, 42S, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 286];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 291];
- (18I, 25H, 29V, 32R, 34S, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 292];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82W, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 293];
- (18I, 23A, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 294];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 295];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 50D, 51R, 55L, 56S, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 296];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 297];
- (18I, 25H, 29R, 32A, 34S, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93s, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 298];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 299];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45M, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 300];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 301];
- (18I, 23A, 25H, 29V, 32R, 34S, 37P, 42D, 45V, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E);-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 302];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 100R, 101M, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 303];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82W, 87S, 93S, 98I, 101A, 105Q, 109E, 100R, 101M, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 304];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 305];
- (18I, 23A, 25H, 29V, 32R, 34S, 37P, 42D, 45V, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 306];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 308];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 309];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 310];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 56S 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 311];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 56S, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 331];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 312]; and
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116W, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 313].
- 2. A polypeptide according to claim 1, further comprising an Alanine residue immediately preceding said modified (15-125)hIL-3 amino acid sequence.
- 3. A polypeptide according to claim 1, further comprising Methionine-Alanine residues immediately preceding said modified (15-125)hIL-3 amino acid sequence.
- 4. The polypeptide of claim 1 selected from the group consisting of:
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 88];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 89]; and
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 90].
- 5. A polypeptide according to claim 4, further comprising an Alanine residue immediately preceding said modified (15-125)hIL-3 amino acid sequence.
- 6. A polypeptide according to claim 4, further comprising Methionine-Alanine residues immediately preceding said modified (15-125)hIL-3 amino acid sequence.
- 7. A mutant human interleukin-3 (hIL-3) polypeptide consisting of a modified (15-125)hIL-3 amino acid sequence selected from the group consisting of:
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E,
- 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 88];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 89];
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 90];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 91];
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 92];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 117S, 120H and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 93];
- (18I, 25H, 29V, 32A, 37S, 42S, 45M, 51R, 55L, 59L, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 117S, 120H and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 94];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 95];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82V, 87S, 93S, 98T, 101A, 105Q, 109E, 116V, 117S, 120H and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 96];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87s, 93S, 98I, 101A, 105Q,
- 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 264];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 265];
- (18I, 25H, 29R, 32N, 37P, 42S, 45V, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 266];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45V, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 267];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45V, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 268];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 49I, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 269];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 49L, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 270];
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 49D, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 271];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45V, 49I, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 272];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45V, 49I, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 273];
- (18I, 19A, 25H, 29R, 32N, 37P, 42S, 45V, 49L, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 274];
- (18I, 19I, 25H, 29R, 32N, 37P, 42S, 45V, 49L, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 981, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 275];
- (18I, 23A, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 280];
- (18I, 25H, 29R, 32A, 37P, 42N, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 281];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 282];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 283];
- (18I, 25H, 29R, 32A, 37P, 42A, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 284];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 285];
- (18I, 25H, 29R, 32A, 37P, 42S, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 286];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 291];
- (18I, 25H, 29V, 32R, 34S, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 292];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82W, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 293];
- (18I, 23A, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 294];
- (18I, 25H, 29R, 32A, 37P, 42S, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 295];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 50D, 51R, 55L, 56S, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 296];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 297];
- (18I, 25H, 29R, 32A, 34S, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 298];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 299];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45M, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 SEQ ID NO: 300];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 301];
- (18I, 23A, 25H, 29V, 32R, 34S, 37P, 42D, 45V, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E);-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 302];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 100R, 101M, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 303];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82W, 87S, 93S, 98I, 101A, 105Q, 109E, 100R, 101M, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 304];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 305];
- (18I, 23A, 25H, 29V, 32R, 34S, 37P, 42D, 45V, 46S, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 306];
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 308];
- (18I, 25H, 29R, 32A, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 309];
- (18I, 25H, 29R, 32A, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 310];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45V, 46S, 50D, 51R, 55L, 56S 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 311];
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 56S, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 331]
- (18I, 23A, 25H, 29R, 32A, 34S, 37P, 42D, 45M, 46S, 50D, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 312]; and
- (18I, 25H, 29R, 32A, 37P, 42A, 45V, 51R, 55L, 60S, 62V, 67N, 69E, 73G, 76A, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 112Q, 116W, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 313].
- 8. A polypeptide consisting of an Alanine residue and a modified (15-125)hIL-3 amino acid sequence according to claim 7, wherein said Alanine residue immediately precedes said modified (15-125)hIL-3 amino acid sequence.
- 9. A polypeptide consisting of a Methionine-Alanine dipeptide fragment and a modified (15-125)hIL-3 amino acid sequence according to claim 7, wherein said Methionine-Alanine fragment immediately precedes said modified (15-125)hIL-3 amino acid sequence.
- 10. A mutant human interleukin-3 (hIL-3) polypeptide comprising the following modified (15-125)hIL-3 amino acid sequence:
- (18I, 25H, 29R, 32N, 37P, 42S, 45M, 51R, 55T, 59L, 62V, 67H, 69E, 73G, 76A, 79R, 82Q, 87S, 93S, 98I, 101A, 105Q, 109E, 116V, 120Q and 123E)-(15-125)hIL-3, [residues 3-113 of SEQ ID NO: 89].
- 11. A polypeptide according to claim 10, further comprising an Alanine residue immediately preceding said modified (15-125)hIL-3 amino acid sequence.
- 12. A polypeptide according to claim 10, further comprising Methionine-Alanine residues immediately preceding said modified (15-125)hIL-3 amino acid sequence.
- 13. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 1.
- 14. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 2.
- 15. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 3.
- 16. A nucleic acid molecule according to claim 15 selected from the group consisting of:
- a DNA having a nucleotide sequence shown in SEQ ID NO: 97;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 100;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 103;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 161;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 98;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 99;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 101;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 102;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 104;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 105;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 332;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 333;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 334;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 335;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 336;
- a DNA having a nucleotide sequence shown SEQ ID NO: 337;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 338;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 339;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 340;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 341;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 342;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 343;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 348;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 349;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 350;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 352;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 353;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 354;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 359;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 360;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 361:
- a DNA having a nucleotide sequence shown in SEQ ID NO: 362;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 363;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 364;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 365;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 366;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 367;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 368;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 369;
- a DNA having a nucleotide sequence shown SEQ ID NO: 370;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 371;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 372;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 373;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 374;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 376;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 377;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 378;
- a DNA having a nucleotide sequence shown SEQ ID NO: 379;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 380;
- a DNA having a nucleotide sequence shown in SEQ ID NO: 381; and
- a DNA having a nucleotide sequence shown in SEQ ID NO: 382.
- 17. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 4.
- 18. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 5.
- 19. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 6.
- 20. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 7.
- 21. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 8.
- 22. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 9.
- 23. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 10.
- 24. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 11.
- 25. A nucleic acid molecule encoding the mutant hIL-3 polypeptide of claim 12.
- 26. A replicable vector comprising the nucleic acid molecule of claim 13, 14, 15, 16, 17, 18, 19, 20 ,21, 22, 23, 24, or 25.
- 27. A host cell comprising said vector of claim 26.
- 28. A method of producing a mutant hIL-3 polypeptide comprising the steps of cultivating said host cell of claim 27 under conditions suitable for the expression of said polypeptide, and recovering said polypeptide.
- 29. A method of stimulating the production of hematopoietic cells in a patient comprising the step of administering the polypeptide of claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 to said patient.
- 30. A composition comprising the mutant hIL-3 polypeptide of claim 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, or 12 and a pharmaceutically acceptable carrier.
- 31. A method of stimulating the production of hematopoietic cells in a patient comprising the step of administering the composition of claim 30 to said patient.
Parent Case Info
This is a continuation-in-part of U.S. application Ser. No. 07/981,044 filed Nov. 24, 1992, now abandoned, which is incorporated herein by reference.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US93/11197 |
11/22/1993 |
|
|
4/6/1995 |
4/6/1995 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO94/12638 |
6/9/1994 |
|
|
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
4877729 |
Clark et al. |
Oct 1990 |
|
4959455 |
Clark et al. |
Oct 1990 |
|
5032395 |
Clark et al. |
Jul 1991 |
|
5166322 |
Shaw et al. |
Nov 1992 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
275598A1 |
Jul 1988 |
EPX |
275598 |
Jul 1988 |
EPX |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
981044 |
Nov 1992 |
|