IL-1 Binding Proteins
AssigneeAbbVie Inc.
InventorsChengbin WU, Dominic J. AMBROSI, Chung-ming HSIEH, Tariq GHAYUR
Life of this patent
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Abstract
Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.
Claims17
A binding protein comprising first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein:
- VD1 is a first heavy chain variable domain;
- VD2 is a second heavy chain variable domain;
- C is a heavy chain constant domain;
- X1 is a linker with the proviso that it is not CH1;
- X2 is an Fc region;
- and
- n is independently 0 or 1;
- and
- wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n,
- wherein:
- VD1 is a first light chain variable domain;
- VD2 is a second light chain variable domain;
- C is a light chain constant domain;
- X1 is a linker with the proviso that it is not CH1;
- X2 does not comprise an Fc region;
- and
- n is independently 0 or 1;
- wherein, in said first polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 60-148, 196, 198, 200, 202, 204, 206, 208 and 210;
- and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 213 and 227;
- wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 149-189, 197, 199, 201, 203, 205, 207, 209 and 211;
- and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 216 and 229;
- and
- wherein the binding protein binds human IL-1β and human IL-1α.
A binding protein comprising first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein:
- VD1 is a first heavy chain variable domain;
- VD2 is a second heavy chain variable domain;
- C is a heavy chain constant domain;
- X1 is a linker with the proviso that it is not CH1;
- X2 is an Fc region;
- and
- n is independently 0 or 1;
- and
- wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n,
- wherein:
- VD1 is a first light chain variable domain;
- VD2 is a second light chain variable domain;
- C is a light chain constant domain;
- X1 is a linker with the proviso that it is not CH1;
- X2 does not comprise an Fc region;
- and
- n is independently 0 or 1;
- wherein, in said first polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 213 and 227;
- and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 60-148, 196, 198, 200, 202, 204, 206, 208 and 210;
- wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 216 and 229;
- and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 149-189, 197, 199, 201, 203, 205, 207, 209 and 211;
- and wherein the binding protein binds human IL-1β and human IL-1α.
3-30. (canceled)
32-45. (canceled)
49-51. (canceled)
A binding protein comprising an antigen binding domain, said binding protein capable of binding human IL-1β, said antigen binding domain comprising six CDRs:
- CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, as defined below:
- CDR-H1:
- X1-Y-D-M-S(SEQ ID NO:190), wherein;
- X1 is S, K or R;
- CDR-H2:
- Y-X2-S-X4-G-G-X7-G-T-Y-Y-P-D-X14-X15-K-G (SEQ ID NO:191), wherein;
- X2 is I or V;
- X4 is S or H;
- X7 is G or A;
- X14 is T or S;
- and
- X15 is V or A;
- CDR-H3:
- G-G-V-X4-K-G-X7-F-D-X10 (SEQ ID NO:192), wherein;
- X4 is T or Y;
- X7 is Y or C;
- and
- X10 is V, E, L, M, Q, or Y;
- CDR-L1:
- (SEQ ID NO:193), wherein;
- X7 is H, Y, or W;
- X8 is N, G, T, Q, E, H, D, or K;
- X9 is Y or W;
- and
- X11 is T, A, or N;
- CDR-L2:
- (SEQ ID NO:194), wherein;
- X1 is N, Q, or D;
- X4 is T, N, I, E, or S;
- X6 is A, M, or E;
- and
- X7 is D, E, S, or A;
- and
- CDR-L3:
- Q-X2-F-W-X5-X6-P-X8-X9 (SEQ ID NO:195), wherein;
- X2 is H or Q;
- X5 is S, N, T, K, R, or M;
- X6 is I or L;
- X8 is Y or A;
- and
- X9 is T, I, and N;
- except that when CDR-H1 is S-Y-D-M-S(SEQ ID NO:17), then:
- CDR-H2 cannot be Y-I-S-S-G-G-G-G-T-Y-Y-P-D-T-V-K-G (SEQ ID NO:18);
- CDR-H3 cannot be G-G-V-T-K-G-Y-F-D-V (SEQ ID NO:19);
- CDR-L1 cannot be R-A-S-G-N-I-H-N-Y-L-T (SEQ ID NO:20);
- CDR-L2 cannot be N-A-K-T-L-A-D (SEQ ID NO:21);
- and
- CDR-L3 cannot be Q-H-F-W-S-I-P-Y-T (SEQ ID NO:22).
53-101. (canceled)
103-116. (canceled)
120-122. (canceled)
Dependencies are inferred from the claim text.