26-03-2020 дата публикации
Номер: US20200095328A1
Принадлежит:
23andMe, Inc.
The present invention provides binding proteins, such as antibodies and antigen-binding fragments, which specifically bind to human interleukin-1 receptor accessory protein (hu-IL1RAP) and fully block the IL-1, IL-33, and IL-36 intracellular signaling pathways. Compositions comprising such binding proteins and methods of making and using such binding proteins are also provided. 1. An anti-IL1RAP antibody comprising: (i) a first light chain hypervariable region (HVR-L1) , a second light chain hypervariable region (HVR-L2) , and a third light chain hypervariable region (HVR-L3) , and/or (ii) a first heavy chain hypervariable region (HVR-H1) , a second heavy chain hypervariable region (HVR-H2) , and a third heavy chain hypervariable region (HVR-H3); wherein:(a) HVR-L1 comprises an amino acid sequence RASENIXXNXX (SEQ ID NO: 10), wherein X at position 7 is Y or W, X at position 8 is S, H, K, L, M, N, Q, R, or Y, X at position 10 is L, A, G, I, M, N, Q, S, T, V, or Y, and X at position 11 is A, G, N, S, or T;(b) HVR-L2 comprises an amino acid sequence GXXNXAD (SEQ ID NO: 36), wherein X at position 2 is A, D, E, F, G, H, I, K, L, M, N, Q, R, S, T, V, W, or Y, X at position 3 is K, G, or N, and X at position 5 is L, F, H, W, or Y;(c) HVR-L3 comprises an amino acid sequence XXFXTXPRT (SEQ ID NO: 62), wherein X at position 1 is Q or S, X at position 2 is H or S, X at position 4 is W, A, F, G, H, I, K, L, M, V, or Y, and X at position 6 is T, I, or V;(d) HVR-H1 comprises an amino acid sequence XXXXXXX (SEQ ID NO: 77), wherein X at position 1 is F, A, D, E, G, H, I, K, M, N, P, Q, R, S, T, W, or Y, X at position 2 is S, E, G, K, P, Q, R, or T, X at position 3 is N, D, E, G, K, Q, or R, X at position 4 is Y, A, D, E, H, S, or V, X at position 5 is A, N, or S, X at position 6 is M, V, or W, and X at position 7 is S, or G;(e) HVR-H2 comprises an amino acid sequence TXXXXXXXXYXLXDVKG (SEQ ID NO: 140), wherein X at position 2 is V, A, N, or S, X at position 3 is T or S, X at ...
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