US 2014/0178389 A1Published application

Il-1 binding proteins

AssigneeAbbVie Inc.

InventorsSusan E. LACY, Lorenzo BENATUIL, Meha CHHAYA, Emma FUNG, Renee MILLER, Ravi CHARI, Sarah J. HEIGHTON, Jacqueline G. BIXBY

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Abstract

The disclosure provides binding proteins that specifically bind to IL-1α and IL-1β. These binding proteins can be organized into DVD-Igs. These proteins can be used to modulate the activity of IL-1α and/or IL-1β and can be used for the treatment immunological diseases such as rheumatoid arthritis, osteoarthritis, psoriasis, multiple sclerosis, and other autoimmune diseases. In addition, their uses in the amelioration and/or treatment of pain in an individual suffering from a disease or disorder associated with IL-1 accumulation.

Claims41

Dependent claims

A binding protein that specifically binds to both IL-1α and IL-1β, said binding protein comprising an IL-1β 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-X2-G-V-S (SEQ ID NO:146), wherein;
X1 is D, E, H, V or Q and X2 is Y, F, D, N, H or S;
CDR-H2:
X3-I-X4-X5-X6-G-X7-T-X8-Y-N-S-P-L-K-S (SEQ ID NO:147), wherein:
X3 is L, V, R, G, F, W, M or I;
X4 is W, G, L, Y, S, R, E or A;
X5 is G, V, R, W, L, D or S;
X6 is G, R, V, W, S, L, I, E or D;
X7 is D, G, E, V, S, A, K, D, Y or Q;
and X8 is Y, F, S, D, V, T or H;
CDR-H3:
X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19M-D-Y (SEQ ID NO:148), wherein;
X9 is Q, D, K, P, H, A, Y, V or T;
X10 is R, T, M, S, I, W, P, N or K;
X11 is T, R, N, Y, W, V, M or K;
X12 is L, M, R, I, G, W, Q, H, F or A;
X13 is W, S, G, R, V, L, K, A, Y or T;
X14 is G, A, R, V, T, P, N, E or D;
X15 is Y, F, N, D, H or S;
X16 is D, Q, H, A, V, L or K;
X17 is L, I, F, S, M or G;
X18 is Y, N, D, V or D;
and X19 is G, A, R, D or W;
CDR-L1:
X20-X21-S-X22-D-I-X23-X24-X25-M-N (SEQ ID NO:149), wherein:
X20 is I or Q;
X21 is T or A;
X22 is T or Q;
X23 is D, P, Y, N, Q, or L;
X24 is V, P, A or F;
and X25 is D, A, P, N, Y or V;
CDR-L2 have the sequence X26-X27-X28-X29-L-X30-X31 (SEQ ID NO:150), wherein:
X26 is S or Y;
X27 is Q, H, P, K or R;
X28 is G or A;
X29 is N or S;
X30 is T, S, I, M or A;
and X31 is P, L, S or T;
and
CDR-L3:
X32-Q-X33-X34-X35-X36-X37-L-T (SEQ ID NO:151), wherein;
X32 is L or Q;
X33 is S, W, R, K, G or V;
X34 is D, G, K or V;
X35 is N, E, R, M or G;
X36 is L, G, D or F;
and X37 is P or A.

46 more elements

A binding protein that specifically binds to both IL-1α and IL-1β, comprising first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein:

VD 1 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;
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 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs:
30, 31, 32, 33 and 34;
and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
128;
wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs:
36, 37, 38, 39 and 40;
and VD2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:129;
wherein the VD1 of the first polypeptide chain and the VD1 of the second polypeptide chain form a IL-1β antigen binding domain;
and
wherein the VD2 of the first polypeptide chain and the VD2 of the second polypeptide chain form a IL-1α antigen binding domain.

22 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/940,506Filed 12 Jul 2013
Priority: 12 Jul 2012
Published: 26 Jun 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07K 16/245
Interleukins [IL]: il-1
A61P 19/02
Drugs for skeletal disorders: for joint disorders, e.g. arthritis, arthrosis
A61K 2039/505
Medicinal preparations containing antigens or antibodies: comprising antibodies
C07K 2317/24
Characterized by taxonomic origin: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered