Il-10 muteins and fusion proteins thereof
AssigneeAmgen Inc.
InventorsHailing HSU, Ian FOLTZ, Marissa MOCK, Victor Mitch LUNA, Ming ZHANG, Sharon Lynn WANNBERG, Gamze Ozlem CAMDERE TAPIA, Timothy Patrick RILEY
Life of this patent
Estimating the term…
Abstract
The present disclosure relates, in general, to muteins of IL-10 that are stable as monomers, antigen binding proteins that bind to TREM-1, and antigen binding proteins comprising IL-10 muteins and antigen binding moieties, e.g., anti-TREM-1 antibodies, and compositions thereof. The disclosure also provides methods of treating inflammatory disease, such as inflammatory bowel disease or ulcerative colitis, using the compositions.
Claims22
-4. (canceled)
An antigen-binding protein, wherein the antigen-binding protein:
- a. is an antibody or antibody fragment;
- b. binds to human TREM-1 having the amino acid sequence set forth in SEQ ID NO:
- 20;
- c. comprises a light chain variable domain comprising:
- i. a light chain CDR1 amino acid sequence selected from SEQ ID NOS:
- 30, 50, 70, 90, 110, 130, 150, 170, 190, 210, 230, 250, 270, 290 and 2190;
- ii. a light chain CDR2 amino acid sequence selected from SEQ ID NOS:
- 31, 51, 71, 91, 111, 131, 151, 171, 191, 211, 231, 251, 271, 291 and 2191;
- iii. a light chain CDR3 amino acid sequence selected from SEQ ID NOS:
- 32, 52, 72, 92, 112, 132, 152, 172, 192, 212, 232, 252, 272, 292 and 2192;
- and
- d. comprises a heavy chain variable domain comprising:
- i. a heavy chain CDR1 amino acid sequence selected from SEQ ID NOS:
- 36, 56, 76, 96, 116, 136, 156, 176, 196, 216, 236, 256, 276, 296 and 2196;
- ii. a heavy chain CDR2 amino acid sequence selected from SEQ ID NOS:
- 37, 57, 77, 97, 117, 137, 157, 177, 197, 217, 237, 257, 277, 297 and 2197;
- and
- iii. a heavy chain CDR3 amino acid sequence selected from SEQ ID NOS:
- 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, 238, 258, 278, 298 and 2198.
-34. (canceled)
-40. (canceled)
An isolated antigen-binding protein, wherein the antigen-binding protein:
- a. is an antibody or antibody fragment;
- b. binds to human TREM-1 having the amino acid sequence set forth in SEQ ID NO:
- 20;
- c. comprises a light chain variable domain comprising:
- i. a light chain CDR1 comprising an amino acid sequence X1ASQSX2X3X4NLA (SEQ ID NO:
- 2199), wherein X1 is R or Q, wherein X2 is V or I, wherein X3 is N or S, and wherein X4 is S, H, I, V or A;
- ii. a light chain CDR2 comprising an amino acid sequence GAX1X2RAT (SEQ ID NO:
- 2200), wherein X1 is S or Y, and wherein X2 is T or I;
- and
- iii. a light chain CDR3 comprising an amino acid sequence QX1X2X3X4X5X6PX7T (SEQ ID NO:
- 2201);
- wherein X1 is Q, H or E, wherein X2 is F or Y, wherein X3 is K, Y or I, wherein X4 is N, T, L, I, or M;
- wherein X5 is W, F, H or Y, wherein X6 is absent or P;
- wherein X7 is W, N, Y, H or L;
- and
- d. comprises a heavy chain variable domain comprising:
- i. a heavy chain CDR1 comprising an amino acid sequence X1X2X3MX4 (SEQ ID NO:
- 2202), wherein X1 is A, R, T or S, wherein X2 is Y or N, wherein X3 is A or W, and wherein X4 is S or N;
- ii. a heavy chain CDR2 comprising an amino acid sequence X1X2X3X4X5X6 X7 X8 X9YYX10 X11X12VKG (SEQ ID NO:
- 2205), wherein X1 is T, E, or S, wherein X2 is absent or is M, V, or I, wherein X3 is S, R or K, wherein X4 is G or Q, wherein X5 is S, D or H, wherein X6 is G, S L, or A, wherein X7 is S, G, or R, wherein X8 is T, S, P or E, wherein X9 is T or I, wherein X10 is A or V, wherein X11 is D or E, and wherein X12 is S or A;
- and
- iii. a heavy chain CDR3 comprising an amino acid sequence X1X2X3X4X5X6 X7 F X8YYX9 (SEQ ID NO:
- 2203), wherein X1 is V, E, A or G, wherein X2 is A, F, Y or G, wherein X3 is G, S, Y or W, wherein X4 is S or R, wherein X5 is absent or is N, wherein X6 is F, S, Y, or absent, wherein X7 is L or F or absent, wherein X8 is D or E, and wherein X9 is Y, H or S.
An isolated antigen-binding protein, wherein the antigen-binding protein:
- a. is an antibody or antibody fragment;
- b. binds to human TREM-1 having the amino acid sequence set forth in SEQ ID NO:
- 20;
- c. comprises a light chain variable domain comprising:
- i. a light chain CDR1 comprising an amino acid sequence QASX1DIX2X3X4LN (SEQ ID NO:
- 2204), wherein X1 is R or Q, wherein X2 is R, S, N or F, wherein X3 is K or N, and wherein X4 is H, Y or D;
- ii. a light chain CDR2 comprising an amino acid sequence X1X2X3X4LET (SEQ ID NO:
- 2206), wherein X1 is D, G or H, wherein X2 is A, V or T, wherein X3 is S, A or Y, and wherein X4 is T or N;
- iii. a light chain CDR3 comprising an amino acid sequence QX1YX3X4X5PX6T (SEQ ID NO:
- 2207), wherein X1 is Q or H, wherein X2 is D, A or G, wherein X3 is N or K;
- wherein X4 is L or I, and wherein X5 is I or L;
- and
- d. comprises a heavy chain variable domain comprising:
- i. a heavy chain CDR1 comprising an amino acid sequence X1YDIN (SEQ ID NO:
- 2208), wherein X1 is R or S;
- ii. a heavy chain CDR2 comprising an amino acid sequence X1X2NPX3X4GX5X6GX7 X8 X9X10FX11X12 (SEQ ID NO:
- 2209), wherein X1 is W or R, wherein X2 is M or L, wherein X3 is N, Q, or K, wherein X4 is S, A, or R, wherein X5 is N, or Q, wherein X6 is S, A, or T, wherein X7 is S, Q, or Y, wherein X8 is V or T, wherein X9 is Q or K, wherein X10 is K or N, wherein X11 is R or Q, and wherein X12 is G or D;
- and
- iii. a heavy chain CDR3 comprising an amino acid sequence X1X2X3X4 X5X6 X7 X8 X9X10X11X12FX13X14 (SEQ ID NO:
- 2210);
- wherein X1 is G, L or R, wherein X2 is G, I, or R, wherein X3 is Y, R, I, G, or A, wherein X4 is T, S, Y, or V, wherein X5 is S or Y, wherein X6 is S, A, I, or R, wherein X7 is W, A, or S, wherein X8 is absent or is S, wherein X9 is absent or is F, W, or Y, and wherein X10 is R, S, H, K, or E, wherein X11 is W, H, Y, or F, wherein X12 is Y, V, A, or S, wherein X13 is D or Q, and wherein X14 is L, Y, I, or H.
An anti-TREM-1 antibody comprising a heavy chain amino acid sequence of SEQ ID NO:
- 1905 and a light chain amino acid sequence of SEQ ID NO:
- 2554.
Dependencies are inferred from the claim text.