Il-10 muteins and fusion proteins thereof

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 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 comprising an 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 comprising an 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 comprising an 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 comprising an 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 comprising an amino acid sequence selected from SEQ ID NOS:
• 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, 238, 258, 278, 298 and 2198.

An antigen binding protein comprising an antigen-binding moiety and one or two IL-10 moieties wherein:

• a. the antigen-binding moiety is an antibody or antibody fragment,
• b. each IL-10 moiety is independently monovalent or bivalent,
• c. each IL-10 moiety is independently selected from one or more human IL-10 muteins having sequences that are 90% identical to SEQ ID NO:
• 2, and
• d. at least one IL-10 moiety is covalently bound to the antigen-binding moiety.

An antigen binding protein comprising:

• (a) a polypeptide sequence having the formula A-L-M or M-L-A, wherein
• i) A is an immunoglobulin heavy chain of an IgG antibody that binds to a TREM-1 protein set out in SEQ ID NO:
• 20,
• ii) L is a linker peptide comprising from 4 to 20 amino acids and
• iii) M is a mutein of IL-10 having at least 90% sequence identity to wt IL-10 set out in SEQ ID NO:
• 2;
• and
• (b) an immunoglobulin light chain of an IgG antibody that binds TREM-1 protein set out in SEQ ID NO:
• 20,
• wherein the immunoglobulin heavy chain of (a) and the immunoglobulin light chain of (b) form an IgG antibody moiety that binds TREM-1, wherein the protein comprises one or two molecules of the polypeptide of (a) and one or two molecules of the light chain of (b), optionally wherein only 1 polypeptide of (a) comprises an M moiety.

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 X1ASQSX 2X3X4NLA (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 GAX 1X2RAT (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 QX 1X2X 3X4X 5X6PX7T (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 X 1X2X3MX4 (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 X 1X2X 3X4X 5X6 X 7 X8 X9YYX10 X 11X12VKG (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 X 1X2X 3X4X 5X6 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 QASX1DIX 2X3X4LN (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 X 1X2X 3X4LET (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 QX1YX 3X4X5PX6T (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 XiYDIN (SEQ ID NO:
• 2208), wherein X1 is R or S;
• ii. a heavy chain CDR2 comprising an amino acid sequence X 1X2NPX 3X4GX 5X6GX7 X8 X 9X10FX 11X12 (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 X 1X2X 3X4 X 5X6 X 7 X8 X 9X10X 11X12FX 13X14 (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.