# US 2023/0265145 A1 · Il-10 muteins and fusion proteins thereof

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- Number: US 2023/0265145 A1
- Document ID: US20230265145A1
- Status: Published application
- Kind: A1
- Application number: 18/001,913
- Filed: 2021-06-25
- Published: 2023-08-24
- Earliest claimed: 2020-06-26
- Assignees: Amgen Inc.
- Applicants: Amgen Inc.
- Inventors: Hailing HSU; Ian FOLTZ; Marissa MOCK; Victor Mitch LUNA; Ming ZHANG; Sharon Lynn WANNBERG; Gamze Ozlem CAMDERE TAPIA; Timothy Patrick RILEY
- Web page: https://patentgrep.com/patent/US20230265145A1

## CPC

- C07K 14/5428: {IL-10}
- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/60: characterized by non-natural combinations of immunoglobulin fragments
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C07K 2319/00: Fusion polypeptide
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

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.

## Claims

### Claim 1

A human interleukin-10 (IL-10) mutein comprising an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 2, wherein said IL-10 mutein has at least one mutation selected from a mutation in helical loop AB, helical loop CD, helical loop DE, helix A, helix B, helix C, helix D, helix E and/or helix F.

### Claim 2 (depends on 2)

The IL-10 mutein of claim 2, wherein the mutation is one or more of R27L, K34D, D41G, L46K, Q38E, Q38R, Q38D, K138L, K138D, I87A, H14Q, F15Y, M22V, K49T, K49S, F56Y, K57N, Y59T, L60Q, Q63E, Q63L, E67C, Q70E, Q70K, M77R, M77V, Q79R, Q79C, D84R, A89P, H90E, H90Q, S93E, S93Q, T100R, L103E, H109D, R110P, R110Q, L112V, E115K, N116D, A127M, K130Q, I136C, Y137C, M154V, M156C, K157N, orN160D of SEQ ID NO: 2, optionally comprising addition of 6 amino acids between helix D and helix E.

### Claim 3 (depends on 1)

The IL-10 mutein of claim 1, wherein the IL-10 mutein has the amino acid sequence set out in any one of SEQ ID NOs: 3-10 or SEQ ID NOS: 2138, 2140, 2142, 2144, 2146, 2148, 2150, 2152, 2154, 2156, 2158, 2160, 2162, 2164, 2166, 2168, 2170 2172, 2174, 2176, 2178, 2180, 2182, 2360, 2362, 2364, 2366, 2368, 2370, 2372, 2374, 2376, 2378, 2380, 2382, 2384, 2386, 2388, 2390, 2392, 2394, 2396, 2398, 2400, 2402, 2404, 2406, 2408, 2410, 2412, 2414, 2416, 2418, 2420, 2422, 2424, 2426, 2428, 2430, 2432, 2434, 2436, 2438, 2440, 2442, 2444, 2446, 2448, 2450, 2452, 2454, 2456, 2458, 2460, 2462, 2464, 2466, 2468, 2470, 2472, 2474, 2476, 2478, 2480, 2482, 2484, 2486, 2488, 2490, 2492, 2494, 2496, 2500, 2502, 2504, 2506, 2508, 2510, 2512, 2514, 2516, 2518, 2520, 2522, 2524, 2526, 2528, 2530, 2532, 2534, 2536, 2538, 2540 or 2777-2791.

### Claim 4 (depends on 1)

An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the IL-10 mutein of claim 1.

### Claim 5

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.

### Claim 6 (depends on 5)

The antigen-binding protein of claim 5 wherein the antigen binding protein comprises a set of CDR amino acid sequences selected from:
i) SEQ ID NO: 30 (LCDR1), SEQ ID NO: 31 (LCDR2), SEQ ID NO: 32 (LCDR3), SEQ ID NO: 36 (HCDR1), SEQ ID NO: 37 (HCDR2) and SEQ ID NO: 38 (HCDR3);
ii) SEQ ID NO: 50 (LCDR1), SEQ ID NO: 51 (LCDR2), SEQ ID NO: 52 (LCDR3), SEQ ID NO: 56 (HCDR1), SEQ ID NO: 57 (HCDR2) and SEQ ID NO: 58 (HCDR3);
iii) SEQ ID NO: 70 (LCDR1), SEQ ID NO: 71 (LCDR2), SEQ ID NO: 72 (LCDR3), SEQ ID NO: 76 (HCDR1), SEQ ID NO: 77 (HCDR2) and SEQ ID NO: 78 (HCDR3);
iv) SEQ ID NO: 90 (LCDR1), SEQ ID NO: 91 (LCDR2), SEQ ID NO: 92 (LCDR3), SEQ ID NO: 96 (HCDR1), SEQ ID NO: 97 (HCDR2) and SEQ ID NO: 98 (HCDR3);
v) SEQ ID NO: 110 (LCDR1), SEQ ID NO: 111 (LCDR2), SEQ ID NO: 112 (LCDR3), SEQ ID NO: 116 (HCDR1), SEQ ID NO: 117 (HCDR2) and SEQ ID NO: 118 (HCDR3);
vi) SEQ ID NO: 130 (LCDR1), SEQ ID NO: 131 (LCDR2), SEQ ID NO: 132 (LCDR3), SEQ ID NO: 136 (HCDR1), SEQ ID NO: 137 (HCDR2) and SEQ ID NO: 138 (HCDR3);
vii) SEQ ID NO: 150 (LCDR1), SEQ ID NO: 151 (LCDR2), SEQ ID NO: 152 (LCDR3), SEQ ID NO: 156 (HCDR1), SEQ ID NO: 157 (HCDR2) and SEQ ID NO: 158 (HCDR3);
viii) SEQ ID NO: 170 (LCDR1), SEQ ID NO: 171 (LCDR2), SEQ ID NO: 172 (LCDR3), SEQ ID NO: 176 (HCDR1), SEQ ID NO: 177 (HCDR2) and SEQ ID NO: 178 (HCDR3);
ix) SEQ ID NO: 190 (LCDR1), SEQ ID NO: 191 (LCDR2), SEQ ID NO: 192 (LCDR3), SEQ ID NO: 196 (HCDR1), SEQ ID NO: 197 (HCDR2) and SEQ ID NO: 198 (HCDR3);
x) SEQ ID NO: 210 (LCDR1), SEQ ID NO: 211 (LCDR2), SEQ ID NO: 212 (LCDR3), SEQ ID NO: 216 (HCDR1), SEQ ID NO: 217 (HCDR2) and SEQ ID NO: 218 (HCDR3);
xi) SEQ ID NO: 230 (LCDR1), SEQ ID NO: 231 (LCDR2), SEQ ID NO: 232 (LCDR3), SEQ ID NO: 236 (HCDR1), SEQ ID NO: 237 (HCDR2) and SEQ ID NO: 238 (HCDR3);
xii) SEQ ID NO: 250 (LCDR1), SEQ ID NO: 251 (LCDR2), SEQ ID NO: 252 (LCDR3), SEQ ID NO: 256 (HCDR1), SEQ ID NO: 257 (HCDR2) and SEQ ID NO: 258 (HCDR3);
xiii) SEQ ID NO: 270 (LCDR1), SEQ ID NO: 271 (LCDR2), SEQ ID NO: 272 (LCDR3), SEQ ID NO: 276 (HCDR1), SEQ ID NO: 277 (HCDR2) and SEQ ID NO: 278 (HCDR3);
xiv) SEQ ID NO: 290 (LCDR1), SEQ ID NO: 291 (LCDR2), SEQ ID NO: 292 (LCDR3), SEQ ID NO: 296 (HCDR1), SEQ ID NO: 297 (HCDR2) and SEQ ID NO: 298 (HCDR3); or
xv) SEQ ID NO: 2190 (LCDR1), SEQ ID NO: 2191 (LCDR2), SEQ ID NO: 2192 (LCDR3), SEQ ID NO: 2196 (HCDR1), SEQ ID NO: 2197 (HCDR2) and SEQ ID NO: 2198 (HCDR3).

### Claim 7 (depends on 5)

The antigen-binding protein of claim 5, comprising:
a. a light chain variable domain comprising an amino acid sequence selected from the group consisting of:
i. a sequence at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 41, 61, 81, 101, 121, 141, 161, 181, 201, 221, 241, 261, 281, 301 and 2185;
ii. a sequence encoded by a polynucleotide sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 41, 61, 81, 101, 121, 141, 161, 181, 201, 221, 241, 261, 281, 301 and 2185; or
iii. a sequence encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of a nucleic acid sequence selected from SEQ ID NOS: 39, 59, 79, 99, 119, 139, 159, 179, 199, 219, 239, 259, 279, 299 and 2183; and
b. a heavy chain variable domain comprising an amino acid sequence selected from the group consisting of:
i. a sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 42, 62, 82, 102. 122, 142, 162, 182, 202, 222, 242, 262, 282, 302 and 2186;
ii. a sequence encoded by a polynucleotide sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 42, 62, 82, 102. 122, 142, 162, 182, 202, 222, 242, 262, 282, 302 and 2186; or
iii. a sequence encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of a nucleic sequence selected from SEQ ID NOS: 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 and 2184.

### Claim 8 (depends on 5)

The antigen binding protein of claim 5, wherein the antigen binding protein comprises:
i) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 41 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 42;
ii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 61 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 62;
iii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 81 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 82;
iv) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 101 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 102;
v) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 121 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 122;
vi) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 141 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 142;
vii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 161 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 162;
viii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 181 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 182;
ix) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 201 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 202;
x) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 221 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 222;
xi) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 241 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 242;
xii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 261 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 262;
xiii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 281 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 282;
xiv) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 301 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 302; or
xv) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 2185 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 2186.

### Claim 9 (depends on 5)

An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the heavy chain variable domain and/or the light chain variable domain of claim 5.

### Claim 10

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.

### Claim 11

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.

### Claim 12 (depends on 10)

The antigen binding protein of claim 10, wherein:
a. each IL-10 moiety comprises an amino acid sequence that is at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 2, and
b. each IL-10 moiety independently comprises at least one mutation selected from a mutation in helical loop AB, helical loop CD, helical loop DE, helix A, helix B, helix C, helix D, helix E and/or helix F.

### Claim 13 (depends on 10)

The antigen binding protein of claim 10, wherein each IL-10 moiety independently comprises:
i) a mutation in one or more of residues N10, H14, F15, P20, M22, L23, R24, R27, D28, K34, T35, Q38, M39, K40, D41, Q42, L43, D44, N45, L46, L47, L48, K49, F56, K57, Y59, L60, Q63, E67, Q70, M77, Q79, N82, Q83, D84, P85, D86, 187, A89, H90, S93, T100, L103, H109, R110, L112, E115, N116, A127, K130, I136, Y137, K138, S141, E142, D144, I145, E151, M154, M156, K157, orN160 of SEQ ID NO: 2 or an addition of 4-8 amino acids between helix D and helix E; and/or
ii) one or more mutations selected from the group consisting of N10Q, N10I, N10K, R27L, K34D, D41G, L46K, Q38E, Q38R, Q38D, K138L, K138D, I87A, H14Q, F15Y, M22V, K49T, K49S, F56Y, K57N, Y59T, L60Q, Q63E, Q63L, E67C, Q70E, Q70K, M77R, M77V, Q79R, Q79C, D84R, A89P, H90E, H90Q, S93E, S93Q, T100R, L103E, H109D, R110P, R110Q, L112V, E115K, N116D, N110Q, A127M, K130Q, I136C, Y137C, M154V, M156C, K157N, or N160D of SEQ ID NO: 2, optionally comprising an addition of six amino acids between helix D and helix E.

### Claim 14 (depends on 10)

The antigen binding protein of claim 10, wherein the IL-10 moiety has the amino acid sequence set out in any one of SEQ ID NOS: 3-10 or SEQ ID NOS: 2138, 2140, 2142, 2144, 2146, 2148, 2150, 2152, 2154, 2156, 2158, 2160, 2162, 2164, 2166, 2168, 2170 2172, 2174, 2176, 2178, 2180, 2182, 2360, 2362, 2364, 2366, 2368, 2370, 2372, 2374, 2376, 2378, 2380, 2382, 2384, 2386, 2388, 2390, 2392, 2394, 2396, 2398, 2400, 2402, 2404, 2406, 2408, 2410, 2412, 2414, 2416, 2418, 2420, 2422, 2424, 2426, 2428, 2430, 2432, 2434, 2436, 2438, 2440, 2442, 2444, 2446, 2448, 2450, 2452, 2454, 2456, 2458, 2460, 2462, 2464, 2466, 2468, 2470, 2472, 2474, 2476, 2478, 2480, 2482, 2484, 2486, 2488, 2490, 2492, 2494, 2496, 2500, 2502, 2504, 2506, 2508, 2510, 2512, 2514, 2516, 2518, 2520, 2522, 2524, 2526, 2528, 2530, 2532, 2534, 2536, 2538, 2540 or 2777-2791.

### Claim 15 (depends on 10)

The antigen binding protein of claim 10, that has a heavy chain amino acid sequence set out in any one of SEQ ID NOS: 863, 865, 867, 869, 871, 873, 875, 877, 879, 881, 883, 885, 887, 889, 891, 893, 895, 897, 899, 901, 903, 905, 907, 909, 911, 913, 915, 917, 919, 921, 923, 925, 927, 929, 931, 933, 935, 937, 939, 941, 943, 945, 947, 949, 951, 953, 955, 957, 959, 961, 963, 965, 967, 969, 971, 973, 975, 977, 979, 981, 983, 985, 987, 989, 991, 993, 995, 997, 999, 1001, 1003, 1005, 1007, 1009, 1011, 1013, 1015, 1017, 1019, 1021, 1023, 1025, 1027, 1029, 1031, 1033, 1035, 1037, 1039, 1041, 1043, 1045, 1047, 1049, 1051, 1053, 1055, 1057, 1059, 1061, 1063, 1065, 1067, 1069, 1071, 1073, 1075, 1077, 1079, 1081, 1083, and 1085.

### Claim 16 (depends on 10)

The antigen binding protein of claim 10, that has a light chain amino acid sequence set out in any one of SEQ ID NOS: 864, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 886, 888, 890, 892, 894, 896, 898, 900, 902, 904, 906, 908, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938, 940, 942, 944, 946, 948, 950, 952, 954, 956, 958, 960, 962, 964, 966, 968, 970, 972, 974, 976, 978, 980, 982, 984, 986, 988, 990, 992, 994, 996, 998, 1000, 1002, 1004, 1006, 1008, 1010, 1012, 1014, 1016, 1018, 1020, 1022, 1024, 1026, 1028, 1030, 1032, 1034, 1036, 1038, 1040, 1042, 1044, 1046, 1048, 1050, 1052, 1054, 1056, 1058, 1060, 1062, 1064, 1066, 1068, 1070, 1072, 1074, 1076, 1078, 1080, 1082, 1084, and 1086.

### Claim 17 (depends on 10)

The antigen binding protein of claim 10, that has a heavy chain amino acid sequence set out in any one of SEQ ID NOS: 863, 865, 867, 869, 871, 873, 875, 877, 879, 881, 883, 885, 887, 889, 891, 893, 895, 897, 899, 901, 903, 905, 907, 909, 911, 913, 915, 917, 919, 921, 923, 925, 927, 929, 931, 933, 935, 937, 939, 941, 943, 945, 947, 949, 951, 953, 955, 957, 959, 961, 963, 965, 967, 969, 971, 973, 975, 977, 979, 981, 983, 985, 987, 989, 991, 993, 995, 997, 999, 1001, 1003, 1005, 1007, 1009, 1011, 1013, 1015, 1017, 1019, 1021, 1023, 1025, 1027, 1029, 1031, 1033, 1035, 1037, 1039, 1041, 1043, 1045, 1047, 1049, 1051, 1053, 1055, 1057, 1059, 1061, 1063, 1065, 1067, 1069, 1071, 1073, 1075, 1077, 1079, 1081, 1083, and 1085 and a corresponding light chain amino acid sequence set out in SEQ ID NOS: 864, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 886, 888, 890, 892, 894, 896, 898, 900, 902, 904, 906, 908, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938, 940, 942, 944, 946, 948, 950, 952, 954, 956, 958, 960, 962, 964, 966, 968, 970, 972, 974, 976, 978, 980, 982, 984, 986, 988, 990, 992, 994, 996, 998, 1000, 1002, 1004, 1006, 1008, 1010, 1012, 1014, 1016, 1018, 1020, 1022, 1024, 1026, 1028, 1030, 1032, 1034, 1036, 1038, 1040, 1042, 1044, 1046, 1048, 1050, 1052, 1054, 1056, 1058, 1060, 1062, 1064, 1066, 1068, 1070, 1072, 1074, 1076, 1078, 1080, 1082, 1084, and 1086.

### Claim 18 (depends on 10)

The antigen binding protein of claim 10, that has a heavy chain amino acid sequence set out in any one of SEQ ID NOS: 1883, 1885, 1887, 1889, 1891, 1893, 1895, 1897, 1899, 1901, 1903, 1905, 1907, 1909, 1911, 1913, 1915, 1917, 1919, 1921, 1923, 1925, 1927, 1929, 1931, 1933, 1935, 1937, 1939, 1941, 1943, 1945, 1947, 1949, 1951, 1953, 1955, 1957, 1959, 1961, 1963, 1965, 1967, 1969, 1971, 1973, 1975, 1977, 1979, 1981, 1983, 1985, 1987, 1989, 1991, 1993, 1995, 1997, 1999, 2001, 2003, 2005, and 2007.

### Claim 19 (depends on 10)

The antigen binding protein of claim 10, that has the light chain amino acid sequence set out in any one of SEQ ID NOS: 2543, 2544, 2545, 2546, 2547, 2548, 2549, 2550, 2551, 2552, 2553, 2554, 2555, 2556, 2557, 2558, 2559, 2560, 2561, 2562, 2563, 2564, 2565, 2566, 2567, 2568, 2569, 2570, 2571, 2572, 2573, 2574, 2575, 2576, 2577, 2578, 2579, 2580, 2581, 2582, 2583, 2584, 2585, 2586, 2587, 2588, 2589, 2590, 2591, 2592, 2593, 2594, 2595, 2596, 2597, 2598, 2599, 2600, 2601, 2602, 2603, 2604, 2605.

### Claim 20 (depends on 10)

The antigen binding protein of claim 10, that has a heavy chain amino acid sequence set out in any one of SEQ ID NOS: 1883, 1885, 1887, 1889, 1891, 1893, 1895, 1897, 1899, 1901, 1903, 1905, 1907, 1909, 1911, 1913, 1915, 1917, 1919, 1921, 1923, 1925, 1927, 1929, 1931, 1933, 1935, 1937, 1939, 1941, 1943, 1945, 1947, 1949, 1951, 1953, 1955, 1957, 1959, 1961, 1963, 1965, 1967, 1969, 1971, 1973, 1975, 1977, 1979, 1981, 1983, 1985, 1987, 1989, 1991, 1993, 1995, 1997, 1999, 2001, 2003, 2005, and 2007, and a corresponding light chain amino acid sequence set out in SEQ ID NOS: 2543, 2544, 2545, 2546, 2547, 2548, 2549, 2550, 2551, 2552, 2553, 2554, 2555, 2556, 2557, 2558, 2559, 2560, 2561, 2562, 2563, 2564, 2565, 2566, 2567, 2568, 2569, 2570, 2571, 2572, 2573, 2574, 2575, 2576, 2577, 2578, 2579, 2580, 2581, 2582, 2583, 2584, 2585, 2586, 2587, 2588, 2589, 2590, 2591, 2592, 2593, 2594, 2595, 2596, 2597, 2598, 2599, 2600, 2601, 2602, 2603, 2604, 2605.

### Claim 21 (depends on 10)

The antigen binding protein of claim 10, that has a heavy chain amino acid sequence set out in any one of SEQ ID NOS: 2011, 2013, 2015, 2017, 2019, 2021, 2026, 2025, 2027, 2029, 2031, 2033, 2035, 2037, 2039, 2041, 2043, 2045, 2047, 2049, 2051, 2053, 2055, 2057, 2059, 2061, 2063, 2065, 2067, 2069, 2071, 2073, 2075, 2077, 2079, 2081, 2083, 2085, 2087, 2089, 2091, 2093, 2095, 2097, 2099, 2101, 2103, 2105, 2107, 2109, 2111, 2113, 2115, 2117, 2119, 2121, 2123, 2125, 2127, 2129, 2131, 2133, and 2135.

### Claim 22 (depends on 10)

The antigen binding protein of claim 10, that has a light chain amino acid sequence set out in any one of SEQ ID NOS: 2233, 2235, 2237, 2239, 2241, 2243, 2245, 2247, 2249, 2251, 2253, 2255, 2257, 2259, 2261, 2263, 2265, 2267, 2269, 2271, 2273, 2275, 2277, 2279, 2281, 2283, 2285, 2287, 2289, 2291, 2293, 2295, 2297, 2299, 2301, 2303, 2305, 2307, 2309, 2311, 2313, 2315, 2317, 2319, 2321, 2323, 2325, 2327, 2329, 2331, 2333, 2335, 2337, 2339, 2341, 2343, 2345, 2347, 2349, 2351, 2353, 2355, and 2357.

### Claim 23 (depends on 10)

The antigen binding protein of claim 10, that has a heavy chain amino acid sequence set out in any one of SEQ ID NOS: 2011, 2013, 2015, 2017, 2019, 2021, 2026, 2025, 2027, 2029, 2031, 2033, 2035, 2037, 2039, 2041, 2043, 2045, 2047, 2049, 2051, 2053, 2055, 2057, 2059, 2061, 2063, 2065, 2067, 2069, 2071, 2073, 2075, 2077, 2079, 2081, 2083, 2085, 2087, 2089, 2091, 2093, 2095, 2097, 2099, 2101, 2103, 2105, 2107, 2109, 2111, 2113, 2115, 2117, 2119, 2121, 2123, 2125, 2127, 2129, 2131, 2133, and 2135, and a corresponding light chain amino acid sequence set out in SEQ ID NOS: 2233, 2235, 2237, 2239, 2241, 2243, 2245, 2247, 2249, 2251, 2253, 2255, 2257, 2259, 2261, 2263, 2265, 2267, 2269, 2271, 2273, 2275, 2277, 2279, 2281, 2283, 2285, 2287, 2289, 2291, 2293, 2295, 2297, 2299, 2301, 2303, 2305, 2307, 2309, 2311, 2313, 2315, 2317, 2319, 2321, 2323, 2325, 2327, 2329, 2331, 2333, 2335, 2337, 2339, 2341, 2343, 2345, 2347, 2349, 2351, 2353, 2355, and 2357.

### Claim 24 (depends on 10)

The antigen binding protein of claim 10, wherein the antigen binding moiety is an anti-TREM-1 antigen-binding moiety comprising:
a. a light chain variable domain comprising:
i. a light chain CDR1 sequence 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 sequence 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 2190;
iii. a light chain CDR3 sequence 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
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 sequence 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 sequence 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 sequence 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.

### Claim 25 (depends on 10)

The antigen-binding protein of claim 10, wherein the antigen binding moiety is an anti-TREM-1 antigen-binding moiety comprising a set of CDR amino acid sequences selected from:
i) SEQ ID NO: 30 (LCDR1), SEQ ID NO: 31 (LCDR2), SEQ ID NO: 32 (LCDR3), SEQ ID NO: 36 (HCDR1), SEQ ID NO: 37 (HCDR2) and SEQ ID NO: 38 (HCDR3);
ii) SEQ ID NO: 50 (LCDR1), SEQ ID NO: 51 (LCDR2), SEQ ID NO: 52 (LCDR3), SEQ ID NO: 56 (HCDR1), SEQ ID NO: 57 (HCDR2) and SEQ ID NO: 58 (HCDR3);
iii) SEQ ID NO: 70 (LCDR1), SEQ ID NO: 71 (LCDR2), SEQ ID NO: 72 (LCDR3), SEQ ID NO: 76 (HCDR1), SEQ ID NO: 77 (HCDR2) and SEQ ID NO: 78 (HCDR3);
iv) SEQ ID NO: 90 (LCDR1), SEQ ID NO: 91 (LCDR2), SEQ ID NO: 92 (LCDR3), SEQ ID NO: 96 (HCDR1), SEQ ID NO: 97 (HCDR2) and SEQ ID NO: 98 (HCDR3);
v) SEQ ID NO: 110 (LCDR1), SEQ ID NO: 111 (LCDR2), SEQ ID NO: 112 (LCDR3), SEQ ID NO: 116 (HCDR1), SEQ ID NO: 117 (HCDR2) and SEQ ID NO: 118 (HCDR3);
vi) SEQ ID NO: 130 (LCDR1), SEQ ID NO: 131 (LCDR2), SEQ ID NO: 132 (LCDR3), SEQ ID NO: 136 (HCDR1), SEQ ID NO: 137 (HCDR2) and SEQ ID NO: 138 (HCDR3);
vii) SEQ ID NO: 150 (LCDR1), SEQ ID NO: 151 (LCDR2), SEQ ID NO: 152 (LCDR3), SEQ ID NO: 156 (HCDR1), SEQ ID NO: 157 (HCDR2) and SEQ ID NO: 158 (HCDR3);
viii) SEQ ID NO: 170 (LCDR1), SEQ ID NO: 171 (LCDR2), SEQ ID NO: 172 (LCDR3), SEQ ID NO: 176 (HCDR1), SEQ ID NO: 177 (HCDR2) and SEQ ID NO: 178 (HCDR3);
ix) SEQ ID NO: 190 (LCDR1), SEQ ID NO: 191 (LCDR2), SEQ ID NO: 192 (LCDR3), SEQ ID NO: 196 (HCDR1), SEQ ID NO: 197 (HCDR2) and SEQ ID NO: 198 (HCDR3);
x) SEQ ID NO: 210 (LCDR1), SEQ ID NO: 211 (LCDR2), SEQ ID NO: 212 (LCDR3), SEQ ID NO: 216 (HCDR1), SEQ ID NO: 217 (HCDR2) and SEQ ID NO: 218 (HCDR3);
xi) SEQ ID NO: 230 (LCDR1), SEQ ID NO: 231 (LCDR2), SEQ ID NO: 232 (LCDR3), SEQ ID NO: 236 (HCDR1), SEQ ID NO: 237 (HCDR2) and SEQ ID NO: 238 (HCDR3);
xii) SEQ ID NO: 250 (LCDR1), SEQ ID NO: 251 (LCDR2), SEQ ID NO: 252 (LCDR3), SEQ ID NO: 256 (HCDR1), SEQ ID NO: 257 (HCDR2) and SEQ ID NO: 258 (HCDR3);
xiii) SEQ ID NO: 270 (LCDR1), SEQ ID NO: 271 (LCDR2), SEQ ID NO: 272 (LCDR3), SEQ ID NO: 276 (HCDR1), SEQ ID NO: 277 (HCDR2) and SEQ ID NO: 278 (HCDR3);
xiv) SEQ ID NO: 290 (LCDR1), SEQ ID NO: 291 (LCDR2), SEQ ID NO: 292 (LCDR3), SEQ ID NO: 296 (HCDR1), SEQ ID NO: 297 (HCDR2) and SEQ ID NO: 298 (HCDR3); or
xv) SEQ ID NO: 2190 (LCDR1), SEQ ID NO: 2191 (LCDR2), SEQ ID NO: 2192 (LCDR3), SEQ ID NO: 2196 (HCDR1), SEQ ID NO: 2197 (HCDR2) and SEQ ID NO: 2198 (HCDR3).

### Claim 26 (depends on 10)

The antigen binding protein of claim 10, wherein the anti-TREM-1 antigen-binding moiety comprises:
a. a light chain variable domain comprising an amino acid sequence selected from the group consisting of:
i. a sequence at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 41, 61, 81, 101, 121, 141, 161, 181, 201, 221, 241, 261, 281, 301 and 2185;
ii. a sequence encoded by a polynucleotide sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 41, 61, 81, 101, 121, 141, 161, 181, 201, 221, 241, 261, 281, 301 and 2185;
iii. a sequence encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of a nucleic acid sequence selected from SEQ ID NOS: 39, 59, 79, 99, 119, 139, 159, 179, 199, 219, 239, 259, 279, 299 and 2183; and
b. a heavy chain variable domain comprising an amino acid sequence selected from the group consisting of:
i. a sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 42, 62, 82, 102. 122, 142, 162, 182, 202, 222, 242, 262, 282, 302 and 2186;
ii. a sequence encoded by a polynucleotide sequence that is at least 80% identical to an amino acid sequence selected from SEQ ID NOS: 42, 62, 82, 102. 122, 142, 162, 182, 202, 222, 242, 262, 282, 302 and 2186;
iii. a sequence encoded by a polynucleotide that hybridizes under moderately stringent conditions to the complement of a polynucleotide consisting of a nucleic sequence selected from SEQ ID NOS: 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300 and 2184.

### Claim 27 (depends on 10)

The antigen binding protein of claim 10, wherein the antigen binding moiety is an anti-TREM-1 antigen-binding moiety comprising:
i) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 41 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 42;
ii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 61 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 62;
iii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 81 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 82;
iv) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 101 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 102;
v) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 121 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 122;
vi) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 141 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 142;
vii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 161 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 162;
viii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 181 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 182;
ix) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 201 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 202;
x) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 221 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 222;
xi) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 241 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 242;
xii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 261 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 262;
xiii) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 281 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 282;
xiv) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 301 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 302; or
xv) an amino acid sequence at least 90% identical to a light chain variable domain set out in SEQ ID NO: 2185 and an amino acid sequence at least 90% identical to a heavy chain variable domain set out in SEQ ID NO: 2186.

### Claim 28 (depends on 24)

The antigen binding protein of claim 24,, wherein:
a. the antigen binding protein comprises two light chains and two heavy chains:
b. each heavy chain comprises an IL-10 moiety attached at the C-terminus of the heavy chain;
c. each heavy-chain-IL-10 moiety antigen binding protein comprises an amino acid sequence at least 90% identical to a sequence selected from SEQ ID NOS: 863, 865, 867, 869, 871, 873, 875, 877, 879, 881, 883, 885, 887, 889, 891, 893, 895, 897, 899, 901, 903, 905, 907, 909, 911, 913, 915, 917, 919, 921, 923, 925, 927, 929, 931, 933, 935, 937, 939, 941, 943, 945, 947, 949, 951, 953, 955, 957, 959, 961, 963, 965, 967, 969, 971, 973, 975, 977, 979, 981, 983, 985, 987, 989, 991, 993, 995, 997, 999, 1001, 1003, 1005, 1007, 1009, 1011, 1013, 1015, 1017, 1019, 1021, 1023, 1025, 1027, 1029, 1031, 1033, 1035, 1037, 1039, 1041, 1043, 1045, 1047, 1049, 1051, 1053, 1055, 1057, 1059, 1061, 1063, 1065, 1067, 1069, 1071, 1073, 1075, 1077, 1079, 1081, 1083, and 1085; and
d. each light chain-IL-10 moiety comprises an amino acid sequence at least 90% identical to a sequence selected from SEQ ID NOS: 864, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 886, 888, 890, 892, 894, 896, 898, 900, 902, 904, 906, 908, 910, 912, 914, 916, 918, 920, 922, 924, 926, 928, 930, 932, 934, 936, 938, 940, 942, 944, 946, 948, 950, 952, 954, 956, 958, 960, 962, 964, 966, 968, 970, 972, 974, 976, 978, 980, 982, 984, 986, 988, 990, 992, 994, 996, 998, 1000, 1002, 1004, 1006, 1008, 1010, 1012, 1014, 1016, 1018, 1020, 1022, 1024, 1026, 1028, 1030, 1032, 1034, 1036, 1038, 1040, 1042, 1044, 1046, 1048, 1050, 1052, 1054, 1056, 1058, 1060, 1062, 1064, 1066, 1068, 1070, 1072, 1074, 1076, 1078, 1080, 1082, 1084, and 1086.

### Claim 29 (depends on 10)

The antigen binding protein of claim 10, wherein the antigen binding protein has a heavy chain-IL-10 moiety amino acid sequence selected from the group consisting of SEQ ID NOS: 2137, 2139, 2141, 2143, 2145, 2147, 2149, 2151, 2153, 2155, 2157, 2159, 2161, 2163, 2165, 2167, 2169, 2171, 2173, 2175, 2177, 2179, 2181, 2359, 2361, 2363, 2365, 2367, 2369, 2371, 2373, 2375, 2377, 2379, 2381, 2383, 2385, 2387, 2389, 2391, 2393, 2395, 2397, 2399, 2401, 2403, 2405, 2407, 2409, 2411, 2143, 2415, 2417, 2419, 2421, 2423, 2425, 2427, 2429, 2431, 2433, 2435, 2437, 2439, 2441, 2443, 2445, 2447, 2449, 2451, 2453, 2455, 2457, 2459, 2461, 2463, 2465, 2467, 2469, 2471, 2473, 2475, 2477, 2479, 2481, 2483, 2485, 2487, 2489, 2491, 2493, 2495, 2497, 2498, 2499, 2501, 2503, 2505, 2507, 2509, 2511, 2513, 2515, 2517, 2519, 2521, 2523, 2525, 2527, 2529, 2531, 2533, 2535, 2537, 2539 and 2726-2776.

### Claim 30 (depends on 10)

The antigen binding protein of claim 10 wherein the antigen binding protein has a heavy chain-IL-10 moiety amino acid sequence selected from the group consisting of SEQ ID NOS: 2727-2732.

### Claim 31 (depends on 30)

The antigen binding protein of claim 30 comprising the heavy chain amino acid sequence of SEQ ID NO: 2727 or 2728, and the light chain amino acid sequence set out in SEQ ID NO: 976 or SEQ ID NO: 2554.

### Claim 32 (depends on 30)

The antigen binding protein of claim 30 comprising the heavy chain amino acid sequence of SEQ ID NO: 2729, 2730, 2731 or 2732, and the light chain amino acid sequence set out in and SEQ ID NO: 992 or SEQ ID NO: 2555.

### Claim 33 (depends on 24)

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;
d. at least one IL-10 moiety is covalently bound to the antigen-binding moiety, and/or
e. the antigen-binding moiety competes for binding to a human TREM-1 protein with the antigen binding moiety of claim 24 .

### Claim 34 (depends on 10)

An isolated nucleic acid molecule comprising a nucleotide sequence that encodes the heavy chain region and/or the light chain region of the antigen binding protein of claim 10.

### Claim at position 35

35-36. (canceled)

### Claim 37 (depends on 1)

A composition comprising
the IL-10 mutein of claim 1 and a pharmaceutically acceptable carrier .

### Claim at position 37

38-40. (canceled)

### Claim 41

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.

### Claim 42 (depends on 41)

The isolated antigen binding protein of claim 41, wherein the antigen binding protein comprises:
a. a light chain variable domain comprising:
i. a light chain CDR1 comprising an amino acid sequence RASQSVNSNLA (SEQ ID NO: 2212);
ii. a light chain CDR2 comprising an amino acid sequence GASTRAT (SEQ ID NO: 2219);
iii. a light chain CDR3 comprising an amino acid sequence QQFKNWPPT (SEQ ID NO: 2222); and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 comprising an amino acid sequence AYAMS (SEQ ID NO: 2227);
ii. a heavy chain CDR2 comprising an amino acid sequence TSGSGSTTYYADSVKG (SEQ ID NO: 2230); and
iii. a heavy chain CDR3 comprising an amino acid sequence VAGSNFLFDY (SEQ ID NO: 2670).

### Claim 43

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.

### Claim 44 (depends on 43)

The antigen binding protein of claim 43, wherein the antigen binding protein comprises:
a. a light chain variable domain comprising:
i. a light chain CDR1 comprising an amino acid sequence QASQDIRKHLN (SEQ ID NO: 2213);
ii. a light chain CDR2 comprising an amino acid sequence DASNLET (SEQ ID NO: 2220); and
iii. a light chain CDR3 comprising an amino acid sequence QHYDNLPIT (SEQ ID NO: 2223); and
b. a heavy chain variable domain comprising:
i. a heavy chain CDR1 comprising an amino acid sequence RYDIN (SEQ ID NO: 2228);
ii. a heavy chain CDR2 comprising an amino acid sequence WMNPNSGNSSVQKFRG (SEQ ID NO: 2231); and
iii. a heavy chain CDR3 comprising an amino acid sequence GGYTSSWRWYFDL (SEQ ID NO: 2671) or GGYTSSWSRWYFDL (SEQ ID NO: 2672).

### Claim 45 (depends on 37)

A method of treating an inflammatory disease in a subject in a need thereof comprising administering to the subject the composition of claim 37.

### Claim 46 (depends on 45)

The method of claim 45, wherein the inflammatory disease is selected from the group consisting of inflammatory bowel disease, ulcerative colitis, Crohn’s disease, irritable bowel syndrome, rheumatoid arthritis, psoriasis, psoriatic arthritis, and cytokine release syndrome (CRS).

### Claim 47 (depends on 5)

A composition comprising the anti-TREM-1 antigen-binding protein of claim 5 and a pharmaceutically acceptable carrier.

### Claim 48 (depends on 47)

A method of treating an inflammatory disease in a subject in a need thereof comprising administering to the subject the composition of claim 47.

### Claim 49 (depends on 48)

The method of claim 48, wherein the inflammatory disease is selected from the group consisting of inflammatory bowel disease, ulcerative colitis, Crohn’s disease, irritable bowel syndrome, rheumatoid arthritis, psoriasis, psoriatic arthritis, and cytokine release syndrome (CRS).

### Claim 50 (depends on 10)

A composition comprising the antigen binding protein of claim 10 and a pharmaceutical carrier.

### Claim 51 (depends on 50)

A method of treating an inflammatory disease in a subject in a need thereof comprising administering to the subject the composition of claim 50.

### Claim 52 (depends on 51)

The method of claim 51, wherein the inflammatory disease is selected from the group consisting of inflammatory bowel disease, ulcerative colitis, Crohn’s disease, irritable bowel syndrome, rheumatoid arthritis, psoriasis, psoriatic arthritis, and cytokine release syndrome (CRS).