ANTI-TREM2 ANTIBODIES AND METHODS OF USE

1 . An antibody that specifically binds to TREM2, comprising a VH comprising CDRH1, CDRH2, and CDRH3, and a VL comprising CDRL1, CDRL2, and CDRL3, wherein the CDRH1, CDRH2, and CDRH3 comprise the CDRH1, CDRH2, and CDRH3 amino acid sequences of a VH amino acid sequence set forth in any one of SEQ ID NOs: 87-109; and comprising the CDRL1, CDRL2, and CDRL3 comprise the CDRL1, CDRL2, CDRL3 amino acid sequences of a VL amino acid sequence set forth in any one of SEQ ID NOs: 110-125.

2 . The antibody of claim 1 , wherein the VH amino acid sequence and the VL amino acid sequence are as set forth in: SEQ ID NOs: 87 and 110; 88 and 111; 89 and 112; 90 and 113; 91 and 114; 92 and 115; 93 and 116; 94 and 117; 95 and 118; 96 and 119; 97 and 120; 98 and 121; 99 and 119; 100 and 122; 101 and 110; 102 and 123; 103 and 115; 104 and 118; 105 and 124; 106 and 125; 107 and 110; 108 and 111; or 109 and 121, respectively.

3 - 14 . (canceled)

15 . The antibody of claim 1 , wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 each comprise the amino acid sequence of the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 selected from the group consisting of:

(a) the CDRH1 sequence set forth in SEQ ID NO: 19, the CDRH2 sequence set forth in SEQ ID NO: 32, the CDRH3 sequence set forth in SEQ ID NO: 42, the CDRL1 sequence set forth is SEQ ID NO: 60, the CDRL2 sequence set forth in SEQ ID NO: 66, and the CDRL3 sequence set forth in SEQ ID NO: 71;

(b) the CDRH1 sequence set forth in SEQ ID NO: 20, the CDRH2 sequence set forth in SEQ ID NO: 33, the CDRH3 sequence set forth in SEQ ID NO: 43, the CDRL1 sequence set forth is SEQ ID NO: 60, the CDRL2 sequence set forth in SEQ ID NO: 66, and the CDRL3 sequence set forth in SEQ ID NO: 72;

(c) the CDRH1 sequence set forth in SEQ ID NO: 21, the CDRH2 sequence set forth in SEQ ID NO: 34, the CDRH3 sequence set forth in SEQ ID NO: 44, the CDRL1 sequence set forth is SEQ ID NO: 61, the CDRL2 sequence set forth in SEQ ID NO: 67, and the CDRL3 sequence set forth in SEQ ID NO: 73;

(d) the CDRH1 sequence set forth in SEQ ID NO: 22, the CDRH2 sequence set forth in SEQ ID NO: 34, the CDRH3 sequence set forth in SEQ ID NO: 45, the CDRL1 sequence set forth is SEQ ID NO: 62, the CDRL2 sequence set forth in SEQ ID NO: 67, and the CDRL3 sequence set forth in SEQ ID NO: 74;

(e) the CDRH1 sequence set forth in SEQ ID NO: 23, the CDRH2 sequence set forth in SEQ ID NO: 35, the CDRH3 sequence set forth in SEQ ID NO: 46, the CDRL1 sequence set forth is SEQ ID NO: 63, the CDRL2 sequence set forth in SEQ ID NO: 68, and the CDRL3 sequence set forth in SEQ ID NO: 75;

(f) the CDRH1 sequence set forth in SEQ ID NO: 24, the CDRH2 sequence set forth in SEQ ID NO: 36, the CDRH3 sequence set forth in SEQ ID NO: 47, the CDRL1 sequence set forth is SEQ ID NO: 63, the CDRL2 sequence set forth in SEQ ID NO: 68, and the CDRL3 sequence set forth in SEQ ID NO: 76;

(g) the CDRH1 sequence set forth in SEQ ID NO: 21, the CDRH2 sequence set forth in SEQ ID NO: 34, the CDRH3 sequence set forth in SEQ ID NO: 48, the CDRL1 sequence set forth is SEQ ID NO: 64, the CDRL2 sequence set forth in SEQ ID NO: 69, and the CDRL3 sequence set forth in SEQ ID NO: 77;

(h) the CDRH1 sequence set forth in SEQ ID NO: 25, the CDRH2 sequence set forth in SEQ ID NO: 37, the CDRH3 sequence set forth in SEQ ID NO: 49, the CDRL1 sequence set forth is SEQ ID NO: 64, the CDRL2 sequence set forth in SEQ ID NO: 69, and the CDRL3 sequence set forth in SEQ ID NO: 78;

(i) the CDRH1 sequence set forth in SEQ ID NO: 26, the CDRH2 sequence set forth in SEQ ID NO: 37, the CDRH3 sequence set forth in SEQ ID NO: 50, the CDRL1 sequence set forth is SEQ ID NO: 64, the CDRL2 sequence set forth in SEQ ID NO: 69, and the CDRL3 sequence set forth in SEQ ID NO: 79;

(j) the CDRH1 sequence set forth in SEQ ID NO: 27, the CDRH2 sequence set forth in SEQ ID NO: 38, the CDRH3 sequence set forth in SEQ ID NO: 51, the CDRL1 sequence set forth is SEQ ID NO: 65, the CDRL2 sequence set forth in SEQ ID NO: 70, and the CDRL3 sequence set forth in SEQ ID NO: 80;

(k) the CDRH1 sequence set forth in SEQ ID NO: 28, the CDRH2 sequence set forth in SEQ ID NO: 39, the CDRH3 sequence set forth in SEQ ID NO: 52, the CDRL1 sequence set forth is SEQ ID NO: 65, the CDRL2 sequence set forth in SEQ ID NO: 70, and the CDRL3 sequence set forth in SEQ ID NO: 81;

(1) the CDRH1 sequence set forth in SEQ ID NO: 29, the CDRH2 sequence set forth in SEQ ID NO: 40, the CDRH3 sequence set forth in SEQ ID NO: 53, the CDRL1 sequence set forth is SEQ ID NO: 65, the CDRL2 sequence set forth in SEQ ID NO: 70, and the CDRL3 sequence set forth in SEQ ID NO: 82;

(m) the CDRH1 sequence set forth in SEQ ID NO: 30, the CDRH2 sequence set forth in SEQ ID NO: 38, the CDRH3 sequence set forth in SEQ ID NO: 53, the CDRL1 sequence set forth is SEQ ID NO: 65, the CDRL2 sequence set forth in SEQ ID NO: 70, and the CDRL3 sequence set forth in SEQ ID NO: 80;

(n) the CDRH1 sequence set forth in SEQ ID NO: 19, the CDRH2 sequence set forth in SEQ ID NO: 32, the CDRH3 sequence set forth in SEQ ID NO: 54, the CDRL1 sequence set forth is SEQ ID NO: 60, the CDRL2 sequence set forth in SEQ ID NO: 66, and the CDRL3 sequence set forth in SEQ ID NO: 83;

(o) the CDRH1 sequence set forth in SEQ ID NO: 19, the CDRH2 sequence set forth in SEQ ID NO: 32, the CDRH3 sequence set forth in SEQ ID NO: 55, the CDRL1 sequence set forth is SEQ ID NO: 60, the CDRL2 sequence set forth in SEQ ID NO: 66, and the CDRL3 sequence set forth in SEQ ID NO: 71;

(p) the CDRH1 sequence set forth in SEQ ID NO: 22, the CDRH2 sequence set forth in SEQ ID NO: 34, the CDRH3 sequence set forth in SEQ ID NO: 56, the CDRL1 sequence set forth is SEQ ID NO: 62, the CDRL2 sequence set forth in SEQ ID NO: 67, and the CDRL3 sequence set forth in SEQ ID NO: 84;

(q) the CDRH1 sequence set forth in SEQ ID NO: 23, the CDRH2 sequence set forth in SEQ ID NO: 35, the CDRH3 sequence set forth in SEQ ID NO: 47, the CDRL1 sequence set forth is SEQ ID NO: 63, the CDRL2 sequence set forth in SEQ ID NO: 68, and the CDRL3 sequence set forth in SEQ ID NO: 76;

(r) the CDRH1 sequence set forth in SEQ ID NO: 21, the CDRH2 sequence set forth in SEQ ID NO: 34, the CDRH3 sequence set forth in SEQ ID NO: 57, the CDRL1 sequence set forth is SEQ ID NO: 64, the CDRL2 sequence set forth in SEQ ID NO: 69, and the CDRL3 sequence set forth in SEQ ID NO: 79;

(s) the CDRH1 sequence set forth in SEQ ID NO: 27, the CDRH2 sequence set forth in SEQ ID NO: 38, the CDRH3 sequence set forth in SEQ ID NO: 58, the CDRL1 sequence set forth is SEQ ID NO: 65, the CDRL2 sequence set forth in SEQ ID NO: 70, and the CDRL3 sequence set forth in SEQ ID NO: 85; and

(t) the CDRH1 sequence set forth in SEQ ID NO: 31, the CDRH2 sequence set forth in SEQ ID NO: 41, the CDRH3 sequence set forth in SEQ ID NO: 59, the CDRL1 sequence set forth is SEQ ID NO: 60, the CDRL2 sequence set forth in SEQ ID NO: 66, and the CDRL3 sequence set forth in SEQ ID NO: 86.

16 - 17 . (canceled)

18 . The antibody of claim 1 , wherein the VH comprises an amino acid sequence set forth in any one of SEQ ID NOs: 87-109 and the VL comprises an amino acid sequence set forth in any one of SEQ ID NOs: 110-125.

19 - 27 . (canceled)

28 . The antibody of claim 1 , wherein the antibody is an antagonist or a reverse agonist.

29 . The antibody of claim 1 , further comprising heavy and/or light chain constant regions.

30 - 35 . (canceled)

36 . The antibody of claim 29 , wherein the antibody comprises:

(a) a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 164 or SEQ ID NO: 165, and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 161;

(b) a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 166 or SEQ ID NO: 167, and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 162; or

(c) a heavy chain comprising an amino acid sequence set forth in SEQ ID NO: 168 or SEQ ID NO: 169, and a light chain comprising an amino acid sequence set forth in SEQ ID NO: 163.

37 . An antibody that competes for binding to TREM2 with, or binds to the same epitope as, the antibody of claim 1 .

38 . A polypeptide comprising a VH comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of a VH amino acid sequence set forth in any one of SEQ ID NOs: 87-109.

39 . (canceled)

40 . A polypeptide comprising a VL comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of a VL amino acid sequence set forth in any one of SEQ ID NOs: 110-125.

41 - 42 . (canceled)

43 . The antibody of claim 1 , wherein the antibody is conjugated to a cytotoxic agent, cytostatic agent, toxin, radionuclide, or detectable label.

44 . A polynucleotide or polynucleotides encoding a VH and/or a VL, or a heavy chain and/or a light chain of the antibody of claim 1 .

45 . An expression vector comprising the polynucleotide or polynucleotides of claim 44 .

46 . A host cell comprising

the polynucleotide or polynucleotides of claim 44 .

47 . A method for producing an antibody that binds to human TREM2, comprising culturing the host cell of claim 46 under conditions which permit expression of the antibody.

48 . A composition comprising the antibody of claim 1 , and at least one pharmaceutically acceptable carrier.

49 . (canceled)

50 . A method of reducing binding of low-density lipoprotein (LDL) to TREM2 in a subject, wherein the method comprises administering to the subject an effective amount of the antibody of claim 1 .

51 . A method of reducing efferocytosis in a subject, wherein the method comprises administering to the subject an effective amount of the antibody of claim 1 .

52 . A method of reprogramming macrophages in a subject, wherein the method comprises administering to the subject an effective amount of the antibody of any one of claim 1 .

53 . A method of slowing, reducing, or inhibiting tumor growth in a subject, wherein the method comprises administering to the subject an effective amount of the antibody of claim 1 .

54 - 62 . (canceled)