MONOVALENT ANTI-MERTK ANTIBODIES AND METHODS OF USE THEREOF

1 . An antibody that binds to human Mer Tyrosine Kinase (MerTK), wherein the antibody contains no more than one antigen-binding domain that binds to human MerTK.

2 . The antibody of claim 1 , wherein the antigen-binding domain that binds to human MerTK binds to the Ig1 domain of MerTK protein.

3 . The antibody of claim 1 or 2 , wherein the antigen-binding domain that binds to human MerTK competitively inhibits binding to human MerTK of an antibody comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:9 and a variable light chain comprising the amino acid sequence of SEQ ID NO:10.

4 . The antibody of any one of claims 1-3 , wherein the antigen-binding domain that binds to human MerTK binds to the same epitope of human MerTK as an antibody comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:9 and a variable light chain comprising the amino acid sequence of SEQ ID NO:10.

5 . The antibody of any one of claims 1-4 , wherein the antigen-binding domain that binds to human MerTK comprises an HVR-H1 comprising amino acids 31-35 of SEQ ID NO:9, an HVR-H2 comprising amino acids 50-66 of SEQ ID NO:9, an HVR-H3 comprising amino acids 99-109 of SEQ ID NO:9, an HVR-L1 comprising amino acids 24-34 of SEQ ID NO:10, an HVR-L2 comprising amino acids 50-56 of SEQ ID NO:10, and an HVR-L3 comprising amino acids 89-97 of SEQ ID NO:10.

6 . The antibody of any one of claims 1-4 , wherein the antibody comprises the HVRs of the 16.2 antibody, optionally wherein the HVRs are the Kabat-defined HVRs, the Chothia-defined HVRs, the AbM-defined HVRs, or the contact-defined HVRs.

7 . The antibody of any one of claims 1-6 , wherein the antigen-binding domain that binds to human MerTK comprises a variable heavy chain comprising an amino acid sequence that is at least 85%, at least 90%, or at least 95% identical to the amino acid sequence of SEQ ID NO:9.

8 . The antibody of any one of claims 1-7 , wherein the antigen-binding domain that binds to human MerTK comprises a variable light chain comprising an amino acid sequence that is at least 85%, at least 90%, or at least 95% identical to the amino acid sequence of SEQ ID NO:10.

9 . The antibody of any one of claims 1-8 , wherein the antigen-binding domain that binds to human MerTK comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO:9 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:10.

10 . The antibody of claim 1 or 2 , wherein the antigen-binding domain that binds to human MerTK competitively inhibits binding to human MerTK of an antibody comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:13 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 14.

11 . The antibody of any one of claims 1, 2 and 10 , wherein the antigen-binding domain that binds to human MerTK binds to the same epitope of human MerTK as an antibody comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO:13 and a variable light chain comprising the amino acid sequence of SEQ ID NO:14.

12 . The antibody of any one of claims 1, 2, 10, and 11 , wherein the antigen-binding domain that binds to human MerTK comprises an HVR-H1 comprising amino acids 31-35 of SEQ ID NO:13, an HVR-H2 comprising amino acids 50-66 of SEQ ID NO:13, an HVR-H3 comprising amino acids 99-108 of SEQ ID NO:13, an HVR-L1 comprising amino acids 24-34 of SEQ ID NO:14, an HVR-L2 comprising amino acids 50-56 of SEQ ID NO:14, and an HVR-L3 comprising amino acids 89-97 of SEQ ID NO: 14.

13 . The antibody of any one of claims 1, 2, 10, and 11 , wherein the antibody comprises the HVRs of the 13.11 antibody, optionally wherein the HVRs are the Kabat-defined HVRs, the Chothia-defined HVRs, the AbM-defined HVRs, or the contact-defined HVRs.

14 . The antibody of any one of claims 1, 2, and 10-13 , wherein the antigen-binding domain that binds to human MerTK comprises a variable heavy chain comprising an amino acid sequence that is at least 85%, at least 90%, or at least 95% identical to the amino acid sequence of SEQ ID NO:13.

15 . The antibody of any one of claims 1, 2, and 10-14 , wherein the antigen-binding domain that binds to human MerTK comprises a variable light chain comprising an amino acid sequence that is at least 85%, at least 90%, or at least 95% identical to the amino acid sequence of SEQ ID NO:14.

16 . The antibody of any one of claims 1, 2, and 10-15 , wherein the antigen-binding domain that binds to human MerTK comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO:13 and/or a variable light chain comprising the amino acid sequence of SEQ ID NO:14.

17 . The antibody of any one of claims 1-16 , wherein the antibody is of the IgG class, the IgM class, or the IgA class.

18 . The antibody of claim 17 , wherein the antibody is of the IgG class, optionally wherein the antibody has an IgG1, an IgG2, or an IgG4 isotype.

19 . The antibody of claim 17 , wherein the antibody is an IgG1 antibody.

20 . The antibody of claim 17 , wherein the antibody is an IgG4 antibody.

21 . The antibody of any one of claims 1-20 , wherein the antibody comprises (a) a first heavy chain or a fragment thereof and a first light chain or a fragment thereof, wherein the first heavy chain or fragment there of and the first light chain or fragment thereof together form the antigen-binding domain that binds to human MerTK and (b) a second heavy chain or fragment thereof and/or a second light chain or fragment thereof, wherein the second heavy chain or fragment thereof and/or the second light chain or fragment thereof do not form an antigen-binding domain that binds to human MerTK.

22 . The antibody of claim 21 , wherein the second heavy chain or fragment thereof does not contain a variable heavy chain.

23 . The antibody of claim 21 or 22 , wherein the second light chain or fragment thereof does not contain a variable light chain.

24 . The antibody of any one of claims 21-23 , wherein the antibody does not comprise a second light chain or fragment thereof.

25 . The antibody of any one of claims 21-24 , wherein the second heavy chain or fragment thereof comprises a CH2 domain and a CH3 domain, optionally wherein the second heavy chain or fragment thereof further comprises a hinge domain.

26 . The antibody of any one of claims 1-25 , wherein the antibody comprises an Fc region comprising a first polypeptide and a second polypeptide wherein:

(a) the first polypeptide comprises the amino acid substitution T366Y, and the second polypeptide comprises the amino acid substation Y407T;

(b) the first polypeptide comprises the amino acid substitution T366W, and the second polypeptide comprises the amino acid substitutions T366S, L368W, and Y407V;

(c) the first polypeptide comprises the amino acid substitution T366W, and the second polypeptide comprises the amino acid substitutions T366S, L368A, and Y407V;

(d) the first polypeptide comprises the amino acid substitutions T366W, and S354C and the second polypeptide comprises the amino acid substitutions T366S, L368A, Y407V, and Y349C;

(e) the first polypeptide comprises the amino acid substitutions T350V, L351Y, F405A, Y407V, and the second polypeptide comprises the amino acid substitutions T350V, T366L, K392L, and T394W;

(f) the first polypeptide comprises the amino acid substitutions K360D, D399M, and Y407A, and the second polypeptide comprises the amino acid substitutions E345R, Q347R, T366V, and K409V;

(g) the first polypeptide comprises the amino acid substitutions K409D and K392D, and the second polypeptide comprises the amino acid substitutions D399K and E356K;

(h) the first polypeptide comprises the amino acid substitutions K360E and K409W, and the second polypeptide comprises the amino acid substitutions Q347R, D399V, and F405T;

(i) the first polypeptide comprises the amino acid substitutions L360E, K409W, and Y349C, and the second polypeptide comprises the amino acid substitutions Q347R, D399V, F405T, and S354C; or

(j) the first polypeptide comprises the amino acid substitutions K370E and K409W, and the second polypeptide comprises the amino acid substitutions E357N, D399V, and F405T;

wherein the substitution is according to EU numbering.

27 . The antibody of any one of claims 1-26 , wherein the antibody comprises a knob mutation and a hole mutation.

28 . The antibody of claim 27 , wherein the knob mutation comprises the amino acid substitution T366W according to EU numbering.

29 . The antibody of claim 27 or 28 , wherein the hole mutation comprises the amino acids substitutions T366S, L368A, and Y407V according to EU numbering.

30 . The antibody of any one of claims 1-29 , wherein the antibody comprises an Fc region comprising an amino acid substitution, addition, or deletion that promotes heterodimerization.

31 . The antibody of any one of claims 1-30 , wherein the antibody contains no more than one light chain or fragment thereof.

32 . The antibody of any one of claims 1-31 , wherein the antibody comprises no more than a single heavy chain of an IgG or fragment thereof and a single light chain of an IgG or a fragment thereof.

33 . The antibody of any one of claims 1-18 and 20-32 , wherein the antibody comprises the amino acid substitution S228P according to EU numbering.

34 . The antibody of any one of claims 1-33 , wherein the antibody comprises the amino acid substitutions L234A, L235A, and P331S (LALAPS) accordingly to EU numbering.

35 . The antibody of any one of claims 1-34 , wherein the antibody comprises the amino acid substitutions N325S and L328F (NSLF) according to EU numbering.

36 . The antibody of any one of claims 1-9, 17-19, 21-25, 31, and 32 , wherein the antibody comprises a heavy chain comprising amino acids 1-449 of SEQ ID NO:17 or the amino acid sequence of SEQ ID NO:17.

37 . The antibody of any one of claims 1-9, 17-19, 21-25, 31, 32, and 34 , wherein the antibody comprises a heavy chain comprising amino acids 1-449 of SEQ ID NO:18 or the amino acid sequence of SEQ ID NO:18.

38 . The antibody of any one of claims 1-9, 17-19, 21-25, 31, 32, and 35 , wherein the antibody comprises a heavy chain comprising amino acids 1-449 of SEQ ID NO:19 or the amino acid sequence of SEQ ID NO:19.

39 . The antibody of any one of claims 1-9, 17, 18, 20-25, 31, and 32 , wherein the antibody comprises a heavy chain comprising amino acids 1-446 of SEQ ID NO:20 or the amino acid sequence of SEQ ID NO:20.

40 . The antibody of any one of claims 1-9, 17-19, and 21-31 , wherein the antibody comprises a heavy chain comprising amino acids 1-453 of SEQ ID NO:29 or the amino acid sequence of SEQ ID NO:29.

41 . The antibody of claims 1-9, 17-19, 21-31, and 34 , wherein the antibody comprises a heavy chain comprising amino acids 1-449 of SEQ ID NO:30 or the amino acid sequence of SEQ ID NO:30.

42 . The antibody of claims 1-9, 17-19, 21-31, and 35 , wherein the antibody comprises a heavy chain comprising amino acids 1-449 of SEQ ID NO:31 or the amino acid sequence of SEQ ID NO:31.

43 . The antibody of any one of claims 1-9, 17, 18, and 20-31 , wherein the antibody comprises a heavy chain comprising amino acids 1-446 of SEQ ID NO:32 or the amino acid sequence of SEQ ID NO:32.

44 . The antibody of any one of claims 1-9, 17, 18, 20-31, and 33 , wherein the antibody comprises a heavy chain comprising amino acids 1-447 of SEQ ID NO:33 or the amino acid sequence of SEQ ID NO:33.

45 . The antibody of any one of claims 1-9, 17-19, and 21-35 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:21.

46 . The antibody of any one of claims 1, 2, 10-19, 21-25, 31, and 32 , wherein the antibody comprises a heavy chain comprising amino acids 1-448 of SEQ ID NO:22 or the amino acid sequence of SEQ ID NO:22.

47 . The antibody of any one of claims 1, 2, 10-19, 21-25, 31, 32, and 34 , wherein the antibody comprises a heavy chain comprising amino acids 1-448 of SEQ ID NO:23 or the amino acid sequence of SEQ ID NO:23.

48 . The antibody of any one of claims 1, 2, 10-19, 21-25, 31, 32, and 35 , wherein the antibody comprises a heavy chain comprising amino acids 1-448 of SEQ ID NO:24 or the amino acid sequence of SEQ ID NO:24.

49 . The antibody of any one of claims 1, 2, 10-18, 20-25, 31, and 32 , wherein the antibody comprises a heavy chain comprising amino acids 1-445 of SEQ ID NO:25 or the amino acid sequence of SEQ ID NO:25.

50 . The antibody of any one of claims 1, 2, 10-19, and 21-31 , wherein the antibody comprises a heavy chain comprising amino acids 1-448 of SEQ ID NO:34 or the amino acid sequence of SEQ ID NO:34.

51 . The antibody of any one of claims 1, 2, 10-19, 21-31, and 34 , wherein the antibody comprises a heavy chain comprising amino acids 1-448 of SEQ ID NO:35 or the amino acid sequence of SEQ ID NO:35.

52 . The antibody of any one of claims 1, 2, 10-19, 21-31, and 35 , wherein the antibody comprises a heavy chain comprising amino acids 1-448 of SEQ ID NO:36 or the amino acid sequence of SEQ ID NO:36.

53 . The antibody of any one of claims 1, 2, 10-18, and 20-31 , wherein the antibody comprises a heavy chain comprising amino acids 1-445 of SEQ ID NO:37 or the amino acid sequence of SEQ ID NO:37.

54 . The antibody of any one of claims 1, 2, 10-18, 20-31, and 33 , wherein the antibody comprises a heavy chain comprising amino acids 1-445 of SEQ ID NO:38 or the amino acid sequence of SEQ ID NO:38.

55 . The antibody of any one of claims 1, 2, 10-19, and 21-35 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:26.

56 . The antibody of any one of claims 1-19, 21-31, 34, and 35 , wherein the antibody comprises a heavy chain constant region comprising amino acids 1-226 of SEQ ID NO:40 or the amino acid sequence of SEQ ID NO:40.

57 . The antibody of any one of claims 1-19, 21-31, 34, and 35 , wherein the antibody comprises a heavy chain constant region comprising amino acids 1-226 of SEQ ID NO:41 or the amino acid sequence of SEQ ID NO:41.

58 . The antibody of any one of claims 1-19, 21-31, 34, and 35 , wherein the antibody comprises a heavy chain constant region comprising amino acids 1-226 of SEQ ID NO:42 or the amino acid sequence of SEQ ID NO:42.

59 . The antibody of any one of claims 1-18, 20-31, 34, and 35 , wherein the antibody comprises a heavy chain constant region comprising amino acids 1-228 of SEQ ID NO:43 or the amino acid sequence of SEQ ID NO:43.

60 . The antibody of any one of claims 1-19, 21-31, and 33-35 , wherein the antibody comprises a heavy chain constant region comprising amino acids 1-228 of SEQ ID NO:44 or the amino acid sequence of SEQ ID NO:44.

61 . The antibody of any one of claims 1-9, 17-19, 21-31, and 56 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-453 of SEQ ID NO:29 or the amino acid sequence of SEQ ID NO:29, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:21, and (iii) a fragment of a heavy chain comprising amino acids 1-226 of SEQ ID NO:40 or the amino acid sequence of SEQ ID NO:40.

62 . The antibody of any one of claims claims 1-9, 17-19, 21-31, 34, and 57 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-449 of SEQ ID NO:30 or the amino acid sequence of SEQ ID NO:30, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:21, and (iii) a fragment of a heavy chain comprising amino acids 1-226 of SEQ ID NO:41 or the amino acid sequence of SEQ ID NO:41.

63 . The antibody of any one of claims 1-9, 17-19, 21-31, 35, and 58 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-449 of SEQ ID NO:31 or the amino acid sequence of SEQ ID NO:31, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:21, and (iii) a fragment of a heavy chain comprising amino acids 1-226 of SEQ ID NO:42 or the amino acid sequence of SEQ ID NO:42.

64 . The antibody of any one of claims 1-9, 17, 18, 20-31, and 59 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-446 of SEQ ID NO:32 or the amino acid sequence of SEQ ID NO:32, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:21, and (iii) a fragment of a heavy chain comprising amino acids 1-228 of SEQ ID NO:43 or the amino acid sequence of SEQ ID NO:43.

65 . The antibody of any one of claims 1-9, 17, 18, 20-31, 33, and 60 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-446 of SEQ ID NO:33 or the amino acid sequence of SEQ ID NO:33, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:21, and (iii) a fragment of a heavy chain comprising amino acids 1-228 of SEQ ID NO:44 or the amino acid sequence of SEQ ID NO:44.

66 . The antibody of any one of claims 1, 2, 10-19, 21-31, and 56 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-448 of SEQ ID NO:34 or the amino acid sequence of SEQ ID NO:34, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:26, and (iii) a fragment of a heavy chain comprising amino acids 1-226 of SEQ ID NO:40 or the amino acid sequence of SEQ ID NO:40.

67 . The antibody of any one of claims claims 1, 2, 10-19, 21-31, 34, and 57 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-448 of SEQ ID NO:35 or the amino acid sequence of SEQ ID NO:35, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:26, and (iii) a fragment of a heavy chain comprising amino acids 1-226 of SEQ ID NO:41 or the amino acid sequence of SEQ ID NO:41.

68 . The antibody of any one of claims 1, 2, 10-19, 21-31, 35, and 58 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-448 of SEQ ID NO:36 or the amino acid sequence of SEQ ID NO:36, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:26, and (iii) a fragment of a heavy chain comprising amino acids 1-226 of SEQ ID NO:42 or the amino acid sequence of SEQ ID NO:42.

69 . The antibody of any one of claims 1, 2, 10-18, 20-31, and 59 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-445 of SEQ ID NO:37 or the amino acid sequence of SEQ ID NO:37, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:26, and (iii) a fragment of a heavy chain comprising amino acids 1-228 of SEQ ID NO:43 or the amino acid sequence of SEQ ID NO:43.

70 . The antibody of any one of claims 1, 2, 10-18, 20-31, 33, and 60 , wherein the antibody comprises (i) a heavy chain comprising amino acids 1-445 of SEQ ID NO:38 or the amino acid sequence of SEQ ID NO:38, (ii) a light chain comprising the amino acid sequence of SEQ ID NO:26, and (iii) a fragment of a heavy chain comprising amino acids 1-228 of SEQ ID NO:44 or the amino acid sequence of SEQ ID NO:44.

71 . The antibody of any one of claims 1-70 , wherein the antibody binds to M2c-differentiated human macrophages with a Kd of no more than 100 nM as measured by Fluorescence-Activated Cell Sorting (FACS).

72 . The antibody of claim 71 , wherein the antibody binds to M2c-differentiated human macrophages with a Kd of no more than 10 nM as measured by FACS.

73 . The antibody of any one of claims 1-72 , wherein the antibody binds to CHO cells overexpressing human MerTK (CHO-huMerTK OE) with a Kd of no more than 50 nM as measured by FACS.

74 . The antibody of claim 73 , wherein the antibody binds to CHO-huMerTK OE with a Kd of no more than 10 nM as measured by FACS.

75 . The antibody of any one of claims 1-74 , wherein the antibody reduces efferocytosis by a phagocytic cell.

76 . The antibody of claim 75 , wherein the antibody reduces efferocytosis with an IC50 value of no more than 50 nM.

77 . The antibody of claim 75 , wherein the antibody reduces efferocytosis with an IC50 value of about 0.13 nM to about 30 nM.

78 . The antibody of claim 75 , wherein the antibody reduces efferocytosis with an IC50 value of about 4 nM to about 37 nM.

79 . The antibody of claim 75 , wherein the antibody reduces efferocytosis with an IC50 value of no more than 5 nM.

80 . The antibody of any one of claims 75-79 , wherein the phagocytic cell is a macrophage, a tumor-associated macrophage, or a dendritic cell.

81 . The antibody of claim 80 , wherein the phagocytic cell is a macrophage.

82 . The antibody of any one of claims 1-81 , wherein the antibody inhibits pAKT activity in the presence of Gas6.

83 . The antibody of any one of claims 1-82 , wherein the antibody binds to human MerTK with a Kd of no more than 100 nM, optionally with a Kd of about 50 nM.

84 . The antibody of any one of claims 1-83 , wherein the antibody binds to human MerTK with a Kd of no more than 5 nM, optionally with a Kd of about 2 nM.

85 . The antibody of any one of claims 1-84 , wherein the antibody binds to cynomolgus MerTK.

86 . The antibody of claim 85 , wherein the antibody binds to cynomolgus MerTK with a Kd of no more than 100 nM, optionally with a Kd of about 60 nM.

87 . The antibody of claim 85 , wherein the antibody binds to cynomolgus MerTK with a Kd of no more than 5 nM, optionally with a Kd of about 3 nM.

88 . The antibody of any one of claims 1-87 , wherein the antibody binds to murine MerTK.

89 . The antibody of claim 88 , wherein the antibody binds to murine MerTK with a Kd of no more than 50 nM, optionally with a Kd of about 40 nM.

90 . The antibody of any one of claims 1-87 , wherein the antibody does not bind to murine MerTK.

91 . The antibody of any one of claims 1-90 , wherein the antibody reduces binding of ProS to MerTK.

92 . The antibody of any one of claims 1-91 , wherein the antibody reduces binding of Gas6 to MerTK.

93 . The antibody of any one of claims 1-92 , wherein the antibody reduces binding of ProS to MerTK and reduces the binding of Gas6 to MerTK.

94 . The antibody of any one of claims 1-93 , wherein the antibody is a murine antibody, a human antibody, a humanized antibody, a monoclonal antibody, a conjugated antibody, or a chimeric antibody

95 . A humanized form of the antibody of any one of claims 1-94 .

96 . The antibody of any one of claims 1-95 , wherein the antibody is a recombinant antibody.

97 . The antibody of any one of claims 1-96 , wherein the antibody is an isolated antibody.

98 . An isolated nucleic acid comprising a nucleotide sequence encoding the antibody of any one of claims 1-97 .

99 . A vector comprising the nucleic acid of claim 98 .

100 . An isolated host cell comprising the nucleic acid of claim 98 or the vector of claim 99 .

101 . An isolated host cell comprising (i) a nucleic acid comprising a nucleic acid sequence encoding a VH of the antibody of any one of claims 1-97 and (ii) a nucleic acid comprising a nucleic acid sequence encoding a VL of the anti-MerTK antibody.

102 . An isolated host cell comprising (i) a nucleic acid comprising a nucleic acid sequence encoding the heavy chain of the antibody of any one of claims 1-97 and (ii) a nucleic acid comprising a nucleic acid sequence encoding the light chain of the anti-MerTK antibody.

103 . The isolated host cell of claim 102 , further comprising a nucleic acid comprising a nucleic acid sequence encoding a heavy chain fragment, wherein the heavy chain fragment does not contain a variable heavy chain domain.

104 . The isolated host cell of claim 103 , wherein the heavy chain fragment comprises a CH2 domain and a CH3 domain, optionally wherein the second heavy chain or fragment thereof further comprises a hinge domain.

105 . A method of producing an antibody that binds to human MerTK, the method comprising culturing the cell of any one of claims 100-104 so that the antibody is produced.

106 . The method of claim 105 , further comprising recovering the antibody produced by the cell.

107 . An antibody produced by the method of claim 105 or 106 .

108 . A pharmaceutical composition comprising the antibody of any one of claims 1-97 and 107 and a pharmaceutically acceptable carrier.

109 . The pharmaceutical composition of claim 108 , further comprising an anti-PD-L1 antibody, an anti-PD-L2 antibody, or an anti-PD-1 antibody.

110 . The pharmaceutical composition of claim 108 , further comprising an anti-PD-L1 antibody

111 . The pharmaceutical composition of claim 110 , wherein the anti-PD-L1 antibody is atezolizumab.

112 . A method of treating cancer in an individual, the method comprising administering to the individual a therapeutically effective amount of the antibody of any one of claims 1-97 and 107 or the pharmaceutical composition of any one of claims 108-111 .

113 . The method of claim 112 , wherein the cancer is colon cancer, ovarian cancer, liver cancer, or endometrial cancer.

114 . The method of claim 112 or 113 , wherein the administration does not lead to a retinal pathology in the individual.

115 . The method of any one of claims 112-114 , further comprising administering an anti-PD-L1 antibody, an anti-PD-L2 antibody, or an anti-PD-1 antibody to the individual.

116 . The method of any one of claims 112-114 , further comprising administering an anti-PD-L1 antibody to the individual.

117 . The method of claim 116 , wherein the anti-PD-L1 antibody is atezolizumab.

118 . A method for detecting MerTK in a sample comprising contacting said sample with the antibody of any one of claims 1-97 and 107 .