ANTI-MS4A4A ANTIBODIES AND METHODS OF USE THEREOF
The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal antibodies, humanized antibodies and antibody fragments, that specifically bind a MS4A4A polypeptide, e.g., a mammalian MS4A4A or human MS4A4A, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.
1 - 85 . (canceled)
86 . A method of detecting MS4A4A protein in an individual or in a tissue sample derived from an individual comprising contacting the individual or the tissue sample derived from an individual with an isolated antibody that binds to the MS4A4A protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: an HVR-H1 comprising an amino acid sequence of SEQ ID NO:308; an HVR-H2 comprising an amino acid sequence of SEQ ID NO:309; and an HVR-H3 comprising an amino acid sequence of SEQ ID NO:310; and the light chain variable region comprises: an HVR-L1 comprising an amino acid sequence of SEQ ID NO:314; an HVR-L2 comprising an amino acid sequence of SEQ ID NO:315; and an HVR-L3 comprising an amino acid sequence of SEQ ID NO:316.
87 . A method of detecting MS4A4A protein in an individual or in a tissue sample derived from an individual comprising contacting the individual or the tissue sample derived from an individual with an isolated antibody that binds to the MS4A4A protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: an HVR-H1 comprising the amino acid sequence of SEQ ID NO:94; an HVR-H2 comprising the amino acid sequence of SEQ ID NO:96; and an HVR-H3 comprising the amino acid sequence of SEQ ID NO:102; and the light chain variable region comprises: an HVR-L1 comprising the amino acid sequence of SEQ ID NO:104; an HVR-L2 comprising the amino acid sequence of SEQ ID NO:105; and an HVR-L3 comprising the amino acid sequence of SEQ ID NO:107.
88 . A method of detecting MS4A4A protein in an individual or in a tissue sample derived from an individual comprising contacting the individual or the tissue sample derived from an individual with an isolated antibody that binds to the MS4A4A protein, wherein the antibody comprises a heavy chain variable region comprising an HVR-H1, HVR-H2, and HVR-H3 and a light chain variable region comprising an HVR-L1, HVR-L2, and HVR-L3, wherein the antibody comprises the HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 of SEQ ID NOs: 94, 98, 100, 103, 105, and 107, respectively; SEQ ID NOs: 94, 96, 101, 103, 106, and 107, respectively; SEQ ID NOs: 94, 99, 100, 104, 105, and 107, respectively; SEQ ID NOs: 116, 118, 124, 130, 139, and 144, respectively; SEQ ID NOs: 116, 118, 124, 132, 139, and 144, respectively; SEQ ID NOs: 116, 118, 124, 133, 139, and 144, respectively; SEQ ID NOs: 116, 118, 124, 136, 139, and 144, respectively; SEQ ID NOs: 116, 118, 124, 130, 139, and 145, respectively; SEQ ID NOs: 116, 118, 124, 138, 141, and 144, respectively; SEQ ID NOs: 116, 118, 124, 130, 141, and 144, respectively; SEQ ID NOs: 116, 118, 125, 130, 139, and 145, respectively; SEQ ID NOs: 116, 118, 127, 131, 139, and 144, respectively; SEQ ID NOs: 116, 118, 129, 131, 139, and 144, respectively; SEQ ID NOs: 116, 118, 129, 132, 139, and 144, respectively; SEQ ID NOs: 116, 118, 129, 133, 139, and 144, respectively; SEQ ID NOs: 116, 118, 129, 134, 139, and 144, respectively; SEQ ID NOs: 116, 118, 129, 135, 139, and 144, respectively; SEQ ID NOs: 116, 118, 129, 136, 139, and 144, respectively; SEQ ID NOs: 147, 149, 154, 156, 160, and 163, respectively; SEQ ID NOs: 146, 150, 154, 156, 160, and 163, respectively; SEQ ID NOs: 147, 149, 154, 157, 159, and 163, respectively; SEQ ID NOs: 147, 151, 154, 156, 160, and 163, respectively; SEQ ID NOs: 147, 151, 154, 158, 159, and 163, respectively; SEQ ID NOs: 146, 152, 154, 156, 161, and 163, respectively; SEQ ID NOs: 146, 153, 154, 158, 159, and 163, respectively; or SEQ ID NOs: 311, 312, 313, 317, 318, and 319, respectively.
89 . The method of claim 86 , wherein the individual is a human.
90 . The method of claim 86 , wherein the detecting comprises quantifying antigen-bound antibody.
91 . The method of claim 86 , wherein the detecting in the tissue sample is performed by immunofluorescence microscopy, immunocytochemistry, immunohistochemistry, ELISA, FACS analysis, immunoprecipitation, or micro-positron emission tomography.
92 . The method of claim 86 , wherein the detecting in the individual is performed by positron emission tomography (PET), X-ray computed tomography, single-photon emission computed tomography (SPECT), computed tomography (CT), or computed axial tomography (CAT).
93 . The method of claim 86 , wherein the antibody is radiolabeled.
94 . The method of claim 87 , wherein the individual is a human.
95 . The method of claim 87 , wherein the detecting comprises quantifying antigen-bound antibody.
96 . The method of claim 87 , wherein the detecting in the tissue sample is performed by immunofluorescence microscopy, immunocytochemistry, immunohistochemistry, ELISA, FACS analysis, immunoprecipitation, or micro-positron emission tomography.
97 . The method of claim 87 , wherein the detecting in the individual is performed by positron emission tomography (PET), X-ray computed tomography, single-photon emission computed tomography (SPECT), computed tomography (CT), or computed axial tomography (CAT).
98 . The method of claim 87 , wherein the antibody is radiolabeled.
99 . The method of claim 88 , wherein the individual is a human.
100 . The method of claim 88 , wherein the detecting comprises quantifying antigen-bound antibody.
101 . The method of claim 88 , wherein the detecting in the tissue sample is performed by immunofluorescence microscopy, immunocytochemistry, immunohistochemistry, ELISA, FACS analysis, immunoprecipitation, or micro-positron emission tomography.
102 . The method of claim 88 , wherein the detecting in the individual is performed by positron emission tomography (PET), X-ray computed tomography, single-photon emission computed tomography (SPECT), computed tomography (CT), or computed axial tomography (CAT).
103 . The method of claim 88 , wherein the antibody is radiolabeled.
104 . The method of claim 86 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:304, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:305.
105 . The method of claim 87 , wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:14, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:22.
106 . The antibody of claim 88 , wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region comprise the amino acid sequences of SEQ ID NOs:12 and 17, respectively; SEQ ID NOs:13 and 21, respectively; SEQ ID NOs:15 and 22, respectively; SEQ ID NOs:47 and 55, respectively; SEQ ID NOs:47 and 63, respectively; SEQ ID NOs:47 and 64, respectively; SEQ ID NOs:47 and 67, respectively; SEQ ID NOs:47 and 69, respectively; SEQ ID NOs:47 and 71, respectively; SEQ ID NOs:47 and 73, respectively; SEQ ID NOs:48 and 69, respectively; SEQ ID NOs:50 and 62, respectively; SEQ ID NOs:53 and 62, respectively; SEQ ID NOs: 53 and 63, respectively; SEQ ID NOs: 53 and 64, respectively; SEQ ID NOs: 53 and 65, respectively; SEQ ID NOs: 53 and 66, respectively; SEQ ID NOs: 53 and 67, respectively; SEQ ID NOs: 76 and 86, respectively; SEQ ID NOs: 77 and 87, respectively; SEQ ID NOs: 78 and 88, respectively; SEQ ID NOs: 79 and 89, respectively; SEQ ID NOs: 80 and 90, respectively; SEQ ID NOs: 81 and 91, respectively; SEQ ID NOs: 82 and 91, respectively; SEQ ID NOs: 83 and 92, respectively; SEQ ID NOs: 84 and 93, respectively; or SEQ ID NOs:306 and 307, respectively.
107 . The antibody method of claim 86 , wherein the antibody is an antibody fragment.
108 . The antibody method of claim 107 , wherein the antibody fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.
109 . The antibody method of claim 87 , wherein the antibody is an antibody fragment.
110 . The antibody method of claim 109 , wherein the antibody fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.
111 . The antibody method of claim 88 , wherein the antibody is an antibody fragment.
112 . The antibody method of claim 111 , wherein the antibody fragment is a Fab, Fab′, Fab′-SH, F(ab′)2, Fv or scFv fragment.