Methods for treatment of cancer with an anti-tigit antagonist antibody
US-2024424092-A1 · Dec 26, 2024 · US
US2016355583A1 · US · A1
| Field | Value |
|---|---|
| Publication number | US-2016355583-A1 |
| Application number | US-201615165150-A |
| Country | US |
| Kind code | A1 |
| Filing date | May 26, 2016 |
| Priority date | Jun 5, 2015 |
| Publication date | Dec 8, 2016 |
| Grant date | — |
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The present invention relates to isolated antibodies and antigen-binding fragments thereof which bind human BMP9 and compositions and methods of use thereof.
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What is claimed is: 1 . An isolated antibody or antigen-binding fragment thereof, which binds human BMP9 and comprises: (a) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 61, 62 and 63, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 71, 72 and 73, respectively; (b) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 64, 65 and 66, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 74, 75 and 76, respectively; (c) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 1, 2 and 3, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 11, 12 and 13, respectively; (d) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 4, 5 and 6, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 14, 15 and 16, respectively; (e) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 21, 22 and 23, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 31, 32 and 33, respectively; (f) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 24, 25 and 26, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 34, 35 and 36, respectively; (g) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 41, 42 and 43, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 51, 52 and 53, respectively; (h) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 44, 45 and 46, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 54, 55 and 56, respectively; (i) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 81, 82 and 83, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 91, 92 and 93, respectively; (j) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 84, 85 and 86, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 94, 95 and 96, respectively; (k) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 101, 102 and 103, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 111, 112 and 113, respectively; (l) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 104, 105 and 106, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 114, 115 and 116, respectively; (m) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 121, 122 and 123, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 131, 132 and 133, respectively; (n) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 124, 125 and 126, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 134, 135 and 136, respectively; (o) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 141, 142 and 143, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 151, 152 and 153, respectively; (p) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 144, 145 and 146, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 154, 155 and 156, respectively; (q) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 161, 162 and 163, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 171, 172 and 173, respectively; or (r) the HCDR1, HCDR2, and HCDR3 sequences of SEQ ID NOs: 164, 165 and 166, respectively, and the LCDR1, LCDR2, and LCDR3 sequences of SEQ ID NOs: 174, 175 and 176, respectively. 2 . The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising: (a) A VH sequence of SEQ ID NO: 67; (b) A VH sequence of SEQ ID NO: 7; (c) A VH sequence of SEQ ID NO: 27; (d) A VH sequence of SEQ ID NO: 47; (e) A VH sequence of SEQ ID NO: 87; (f) A VH sequence of SEQ ID NO: 107; (g) A VH sequence of SEQ ID NO: 127; (h) A VH sequence of SEQ ID NO: 147; or (i) A VH sequence of SEQ ID NO: 167. 3 . The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising: (a) A VL sequence of SEQ ID NO: 77; (b) A VL sequence of SEQ ID NO: 17; (c) A VL sequence of SEQ ID NO: 37; (d) A VL sequence of SEQ ID NO: 57; (e) A VL sequence of SEQ ID NO: 97; (f) A VL sequence of SEQ ID NO: 117; (g) A VL sequence of SEQ ID NO: 137; (h) A VL sequence of SEQ ID NO: 157; or (i) A VL sequence of SEQ ID NO: 177. 4 . The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising: (a) A VH sequence of SEQ ID NO: 67 and a VL sequence of SEQ ID NO: 77; (b) A VH sequence of SEQ ID NO: 7 and a VL sequence of SEQ ID NO: 17; (c) A VH sequence of SEQ ID NO: 27 and a VL sequence of SEQ ID NO: 37; (d) A VH sequence of SEQ ID NO: 47 and VL sequence of SEQ ID NO: 57; (e) A VH sequence of SEQ ID NO: 87 and a VL sequence of SEQ ID NO: 97; (f) A VH sequence of SEQ ID NO: 107 and a VL sequence of SEQ ID NO: 117; (g) A VH sequence of SEQ ID NO: 127 and a VL sequence of SEQ ID NO: 137; (h) A VH sequence of SEQ ID NO: 147 and VL sequence of SEQ ID NO: 157; or (i) A VH sequence of SEQ ID NO: 167 and a VL sequence of SEQ ID NO: 177. 5 . The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising: (d) A heavy chain sequence of SEQ ID NO: 69; (b) A heavy chain sequence of SEQ ID NO: 9; (a) A heavy chain sequence of SEQ ID NO: 29; (c) A heavy chain sequence of SEQ ID NO: 49; (e) A heavy chain sequence of SEQ ID NO: 89; (f) A heavy chain sequence of SEQ ID NO: 109; (g) A heavy chain sequence of SEQ ID NO: 129; (h) A heavy chain sequence of SEQ ID NO: 149; or (i) A heavy chain sequence of SEQ ID NO: 169. 6 . The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising: (a) A light chain sequence of SEQ ID NO: 79; (b) A light chain sequence of SEQ ID NO: 19; (c) A light chain sequence of SEQ ID NO: 39; (d) A light chain sequence of SEQ ID NO: 59; (e) A light chain sequence of SEQ ID NO: 99; (f) A light chain sequence of SEQ ID NO: 119; (g) A light chain sequence of SEQ ID NO: 139; (h) A light chain sequence of SEQ ID NO: 159; or (i) A light chain sequence of SEQ ID NO: 179. 7 . The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising: (a) A heavy chain sequence of SEQ ID NO: 69; and a light chain sequence of SEQ ID NO: 79; (b) A heavy chain sequence of SEQ ID NO: 9; and a light chain sequence of SEQ ID NO: 19; (c) A heavy chain sequence of SEQ ID NO: 29; and a light chain sequence of SEQ ID NO: 39; (d) A heavy chain sequence of SEQ ID NO: 49; and a light chain sequence of SEQ ID NO: 59; (e) A heavy chain sequence of SEQ ID NO: 89; and a light chain sequence of SEQ ID NO: 99; (f) A heavy chain sequence of SEQ ID NO: 109; and a light chain sequence of SEQ ID NO: 119; (g) A heavy chain sequence of SEQ ID NO: 129; and a light chain sequence of SEQ ID NO: 139; (h) A heavy chain sequence of SEQ ID NO: 149; and a light chain sequence of SEQ ID NO: 159; or (i) A heavy chain sequence of SEQ ID NO: 169; and a light chain sequence of SEQ ID NO: 179. 8 . The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated antibody or antigen-binding fragment is an IgG, or is derived from an IgG. 9 . The isolated antibody or antigen-binding fragment thereof of claim 8 , wherein the IgG is selected from the group consisting of an IgG1, an IgG2, an IgG3 and an IgG4. 10 . The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated antibody or antigen-binding fragment is selected from the group consisting of: a monoclonal antibody, a chimeric antibody, a single chain antibody, a Fab and a scFv. 11 . The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof is a component of an immunoconjugate. 12 . The isolated antibody or antigen-binding fragment thereof o
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