JPWO2020214995A5 - - Google Patents

Claims (43)

An isolated antibody that binds to MerTK, said antibody binding to a fibronectin-like domain or immunoglobulin-like domain of MerTK . An isolated antibody that binds to MerTK, comprising: (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:4; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:5; and (c) SEQ ID NO:6. (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 1; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 2; 2. The antibody of claim 1 , comprising an HVR-L3 comprising amino acid sequence . (a) a heavy chain variable domain (VH) comprising a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:83; and (b) having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:65. 3. The antibody of claim 1 or 2 , comprising a light chain variable domain (VL) comprising the sequence. 4. The antibody of claim 3 , comprising a VH comprising the amino acid sequence of SEQ ID NO:83 and a VL comprising the amino acid sequence of SEQ ID NO:65 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 8, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 9 . 1. The antibody according to 1 . (a) a heavy chain variable domain (VH) comprising a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:86; and (b) a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:68. 6. The antibody of claim 5 , comprising a light chain variable domain (VL ) comprising: 7. The antibody of claim 6 , comprising a VH comprising the amino acid sequence of SEQ ID NO:86 and a VL comprising the amino acid sequence of SEQ ID NO:68 . The antibody of any one of claims 5-7 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:103 and a light chain comprising the amino acid sequence of SEQ ID NO:111 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 16; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 17; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 18 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15 . 1. The antibody according to 1 . (a) a heavy chain variable domain (VH) comprising a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:89 and (b) a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:70 10. The antibody of claim 9 , comprising a light chain variable domain (VL ) comprising: 11. The antibody of claim 10, comprising a VH comprising the amino acid sequence of SEQ ID NO:89 and a VL comprising the amino acid sequence of SEQ ID NO:70 . 12. The antibody of any one of claims 9-11 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:105 and a light chain comprising the amino acid sequence of SEQ ID NO:113 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 22; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 23; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 24 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 19, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 20, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 21 . 1. The antibody according to 1 . (a) a heavy chain variable domain (VH) comprising a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:92 and (b) a sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO:73 14. The antibody of claim 13 , comprising a light chain variable domain (VL ) comprising: 15. The antibody of claim 14 , comprising a VH comprising the amino acid sequence of SEQ ID NO:92 and a VL comprising the amino acid sequence of SEQ ID NO:73 . 16. The antibody of any one of claims 13-15 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:107 and a light chain comprising the amino acid sequence of SEQ ID NO:115. ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 27; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 29 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 25, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26 . 1. The antibody according to 1 . 18. The antibody of claim 17 , comprising a VH comprising the amino acid sequence of SEQ ID NO:93 and a VL comprising the amino acid sequence of SEQ ID NO:74 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:33, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:34, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:35, The antibody of claim 1 . 20. The antibody of claim 19 , comprising a VH comprising the amino acid sequence of SEQ ID NO:94 and a VL comprising the amino acid sequence of SEQ ID NO:75 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 38; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 39; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 40 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 36, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 37 . 1. The antibody according to 1 . 22. The antibody of claim 21 , comprising a VH comprising the amino acid sequence of SEQ ID NO:95 and a VL comprising the amino acid sequence of SEQ ID NO:76 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 44; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 45; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 46 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 41, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 42, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 43 . 1. The antibody according to 1 . 24. The antibody of claim 23 , comprising a VH comprising the amino acid sequence of SEQ ID NO:96 and a VL comprising the amino acid sequence of SEQ ID NO:77 . An isolated antibody that binds to MerTK, comprising: (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:50; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:51; and (c) SEQ ID NO:52. (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:47; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:48; and (f) the amino acid sequence of SEQ ID NO:49. an antibody comprising HVR-L3 comprising 26. The antibody of claim 25 , comprising a VH comprising the amino acid sequence of SEQ ID NO:99 and a VL comprising the amino acid sequence of SEQ ID NO:80 . 27. The antibody of claim 25 or 26 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:109 and a light chain comprising the amino acid sequence of SEQ ID NO:117 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 56; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 57; (c) HVR- H3 comprising the amino acid sequence of SEQ ID NO: 58; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO:53, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:54, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:55 . 1. The antibody according to 1 . 29. The antibody of claim 28, comprising a VH comprising the amino acid sequence of SEQ ID NO:100 and a VL comprising the amino acid sequence of SEQ ID NO:81 . ( a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 62; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 63; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64 ; ) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 59, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 60, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 61 . 1. The antibody according to 1 . 31. The antibody of claim 30 , comprising a VH comprising the amino acid sequence of SEQ ID NO:101 and a VL comprising the amino acid sequence of SEQ ID NO:82 . 32. The antibody of any one of claims 1-31 , which is a full length IgG1 antibody, IgG2 antibody, IgG3 antibody or IgG4 antibody. 33. The antibody of claim 32 , comprising a L ALAPG mutation. 34. The antibody of any one of claims 1-33 , which is a monoclonal antibody. 34. The antibody of any one of claims 1-33 , which is a humanized antibody or a chimeric antibody. 34. The antibody of any one of claims 1-33 , which is an antibody fragment that binds to MerTK . An isolated nucleic acid encoding the antibody of any one of claims 1-36 . A vector comprising the nucleic acid of claim 37 . A host cell comprising the vector of claim 38 . Producing an anti-MerTK antibody, comprising culturing the host cell of claim 39 in a cell culture under conditions suitable for expression of the antibody , and recovering the anti-MerTK antibody from the cell culture. Method. Use of an antibody according to any one of claims 1-36 in the manufacture of a medicament. 42. Use according to claim 41 , wherein the medicament is for treating cancer. A medicament for the treatment of cancer comprising an antibody according to any one of claims 1-36.