CPC C07K 16/18 (2013.01) [C07K 14/47 (2013.01); G01N 33/68 (2013.01); C07K 2317/14 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/92 (2013.01); G01N 2333/47 (2013.01); G01N 2440/36 (2013.01)] | 19 Claims |
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to K63-linked polyubiquitin, comprising: the HVR-L1 sequence of SEQ ID NO: 3; the HVR-L2 sequence of SEQ ID NO: 16, optionally having a substitution of an F at position 1 and an A at position 2, or one substitution selected from the following:
(i) an A at position 2,
(ii) a V at position 4, or
(iii) an S at position 4;
the HVR-L3 sequence of SEQ ID NO: 4;
the HVR-H1 sequence of SEQ ID NO: 5;
the HVR-H2 sequence of SEQ ID NO: 68, wherein
(a) if HVR-L2 is unsubstituted SEQ ID NO: 16, then HVR-H2 is unsubstituted SEQ ID NO: 68,
(b) if HVR-L2 is SEQ ID NO: 16 substituted with an F at position 1 and an A at position 2, then HVR-H2 has a substitution of an S at position 8 of SEQ ID NO: 68,
(c) if HVR-L2 is SEQ ID NO: 16 substituted with an A at position 2, then HVR-H2 is SEQ ID NO: 68 substituted with an S at position 8, or with a V and S at positions 3 and 8, respectively, or with a D, S, and S at positions 1, 3, and 8, respectively,
(d) if HVR-L2 is SEQ ID NO: 16 substituted with a V at position 4, then HVR-H2 is SEQ ID NO: 68 substituted with a Y and S at positions 3 and 8 of SEQ ID NO: 68, respectively, or with a T and S at positions 3 and 8 of SEQ ID NO: 68, respectively, and
(e) if HVR-L2 is SEQ ID NO: 16 substituted with an S at position 4, then HVR-H2 is SEQ ID NO: 68 substituted with an S at position 8 of SEQ ID NO: 68 or with a T and F at positions 3 and 8 of SEQ ID NO: 68, respectively, and
the HVR-H3 sequence of SEQ ID NO: 6.
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