Methods and compositions for targeting polyubiquitin

An isolated antibody or antigen-binding fragment thereof that specifically binds to K63-linked polyubiquitin, comprising:

• the HVR-H1 sequence of SEQ ID NO:
• 5;
• the HVR-H2 sequence of SEQ ID NO:
• 61, optionally having one substitution selected from the following:
• (i) a D at position 1,
• (ii) an A at position 3,
• (iii) a T at position 3, or
• (iv) an L at position 6;
• the HVR-H3 sequence of SEQ ID NO:
• 6;
• the HVR-L1 sequence of SEQ ID NO:
• 3;
• the HVR-L2 sequence of SEQ ID NO:
• 9, wherein:
• (a) if HVR-H2 is SEQ ID NO:
• 61, then HVR-L2 optionally has a substitution of an R at position 4,
• (b) if HVR-H2 is SEQ ID NO:
• 61 substituted with a D at position 1, then HVR-L2 optionally has a substitution of a A, S, or T at position 4 of SEQ ID NO:
• 9;
• (c) if HVR-H2 is SEQ ID NO:
• 61 substituted with an A at position 3, then HVR-L2 optionally has a substitution of an A, L, or N at position 4 of SEQ ID NO:
• 9;
• and
• (d) if HVR-H2 is SEQ ID NO:
• 61 substituted with a T at position 3, then HVR-L2 optionally has a substitution of a T at position 4 of SEQ ID NO:
• 9;
• and
• the HVR-L3 sequence of SEQ ID NO:
• 4.