Patent ID: 8679490

Claim:
A phage display antibody fragment library comprising a plurality of at least about 1×10 4 distinct antibody fragments, or a plurality of polynucleotides encoding the plurality of at least about 1×10 4 distinct antibody fragments, wherein each antibody fragment comprises a heavy chain variable domain (V H ) and a light chain variable domain (V L ) from a source antibody, wherein V H comprises a variant hypervariable region 3 (HVR-H3) wherein: (i) the variant HVR-H3 comprises an amino acid sequence: X1-X2-(X3)n-X4-D-X5 (SEQ ID NO: 18) wherein X1-X5 are naturally occurring amino acids other than cysteine, and X1 is position 95 according to the Kabat numbering system, and n=4-17; and at least one variant HVR selected from HVR-H2 and HVR-H1, wherein (ii) the variant HVR-H2 comprises an amino acid sequence: V-S-X1-I-X2-X3-X4-X5-G-X6-T-X7-Y-A-D-S-V-K-G (SEQ ID NO: 10) wherein X1-X7 are naturally occurring amino acids other than cysteine, and X1 is position 50 according to the Kabat numbering system; and (iii) the variant HVR-H1 comprises an amino acid sequence: G-X1-X2-F-X3-X4-X5-X6-X7-S-W-V (SEQ ID NO: 11) wherein X1-X7 are naturally occurring amino acids other than cysteine, wherein G is position 26 and X1 is position 27 according to the Kabat numbering system, wherein the distinct antibody fragments of the phage display antibody fragment library have amino acid diversity at position 99 or 100 of HVR-H3 and amino acid diversity at least at position 28, 30, 31, 32 or 33 of HVR-H1 or position 54 of HVR-H2, according to the Kabat numbering system, and wherein at least one of the distinct antibody fragments is capable of binding a target antigen of interest.