Binding polypeptides with restricted diversity sequences

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise a variant CDRH3 that comprises an amino acid sequence:

• (X1)n-A-M
• wherein X1 is an amino acid encoded by a restricted codon set that encodes 10 or fewer amino acids, and n=3 to 20.

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise a variant CDRH2 that comprises an amino acid sequence:

• X1-I-X2-P-(X3)n-G-X4-T-X5-Y-A
• (SEQ ID NO:131)
• wherein X1, X2, X3, X4 and/or X5 is an amino acid encoded by a restricted codon set that encodes 10 or fewer amino acids, and n=1 to 2.

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise a variant CDRH1 that comprises an amino acid sequence:

• G-F-X1-I-(X2)n-I
• (SEQ ID NO:132)
• wherein X1 and/or X2 is an amino acid encoded by a restricted codon set that encodes 10 or fewer amino acids, and n=2 to 4.

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise a variant CDRL3 that comprises an amino acid sequence:

• Q-X1-(X2)n-P-X3-T-F
• (SEQ ID NO:133)
• wherein X1 is Q or missing, and X2 and/or X3 is an amino acid encoded by a restricted codon set that encodes 10 or fewer amino acids, and n=2 to 4.

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise a variant CDRL2 that comprises an amino acid sequence:

• Y-X1-A-S-X2-L
• (SEQ ID NO:134)
• wherein X1 and/or X2 is an amino acid encoded by a restricted codon set that encodes 10 or fewer amino acids.

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise a variant CDRL1 that comprises an amino acid sequence:

• S-Q-(X1)n-V
• (SEQ ID NO:136)
• wherein X1 is an amino acid encoded by a restricted codon set that encodes 10 or fewer amino acids, and n=3 to 5.

A library comprising a plurality of at least 1×104 distinct polypeptide sequences, wherein the plurality of polypeptide sequences comprise at least one variant CDR selected from CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3, wherein at least one variant CDR has a variant amino acid in at least one solvent accessible and highly diverse amino acid position, wherein the variant amino acid in the at least one solvent accessible and highly diverse amino acid position is encoded by a restricted codon set that encodes 10 or fewer amino acids.

A library comprising a plurality of polypeptides, wherein the plurality of polypeptide sequences comprise at least one variant CDR selected from CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, wherein at least one variant CDR has a variant amino acid in at least three solvent accessible and highly diverse amino acid positions, wherein the variant amino acid in the at least three solvent accessible and highly diverse amino acid positions is encoded by a restricted codon set that encodes no more than 4 amino acids, and wherein the library has at least 1×104 distinct antibody variable domain sequences.