Patent ID: 8293233

Claim:
A method of identifying stable human or humanized target VH and/or VL antibody fragments, comprising: (a) obtaining a VH and/or VL phage display library and reducing the library size, yielding a phage display library expressing a variety of VH and/or VL antibody fragments, wherein the library size is reduced by panning against a target antigen, panning against a non-specific binder, or chromatography using a hydrophobic interaction column or otherwise removing wild type phage without inserts from the library; (b) allowing infection of a bacterial lawn by the library phage; (c) identifying phage which form larger than average plaques on the bacterial lawn; (d) isolating the larger plaque phage in step (c); and (e) determining the sequence or other characteristics of the VH and/or VL antibody fragments expressed by the phage forming larger plaques, wherein the human or humanized VH or VL antibody fragment expressed in the larger plaque phage isolated in step (d) i) is soluble, ii) is monomeric, iii) is nonaggregating, iv) has relatively high thermal refolding efficiency v) has relatively high melting temperature, vi) maintains its functionality following long incubation at 37° C., vii) is relatively resistant to chemical denaturants, viii) is relatively resistant to proteases, ix) has a relatively long shelf life at or above room temperature, at 4° C., or below 0° C., or x) any combination of the above; when compared to a human or humanized VH or VL antibody fragment expressed in average plaque-forming phage.