Nerve growth factor (NGF) is indispensable during normal embryonic development 
and critical for the amplification of pain signals in adults. Intervention in 
NGF signaling holds promise for the alleviation of pain resulting from human 
diseases such as osteoarthritis, cancer and chronic lower back disorders. We 
developed a fast, high-fidelity method to convert a hybridoma-derived 
NGF-targeted mouse antibody into a clinical candidate. This method, termed 
Library Scanning Mutagenesis (LSM), resulted in the ultra-high affinity antibody 
tanezumab, a first-in-class anti-hyperalgesic specific for an NGF epitope. 
Functional and structural comparisons between tanezumab and the mouse 911 
precursor antibody using neurotrophin-specific cell survival assays and X-ray 
crystal structures of both Fab-antigen complexes illustrated high fidelity 
retention of the NGF epitope. These results suggest the potential for wide 
applicability of the LSM method for optimization of well-characterized 
antibodies during humanization.