Example:

Human MIP-1alpha: a chemokine with therapeutic potential

Problem:

Protein aggregation causes production issues at scale & increases inflammatory properties of the product

Solution:

High-throughput, systematic & site-directed mutagenesis identified key amino acids responsible for protein aggregation. Development of a yeast secretion system for expression of pyrogen-free protein enabled rapid analytical ultracentrifugation assessment of aggregation & preclinical evaluation of the properties of the analogues leading to selection of BB-10010 as a candidate protein.

Reference Link:

Hunter MG, Bawden L, Brotherton D, Craig S, Cribbes S, Czaplewski LG, Dexter TM, Drummond AH, Heyworth CM, Lord BI, McCourt M, Varley PG, Wood LM, Edwards RM, Lewis PJ.  BB-10010: An active variant of human macrophage inflammatory protein-1 alpha with improved pharmaceutical properties.  Blood 86 (12) 4400-4408, 1995.

Czaplewski LG, McKeating J., Craven CJ, Higgins LD, Appay V, Brown A, Dudgeon T, Howard LA, Meyers T, Owen J, Palan SR, Tan P, Wilson G, Woods NR, Heyworth CM, Lord BI, Brotherton D, Christison R, Craig S, Cribbes S, Edwards RM, Evans SJ, Gilbert R, Morgan P, Randle E, Schofield N, Varley PG, Waltho JP, Hunter MG. Identification of amino acid residues critical for aggregation of human CC chemokines MIP-1alpha, MIP-1 beta, and RANTES: characterisation of active disaggregated variants. JBC 274, 16077-16084, 1999.