
Implementation of an in Silico Antibody Engineering Environment to engineer therapeutic antibodiesAward last edited on: 7/10/2015
Sponsored Program
SBIRAwarding Agency
NSFTotal Award Amount
$172,987Award Phase
1Solicitation Topic Code
-----Principal Investigator
Juan Carlos AlmagroCompany Information
Phase I
Contract Number: ----------Start Date: ---- Completed: ----
Phase I year
2015Phase I Amount
$172,987This SBIR Phase I project proposes the development of an automated antibody humanization platform. Humanization methods are key to engineering nonhuman antibodies for human therapy, and their development has been driven by three main goals: (1) Increase human content to minimize immunogenic reactions; (2) preserve binding profile to retain potency and minimize costs in further engineering processes, e.g., affinity maturation; and (3) secure intellectual property. The proposed platform aims to maximize all three of these goals as follows. First, knowledge-based rules will be used to select human germline genes as framework region (FR) donors for nonhuman Complementary-Determining Regions (CDRs) grafting. It is expected that the selected FRs preserve binding and facilitate further development of the therapeutic antibody. Second, the CDRs will be humanized. CDR grafting protocols typically do not modify the CDRs; however, based on work published by the PI, it is anticipated that the number of nonhuman residues in the CDRs can be reduced significantly without impacting binding. If so, the final product will be indistinguishable from human antibodies isolated from transgenic mice or phage display libraries. As proof of concept, the biochemical and biophysical profiles of designs generated by our computational platform will be assessed experimentally.
Phase II
Contract Number: ----------Start Date: ---- Completed: ----