Engineering monoclonal antibodies to improve stability and production titer

Abstract

Provided herein are methods directed to engineering monoclonal antibodies and antibody variants to improve stability and their production in culture. Specifically, the monoclonal antibodies can be engineered at heavy chain residue 56 (AHo numbering) to a glycine, alanine, or serine, and / or engineered at position 80 (AHo) to be a hydrophobic residue such as alanine, isoleucine, phenylalanine, leucine, methionine, or valine.

Description

[0001] related application [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 787,867, filed January 3, 2019, which is hereby incorporated by reference in its entirety. technical field [0003] Topics presented relate to the field of protein engineering. Specifically, the proposed subject matter relates to engineering antibodies, especially monoclonal antibodies and variants thereof, to improve their stability and yield. Background technique [0004] Recombinantly produced monoclonal antibodies (mAbs) (and their active fragments) are important therapeutic tools. However, due to the complexity of these molecules, many challenges need to be faced in order to facilitate the production, storage and therapeutic administration of these molecules. [0005] Two challenges relate to yield and stability. mAbs are produced in bioreactors from engineered cells such as Chinese Hamster Ovary (CHO) cells. However, production levels may be low and may va...

AI Technical Summary

Problems solved by technology

However, production levels may be low and may vary from mAb to mAb

Low production levels increase production costs, including production time, manpower, and resources consumed (e.g., components required for bioreactor operation)

In addition, lack of stability can affect the "shelf life" of mAbs

Degraded mAbs may be less potent, and fragmented mAbs may present immunological risks

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