inebilizumab   

GtoPdb Ligand ID: 7992

Synonyms: HB12 [6] | inebilizumab-cdon | MEDI 551 | MEDI-551 | MEDI551 | Uplizna®
inebilizumab is an approved drug (FDA (2020))
Compound class: Antibody
Comment: Inebilizumab is a humanized monoclonal antibody (mAb) directed against CD19, a cell-surface antigen expressed on cells of B cell lineage. Inebilizumab has potential immunomodulating and antineoplastic activities. Tested preclinically as a mouse anti-CD19 mAb (clone HB12; [6]), and initially humanized by Cellective Therapeutics, Inc. (a spinout company from Duke University where the antibody began its life) prior to being acquired by MedImmune (now part of Astra Zeneca) for commercial development.

Peptide sequence and structural information for this antibody are available from its IMGT/mAb-db record. A protein BLAST search of patented sequences reveals 100% matches between the heavy and light variable sequences of inebilizumab and sequences 106 and 111 respectively, in patent US8323653 B2 [1]. A detailed peptide sequence analysis suggests that inebilizumab is likely to be clone 16C4 in this patent.
Bioactivity Comments
Inebilizumab exhibits ADCC in vitro and in vivo [5], and mediates in vitro ADCC and antibody-dependent cellular phagocytosis (ADCP) activities of primary human natural killer (NK) cells and macrophages against precursor-B acute lymphoblastic leukemia (ALL) cell lines and pediatric patient blasts [4]. These effects of inebilizumab are also described in patent US8323653 B2 [1]. The data in the table below is the preferred affinity quoted in the patent as no precise affinity constant is provided for 16C4 binding to CD19.
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
CD19 Hs Antibody Binding 9.3 – 10.3 pKd - 1
pKd 9.3 – 10.3 (Kd 5x10-10 – 5x10-11 M) [1]