Variant cd3-binding domains and their use in combination therapies for the treatment of disease

• Main Authors: Ralph Froman ALDERSON, Chia-Ying Kao LAM, Gurunadh Reddy CHICHILI, Ling HUANG, Ezio BONVINI, Leslie S. JOHNSON, Paul A. MOORE
• Format: Patent
• Language: English; Hebrew
• Published: 30.09.2020

The present invention is directed to DA×CD3 Binding Molecules comprising a vCD3-Binding Domain, which comprises a CDRH1 Domain, a CDRH2 Domain, a CDRH3 Domain, a CDRL1 Domain, a CDRL2 Domain, and a CDRL3 Domain, at least one of which differs in amino acid sequence from the amino acid sequence of the corresponding CDR of a rCD3-Binding Domain, wherein the DA×CD3 Binding Molecule comprising such vCD3-Binding Domain exhibits an altered affinity for CD3, relative to a DA×CD3 Binding Molecule comprising such rCD3-Binding Domain. The invention particularly concerns to such DA×CD3 Binding Molecules comprising a vCD3-Binding Domain which exhibit reduced affinity for CD3 and are capable of mediating redirected killing of target cells expressing a DA and exhibit lower levels of cytokine release relative to a DA×CD3 Binding Molecule comprising a rCD3-Binding Domain. The invention particularly concerns the use of DA×CD3 Binding Molecules comprising a vCD3-Binding Domain in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).