Anti-dengue virus antibodies, polypeptides containing variant Fc regions, and methods of use

Inventors

Sampei, Zenjiro • KOO, Xing'er Christine • Fink, Katja • ZUEST, Roland

Assignees

Chugai Pharmaceutical Co Ltd • Agency for Science Technology and Research Singapore • Chugai Pharmabody Research Pte Ltd

Abstract

The disclosure provides anti-DENV antibodies and methods of making and using the same. Nucleic acids encoding anti-DENV antibodies and host cells comprising the nucleic acids are also provided. The anti-DENV antibodies have uses that include treating DENV infection. The disclosure also provided polypeptides containing a variant Fc region and methods of making the same. Nucleic acids encoding polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include treating a viral infection. Also claimed is a polypeptide comprising a Fc variant comprising at least one amino acid alteration in a parent Fc region, wherein the variant Fc region has a substantially decreased FcYR-binding activity and does not have a substantially decreased C1 q-binding activity when compared to the parent Fc region.

Core Innovation

The disclosure provides anti-dengue virus (DENV) antibodies that bind to the DENV E protein. The antibodies are isolated antibodies including an isolated antibody, a monoclonal antibody, and an IgG, and the variable regions are defined by specific hypervariable regions (HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3). The hypervariable region amino-acid sequence sets are given as SEQ ID NO combinations that specify which HVR sequences are present in the antibody.

A further aspect of the disclosure is Fc engineering of the antibody or polypeptide through a variant Fc region and a parent Fc region. The engineered variant Fc region substantially decreases FcγR-binding activity while maintaining substantially unchanged or not substantially decreased C1q-binding activity, as compared to the parent Fc region. This functional selectivity is tied to reducing the risk associated with antibody-dependent enhancement (ADE).

The disclosure further includes antibody/polypeptide compositions and therapeutic use related to DENV, including compositions comprising nucleic acids encoding the antibodies/polypeptides, host cells, pharmaceutical formulations, and medicaments. It also describes assay modalities for characterizing FcγR and C1q binding activities, including binding measurements to FcγRs and C1q using BIACORE/SPR and ELISA.

Claims Coverage

The provided material includes three independent claims. Across these independent claims, the inventive features center on DENV E-protein binding antibody variable-region sequence definitions and Fc engineering defined by substantially decreased FcγR-binding activity with substantially unchanged or not substantially decreased C1q-binding activity, plus additional sequence combinations in the claim set.

Across the independent claims, the coverage centers on isolated antibodies that bind the DENV E protein and are defined by enumerated variable-region sequence identifiers or VH/VL/CH/CL combinations. Fc engineering is reflected in the claim set by substantially decreased FcγR-binding activity while substantially preserving C1q-binding activity relative to a parent Fc region.

Stated Advantages

Documented Applications