Anti-CD30 and anti-CD3 bispecific antibodies and methods of immunotherapy for CD30+ malignancies

Inventors

Medin, Jeffrey A. • Lum, Lawrence G. • Oldham, Robyn A. A. • Thakur, Archana

Assignees

Medical College of Wisconsin • UVA Licensing and Ventures Group • University of Virginia UVA

Abstract

The present invention provides novel bispecific antibodies that bind to human CD30 and uses thereof. Methods of treating cancer using the bispecific antibodies described herein are also provided.

Core Innovation

The invention relates to isolated bispecific antibodies capable of binding human CD30 and CD3, where the bispecific antibody comprises an anti-CD30 antibody or antigen binding portion thereof and an anti-CD3 antibody or antigen binding portion thereof. The anti-CD30 binding portion is defined by specified light chain variable domain CDRL1, CDRL2, and CDRL3 regions and specified heavy chain variable domain CDRH1, CDRH2, and CDRH3 regions, with the CDR regions defined as SEQ ID NOs or sequences with at least 90% similarity to the SEQ ID NOs.

In the disclosed embodiments, multiple anti-CD30 antibody CDR-defined combinations are provided, including sets associated with SEQ ID NOs 2, 3, and 4; 10, 11, and 12; 18, 19, and 20; 26, 27, and 28; and 34, 35, and 36, together with corresponding heavy chain variable domain CDRH1, CDRH2, and CDRH3 regions associated with SEQ ID NOs 6, 7, and 8; 14, 15, and a CDRH3 region listed as GAY; 22, 23, and 24; 30, 31, and 32; and 38, 39, and 40. The anti-CD3 component is described as the OKT3 antibody, and a preferred NK-cell targeting variant is described by selection of the T-cell antigen as CD3 and the NK-cell antigen as CD16 in the provided summary.

The background problem being solved is the need for bispecific immunotherapy concepts for CD30+ malignancies, including hematologic malignancies, through targeting CD30 and T-cell- or NK-cell associated antigens. The document further characterizes the CD30 binding antibodies and their bispecific formats using binding characterization concepts including flow cytometry, ELISA, and competition/blocking, and discusses functional bispecific immunotherapy outcomes described as T-cell activation with IL-2 and IFN-gamma and CD30+ tumor cytotoxicity, including specificity versus CD30− cells.

Claims Coverage

The independent claims cover isolated bispecific antibodies that bind human CD30 and CD3, with anti-CD30 binding portions defined by CDRL/CDRH sequences as SEQ ID NOs or sequences with specified similarity. Across the independent claims, the core inventive features are the CDR-defined anti-CD30 antibody binding portion, the requirement to bind CD3, and optional narrowing by exact CDR sequences and conjugation/linker architecture in dependent claims. The inventive feature scope is grounded in multiple alternative CDR sets for the anti-CD30 component.

Overall, the independent claims define isolated bispecific antibodies binding human CD30 and CD3 by specifying anti-CD30 CDR-defined light- and heavy-chain variable domain regions via SEQ ID NOs or similarity-defined variants, including at least 90% similarity. The scope is further specified in other independent claims by exact SEQ ID CDR sequences for the anti-CD30 component, including a CDRH3 region listed as GAY, with CD3 binding being further narrowed in dependent claims to OKT3 from an ATCC accession.

Stated Advantages

Documented Applications