Engineered anti-IL-2 antibodies

Inventors

AMIT, Inbar • Levin, Itay • NIMROD, Guy • FISCHMAN, Sharon • BARAK FUCHS, Reut • STRAJBL, Marek • WYANT, Timothy • ZHENIN, Michael • BLUVSHTEIN YERMOLAEV, Olga • SASSON, Yehezkel • GROSSMAN, Noam • LEVITIN, Natalia • OFRAN, Yanay

Assignees

Biolojic Design Ltd • Aulos Bioscience Inc

Abstract

Described herein are engineered anti-IL-2 antibodies with modified amino acid sequences. The engineered antibodies would confer modified receptor binding specificity to an IL-2-anti-IL2 antibody complex, inhibiting the binding of IL-2 to CD25. The engineered anti-IL-2 antibodies would facilitate expansion of subsets of effector immune cells and decrease undesirable effects caused by IL-2. Thus, the engineered anti-IL-2 antibodies would be useful in treating disease such as cancer and infection.

Core Innovation

The invention relates to engineered anti-IL-2 antibodies and pharmaceutical compositions. The antibodies bind IL-2 at a predefined epitope to completely block IL-2 binding to CD25 (IL-2Rα) while preserving or sparing CD122 (IL-2Rβ) binding. This redirects IL-2 activity to selectively activate or expand effector immune cells while reducing IL-2-induced activation of regulatory T cells and IL-2-associated toxicities.

The disclosed approach is described as promoting differential growth of subsets of immune cells while decreasing undesirable effects caused by IL-2. In particular, the patent links the antibody binding behavior to outcomes including reduced regulatory T cells (FoxP3+ Tregs) and reduced IL-2-induced pulmonary edema and vascular leak syndrome (VLS). The immune cell subsets described include effector immune cells such as memory phenotype CD8+ T cells and NK/NKT cells.

The patent further provides specific anti-IL-2 antibody definitions using VH and VL complementarity determining regions (HCDRs and LCDRs) with amino acid sequences defined by SEQ ID NOs. It also describes antibody formats and pharmaceutical formulation components, including optional inclusion of IL-2, and optional Fc-gamma receptor binding-reducing heavy-chain mutation options. Combination therapy is described with immune checkpoint inhibitors targeting immune checkpoint pathways such as PD-1, PD-L1, CTLA-4, TIGIT, and TIM-3 and additional checkpoint targets listed in the document.

Claims Coverage

The independent claims cover four inventive features: an isolated anti-IL-2 antibody with defined VH/VL CDR sequences, a composition comprising the antibody and a pharmaceutically acceptable carrier, a method of treating cancer or SARS-CoV-2 viral infection by administration of the composition, and a method of protecting against pulmonary edema and lung tissue damage caused by SARS-CoV-2 or IL-2. Each feature is grounded in specific SEQ ID NO-defined CDR constraints.

Across the independent claims, the core coverage is anti-IL-2 antibodies defined by specific VH/VL CDR amino-acid sequences, their formulation with a pharmaceutically acceptable carrier, and their administration to treat cancer or SARS-CoV-2 infection with immune-cell subset modulation and reduced undesirable IL-2 effects, including protection against pulmonary edema and lung tissue damage.

Stated Advantages

Documented Applications