Anti-il-2 antibodies and compositions and uses thereof

Inventors

Rondon, Isaac J. • Crellin, Natasha • Bessette, Paul • Trotta, Eleonora • Bluestone, Jeffrey A. • Ely, Lauren K. • Garcia, Kenan C.

Assignees

Pfizer Inc • University of California San Diego UCSD • Leland Stanford Junior University

Abstract

The present invention provides antibodies, or antigen-binding portions thereof, which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2Rα and IL-2Rβ. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2.

Core Innovation

The invention relates to isolated antibodies and antigen-binding portions that specifically bind human interleukin-2 (IL-2). The antibodies are characterized by defined heavy chain complementarity determining regions and light chain complementarity determining regions, with specific HCDR and LCDR sequence identities provided in the sequence listing and variable-domain definitions using Kabat CDR, Chothia CDR, and extended CDR mappings.

The disclosure further includes antibody format features and constant-region definitions for IgG antibody embodiments, including heavy chain constant-region sequence requirements and light chain constant-region options. It also includes isolated nucleic acids, vectors, and host cells for producing the antibody variants, together with sequence-to-family mappings that associate antibody families with heavy and light variable domain identifiers.

The antibodies are described in terms of IL-2 epitopes and functional effects on IL-2 receptor engagement, including reduction of IL-2 binding to IL-2Rα and IL-2Rβ and functional bias toward Tregs over effector CD8+ T cells. The treatment context is administration of an antibody in complex with IL-2 for treating or preventing autoimmune and inflammatory diseases, including type 1 diabetes.

Claims Coverage

The provided material shows one independent claim covering a method for treating type 1 diabetes with a specifically IL-2-binding isolated antibody, with administration in complex with IL-2. The claim is constrained by six complementarity determining region elements defined by specified sequence IDs, and the dependent refinements add antibody format and sequence constraints.

Across the independent claim and the provided dependent refinements, the coverage centers on IL-2-targeting isolated antibodies defined by specific HCDR/LCDR sequences and used for treating type 1 diabetes where IL-2 activity is causative or associated, with administration required in complex with IL-2.

Stated Advantages

Documented Applications