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
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Publication Number
US-11459385-B2
Publication Date
2022-10-04
Expiration Date
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 provides an isolated antibody or antigen-binding portion that specifically binds human IL-2. The antibody is defined by complementarity determining regions comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, with specified SEQ ID NOs for the defined sequence set.
The invention relates to IL-2-binding human antibodies and antigen-binding portions that target human IL-2 helices A/C and the B-C loop. The binding profile includes altered IL-2 receptor binding intended to preferentially suppress CD8 signaling while sparing or expanding regulatory T cell function, with structural and binding evidence supporting the described mechanism.
The disclosed content includes human IL-2 antibody complementarity-determining regions, together with SEQ ID mappings and predefined CDR options. It includes antibodies and variable domain sequences such as F5.1.11.02, sequence listing tables, and a table mapping sequence identifiers to monoclonal antibody variable domains.
Claims Coverage
The provided independent claim covers an isolated antibody or antigen-binding portion specifically binding human IL-2, characterized by six sequence-defined complementarity determining regions with specified SEQ ID NOs. The claim coverage is focused on the sequence-defined antibody and extends in the inputs to related antibody formats and compositions.
Isolated antibody binding human IL-2 via defined HCDR1-3 and LCDR1-3
An isolated antibody or antigen-binding portion that specifically binds human IL-2, comprising HCDR1 comprising SEQ ID NO: 208, HCDR2 comprising SEQ ID NO: 211, HCDR3 comprising SEQ ID NO: 213, LCDR1 comprising SEQ ID NO: 214, LCDR2 comprising SEQ ID NO: 215, and LCDR3 comprising SEQ ID NO: 216.
IgG format for the antibody
The antibody, or the antigen-binding portion, is an IgG antibody.
Humanized antibody variant
The antibody, or the antigen-binding portion, is a humanized antibody.
Variable-region identity constraints relative to defined SEQ ID numbers
The antibody, or the antigen-binding portion, has a heavy chain variable region at least 95% identical to SEQ ID NO:31 and a light chain variable region at least 95% identical to SEQ ID NO:32.
Encoding isolated nucleic acid for antibody chains
An isolated nucleic acid encodes the heavy chain, the light chain, or both of the antibody or antigen-binding portion.
Pharmaceutical composition with antibody complexed with human IL-2 and a carrier or excipient
A pharmaceutical composition includes the antibody or antigen-binding portion complexed with human IL-2 and a pharmaceutically acceptable carrier or excipient.
Coverage is anchored on an isolated, human-IL-2-specific antibody defined by exact HCDR1/2/3 and LCDR1/2/3 SEQ ID numbers, with further narrowing through IgG and humanized formats, variable-region identity constraints, and extensions to nucleic acids and pharmaceutical compositions complexed with human IL-2 and pharmaceutically acceptable carriers or excipients.
Stated Advantages
Reduces IL-2 binding to IL-2Rα and IL-2Rβ.
Inhibits STAT5 phosphorylation in CD8+ T cells more than in Tregs.
Can shift the Treg/non-Treg balance, including via FOXP3, CD25, and ICOS maintenance and/or induction.
Preferential suppression of CD8 signaling while sparing or expanding regulatory T cell function.
Increased FOXP3, CD25, and ICOS, with increased Treg/CD8 or Treg/NK ratios.
Mechanistically supported receptor binding modulation based on IL-2Rα versus IL-2Rβ comparisons and structural occlusion of an IL-2Rβ site while not occluding CD25/γc sites.
Documented Applications
Therapeutic use for autoimmune diseases and inflammation.
Therapeutic use for immunosuppression.
Administration in an antibody–IL-2 complex context.
Therapeutic use for IL-2-mediated inflammatory and autoimmune diseases and immunosuppression.
Diagnostic/imaging uses using the disclosed antibodies and associated formats.
Use of kits related to the disclosed antibodies and formats.
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