Antibodies to CD122
Inventors
Tso, J. Yun • Tsurushita, Naoya • Landolfi, Nicholas F. • Kumar, Shankar
Assignees
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Publication Number
US-9028830-B2
Publication Date
2015-05-12
Expiration Date
Abstract
The invention provides monoclonal antibodies that specifically bind to CD122, which is one component of receptors for IL-2 and IL-15. The monoclonal antibodies have the capacity for substantial inhibition of both IL-2 and IL-15 mediated functions by inhibiting binding of these cytokines to their receptors. The monoclonal antibodies can be used for inhibiting undesired immune responses or treatment of cancer, among other applications.
Core Innovation
The invention relates to isolated monoclonal antibodies that specifically bind to CD122 (SEQ ID NO:73) and substantially inhibit both IL-2 and IL-15 receptor-mediated signaling. The antibodies are defined with antibody epitope and functional determinants that substantially interfere with signaling mediated through the IL-2 and IL-15 receptor pathways.
The antibodies are further defined by specific antibody CDR identity and sequence relationships, including defined light chain CDRs and heavy chain CDRs. One disclosed embodiment is an isolated monoclonal antibody defined by three light chain CDRs designated SEQ ID NOS. 27-29 and three heavy chain CDRs designated SEQ ID NOS. 22-24, where CD122 specificity is referenced to SEQ ID NO:73.
The specification includes epitope mapping and functional determinant definition by CD122 residue substitutions and the resulting effects on signaling and growth phenotypes. Functional support described in the document includes inhibition of IL-15 trans-presentation and IL-2-mediated proliferation, together with epitope mapping using chimeric CD122 domain constructs and single amino-acid mutants.
Claims Coverage
Independent claim coverage is provided by two independent claims (clm-00001 and clm-00007). The claims define CD122-binding monoclonal antibodies through specific light-chain and heavy-chain CDR composition, including humanized, chimeric, and ABC2 embodiments.
Cd122-binding antibody defined by light-chain and heavy-chain CDR sequences
An isolated monoclonal antibody that specifically binds to CD122 (SEQ ID NO:73) comprising three light chain CDRs designated SEQ ID NOS. 27-29 respectively and three heavy chain CDRs designated SEQ ID NOS. 22-24 respectively.
Humanized or chimeric ABC2 antibody defined by ABC2 light-chain and heavy-chain CDR sequences
A humanized or chimeric ABC2 antibody that specifically binds to CD122, comprising a light chain comprising three CDRs of the ABC2 light chain (SEQ ID NO:30) and a heavy chain comprising three CDRs of the ABC2 heavy chain (SEQ ID NO:25).
Across the independent claims, coverage is centered on isolated monoclonal antibodies that specifically bind CD122, with inventive features defined by particular sets of light-chain and heavy-chain CDR sequences, including humanized and chimeric ABC2 formats.
Stated Advantages
Substantially inhibits both IL-2 and IL-15 receptor-mediated signaling.
Substantially inhibits IL-15 trans-presentation.
Substantially inhibits IL-2-mediated proliferation.
Documented Applications
No documented applications found
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