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Publication Number
US-12534534-B2
Publication Date
2026-01-27
Expiration Date
Abstract
The present application relates to antibody molecules that bind CD137. The antibody molecules find application in the treatment and diagnosis of diseases and disorders, such as cancer and infectious diseases.
Core Innovation
The invention relates to an antibody molecule that binds to CD137, where the antigen-binding site comprises specified VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences defined according to the IMGT numbering scheme or the Kabat numbering scheme. The description includes specified SEQ ID NO combinations defining CD137-binding antibody molecules with particular antigen-binding site sequence identities, including anti-CD137 antibodies such as FS30-5, FS30-10, FS30-15, FS30-16, and a cross-reactive FS30-35 clone.
The disclosed anti-CD137 antibodies are assessed for cell-binding specificity to human CD137 and cynomolgus CD137, with no binding to OX40. Agonistic T-cell activation is described as crosslinking-dependent, with IL-2 production observed when crosslinked and no activity without crosslinking, and ligand-binding behavior toward CD137L is described as complete, partial, or non-blocking binding.
The invention further addresses antibody-mediated CD137 agonistic activity and Fc-associated effects by introducing CH2 domain modifications that reduce or eliminate binding between the CH2 domain and one or more Fc receptors. In additional embodiments, the invention provides multispecific and conditional agonist antibody formats, including a second antigen-binding site for OX40 in a modified CH3 domain, and describes pharmaceutical and diagnostic uses for the CD137-binding antibody molecules, including compositions and detection of CD137+ cells.
Claims Coverage
The provided claim coverage identifies five inventive features. The independent scope centers on CD137-binding antibody molecules defined by specified VH and VL CDR1/2/3 sets using either the IMGT or Kabat numbering scheme, with additional features covering Fc receptor-reducing CH2 modifications, a second OX40-binding site in a modified CH3 domain, specified heavy-chain sequences, and nucleic acids encoding the antibody.
Specified CD137-binding antigen-binding site CDR sets
An antibody molecule that binds to CD137, wherein the antigen-binding site comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 set forth in specified combinations of SEQ ID NOs, wherein the CDR sequences are defined according to the IMGT numbering scheme or the Kabat numbering scheme.
CH2 domain modified to reduce or eliminate Fc receptor binding
An antibody molecule in which the antigen-binding site corresponds to the specified CD137-binding CDR configuration, and wherein a CH2 domain of the antibody molecule is modified to reduce or eliminate binding between the CH2 domain and one or more Fc receptors.
Second OX40-binding antigen-binding site in a modified CH3 domain
An antibody molecule that includes a second antigen-binding site for OX40 formed in a modified CH3 domain via specified amino acid substitutions in AB, CD, and EF structural loops, yielding particular loop sequences defined using IMGT residue positions.
Specified heavy-chain sequence identities
An antibody molecule characterized by comprising one of the specified heavy-chain sequences identified as SEQ ID NOs.
Nucleic acids encoding the CD137-binding antibody
A nucleic acid molecule or multiple nucleic acid molecules encoding the antibody molecule comprising the specified CD137-binding antigen-binding site CDR configuration.
The core inventive scope is CD137-binding antibodies defined by specified VH/VL CDR1/2/3 sets using IMGT or Kabat numbering and SEQ ID NO combinations, optionally combined with CH2 modifications to reduce or eliminate Fc receptor binding, multispecific architectures including an OX40-binding site in a modified CH3 domain, restrictions to specified heavy-chain sequences, and nucleic acids encoding the antibody.
Stated Advantages
Mitigation of FcγR-dependent crosslinking is described as a benefit associated with CH2 domain modifications that reduce or abrogate effector functions.
Avoidance of liver inflammation observed with prior anti-CD137 mAbs is described.
Documented Applications
Pharmaceutical uses for cancer are described in the document for the CD137-binding antibody molecules and pharmaceutical compositions.
Pharmaceutical uses for infectious diseases are described in the document for the CD137-binding antibody molecules and pharmaceutical compositions.
Diagnostic uses are described, including detecting CD137+ cells using the CD137-binding antibody molecules.
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