Antibodies that bind CD3 Epsilon
Inventors
Sato, Aaron • Liu, Qiang • Mathieu, Mary • WANG, Linya
Assignees
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Abstract
Provided herein are methods and compositions relating to CD3 libraries having nucleic acids encoding for a scaffold comprising a CD3 domain. CD3 libraries described herein encode for immunoglobulins such as antibodies.
Core Innovation
The invention is directed to CD3 epsilon (CD3ε)-targeting antibodies and antibody fragments that bind CD3ε and include amino acid sequences as set forth in SEQ ID NOs: 25-32. The disclosure also includes antibody variants and characterized antibody formats for CD3ε binding.
A key aspect of the invention is the definition of CD3ε-binding antibodies by specific sequence sets and, in some embodiments, by quantitative binding affinity thresholds using K_D. The disclosure specifies K_D limits such as K_D <75 nM, K_D <50 nM, K_D <25 nM, and K_D <10 nM for CD3ε-binding antibodies, including variants associated with improved binding/function.
The disclosure further includes antigen-binding antibody constructs such as CD3-ERBB bispecific antibodies and provides described characterization of binding and cytotoxicity outcomes for selected clones. Documented characterization includes binding measurements and comparisons showing improved binding/cytotoxicity for selected antibodies, along with exemplary CD3ε immunoglobulin sequences and additional antibody sequences for constructs.
Claims Coverage
The independent claim is clm-00001 and is focused on CD3ε-binding antibodies defined by amino acid sequence sets from SEQ ID NOs: 25-32. Dependent claims refine the independent claim by adding quantitative affinity constraints via K_D thresholds and by specifying particular antibody types/formats and nucleic-acid encoding.
CD3 epsilon binding antibodies with SEQ ID sequences
An antibody or antibody fragment thereof that binds CD3 epsilon, comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 25-32.
CD3 epsilon binding with K_D <75 nM
An antibody or antibody fragment that binds CD3 epsilon with a dissociation constant (K_D) of less than 75 nM.
CD3 epsilon binding with K_D <50 nM
An antibody or antibody fragment that binds CD3 epsilon with a dissociation constant (K_D) of less than 50 nM.
CD3 epsilon binding antibody formats
The antibody or antibody fragment is one of the specified antibody types, including monoclonal antibody, bi-specific antibody, multispecific antibody, grafted antibody, humanized antibody, synthetic antibody, chimeric antibody, camelized antibody, single chain antibody, single-domain antibody, diabody, intrabody, or antigen-binding fragments.
Chimeric or humanized CD3 epsilon binders
The antibody or antibody fragment is chimeric or humanized.
Isolated nucleic acid encoding the CD3 epsilon-binding antibody
An isolated nucleic acid encoding the antibody or an antibody fragment as defined by the CD3 epsilon sequence-binding requirement.
Overall, the claim set covers CD3ε-binding antibodies defined by SEQ ID NOs: 25-32, optionally further limited by K_D affinity thresholds, and limited to specified antibody types including chimeric/humanized and other formats, with nucleic acids encoding the defined antibodies.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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