Antigenic GM-CSF peptides and antibodies to GM-CSF

Inventors

Sass, Philip M. • Nicolaides, Nicholas C. • Grasso, Luigi • Li, Jian • Chao, Qimin • Routhier, Eric • Ebel, Wolfgang

Assignees

Eisai Inc

Abstract

Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.

Core Innovation

The invention provides fully human monoclonal antibodies that specifically bind to granulocyte-macrophage colony stimulating factor (GM-CSF), including neutralizing antibodies against GM-CSF mediated activity. The antibodies are recombinant monoclonal antibodies comprising heavy-chain and light-chain complementarity determining regions selected to bind GM-CSF, with antigen specificity and no cross-reactivity with unrelated antigens.

The antibodies are further characterized by defined CDR sequences, including heavy-chain CDR1 of SEQ ID NO: 40, CDR2 of SEQ ID NO: 41, and CDR3 of SEQ ID NO: 42, and light-chain CDR1 of SEQ ID NO: 43, CDR2 of SEQ ID NO: 44, and CDR3 of SEQ ID NO: 45. Epitope mapping is documented by peptide regions corresponding to SEQ ID NOs: 35-39, and binding affinity values are provided for E10 and G9.

The invention also includes recombinant antibody production and related cell-derived antibody sourcing, including hybridoma generation using human hybridomas with patient-derived cells from PAP (pulmonary alveolar proteinosis). A deposited cell source is identified as ATCC Accession No. PTA-8173 for antibodies comprising six CDRs, and therapeutic use is described for GM-CSF mediated inflammatory disease.

Claims Coverage

The independent claims are clm-00001, clm-00005, and clm-00006, with three main groups of inventive features: recombinant antibodies defined by heavy- and light-chain CDR sequence identifiers, antibodies defined by an epitope sequence identifier, and antibodies defined by CDRs derived from a specific deposited cell (ATCC Accession No. PTA-8173).

Across the independent claims, the patent coverage is anchored in recombinant monoclonal antibodies that bind GM-CSF, defined either by explicit heavy/light CDR sequence identifiers, by an explicitly defined GM-CSF epitope amino-acid sequence (SEQ ID NO:37), or by a CDR set originating from the deposited cell ATCC Accession No. PTA-8173.

Stated Advantages

Documented Applications