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Publication Number
US-10759860-B2
Publication Date
2020-09-01
Expiration Date
Abstract
This disclosure relates generally to an EGFR antibody and its therapeutic effects on tumor inhibition in vitro and in vivo, alone or in combination with various chemotherapeutic agents. In particular, the present disclosure relates to methods for the treatment of cancer, comprising administering an EGFR antibody, alone or in combination with a chemotherapeutic agent.
Core Innovation
The invention relates to an antibody that binds epidermal growth factor receptor (EGFR) and is defined by a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO:2 together with a light chain consisting of the amino acid sequence set forth in SEQ ID NO:1. The antibody comprises N-acetylneuraminic acid (NANA) and lacks galactose-α-1,3-galactose, and includes N-glycan features at amino acid residues Asn88 and Asn302, where the N-glycan at Asn88 comprises NANA.
In described embodiments, the EGFR-binding antibody includes disulfide bonds between Cys23 and Cys88, Cys134 and Cys184, and Cys214 and Cys225 of the light chain (SEQ ID NO:1), and between Cys22 and Cys95, Cys146 and Cys202, Cys266 and Cys326, and Cys372 and Cys430 of the heavy chain (SEQ ID NO:2). The antibody therefore combines defined polypeptide sequences with specified carbohydrate and connective structural features.
The invention is presented as an EGFR-binding human/mouse chimeric monoclonal antibody, referred to as LR004, engineered as an improved alternative to Erbitux (cetuximab). The document further describes physicochemical and biological evaluations, including EGFR phosphorylation inhibition, anti-tumor activity, pharmacokinetics, thermostability data, and hypersensitivity considerations versus cetuximab.
Claims Coverage
The independent claims identified in the provided content center on one inventive feature: an EGFR-binding antibody with specific heavy/light sequences and defined carbohydrate/disulfide features. The claim content also includes hypersensitivity testing and optional conjugation as related uses.
Defined EGFR-binding chimeric antibody with NANA and lack of galactose-α-1,3-galactose
An antibody that binds epidermal growth factor receptor (EGFR) comprising a heavy chain consisting of the amino acid sequence set forth in SEQ ID NO:2 with a light chain consisting of the amino acid sequence set forth in SEQ ID NO:1, wherein the antibody comprises N-acetylneuraminic acid (NANA) and lacks galactose-α-1,3-galactose, including disulfide bonds between specified cysteine residues, and wherein SEQ ID NO:2 comprises N-glycan at amino acid residues Asn88 and Asn302 with the N-glycan at Asn88 comprising NANA.
The claim coverage centers on an EGFR-binding antibody characterized by specific SEQ ID NO:1 and SEQ ID NO:2 heavy/light sequences, defined disulfide bond connectivity, and defined Fc carbohydrate features including NANA at Asn88 and absence of galactose-α-1,3-galactose.
Stated Advantages
More thermostable than Erbitux (cetuximab).
Does not trigger hypersensitivity in subjects who are hypersensitive to, or predisposed to, hypersensitivity reactions to cetuximab.
Documented Applications
Treatment of EGFR-expressing cancers alone or in combination with chemotherapeutic agents.
Use of the antibody in therapy as conjugated to detectable markers or therapeutic/cytotoxic agents.
Hypersensitivity risk stratification for cetuximab using serum anti-cetuximab IgE and anti-galactose-α-1,3-galactose IgE measurements.
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