Antibodies with engineered CH2 domains, compositions thereof and methods of using the same
Inventors
Assignees
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Publication Number
US-12398197-B2
Publication Date
2025-08-26
Expiration Date
Abstract
The present disclosure relates to antibodies and antibody conjugates having one or more site-specific mutations in the CH2 domain of the heavy chain. The antibody variants disclosed herein can have improved characteristics (e.g., thermal stability, antibody yields, antibody titers, cell-killing) relative to a parent or wild type antibody, including aglycosylated parent or wild type antibodies. Pharmaceutical compositions, diagnostic compositions and kits comprising the same, as well as methods of using these compositions and kits for therapeutic and diagnostic purposes, are also described.
Core Innovation
The invention concerns IgG antibody conjugates in which engineered heavy-chain CH2-domain substitutions are combined with at least one non-natural amino acid substitution. The antibody is conjugated to one or more therapeutic or labeling moieties. The described variants are proposed to improve or preserve antibody yield, assembly, solubility, and thermal stability, including in aglycosylated antibodies.
The independent claim describes an IgG antibody comprising specified CH2-domain substitutions and at least one non-natural amino acid substitution bearing a conjugation-compatible moiety. Experimental assessments evaluate engineered IgG variants for heavy-chain yield, solubility, antibody titer, and assembly efficiency. Because the provided content omits background text, the underlying problem being solved is not explicitly described in patent.
Claims Coverage
The claims identify one independent claim with two inventive features directed to producing an IgG antibody conjugate with specified substitutions.
Specified heavy-chain CH2-domain substitutions
The IgG antibody comprises at least one heavy-chain CH2-domain substitution selected from V264S; V264S and V303R; V264S and V305R; or V264S, V303R, and V305R, according to the EU numbering scheme.
Non-natural amino acid substitution and conjugation
The antibody comprises at least one non-natural amino acid substitution bearing a moiety selected from amino, carboxy, acetyl, hydrazino, hydrazido, semicarbazido, sulfanyl, azido, alkynyl, and tetrazine, and is conjugated to one or more therapeutic or labeling moieties.
The independent claim combines specified heavy-chain CH2-domain substitutions with a non-natural amino acid substitution to produce an antibody conjugate linked to therapeutic or labeling moieties.
Stated Advantages
The described variants are proposed to improve or preserve antibody yield, assembly, solubility, and thermal stability, including in aglycosylated antibodies.
Experimental data report increased yields for selected variants and improved assembly efficiency of approximately 50–80% for tested CH2 variants.
Documented Applications
Producing an IgG-class antibody conjugate linked to one or more therapeutic or labeling moieties, including therapeutic and diagnostic conjugates.
Compositions and kits comprising the engineered antibody conjugates.
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