Transglutaminase Conjugation Method with a Glycine Based Linker

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention provides a novel method for site-specific conjugation of payloads (such as drugs, imaging agents, or other functional molecules) to antibodies using microbial transglutaminase (MTG) and a glycine-based peptide linker. This approach allows for efficient and precise attachment of various payloads to a conserved glutamine residue (Q295) on antibodies—particularly IgG antibodies—without the need for removing antibody glycosylation or genetic modification of the antibody, leading to highly uniform (homogeneous) antibody-payload conjugates.

Use CasesContent extracted from patent full text and abstract with AI.

• Development and manufacture of antibody-drug conjugates (ADCs) for targeted cancer therapies, enabling delivery of cytotoxic agents directly to tumor cells.
• Creation of antibody conjugates for in vivo diagnostic imaging, such as PET/SPECT or fluorescence-based imaging for tumor localization and margin detection during surgery.
• Combination (dual) labeling of antibodies with two different payloads (e.g., a toxin and an imaging agent, or two drugs), expanding therapeutic or diagnostic capability in a single molecule.
• Generation of antibody conjugates for the treatment of autoimmune, infectious, and inflammatory diseases by delivering relevant payloads (e.g., cytokines, anti-inflammatory agents) to affected tissues.
• Production of highly controlled and reproducible antibody conjugates for preclinical research, screening, and clinical trial applications.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables site-specific and stoichiometric conjugation of payloads to antibodies, resulting in highly homogeneous products with predictable properties and improved therapeutic index.
• Maintains the native glycosylation and structural integrity of the antibody, avoiding the need for deglycosylation or mutagenesis, thereby preserving antibody function (e.g., ADCC activity) and reducing immunogenicity risks.
• Accelerates the manufacturing process and increases flexibility, allowing the rapid production of large libraries of antibody-payload conjugates with diverse linker and payload combinations.
• Supports dual or multi-payload attachment, providing new therapeutic and diagnostic strategies (such as dual-drug ADCs or multimodal imaging).
• Reduces regulatory, safety, and manufacturing concerns associated with antibody engineering or complex chemical modifications, supporting scalable and GMP-compliant production.

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Inventors & Applicants

Patent Abstract

The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising or having the peptide structure (shown in N->C direction) Gly-(Aax)m-B- (Aax)n via the N-terminal primary amine of the N-terminal glycine (Gly) residue to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody.