title: Engineered hapten-binding antibody derivatives for modulation of pharmacokinetic properties of small molecules and targeted payload delivery.
abstract: Hapten-binding antibodies have for more than 50 years played a pivotal role in immunology, paving the way to antibody generation (as haptens are very important and robust immunogens), to antibody characterization (as the first structures generated more than 40 years ago were those of hapten binders), and enabled and expanded antibody engineering technologies. The latter field of engineered antibodies evolved over many years and many steps resulting in recombinant humanized or human-derived antibody derivatives in multiple formats. Today, hapten-binding antibodies are applied not only as reagents and tools (where they still play an important part) but evolved also to engineered targeting and pretargeting vehicles for disease diagnosis and therapy. Here we describe recent applications of hapten-binding antibodies and of engineered mono- and bispecific hapten-binding antibody derivatives. We have designed and applied these molecules for the modulation of the pharmacokinetic properties of small compounds or peptides. They are also integrated as additional binding entities into bispecific antibody formats. Here they serve as non-covalent or covalent coupling modules to haptenylated compounds, to enable targeted payload delivery to disease tissues or cells.
authors: 1Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Penzberg, Germany.
authors: Stefan
authors: S
authors: Dengl
authors: 1Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Penzberg, Germany.
authors: Claudio
authors: C
authors: Sustmann
authors: 1Roche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, Penzberg, Germany.
authors: Ulrich
authors: U
authors: Brinkmann
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D016503:Drug Delivery Systems; D006241:Haptens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D011485:Protein Binding; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins
chemical_list: D018033:Antibodies, Bispecific; D000954:Antigens, Surface; D015415:Biomarkers; D006241:Haptens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins
keywords: biotin; digoxigenin; protein engineering; protein structure; targeted therapy