Biosynth GmbH is a specialist for the chemical conjugation of biologics with a proven track record in the development of PEGylated biologics and biosimilars, as well as chemically modified drugs, such as ADCs, and conjugate vaccines. We provide customized solutions from research & development of bioconjugation to production of bioconjugate drugs.
Biologics have gained substantial relevance as therapeutics during the past decades. Even though often used as single compound, many biologics have also been chemically conjugated to other entities, providing so-called bioconjugate drugs. Particular reasons for such bioconjugation can be half-life extension, targeted delivery and immune stimulation. Depending on the intended purpose, biologics are conjugated to synthetic polymers, cytotoxic small molecules, or antigens. Thus, bioconjugate drugs is a generic term for a heterogeneous class of biologics modified with a variety of chemical entities.
PEGylation of proteins – PEGylated biologics
Many biologics such as growth factors, cytokines, enzymes, antibodies, peptides, or nucleic acids have been modified with polyethylene glycol (so-called PEGylated) to overcome insufficient half-life and to become successful pharmaceuticals. Indeed, PEGylation is the most established and best validated strategy for half-life extension (HLE) today. Prominent examples of PEGylated proteins are Cimzia®, Pegasys® or Neulasta®, which are block buster products on the market. Biosimilars of the most successful PEG proteins have been developed or are currently under development. Due to the unique properties of PEG, PEGylation is not only suitable for proteins but also for peptides, nucleotides, small-molecules and antibodies. Biosynth GmbH offers PEGylation services for new biological entities (NBEs) and for biosimilars of PEGylated proteins.
PEGylation requires activated PEGs as key starting materials to react with biologics of interest. Several different chemistries have been developed for this purpose and celares offers tailor-made PEGs with known active groups but also with new activation chemistry.
Besides protein modification, PEG is also an ideal reagent for labeling or crosslinking of biologics providing functionalized proteins or protein-protein conjugates as well as protein multimers. Depending on structure of the target, i.e. protein complexes, such protein multimers exhibit large multivalent effects (avidity).
Antibody drug conjugates (ADC)
ADCs belong to a new type of targeted therapy where cytotoxic drugs are conjugated to scaffold proteins, antibodies or antibody fragments which specifically target disease(s) associated tissues or cells. Several different strategies for antibody conjugation and several linker technologies have been examined for ADC development. A prominent example for an antibody-drug conjugate (ADC) is, e.g., Kadcyla®. Due to their hydrophilic nature, PEG-based linkers are particularly well suited to compensate the hydrophobicity of many small-molecule drugs and in this way reduce drawbacks of con-ventional payloads. Biosynth GmbH offers ADC development services using conventional linker and also novel, DAR enhancing and hydrophilic linker.
The success of vaccination is dependent on the immune stimulus triggered by an antigen. Several antigens derived from pathogens are not sufficiently immunogenic. Bioconjugation of such antigens to highly immunogenic carrier proteins has become a powerful approach to produce highly effective conjugate vaccines via T-cell activation. Various conjugate vaccines can be synthesized through a covalent linkage of a carrier protein to a protein, peptide, lipid, oligonucleotide, polymer, nanoparticle, or small molecule. Further information about celares’ services on conjugate vaccines can be found here.