Custom Bioconjugation Services, From Concept to GMP Production

Biosynth is empowering advancements in drug delivery and biomolecule analysis with our complete custom bioconjugation services. Our offering well and truly blurs the interface between chemistry and biology and spans the development of tailored PEGylated biomolecules and conjugate vaccines to crafting customized polymers, linker components and activated PEGs. Biosynth is your go-to for new and upcoming bioconjugate drugs, conjugate vaccines, and polymer innovations. Read our article to find out more about our comprehensive services and why bioconjugation is a necessity in scientific progression. ?

Biosynth’s diverse library of bioconjugates:

·?????Antigen-conjugated carrier proteins - so-called conjugate vaccines that enable vaccination against poorly immunogenic antigens

·?????Lipid-conjugates facilitate controlled and targeted drug delivery.

·?????Enzyme-substrate conjugates enable sensitive enzyme assays

·?????Fluorescent protein fusions, which aid molecular biologists in tracking protein localization

·?????Biosynth's expertise in PEGylation enhances the stability and circulation of therapeutic proteins and protein-antigen conjugates crucial for immunization studies.

How is Bioconjugation Pushing the Boundaries of Science?

Bioconjugation is the covalent linkage of a biological molecule, such as a protein peptide or oligonucleotide, to a synthetic molecule or another biological molecule. This ability to chemically link molecules and biomolecules has opened an expansive world of state-of-the-art diagnostics, therapeutics, and research tools.

Bioconjugation enables the creation of new molecules with novel properties that cannot be achieved with traditional chemistry. For example molecules with increased stability, improved targeting, potency, or the ability to deliver therapeutic agents to specific cells or tissues.

Bioconjugated molecules have a strong positioning in many areas of science such as:

Drug development - Bioconjugation can generate new drug conjugates that are more effective and less toxic than traditional drugs e.g. peptide drug conjugates and antibody drug conjugates.

Diagnostics – To produce new diagnostic probes and imaging agents to detect and image diseases. One instance is the use of tumor-homing peptides which can penetrate tumor cells and target tumors with specific lineages. During in vivo tumor imaging applications, these peptides are bioconjugated to labels such as fluorescein dyes or near-infrared dyes, namely 5-aminolevulinic acids and indocyanine green, allowing an operator to directly visualize a tumor in real-time.

Theranostics - Bioconjugation forms the basis of theranostics, an image-guided therapy that can diagnose and treat diseases. Biomolecules are used to deliver radioactive markers and therapies to a therapeutic target. Modern imaging techniques use the radioactive isotopes of certain metal ions, in combination with targeting peptides. A chelating agent can be bioconjugated to peptides to carry the radioactive metal ion, thus improving the delivery of the conjugate through cellular targets. Visit our theranostics webpage to discover another of Biosynth’s specialties.

Gene therapy - Bioconjugation can deliver gene therapy vectors to specific cells or tissues, to treat genetic diseases, cancer, and other conditions.

Materials science - Bioconjugation can create new biomaterials with novel properties such as drug delivery systems, implantable devices, and tissue engineering scaffolds.

The possibilities that bioconjugation brings to the table are endless, and the future of scientific and medical progression depends on it. That is why Biosynth has positioned itself as a leader in the manufacture of bioconjugates, bringing all the latest bioconjugation technology to our customers. Read on for more about our services.

Bioconjugation Services

Biosynth are experts in all bioconjugation methods, including PEGylation and glycoconjugation, as well as with small molecule or peptide coupling. We can even support our customers at any stage of bioconjugate development ranging from first feasibility studies, through process and analytical method development, to the manufacturing of bulk drug substance (DS) for first-in-man studies. Services modules can be selected individually or as whole packages and all bioconjugation services are accompanied by analytics.

Bioconjugation alters the parent biomolecule's properties and requires a scalable and robust manufacturing process. With a skilled bioconjugation team, Biosynth specializes in developing, optimizing, and scaling these processes. This includes customizing workflows, optimizing individual steps, and designing scalable purification methods, while also qualifying analytical methods, generating reference standards and performing stability studies.

Bioconjugate Manufacture

We can manufacture bioconjugates from μg through to a multi-gram scale. The manufacture of proof-of-principle (PoC) or Tox material is carried out following standard operating procedures (SOPs) generated during process development. Drug substances for first clinical trials in humans are produced according to the EU-GMP guidelines part II: Basic Requirements for Active Substances used as Starting Materials. No matter the product Biosynth does not compromise on the technical quality.

·?????? Establishment of process and documents

·?????? Establishment of analytical methods for incoming goods testing

·?????? Purchase and testing of starting materials

·?????? Campaign production of bioconjugate in cleanroom

·?????? Release testing and certificate of analysis

·?????? Batch release of bulk API

Conjugate Vaccine Development Services

As specialists in bioconjugation, we support customer projects in a variety of conjugate vaccine constructs using common carrier proteins such as CRM197 and tetanus toxoid. CRM197 conjugates are driving vaccine progression and replaces traditional weak polysaccharide antigen-based vaccines which are mostly ineffective at stimulating an immune response in certain populations. Instead, our conjugate vaccines link these polysaccharides to carrier proteins allowing for more effective recognition by the immune system, thus creating a stronger and long-lasting immune response. These conjugate vaccines have already demonstrated a positive impact in vaccines against diseases such as Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, and Neisseria meningitidis.

Processes and Techniques

As the modification of a biomolecule often changes the biomolecule’s physico-chemical properties, specific purification strategies and materials need to be developed individually for each bioconjugate. Furthermore, some biomolecules require an activation step before conjugation. Biosynth can perform many techniques to ensure the successful manufacture of bioconjugates.

·?????? Activation of capped thiol-groups

·?????? Reduction and re-folding (oxidation) of disulfide-bridged proteins and peptides

·?????? Conjugation chemistries (e.g reductive amination, activated esters or carbonates, thiol- reactive groups, click chemistry, and enzymatic conjugation)

·?????? Chromatography IEX, RP, SEC and more

·?????? Tangential-flow filtration/ultrafiltration TFF

·?????? Batch size may range from 100 mg to 100 g

·?????? Sterile filtration of drug substances in UDAF

·?????? Chemical compound and linker manufacturing:

Analysis of Biomolecules and Bioconjugates

As bioconjugation specialists, our team of scientists in Berlin can perform the analytical characterization of complex large molecules, such as artificial polymers, biomolecules, and bioconjugates. We offer several customized solutions for your analytical requirements on qualified state-of-the-art analytical equipment. This includes the development, qualification, and validation of analytical methods.

Our focus is the structural and physico-chemical characterization of pharmaceutical products and excipients as well as impurities. Most analytical methods are performed in-house for structural characterization. For routine testing of particulate matters, bioburden, residual solvents, and heavy metals we have GMP-certified partners.

Our analytical services comprise:

·?????? Method transfer from client to our site or vice versa

·?????? Development of analytical methods

·?????? Qualification and validation of analytical methods

·?????? Evaluation of key starting materials or excipients for drug manufacturing

·?????? Comparability exercise for biosimilar products

·?????? Stability testing according to ICH guidelines

·?????? Characterization of reference products, main compound, and impurities

·?????? Analytics in biological samples

·?????? Routine testing of samples

·?????? Release testing for drug substance (DS) and drug product (DP) according to GMP

For more information about our analytical services for bioconjugates and chemical polymers visit our website.

Why Choose Biosynth for your Bioconjugate Project?

Innovation and Expertise

Innovation is at the heart of our company and our experts strive to create technologies that are world-leading. Our team of highly skilled chemists have decades of experience in synthetic organic chemistry and have successfully solved a variety of issues, often associated with polymers relevant to pharmaceutical applications such as activated polyethylene glycols (PEGs), PEG block-copolymers, polyimines, and hyperbranched polyglycerols among other hydrophilic or amphiphilic polymers. We can find solutions to structural and functional reproducibility problems, as well as yield and purification issues.

Fully-equipped facilities and flexibility

Our Berlin manufacturing facility is fully equipped with the latest technological standards and allows the delivery of small molecules and polymers at 100 g to kg and bioconjugates at mg to 100g batches. With different TFF systems, 10 L and 60 L double jacket glass reactors, and a cleanroom class D (ISO 8) manufacturing suite, our state-of-the-art laboratories are capable of taking on the most complex projects. We even have a QC lab for GMP-compliant release testing of drug substances and drug products.

·??????Temperature-controlled reaction and stirring block for operating volumes between 250 and 1000 μL

·??????Double-jacketed reactors for operating volumes between 25 mL and 60 L

·???????kta chromatography systems for flow rates between 10 – 150 mL/min, equipped with UV, conductivity, and pH detectors

·??????Tangential-flow systems for the operation of 50 cm2 and up to 1 m2 membrane area

·??????Christ freeze dryers (lab and pilot system)

·??????Laminar air flow systems

·??????Manufacturing suite cleanroom class D / ISO 8 (with UDAF system for final filtration)

·??????Qualified and monitored storage facilities

·??????Qualified analytical equipment for the analysis and characterization of bioconjugates

Our facilities are designed so that your bioconjugate project can be flexible and tailored to your specific needs.

Unique to the Field

Biosynth is unique in that our expertise and capabilities run across chemicals, peptides, and key biologics, giving our customers the scope to create any type of bioconjugate. Our services are at the edge of innovation and do not end at the supply of your bioconjugate but extend into the supply of your custom peptide, antibody, enzyme, biological reagents, buffer component, polymer, and more. We strive to de-risk our customer’s supply chains and supply all the critical raw materials and services that the pharmaceutical, vaccine, and diagnostics industries may need.

Discover Biosynth’s bioconjugate services for yourself. We are the company of choice for high-quality and high-purity compounds. Whether you need pharmaceuticals, excipients, or reagents for diagnostics, our bioconjugate services are perfect for you. Contact a member of our team.