Protein Sciences

GBI's downstream process development group has well over 50 years of experience in developing and refining purification processes. With an extensive background in the purification of monoclonal antibodies (including IgG, IgA and IgM subclasses) and recombinant proteins from mammalian, as well as plant and animal transgenic systems, GBI can quickly develop a purification process for clients that will maximize yields for the target molecule, meet required purity levels, and be compliant with the regulatory requirements for product's development status.

GBI has experience with affinity, ion exchange, hydrophobic interaction, mixed mode, MEP chromatography, and other processes. Our experience includes UF processes using TFF technologies in both flat plate and hollow fiber formats. Viral clearance techniques employed include low pH inactivation and nanofiltration. We work closely with filtration media providers to develop a filtration process that works within the confines of your process and product requirements and provides the necessary viral removal.

As the product proceeds through its clinical evaluation, GBI can optimize and refine the purification process including the testing and establishment of parameter limits. When the product reaches Phase III clinical testing and beyond, GBI will have developed a process that can be transferred for commercial manufacturing and ready for qualification runs with a minimum of problems.

• Develop product quality, process economics, and scalability
• Resin-reuse (e.g. Protein A column)
• Product safety and compliant (e.g., viral inactivation and removal)

  Viral clearance studies are managed by GBI using a contract biological safety testing organization. GBI can perform the necessary scale down validation to assure that the process transferred to the testing organization is representative of the full-scale process. GBI can provide an onsite scientist at the testing organization to assure that your process is run according to its requirements to avoid comparability questions on the results. The scale down validation and viral clearance studies are assembled into one package for submission to regulatory agencies or other manufacturers.

Artist’s interpretation of an HIV infected T cell being selectively destroyed by an antibody-chelant-radio isotope manufactured with the help of Goodwin Biotechnology and Macrocyclics*

GBI offers a unique and unrivalled expertise in the research, development, validation and multi-gram manufacture of bioconjugates. GBI has many years of experience and multiple patents pending in protein modifications through chemical conjugation of cancer drugs, protein toxins, bifunctional ligands and metal chelates (for radio-isotope labeling), antibodies and other biological molecules onto monoclonal antibodies and recombinant proteins. Conjugation of antibodies with other molecules is a specialty of GBI's development and manufacturing groups. Some typical examples of conjugates manufactured include: Coupling of small molecule (cancer drug) to antibody Conjugation of various molecules to carrier proteins such as KLH and albumin as immunogens for antibody generation Conjugation of toxins to antibody Conjugation of two antibodies (full length and fragments) Conjugation of Genomic DNA to antibody Coupling of metal chelates onto recombinant proteins and antibodies (including the difficult IgMs) for radiolabeling Adsorption of aluminum hydroxide gels onto antibody Biotinylation of proteins for use with streptavidin- or avidin-based reagents Enzyme labeled antibodies for signal generation in diagnostic applications Development of key properties of therapeutic proteins in the optimization of in-vitro and in-vivo performance

Whether the conjugate is a drug toxin (small molecule cancer drugs, plant protein toxins), chelating agents for radio isotopes labeling (diagnostics and therapeutics), adjuvants such as Aluminum Hydroxide-Antibody conjugate, or other antibodies, GBI has the ability to develop and perform them at GMP compliant manufacturing scales for clinical applications.

The development group fully understands the issues involved with these processes such as incorporation levels, active site masking and isotope uptake and stability. The manufacturing group has utilized these processes in the production of multi-gram lots of conjugated antibodies that have been administrated in clinical trials throughout the world.

GBI has both the expertise and experience in protein modification utilizing either chemical conjugation or enzymatic digestion. Antibody modification through enzyme digestion is another GBI staff specialty. The production of Fab and F(ab')2 fragments and their subsequent purification can be achieved to a client's specifications. These processes are GMP compliant and scalable to multi-gram lot sizes for clinical applications.

Click here to see:

• A selection of our bioconjugation projects
• Our list of publications
• The presentation from PEGS
• Our patents that are pending
• A few case summaries on bioconjugation

Dr. Muctarr Sesay’s perspective on the field of Bioconjugation.