Creative BioMart is a well-known expert who is committed to developing a variety of protein therapies to improve the effectiveness and safety of protein therapy, and to allow the production of new types of proteins and effects. With years of experience, we provide customized services for coagulation factors as protein therapeutics to precisely meet customer requirements.

Introduction of Therapeutic Coagulation Factors

The intrinsic coagulation cascade is a tightly regulated protease and cofactor-dependent expansion system that ensures stable clot formation after injury. Deficiencies in coagulation cofactor VⅢ (FVⅢ) or the corresponding coagulation protease factor IX (FIX) cause the X-chromosome inherited bleeding disorders hemophilia A and hemophilia B, respectively. These coagulation disorders are associated with bleeding events affecting soft tissues, joints, and muscles. More than one million patients currently suffer from hemophilia and other congenital coagulation factor deficiencies in the worldwide. Bioengineering techniques for some therapeutic proteins have been successfully developed to produce or improve FVⅢ, FIX and FVⅡa, such as the addition of polyethylene glycol (PEG) to polymerize and polysialic acid (PSA), the use of PEG-modified liposomes (PEG-Lip) alternative recipes, etc.

Fig 1. Examples of bioengineering strategies to improve the functional properties of rFVⅢ. (Pipe S W, 2010)

Services

The production of recombinant coagulation factors has increased the capacity of global replacement therapy and facilitated aggressive preventive treatment. However, this comes at a high price, and barriers to widespread adoption of preventive measures remain. As a leading service provider of protein engineering, Creative BioMart has established a powerful coagulation factors-based protein therapeutics platform, providing services for the production of coagulation factors and improving their performance. We have produced therapeutic coagulation factors with higher production efficiency, greater potency and resistance to inactivation, prolonged plasma half-life, and reduced immunogenicity.

Promising new bioengineering strategies are driven by detailed structural and functional analyses of coagulation proteins, complemented by high-resolution crystal structures. Our scientists are committed to developing a variety of bioengineering strategies to successfully overcome some of the remaining challenges in hemophilia treatment, including but not limited to:

• Pegylation: our strategy achieves preservation of procoagulant activity and improved pharmacokinetics by screening targeted pegylated rFVⅢ mutants linked to free surface-exposed cysteine residues introduced by mutagenesis FVⅢ.
• Polysialylation: our strategy is used to increase the size of proteins. PSA modification was explored by direct binding of rFVⅢ, FIX, FVⅡa.
• Glycolated liposomes: our strategy is used to extend the half-life of several therapeutic proteins including FVⅢ.
• Alternative expression systems: our strategy is used to enhance the expression of rFIX in stable cell lines.
• Alternative hemostatic agents: our synthetically designed peptide sequences were screened and tested for their ability to bind to inhibitory antibodies, effectively neutralizing anti-FVⅢ antibodies in vitro.

Creative BioMart is committed to designing customized therapeutic coagulation factors for global biopharmaceutical companies. Our scientists produce FVⅢ, FIX and engineer novel hemostatic agents. In addition, protein engineering technologies offer novel non-factorial therapies for hemophilia that aim to rebalance the hemostatic system by lowering endogenous anticoagulants to compensate for the reduced procoagulant activity caused by FVⅢ or FIX deficiency. We will work with you to develop the most appropriate strategy and provide the most meaningful data for your research for accelerating the research of life sciences. If you are interested in our services, please do not hesitate to contact us for more information.

References

1. Pipe S W. (2010) Hemophilia: new protein therapeutics. 2010, the American Society of Hematology Education Program Book. 2010(1): 203-209.
2. Samelson-Jones B J, Arruda V R. (2019) Protein-engineered coagulation factors for hemophilia gene therapy. Molecular Therapy-Methods & Clinical Development. 12: 184-201.

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