DIREVO announces validation of bestMab(TM)
Powerful new approach for the optimization of therapeutic antibodies generates optiMIRA(TM), an enhanced version of Adalimumab (Humira®)
The bestMab(TM) technology comprises a novel, integrated, and highly effective platform for improving the properties of therapeutic antibodies. The platform achieves this without making use of display technologies, and is applicable to all types of antibodies from any origin, including antibodies derived from either immunized mice or recombinant antibody libraries. Significantly, the bestMab(TM) process identifies virtually all mutations that can improve the antibody of interest. Using bestMab(TM), DIREVO optimized the marketed antibody, Humira®, to generate optiMIRA(TM), which binds to TNFa with an exceptional binding strength (femtomolar affinity).
"This is a major technical and commercial breakthrough in antibody engineering that has the potential to significantly enhance antibody drug development," said Dr. Thomas von Rüden, CEO of DIREVO. "I am very proud of our interdisciplinary team of scientists and technicians who have made this important contribution to a key area of antibody R&D."
DIREVO will use bestMab(TM) as a proprietary cornerstone of its therapeutic antibody platform. Based on bestMab(TM), DIREVO will generate superior 2nd generation antibodies and improve success rates of antibodies in development, both for internal proprietary programs and through partnerships with the pharmaceutical and biopharmaceutical industries.
More about bestMab(TM)
The bestMab(TM) technology relies on DIREVO's leading protein engineering platform, which is characterized by highly predictive screens of high throughput. These screens allow effective antibody engineering using the more informative "clonal" and "solution-based" assays, as opposed to the more traditional use of display technology. Another distinctive feature of the bestMab(TM) approach is its more comprehensive and efficient approach to the engineering of antibody properties. This respectively translates into the more complete generation of IP covering all changes that can improve a given antibody, as well as into antibodies that reach product qualification goals with fewer mutations.
Using the bestMab(TM) approach, highly valuable synergistic interactions can be identified by the extensive generation and testing of a large number of combinatorial antibody libraries. In each library, two antibody binding region (complementarity determining region, or CDR) positions are paired for simultaneous co-optimization. This approach is then extended to every residue in all six CDRs, to yield a large number of such "paired-saturation" libraries. Extensive exploitation of such an approach is only possible using screens of very high throughput. For example, in the first screening round, well over 100,000 variants were individually and quantitatively screened to compare their properties on a proprietary platform that allows over 50,000 variants to be screened per day.
Elements of the bestMab(TM) approach thus ensure that:
(i) virtually every amino acid substitution that can improve a given antibody is identified,
(ii) synergistic interactions that are typically missed in other approaches are identified,
(iii) the number of mutations is minimized because the antibody receives the optimal combination of amino acid exchanges,
(iv) so called "neutral mutations" that do not contribute to improvement are excluded and
(v) the entire process is rapid and reliable.
A further important attribute of this DIREVO screening platform is its facility in the simultaneous optimization of multiple parameters. These include, in addition to increasing affinity, engineering binding specificity and improving the antibody's inherent expressibility, stability, pH binding profile, and other important antibody characteristics.
The DIREVO bestMab(TM) optimization program for Humira® yielded a complete series of variants with successively improved affinities. The best variant created by the bestMab(TM) process, optiMIRA(TM), shows 300-times tighter antigen binding than Humira®. It also binds TNFa more than 15-fold tighter than cb1-3, the previously most advanced optimized Humira® derivative, which was generated using display technology (Rajpal et al. (2005) PNAS; 102:8466-8471). The series of improved antibodies generated by bestMab(TM) also included a variant with binding strength equal to cb1-3, but with 40% fewer mutations. The increased binding strength demonstrated in these optimized antibodies also translated into biological potency as determined in experiments measuring protection against TNFa-induced cell killing.
DIREVO Industrial Biotechnology GmbH
DIREVO Biotech AG generates superior bioengineered products and processes for industrial and pharmaceutical markets by enhancing nature's potential. The Company's portfolio includes optimized proteins, optimized bioprocesses and other bio-molecules, in research, in commercial development and on the market. Direvo develops products both independently and with global leaders such as Danisco/Genencor, Nestlé, AstraZeneca/MedImmune and Pfizer. Direvo Biotech is committed to a tailored approach to addressing customer needs and market opportunities.
Direvo's biopharmaceutical business focuses on therapeutic antibodies and proteases. Applying its powerful and proven protein engineering capabilities, Direvo generates improved second generation therapeutics and discovers and optimizes novel first-generation therapeutics. Direvo offers early stage partnering from internal discovery programs as well as collaborations on the optimization of a wide range of therapeutic proteins.
DIREVO Biotech AG is privately held and located in Cologne, Germany. Additional information is available at: www.direvo.com
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