The issued patent covers the use of the company's proprietary Morphodoma platform technology that can rapidly evolve host cells expressing antibodies to yield sublines expressing variant gene products with enhanced binding affinity as well as cell lines with improved titer yields for scaleable manufacturing. The genetic diversity that can be generated by the Morphodoma process can be applied to virtually any antibody production cell line, including hybridoma cells and standard manufacturing cell lines such as CHO and NSO. Morphotek's vast patent estate includes over 50 issued/filed patents in the U.S. and abroad.
Dr. Nicholas Nicolaides, President and Chief Executive Officer of Morphotek, commented, "This is a dominant patent for protecting the use of our technology to develop high-affinity antibodies and high-titer production lines. The patent covers broad applications of this technology to accelerate the development of efficacious human, humanized or chimeric antibodies as well as the development of high-titer cells for scaleable manufacturing."
"The invention described in this patent outlines a very powerful application of our MORPHODOMA(R) process to generate genetic diversity within an existing antibody cell line to further optimize antibody affinity and/or the host cell line's productivity," added Dr. Philip M. Sass, Executive Vice President and Chief Operating Officer. "It is one of several patents that cover the application of our morphogenics platform to generate novel therapeutics and corresponding high-titer manufacturing cell lines in an expeditious manner."
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Gene-regulatory networks are interconnected sets of genes that control the expression of particular genes in a cell. In E. coli, for example, the rise in temperature that occurs inside the human body activates a particular set of genes that make the bacteria much more virulent.
Via experiments on the tailored strains of E. coli, the project team will first focus on understanding how specific gene-regulatory structures, which are common among all cells of a population, give rise to different phenotypes within a cell population. Once a link is established between gene-regulatory architecture and cell population heterogeneity, the team will shift focus and concentrate on the interplay between cell population heterogeneity and adaptation dynamics. For example, how does the proportion of phenotypes within a population change when temperature rises or falls?
Two other Rice research groups ” that of Kyriacos Zygourakis, the A.J. Hartsook Professor and chair of the Department of Chemical Engineering, and Ka-Yiu San, the E.D. Butcher Professor of Bioengineering ” will characterize the temporal changes in cell population phenotype using a combination of flow cytometry and fluorescence microscopy.
All of the experimental evidence will feed back into the modeling efforts of Mantzaris' group, which will attempt to develop a predictive scheme that bioengineers and medical researchers can use to design test populations of cells that have tailored and predictable distributions of phenotypes. Designing cell populations with such specificity could be a real boon to scientists testing the effects of new drugs and experimental therapies on bacterial pathogens.
By unveiling the relationship between gene-regulatory architecture and cell-to-cell phenotypic variability we hope to gain insight into fundamental biological and medical issues, such as developmental processes and cancer, where cell population heterogeneity is bound to be important, said Mantzaris.
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