The MorphoSys subsidiary Sloning BioTechnology signed a license and technology transfer agreement for its Slonomics® platform with Pfizer. Under terms of the deal the Slonomics platform for fabricating gene and protein libraries will be installed at Pfizer’s Rinat Neuroscience subsidiary in South San Francisco. Sloning will receive an up-front fee and annual license fees.
“Rinat started using Sloning's services in 2009, and we were impressed by the diversity and quality of the libraries delivered,” notes Jaume Pons, Ph.D., CSO at Rinat. “We therefore decided to use this innovative technology platform further for our R&D activities.”
MorphoSys acquired Germany-based Sloning BioTechnology in October, for €19 million (about $25.4 million) in cash. Sloning's core technology enables the precise construction of protein libraries comprising defined mixtures of amino acids at predetermined positions. MorphoSys claims the platform will enable a much more flexible approach to generating optimized proteins, including antibodies.
"Current antibody-generation technologies use an initial repertoire, which largely determines the properties of the resulting antibody,” pointed out MorphoSys CSO Marlies Sproll, Ph.D., when the firm announced its acquisition of Sloning. “We intend to use Slonomics as the basis of a fundamentally different approach, which will rapidly test multiple generations of antibodies, equivalent to screening many billions of molecules, to isolate the best possible candidate." The firm expects to shorten the time needed to generate an antibody drug candidate by a third and, even more importantly, to increase the proportion of programs reaching clinical development to 50%, Dr. Sproll added.
Traditional methods for library generation rely on individually designed and synthesized single-stranded oligos that have to be joined (ligated) together, Sloning explains. In contrast, the Slonomics platform uses a library of premade double-stranded triplets that act as universal building blocks for thousands of gene-syntheses processes. The triplet library represents all possible sequence combinations necessary to build any desired DNA molecule, the firm claims.
These standardized building blocks are then combined by means of a series of validated reaction steps, which allows for the process to be fully automated. Sloning says the double-stranded structure of the building blocks guarantees a stable and reliable synthesis process, irrespective of the desired sequence.
A number of different SlonoMax® libraries are available, dependent on the mutation pattern and codon ratios. The SlonoMax-Single library has only one position mutated, while the SlonoMax-Select library has multiple sites in the protein mutated. SlonoMax-Screen contains the complete set of mutants in a defined representation ratio, and SlonoMax-Stretch contains all possible mutants from a protein mutated in a number of nested positions. The SlonoMax-Search library type contains all possible mutations of a protein but, Sloning stresses, without the limitations seen in error-prone PCR, such as an incomplete set of possible mutations, unwanted mutations, and unequal distribution of mutations.
Sloning is separately exploiting its Slonomics platform through a personalized gene-synthesis service, SlonoGene™, for industrial customers. The SlonoGene offering comprises synthesis, sequence verification, and E. coli cloning of any desired gene construct up to 8,000 base-pairs in length. The firm can also use its informatics software to carry out codon optimization of expression constructs for all desired host systems, and carry out parallel synthesis of individually characterized gene mutants, according to required specifications.