Cobra Biologics, an international CDMO of biologics and pharmaceuticals, has been contracted to develop a second cell line for Alligator Bioscience AB, a Swedish biotechnology company.

Alligator has requested further support from the team at Cobra to develop the cell line for production of new drug candidate ADC-1015, a bispecific immune activator developed to induce superior immune activation. Cobra is using their expression system maxXpress, along with a historically documented master cell bank (CHO-S) and chemically defined media. This delivers a time saving cell line development and clone selection process suitable for GMP manufacture.

In May 2015 Cobra released details of it’s involvement in manufacturing immuno-oncology antibody ADC-1013, as part of Alligator’s phase 1 trial in advanced solid tumours. Earlier this month, as a result of the company’s ‘exceptional achievements within the life-science industry’, Alligator won the coveted SwedenBIO Award 2016.

Peter Coleman, CEO Cobra Biologics, commented, “Cobra has been manufacturing protein therapeutics since 1995 and our maximum protein expression platform, maxXpress, has proven to be very popular to customers looking for both speed and quality. I am delighted that Cobra has the opportunity to continue working with Alligator on their promising clinical programs and would like to congratulate the team on their prestigious SwedenBIO Award.”

Dr Per Norlén, CEO, Alligator Bioscience, commented, “Alligator has a long-standing and successful collaboration with Cobra and has seen very good results using their maxXpress system. We are very happy to continue the collaboration with Cobra on our ADC-1015 drug development program.”

Eukaryotic genes are organised into chromatin domains, which exist in either a ‘closed’ state in which the genes are tightly condensed with proteins and are transcriptionally silent, or in an ‘open’ de-condensed state: a prerequisite for efficient gene expression.

When transfected genes integrate into mammalian chromosomes the structure of the chromatin at the site of integration has a profound effect on expression of the transgene. Consequently, only relatively rare transfected clones in which the expression vector has integrated into open chromatin show efficient expression of the transgene.

maxXpress Ubiquitous Chromatin Opening Elements (UCOEs) have been isolated which ensure efficient expression in a wide range of cell types including CHO-K1, CHO-S, HeLa, SP2/0 and NSO cells. UCOE containing vectors have been shown to markedly enhance the expression of a wide variety of intracellular, secreted and membrane-bound proteins. Inclusion of a UCOE (4-8 kb in size) in a eukaryotic expression vector permits efficient expression in the vast majority of stable clones, whereas with conventional vectors only a minor proportion of transfectants demonstrate high-level expression.

There is therefore no need for amplification and expression has been demonstrated to be stable over 130 generations. The combination of UCOE and CHO-S allows the generation of high yields of recombinant proteins.