Neugenesis in the News
Reproduced from BioCentury, August 5, 1996, with permission.
Neugenesis: Beyond basic expression
Neugenesis Corp.
Honolulu, Hawaii
Technology: Fungal Systems for engineering and production of mammalian
proteins
Disease focus: N/A
Clinical status: N/A
Founded: 1993 by W. Dorsey Stuart
Corporate partners: Two undisclosed companies
University collaborators: University of Hawaii, Leeds University
Number of employees: 8
Funds raised: $ 1.7 million
Investors: Board members; private individuals; Keokea Hawaii; and HMS Hawaii
CEO: W. Dorsey Stuart
Patents: None issued [Updated in March,
1997 Press Release, ed.]
They're not glamorous, but cost-effective expression systems for the production of recombinant proteins are at the heart of biotechnology. Familiar factories for the production of proteins include E. coli and Chinese hamster ovary (CHO) cells. Less common are systems utilizing yeast, Aspergillus, insect cells, plants and transgenic animals.
Neugenesis Corp. (Honolulu, Hawaii) has developed a different system, dubbed Neu BIOS™, based on a well-studied filamentous fungus, Neurospora crassa. The company believes the system will meet requirements for both competitive pricing and quality assurance, by combining the cost advantages of bacterial expression with the biological features of mammalian cell culture.
Technology apex
The apex of the company's technology is CombiKARYON™. As the name implies, the technology is a combinatorial approach to the generation and selection of improved, intact, heteromeric proteins. Heteromeric, or multimeric, proteins, such as monoclonal antibodies, are composed of at least two non-identical polypeptide chains. The company, which recently filed for patents on the technology, believes that CombiKARYON™ represents the only way to produce combinatorial libraries of intact multimeric proteins.
To understand how Combi KARYON™ works, it's necessary to start with the NeuBIOS™ system. NeuBIOS™ has the ability to fold and trim complex mammalian proteins correctly, to glycosylate proteins, and to secrete them into inexpensive liquid media, making downstream processing and purification simple and inexpensive, according to the company. The fungus-based system also doesn't express toxins and the system has no known viruses.
Wild strains of Neurospora typically produce more than a gram per liter of secreted proteins when grown on a liquid minimal medium for several days. The company's goal is to engineer a host cell capable of producing and secreting recombinant products at levels measured in grams per liter and at initial purities of more than 90 percent.
Neugenesis aims to use Neu BIOS™ to produce high value recombinant mammalian proteins, including human biopharmaceuticals and proteins for research and development use. To date, Neugenesis has been able to produce cytokines, monoclonal antibodies, a thrombolytic protein, and insulin-like proteins.
First product
The company is producing its first commercial product: recombinant human macrophage colony stimulating factor (M-CSF). Neugenesis has signed an agreement with an undisclosed company to sell M-CSF to the research community.
The company's second production system, NeuKARYON™, is designed as an alternative to conventional recombinant production of MAbs. The conventional approach to the production and assembly of the light and heavy chains that comprise MAbs has been to transform the genes for both subunits into a single host cell, which then produces the intact antibody.
Using NeuKARYON™, two individually transformed strains of N. crassa, one producing high levels of the light subunit and the other producing high levels of the heavy subunit, are fused to form a multicellular, multinucleate strain (heterokaryon), which produces both subunits and processes them into the intact MAb.
Neugenesis has demonstrated the feasibility of the technology under a Phase I SBIR grant from the NIH. The genes used in the project code for an undisclosed humanized MAb.
NeuKARYON™ has the ability to select for equal production of each subunit before the cells are fused. But even more important to the company is that the technology provides the combinatorial capability that underlies CombiKARYON™.
CombiKARYON™ begins with the ability of the NeuKARYON™ system to take two fungal strains, each producing a single subunit, and fuse them to form a multicellular, multinucleate strain. In the CombiKARYON™ system, variants of each subunit gene are generated by standard techniques and then are inserted into host cells to produce libraries of strains.
Individual strains producing variants of the first subunit are then fused with strains producing variants of the second subunit to create unique combinations. The system can also be used to create combinations of more than two subunits.
Building the business
The molecules produced with the technology can be screened for desired characteristics, such as increased activity, binding affinity or specificity. Cultures of desired combinations then can be expanded to produce milligram quantities of protein.
The company's goal is to generate cash flow in the near term through product sales into the R&D reagent industry, as well as through corporate alliances. Within the biotherapeutics market, Neugenesis sees opportunities in the production of products that are in development, as well as in the production of proteins whose patents have expired. As products such as growth hormone come off patent, Iow-cost expression systems will take on new significance.
Neugenesis was founded as a virtual company in 1993 by W. Dorsey Stuart, Professor of genetics and molecular biology at the University of Hawaii School of Medicine. Stuart is president and CEO and chief scientific officer. Ronald Cape, founder of Cetus Corp. and chairman of Darwin Molecular Corp. (Bothell, Wash.), recently was named chairman.
The company has obtained $1.7 million from a combination of private investors, board members and their families, the University of Hawaii, and two local venture capital firms, Keokea Hawaii and HMS Hawaii.