Lilliputian meets Brobdingnagian
Astellas Pharma signs a license agreement with Evec for a fully human antibody
SAPPORO, Japan—Evec Inc. and Astellas Pharma Inc. haveentered into a license agreement for one of Evec's fully human antibodiesagainst infectious diseases. Based on the agreement, Astellas has worldwideexclusive development, manufacturing and commercialization rights for theprogram. In return, Evec expects to receive an upfront payment of approximately$7.86 million upon signing the license agreement and milestone payments,depending on development and sales phases from Astellas, totaling up to $17million. Astellas will also pay additional royalties associated with potentialsales. The development stage of the program is preclinical.
A 13-employee laboratory launched in 2003, Evec developedits own technology for producing fully human antibodies in order to circumventU.S. and European patents, which the company claims are too expensive tolicense. The company says it now has a dozen patents granted or pending.
The company founder and chairman, Dr. Kenza Takada, notesthat "human blood teems with highly active antibodies which can never beinduced by the mouse immunizing method. Evec has the unique technique todevelop antibodies from human blood lymphocytes by using Epstein-Barr (EB)virus that induces B-lymphocytes to proliferate. I am confident that ourtechnique will replace the currently major one to develop antibodies usingmouse, and will be the standard method of antibody development."
Most of the antibody medicines currently available are ofchimeric or humanized antibody, which is a modification of mouse antibody withreplacement of the mouse element. Recently, however, Evec notes that fullyhuman antibodies containing no mouse elements are coming to the fore. Evec hasdevised a technique to develop fully human antibodies from B-lymphocytes, cellsresponsible for antibody production in humans.
Evec points out on its website that humans are exposed tovarious antigens, from infections, for example. On each exposure,antibody-producing lymphocytes are activated, which then remain as memoryB-lymphocytes.
"Our peripheral B-lymphocyte population can be considered asa library of memory B-lymphocytes expressing antibodies," Takada says.
His technique uses the EB virus to induce proliferation ofB-lymphocytes and promote antibody production. In in-vitro experiments, EB virus-infected lymphocytes stablyproliferate over six months, while non-infected lymphocytes die within a weekor so, according to Evec.
"We develop antibodies by using the EB virus activity toproliferate B lymphocytes. B-lymphocytes are separated from 10～20 ml blood, and infected with EB virus.From the proliferated B-lymphocytes, cell clones producing the antibody ofinterest are separated. The clone separation is carried out by a combination ofthe clone culture method (repeating dilution culture) and the sorting method(selectively separating the antibody of interest with the use of FACS). Afterthe separation, the antibody gene is cloned and transfected into CHO cells forantibody production. Namely, the EB virus is used merely as a means to isolateantibody genes from blood lymphocytes. There is no risk for contamination ofthe antibody with EB virus," Takada states.
The highest binding activity of the antibodies developed bymouse immunization is around 10-9M, and those of the antibodymedicines already in the market are much the same, says Takada. In contrast,the binding activity of Evec's antibodies developed from blood B-lymphocytes is10-11M, 100 times higher than that of mouse antibody, he asserts.
Based in Tokyo, Astellas hopes to strengthen its pipeline ininfectious diseases therapies through its collaboration with Evec. It iscurrently Japan's second largest pharmaceutical company and ranks within thetop 20 in the global market. Astellas Pharma U.S. Inc., the company's U.S.affiliate, reported North American sales of $1.9 billion in 2009. The companyemploys 1,900 and is headquartered in Deerfield, Ill.