GenPharm publishes high affinity human antibodies from transgenic mice.

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--July 1, 1996--GenPharm International, Inc. published today in the July issue of Nature Biotechnology the generation of high affinity human IgG antibodies.

These human monoclonal antibodies had affinity levels suitable for therapeutic use with their binding constants reaching 10(10) M(-1). The antibodies were produced from GenPharm's HuMAb-Mouse, a transgenic mouse line containing human antibody genes that rearrange to form high affinity human antibodies. The mice can be used to generate monoclonal human antibodies to a wide variety of antigens, including human antigens.

In a research commentary in Nature Biotechnology, the distinguished British academic, Professor Michael Neuberger from the MRC Laboratories in Cambridge, England, wrote: "The results of Fishwild et al. (GenPharm) provide powerful support for the usefulness of the transgenic minilocus technology." Professor Neuberger went on to note, "The primary repertoire generated in these animals is indeed sufficiently diverse to be useful for isolating antibodies against a wide variety of antigens."

"We are delighted by the publication of this work and the acknowledgment of the capability of our HuMAb-Mouse system," commented Jonathan MacQuitty, Ph.D., Chief Executive Officer of GenPharm International. "The next object for our antibodies is to bring some of them to the clinic."

GenPharm International, Inc. is a world leader in the development of human monoclonal antibodies from transgenic mice for therapeutic and diagnostic uses. GenPharm's transgenic HuMAb-Mouse contains key sequences from unrearranged human antibody genes as well as having inactivated mouse antibody genes. The human sequences code for both the human heavy and light chain segments of human antibodies. The human gene sequences function well in the mouse undergoing rearrangement to provide a wide antibody repertoire similar to that in humans. Most importantly, the human antibodies in the transgenic mice undergo class switching and somatic mutation from low affinity IgM class antibodies to high affinity human IgG class antibodies.

GenPharm has now generated, using its transgenic mouse system, human IgG antibodies with affinities that exceed 10(10). Antibodies for commercial therapeutic use need affinities in this range to have clinical utility. In addition, because these antibodies are generated from human sequences, they should avoid the rejection problems that have often afflicted mouse-based antibodies.

Another important feature of GenPharm's HuMAb-Mouse is its ability to react against human antigens. Thus, unlike most antibodies produced in humans, GenPharm's mice can generate human antibodies with high affinity against human antigens. This allows for the possibility of using human antibodies to control a wide range of inflammatory conditions, autoimmune diseases and cancers. GenPharm has already generated human IgG antibodies to various human antigens, including IgE, CD4 and the cancer antigen CEA.

Because the human sequences in the HuMAb-Mouse can generate high affinity human IgG directly in the mice, it is unnecessary to modify the human antibodies produced any further, either to "humanize" the antibodies or to improve their affinity or specificity. Because the antibodies have been matured in vivo, they naturally have the specificity and affinity necessary for proper binding to the target antigen.

CONTACT: GenPharm International

Jonathan MacQuitty, 415/988-2401