Subject: GenPharm Expects Patent on Immunodeficient Mouse
Date: Published: 5/11/92 (128 lines)
Source: Wall Street Journal. Copyright Dow Jones & Co. Inc.

    Enterprise:
    GenPharm Expects Patent on Immunodeficient Mouse
    ---
    Genetically Engineered Rodent Would
    Be Used by Medical Researchers
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    By Marilyn Chase
    Staff Reporter of The Wall Street Journal

    MOUNTAIN VIEW, Calif.  -- Jonathan MacQuitty, president of
 GenPharm International, believes he has built a better mouse.
    The private, four-year-old biotechnology firm emerged from
 obscurity when Dr. MacQuitty asserted GenPharm will soon
 receive a patent on a genetically engineered mouse for
 medical research.
    If his forecast holds true, GenPharm would leapfrog
 several better-known biotech teams and break a four-year
 hiatus in the issuance of animal patents, a bureaucratic
 logjam that now encompasses 180 applications.
    What's at stake is a patent covering a tiny research
 powerhouse:  an immunodeficient mouse.  These mice are lab
 animals, purged of their mousey immune system and then given
 cell or tissue transplants to endow them with a human-like
 immune system.  The goal is to adapt them as perfect lab
 surrogates for the study of a variety of human ailments,
 including AIDS, cancer and genetic disorders.
    So far, such mouse research has been dominated by three
 groups:  Systemix Inc. of Palo Alto, Calif.; the Medical
 Biology Institute of La Jolla, Calif.; and the Weizmann
 Institute of Rehovot, Israel.  More recently, Immunex Corp. of
 Seattle teamed up with the University of Toronto to give mice
 a cocktail of human growth factors and induce them to produce
 the whole repertoire of red and white blood cells.
    "It's a very hot field," says Dr. MacQuitty, a 39-year-old
 graduate of Oxford and the University of Sussex.  A Genentech
 Inc. alumnus, Dr. MacQuitty founded GenPharm in 1988 and
 raised $23 million of venture capital from such sources as
 Institutional Venture Partners of Menlo Park, Calif.  He
 planned to take the company public in April, but a stock
 offering was aborted when the market soured on biotech.  "The
 window slammed, but we have $14 million in the bank," he
 said, unfazed.  Neither is he fazed by his rivals.
    "What Systemix did with its mouse was an improvement over
 preceding work, but it's not the holy grail, not ideal," says
 Dr. MacQuitty.
    The Systemix mouse, known as SCID (for severe combined
 immune deficiency) starts with a natural mutant mouse that
 lacks an immune system.  Then scientists install a human
 immune system through transplants of human tissue like fetal
 thymus gland.  But this model -- because it is natural --
 allows remnants of mouse immune reactions to "leak" through,
 clouding the transplanted human immune reactions, he charges.
    "It's not a stable platform for doing experiments," says
 Dr. MacQuitty.  His competitors deny this, arguing they can
 easily screen out the few mice whose immune systems "leak."
    Dr. MacQuitty's mouse, called TIM for transgenic
 immunodeficient mouse, is different because GenPharm
 scientists knock out its immune system with genetic
 engineering techniques while the mouse is an embryo.  The
 mouse then has offspring that are consistently
 immunodeficient, allowing transplanted human immune responses
 to appear truer and cleaner.
    "We can make a very precise change, a very specific
 removal of precise elements of the immune system, such as
 T-cells, B-cells or natural killer cells," Dr. MacQuitty
 asserts.
    However, he acknowledges that he has done few experiments
 and published little to back his claim of superiority and
 patent primacy.  It is an audacious stance that has made
 competitors bristle.
    "We've known they were working on transgenic mice for some
 time," says Linda Sonntag, president of Systemix.  "But
 there's no reason to believe a transgenic mouse is superior
 to a naturally occurring one."  Systemix filed a patent
 application on its mouse in 1987.
    "I'm confused about what MacQuitty's announcement means,"
 says Donald Mosier of Medical Biology Institute, a sometime
 GenPharm collaborator that applied for its own patent in
 1988.  "These patent applications have been stuck in the
 patent commissioner's office for some time."
    To be patentable, an invention must be useful,
 "non-obvious" and somehow rendered practical.  Dr. Mosier said
 the GenPharm claim might have some edge in the "non-obvious"
 category because it isn't a natural mutant.  "It would be a
 technical advance not to have to screen out the `leaky' mice,
 but I wouldn't characterize it as a major advance," he said.
    In Arlington, Va., a spokesman for the U. S. Patent and
 Trademark Office refused to coment on the status of any
 individual application.  However, Dr. MacQuitty said Friday
 his patent examiner assured him that his application -- which
 got a notice of "allowable claims" -- has the inside track.
 The next step is a formal notice of allowance, followed by
 routine payment of a fee, and publication of the patent
 within three months, he says.
    A patent -- conferring 17 years of market protection and
 potentially lucrative royalties -- is an event devoutly
 wished by animal engineers but long postponed by the patent
 office.  It hasn't happened since 1988, when researchers at
 Harvard University won a patent covering the so-called
 Oncomouse, a mouse used in cancer research, and licensed to
 Du Pont Co. 
    Indeed, Dr. MacQuitty says he is expecting a second patent
 to be issued soon covering a mouse related to DuPont's
 Oncomouse -- this one called called PIM -- which GenPharm is
 already selling to the National Institutes of Health and to
 pharmaceutical companies to test whether a drug is a
 carcinogenic.
    Word of GenPharm's patent chutzpah set off new alarms
 among animal rights groups, which have decried the practice
 of reinventing nature ever since the landmark Chakrabarty
 case, in which the U. S. Supreme Court in 1981 affirmed the
 patent on an oil-eating microorganism by General Electric
 scientists.
    Such protests "have no impact on us," says the Patent
 Office spokesman.  "We're controlled by legislation.
    "We have a large backlog, a new area of science, and too
 few examiners, who are overwhelmed with applications," the
 spokesman said, explaining the four-year recess in animal
 patents.  "It's new territory and we're proceeding with
 caution."

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