Abbott Scientists Create One Molecule With Two Antibody Functions

Abbott Scientists Create One Molecule With Two Antibody Functions

October 18, 2007

First Combination of Large Molecules to Show Drug-like
Properties and Manufacturing Feasibility


    ABBOTT PARK, Ill., Oct. 18 /Xinhua-PRNewswire/ --
Abbott (NYSE: ABT) reported today that its scientists are
the first to discover a proprietary technology that
combines the function and specificity of two or more
monoclonal antibodies (mAbs) into one molecular entity that
demonstrates drug-like properties and manufacturing
feasibility.  These molecules, called dual-variable domain
Ig (DVD-Ig(TM)) (
http://www.abbott.com/global/url/content/en_US/60.15:15/feature/Feature_0029.htm
), will allow for development of individual drug candidates
that target multiple disease-causing molecules in various
therapeutic categories.

    Published online earlier this week in Nature
Biotechnology (
http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt1345.html
), this landmark study demonstrates a completely new
platform that may be relevant to cancer, autoimmune
diseases and other complicated conditions in which multiple
disease-mediators are at play.  Simultaneous blockage of
multiple targets using DVD-Ig agents may increase efficacy
in comparison to inhibition of a single target using a mAb.
 

    "Combining the specificity of two or more
antibodies into one drug has been a significant challenge
for researchers looking at next generation biologic
therapies," said Abbott Scientists Chengbin Wu, Ph.D.
and Tariq Ghayur, Ph.D., who designed the DVD-Ig molecules
and led the research team.  "Abbott's approach is
remarkably versatile and efficient in creating a single
molecular entity with drug-like properties and the ability
to target multiple disease mediators.  We are very excited
about the doors this opens in drug development across a
range of therapeutic areas."  

    The process of combining two or more mAbs involves the
use of molecular biology techniques, such as polymerase
chain reaction (PCR), to link the regions (variable
domains) of two different antibodies that target specific
disease-causing molecules.  The resulting molecule has two
different (dual) variable domains, each of which targets a
different disease-causing antigen.

    While other public and private research programs have
endeavored to combine two antibodies into one entity, the
results have been limited by poor pharmacokinetics,
stability and manufacturing feasibility.  

    Addressing only one disease target with a traditional
mAb can result in limited efficacy because the disease can
progress on multiple levels.  For example, in rheumatoid
arthritis (RA) distinct disease mediators (mechanisms)
contribute towards various aspects of the disease such as
inflammation, angiogenesis, pannus formation (thickened
layers of granulation tissue) and bone and cartilage
erosion.  Therefore, targeting two or more disease
mechanisms in RA may show far greater efficacy than
targeting a single mechanism. 

    Using the DVD-Ig technology, research teams at Abbott
have already created a single drug candidate that targets
multiple disease components, one of which is TNF-alpha, a
well-established target in RA.  Preclinical evaluation of
this drug candidate is underway. 

    Abbott's DVD-Ig approach has distinct technological,
scientific and drug development advantages compared to mAbs
and to previous efforts to create a multi-specific antibody.
 The approach is compatible with any antibody, including
humanized mAbs, fully-human mAbs and chimeric mAbs, and can
potentially be extended beyond antibodies to receptor
proteins and other, similar molecules.  DVD-Ig drugs also
may have improved efficacy because they target multiple
disease-causing molecules, and can address redundant
disease processes, in which two different molecules have
the same disease-causing effect.  

    Abbott has completed technology validation on the
DVD-Ig program, and is currently confirming process
development and manufacturing for the technology platform. 
Concurrently, preclinical work has been conducted on a
variety of combinations at Abbott to date.

    About Abbott

    Abbott is a global, broad-based health care company
devoted to the discovery, development, manufacture and
marketing of pharmaceuticals and medical products,
including nutritionals, devices and diagnostics.  The
company employs 65,000 people and markets its products in
more than 130 countries.


    For more information, please contact:

    Media
     Laura Weber
     Abbott
     Tel:   [phone]

    Financial
     Lawrence Peepo
     Abbott
     Tel:   [phone]