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Last updated on April 18, 2014 at 17:24 EDT

Crescendo Biologics Announces First ‘Triple Knockout’ Mouse

September 29, 2010

CAMBRIDGE, England, September 29, 2010 /PRNewswire/ –

– Mice Lacking Endogenous Antibody Polypeptides Offer Powerful New Tool
for Antibody Fragment Development

Crescendo Biologics Limited (Crescendo) today announces it has
established a colony of engineered mice completely devoid of endogenous
antibody polypeptides. The proprietary ‘triple knockout’ mice are believed to
be unique and have the immunoglobulin heavy chain (IgH), kappa light chain
and lambda light chain loci all functionally silenced by large-scale genomic
deletion.

This is a significant advance over previous knockout mice which retain
intact lambda light chain. While lambda light chain accounts for at most 10%
of the light chains in mouse antibodies, Crescendo believes that knockout of
all light chain expression is critical for the efficient generation of human
heavy chain antibodies in transgenic mice. The new knockout mouse thus offers
an enhanced background for the generation of new antibody therapeutics and is
a key step in the establishment of Crescendo’s world-leading VH antibody
fragment platform. VH fragments are the smallest fragments that retain
antibody binding, and have many desirable properties as potential
therapeutics.

In a parallel development, Crescendo has also demonstrated the potential
of its first generation yeast artificial chromosome (YAC) with the successful
expression of human antibodies. Working with Professor Lluis Montoliu at the
Centro Nacional de Biotecnologia (a centre belonging to the Spanish National
Research Council, CSIC) in Madrid, transgenic mice have been generated by
oocyte microinjection with a first YAC comprising several human V genes, all
human D and J genes and a C region engineered for expression in the absence
of light chains. This YAC has been shown to rearrange and express human
antibodies in wild type mice.

“Today’s announcement marks an important milestone in the development of
our highly innovative antibody fragment technology,” said Mike Romanos, CSO
of Crescendo Biologics. “We have successfully delivered what we believe to be
a unique asset in our triple knockout mice, and have also made significant
steps in the generation of YACs which direct the production of human heavy
chain antibodies. When combined, and with further developments in our YAC
technology, we believe we will have the strongest platform for the generation
of new VH fragment therapeutics and can harness the great benefits they will
bring as therapeutics.”

The Crescendo approach is aimed at bringing together two highly desirable
characteristics of antibody platforms – human origin and in vivo maturation -
to allow rapid creation of high affinity fragments. The company intends to
progress at least one VH-based product to the clinic.

Crescendo is now working to generate mice that combine its newly
developed YAC and the triple knockout mouse, in order to generate a first
generation Crescendo mouse platform. In addition, Crescendo is generating
additional YAC transgenics to progress towards the best in class mouse.

About Crescendo Biologics Ltd

Crescendo Biologics will apply highly innovative antibody fragment
technologies to the development of new targeted therapeutics. The Crescendo
transgenic mouse platform under development has the potential to rapidly and
predictably generate high-affinity human heavy chain antibodies that readily
yield VH fragments that have no requirement for humanisation. This is
combined with a powerful in vitro ribosome display technology which offers
significant advantages over existing approaches in antibody optimisation. VH
fragments provide great flexibility as a starting point for the development
of new targeted therapeutics combining the specificity and binding affinity
of antibodies with certain desirable characteristics of small molecules.

Crescendo’s technologies were invented by scientists at the Babraham
Institute, Cambridge (UK). The Company has raised GBP4.5 million in seed
funding from leading life sciences investors, Sofinnova Partners with Aitua,
Avlar BioVentures and the Rainbow Seed Fund also participating.
http://www.crescendobiologics.com

    Contacts

    Mike Romanos/Amanda Bettison
    Crescendo Biologics
    Tel: +44-(0)1223-497140
    Email: mromanos/abettison@crescendobiologics.com

    Chris Gardner
    Citigate Dewe Rogerson
    Tel: +44-(0)207-638-9571
    Email: chris.gardner@citigatedr.co.uk

SOURCE Crescendo Biologics Ltd


Source: newswire