Crescendo Biologics Announces First 'Triple Knockout' Mouse

By Crescendo Biologics Ltd, PRNE
Tuesday, September 28, 2010

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

CAMBRIDGE, England, September 29, 2010 - 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.
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

Contacts: Mike Romanos/Amanda Bettison, Crescendo Biologics, Tel: +44-(0)1223-497140, Email: mromanos/abettison at crescendobiologics.com. Chris Gardner, Citigate Dewe Rogerson, Tel: +44-(0)207-638-9571, Email: chris.gardner at citigatedr.co.uk

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