[Pharm-policy] Els Toreele on the "Winter II" antibody expression library patent

[James Love]

-------- Original Message --------
Subject: Re: [Ip-health] Patent on "Winter II" antibody expression library
Date: Fri, 06 Jul 2001 16:06:38 +0200
From: Els Torreele <etorreel@vub.ac.be>
To: James Love <love@cptech.org>

> Els Torreele wrote:
  dear Jamie,
  a rather late reply . . . 

The US Winter2 patent is based on an earlier European patent (EP368684, granted
in 1994).

The European Winter2 patent is entitled "Cloning immunoglobulin variable domain
sequences" (inventor: a.o. Greg Winter, hence the name), and has a very broad
claim on the cloning of immunoglobulin (=antibody) variable regions using PCR.
These variable regions are the interesting parts of an antibody molecule, the
parts you want to use in diagnostics, therapeutics.
If you want to produce these parts in sufficient quantities, you want/need to
express these recombinantly. For that, you need to clone them, which is a very
general and basic recombinant DNA technology procedure. But apparently the
cloning of these antibody parts has been accepted as something inventive, and
this broad claim was accepted in the Winter2 patent.

Importantly, the European Winter2 patent also contains a very broad claim on the
generation and use of expression libraries of repertoires of immunoglobulin
variable domains. The immunoglobulin repertoire is the full collection of
antibodies (or their genes) of an individual. This is a very large and powerful
collection: it is thought to contain antibodies recognising virtually any
molecule (or antigen). The major challenge in antibody technology or
antibody-based diagnostics/therapeutics is to identify/find/isolate/select in
this huge (natural) collection, the antibody of interest for you (e.g.
specifically recognising a certain type a cancer cells).
THE most powerful way to do this (generally used) is to generate an expression
library. This is a collection of cells (usually bacteriophages) that each
express on their surface one particular antibody (or only its variable domain,
the interesting part). Such an expression library can easily be screened against
antigens of interest, to look for and pick up the antibody of interest (which
can then be produced in larger quantities and purified via other systems).
To generate such an expression library, you start with B-cells of an (immunised)
individual, from which you CLONE the variable parts of the antibodies (see
above) and transfer these to the phages.

The recently granted US patent (US 6,248,516) is entitled
"Single domain ligands, receptors  comprising said ligands, methods for their
production, and use of said ligands and receptors".
Looking at the accepted claims however, it seems the patent focuses mainly on
antibody expression libraries (including methods for producing them).

Thus, this Winter2 patent is indeed extremely large, and gives Cambridge
Antibody Technology (CAT) the exclusive rights to some of the basic technologies
for anything you want to do in the antibody area: cloning of the variable domain
and antibody expression libraries.
Note that CAT in addition controls the patents on:
- phage display (needed for the expression libraries)
- the isolation of human antibodies to human proteins by phage display (which is
the method for selecting the antibodies of interest)