Summary Strategic IP Management class 2: Patent Portfolios and IP Lifecycles (D0O43A)

Samenvatting Strategic IP
management Class 2:
Case  Alnylam Pharmaceuticals - Building
Value from the IP Estate
This is a thorough and detailed summary of the Alnylam Pharmaceuticals case, focusing on
their intellectual property (IP) strategy, the scientific basis, and the legal challenges.

1. The Scientific Breakthrough: RNA Interference (RNAi)
At the heart of Alnylam's technology is RNA interference (RNAi), a natural process in cells
that allows genes to be "turned off."

 Mechanism: While traditional drugs often block proteins, RNAi works "upstream" by
turning off genes at the RNA level before they are translated into harmful proteins.

 Historical Context: The discovery that double-stranded RNA (dsRNA) could turn off
genes earned Andrew Fire and Craig Mello the Nobel Prize in 2006.

 The Tuschl Discovery: The key step towards human application came from Tom
Tuschl. He discovered that small fragments of RNA (siRNA) of 19-23 base pairs could
effectively disable genes in human cells without triggering a lethal immune response.

2. Alnylam's Strategy: IP Consolidation
Alnylam was founded in 2002 with a very specific focus on controlling the IP landscape. CEO
John Maraganore wanted to prevent the "fragmentation of value" that had previously
occurred with technologies such as monoclonal antibodies.

The strategy rested on four pillars:

 Division of use fields: The technology was divided into laboratory reagents (for
researchers) and therapeutic uses.

 Building an "IP Estate": The systematic collection of all crucial patents ("frontier
patents") in the field.

 Selective Licensing: Granting licenses to raise capital without having to sell shares
(non-dilutive funding).

 Investment in R&D: Use the proceeds for research into the biggest challenge: the
delivery of siRNA to the right cells in the body.


3. The "IP Estate" and the Key Patents

,Alnylam identified eight "must-have" patents to ensure their freedom to operate.

 Tuschl I: Jointly owned by Max Planck, MIT, the Whitehead Institute, and UMass. It
focused on early discoveries in fruit flies.

 Tuschl II: Exclusively licensed to Alnylam. This included the crucial discovery of siRNA
in human cells.

 Kreutzer-Limmer: Alnylam acquired Ribopharma AG to acquire these early patents on
siRNA in mammalian cells.

4. Legal Battle: Tuschl I vs. Tuschl II
A major dispute arose over the settlement of the patents.

 The Conflict: Alnylam and the Max Planck Institute sued Whitehead, MIT, and UMass.
The allegation was that the opposing party attempted to use details of the (exclusive)
Tuschl II invention to broaden the claims of the (shared) Tuschl I patent.

 The Stakes: If Tuschl I were broadened to include human applications, competitors
(such as Sirna Therapeutics, which licensed Tuschl I through UMass) would gain
access to the technology that Alnylam wanted to keep for itself.

 Cause: Critics argued that Alnylam erred by not securing UMass's rights to Tuschl I at
the outset.

5. Business Results and Future
Alnylam managed to raise nearly $1 billion, $700 million of which came through strategic
licensing deals with major pharmaceutical companies such as Novartis, Roche, and Takeda.

The biggest remaining challenges described in the text are:

 Delivery: Developing safe methods (such as nanoparticles) to deliver siRNA to specific
organs.

 Competition: Large companies like Merck (which acquired siRNA for $1.1 billion)
attempted to build their own IP positions and challenge Alnylam's patents.

 The "Patent Clock": The need to get actual drugs onto the market within the patent
term (usually 20 years).




Preparation questions
 What are the main building blocks of Alnylam’s patent portfolio? 

, o The "Eight Frontier Patents": Alnylam identified eight "must-have" patents
considered essential for anyone developing RNAi therapeutics.

o Tuschl I & II: These are foundational patents. Tuschl I (jointly owned) covers
early work in fruit flies, while Tuschl II (exclusively licensed to Alnylam) covers
the breakthrough discovery of siRNA activity in human cells.

o Kreutzer-Limmer Patents: Alnylam acquired the company Ribopharma AG
specifically to gain control over this patent family, which relates to short
dsRNA fragments in mammalian cells.

o Strategic Cross-Licenses: Alnylam secured freedom to operate through cross-
licenses with other IP holders, such as the Crooke patents (from Isis
Pharmaceuticals) and Benitec.

o Professor:
 Tuschl I  basic structure of the RNAi structures for simple cells (in
fruit flies)
 Co-owned by Max Planck, MIT, the Whitehead Institute, and
UMass  alnylam has a non-exclusive license for it (so other
companies also have a license such as sirnath)
 The patent was still pending
 Tuschl II  structure of RNA strand so it also work on human cells
 Max Planck only owns it bcs the follow-up research was only
done by researchers from there  alnylam has exclusive
license
 The patent was granted although it was younger bcs there was
no dispute with co-ownership
 Six other patents but Alnylam doesn’t own any of them, they did
licensing, cross-licensing, acquiring and even licensing where they
have the right to license themselves to other companies




 Why are the co-owners of the Tuschl-I patent fighting over the prosecution?  The
co-owners of the Tuschl-I patent (Max Planck, MIT, Whitehead, and UMass) are in a
legal dispute over its prosecution (the process of interacting with the patent office)
for the following reasons: