H I R S C H & PAR T N E R S
Avocat Solicitor Rechtsanwalt
PATENT LIFE CYCLE MANAGEMENT
Strategies for originators and tactics for generics
Dr Denis Schertenleib
Avocat & Solicitor
Partner Hirsch & Associés
Paris France
ds@hirschlex.com
25 years is both too long and
too short
Originators are burdened with increasing
costs for developing drugs
 Originators have less and less blockbuster
drugs in the pipeline
 The costs of novel drugs are perceived as
too high even for developed economies

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There is a real pressure for

Originators to increase the duration of their
monopoly beyond 25 years.

Generics to break that monopoly.
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Second generation patents

These patents seek to protect a drug after
the original patent on the drug has
expired.

They protect some form of variation or
improvement.
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Second generation patents examples

Second therapeutic use

Crystalline polymorphs

Single enantiomers
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Dr Denis Schertenleib
Second therapeutic use

Claims to a further medical use of a
substance for which a therapeutic use was
known.

E.g. a claim to the use of aspirin for
fluidifying blood whereas aspirin was
known as a pain killer for decades.
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Second therapeutic use

Valid since EPO decision G5/83 if drafted in
swiss type format:
Use of product X for the manufacture of a medicament
for treating illness Y

Until EPC 2000 validity was challenged at
national level.
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2nd therapeutic use – EPC 2000

EPC 2000 clearly removed any ambiguity
as to validity of 2nd therapeutic use.

EPC 2000 allows straightforward drafting
of 2nd therapeutic use claim:
Product X for treating illness Y
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Dr Denis Schertenleib
therapeutic use – dosage
regimen
nd
2
Can dosage regimen be a patentable new
use:
 Eg: Fosamax

 known
to use Fosamax every day at 10mg
 Patent on use of Fosamax once a week at 70
mg
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therapeutic use – dosage
regimen
nd
2

Problem with EPC as methods of therapy
are not patentable.

Is a dosage regimen a method of therapy
in disguise?
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therapeutic use – dosage
regimen
nd
2





Under EPC case law : unpatentable (T317/95)….
Until T1020/03.
BUT referral to enlarged EPO Board pending G2/08
In the UK: unpatentable under Bristol-Myer Squibbs
(2001).
But now under Actavis UK Ltd v Merck & Co Inc CA
2008: potentially patentable to follow EPO
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therapeutic use – valid new
uses
nd
2

T290/86, T486/01, T189/95, T254/93 and finally
T1020/03:
illnesses (sildenafil: viagra® and now for
pulmonary hypertension)
 New patient groups (Diovan® for adolescents)
 New

Overall : need to open a new field of clinical
application
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therapeutic use – invalid
new uses
nd
2

T486/01 – a claimed use characterised by giving
more information about a mode of action all
ready practised was not novel.

T836/01 - a claimed use which specified a
different mechanism of action could be novel
over prior art disclosing the same use as it
opened new therapeutic possibilities
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nd
2
therapeutic use infringement




It is not the product that is protected but the use.
There is a need to show intended use not merely
possibility of use.
Need to resort to evidence such as advertisement,
marketing authorizations, user notices (Wyeth v Abbott
Paris Court of Appeal 2004)
What if stated illness is different from patented use:




Allergic rhinitis v hayfever
Alzheimer v alzheimer caused by a specified trauma
Reducing mortality form illness v treating symptoms of illness
Always remember the validity /infringement squeeze
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Cristalline polymorphs

Complex molecules
can crystallize in may
ways:

Diamond, coal and
carbon nanotubes are
different crystal
structure of the same
compounds
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Cristalline polymorphs

Different crystal structure can result from:
 Crystallization
parameters (solvent,
temperature )
 Hydration
 Cristal partners (co-crystals)
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Cristalline polymorphs – relevance?

New polymorphs can have enhanced:
 Stability
and Shelf life
 Improved production process and handling
 Biovailability

Examples include: Ranitidine (Zantac®),
Paroxetine (Deroxat®), Cefnidir (Omnicef ®)
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Cristalline polymorphs –
commercial relevance

Useful to extend patent monopoly if the
market switches.

Generic that uses the “old” crystalline form
can be seen as “outdated” even if no
actual benefit result.
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Cristalline polymorphs – patent
definition?
At present cannot be defined directly by
structure
 Need to show X-ray or Infrared absorption
data.
 These are akin to identification by
fingerprinting

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Cristalline polymorphs – Xray data

Atorvastatin:
form V
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form VI
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Dr Denis Schertenleib
Cristalline polymorphs – Xray data

The products claimed are defined by selecting
characteristic peak

Claim 1 : Crystalline atorvastatin hemi-calcium
characterized by a PXRD pattern having peaks
at 3.8, 8.0, 8.9, and 10.4±0.2 degrees 2 theta.
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Cristalline polymorphs – Issue with
validity - Novelty
How different should X ray spectra be?
 Should peaks be of different heights,
different positions?
 Lord Justice Jacob in Laboratoire Servier v
Apotex 2008 CA:

 “The
individual peaks of the table should not
have too much significance attached to them
–it is the overall set that matters”
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Dr Denis Schertenleib
Cristalline polymorphs – Issue with
validity - Novelty

Was the “new” polymorph already manufactured
in the past?

Polymorphs are know to interconvert or revert
spontaneously to other forms.

Servier v Apotex
form a was the inevitable product of the
prior art protocols.
 Patented
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Cristalline polymorphs – Issue with
validity – Inventive step




Often polymorph patents claim several new
forms at once but do not state what the new
polymorph is for?
Often polymorph patent make vague claims
about improved stability with no data
Problems with inventive step under the EPO
problem/solution approach.
Is there an invention or a crystalline oddity?
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Cristalline polymorphs –
Infringement





What if some peaks are different?
What if the X ray spectra of the alleged infringement is
more similar to the prior art X ray spectra?
The novelty/infringement squeeze
Evidential problems arise easily as excipient peaks (such
as lactose) easily mask the relevant peaks.
The Lord Chief Justice in Servier v Apotex: “The
evidence gave the case the spurious veneer of technical
complexity”
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Enantiomers

Molecules can have
asymmetric shapes
so that a mirror image
of them is different
form the original

They are called chiral
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Dr Denis Schertenleib
Chiral molecules

Chiral molecules can exist in the two mirror
image form. They are called enantiomers.

A mixture of both enantiomers is called racemic

The two enantiomers are called the L and the D
form (or + and – or S and R ).
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Dr Denis Schertenleib
Enantiomers – medical
relevance?

Often drugs can exist in
the L and the D form.

One form can be
therapeutic and the other
toxic.

Thalidomide: one
enantiomer was
therapeutic and the other
was teratogenic.
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Dr Denis Schertenleib
Enantiomers – commercial
relevance: “patent and switch”

Useful to extend patent monopoly if the market switches.

Generic that uses the “old” racemic form form can be
seen as “outdated” even if no actual benefit result.

Eg: Zyrtec® : racemic form of cetirizine outdone by the
“new” L-cetirizine : Xyzall®.

Actual clinical benefit still controversial.
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Enantiomers – patentability


Novelty : T1046/97: enantiomers can be novel of
the racemic mixture.
But are they inventive over growing literature in
the last 20 years prompting the skilled worker to
investigate individual enantiomers?
 See
T944/04 obvious to try out individual enantiomers
 See Ranbaxy attack on Lipitor®; English Court of
Appeal : skilled worked would investigate the
properties of the enantiomers.
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Dr Denis Schertenleib
Enantiomers – defending
infringement claims

Extrinsic evidence of speculative results.

Some patentee file on the same day pairs
application each directed to one of the two
enantiomers.
But is this an invention or a wild guess?

 Patent
require some credible evidence of claimed
effect: see T1329/04, T609/02 and T715/03.
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Dr Denis Schertenleib