H I R S C H & PAR T N E R S

Av o c a t So l i c i t or R e c ht sa n wa l t

PATENT LIFE CYCLE MANAGEMENT

Strategies for originators and tactics for generics

Dr Denis Schertenleib
Avocat & Solicitor
Partner Hirsch & Associs
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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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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2nd therapeutic use dosage

regimen
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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2nd therapeutic use dosage

regimen

Problem with EPC as methods of therapy

are not patentable.

Is a dosage regimen a method of therapy

in disguise?

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2nd therapeutic use dosage

regimen

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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2nd therapeutic use valid new

uses

T290/86, T486/01, T189/95, T254/93 and finally

T1020/03:
New

illnesses (sildenafil: viagra and now for

pulmonary hypertension)
New patient groups (Diovan for adolescents)

Overall : need to open a new field of clinical

application

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2nd therapeutic use invalid new

uses

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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2nd 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

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 10.40.2 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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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 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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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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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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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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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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