Amgen Vs Hoechst Patent Dispute

Amgen Vs Hoechst
1Manish Bhangale MIPLC 2012-2013

Preliminary Details
The Patentee: (Plaintiff)
Kirin-Amgen Inc ("Amgen"), a Californian pharmaceutical
company, is the proprietor of a European patent (EP
0148605B2) relating to the production of erythropoietin
("EPO") by recombinant DNA technology.
EPO is a hormone made in the kidney which stimulates the
production of red blood cells by the bone marrow.

Preliminary Details
The accused Infringers: (Defendants)
Transkaryotic Therapies Inc ("TKT") is a Massachusetts
corporation. It has also developed a method of making
EPO, which it markets under the name Dynepo. It uses
a process which it calls "gene activation" and the
product been referred to in this appeal as "GA-EPO".
Hoechst Marion Roussel Ltd ("Hoechst") is the English
subsidiary of a well-known multinational
pharmaceutical company which has been proposing to
import GA-EPO into the United Kingdom.

The Issues
Amgen claims that GA-EPO infringes the claims
of the patent in suit
TKT and Hoechst claim a declaration of non-
infringement and revocation of the patent.
The only allegations of infringement in the
United Kingdom arise out of the importation
of the drug by Hoechst.

Amgen Technology
Dr Lin isolated the gene which coded for human EPO
from a human donor cell and then introduced it into a
mammalian cell in culture which had been derived
from the ovary of a Chinese hamster (a "CHO cell").
As part of the hamster DNA, the exogenous gene
expressed EPO.

Amgen Technology
The essence of the technique :
“the introduction of an exogenous DNA
sequence coding for EPO into a host cell in
which it would be expressed.”

Trankaryotic(TKT) Technology
TKT employed “gene activation method”
The EPO is expressed in a human cell by an endogenous
gene naturally present or by cells derived by replication
from such a cell.
The TKT technique involves introducing the necessary
control sequence upstream of the EPO gene. The control
sequence is accompanied by other bits of machinery.
This could not have been done at the time of the patent
but can now be done by using a phenomenon called
"homologous recombination".

Comparison
Amgen Technology
EPOGEN (AMGEN) is made by
an exogenous DNA
sequence coding for EPO
which has been introduced
into an host cell.(OHM cell)
TKT Technology
GA-EPO(TKT) is made by an
endogenous DNA sequence
coding for EPO in a human
cell into which an
exogenous upstream
control sequence has been
inserted.

Claims
There are 31 claims but we need concern ourselves only
with claims 1, 19 and 26.
Claim 1 :
"A DNA sequence for use in securing expression in a
procaryotic or eucaryotic host cell of a polypeptide
product having at least part of the primary structural ……..
erythropoietin to allow possession of the biological
property ..and red blood cells and to increase
[haemoglobin] synthesis or iron uptake, said DNA sequence
selected from the group consisting of:
– the DNA sequences set out in Tables V and VI or their
complementary strands;……….

Claims
• Claim 19 : (A product by process claim)
"A recombinant polypeptide having… the primary
structural conformation of human or monkey
erythropoietin as set forth in Table VI or Table V
or possessing the biological property … red blood
cells to … and characterised by being the product
of eucaryotic expression of an exogenous DNA
sequence and which has a higher molecular
weight by SDS-PAGE from erythropoietin
isolated from urinary sources."

Claims
• Claim 26
• "A polypeptide product of the expression in a
eucaryotic host cell of a DNA sequence according
to any of claims 1, 2, 3, 5, 6 and 7."
Claims 2, 3, 5, 6 and 7 are all dependent on claim
1 in the sense that if the TKT method does not
involve using a "DNA sequence for use in securing
expression [of EPO] in a…host cell" within the
meaning of claim 1, it would not infringe any of
the other claims either.

Decisions of the Lower Courts
• The trial judge held that claim 19 was invalid
(for insufficiency) but that claim 26 was valid
and infringed.
• The Court of Appeal (Aldous, Hale and Latham
LJJ) held that both claims were valid but that
neither was infringed.

Decisions of the Lower Courts
Amgen against the decision that, as a matter
of construction, the TKT process is not within
the claims
TKT against the rejection of its attack on the
claims for insufficiency and (in the case of
claim 26) anticipation.

Claim Construction
The most important provision is article 69 of
the EPC, which applies to infringement
proceedings in the domestic courts of all
Contracting States:

"Protocol on the Interpretation of
Article 69":
"Article 69 should not be interpreted in the
sense that the extent of the protection
conferred by a European patent is to be
understood as that defined by the strict, literal
meaning of the wording used in the
claims, the description and drawings being
employed only for the purpose of resolving an
ambiguity found in the claims.

Article 69":
Neither should it be interpreted in the sense
that the claims serve only as a guideline and
that the actual protection conferred may
extend to what, from a consideration of the
description and drawings by a person skilled in
the art, the patentee has contemplated.

UK Approach Vs German Approach
Manish Bhangale MIPLC 2012-2013 17

Article 69":
On the contrary, it is to be interpreted as
defining a position between these extremes
which combines:
a fair protection for the patentee with a
reasonable degree of certainty for third
parties."

Claim construction
It came to be recognised that the author of a
document such as a contract or patent
specification is using language to make a
communication for a practical purpose and
that a rule of construction which gives his
language a meaning different from the way it
would have been understood by the people to
whom it was actually addressed is liable to
defeat his intentions. (Para 30)

Claim construction
• "A patent specification should be given a
purposive construction rather than a purely
literal one derived from applying to it the kind
of meticulous verbal analysis in which lawyers
are too often tempted by their training to
indulge."
Lord Diplock in Catnic Components Ltd v Hill & Smith
Ltd [1982] RPC 183, 243

Claim construction
The courts felt unable to escape from
interpretations which "unsparing logic"
appeared to require and which prevented
them from according the patentee the full
extent of the monopoly which the person
skilled in the art would reasonably have
thought he was claiming.(Para 41)

Claim Construction
It will be recalled that claim 1 is to a DNA
sequence, selected from the sequences set
out in Table VI or related sequences, for
securing the expression of EPO in a "host cell".

Claim Construction
The chief question of construction:
“whether the person skilled in the art would
understand "host cell" to mean a cell which is
host to the DNA sequence which coded for
EPO.”
In the TKT process, it is host to the control
sequence and other machinery introduced by
homologous recombination. (Para 53)

Claim Construction
• "I am of the view that a cell is not a 'host cell' unless it
is host to exogenous DNA encoding for EPO or its
analogue. Such a conclusion is based in part on the
teaching of the [patent in suit].
• The terms 'host' and 'host cell' are used consistently to
describe cells which have been transfected with
exogenous or foreign DNA (ie DNA from outside that
particular cell) which encodes EPO, with a view to
securing expression of EPO in those host cells.

Claim Construction
The patentee regarded it as essential to his
invention that the DNA of which high level
expression was sought should not have its
origin in the genome of the host cell.
That would clearly exclude the DNA sequence
which expresses GA-EPO, which forms part of
the genome of the host cell.(Para 57)

Claim Construction
• The person skilled in the art would not regard the
endogenous coding sequence which expressed
GA-EPO as falling within claim 1. It followed that
GA-EPO was not the expression of a DNA
sequence within claim 1 and therefore did not
infringe claim 26.
• The person skilled in the art would not regard
GA-EPO as "the product of … expression of an
exogenous DNA sequence" within claim 19.

Claim Construction
No one suggests that "an exogenous DNA
sequence coding for EPO" can have some looser
meaning which includes "an endogenous DNA
sequence coding for EPO".(Para 66)
The effect of the construction for which Amgen
contends is that claim 1 should be read as
including any DNA sequence, whether exogenous
or endogenous, which expresses EPO in
consequence of the application to the cell of any
form of DNA recombinant technology.(Para 78)

Claim Construction
The man skilled in the art would not have
understood the claim as sufficiently general to
include gene activation. He would have
understood it to be limited to the expression
of an exogenous DNA sequence which coded
for EPO.(Para 80)

Claim Construction
For these reasons I would hold that TKT did not
infringe any of the claims and dismiss
Amgen's appeal.(Para 85)

Novelty of Claim 26
Claim 26 is to a product, namely a polypeptide
which is the expression in a host cell of a DNA
sequence in accordance with claim 1.
The question is whether it is new or the same
as the EPO which was already part of the state
of the art, namely the uEPO which Miyake and
others had purified from urine.(Para 87)

Novelty of Claim 26
The Technical Board found on the evidence
that EPO which complied with these
descriptions would not necessarily be
different from uEPO. (Para 92)

Novelty of Claim 26
As a fact that there was no difference between uEPO
and EPO made according to claim 26. He drew no
distinction between EPO made in accordance with
claim 19 and EPO made in accordance with claim
26, calling them both recombinant EPO ("rEPO"). He
found (at paragraphs 545 to 557) that there was no
necessary distinction between rEPO and uEPO. (Para
96)
I would therefore allow this part of the appeal and
declare claim 26 invalid on the ground of anticipation.
(Para 101)

Insufficiency of claim 19
The particular expression which ultimately
proved fatal to claim 19 was :
“which has a higher molecular weight by SDS-
PAGE from erythropoietin isolated from
urinary sources.”

The patentee tried to differentiate the
polypeptide in claim 19 by adding a limitation
:
"and which has higher molecular weight by
SDS-PAGE from erythropoietin isolated from
urinary sources."

"First, some rEPOs have a higher apparent
molecular weight by SDS-PAGE than some
uEPOs; secondly, some rEPOs have the same
apparent molecular weight as some uEPOs;
• thirdly, no rEPOs have a lower apparent
molecular weight than any uEPOs."
(Findings of the Judge in Para 121)

"It appears to me that the variations in
apparent molecular weight between different
batches of urinary EPO, coupled with the fact
that it is clear that many recombinant EPOs do
not satisfy the test, would put the skilled
addressee seeking to discover whether his
product was within claim 19, and seeking to
discover this in a reasonable way, in an
unsatisfactory, indeed, an impossible
position."

CONCLUSION
The result is that I would allow TKT's appeal
and revoke the patent on the ground that
claim 19 is insufficient (section 72(1)(c)) and
claim 26 is anticipated (section 72(1)(a)).

THANK YOU !

Amgen Vs Hoechst Patent Dispute

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Amgen Vs Hoechst Patent Dispute