Fuzzy boundaries and
infringement:
Generics (Mylan) v Yeda & Teva
RSC Law Group Seminar
28 November 2013
Generics (UK) Limited t/a Mylan v Yeda and Teva
Relevance of the case
• Claims with a “fuzzy boundary”
• Construction
• Infringement
• Sufficiency
What’s it all about?
•Copolymer-1:
•Developed in the late 1960s at the Weizmann Institute
•Synthetic polypeptide
•Unlike naturally-occurring proteins, which are generally a single
species, it is a mixture of different polypeptides of different lengths and
different amino acid sequences
•Random copolymer consisting of 4 amino acids (alanine, glutamic acid,
lysine and tyrosine)
•Shown to be of help as a suppressive agent for EAE and diseases of a
similar nature, such as Multiple Sclerosis
• Teva now markets copolymer-1 for the treatment of MS under the
brand name Copaxone
The Patent (EP (UK) 0 762 888)
The patent relates to “an improved composition of copolymer-1”
Claim 1: “A copolymer-1 fraction, wherein said fraction contains less than
5% of species of copolymer-1 having a molecular weight over 40
kilodaltons and wherein over 75% of said fraction is within a molecular
weight range from 2 kilodaltons to 20 kilodaltons.”
Copolymer-1 defined at [0002] and [0003] as: “a mixture of polypeptides
composed of alanine, glutamic acid, lysine and tyrosine in a molar ratio of
approximately 6:2:5:1.”
Definition accepted by both parties.
Construction
• Principles of construction set out by the House of Lords in Kirin-Amgen
• The question is always what the person skilled in the art would have
understood the patentee to be using the language of the claim to
mean.
• In the present case, an issue arose as to what the skilled person would
understand the patentee to mean by “a molar ratio of approximately
6:2:5:1”
• This equates to a molar fraction of 42.9% alanine, 14.3% gluatmic acid,
35.7% lysine, 7.1% tyrosine
Construction
•
Mylan’s contention on construction
• “approximately” covered compositions in which the molar fraction of
any single amino acids did not differ from those percentages by more
than ±10% of their value.
• Rejected – amounts to placing a rigid numerical limitation on the
claim, which the patentee had chosen not to do.
•
Teva’s contention on construction
• “approximately” reflects the fact that copolymer-1 is a random
copolymer whose composition is not precisely defined; and
• claim embraces compositions in which the molar ratios of the amino
acids correspond to the 4 prior art copolymer-1 compositions
mentioned in the patent.
Construction
•
It was common ground that the skilled team would appreciate that two
reasons why the inventors had referred to the molar ratio as being
approximate were to allow for:
1.
The variability in amino acid analysis; and
2.
The variability in syntheses of materials such as copolymer-1
• The burden of interpretation of the claim would therefore fall on the
following members of the notional skilled team:
•
•
The analytical chemist with expertise in amino acid analysis; and
The synthetic chemist.
Construction
• At first instance, Arnold J held:
1.As to the variability in amino acid analysis – the skilled person would
know from his CGK that amino acid analysis should have a
reproducibility of ±5% or better (although in practice, many labs did not
achieve such a low level); and
2.As to the variability in synthesis of copolymer-1 – the skilled person
would know that repeat syntheses of copolymer-1 would not result in
the same composition but he would not have known the degree of
variation to be expected in manufacture.
Construction
• Arnold J then considered what could be taken from the prior art.
• The patent referred to 4 pieces of prior art, each of which disclosed a
copolymer-1 with a different molar fraction.
• In one prior art batch, the figure for lysine differed by 16% from the
figure for exactly 6:2:5:1 – 30% (prior art) vs 35.7% (exact)
• Nonetheless, Arnold J held that the skilled person would conclude that
all the compositions disclosed by these documents fell within the
definition “approximately 6:2:5:1”.
Construction
• Arnold J then had to resolve a dispute as to the correct approach to the
assessment of differences in molar ratio:
•
= difference in the proportion of each amino acid as a percentage of
that proportion (i.e. difference relative to that amino acid) – Mylan’s
contention; or
• = difference as a percentage of the whole composition (i.e. difference
relative to the whole) – Teva’s contention?
• Mylan’s contention was to be preferred
• But the quantitative limits that Mylan sought to impose (variability in
amino acid analysis is ±5% for each amino acid and that figure should
be doubled to allow for variability in synthesis) should be rejected.
• Teva’s approach had “very little logic to it”.
Construction
• The Judge then considered the following illustrations prepared by Teva’s expert:
Illustrative copolymer-1
with 70 amino acids:
Mylan’s product:
• The illustration shows that because tyrosine is the least abundant, a change in a single amino acid
from lysine to tyrosine – the swapping of a single amino acid being the sort of change the skilled
person would regard as being within the term “approximately” – could result in a relative difference in
tyrosine of 29.6% and change the molar ratio from 6:2:5:1 to 4.6:1.6:3.7:1.0.
• The skilled person would therefore accept a greater deviation, expressed in terms of relative
difference, in the proportion of tyrosine as being encompassed by "approximately 6:2:5:1" than in the
case of the other amino acids.
Construction – Conclusion at First Instance
•
The skilled team would conclude that the claim was one that had a
fuzzy boundary: it is not possible to say where the boundary lies.
•
In forming this conclusion, Arnold J relied on the fact that the skilled
person would take into account:
• Variations in amino acid synthesis (±5%)
• Variations in synthesis of copolymer-1
• Effect of changes in molar ratio in terms of numbers of amino acids as
shown by the illustrations and would therefore be inclined to accept
greater deviation in proportion of tyrosine
• Variations in the prior art batches referred to in the patent
Construction – Conclusion on Appeal
•
On the contrary, the Court of Appeal held that the only evidence which
was relevant to construction was that:
• the skilled team would understand that “approximately” was used to
allow for variations in amino acid analysis and variability in copolymer1 synthesis; and
• the skilled person would be concerned that variations might affect the
known efficacy and safety of copolymer-1.
Construction – Conclusion on Appeal
•
In respect of the illustrations:
• It was wrong to think of copolymer-1, a mixture of random copolymers
of differing chain lengths, as a single species of defined structure and
chain length for which the change of a single amino acid might
represent the smallest change possible;
• If manufacturing tolerances result in more tyrosine ending up in the
copolymer, it did not follow that the chains will all be extended by the
same amount;
• The amount of tyrosine which ends up in the copolymer chains is
infinitely variable.
Construction – Conclusion on Appeal
•
The correct question in defining the limits of the fuzzy boundary was
therefore whether the ratio of amino acids in any sample was within the
variability which could arise from amino acid analysis and coolymer-1
synthesis.
• If yes, the sample was within the claim;
• If no, the sample was outside the claim.
•
It did not matter that the skilled person would not have known how to
quantify the maximum degree of variability
Declaration of Non-Infringement
•
The Mylan product differed from one in which the molar ratios were
6:2:5:1 because the molar fraction of tyrosine was 29.6% greater.
•
On Arnold J’s wide construction of “approximately 6:2:5:1”, which was
based in part of the illustrations, the Mylan product was held to be
within the scope of the claim.
•
The Court of Appeal held that it would not have felt justified in reaching
this conclusion since it did not regard the illustrations as having a role
to play.
Declaration of Non-Infringement
•
BUT it was for Mylan to establish that their product did not infringe
(since it was Mylan who had applied for a declaration of noninfringement).
•
Mylan had not adduced sufficient evidence to justify a finding that they
did not infringe.
•
“no evidence to show that a 29.6% variation in the molar fraction of one
amino acid is greater than that which could occur from amino acid
analysis and copolymer-synthesis”
•
The Judge was therefore right to refuse the declaration of noninfringement, albeit for different reasons.
•
So could Mylan have provided better evidence? Judgment is silent.
Insufficiency
•
There is an interplay between construction and insufficiency. This was
described by Arnold J at first instance as follows:
"… it is necessary to distinguish between claims that are difficult to construe or that
have a "fuzzy boundary" on the one hand from claims that are truly ambiguous
on the other. It is regrettably common for claims to be difficult to construe, but
the court will nevertheless strive to give such claims a sensible meaning having
regard to the inventor's purpose. It is also common for claims to have a fuzzy
boundary, because an integer of the claim involves some question of degree or
an imprecise functional limitation. It is well established that is not itself
objectionable. If a claim is truly ambiguous, so that it is unclear what is the
correct test to determine whether or not a product or process infringes,
however, then the claim is insufficient..."
Insufficiency
•
Mylan’s ambiguity-type insufficiency plea was rejected at first instance
and on appeal since it was possible to come to a conclusion as to what
the claim meant.
•
Thus Arnold J was right to dismiss the revocation action and to refuse
the declaration of non-infringement.
•
The decision has not been appealed to the Supreme Court.
How have numerical ranges in a claim been construed in other
cases?
•
PLG Research v Ardon – no evidence that 75% limitation, as opposed
to say 76% or 74% would be seen to be crucial by the skilled
addressee
•
Lubrizol Corp v Esso – 1.3 in the claim was construed as “1.3 to two
significant figures” in accordance with the scientific convention that
numbers are given to the number of figures that are significant
•
Halliburton v Smith – likewise “between 31% and 35%” meant the
number to two significant figures
•
Rhone-Poulenc v Dikloride – 5% was held to fall within “4.8% or less”
EPO Examiners Guidelines on Numerical Ranges
•
Skilled person knows numerical values relating to measurements are
subject to measurement errors which place limits on their accuracy.
•
For this reason, the general convention in the scientific and technical
literature is applied: the last decimal place of a numerical value
indicates its degree of accuracy.
•
Where no other error margins are given, the maximum margin should
be ascertained by applying the rounding-off convention to the last
decimal place e.g. for 3.5cm, the error margin is 3.45 – 3.54.
•
When interpreting ranges of values, the skilled person proceeds on the
same basis.
Conclusions?
•
In all cases, the key question is always what the person skilled in the
art would have understood the patentee to be using the language of the
claim to mean.
•
In considering the construction of numerical limits, what the skilled
person would understand to be the expected precision of the
measurement appears to be material.
•
In all the cases we have looked at, the claim has been given a
construction which extends beyond the strict numerical limits in the
claim.
Thank you
Graham Burnett-Hall
Partner
Marks & Clerk Solicitors LLP
T +44 (0)20 7420 0265
E [email protected]