Oxford Immunotec Ltd. v. Qiagen N.V. et al

Filing 188

Judge Nathaniel M. Gorton: ORDER entered. MEMORANDUM AND ORDER(Lima, Christine)

United States District Court
District of Massachusetts
Oxford Immunotec Ltd.,
Plaintiff,
v.
Qiagen, Inc. et al.,
Defendants.

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Civil Action No.
15-13124-NMG

MEMORANDUM & ORDER
GORTON, J.
Plaintiff Oxford Immunotec Ltd. (“plaintiff” or “Oxford”)
alleges defendants Qiagen, Inc., Quest Diagnostics, Inc. and
Laboratory Corporation of America Holdings (collectively,
“defendants”) infringed six of its patents relating to a method
and kit for diagnosing tuberculosis.
The Court held a Markman hearing on June 8, 2017, during
which the parties presented tutorials on the subject technology
and disputed the meaning of eleven groups of terms that are
included in 16 claims of the patents-in-suit.
I.

Overview of the Patented Technology
Oxford is owner of six different patents describing a

method and kit for diagnosing tuberculosis in vitro (outside of
the human body).

Five of the six patents-in-suit (collectively,

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“the ’646 patent family”) share a common specification.

Those

five patents, each entitled “Tuberculosis Diagnostic Test,” are:
1)

U.S. Patent No. 7,632,646 (“the ’646 patent”), issued
on December 15, 2009,

2)

U.S. Patent No. 7,901,898, (“the ’898 patent”), issued
on March 8, 2011,

3)

U.S. Patent No. 8,216,795, (“the ’795 patent”), issued
on July 10, 2012,

4)

U.S. Patent No. 8,507,211, (“the ’211 patent”), issued
on August 13, 2013 and

5)

U.S. Patent No. 9,005,902 (“the ’922 patent”), issued
on April 14, 2015.

The sixth patent-in-suit, U.S. Patent No. 8,617,821 (“the
’821 patent”), entitled “Assay Method for Peptide Specific TCells,” has a different specification.

It was issued on

December 31, 2013.
Oxford’s amended complaint contains six counts alleging
infringement of those six patents, in violation of 35 U.S.C.
§ 271(a)-(c).
II.

Analysis
A.

Principals of Claim Construction

In analyzing a patent infringement action, a court must
1) determine the meaning and scope of the patent claims asserted
to be infringed and 2) compare the properly construed claims to
the infringing device. Markman v. Westview Instruments, Inc., 52
F.3d 967, 976 (Fed. Cir. 1995) (en banc), aff’d, 517 U.S. 370

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(1996).

The first step, known as claim construction, is an

issue of law for the court to decide. Id. at 979.

The second

step is determined by the finder of fact. Id.
The Court’s responsibility in construing claims is to
determine the meaning of claim terms as they would be understood
by persons of ordinary skill in the relevant art. Bell Atl.
Network Servs., Inc. v. Covad Commc’ns Grp., Inc., 262 F.3d
1258, 1267 (Fed. Cir. 2001).

The meanings of the terms are

initially discerned from three sources of intrinsic evidence:
1) the claims themselves, 2) the patent specification and 3) the
prosecution history of the patent. See Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1582–83 (Fed. Cir. 1996).
The claims themselves define the scope of the patented
invention. See Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed.
Cir. 2005) (en banc).

Claim terms are generally given their

“ordinary and customary meaning,” which is the meaning that a
person skilled in the art would attribute to the claim term. See
id. at 1312-13.

Even if a particular term has an ordinary and

customary meaning, however, a court may need to examine the
patent as a whole to determine if that meaning controls. Id. at
1313 (“[A] person of ordinary skill in the art is deemed to read
the claim term . . . in the context of the entire
patent . . . .”); see also Medrad, Inc. v. MRI Devices Corp.,
401 F.3d 1313, 1319 (Fed. Cir. 2005) (noting that a court cannot

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construe the ordinary meaning of a term “in a vacuum”).
Ultimately, the correct construction will be one that
stays true to the claim language and most naturally
aligns with the patent’s description of the invention.
Phillips, 415 F.3d at 1316 (quoting Renishaw PLC v. Marposs
Societa’ Per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998)).
The patent specification is “the single best guide to the
meaning of a disputed term” because it
may reveal a special definition given to a claim
term . . . that differs from the meaning it would
otherwise possess . . . [such as] an intentional
disclaimer, or disavowal, of claim scope by the
inventor.
Id. at 1316, 1321.
The Court should also consult the prosecution history
to see how the inventor and PTO understood the patent and
to ensure the patentee does not argue in favor of an
interpretation it has disclaimed. Id. at 1317.
In the rare event that analysis of the intrinsic evidence
does not resolve an ambiguity in a disputed claim term, the
Court may turn to extrinsic evidence, such as inventor and
expert testimony, treatises and technical writings. Id. at 1317.
Although extrinsic evidence may be helpful in construing claims,
the intrinsic evidence is afforded the greatest weight in
determining what a person of ordinary skill would have

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understood a claim to mean. V-Formation, Inc. v. Benetton Grp.
SpA, 401 F.3d 1307, 1310-11 (Fed. Cir. 2005).
B.

The ’646 Patent Family
1.

The Technology

When the body encounters a pathogen such as Mycobacterium
tuberculosis (“M. tuberculosis”), proteins from that pathogen
are broken down into pieces known as peptides comprised of
strings of amino acids.

When T cells, cells that mediate immune

responses in the body, first encounter a harmful peptide, they
become “antigen-experienced”.

Then, in a process known as

activation, T cells that encounter that peptide again can bind
to it.

Once activated, the T cells release so-called cytokines,

such as IFN-γ, which act as chemical messengers in order to
elicit a full immune response.
The ’646 patents-in-suit are drawn to a method for
diagnosing tuberculosis whereby T cells are placed in contact
with peptides from a protein known as ESAT-6, a product of M.
tuberculosis.

After that contact, someone can measure the level

of cytokines released (e.g., IFN-γ) to determine whether there
is a tuberculosis infection.

The invention also provides a kit

for carrying out the claimed method.

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2.

Disputed Claim Terms
a.

The preambles

At the Markman hearing, the parties notified the Court that
there are no longer any viable disputes as to the language of
the preambles in the ’646 patent family (and the ’821 patent).
Accordingly, the Court will not construe the meaning or scope of
such terms.
b.

“Peptides represented by” (claims 1, 2, 7,
10 of the ’646 patent, claims 1, 2, 17, 19
of the ’898 patent) and “peptide SEQ ID NO:
[1-11]”/”SEQ ID NO: [1-11]” (claims 1, 2,
17, 18 of the ’795 patent, claims 1, 2, 17,
18 of the ’211 patent and claims 1, 19 of
the ’902 patent)

The parties dispute the scope of the above-listed claim
terms. See O2 Micro Int’l Ltd. v. Beyond Innovation Tech Co.,
521 F.3d 1351, 1362 (“When the parties present a fundamental
dispute regarding the scope of a claim term, it is the court’s
duty to resolve it.”).
In light of several references to peptides identified as
SEQ ID NOs: 1 through 11 in the ’646 patent family, defendants
contend that the term “represented by” refers only to peptides
so identified.

Plaintiff disagrees, primarily relying upon the

definition “represented by,” which is open-ended and synonymous
with the term “comprising”.
The Federal Circuit Court of Appeals has “repeatedly
warned” against confining claim terms to specific embodiments in

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the specification. Phillips, 415 F.3d at 1323.

Thus, although

plaintiff makes several references to peptides in the form of
SEQ ID NOs 1 to 8 in the patent specification, those references
are insufficient to limit plaintiff’s claim term only to
peptides in those forms.
Moreover, the ’646 patent specification explains that
plaintiff’s invention could be achieved by using “analogues”
consisting of chains of 8 to 80 amino acids.

Those chains

differ significantly in numbers of amino acids from the peptides
identified as SEQ ID NOs: 1 through 8 which contain exactly 15
amino acids each.

In the context of the entire patent,

therefore, the open-ended meaning of “represented by” comports
with the inventor’s description of the patent in the
specification. Id. at 1313, 1316.
The Court thus construes “peptides represented by” SEQ ID
NOs: 1 to 11 to mean “peptides comprising” SEQ ID NOs: 1 to 11.
With respect to the term “peptide SEQ ID NO: 1” or “SEQ ID
NO: 1,” in claims 1, 2, 17 and 18 of the ’795 patent, claims 1,
2, 17 and 18 of the ’211 patent and claims 1 and 19 of the ’902
patent, the Court concludes that no construction is necessary.
A peptide SEQ ID NO: 1, for example, is exactly what it is
defined as in the ’646 patent family specifications:

a specific

sequence of 15 amino acids identified in the ESAT-6 protein as
SEQ ID NO: 1.

Defendants’ proposed construction thus adds

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unnecessary language to the subject claim terms. See Harris
Corp. v. IXYS Corp., 114 F.3d 1149, 1152 (Fed. Cir. 1997)
(rejecting construction of a term that “contribute[d] nothing
but meaningless verbiage”).
c.

“Panel of eight peptides” (claims 1, 7 of
the ’646 patent) and “peptide panel” (claims
1, 2, 17, 18 of the ’795 patent, claims 1,
2, 17, 18 of the ’211 patent and claims 1,
19 of the ’902 patent)

First, the Court will construe the phrase “panel of eight
peptides” in claims 1 and 7 of the ’646 patent as “eight
peptides”.

Defendants’ argument that the panel must consist of

eight unique peptides is unsupported by the intrinsic record.
In addition to the use of open-ended language in the claim, the
patent specification allows for panels that do not consist only
of peptides with the SEQ ID NOs 1 through 8:
The invention also provides one or more of the
peptides or analogues selected from the peptides
represented by SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9,
10 or 11 and analogues thereof . . . .
’646 Patent, col. 3 ln. 42-45.

The Court will not construe the

claim to exclude a recited embodiment of the invention. See
Funai Elec. Co. v. Daewoo Elecs. Corp., 616 F.3d 1357, 1371
(Fed. Cir. 2010) (citing Hoechst Celanese Corp. v. BP Chems.
Ltd., 78 F.3d 1575, 1581 (Fed. Cir. 1996) (noting that “a claim
construction that excludes a preferred embodiment is rarely, if
ever, correct”).

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Similarly, intrinsic evidence does not support defendants’
proposed construction of the phrase “peptide panel”.
The use of the word “comprising” in the disputed claims
indicates that the claims are open-ended.1 CIAS, Inc. v. Alliance
Gaming Corp., 504 F.3d 1356, 1359-60 (Fed. Cir. 2009).
Moreover, the specifications provide that ESAT-6 peptides or
their analogues may be used.

Because the meaning of the phrase

“peptide panel” is otherwise clear, the Court will not further
construe the phrase.
d.

“Determining,” “detecting” and “to detect”
“a recognition response” to a “peptide
panel” (claims 1, 6 of the ’646 patent,
claims 1, 21, 22 of the ’795 patent, claims
1, 17 of the ’211 patent and claims 1, 19 of
the ’902 patent) and “determining” a
“recognition response” to a “peptide” (claim
1 of the ’821 patent)

The parties dispute both the meaning of “determining,”
“detecting” and “to detect” and the scope of “peptide” and
“peptide panel” in claims 1 and 6 of the ’646 patent, claim 1 of
the ’898 patent, claims 1, 21 and 22 of the ’795 patent, claims
1 and 17 of the ’211 patent and claims 1 and 19 of the ’902
patent.

First, defendant’s proposed construction of

“determining,” “detecting” and “to detect” amounts to excess

1

For example, claim 2 of the ’795 patent recites:
The method of claim 1, wherein the peptide panel
further comprises one or more epitopes contained
within one or more peptides selected from the group of
consisting of: [peptides SEQ ID NOs 2-11].
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verbiage.

Further construction of “determining” is not required

because the meaning is “readily apparent”. See Phillips, 415
F.3d at 1314.
Defendant’s suggestion to expand the term “peptide panel”
to read “the panel of eight peptides represented by SEQ ID NOs:
1 to [11]” is also unnecessary.
For example, claim 1 of the ’646 patent recites, in full:
A method of diagnosing infection in a human host by,
or exposure of a human host to, a mycobacterium that
expresses ESAT-6, which method comprise the steps of:
(i)

contacting a population of T cells from the
host with a panel of eight peptides
represented by SEQ ID NOS: 1 to 8, and

(ii) determining in vitro whether T cells of the
T cell population show a recognition
response to the panel by detecting IFN-γ
secretion from the T cells.
When read in context of the entire claim, “peptide panel” in the
second limitation refers to “a panel of eight peptides
represented by SEQ ID NOS: 1 to 8” as provided in the first
limitation.

Defendant’s construction merely restates what is

already been recited in the subject claim. U.S. Surgical Corp.
v. Ethicon, Inc., 103 F.3d 1554, 1568 (Fed. Cir. 1997)
(explaining that the district judge need not “repeat or restate
every claim term”).
That analysis also applies to claim 1 of the ’898 patent
which differs from the disputed claims of the ’646 patent family

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in ways that are irrelevant to the dispute.

Thus, the Court

will adopt plaintiff’s constructions with respect to claim 1 of
the ’646 patent and claim 1 of the ’898 patent.
e.

“Detecting IFN-γ” “secretion” or
“production” from or by the T cells (claim 1
of the ’646 patent, claims 9, 16 of the ’795
patent, claims 9, 16 of the ’211 patent,
claims 10, 18 of the ’902 patent)

Here, the parties dispute the phrase “detecting IFN-γ”
“secretion” or “production” from or by the T cells in claim 1 of
the ’646 patent, claims 9 and 16 of the ’795 patent, claims 9
and 16 of the ’211 patent and claims 10 and 18 of the ’902
patent.

Defendants add additional wording to explain the

meaning of “detecting” as well as limit the term “panel” to
“eight peptides represented by SEQ ID NOs: 1 to 8”.

Plaintiff

responds that no construction of the term is necessary.

The

Court agrees with plaintiff.
Just as with the word “determining,” defendant’s proposed
construction of “detecting” amounts to unnecessary language.
The meaning of the word “detecting” is clear. Phillips, 415 F.3d
at 1314.
Second, for the same reasons as those just explained,
“panel” will not be construed as defendants proffer.

Their

construction adds words that are already provided in the claim.

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f.

“Population of T cells” (claim 1 of the ’646
patent, claim 1 of the ’898 patent and
claims 1, 17 of the ’211 patent)

Defendants’ proposed construction attempts to limit the
scope of the term “T cells” in claim 1 of the ’646 patent, claim
1 of the ’898 patent and claims 1 and 17 of the ’211 patent to
only those T cells that are “in the form of peripheral blood
mononuclear cells or mononuclear cells isolated from a sample
from the host”.

That construction is unsupported by the

intrinsic record.
The claim language itself does not make such a limitation
and the specifications in the ’646 patent family provide that
the T cells removed from the host can be used in several forms:
Generally the T cells which are contacted in the
method are taken from the host in a blood
sample . . . . The sample may be added directly to
the assay or may be processed first . . . .
Peripheral blood mononuclear cells], [mononuclear
cells], and T cells can be separated from the
sample. . . . Preferably the T cells used in the
assay are in the form of unprocessed or diluted
samples or are freshly isolated T cells. . . .
’646 Patent, col. 4 ln. 34-37, 48-49, 52-53 (emphasis added).
Defendants’ proposed construction is thus an optional not
mandatory embodiment of the invention.

Moreover, the proposed

construction ignores a preferred embodiment of the invention
(that the T cells are unprocessed before being placed into an
assay). See Funai Elec. Co., 616 F.3d at 1371.

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Accordingly, the Court will construe the term “population
of T cells” as recited in claim 1 of the ’646 patent, claim 1 of
the ’898 patent and claims 1 and 17 of the ’211 patent as “T
cells that have been removed from a host or subject”.
g.

“One or more epitopes contained within”
(claims 1, 2 of the ’795 patent, claims 1, 2
of the ’211 patent and claims 1, 19 of the
’902 patent)

Defendants aver that the term “one or more epitopes
contained within” is indefinite because 1) it is unclear what
kinds of epitopes the claims are referring to and 2) the
epitopes will vary from person to person as a result of genetic
differences.
A patent is indefinite
if its claims, read in light of the specification
delineating the patent, and the prosecution history,
fail to inform, with reasonable certainty, those
skilled in the art about the scope of the invention.
Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120,
2124 (2014).
As the plaintiff correctly explains, the inventor did not
have to list the precise length or size of all the epitopes
within a peptide. See All Dental Prodx, LLC. v. Advantage Dental
Prods., Inc., 309 F.3d 774, 779-80 (Fed. Cir. 2002) (concluding
that the term “original unidentified mass” met the definiteness
requirement even though no specific size or shape of the mass
was recited in the patent).

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Defendants’ second contention is also unpersuasive because
individual genetic variations typically do not render a claim
term indefinite. Young v. Lumenis, Inc., 492 F.3d 1336, 1346-47
(Fed. Cir. 2007) (rejecting an indefiniteness challenge based
upon variations in anatomy).
Accordingly, the Court concludes that the term “one or more
epitopes contained within,” recited in claims 1 and 2 of the
’795 patent, claims 1 and 2 of the ’211 patent and claims 1 and
19 of the ’902 patent, is sufficiently definite.
C.

The ’821 Patent
1.

The Technology

The ’821 patent is drawn to an “assay,” an investigative
procedure, for identifying the presence of activated peptidespecific T cells and the corresponding cytokine secretions.
2.

Disputed Claim Terms
a.

“Determining whether said T cells are
activated” (claims 1, 6) and “activation of
said T cells is determined by” (claim 3)

As with the term “determining” in the ’646 patent family,
the parties dispute the use of the term in claims 1, 3 and 6 of
the ’821 patent.

For the reasons explained above, the Court

concludes that defendants’ proposed constructions add
unnecessary language to the claims.

Accordingly, the court will

adopt plaintiff’s construction with respect to claims 1 and 6

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and concludes that no construction is needed for claim 3. See
Phillips, 415 F.3d at 1314.
b.

“Wherein activation of said T cells
identifies the presence of Mycobacterium
tuberculosis-specific immediate effector T
cells” (claims 1, 6)

Defendant’s construction of the language in claims 1 and 6
regarding “the presence of Mycobacterium tuberculosis-specific
immediate effector T cells” adds excess language.

No

construction of that phrase is needed. See id.
c.

“Providing a sample from said subject
containing T cells” (claims 1, 6) and “T
cells are peripheral mononuclear cells”
(claim 2)

As for several claims in the ’646 patent family, defendants
attempt to limit claims 1 and 6 in the ’821 patent to specific
kind of isolated T cell.

For similar reasons to those described

above, the Court will not so limit the claims.
The specification is not, as defendants claim, drawn only
to an ELISPOT assay which tests for the presence of IFN-γ and
requires the kind of T cell defendants’ proposed construction
recites.

Rather the specification provides that the ELISPOT

assay is the “preferred” embodiment of the invention but that
cytokines other than IFN-γ may be tested for and thus possibly
necessitating the need for other assays.
Furthermore, defendant’s proposed construction of the
language in claims 1 and 6 would render claim 2 meaningless

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because claim 2 specifically recites that the T cells are
“peripheral blood mononuclear cells”. See Evntl. Designs Ltd. v.
Union Oil Co. of Cal., 713 F.2d 693, 699 (Fed. Cir. 1983) (“It
is improper for courts to read into an independent claim a
limitation explicitly set forth in another claim.”).
Defendants also request that the Court construe claim 2 by
adding the word “isolated” in front of “T cells” but here, too,
the patent specification is not limited to only isolated T cells
and, therefore, the Court declines to construe claim 2 of the
’821 patent.
d.

“Peptide subfragment of ESAT-6 that contains
a CD8+ epitope” and “immunogenic amount”
(claims 1, 6)

Defendants submit that the term “peptide subfragment of
ESAT-6 that contains a CD8+ epitope” in claims 1 and 6 of the
‘821 patent is indefinite for two reasons:

1) the patent and

prosecution history do not list the specific length and sequence
of the claimed peptide fragments and 2) the peptide subfragments
will react differently in people with different genetic
backgrounds.

The Court disagrees.

As plaintiff submits, it is not required to list all
possible lengths and sequences that practice the claimed
invention. All Dental Prodx, LLC., 309 F.3d at 779-80.
Moreover, individual genetic variations typically do not render
a claim term indefinite. Young, 492 F.3d at 1346-47.

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Therefore, the Court concludes that the term “peptide
subfragment of ESAT-6 that contains a CD8+ epitope” in claims 1
and 6 of the ’821 patent is not indefinite and no further
construction is necessary.
The term “immunogenic amount” in claims 1 and 6 of the ’821
patent is also sufficiently definite.
A term is not indefinite, as defendants contend, merely
because of the possibility of variations in experimental
conditions. Enzo Biochem, Inc. v. Applera Corp., 599 F.3d 1325,
1335-36 (Fed. Cir. 2010) (concluding that a claim term was not
indefinite even though the length and sequence of the subject
DNA strand would vary depending on the experimental conditions).
Whether a particular peptide is “immunogenic” involves
scientific analysis not subjective opinion that is explained and
exemplified through a preferred embodiment in the ’821 patent
specification. See id. at 1326 (“[T]he binding strength of a DNA
strand will depend on the length and sequence of the strand, not
on the subjective opinion of the particular chemist performing
the hybridization.”).
Also, as previously noted, individual variations in human
genetics is an insufficient ground to find a term indefinite.
“Immunogenic amount” is not indefinite because the ’821 patent
specification teaches a person having ordinary skill in the art
how to determine whether a peptide is immunogenic. See Young,

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492 F.3d at 1346-47 (rejecting an indefiniteness challenge to
the term “near” even though “the size of the appendage and the
amount of skin required to be incised will vary from animal to
animal” because “a person having ordinary skill in the art would
know where to make the cut”).
MARKMAN ORDER
In accordance with the foregoing,
1)

with respect to United States Patent Nos. 7,632,646,
7,901,898, 8,216,795, 8,507,211 and 9,005,902:
a)

“peptides represented by” means:
“peptides comprising”;

b)

“peptide SEQ ID NO: [1-11]”/”SEQ ID NO: [1-11]”
are accorded their plain and ordinary meaning;

c)

“panel of eight peptides” means:
“eight peptides”;

d)

“peptide panel” is accorded its plain and
ordinary meaning;

e)

“determining,” “detecting” and “to detect” “a
recognition response” to a “peptide panel” means:
“determining,” “detecting” or “to detect”
“whether the T cells respond to the peptide
panel”;

f)

“determining” a “recognition response” to a
“peptide” means:
“determining whether the T cells respond to the
peptide”;

g)

“detecting IFN-γ” “secretion” or “production” is
accorded its plain and ordinary meaning;

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h)

“population of T cells” means:
“T cells that have been removed from a host or
subject”; and

i)
2)

“one or more epitopes contained within” is
accorded its plain and ordinary meaning; and

with respect to U.S. Patent No. 8,617,821:
a)

“determining whether said T cells are activated”
means:
“determining whether the T cells respond”;

b)

“activation of said T cells is determined by” is
accorded its plain and ordinary meaning;

c)

“wherein activation of said T cells identifies
the presence of Mycobacterium tuberculosisspecific immediate effector T cells” is accorded
its plain and ordinary meaning;

d)

“providing a sample from said subject containing
T cells” means:
“T cells that have been removed from the
subject”;

e)

“T cells are peripheral mononuclear cells” is
accorded its plain and ordinary meaning;

f)

“peptide subfragment of ESAT-6 that contains a
CD8+ epitope” is accorded its plain and ordinary
meaning; and

g)

“immunogenic amount” is accorded its plain and
ordinary meaning.

So ordered.
/s/ Nathaniel M. Gorton
d
Nathaniel M. Gorton
United States District Judge
Dated June 14, 2017

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