Case 4:09-cv-11362-FDS Document 45 Filed 12/23/10 Page 1 of 8

UNITED STATES DISTRICT COURT

DISTRICT OF MASSACHUSETTS
_______________________________________
)
BAYER HEALTHCARE LLC, )
) Civil No.
Plaintiff, ) 09-cv-11362-FDS
)
v. )
)
CENTOCOR ORTHO BIOTECH, INC. )
)
Defendant. )
)

MEMORANDUM AND ORDER ON CLAIM CONSTRUCTION

SAYLOR, J.

This is an action alleging patent infringement. The dispute involves a composition that is

used in pharmaceuticals to combat autoimmune diseases—specifically, an antibody that binds to

human tumor necrosis factor alpha (“TNFα”). Plaintiff Bayer HealthCare LLC holds the patent at

issue; defendant Centocor Ortho Biotech, Inc. manufactures an allegedly infringing product under

the trade name Simponi.

The parties’ respective allegations hinge on the construction of the claims of Bayer’s U.S.

Patent No. 5,654,407 (the “‘407 patent”). The Court conducted a Markman hearing with respect

to the construction of claim 1, which the parties agree is the relevant claim to be construed. The

claim reads as follows:

A composition comprising human monoclonal antibodies that bind specifically to

human tumor necrosis factor alpha.

Abbott and Centocor dispute all three sets of terms in this claim: (1) “composition,” (2) “human

monoclonal antibodies,” and (3) “bind specifically to human tumor necrosis factor alpha.”
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I. Background

The ’407 patent was filed by Bayer in 1995 as a continuation of an application filed in

1993. It is directed to certain antibodies that are designed to attach to a naturally occurring

protein in the human body called tumor necrosis factor alpha (“TNFα”). TNFα is involved in

regulation of the immune system, a role it performs by triggering inflammation in response to

invasion by a foreign entity. Overproduction of TNFα can lead to excessive inflammation that can

result in tissue damage. This occurs in diseases such as rheumatoid arthritis, Crohn’s disease, and

psoriasis, which are known as autoimmune diseases because of the way the body’s own immune

system – in this case, through TNFα – targets healthy human tissue instead of foreign

contaminants.

Antibodies are proteins that target harmful foreign substances, or “antigens,” such as

viruses or bacteria. Antibodies attach themselves to an antigen by binding with a portion of the

antigen called an “epitope.” Bayer invented an antibody that binds to TNFα. By occupying

TNFα’s epitopes, this antibody, which Bayer named “B5,” prevents TNFα from binding to

receptors in tissues where it can cause damage. This process is known as “neutralization” of

TNFα.

In order for an antibody to effectively neutralize TNFα, it must attach to TNFα with

sufficient strength. The strength of an antibody’s interaction with an antigen is called its “affinity”

for the antigen. An important quality of therapeutic antibodies is the “specificity” of the agent for

a target antigen. If an antibody is not specific to its target antigen, it will bind to other proteins,

which has a number of negative consequences. Among other things, the targeting of other

proteins can cause unintended side effects, and reduces the number of antibodies reaching and

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neutralizing the actual target, thus weakening its effect.

In its specification to the ’407 patent, Bayer discloses that it was successful only in

producing low-affinity antibodies for TNFα that do not neutralize the protein. This was a

consequence, among other things, of the fact that the inventors used a technique to produce

antibodies called the “human hybridoma” method. This technique, developed in the 1970s,

utilizes native human antibody-producing cells called “B cells.” By exposing B cells to TNFα as

an antigen, the cells would begin producing antibodies to combat it. However, this method’s

reliance on native B cell populations is a critical weakness that ultimately limits this technique’s

suitability for generating high-affinity, neutralizing anti-TNFα antibodies. Healthy humans, like

other animals, generally do not possess circulating B cells that generate high-affinity, neutralizing

antibodies to their own proteins. There is limited clinical use for antibodies that attach to TNFα

with only low affinity and do not neutralize it.

Genetic engineering techniques – which existed, but were essentially in their infancy, and

therefore not commonplace in 1993 when the parent application of the ’407 patent was filed –

avoid the weaknesses of the human hybridoma methods. The most common of these techniques

are phage display and transgenic mouse techniques. Both of these techniques involve splicing and

recombining DNA. The resultant antibodies produced are known as “recombinant antibodies.”

The allegedly infringing product, Centocor’s biologic drug Simponi (“biologic” refers to

drugs developed using biotechnology), is created with transgenic mouse techniques and contains

antibodies that exhibit high affinity and specificity for TNFα.

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II. Analysis

A. Construction of the ’407 Patent Claims

As noted above, the parties dispute the terms (1) “composition,” (2) “human monoclonal

antibodies,” and (3) “bind specifically to human tumor necrosis factor alpha.” Centocor’s and

Bayer’s proposed constructions are substantially similar to those proposed by the parties in Abbott

Labs. v. Bayer Healthcare LLC, No. 09-cv-40002-FDS (D. Mass. Jan. 5, 2009). After carefully

considering the additional arguments raised in this case, the Court adopts the claim construction

set forth in Abbott, with two relatively minor adjustments that do not affect the Court’s ultimate

interpretation of the terms. The minor adjustments are discussed below.1

1. “Binds to an Epitope Shared by Human and Mouse TNFα”

In addition to interpretations that parallel those proposed by Abbott, Centocor’s suggested

construction requires that an antibody covered by the patent bind to an epitope shared by human

and mouse TNFα. Centocor asserts that a fair reading of the patent shows that the inventors

intended the specific embodiment in the specification—B5—to be strictly coextensive with the

claims. Because B5 binds both to human and mouse TNFα, Centocor contends that the claims

should also be so limited. (‘407 patent, col. 20, ll. 33-35).

Although it is true that the ‘407 patent describes only one specific embodiment, the

Federal Circuit “has expressly rejected the contention that if a patent describes only a single

embodiment, the claims of the patent must be construed as being limited to that embodiment.“

Phillips v. AWH Corp., 415 F.3d 1303, 1323 (Fed. Cir. 2005) (en banc) (internal citations

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The second change concerns the Court’s original validity analysis in its original claim construction
order. To keep the two orders consistent, the Court will also issue an amended order in Abbott Labs v. Bayer
Healthcare reflecting this change.

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omitted). The key inquiry is “whether the patentee is setting out specific examples of the

invention to accomplish those goals, or whether the patentee instead intends for the claims and the

embodiments in the specification to be strictly coextensive.” Id. “The manner in which the

patentee uses a term within the specification and claims usually will make the distinction

apparent.” Id.

Here, a fair reading of the ‘407 patent shows that the specific embodiment—with its

characteristic of binding to mouse TNFα—was provided only as an example. First, the

specification contains a specific disclaimer to that effect. (‘407 patent, col. 22, ll. 64-67 (“The

present embodiments are . . . illustrative and not restrictive . . .”)). Second, the specification

clearly focuses on applications in human medicine—applications for which the ability to bind to

mouse TNFα is irrelevant. (‘407 patent, col. 19, ll. 34-36 (“[a] primary advantage of this

invention is that it comprises a human anti-TNF antibody and, as such, it is expected to be far less

immunogenic [when used in humans].”); col. 19, ll. 4-33 (describing primarily human

applications). Third, the inventors included the characteristic of binding to mouse TNFα in a

dependent claim (claim 4), clearly suggesting that they intended the invention to be broader than

B5. (‘407 patent, col. 20, ll. 13-14 (“[Claim] 4. The composition of claim 1 wherein the

antibodies also bind to mouse tumor necrosis factor alpha.”)). As a result, Centocor’s contention

that the inventors intended the embodiment and the patent to be coextensive should be rejected.

The doctrine of claim differentiation also counsels against Centocor’s proposed

construction. Under that doctrine, “the presence of a dependent claim that adds a particular

limitation gives rise to a presumption that the limitation in question is not present in the

independent claim.” Phillips, 415 F.3d at 1315. If the independent claim contained all of the

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same requirements as the dependent claim, it would be as narrow as the dependent claim and the

separate dependent claim would serve no purpose. Here, reading a mouse TNFα limitation into

claim 1 would make it indistinguishable from claim 4.

In summary, because both the specification and the claims clearly conceive of a broader

invention, there is no logical ground for limiting them as Centocor proposes.

2. Enablement

In the Court’s previous order, it determined that the ‘407 patent should be construed

narrowly to avoid potential invalidity issues. The order stated as follows:

Enablement analysis is distinct from claim construction, and is not normally

addressed at the claim construction stage. See Phillips, 415 F.3d 1303, 1327 (“we
have certainly not endorsed a regime in which validity analysis is a regular
component of claim construction”). Nonetheless, a patent should be construed
narrowly when possible to avoid potential invalidity issues. See Wang Labs., Inc. v.
America Online, Inc., 197 F.3d 1377, 1383 (Fed. Cir. 1999) (“claims should be
construed, when feasible, to sustain their validity”). It is clear from the foregoing
discussion that Bayer’s construction of the claim language would include a
purported invention (a high-affinity, neutralizing antibody) that the specification
does not teach those skilled in the art how to make. For that reason, the claim
should be construed narrowly to avoid inclusion of high-affinity and neutralizing
antibodies.

Memorandum and Order on Claim Constr. at 17, Abbott Labs., No. 09-cv-40002-FDS (filed Oct.

20, 2010). Upon further consideration of the Federal Circuit’s en banc decision in Phillips v.

AWH Corp. and its progeny, however, the Court has determined that the question of enablement

is not properly reached at this stage in the proceedings. The Phillips court made clear that the

maxim that claims should be construed to preserve their validity should not be a regular

component of claim construction and instead should be limited “to cases in which the court

concludes, after applying all the available tools of claim construction, that the claim is still

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ambiguous.” 415 F.3d at 1327. Subsequent cases have affirmed that point. See, e.g., Broadcom

Corp. v. Qualcomm, Inc., 543 F.3d 683, 690 (Fed. Cir. 2008) (rejecting validity-based claim

construction argument); MBO Labs., Inc. v. Becton, Dickinson & Co., 474 F.3d 1323, 1332 (Fed.

Cir. 2007) (“[V]alidity construction should be used as a last resort.”); Bone Care Int’l, LLC v.

Pentech Pharms., Inc., 2010 WL 3023423, at *4 (N.D. Ill. July 30, 2010) (declining to construe

claim to preserve its validity because claim terms were not ambiguous); Balivi Chem. Corp. v.

JMC Ventilation Refrigeration, 2008 WL 2746029, at *8 (D. Idaho July 11, 2008) (same); 3Com

Corp. v. D-Link Sys., Inc., 473 F. Supp. 2d 1001, 1008 (N.D. Cal. 2007) (same); cf. Medtronic,

Inc. v. Brainlab Medizinische Computersysteme GmbH, 222 Fed. Appx. 952, 956 (Fed. Cir.

2007) (resolving ambiguity by applying validity maxim); AFG Industries, Inc. v. Cardinal IG Co.,

224 Fed. Appx. 956, 960 (Fed. Cir. 2007) (same).

Prior to addressing validity in its Abbott order, the Court determined that “human

monoclonal antibodies” did not include high-affinity and neutralizing antibodies because it was the

only approach that was faithful to the specification. See Abbott Memorandum and Order at 14-

16. Because any ambiguity in the term was resolved on alternate grounds, it was neither

necessary nor proper to consider validity in the claim construction order at that point.

III. Conclusion

For the foregoing reasons, the following are the constructions of the disputed claim terms:

the term “composition” needs no construction;

the term “human monoclonal antibodies” means “human monoclonal antibodies (that

is, ‘antibodies with amino acid sequences that are identical, apart from post-translational events

that result in minor modifications in amino acid sequences at the ends of amino acid chains and

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that do not affect the antibodies’ binding characteristics’) that are low-affinity and non-

neutralizing”; and

the term “bind specifically to human tumor necrosis factor alpha” means “bind to human

tumor necrosis factor alpha with materially greater affinity than (i) to human tumor necrosis factor

beta and (ii) to antigens commonly recognized by polyreactive natural autoantibodies (i.e., by

naturally occurring antibodies known to bind to a variety of antigens, including antigens naturally

found in humans).”

So Ordered.

/s/ F. Dennis Saylor

F. Dennis Saylor IV
Dated: December 23, 2010 United States District Judge