United States Court of Appeals
for the Federal Circuit
__________________________
CENTOCOR ORTHO BIOTECH, INC. AND
NEW YORK UNIVERSITY,
Plaintiffs-Appellees,
v.
ABBOTT LABORATORIES, ABBOTT
BIORESEARCH CENTER, INC.,
AND ABBOTT BIOTECHNOLOGY LTD.,
Defendants-Appellants.
__________________________
2010-1144
__________________________
Appeal from the United States District Court for the
Eastern District of Texas in case no. 07-CV-0139, Judge
T. John Ward.
__________________________
Decided: February 23, 2011
__________________________
DIANNE B. ELDERKIN, Akin Gump Strauss Hauer &
Feld LLP, of Philadelphia, Pennsylvania, argued for
plaintiffs-appellees. With her on the brief were BARBARA
L. MULLIN, STEVEN D. MASLOWSKI, ANGELA VERRECCHIO,
and MATTHEW A. PEARSON. Of counsel on the brief were
PHILIP S. JOHNSON and ERIC I. HARRIS, Johnson & John-
son, of New Brunswick, New Jersey.
CENTOCOR v. ABBOTT LABS 2
WILLIAM F. LEE, Wilmer Cutler Pickering Hale and
Dorr LLP, of Boston, Massachusetts argued for defen-
dants-appellants. With him on the brief were WILLAIM G.
MCELWAIN, AMY K. WIGMORE, THOMAS G. SAUNDERS, and
ARTHUR W. COVIELLO, of Washington, DC.
OAKAR LIIVAK, Cornell Law School, of Ithaca, New
York, for amicus curiae Professor Oskar Liivak.
MARK J. STEWART, Eli Lilly and Company, of Indian-
apolis, Indiana, for amicus curiae Eli Lilly and Company.
With him on the brief were ALEJANDRO MARTINEZ, PAUL
R. CANTRELL, AMY E. HAMILTON, and ROBERT A.
ARMITAGE,
__________________________
Before BRYSON, CLEVENGER, and PROST, Circuit Judges.
PROST, Circuit Judge.
This patent infringement suit involves pharmaceuti-
cal antibodies used to treat arthritis. The patent owners,
Centocor Ortho Biotech, Inc. and New York University
(collectively, “Centocor”) sued Abbott Laboratories, Abbott
Bioresearch Center, Inc., and Abbott Biotechnology Ltd.
(collectively, “Abbott”), alleging that Abbott’s Humira®
antibody infringes claims 2, 3, 14, and 15 (“the asserted
claims”) of U.S. Patent No. 7,070,775 (“’775 patent”).
After a five-day trial, the jury found Abbott liable for
willful infringement. The jury rejected Abbott’s argument
that the asserted claims were invalid, and awarded
Centocor over $1.67 billion in damages.
Abbott moved for judgment as a matter of law
(“JMOL”) on invalidity, noninfringement, damages, and
willfulness. The district court granted Abbott’s motion for
3 CENTOCOR v. ABBOTT LABS
JMOL of no willful infringement but denied Abbott’s
other JMOL motions. Abbott appeals the district court’s
denial of its JMOL motions. Because the asserted claims
of the ’775 patent lack written description under 35
U.S.C. § 112, we need not reach Abbott’s other invalidity
arguments, its infringement arguments, or the question of
damages. We reverse the district court’s denial of JMOL
on this ground and hold the asserted claims invalid for
failure to meet the statutory written description require-
ment.
BACKGROUND
The technology in this case involves antibodies to hu-
man tumor necrosis factor α (“TNF-α”). Overproduction of
TNF-α can lead to various autoimmune conditions, includ-
ing arthritis. Although TNF-α antibodies have the poten-
tial to reduce the harmful activity caused by excess TNF-
α, the human body does not typically make antibodies to
human TNF-α. As a result, pharmaceutical companies
have been keenly interested in engineering antibodies
that can “neutralize” human TNF-α for use as a drug.
TNF-α was identified long before Centocor and Abbott
began developing therapeutic antibodies. In fact, by 1985,
many researchers had produced antibodies to human
TNF-α. These antibodies were typically produced in mice
and were not suitable for use in human patients for
several reasons. First, many of the antibodies did not
have sufficient binding affinity for human TNF-α. Be-
cause the antibodies must stick to human TNF-α to work,
their binding ability is important. A high affinity anti-
body sticks better than an antibody that binds with low
affinity. If an antibody’s affinity is too low, it will not be a
viable drug. Second, many of the known antibodies did
not have the desired neutralizing activity. While such
CENTOCOR v. ABBOTT LABS 4
antibodies do bind to TNF-α, they do not bind to a place
on TNF-α that reduces the harmful TNF-α activity. Since
such antibodies do not reduce TNF-α activity, they cannot
be used to produce the desired therapeutic effect. In other
words, the activity of an antibody is related to both how
tightly the antibody sticks as well as the specific location
on TNF-α where the antibody binds. Third, human pa-
tients frequently have immunological reactions when they
are treated with antibodies produced in mice or other non-
human species. This is because the human immune
system recognizes foreign proteins and attacks them. By
engineering foreign antibodies to look more human,
scientists try to trick the human immune system and
prevent this undesirable immune response. Given these
therapeutic limitations of the known TNF-α antibodies,
pharmaceutical companies sought to develop an antibody
with (1) high affinity, (2) neutralizing activity, and (3)
reduced immunogenicity.
In developing their therapeutic TNF-α antibodies,
Centocor and Abbott pursued very different strategies.
Centocor’s path began by identifying a mouse antibody to
human TNF-α that had both high affinity and neutraliz-
ing activity (“the A2 mouse antibody”). While this anti-
body had two of the key properties, the mouse antibody
was of limited therapeutic use because it would produce
an undesirable immune response in humans. To tackle
this immunogenicity problem, Centocor decided to use
known techniques to modify its mouse antibody to make it
look more human. By keeping the parts of the mouse
antibody that are responsible for the affinity and the
neutralizing activity and changing the less critical por-
tions of the antibody to make these portions more human,
scientists sought to preserve the activity of the antibody
while reducing its immunogenicity.
5 CENTOCOR v. ABBOTT LABS
For purposes of discussion in this appeal, antibodies
basically consist of two regions: a “constant region” and a
“variable region.” As Centocor’s inventor explained to the
jury, “the variable regions are really what determines
what the antibody is.” J.A. 18300, 159:10-12. The vari-
able region is the portion responsible for sticking to TNF-
α. The variable region is also the portion of the antibody
that determines where on TNF-α the antibody will bind.
Making changes in the variable region can thus have a
dramatic effect on the affinity and activity of the anti-
body. Even a small change in the variable region can
result in an antibody that does not bind to TNF-α or fails
to have neutralizing activity. Centocor avoided the poten-
tial pitfalls associated with modifying the variable region
by focusing on the constant region. By exchanging the A2
mouse antibody’s mouse constant region with a known
human constant region, Centocor produced a “chimeric”
antibody with a mouse variable region and a human
constant region. See, e.g., Chiron Corp. v. Genentech, Inc.,
363 F.3d 1247, 1250-52 (Fed. Cir. 2004) (discussing anti-
body structure and chimeric antibodies). The resulting
chimeric antibody was less immunogenic than the A2
mouse antibody because it contained significantly less
mouse protein. At the same time, Centocor’s chimeric
antibody possessed similar binding and activity to the A2
mouse antibody because they both had the same variable
region. Because the chimeric antibody contained a mouse
variable region, it was not considered to be “fully human.”
A chimeric antibody still contains foreign protein, so it is
more likely to elicit an immune response than a fully-
human antibody.
Centocor filed a patent application disclosing both its
A2 mouse antibody and the chimeric antibody in 1991.
The application discussed the immunogenicity problem
and the difficulties associated with making a fully-human
CENTOCOR v. ABBOTT LABS 6
antibody to a human protein like TNF-α. The application
presented chimeric antibodies as the solution to these
problems. The 1991 application included eighteen exam-
ples detailing methods for making a mouse antibody with
high affinity and neutralizing activity and making a
corresponding chimeric antibody based on the mouse
antibody. The application included claims to Centocor’s
A2 mouse antibody and chimeric antibodies.
Centocor subsequently filed a series of continuation-
in-part (“CIP”) applications. In 1993, the U.S. Patent and
Trademark Office (“PTO”) rejected certain pending claims
in a CIP application because they encompassed antibodies
with “less than an entire mouse variable region[].” J.A.
38601. The PTO asserted that the specification only
enabled antibodies with fully-mouse variable regions.
Instead of responding to the rejections, Centocor filed a
new CIP application and abandoned the pending applica-
tion. In due course, the PTO issued the same rejection.
Again, instead of responding, Centocor abandoned its
application and filed three substantially identical CIP
applications in 1994. These 1994 CIP applications added
new matter that Centocor now relies on as evidence of
written description to support the asserted claims. Al-
though Centocor made these few additions, it did not
present claims to human variable regions when it filed
the 1994 CIP applications.
While Centocor focused its efforts on making a chi-
meric antibody, Abbott pursued an alternative path and
sought to engineer a fully-human antibody. As discussed
above, there is a progression from making a mouse anti-
body to obtaining the corresponding chimeric antibody.
This is because the two antibodies contain the same
variable region. In contrast, no corresponding progression
exists with respect to making a fully-human antibody.
7 CENTOCOR v. ABBOTT LABS
J.A. 18462 (comparing the process of constructing a
chimeric antibody from a mouse antibody with the process
of making a human antibody). One of skill in the art
cannot look at a mouse variable region and know how to
turn it into a human variable region with the same affin-
ity and activity as the mouse antibody. 1
Abbott decided to work with collaborators to construct
a fully-human antibody from scratch. First, Abbott’s
collaborators created an enormous phage display library
containing a spectrum of human variable regions. They
searched this library for variable regions that bind to
human TNF-α. In the process, they developed a technique
known as “guided selection” to help identify variable
regions from the library that bind in a specific place so
the variable regions have neutralizing activity. After
identifying human variable regions that bind to human
TNF-α, they used various techniques including “chain
shuffling” and “affinity maturation” to improve the bind-
ing affinity of the variable regions. These human variable
regions were combined with known human constant
regions to create fully-human antibodies. By 1995, Abbott
had created the therapeutic antibody Humira®. Abbott
filed a patent application disclosing this high affinity,
neutralizing, fully-human antibody to human TNF-α in
1996. See U.S. Patent No. 6,090,382. The PTO granted
1 The inventor, Dr. John Ghrayeb, testified that
“anybody who’s experienced would realize that that
variable region that we cloned from a mouse could easily
have been found in a human, so you could make it.” J.A.
18312, 20:11-14. However, Dr. Ghrayeb acknowledged
that, in an earlier application that was incorporated by
reference in the ’775 patent, the inventors had noted the
difficulties in developing human monoclonal antibodies,
and he admitted that the ’775 patent did not offer solu-
tions for those problems. J.A. 18318-19.
CENTOCOR v. ABBOTT LABS 8
the patent in 2000, and Abbott obtained regulatory ap-
proval to market Humira® in 2002.
After the grant of Abbott’s patent and after regulatory
approval of Humira®, Centocor filed its claims to fully-
human antibodies. Because the patent family disclosing
Centocor’s own chimeric antibody was still pending in
2002, Centocor filed the claims as part of a thirteenth
application in the family, explicitly claiming human
variable regions and fully-human antibodies. Asserted
claim 2 and the claim from which it depends are illustra-
tive:
1. An isolated recombinant anti-TNF-α anti-
body or antigen-binding fragment thereof, said
antibody or antigen-binding fragment comprising
a human constant region, wherein said antibody
or antigen binding fragment (i) competitively in-
hibits binding of A2 (ATCC Accession No. PTA-
7045) to human TNF-α, and (ii) binds to a neutral-
izing epitope of human TNF-α in vivo with an af-
finity of at least 1x108 liter/mole, measured as an
association constant (Ka), as determined by
Scatchard analysis.
2. The antibody or antigen-binding fragment
of claim1, wherein the antibody or antigen bind-
ing fragment comprises a human constant region
and a human variable region.
’775 patent col.107 ll.34-46 (emphases added). Independ-
ent claim 1, which is not at issue in this appeal, covers
antibodies with a human constant region and a variable
region from any source. The scope of claim 1 includes, but
is not limited to, chimeric antibodies. Asserted claim 2 is
limited to antibodies with human constant regions and
9 CENTOCOR v. ABBOTT LABS
human variable regions. Asserted claim 3, which also
depends from claim 1, likewise claims antibodies with
human variable regions. Asserted claims 14 and 15
similarly include antibodies with human constant regions
and human variable regions, although these claims are
limited to specific human constant regions. All of the
asserted claims cover human variable regions and fully-
human antibodies like Abbott’s Humira®.
Centocor’s application, which contained a priority
claim to its earlier applications, issued as the ’775 patent
in 2006. Shortly thereafter, it filed this action against
Abbott, alleging that Abbott’s Humira® antibody in-
fringes the asserted claims of the ’775 patent. At trial,
Abbott argued that the asserted claims were invalid. The
jury rejected Abbott’s arguments and found willful in-
fringement of the asserted claims. The jury also found
that the asserted claims were not invalid for anticipation,
lack of enablement, or lack of written description. Abbott
moved for JMOL on the issues of infringement, willful-
ness, and validity. The district court granted Abbott’s
JMOL motion regarding willfulness and denied the other
motions. Abbott now appeals. We have jurisdiction
pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
For issues not unique to patent law, we apply the law
of the regional circuit in which the appeal would other-
wise lie. Thus, we apply Fifth Circuit law when reviewing
the district court’s denial of Abbott’s JMOL motion.
Finisar Corp. v. DirecTV Grp., Inc., 523 F.3d 1323, 1328
(Fed. Cir. 2008). The Fifth Circuit reviews denials of
JMOL de novo. Cambridge Toxicology Grp., Inc. v. Exni-
cios, 495 F.3d 169, 179 (5th Cir. 2007). JMOL is appro-
priate only if the court finds that a “‘reasonable jury
CENTOCOR v. ABBOTT LABS 10
would not have a legally sufficient evidentiary basis to
find for the party on that issue.’” Id. (quoting Fed. R. Civ.
P. 50(a)(1)).
Patents are presumed to be valid and overcoming this
presumption requires clear and convincing evidence.
Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1354
(Fed. Cir. 2010) (en banc). Compliance with the written
description requirement of 35 U.S.C. § 112, ¶ 1 is a ques-
tion of fact, and “‘we review a jury’s determinations of
facts relating to compliance with the written description
requirement for substantial evidence.’” Id. at 1355 (quot-
ing PIN/NIP, Inc. v. Platte Chem. Co., 304 F.3d 1235,
1243 (Fed. Cir. 2002)). A patent also can be held invalid
for failure to meet the written description requirement
based solely on the face of the patent specification. Univ.
of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927 (Fed.
Cir. 2004); PIN/NIP, 304 F.3d at 1247-48 (reversing the
district court’s denial of JMOL because no reasonable
juror could have concluded that the asserted claim was
supported by adequate written description).
The written description requirement of 35 U.S.C.
§ 112, ¶ 1 provides, in pertinent part, that:
The specification shall contain a written descrip-
tion of the invention, and of the manner and proc-
ess of making and using it, in such full, clear,
concise, and exact terms as to enable any person
skilled in the art to which it pertains, or with
which it is most nearly connected, to make and
use the same, and shall set forth the best mode
contemplated by the inventor of carrying out his
invention.
11 CENTOCOR v. ABBOTT LABS
To satisfy the written description requirement, “the
applicant must ‘convey with reasonable clarity to those
skilled in the art that, as of the filing date sought, he or
she was in possession of the invention,’ and demonstrate
that by disclosure in the specification of the patent.”
Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541
F.3d 1115, 1122 (Fed. Cir. 2008) (quoting Vas-Cath Inc. v.
Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991)).
Assessing such “possession as shown in the disclosure”
requires “an objective inquiry into the four corners of the
specification.” Ariad, 598 F.3d at 1351. Ultimately, “the
specification must describe an invention understandable
to [a person of ordinary skill in the art] and show that the
inventor actually invented the invention claimed.” Id. A
“mere wish or plan” for obtaining the claimed invention is
not adequate written description. Regents of the Univ. of
Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566 (Fed. Cir.
1997).
A
The pivotal issue in this case concerns whether the
’775 patent provides adequate written description for the
claimed human variable regions. As noted above, Cento-
cor first sought claims to human variable regions and
fully-human antibodies in 2002. At that time, Abbott had
already discovered and patented a fully-human antibody
to TNF-α that had high affinity and neutralizing activity.
To ensnare Abbott with later-filed claims, Centocor must
use a priority date from an earlier application. Because
Abbott’s application was filed in 1996, Centocor relies on
a priority claim to the 1994 CIP applications. Thus, in
order for Centocor to prevail, the asserted claims must be
supported by adequate written description in the 1994
CIP applications.
CENTOCOR v. ABBOTT LABS 12
The asserted claims cover fully-human antibodies
that possess the same therapeutic properties as Cento-
cor’s chimeric antibody, i.e., high affinity, neutralizing
activity, and binding at a specific place on human TNF-α.
Accordingly, the 1994 CIP applications must provide
written description for an antibody to human TNF-α with
(1) a human constant region, (2) a human variable region,
(3) high affinity for human TNF-α, (4) neutralizing activ-
ity, and (5) the ability to bind to TNF-α in the same place
as Centocor’s A2 mouse antibody (“A2 specificity”).
At trial, Abbott’s expert, Dr. James Marks, testified
about the disclosure in the 1994 CIP applications and
explained why a person of ordinary skill in the art would
not have understood that Centocor had possession of a
high affinity, neutralizing, A2 specific, fully-human
antibody. J.A. 18472-75. On appeal, Abbott emphasizes
that Dr. Marks provided the only expert testimony that
the jury heard about written description. To underscore
the inadequacy of Centocor’s written description, Abbott
points out that the specification does not disclose any
fully-human, high affinity, neutralizing, A2 specific
antibody. Moreover, the specification does not disclose a
single human variable region. Abbott argues that the
only described antibody is the chimeric antibody, which
has a mouse variable region. Abbott also argues that
Centocor has merely disclosed tools that might be used in
an attempt to make the claimed invention—essentially,
that Centocor’s disclosure is no more than a mere wish or
plan for how one might search for a fully-human antibody
that satisfies the claims. Finally, Abbott points to testi-
mony from Centocor’s inventor indicating that the disclo-
sure did not include examples about making a human
antibody because “it was never [Centocor’s] intention to
make a human antibody.” J.A. 18312, 18:19-24. Abbott
13 CENTOCOR v. ABBOTT LABS
contends that Centocor is attempting to claim as its own
the fruit of Abbott’s innovative work.
In response, Centocor points to specific disclosures in
the 1994 CIP applications identified by inventor Dr. John
Ghrayeb as evidence that the asserted claims are ade-
quately described and enabled. Centocor presented no
expert testimony on written description at trial and
instead chose to rest on the ’775 patent specification and
the testimony of its inventors. Without directly relying on
the PTO written description guidelines or what it refers to
as “dicta” in Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir.
2004), Centocor contends on appeal that the ’775 patent
“does much more than what the Guidelines and Noelle
suggest,” in that it not only describes the antibodies by
their binding affinity for TNF-α, but further describes the
antibodies by specifying that they competitively inhibit
binding of the A2 mouse antibody to TNF-α. Centocor
also argues that the written description requirement
demands neither actual reduction to practice nor working
examples to claim an invention.
We turn to the four corners of the 1994 CIP applica-
tions to assess whether their disclosure provides adequate
written description for the asserted claims. Because the
pertinent disclosure from the 1994 applications appears
in the ’775 patent as issued, we refer only to the ’775
patent for clarity.
B
Contrary to Centocor’s assertions, very little in the
’775 patent supports that Centocor possessed a high
affinity, neutralizing, A2 specific antibody that also
contained a human variable region. The overwhelming
majority of the ’775 patent describes the A2 mouse anti-
CENTOCOR v. ABBOTT LABS 14
body and the single chimeric antibody that Centocor made
based on A2’s mouse variable region. The specification
describes the structure and characteristics of the chimeric
antibody in great detail, indicating that it binds to TNF-α
with high affinity, has neutralizing activity, and is A2
specific—characteristics mirrored by the critical claim
limitations in the asserted claims. The specification also
includes the sequence of the human TNF-α protein,
references to cell lines that produce the mouse and chi-
meric antibodies, and numerous examples describing
making and using the chimeric antibody. ’775 patent
col.15 ll.40–54; col.42 l.60–col.68 l.67; col.99 ll.1–40. As
for describing suitable variable regions, the application
only provides amino acid sequence information (a molecu-
lar description of the antibody) for a single mouse variable
region, i.e., the variable region that the mouse A2 anti-
body and the chimeric antibody have in common. Id. at
cols.99–103. However, the mouse variable region se-
quence does not serve as a stepping stone to identifying a
human variable region within the scope of the claims. 2
2 Dr. Marks testified at length about the state of
the art at the time Centocor’s specification was filed and
explained that one of skill in the art would not under-
stand from the disclosure of a mouse variable region that
Centocor was in possession of an antibody with a fully
human variable region. He concluded:
Q. And how do the protein sequences of the mouse
antibody, or the chimeric antibody, compare to a full
human antibody?
A. They’re very different.
Q. And would the disclosure of this sequence infor-
mation teach of one ordinary skill in the art how to make
and use a fully human [antibody]?
A. No.
J.A. 18476, 114:20-115:2.
15 CENTOCOR v. ABBOTT LABS
The undisputed trial testimony indicated that the se-
quence of Centocor’s mouse variable region was “very
different” from the sequence of a human variable region
like the one in Abbott’s fully-human antibody.
In marked contrast to the detailed description of the
claimed chimeric antibodies, Dr. Ghrayeb was able to
point to only a few sentences sprinkled throughout the
’775 patent that mention human antibodies or human
variable regions at all. Id. at col.5 l.57; col.12 l.29; col.16
l.29; col.18 l.60. Dr. Marks testified that the mere fact
that “the words appear” does not reasonably suggest to
one of skill in the art that Centocor was in possession of
such antibodies. J.A. 18493, 16:8-17:22. Further, while
the specification notes that fully-human antibodies can
potentially be produced by human B lymphocytes, it does
not disclose any B lymphocytes that actually produce a
high affinity, neutralizing, A2 specific TNF-α antibody.
Id. at col.15 ll.1–9. 3
In addition, Dr. Ghrayeb highlighted a single refer-
ence to an article describing using phage display technol-
ogy to make low affinity, human antibodies. Id. at col.18
ll.52–53. Dr. Marks, the author of the article, testified at
trial that it teaches low affinity antibodies to red blood
cells. He stated that “the antibodies coming out of [these
early phage libraries] were very low affinity” and ex-
plained that “there's no teaching in this paper about how
to make TNF antibodies.” J.A. 18475, 110:3-19. Dr.
Ghrayeb likewise testified that the article describes using
3 Dr. Marks and Dr. Pablo Casali both testified that
to this day, the human B lymphocyte method has never
been used successfully to make a high-affinity, neutraliz-
ing, fully-human, TNF-α antibody. J.A. 18450, 13:1-6;
18464, 69:2-8.
CENTOCOR v. ABBOTT LABS 16
a phage library to identify antibodies that bind to red
blood cells. J.A. 18310, 10:10-12. The article does not
discuss making fully-human antibodies to human TNF-α,
nor does it discuss making antibodies that bind in a
specific place like the claimed A2 specific antibodies. Dr.
Marks testified that references in the patent addressing
phage display “describe[] very general library technologies
that could be used to make antibodies, including human
antibodies,” J.A. 18474, 108:12-14, but they do not teach
how to isolate or use such antibodies. The fact that a
fully-human antibody could be made does not suffice to
show that the inventors of the ’775 patent possessed such
an antibody.
Besides pointing to these limited references to fully-
human antibodies, none of which relate to the specific
critical limitations in the asserted claims, Centocor sug-
gests that written description for the asserted claims
comes from the limitations described in the claim lan-
guage itself. However, this specific claim language was
not added until 2002 and is not part of the 1994 CIP
applications as filed.
Thus, while the patent broadly claims a class of anti-
bodies that contain human variable regions, the specifica-
tion does not describe a single antibody that satisfies the
claim limitations. See Eli Lilly, 119 F.3d at 1566-69. It
does not disclose any relevant identifying characteristics
for such fully-human antibodies or even a single human
variable region. See id. Nor does it disclose any relation-
ship between the human TNF-α protein, the known
mouse variable region that satisfies the critical claim
limitations, and potential human variable regions that
will satisfy the claim limitations. See id. There is noth-
ing in the specification that conveys to one of skill in the
art that Centocor possessed fully-human antibodies or
17 CENTOCOR v. ABBOTT LABS
human variable regions that fall within the boundaries of
the asserted claims.
At bottom, the asserted claims constitute a wish list of
properties that a fully-human, therapeutic TNF-α anti-
body should have: high affinity, neutralizing activity, and
the ability to bind in the same place as the mouse A2
antibody. The specification at best describes a plan for
making fully-human antibodies and then identifying
those that satisfy the claim limitations. But a “mere wish
or plan” for obtaining the claimed invention is not suffi-
cient. See id. at 1566. At the time the 1994 CIP applica-
tions were filed, it was entirely possible that that no fully-
human antibody existed that satisfied the claims. Be-
cause Centocor had not invented a fully-human, high
affinity, neutralizing, A2 specific antibody in 1994, a
reasonable jury could not conclude that it possessed one.
C
Although it does not fully endorse those positions,
Centocor suggests that our decision in Noelle and the PTO
written description guidelines support the view that fully
disclosing the human TNF-α protein provides adequate
written description for any antibody that binds to human
TNF-α. That suggestion is based on an unduly broad
characterization of the guidelines and our precedent.
The current PTO written description guidelines in-
clude an antibody example. Referencing only an immu-
nology text published in 1976, the PTO guidelines
indicate that a functional claim reciting “an isolated
antibody capable of binding to [protein] X” is adequately
described where the specification fully characterizes
protein X—even if there are no working or detailed pro-
phetic examples of actual antibodies that bind to protein
CENTOCOR v. ABBOTT LABS 18
X. U.S.P.T.O., Written Description Training Materials
Revision 1 March 25, 2008 at 45-46 (available at
http://www.uspto.gov/web/menu/written.pdf) (hereinaf-
ter PTO guidelines). The antibody example presumes
that the applicant is disclosing a novel protein and then
claiming both the protein and an antibody that binds to it.
The PTO guidelines characterize “production of antibodies
against a well-characterized antigen” as “conventional”
and “routine,” given “well developed and mature” anti-
body technology. Id. at 46. The PTO guidelines conclude
that characterization of the protein alone may be suffi-
cient under circumstances where “one of skill in the art
would have recognized that the disclosure of the ade-
quately described [protein] X put the applicant in posses-
sion of antibodies which bind to [protein] X.” 4 Id. In
4 The PTO guidelines explain why disclosure of a
well-characterized protein generally places the possessor
of the protein in possession of antibodies to that protein.
Basically, producing certain types of antibodies is conven-
tional. PTO guidelines at 46. It is routine to raise a
spectrum of antibodies to a known protein simply by
injecting that protein into a host animal that is a different
species. The host generates antibodies to the foreign
protein. For this reason, some antibodies to a well-
characterized protein may be adequately described even
when they are functionally claimed and not actually
produced.
Depending on the state of the art, this reasoning
might not apply to obtaining human antibodies to a
human protein for several reasons. For example, even if
it were ethically possible to use humans as hosts to gen-
erate antibodies, proteins like human TNFα are “self”
proteins, so a human host might not produce effective
antibodies against the antigen. J.A. 18449 (discussing
conventional antibody production techniques and the
difficulties associated with making human antibodies to
self proteins). In fact, the two known high affinity, neu-
tralizing, fully-human antibodies to human TNFα were
not produced using this method.
19 CENTOCOR v. ABBOTT LABS
other words, an applicant can claim an antibody to novel
protein X without describing the antibody when (1) the
applicant fully discloses the novel protein and (2) generat-
ing the claimed antibody is so routine that possessing the
protein places the applicant in possession of an antibody.
In Noelle, we discussed the PTO’s antibody example.
355 F.3d at 1349. The case focused on antibodies to a
protein called CD40CR. Noelle claimed an antibody that
“specifically binds CD40CR.” Id. at 1346. This broad
claim covered antibodies that bind CD40CR from any
species. Noelle also claimed an antibody that specifically
binds human CD40CR, id., yet the specification only
disclosed the mouse CD40CR protein and an antibody to
that protein, id. at 1349. The specification did not de-
scribe any antibodies to human CD40CR or CD40CR from
any other species, nor did it describe any CD40CR protein
from any species except mouse. Id. We concluded that
Noelle’s specification did not provide adequate written
description for such broad claims.
While our precedent suggests that written description
for certain antibody claims can be satisfied by disclosing a
well-characterized antigen, that reasoning applies to
disclosure of newly characterized antigens where creation
of the claimed antibodies is routine. Here, both the
human TNF-α protein and antibodies to that protein were
known in the literature. 5 The claimed “invention” is a
class of antibodies containing a human variable region
that have particularly desirable therapeutic properties:
high affinity, neutralizing activity, and A2 specificity.
5 The ’775 patent specification describes the exist-
ing literature on tumor necrosis factor and the various
polyclonal and monoclonal antibodies previously known in
the art. ’775 patent col.1 l.42–col.3 l.55.
CENTOCOR v. ABBOTT LABS 20
Claiming antibodies with specific properties, e.g., an
antibody that binds to human TNF-α with A2 specificity,
can result in a claim that does not meet written descrip-
tion even if the human TNF-α protein is disclosed because
antibodies with those properties have not been adequately
described.
As discussed above, obtaining a high affinity, neutral-
izing, A2 specific antibody with a human variable region
was not possible in 1994 using “conventional,” “routine,”
“well developed and mature” technology. PTO guidelines
at 46. Centocor highlights Dr. Jochen Salfeld’s testimony
analogizing the antibody-antigen relationship to “a key in
a lock.” J.A. 18436, 154:4-5. What Centocor ignores is
the remainder of Dr. Salfeld’s testimony, which pointed to
the challenges of finding an appropriate antibody on “a
ring with a million keys on it.” Id., 154:2-3. Centocor
simply failed to support its contention that generating
fully-human antibodies with the claimed properties would
be straightforward for a person of ordinary skill in the art
given the state of human antibody technology in 1994.
Unlike the antibody example cited in the PTO guidelines,
therefore, simple possession of the known TNF-α protein
did not place Centocor in possession of the claimed anti-
bodies.
D
In view of the lack of written description in the speci-
fication for fully-human, A2 specific, neutralizing, high
affinity antibodies, Centocor’s argument that an inventor
need not physically make an invention to claim it misses
the mark. Indeed, we have repeatedly indicated that the
written description requirement does not demand either
examples or an actual reduction to practice. Ariad, 598
F.3d at 1352. What it does demand is that one of skill in
21 CENTOCOR v. ABBOTT LABS
the art can “visualize or recognize” the claimed antibodies
based on the specification’s disclosure. Eli Lilly, 119 F.3d
at 1568. In other words, the specification must demon-
strate constructive possession, and the ’775 patent’s
specification fails to do so. Ariad, 598 F.3d at 1352.
Centocor’s asserted claims to fully-human antibodies
“merely recite a description of the problem to be solved
while claiming all solutions to it.” Ariad, 598 F.3d at
1353. The actual inventive work of producing a human
variable region was left for subsequent inventors to
complete.
The scope of Centocor’s right to exclude cannot “over-
reach the scope of [its] contribution to the field of art as
described in the patent specification.” Reiffin v. Microsoft
Corp., 214 F.3d 1342, 1345 (Fed. Cir. 2000). Its fully-
human antibody claims are beyond the scope of its disclo-
sure. As in Ariad, we conclude that the jury lacked
substantial evidence for its verdict that the asserted
claims were supported by adequate written description.
The district court erred when it declined to grant Abbott a
JMOL that the asserted claims fail to satisfy the written
description requirement of 35 U.S.C. § 112.
CONCLUSION
We hold that claims 2, 3, 14, and 15 of the ’775 patent
are invalid for lack of written description. The judgment
below is reversed.
REVERSED