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 & Johnson, 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 defendants-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 Indianapolis, 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 pharmaceutical 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 requirement. 

BACKGROUND

The technology in this case involves antibodies to human tumor necrosis factor α (“TNF-α”). Overproduction of 

TNF-α can lead to various autoimmune conditions, including arthritis. Although TNF-α antibodies have the potential to reduce the harmful activity caused by excess TNFα, 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. Because the antibodies must stick to human TNF-α to work, 

their binding ability is important. A high affinity antibody 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 patients frequently have immunological reactions when they 

are treated with antibodies produced in mice or other nonhuman 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 neutralizing activity (“the A2 mouse antibody”). While this antibody 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 portions 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 variable region is the portion responsible for sticking to TNFα. 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 antibody. 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 potential 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 antibody 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 fullyhuman 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 examples 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 continuationin-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 application. 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. Although 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 chimeric 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 antibody 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 affinity 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 binding 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 solutions for those problems. J.A. 18318-19. 
CENTOCOR v. ABBOTT LABS 8

the patent in 2000, and Abbott obtained regulatory approval to market Humira® in 2002. 

After the grant of Abbott’s patent and after regulatory 

approval of Humira®, Centocor filed its claims to fullyhuman 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 illustrative: 

 1. An isolated recombinant anti-TNF-α antibody 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 inhibits binding of A2 (ATCC Accession No. PTA7045) to human TNF-α, and (ii) binds to a neutralizing epitope of human TNF-α in vivo with an affinity 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 binding fragment comprises a human constant region

and a human variable region. 

’775 patent col.107 ll.34-46 (emphases added). Independent 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 fullyhuman 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 infringes 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 infringement 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, willfulness, 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 otherwise 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. Exnicios, 495 F.3d 169, 179 (5th Cir. 2007). JMOL is appropriate 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 question 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 (quoting 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 description of the invention, and of the manner and process 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, Centocor 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 Centocor’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 activity, 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 testimony from Centocor’s inventor indicating that the disclosure 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 adequately 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 applications 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 chimeric 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 molecular description of the antibody) for a single mouse variable 

region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. Id. at 

cols.99–103. However, the mouse variable region sequence 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 understand 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 information 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 sequence 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 reference to an article describing using phage display technology 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 explained 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, neutralizing, 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 fullyhuman antibodies, none of which relate to the specific 

critical limitations in the asserted claims, Centocor suggests that written description for the asserted claims 

comes from the limitations described in the claim language 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 antibodies that contain human variable regions, the specification 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 relationship 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 nothing 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 antibody 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 sufficient. See id. at 1566. At the time the 1994 CIP applications were filed, it was entirely possible that that no fullyhuman antibody existed that satisfied the claims. Because 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 include an antibody example. Referencing only an immunology 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 prophetic 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) (hereinafter 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” antibody technology. Id. at 46. The PTO guidelines conclude 

that characterization of the protein alone may be sufficient under circumstances where “one of skill in the art 

would have recognized that the disclosure of the adequately described [protein] X put the applicant in possession 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 conventional. 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 wellcharacterized 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 generate 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, neutralizing, 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) generating 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 describe 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 existing 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 description 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, neutralizing, 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 antibodies. 

D 

In view of the lack of written description in the specification 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 demonstrate 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 “overreach 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 fullyhuman antibody claims are beyond the scope of its disclosure. 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