Indiana Law Review


Questioning the Requirement for Written
Description: Enzo Biochem v. Gen-Probe

and Overly Broad Patent Cases

Paula K. Davis*

Introduction

Imagine the following patent claim: "An isolated protein capable of
inhibiting beta-amyloid." Assume that the patent explains that beta-amyloid is
the protein responsible for plaques in the brain associated with Alzheimer's

disease and that inhibition ofbeta-amyloid may be therapeutically useful to treat,
cure, or prevent Alzheimer's disease. The patent relates that the physical and
chemical structures of beta-amyloid are well known, and it explicitly describes

the beta-amyloid molecule and a method for identifying inhibitors of the

molecule. Additionally, the patent explains that proteins in general have been

extensively studied such that it is an advanced field of biochemistry.

Accordingly, proteins can be characterized by numerous methodologies in the art,

and the basic structure ofproteins—the primary, secondary, tertiary, and in some
cases, quaternary structure—can be readily determined by the skilled artisan.
Given that disclosure, a person of ordinary skill might hypothesize generally

about the types of proteins that would inhibit beta-amyloid, but the full scope of

which proteins are encompassed by this claim would be difficult, if not

impossible, to comprehend. The scope could encompass literally billions of

proteins. Should the inventor on this patent, who discovered the method of
identifying inhibitors of beta-amyloid but did not disclose any proteins that

inhibit beta-amyloid, be granted exclusive rights to all proteins discovered to

have this property?

To allow a patent claim of such broad scope would be inconsistent with the
goals of patent law. The scope of the claim is not commensurate with the
inventor's contribution to the field ofAlzheimer's research. He discovered how
to identify proteins that inhibit beta-amyloid; claims to his method may be
patentable by him. Additionally, any proteins that he can characterize by
structure or partial structure correlated with function may be patentable by him.
Nonetheless, this inventor has not conceived of all possible proteins that may
inhibit beta-amyloid. Because the patent system provides exclusivity to inventors

for a specific period, allowing him such a broad scope would exclude other
researchers who are investigating potential treatments, cures, and preventive
methods for Alzheimer's disease using proteins to inhibit beta-amyloid.

Exclusivity would limit research to this inventor, his licensees, and parties
willing to risk an infringement suit later. This limitation could be disastrous for

Alzheimer's research.

* J.D. Candidate, 2004, Indiana University School of Law—Indianapolis; B.S., 1989,
Southeast Missouri State University; admitted to practice before the U.S. Patent & Trademark
Office; Patent Agent at Eli Lilly & Co. Views expressed in this Note are those of the author and
not necessarily the views of Eli Lilly & Co. The author wishes to express much gratitude to
Professor Mark J. Stewart, J.D., Ph.D., for valuable feedback on this Note.



468 INDIANA LAW REVIEW [Vol. 37:467

Despite the possible ruinous results, claims that are nearly as broad, such as

"[a]n isolated antibody capable of binding to Antigen X,"
1

are being advocated

by the United States Patent and Trademark Office (USPTO), and more recently
by the U.S. Court of Appeals for the Federal Circuit, as complying with current
patent law.

2
Lawsuits are being litigated over patents in which the inventor was

granted a claim with very broad scope, but the inventor did not produce even a

single composition. For example, in University ofRochester v. G.D. Searle &
Co.,

3
the U.S. District Court for the Western District of New York granted a

motion for summaryjudgment ofpatent invalidity for failure to meet the written
description requirement of 35 U.S.C. § 1 12, first paragraph.

4 The invalid patent
claimed "a pharmaceutical 'method for selectively inhibiting PGHS-2 activity in
a human host' in which 'the activity of PGHS-1 is not inhibited,"' but the
inventors produced no compositions.

5 The court held that the patent could not
be practiced until a composition was invented for use in the method.6 Thus, the
inventors did not possess the complete invention, and the patent failed to meet

the written description requirement. Permitting such a broad claim is not in

accordance with public policy relating to patent exclusivity. Instead, it frustrates

the practice of patent law by confusing inventors and practitioners regarding the

requirements for obtaining a patent, particularly the written description

requirement.

This Note discusses recent cases dealing with written description law,

particularly with respect to biotechnology,
7
and the associated rise of discord

among judges in the U.S. Court of Appeals for the Federal Circuit. Recent
questions concerning changes in written description law are addressed by

1

.

See Synopsis ofApplication of Written Description Guidelines, at 59-60, available at

http://www.uspto.gov/web/menu/written.pdf (last visited Oct. 22, 2003) [hereinafter Synopsis of

Application].

2. See Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).

3. 249 F. Supp. 2d 216 (W.D.N.Y. 2003).

4. 35 U.S.C. § 1 12 para. 1 (2000). Citations to the written description requirement vary

widely. For consistency, all references to the statute in the text of this Note are stated as "§ 1 12,

first paragraph," and in the footnotes as "35 U.S.C. § 112, para. 1" or in short form as" § 112, para.

1
." The abbreviation "para. 1 " is used rather than "^ 1 " or "(

1

)" because the "authority is organized

in part by indented paragraphs not introduced by paragraph symbols . . ." or by numbered

paragraphs. The Bluebook: A Uniform System of Citation 37 (Columbia Law Review Ass'n

et al. eds., 1 7th ed. 2000). Exceptions to these citations in this Note occur when the statute is cited

otherwise in a quote or in a title; in those situations, the citation is not revised.

5. Univ. ofRochester, 249 F. Supp. 2d at 219-20. Cf Ariad Announces Filing ofLawsuit

Against Eli Lilly Alleging Infringement of Pioneering NF-KB Treatment-Method Patent, at

http://media.corporate-ir.net/media_files/nsd/aria/releases/062502-2.pdf. This case was filed in the

U.S. District Court for the District of Massachusetts on June 25, 2002 and is awaiting trial at the

date of this Note.

6. Univ. ofRochester, 249 F. Supp. 2d at 218.

7. "Biotechnology," "biotechnical," and "biotechnological" are commonly abbreviated as

"biotech" and will hereinafter be referred to as such.



2004] ENZO BIOCHEM V. GEN-PROBE 469

analyzing Enzo Biochem, Inc. v. Gen-Probe, Inc.? a series of cases from 2002.

The second decision in the Enzo series, Enzo II, signifies an inflection point in
the court's concurrence on the use of a discrete written description requirement,

separate from enablement. Suddenly, patent practitioners are uncertain how to
meet the written description requirement.

9
Furthermore, this question is not

likely to be resolved in the near future. The court denied en banc review,
10
and

Enzo Biochem and Gen-Probe settled the remanded case out of court, providing
no resolution to the outstanding questions in the case. In the meantime, attorneys

and agents continue to file patent applications, merely guessing at what the

written description requirements will be and hoping to meet the standard to

protect their clients' rights. This Note addresses the far-reaching implications

that these changes will have on patent practice and the biotech industry in

general.

I. Brief Introduction to Biotechnology and Biotech Patents

A. The Importance ofBiotech Patents

The biotech field is a rapidly growing area of the pharmaceutical industry,
the fruits of which may cure some of today's worst diseases. Yet, drug
development costs money. It is estimated that the average cost to develop a drug

is near $900 million.
11

Thus, biotech drugs share one common need—the need
for economic protection in the form of patent rights. Patent protection provides

exclusive rights, thereby enticing investors by assuring legal protection for their

investment. The prospects of legal protection and possible profit stimulates

investment in the industry, leading to industrial growth, which in turn yields

larger quantities and improved quality ofbiotech drugs. Better drugs improve the

quality of life for people who take them, which is the ultimate goal of every
pharmaceutical company.

Patent protection in biotechnology has been controversial. Critics believe

that no one should have exclusive rights to the essential proteins needed for life,

8. References to the Enzo Biochem, Inc. v. Gen-Probe, Inc. line of cases and the related

court decisions will hereinafter be referred to generically as Enzo, or specifically as Enzo I or Enzo

II for the April 2, 2002 case (opinion at 285 F.3d 1013 (Fed. Cir. 2002)) and the July 1 5, 2002 case

(opinion at 323 F.3d 956 (Fed. Cir. 2002)), respectively. The company, Enzo Biochem, Inc., will

hereinafter be referred to as Enzo Biochem.

9. See, e.g., Edward R. Ergenzinger Jr. & W. Murray Spruill, First Get the Patent: Quirks
ofBiotech Innovation and Innovators Complicate Securing ofRights, LEGALTIMES, Nov. 4, 2002;

Robert C. Scheinfeld & Parker H. Bagley, Enzo Biochem: What Direction is Written Description
Taking? N.Y. L.J., Sept. 25, 2002.

10. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 U.S.P.Q.2d 1618, 1618 (Fed. Cir. 2002).

1 1

.

Price Tag for New Drugs Almost $900 Million, Am. Ass'N OF PHARMACEUTICAL
Scientists Newsmagazine, July 2003, at 8, available at http://www.aaps.org/publications/

newsmagazine/2003/jul03/08.pdf.



470 INDIANA LAW REVIEW [Vol. 37:467

such as insulin or human growth hormone. 12 However, biotech patent protection
has been quite beneficial for the field and for society in general. It has led to

tremendous growth and scientific breakthroughs over the past two decades,
yielding life-saving drugs like Humulin® (human insulin) and Epogen®
(erythropoietin). This growth arises from public disclosure of the invention.

Patent exclusivity is a quid pro quo; the patent owner must disclose his invention
to the public so that others may build upon the technology, modify it, or use the
invention once the patent has expired. Over time, the technology advances to
higher levels.

Nevertheless, one cannot obtain a patent for something he merely wishes to
invent. Specific criteria must be met to demonstrate that the inventor has
conceived ofthe invention and has, at least conceptually, reduced it to practice.

Namely, the inventor must possess, or at least be able to describe, a working
embodiment of his invention, proving that his "invention" is not just a research
plan. Title 35 of the United States Code governs the patentability of inventions.
Specifically, § 112, first paragraph, states, in relevant part, that "[t]he

specification shall contain a written description of the invention . . . ,"
13

Yet,

controversy arises over how to meet the written description requirement, 14

especially in the biotech area.

Written description in the biotech area has developed through a relatively

small number of cases. Over time, the Federal Circuit has attempted to
progressively define the requirement such that patent protection is neither too

narrow nor overly broad. Narrow protection diminishes incentives for
investment by allowing potential infringers to easily modify the invention by

designing around the claims to obtain their own patents, thereby diminishing the
value of a patent. On the other hand, overly broad patent protection retards the
development of new technology by granting protection to future developments
of existing technology. This would give the owner exclusivity over too much
property, arguably more than he has actually conceived.

15
This would hinder

growth in the industry as the patent owner could "hold out" for excessive

licensing fees and cut off entire areas of research.

Consider the beta-amyloid claim previously discussed.
16

That inventor will

effectively be the only scientist researching proteins that inhibit beta-amyloid.

Other possible researchers would avoid the field for fear ofa future infringement

suit; the large investment required for drug discovery would make the risk of a
lawsuit too costly. Nonetheless, the patent owner may not have the resources to
perform extensive research. In essence, he has narrowly limited the field of

1 2. See generally James Bradshaw, Gene Patent Policy: Does Issuing Gene Patents Accord

with the Purposes of the U.S. Patent System?, 37 WILLAMETTE L. REV. 637, 646-53 (2001)

(describing various theories for precluding genetic information from patentability).

13. 35U.S.C. § 112 para. 1 (2000).

1 4. Conflicts in Federal Circuit Patent Law Decisions, 1 1 FED. ClR. B.J. 723, 734 (Pasquale

A. Razzano ed.) (2002) [hereinafter Conflicts].

15. See, e.g., Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473 (Fed. Cir. 1998).

16. See introductory discussion supra.



2004] ENZO BIOCHEM V. GEN-PROBE 47

1

Alzheimer's research, perhaps without even producing a therapeutic product to

help patients with the disease. This example illustrates the importance of

allowing claims that are commensurate with the scope of the invention, rather
than overly broad claims. By construing the written description requirement to
provide a moderate scope of protection, the court is serving the goal of § 112,

first paragraph, and promoting advancement in the technology as well as growth

in the biotech industry.

B. Biotech Terminology

As a scientific discipline, biotechnology and discussions thereof require
understanding ofkey concepts relating to the field, such as complementarity and

hybridization.
17 DNA typically occurs as a double-stranded molecule, meaning

that one strand ofDNA binds to another strand. DNA consists of combinations
of four nucleotides: adenine (A), cytosine (C), guanine (G), and thymine (T).

Binding occurs between the nucleotides of the two strands. In order to bind, a
nucleotide in one strand must be "complementary" to a nucleotide in the other

strand.
,8
Adenine and thymine are complementary (viz. , A binds T); cytosine and

guanine are complementary (viz., C binds G). 19

The process ofjoining two complementary single strands ofDNA is known
as "hybridization."

20
Hybridization will occur if the DNA strands are

complementary.
21 As DNA are often large molecules, some portions of the two

strands may not be complementary, while other portions are. For example,
assume that two strands of DNA have twenty contiguous nucleotides of the
following complementarity: the first ten nucleotides are complementary, the next

five nucleotides are not complementary, and the last five nucleotides are

complementary. In that case, the strands may bind together loosely, but small
environmental changes may break the strands apart. Fundamentally, the more
complementary the strands are, the more stringent the hybridization will be, and
the more difficult it will be to break the strands apart.22 Thus, ifthe sequence of
a strand of DNA is known, and stringent hybridization occurs with another
strand, one can infer that the two strands are complementary to some degree.
Nonetheless, it may be difficult to determine the exact degree ofcomplementarity
and precisely which nucleotides in the strands are not complementary, unless one
knows the sequence of the second strand.

To search for DNA strands that contain a certain sequence or function,
scientists often use nucleotide probes that will hybridize stringently to the

1 7. For a primer in basic principles of molecular biology and biotechnology, see generally

Bruce Alberts et al., Molecular Biology of the Cell (3d ed. 1 994) and James Darnell et

al., Molecular Cell Biology (2d ed. 1990).

1 8. Darnell et al., supra note 1 7, at 88-89.

19. Id.

20. Alberts et al., supra note 1 7, at G- 1 2.

21. Id. at 300.

22. /</. at306.



472 INDIANA LAW REVIEW [Vol. 37:467

DNA.23 The probes are designed to be complementary to a portion ofthe desired
DNA. For example, assume that a scientist knows the sequence of a small
portion (fragment) of a certain DNA of interest to him. Further, assume that the
fragment consists of the sequence "ATGCAG," but the entire DNA is much
larger and has not yet been sequenced. The scientist can prepare a fully
complementary probe with the sequence "TACGTC" and add it to a cell
suspected to contain the DNA of interest. The probe will search for the DNA
with the complementary portion and hybridize to it. A dye or other identifying
label added to the probe will enable the scientist to readily identify it after it

hybridizes to the desired DNA. He can then recover both the probe and the DNA
hybridized to it.

24
Next, the scientist can break the bonds between the probe and

the retrieved strand, and sequence the entire DNA strand obtained. Note,
however, that even though the probe hybridizes to the DNA strand, probes are
usually small sequences ofDNA that only bind a portion ofthe large DNA strand
retrieved.

25
Stringent hybridization to this small portion of the retrieved DNA

tells the scientist nothing about the remaining portion of the DNA sequence.
Another key area of importance to biotech deals with antibodies. An

increasing number of antibodies are being developed and used as therapeutic
drugs to treat disorders such as colorectal cancer, breast cancer, and organ

transplant rejection.
26 An antibody is a protein produced naturally by white

blood cells in response to a foreign molecule or invading organism, such as a

bacterium, that could harm the invaded cell. To protect the cell from harm, the
antibody tightly binds to the invading organism or molecule, known as an
antigen, and either inactivates it or causes it to be destroyed.

27 To avoid
destroying or inactivating the wrong thing, antibodies can distinguish between

similarly structured molecules.
28 The antigen specifically binds to a small region

of the antibody. The remainder of the antibody is not involved in antigen

binding.
29

The structure of antibodies has been studied extensively.
30 As a protein, an

antibody consists of a contiguous sequence of amino acids. This sequence is

composed oftwo regions: a constant region and a variable region. The constant
region occurs in one of only a few different biochemical forms, but the variable

region may occur in a virtually infinite number of forms. This variability
provides an array of antibodies that can bind to an equally large number of

23. Id. atG-19.

24. Id. at 300.

25. Id.

26. Rathin C. Das, Proteins and Antibodies Make Advances as Therapeutic Products, Am.

Clinical Laboratory, June 2001, at 12-14.

27. Alberts et al., supra note 1 7, at G-2.

28. Darnell et al., supra note 1 7, at 65.

29. Id. at 1004-06.

30. Charles A. Janeway, Jr. et al., Immunobiology 1 6 (Sarah Gibbs et al. eds., 5th ed.

2001).



2004] ENZO BIOCHEM V. GEN-PROBE 413

antigens.
31

Thus, the sequence of the variable region of any particular antibody

differs from the variable region of any other antibody.
32

The variable region of the antibody is the portion that binds to the antigen.
However, unlike complementarity in DNA in which A binds to T and C binds to
G, this level of complementarity does not exist between specific amino acids.
Generally, antibodies and antigens bind together based on their shapes and

attractions between the chemical structures.
33

This results in unpredictability of

the antibody sequence. One cannot know the exact sequence of the variable
region of an antibody simply by identifying the antigen that it binds.

Moreover, different antibodies bind to different locations on an antigen.
34

For example, assume the antigen is a protein that consists oftwenty amino acids.
One antibody may bind to the first ten amino acids of the antigen sequence, and
a completely different antibody may bind to the next ten. Additionally,
antibodies may exist that bind to amino acids number two through eleven,
number three through twelve, and so on. Even more, some antibodies may bind
to ten amino acids of the antigen, while others only bind to five amino acids of

the antigen. The variability, and hence the unpredictability, is immense.35

II. Development of the Written Description Requirement

The written description requirement is one of several requirements that a
patent disclosure must include to be valid. This requirement, along with two

others, the enablement and best mode requirements, is specifically stated in 35
U.S.C. § 1 12, first paragraph:

The specification shall contain a written description ofthe 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.

36

Because this area of patent law has changed little from the Patent Act of

1793,
37

the annals are devoid of legislative history on the topic. Sufficient

31. Id.

32. Id. at 100.

33. Such attractions include electrostatic forces, hydrogen bonding, Van der Waals forces,

and hydrophobic forces. Id. at 1 1 -04.

34. Id. at 100-01.

35. Id. at 124.

36. 35 U.S.C. § 1 12 para. 1 (2000).

37. ActofFeb.21, 1793, ch. 11, §3, 1 Stat. 318, 321. Subsequent Patent Acts include: Act

ofJuly 4, 1 836, ch. 357, § 6, 5 Stat. 1 1 7, Act ofJuly 8, 1 870, ch. 230, § 26, 1 6 Stat. 1 98, 20 1 , and

Act of July 19, 1952, ch. 950, § 1, 66 Stat. 792 (codified as amended at 35 U.S.C. §§ 1-376

(2000)). See Mark J. Stewart, Written Description Requirement of 35 U.S.C. § 112(1): The

Standard After Regents ofthe University ofCalifornia v. Eli Lilly & Co., 32 IND. L. REV. 537, 538



474 INDIANA LAW REVIEW [Vol. 37:467

written description ofan invention has been required in case law from at least the

early nineteenth century.
38

Nonetheless, many commentators have associated
modern jurisprudence on the subject with the 1967 case In re Ruschig 39 which
explicated that the written description is a distinct requirement for patentability.

40

Since then, this statute has been construed repeatedly in the case law from the

U.S. Court of Appeals for the Federal Circuit, yet it remains an unsettled area of

law, especially in the context of biotech inventions.
41

Methods used for determining whether a patent application complies with the
written description requirement vary in the case law. Opinions differ with

respect to the degree to which an invention must be described. The two extremes
of the description continuum can be illustrated by the cases Lockwood v.
American Airlines, Inc.

42
and Hyatt v. Boone.

43 Lockwood represents a rigid test
for compliance with the written description requirement, requiring express

disclosure ofall claim elements by explicit description in the patent application.
44

On the other end ofthe spectrum, Hyatt represents a relaxed written description
requirement, allowing the requirement to be met by less than express disclosure

ifthe applicant can show that a skilled artisan reading the application would have
necessarily comprehended and understood the missing description.

45

Biotech cases fall between the two extremes. As a result of the degeneracy
of the genetic code,

46
a narrow claim to DNA may be easily "designed around."

If the patent were restricted to the exact DNA actually reduced to practice, a
subsequent inventor could change a small portion of the biomolecule and still

achieve the same biological activity without infringing the patent. To protect
biotech inventors from this occurrence, claimed biomolecules may be generically
described, providing a group or "genus" of biomolecules which fall within the

scope ofthe patent. In this situation, requiring a rigid description of all elements

of the claimed biomolecules would not provide adequate protection to the

patentee, without listing thousands or perhaps millions ofpossible variations. In

consideration of this, the USPTO and courts may allow patentees to claim

(1999).

38. See, e.g., Evans v. Eaton, 20 U.S. 356 (1822).

39. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319 (Fed. Cir.

2003); Enzo Biochem, Inc. v. Gen-Probe Inc., 63 U.S.P.Q.2d 1618, 1623-24 (Fed. Cir. 2002);

Mark. D. Janis, On Courts Herding Cats: Contending with the 'Written Description " Requirement,

2 WASH. U. J.L. & POL'Y 55, 59 (2000); Janice M. Mueller, The Evolving Application ofthe Written
Description Requirement to Biotechnological Inventions, 13 BERKELEY TECH. L.J. 615, 616-17

(1998).

40. 379 F.2d 990, 995 (C.C.P.A. 1967).

41

.

Conflicts, supra note 14, at 734.

42. 107 F.3d 1565 (Fed. Cir. 1997).

43. 146 F.3d 1348 (Fed. Cir. 1998).

44. 107F.3dat 1572.

45. 146 F.3d at 1354-55.

46. The exact sequence of a biomolecule may vary from species to species, or even among

the same species, yet provide the same biological activity.



2004] ENZO BIOCHEM V. GEN-PROBE 475

sequences within a specific homology, variants, mutants, fragments,

subsequences, and the like, if enough examples are provided to sufficiently

describe the genus being claimed.
47

The liberal "skill of the art" written description requirement of Hyatt is not
typically allowed in biotech patents. The patentee cannot presume that the

skilled artisan would necessarily know that fragments or conservative
substitutions are allowed. Instead, he must describe the claimed genus with some
specificity.

48
For example, the application should define how many amino acids

are required to constitute a "fragment." Assume a protein has fifty amino acids.
Will a fragment often amino acids function the same way? Will five contiguous
amino acids suffice? The application should describe what length of fragment
retains functionality. Moreover, which nucleotides can be substituted at specific

positions in the generic sequence to qualify as a "variant"? The application

should list the possible amino acids that can be substituted and still achieve the

same biological activity. Such a description is a compromise between Lockwood
and Hyatt, the scope of the claims may be so large that it is not feasible to
explicitly describe all possible biomolecules that fall within the scope, but by

specifying which substitutions or fragments are allowed, the skilled artisan can

envision the scope of the claimed invention.

Another conflict regarding the written description requirement is whether the

enablement requirement and the written description requirement, both from

§ 1 12, first paragraph, are separate requirements that must be fulfilled by the

patentee. In the 1991 case Vas-Cath, Inc. v. Mahurkar*
9
the court clarified this

unresolved question by asserting:

35 U.S.C. § 1 12, first paragraph, requires a "written description of the

invention" which is separate and distinct from the enablement

requirement. The purpose of the "written description" requirement is
broader than to merely explain how to "make and use"; the applicant
must also 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.
50

Clearly and succinctly, the Vas-Cath court established the distinction between the

two requirements, seeming to resolve the issue.
51

47. See, e.g., Synopsis ofApplication, supra note 1, at 20-35, 41-47.

48. Regents of Univ. of Cal. v. Eli Lilly & Co., 1 1 9 F.3d 1 559, 1 568 (Fed. Cir. 1 997).
49. 935 F.2d 1555 (Fed. Cir. 1991).

50. Id. at 1563-64.

5 1

.

Debate still remains over this issue. See, e.g., Enzo Biochem, Inc. v. Gen-Probe, Inc., 63

U.S.P.Q.2d 1618, 1622-33 (Fed. Cir. 2002). Many commentators feel that the written description

requirement, especially in the field ofbiotechnology, is merely a heightened form ofthe enablement

requirement
—

"super-enablement." Moba, B.V. v. Diamond Automation, Inc., 325 F.3d, 1306,

1 325 (Fed. Cir. 2003) (quoting Arti Rai, Intellectual Property Rights in Biotechnology: Addressing

New Technology, 34 WAKE FOREST L. Rev. 827, 834-35 (1999) and Mueller, supra note 39, at
617).



476 INDIANA LAW REVIEW [Vol. 37:467

Moreover, Vas-Cath explained that although an exact description of the

claimed subject matter is not required for compliance, "the description must
clearly allow persons of ordinary skill in the art to recognize that [the applicant]

invented what is claimed"
52
and that "compliance with the 'written description'

requirement of § 112 is a question of fact, to be reviewed under the clearly

erroneous standard."
53

Although Vas-Cath did not involve biotechnology, the

Vas-Cath court set a clear standard to be relied upon and expounded upon in
future written description requirement cases.

Prior to Enzo, three landmark biotechnology cases shaped written description

law: Amgen, Inc. v. Chugai Pharmaceutical Co.
5A
Fiers v. Revel,

55
and Regents

ofthe University ofCalifornia v. Eli Lilly & Co. 56 The first ofthese three cases,
Amgen, Inc. v. Chugai, was a patent infringement case.

57 Amgen, Inc. sued
Chugai Pharmaceutical Co. and Genetics Institute, Inc. (GI) for infringement of

Amgen' s patent claiming the DNA sequence encoding human erythropoietin
(EPO), a therapeutic protein used to treat anemia. GI asserted an affirmative

defense ofpatent invalidity under 35 U.S.C. § 102(g),
58
alleging that it conceived

the DNA sequence prior to Amgen's conception. By 1981, GI had isolated and
purified the protein EPO and conceived a "probing strategy" to isolate the gene,
which it successfully reduced to practice in 1984.

59
In 1983, Amgen cloned the

gene encoding EPO, thereby obtaining the structure.
The Amgen court held that conception was not achieved until reduction to

practice occurred. "Conception is the 'formation in the mind of the inventor, of

a definite and permanent idea of the complete and operative invention, as it is

hereafter to be applied in practice.'"
60

"Conception requires both the idea of the

invention's structure and possession of an operative method of making it."
61

Although GI alleged to have conceived in 1 98 1 , the inventor could not define the

52. Vas-Cath, Inc., 935 F.2d at 1563 (quoting In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir.

1989)).

53. Id.

54. 927 F.2d 1200 (Fed. Cir. 1991).

55. 984 F.2d 1 164 (Fed. Cir. 1993).

56. 119 F.3d 1559 (Fed. Cir. 1 997).

57. 927F.2dat 1202.

58. 35 U.S.C. § 102(g) (2000). Section 102(g) provides in relevant part that:

A person shall be entitled to a patent unless

—

(g) before the applicant's invention thereof the invention was made ... by another who

had not abandoned, suppressed, or concealed it. In determining priority of invention

there shall be considered not only the respective dates of conception and reduction to

practice of the invention, but also the reasonable diligence of one who was first to

conceive and last to reduce to practice, from a time prior to the conception by the other.

Id.

59. Amgen, 927 F.2d at 1205-06.

60. Id. at 1 206 (quoting Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1 367, 1 376

(Fed. Cir. 1986), cert, denied, 480 U.S. 947 (1987)).

61. Id. at 1206.



2004] ENZO BIOCHEM V. GEN-PROBE All

DNA "so as to distinguish it from other materials" until 1984.62 In 1981, GI
could only describe the DNA by its principal biological property, i.e., encoding
human EPO, which was "simply a wish to know the identity ofany material with
that biological property."

63
Description merely by biological property was not

sufficient to meet the requirement for conception.
64

Conception is closely related

to written description because, to prove conception, an inventor has to prove by

contemporaneous documentation that he had "a mental picture ofthe structure"

or could define it by its distinguishing characteristics, but not solely by

function.
65

The second landmark biotech case ofthe trilogy, Fiers v. Revel, was a three-
way interference proceeding—three separate inventors filed patent applications
on the same DNA, the DNA encoding human fibroblast beta-interferon (P-IF).66
As the patent system ofthe United States is a "first to invent" system,67 the Fiers
court had to determine which ofthe three inventors was first to invent P-IF—that
is, which inventor had "priority."68 One criterion used by the court was
conception.

The Fiers court stressed that "conception ofa DNA . . . requires a definition
of that substance other than by its functional utility."

69
The court related

conception to written description, stating, "If a conception of a DNA requires a
precise definition, such as by structure, formula, chemical name, or physical

properties, as we have held, then a description also requires that degree of
specificity. To paraphrase the Board, one cannot describe what one has not
conceived."

70

Looking at the descriptions of P-IF in the three patent applications ofFiers,

the court found that only one application contained a description of the DNA
itself.

71
That application set forth the "complete and correct nucleotide

sequence," thereby demonstrating that the inventor was in possession ofthe DNA
as of the application filing date.

72
Consequently, only the application with the

complete DNA sequence met the written description requirement and was
patentable.

62. Id.

63. Id.

64. Id.

65. Id.

66. 984 F.2d 1 164, 1 166 (Fed. Cir. 1993).

67. 35U.S.C. § 102(g) (2000).

68. To establish priority in an interference, InventorA must show that he was first to conceive
ofthe invention and reduce it to practice by actual or constructive reduction to practice (e.g., filing

a patent application). Alternatively, if he were first to conceive but last to reduce to practice, he

must show that he was diligent from a time just prior to the time that Inventor B conceived of the

invention until the time that Inventor A reduced it to practice. See id.
69. Fiers, 984 F.2d at 1169.

70. Id. at 1171.

71. Mat 1172.
72. Id.



478 INDIANA LAW REVIEW [Vol. 37:467

The third landmark biotech case, Regents ofthe University ofCalifornia v.
Eli Lilly & Co., was a patent infringement case.73 The University of California
(UC) obtained a patent claiming cDNA74 encoding vertebrate insulin. To
describe vertebrate insulin, the patent contained the amino acid sequence of
human insulin, already known in the art, and a constructive example ofa method
that could be used to obtain human cDNA. Unlike the inventors in Amgen and
Fiers, UC had actually isolated, cloned, and characterized the rat insulin cDNA.
However, the patent contained no sequence or structural information regarding
which nucleotides constitute human insulin cDNA.75

UC sued Eli Lilly and Company (Lilly), alleging that Lilly infringed its
patent by manufacturing and selling human insulin. Lilly responded that it did
not infringe the patent, and that the patent was invalid for failure to meet the
written description requirement of § 1 1 2, first paragraph.

76
Judge Lourie, writing

for the majority, agreed with Lilly. Reiterating the essence ofFiers, he explained

that providing an enabling disclosure of how one could obtain a biomolecule
does not necessarily provide a written description of that biomolecule.

77
Judge

Lourie then elaborated on the use of generic statements to describe a genus:

In claims to genetic material, however, a generic statement such as

"vertebrate insulin cDNA" or "mammalian insulin cDNA," without
more, is not an adequate written description ofthe genus because it does

not distinguish the claimed genus from others, except by function. It

does not specifically define any of the genes that fall within its

definition. It does not define any structural features commonly
possessed by members of the genus that distinguish them from others.
One skilled in the art therefore cannot, as one can do with a fully
described genus, visualize or recognize the identity of the members of
the genus. A definition by function . . . does not suffice to define the
genus because it is only an indication of what the gene does, rather than

what it is. It is only a definition of a useful result rather than a definition
of what achieves that result.

78

Thus, describing only the rat gene did not adequately describe a genus that

encompassed the human gene.
Furthermore, the court used an obviousness analysis to show UC's lack of

written description for the human cDNA. The mere fact that a description makes
a claimed invention obvious does not necessarily mean that the same description
satisfies the written description requirement.

79
In the cases In re Deuel and In re

Bell, the court held that a claim to a specific DNA was not obvious merely

73. 1 19 F.3d 1559, 1559 (Fed. Cir. 1997).

74. "cDNA" is a form of DNA.

75. Lilly, 1 19 F.3d at 1566-67.

76. Mat 1562.
77. Id. at 1567.

78. Id. at 1568 (citations omitted).

79. Id. at 1567.



2004] ENZO BIOCHEM V. GEN-PROBE 479

because the sequence of the encoded protein and a method for generating the
DNA were known.80 Accordingly, knowledge of the human insulin protein
sequence and a method for generating the cDNA did not make human insulin
cDNA obvious. Moreover, a description that did not render the human cDNA
obvious also did not adequately describe the human cDNA under § 1 12, first
paragraph.

81

UC's "description" of human insulin added nothing new to the art: (1) the
human insulin protein sequence was known;82 (2) the method for generating the
cDNA was known; and (3) the mere words "human insulin cDNA" were known.
The sequence of human insulin cDNA was unknown and remained unknown
after UC filed its patent application. Hence, the court held that UC did not
satisfy the written description requirement for human insulin cDNA and was
indeed invalid.

83

After Lilly, the USPTO promulgated "Guidelines for the Examination of
Patent Applications Under the 35 U.S.C. 112, 1, 'Written Description'

Requirement."
84 The Guidelines are intended to assist USPTO personnel in the

examination of patent applications for compliance with the written description

requirement.
85

Along with the Guidelines, the USPTO published training
materials for patent examiners that include biotech examples such as antibody

and hybridization disclosures.
86

Each example provides a fact pattern, at least

one putative claim, an analysis describing how to determine whether each claim
meets the written description requirement, and a conclusion explaining whether

the claim is adequately described.
87

Application ofthe training materials will be

discussed in more detail in Part IV of this Note.

III. The Enzo Cases

A. Background and Procedural History

Enzo Biochem is the assignee of U.S. Patent 4,900,659 (the '659 patent).
88

The purpose of the invention is to find compositions of matter that are useful in

screening for the bacteria causing the disease gonorrhea, Neisseria gonorrhoeae

(N. gonorrhoeae). Prior to this invention, the bacteria that causes meningitis,

Neisseria meningitidis (N. meningitidis), interfered with the gonorrhea screening

80. In re Deuel, 5 1 F.3d 1 552, 1 558 (Fed. Cir. 1 995); In re Bell, 99 1 F.2d 78 1 , 785 (Fed. Cir.

1993).

81. Lilly, 119F.3dat 1567.

82. Stewart, supra note 37, at 553.

83. Lilly, 119F.3datl575.

84. Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1,

"Written Description" Requirement, 66 Fed. Reg. 1099 (Jan. 5, 2001).

85. Mat 1104.
86. Synopsis ofApplication, supra note 1

.

87. Id.

88. U.S. Patent No. 4,900,659 (issued Feb. 13, 1990).



480 INDIANA LAW REVIEW [Vol. 37:467

process, yielding false positives. Enzo Biochem's patent resolved this
interference problem.

89

The '659 patent claims compositions of matter comprising nucleotide
sequences which preferentially hybridize to N. gonorrhoeae over TV. meningitidis

at a ratio of greater than five to one.
90

Another claim specifically lists the

American Type Culture Collection (ATCC)91 accession numbers ofthree specific
probes

92
that yield a ratio greater than about fifty.

93
It further claims "discrete

nucleotide subsequences"
94
ofthe deposited probes, mutations ofthe probes and

subsequences of the mutations, and mixtures thereof.
95

Enzo Biochem sued Gen-Probe and several other defendants for infringement
ofthe '659 patent.

96
The defendants moved for summaryjudgment, alleging that

the claims were invalid for failure to meet the written description requirement of

§ 1 12, first paragraph. The district court granted the defendants' motion, stating
that the claimed compositions ofmatter were defined only by biological activity

or function (viz., hybridization).
97

Enzo Biochem appealed.
98

B. Enzo/

The Court ofAppeals for the Federal Circuit heard the appeal. Judge Lourie,

the author of numerous other cases involved in the evolution of the written

description requirement,
99

authored the opinion, decided on April 2, 2002. In

89. Id. at cols. 2-3.

90. Id. at Claims 1-3, col. 27, 1. 29 to col. 28, 1. 30.

9 1

.

ATCC is a public depository commonly used for long-term storage ofbiological samples.
The depository effectively serves as a public biotech "bank." It is recognized by most patent offices

worldwide as an approved facility for the deposit of biological samples claimed in patents. A
patentee deposits a sample of an invention in a depository so that the sample is obtainable by the

public. Each sample is given its own unique identifier, known as an accession number, used to

reference the stored material. See generally Patent Depository, ATCC Services, at http://www.atcc.
org/Services/PatentDep.cfm (last visited Oct. 22, 2003)(describing features, fees, and means for

depositing biological materials).

92. U.S. Patent No. 4,900,659 (issued Feb. 13, 1990), Claim 4, col. 28, 11. 31-49.

93. Id. at col. 13,11.9-13.

94. The '659 patent does not define subsequences, but it does define "discrete nucleotide

sequences" as "a nucleotide sequence greater than about 12 nucleotides" in length. Id. at col. 3,

11. 26-29.

95. Id. at Claim 4, col. 28, 11. 31-49.

96. Enzo Biochem, Inc. v. Gen-Probe, Inc., 285 F.3d 1013, 1016 (Fed. Cir.), vacated, 323

F.3d 956 (Fed. Cir. 2002).

97. Id. at 1016.

98. Id. (describing Enzo Biochem, Inc. v. Gen-Probe Inc., No. 99-CV-4548, transcript of

hearing at 28, 42 (S.D.N.Y. Jan. 24, 2001)).

99. E.g., Judge Lourie also authored the following: Regents of Univ. of Cal. v. Eli Lilly &
Co., 119 F.3d 1559 (Fed. Cir. 1997); Lockwood v. Am. Airlines, 107 F.3d 1565 (Fed. Cir. 1997);

In re Deuel, 51 F.3d 1552 (Fed. Cir. 1995); In re Bell, 991 F.2d 781 (Fed. Cir. 1993); Fiers v.



2004] ENZO BIOCHEM V. GEN-PROBE 48

1

accordance with other written description cases of recent years, the Enzo I
opinion continued to require a stringent written description, rejecting biological

function alone as adequate written description. The court affirmed the summary
judgment motion granted by the district court in favor ofthe defendants, holding:

[T]he claimed nucleotide sequence is described only by its binding to N.

gonorrhoeae in a preferential ratio of "greater than about five" with

respect to N meningitidis. While that description of the ability of the
claimed probe to bind to N. gonorrhoeae may describe the probe's
function, it does not describe the probe itself.

100

The court rejected Enzo Biochem's argument that hybridization is a chemical
property, which Fiers lists as a "precise definition" that meets the written

description requirement.
101 When Enzo Biochem argued that binding affinity

satisfies the requirements of the Written Description Guidelines,
102

the court

responded that: 1) the Guidelines are not binding on the court, and 2) the

Guidelines do not "set[] forth a rule that a description of a compound by its
binding affinity is sufficient to satisfy § 112, f l."

103
Instead, functional

characteristics, such as binding affinity, meet the Guidelines' requirements

"when coupled with a known or disclosed correlation between function and
structure."

104
Enzo Biochem did not assert such a correlation. 105

Furthermore, the court rejected Enzo Biochem's argument that reducing the

invention to practice and depositing the nucleotide sequences met the

"possession" test of Vas-Cath, clarifying that possession alone does not always

meet the written description requirement.
106

Reemphasizing the statutory written

description requirement, the court stated that ifthe specification does not contain

a written description, "despite a showing ofpossession, the specification does not

adequately describe the claimed invention."
107 The claimed nucleotide sequences

of the '659 patent were not so unusual that the inventors could not have

described them. Consequently, the deposit did not meet the written description

requirement.
108

Revel, 984 F.2d 1 164 (Fed. Cir. 1993); Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200 (Fed.

Cir. 1991).

100. Enzo, 285 F.3d at 1018.

101. Id.

102. Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1,

"Written Description" Requirement, 66 Fed. Reg. 1099, 1099-1 1 1 1 (Jan. 5, 2001).

103. Enzo, 285 F.3d at 1018-19.

104. Id. at 1019 (citing Guidelines for the Examination of Patent Applications Under the 35

U.S.C. 1 12, 1, "Written Description" Requirement, 66 Fed. Reg. 1099, 1 106 (Jan. 5, 2001)).

105. Id.

106. Id. at 1020.

107. Id. at 1021.

108. Id. at 1022-23.



482 INDIANA LAW REVIEW [Vol. 37:467

C. Rehearing and Vacating ofEnzo /: Enzo 77

Enzo Biochem petitioned for rehearing of the case en banc. 109 The court
denied the en banc request

110
but granted a rehearing of the case by the original

three-judge panel.
111

Again, Judge Lourie wrote the opinion, which vacated the
earlier holding and remanded the case to the district court for factual
determination of whether compositions, which were not specifically deposited,

satisfy the written description requirement.
112

The court's analysis began by stressing that not all functional descriptions
fail to meet the written description requirement.

113
Referencing the USPTO

Guidelines
114

and the Synopsis of Application
115

of the Guidelines, the court

indicated that they "are not binding on [the] court, but may be given judicial
notice to the extent they do not conflict with the statute."

116
According to the

USPTO, the written description requirement is met by "showfing] that an
invention is complete by disclosure of sufficiently detailed, relevant identifying

characteristics . . . i.e., complete or partial structure, other physical and/or

chemical properties, functional characteristics when coupled with a known or
disclosed correlation between function and structure, or some combination of
such characteristics."

117 The court was "persuaded by the Guidelines on this
point and adopt[ed] the PTO's applicable standard" for analysis ofthe issues. 118

The Enzo II court defined the issues as two-fold: 1 ) whether the deposits of
the claimed DNA sequences may constitute an adequate written description of
those sequences, and 2) whether the description requirement is met for all claims

based on functional ability ofthe claimed DNA sequences to hybridize to strains
of TV. gonorrhoeae that are accessible by deposit.

119
Addressing the first issue,

the court reiterated that deposits are typically used to satisfy the enablement

requirement, not the written description requirement.
120

Yet, in a complete

reversal, the court stated that its "prior decision that a deposit may not satisfy the
written description requirement was incorrect," vacating the Enzo I holding.

121

109. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 U.S.P.Q.2d 1618, 1618 (Fed. Cir. 2002).

110. Id.

111. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 960 (Fed. Cir. 2002).

112. Id.

113. Id at 964.

114. Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 1 12, 1,

"Written Description" Requirement, 66 Fed. Reg. 1099 (Jan. 5, 2001).

115. Synopsis ofApplication, supra note 1

.

116. Enzo, 323 F.3d at 964.

1 17. Id. (quoting Guidelines for the Examination of Patent Applications Under the 35 U.S.C.

1 12, 1, "Written Description" Requirement, 66 Fed. Reg. 1099, 1 106 (Jan. 5, 2001)) (emphasis

added by the court).

118. Id

119. Id.

120. Id. at 965.

121. Id. at 960.



2004] ENZO BIOCHEM V. GEN-PROBE 483

The court's rationale provided that Enzo Biochem's deposits were incorporated

by reference into the patent, and a skilled artisan could obtain the sequences from

the depository, if desired.
122

Moreover, the exact sequences may not have been
"reasonably obtainable" at the time of filing due to "severe time constraints in

sequencing DNA," and even if they were obtainable, the sequences were not
known to Enzo Biochem at the time of filing the application. 123 The court held
that compliance with the written description requirement was "grounded on the
fact of the deposit and the accession number" in the body of the patent.

124

However, Enzo Biochem deposited only three sequences. 125 The defendants
argued that the breadth of the claims, which included subsequences, mutants of

sequences and subsequences, and mixtures thereof, was overly broad. Even Enzo
Biochem's own expert testified that the claims covered an "astronomical"
number of variations.

126
Nevertheless, the court felt that it is conceivable a

skilled person may readily understand whether any variations are viable.
Because the level ofskill is a question offact, the court remanded the issue to the

lower court for evaluation of "whether a person of skill in the art would glean

from the written description, including information obtainable from the deposits

of the claimed sequences, subsequences, mutated variants, and mixtures

sufficient to demonstrate possession of the generic scope of the claims."
127

With respect to the second issue, the Enzo II court briefly compared this case
to Lilly, as both involved broad claims to a genus.

128
Looking at the USPTO's

Synopsis of Application of the Guidelines, which includes a hypothetical

example similar to the Lilly case,
129

the court described a contrasting example

involving the use of hybridization properties to satisfy the written description

requirement.
130

Enzo Biochem argued that the functional description of
hybridization coupled with the deposit met the written description requirement.

131

Relying on the USPTO's analysis of hybridization claims in the Synopsis of
Application example, the court held that there was a genuine issue of material

fact regarding whether Enzo Biochem's claims met the written description

requirement, thereby reversing the district court' s grant ofsummaryjudgment for

122. Id. at 965-66.

123. Id. at 966 (referring to U.S. Patent No. 4,900,659 (issued Feb. 13, 1990), col. 3,

11. 40-46).

124. Id. at 970.

125. Id. at 961.

126. Id. at 966.

127. Id.

128. Id. at 967 (citing Regents of Univ. of Cal. v. Eli Lilly & Co., 1 19 F.3d 1559 (Fed. Cir.
1997)).

1 29. Example 1 7: Genus-species with widely varying species. Synopsis ofApplication, supra

note 1, at 61-64.

130. Enzo, 323 F.3d at 967 (citing Example 9: Hybridization, Synopsis ofApplication, at

35-37).

131. Id. at 967-68.



484 INDIANA LAW REVIEW [Vol. 37:467

the defendants.
132 The court remanded the issue to the lower court to "consider

whether one of skill in the art would find the generically claimed sequences
described on the basis of Enzo[ Biochem]'s disclosure of the hybridization

function and an accessible structure, consistent with the PTO Guidelines. If so,
the written description requirement would be met."

133

To conclude, the court discussed the relationship among possession,
reduction to practice, and the written description requirement. Stressing that a

difference exists, the court emphasized that the written description requirement

"is not subsumed by the 'possession' inquiry. A showing of 'possession' is
ancillary to the statutory mandate . . . and that requirement is not met if, despite

a showing of possession, the specification does not adequately describe the
claimed invention."

134 Nor does reduction to practice, without an adequate
description of the invention that was reduced to practice, suffice to describe or
identify the invention under the written description requirement.

135
Noting that

possession and reduction to practice are particularly useful when claiming
priority to an earlier date of filing or invention, the court emphatically pointed

out that an adequate written description is still required. "Such description is the

quidpro quo ofthe patent system; the public must receive meaningful disclosure
in exchange for being excluded from practicing the invention for a limited period

oftime.'"
36

On the same day, the court published the order denying rehearing ofthe case
en banc.

nl
Several ofthejudges attached statements to the order explaining why

they voted either for or against en banc rehearing.
138

Strangely, the commentary

focused largely on the difference, or lack thereof, between the written description

requirement and the enablement requirement of § 112, first paragraph.
139

The dissent voted to rehear the case en banc. 140 Writing for the dissent,
Judge Rader argued that the case should not be remanded to determine whether

the patentee met the written description requirement.
141

According to Rader, the

patentee met the Vas-Cath "possession" test for the written description

requirement by depositing the DNA sequences. 142 Judge Rader expounded upon
his understanding that the written description requirement is not separate from

the enablement requirement by providing a history of written description case

law and describing the factual scenarios under which the court has addressed the

132. /d. at 968.

133. Id.

134. Id. at 969.

135. Id.

136. Id. at 970.

137. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 U.S.P.Q.2d 1618, 1618 (Fed. Cir. 2002).

138. Id. at 1618-33.

139. Id.

140. Id. at 1622-23 (Rader, J., dissenting).

141. Id. (Rader, J., dissenting).

142. Id. (Rader, J., dissenting).



2004] ENZO BIOCHEM V. GEN-PROBE 485

written description requirement.
143

Contrasting Enzo to prior cases, he noted that
Enzo did not involve new matter or priority issues—the types of issues that had
previously been addressed in written description requirement cases.

144 He
warned that both Lilly and Enzo, by supplanting the enablement requirement with
a more arduous written description requirement that is not required by the statute,
threaten to disrupt settled expectations in the inventing community by

u
up[ping]

the ante" required to comply with patentability requirements. 145

Disagreeing with the dissent, Judge Lourie argued that the case should not

be heard en banc merely for the purpose of revising written description law
because "[t]hat law is sound."

146
Reiterating the essence of Vas-Cath, he

emphasized that enablement and written description are separate and distinct,
pointing out the United States Supreme Court's substantiation of a distinct
written description requirement in a recent case.

147
Although the written

description requirement has been "applied rigorously" in recent cases, Judge

Lourie expressed his belief that these cases have not been decided wrongly
because they further the goal of requiring claims to be "commensurate in scope
with what has been disclosed to the public," 148 thereby avoiding overly broad
claims.

In response to Judge Rader' s averment that the written description

requirement "operated solely to police priority,"
149

Judge Lourie explained that,

when trying cases, the court merely addresses the issues raised before them. That
the written description requirement arose in Enzo under different facts than
previous cases was mere evolution ofthe case law.

150
Nothing existed in the law

prior to Enzo to preclude written description cases from arising under situations
other than priority contests.

151

Furthermore, Judge Lourie countered the argument that recent written

description law "elevate[s] 'possession' to the posture of a statutory test of

patentability."
152 He explicated that although possession is a relevant factor for

determining whether an invention has been described, demonstrating possession

is not necessarily the same as providing a written description.
153

Just as written

description law has its critics, it also has advocates who support a robust
requirement

154
and the benefits it provides to the public.

155
According to Lourie,

143. Id. (Rader, J., dissenting).

144. Id. (Rader, J., dissenting).

145. Id. (Rader, J., dissenting).

146. Id. at 1619.

1 47. Id. (citing Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 736-37

(2002)).

148. Id. at 1620.

149. Id. at 1626.

150. Mat 1619.
151. Id.

152. Id. at 1620.

153. Id.

1 54. For critical evaluations ofwritten description law, see, for example, Janis, supra note 39,



486 INDIANA LAW REVIEW [Vol. 37:467

the court has "evolved a consistent body of [written description] law over a
number of years, based on the statute and basic principles of patent law." 156

Thus, there is no reason to rehear Enzo en banc and "rewrite the statute."
157 To

do so would simply delay and frustrate the remand.
158

IV. The Errors of Enzo II

A. Dealing with Deposits

Enzo II does not comport with the written description requirement. Over at
least the past twenty years, as technology has advanced, the law has been

evolving toward more stringent criteria for satisfying the written description
requirement. Federal Circuit cases such as Vas-Cath, Fiers, and Lilly have more
sharply defined what is required to comply with the statute: a separate and
distinct description of the invention that indicates to a skilled artisan that the

inventor was in possession of the invention at the time of filing, 159 described by
more than just function ofthe invention or the method of making and using it, 160

and that endows the skilled artisan with the ability to visualize the identity ofthe
invention.

161 By holding that the deposit of molecules into a public depository
meets the written description requirement, Enzo II deviates from the requirement

that a written description of the invention appear in the patent disclosure.

The only "descriptions" of the DNA sequences claimed in the '659 patent
were the ATCC accession numbers and the function ofthe sequences. Although
the accession number is a unique identifier for a sample, it does not correlate to
the structure, function, or any other characteristic specific to that sample; it is

merely an ordinal number assigned to the sample for tracking it. The Court of
Appeals for the Federal Circuit recognized this in the 1985 case In re Lundak,

where the court found, "An accession number and deposit date add nothing to the
written description of the invention. They do not enlarge or limit the
disclosure."

162
Yet, in Enzo II, the court justified the variance from Lundak by

at 59; Mueller, supra note 39; Rai, supra note 5 1 ; and Harold D. Wegner, An Enzo White Paper:

A New Judicial Standardfor a Biotechnology "Written Description" Under 35 U.S.C. § 112,^1,
1 J. MARSHALL REV. INTELL. PROP. L. 254 (2002). But see Margaret Sampson, The Evolution of

the Enablement and Written Description Requirements Under 35 U.S.C. §112 in the Area of
Biotechnology, 1 5 BERKELEY TECH. LJ. 1233 (2000); Stewart, supra note 37, at 542-46; Scott A.

Chambers, "Written Description" and Patent Examination Under the U.S. Patent and Trademark

Office Guidelines, IP LITIGATOR, Sept.-Oct. 2000, at 9-10.

155. Enzo, 63 U.S.P.Q.2d at 1620-21.

156. Id at 1622.

157. Id

158. /c/. at 1618.

159. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991).

1 60. Fiers v. Revel, 984 F.2d 1 1 64, 1 1 7 1 -72 (Fed. Cir. 1 993).

161. Regents of Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997).
162. 773 F.2d 1216, 1223 (Fed. Cir. 1985).



2004] ENZO BIOCHEM V. GEN-PROBE 487

noting that deposits are often used to meet the enablement requirement "[w]here

the invention involves a biological material and words alone cannot sufficiently
describe how to make and use the invention in a reproducible manner" 163 and
stating that the '659 patent sequences "may not have been reasonably obtainable
and in any event were not known to Enzo when it filed its application." 164 The
court references a statement in the '659 patent which describes the time-intensive
procedure required to sequence the genome of Neisseria gonorrhoeae and
Neisseria meningitidis}

65

However, the '659 patent does not claim DNA of either Neisseria
gonorrhoeae or Neisseria meningitidis. Instead, it claims the DNA ofprobes that
hybridize to those bacteria.

166
Probes are typically much smaller than the DNA

with which they seek to hybridize. Accepting Enzo Biochem's statements that
sequencing large DNA is labor- and time-intensive, the smaller probes should
require much less time to sequence. Furthermore, most probes are synthetic
constructs that are synthesized to have a specific sequence. This suggests that

Enzo Biochem should have known the sequences ofthe probes they generated to
selectively hybridize to the bacteria, especially since the sequences of the

bacteria were at least partially known.
167

Accordingly, the DNA sequences of at
least the three deposited probes should have been "reasonably obtainable" to

Enzo Biochem, even at the time of filing the patent application. In that case,
allowing the deposits to comply with the written description requirement rather

than requiring that the probes be sequenced is not in accordance with patent law

or the public policy behind it.

Moreover, the court could have simply clarified the meaning of possession.

Vas-Cath established that the inventor must convey, to those skilled in the art,

that he was in possession of the invention when the patent application was
filed.

168
Yet, the application may include a constructive reduction to practice,

meaning that the inventor has not yet made the invention but has disclosed how
it will be made and used. In light of this, it is evident that possession does not
necessarily imply tangible possession. Instead, it is related to conception;

possession means that, in the least, the inventor possesses knowledge and
understanding of his final and complete invention. Note that intangible

possession must be differentiated from a mere wish or research plan; the inventor

does not have possession until he knows the precise composition that he will
eventually reduce to practice.

Enzo Biochem could not have met the possession test under these criteria.

1 63. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 965 (Fed. Cir. 2002) (quoting U.S.

Dep't of Commerce, Manual of Patent Examining Procedure § 2402 (Magdalen Y.C.

Greenliefed., 8th ed. 2001)).

164. Id. at 966.

165. U.S. Patent No. 4,900,659 (issued Feb. 13, 1990), col. 3, 11. 40-46.

166. Id. at col. 27, 1. 29 to col. 28, 1. 56.

167. Enzo Biochem, Inc. v. Gen-Probe, Inc., 285 F.3d 1013, 1026 (Fed. Cir. 2000) (Dyk, J.,

dissenting), vacated, 323 F.3d 956 (Fed. Cir. 2002).

168. 935 F.2d 1555, 1563-64 (Fed. Cir. 1991).



488 INDIANA LAW REVIEW [Vol. 37:467

It is true that the patentee had physical possession of the materials that it

deposited. Nevertheless, it did not have mental possession of its invention. Enzo
Biochem was not able to describe the invention that it deposited and claimed it
was because it had not sequenced the invention. In effect, the inventors had
actually reduced the invention to practice without having conceived what the
invention truly was. Until conception was achieved, Enzo Biochem's invention
was not complete or patentable.

By reversing the holding of Enzo I and allowing the deposit to meet the
written description requirement, the court disregarded the public policy behind

the possession test. Possession is required to ensure that the inventor actually

invented what he claims to have invented. If he does not possess the invention,

then he cannot describe the invention. Accordingly, written description is one

measure ofpossession. When the court allowed Enzo Biochem to use its deposit
to meet the written description requirement, it did not ensure that the inventor
was in mental possession ofthe invention. There was no measure ofwhether the
inventor knew what he had invented or not. The court simply knew that Enzo
Biochem reduced the invention to practice, with or without conception.
Permitting this type of"unknown invention" does not provide the public with the
quidthat it must get in return for giving patent term exclusivity to Enzo Biochem.

The "unknown invention" may be harmful to the public in several ways.
First, the public will be unaware of the metes and bounds of the invention. A
prospective inventor, searching the patent literature, may not find the '659 patent
unless he is looking for the same function as claimed by that patent {viz.,

selective hybridization to N. gonorrhoeae). Without finding the '659 patent, he

could invent another use for the claimed sequences, thereby unintentionally

infringing the patent claiming the sequences. Yet, if the sequences were

available in the patent literature, the prospective inventor could search sequence

databases, find the '659 patent, and avoid infringement.

Second, if the prospective inventor does find the '659 patent, he will not be

able to determine the scope of the claims unless he orders the deposits and

analyzes the DNA sequences. Even Judge Lourie felt that this would not accord
with public policy, as evidenced by his statement in Enzo I, "[T]o require the

public to go to a public depository and perform experiments to identify an

invention is not consistent with the statutory requirement to describe one's

invention in the specification."
169

Just over four months later, Judge Lourie

reversed that holding,
170

but he still indicated that "claims [were] being asserted

to cover what was not reasonably described in the patent."
171

Although one

commentator suggests that the "panel had no choice . . .,"
172

the sudden change

169. Enzo, 285F.3dat 1021.

170. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 966 (Fed. Cir. 2002).

171. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 U.S.P.Q.2d 1618, 1619 (Fed. Cir. 2002).

172. Harold C. Wegner, When a Written Description Is Not a "Written Description": When

Enzo Says It 's Not, 1 2 FED. Cm. B.J. 271 , 273 (2002). Wegner suggests that the Supreme Court's

holding in J.EM AG Supply, Inc. v. Pioneer Hi-Bred Int 7, Inc., 534 U.S. 124 (2001) set precedent
with respect to deposits and the written description requirement. In J.E.M., the Court held that



2004] ENZO BIOCHEM V. GEN-PROBE 489

of opinion regarding deposits is most likely indicative of conflict among the
Court of Appeals for the Federal Circuit with respect to the written description

requirement. Whatever the reasoning for the reversal, in a situation like Enzo,

description by deposit does not meet the intended requirement for public

disclosure and merely frustrates the public policy behind granting a patent in the

first place.

Third, the unknown invention does not provide the USPTO with the
necessary information to perform patentability searches. Like a prospective

inventor, the USPTO must obtain a sample and sequence it. Without sequence
information, the USPTO cannot adequately determine whether the invention is
novel and non-obvious. Experimentation would add cost and delay, especially
considering that the USPTO does not have testing facilities to analyze samples.
Consequently, the patentability search cannot be performed effectively, further

harming the public.

B. Adoption oftheUSPTO's Standard

The Enzo II court took judicial notice of the USPTO's Written Description
Guidelines.

173 However, the court erred by implying, in dicta, that it also

deferred to the Synopsis ofApplication
174

ofthe Guidelines because the examples

therein are substantively flawed. Recall that the USPTO promulgated the
Guidelines and the Synopsis ofApplication after Lilly to assist USPTO personnel
in determining patent applicants' compliance with the written description

requirement.
175

Noting that the Guidelines are not binding as law, the Enzo II

court "adopt[s] the PTO's applicable standard for determining compliance with
the written description requirement."

176
Specifically, the court refers to three

examples from the Guidelines: hybridization, genus-species with widely varying

species, and antibodies.
177

1. Analysis ofthe Hybridization Example.—The hybridization example 178

seeds, which were deposited in a public depository, were patentable. Id. at 124. Wegner fails to

consider that a seed is much more complex than a simple nucleic acid sequence such as those in

Enzo. Case law has long held that complex structures may be enabled by deposit. Enzo, 323 F. 3d

at 965. Perhaps, for complex structures, deposition should also satisfy the written description

requirement. Nonetheless, a per se rule that any deposit satisfies the written description

requirement, no matter how simple the molecule is, does not protect public interest in disclosure

of inventions. Instead, such a rule would discourage sequencing any biomolecules.

173. Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1,

"Written Description" Requirement, 66 Fed. Reg. 1099 (Jan. 5, 2001).

1 74. Synopsis ofApplication, supra note 1

.

175. See discussion supra Part II.

176. Enzo, 323 F.3d at 964.

177. Examples 9, 17, and 16, respectively. Synopsis ofApplication, supra note 1, at 35-37,

59-64.

178. Example 9: Hybridization. Id. at 35-37.



490 INDIANA LAW REVIEW [Vol. 37:467

describes a patent specification that discloses a single cDNA (SEQ ID NO: l). 179

The cDNA encodes a protein that binds a specific receptor and stimulates a
certain activity.

180 The specification exemplifies the use of a complementary 1 81

strand to SEQ ID NO: 1 under highly stringent conditions to isolate nucleic acids
which encode proteins that bind the same receptor and stimulate the same activity
as above. The isolated nucleic acids are not sequenced, but their activity is
demonstrated.

182

The claim in the example is directed to "[a]n isolated nucleic acid that
specifically hybridizes under highly stringent conditions to the complement of
the sequence set forth in SEQ ID NO:l, wherein said nucleic acid encodes a
protein that binds to a dopamine receptor and stimulates adenylate cyclase

activity."
183

The USPTO's analysis indicates that SEQ ID NO:l is novel and
unobvious, and it is the only sequence disclosed within the scope ofthe claimed

genus—nucleic acids which hybridize to the complement of SEQ ID NO: 1 and
encode a protein with the specified activity. Yet, the USPTO asserts that because
the hybridization conditions are highly stringent, a skilled person would not
expect substantial variation among species within the scope of the genus. 184

"Thus, a representative number of species is disclosed, since highly stringent
hybridization conditions in combination with the coding function ofDNA and the
level of skill and knowledge in the art are adequate to determine that applicant

was in possession of the claimed invention."
185

According to the Synopsis of

Application, the invention in the hybridization example is adequately

described.
186

This analysis is incorrect for several reasons. First, a complementary strand

to SEQ ID NO: 1 is used as a probe. More likely than not, the target DNA will
not be the same length as the probe. The skilled artisan has no means of

determining, solely from hybridization, which strand is longer, the probe or the

target. Ifthe probe is longer, which nucleic acids on the probe bind with nucleic

acids on the target? Ifthe target is longer, at what location on the target does the

probe hybridize? One simply has no measure for length or binding location on
the target DNA by the mere fact that a probe hybridizes, even if it occurs under
highly stringent conditions.

Second, highly stringent conditions do not guarantee full complementarity.

One would have no means to determine which nucleic acids hybridize and which
ones do not. Moreover, for the nucleic acids that do not hybridize, there is no

179. The sequence identity number (SEQ ID NO) is the label by which DNA or protein
sequences listed in a patent application are identified. Each sequence is given an ordinal number.

1 80. Synopsis ofApplication, supra note 1 , at 35.

181. For every "T" in SEQ ID NO: 1 , the complement contains an "A" and vice versa; for every

"C" in SEQ ID NO: 1, the complement contains a "G" and vice versa.
1 82. Synopsis ofApplication, supra note 1, at 35.

183. Id. at 35-36.

184. /^.at36.

185. Id. at 36-37.

186. Id.



2004] ENZO BIOCHEM V. GEN-PROBE 49

1

way to know which nucleic acid is actually present in the sequence. Considering
the first and second points, the applicant has not described the structure of the

invention. He has no "mental picture of the structure" and thus has not yet
conceived of the invention as claimed.

187

Third, the specification contains no structure-function relationship, as

recommended by the Guidelines where minimal structure is disclosed. 188

Because only one structure was described, the skilled artisan probably would not
know which amino acids correlate to the activity. Accordingly, one would not
know which nucleic acids must be present to encode the functional protein and
which could be varied or deleted.

Fourth, a representative number of species is not disclosed. 189 Only one is
disclosed: SEQ ID NO: 1 . Other species are mere speculation because one cannot
know whether modifications of the disclosed specie will lead to the desired
activity. If not, then these species do not belong to the genus.

In light ofthese considerations, the hybridization example does not comport

with written description law. Instead, hybridization claims merely define a genus

by what the DNA does, not what it is. The claims are not limited to specific
metes and bounds but instead describe an unknown but potentially astronomical
number of compounds of unknown sequences and structures, yielding overly
broad claims.

Enzo Biochem deposited only three DNA sequences. 190 It did not sequence
those DNA, 191 and thus could not describe any characteristic feature of the
sequence. It could only describe the DNA by its function, the ability to hybridize
preferentially to N. gonorrhoeae over N. meningitidis. Yet, in the '659 patent

Enzo Biochem claimed all DNA that preferentially hybridizes in that manner,
including the three deposited sequences, subsequences, mutations of those

sequences and subsequences, and mixtures thereof.
192

Applying the USPTO's analysis of the hybridization example to Enzo, one
might conclude that any sequences, subsequences, or mutations that hybridize N
gonorrhoeae preferentially under highly stringent conditions would be

adequately described. However, as explicated earlier, this analysis would

provide no means for the skilled artisan to envision the length of the
subsequences or mutations that will remain functional. Moreover, only three

representative species were deposited.
193

These species were obtained using

DNA that had not been sequenced; thus, SEQ ID NOs: 1 and 2 (N gonorrhoeae
and N. meningitidis) were not known. Allowing this type of claim to satisfy the

written description requirement would yield extremely broad scope: billions of

187. See Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed. Cir. 1991).

188. Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112,

"Written Description" Requirement, 66 Fed. Reg. 1099, 1 106 (Jan. 5, 2001).

1 89. See Regents of Univ. of Cal. v. Eli Lilly & Co., 1 1 9 F.3d 1 559 (Fed. Cir. 1 997).
190. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 961 (Fed. Cir. 2002).

191. Id. at 966.

192. Mat 961-62.
193. Mat 961.



492 INDIANA LAW REVIEW [Vol. 37:467

DNA could be encompassed. Yet, coverage of that scope would be achieved
without requiring Enzo Biochem to sequence even one DNA ! That scope would
allow the inventor to claim more than he has actually invented, directly
contradicting the public policy of providing the inventor with patent scope that

is commensurate with his contribution to the art.
2. Analysis ofthe Antibody Example.—The antibody example 194 describes

a patent specification teaching that antigen X has been isolated and is useful for
detecting HIV. The specification teaches the method ofisolation and purification
of antigen X and provides a characterization of the antigen in the form of
molecular weight.

195 An example in the specification "contemplates but does not
teach" antibodies which specifically bind to antigen X and asserts that the
contemplated antibodies can be used in immunoassays to detect HIV.

196
The skill

of the art is that antibodies are structurally well characterized, and the constant

and variable regions from a variety of species have been published in the art.
197

A claim is made to "[a]n isolated antibody capable of binding to antigen
X."

198 The claim is directed to any antibody capable ofbinding the antigen. The
USPTO's analysis indicates that antibody-antigen binding technology is mature,
and the level of skill is high and advanced. Antigen X is novel and unobvious. 199

According to the USPTO, the skilled person considering all this would recognize
that the "spectrum of antibodies which bind to antigen X were implicitly
disclosed as a result ofthe isolation ofantigen X."

200
Therefore, the Synopsis of

Application asserts that the written description requirement is satisfied by this

disclosure in the specification.
201

The USPTO's analysis of the antibody example, like that for the
hybridization example, allows an overly broad claim to stand. Consequently, it,

too, is incorrect. Although the general structure ofantibodies is well understood

in the skill ofthe art, it does not follow that the antibody sequence is adequately

described. The antibody is divided into regions of alternating constant and
variable domains. The variable domains vary not only from species to species,

but also from member to member. In other words, one human might not produce
the exact same antibody against a given antigen as the next human would.202 One
antigen introduced into 100 different humans may produce 100 different
antibodies, all of which bind the same antigen and fall within the scope of the

claim.

One cannot readily hypothesize which amino acids will constitute the
variable region. The sequence of the antibody's variable region will depend

194. Example 16: Antibodies. Synopsis ofApplication, supra note 1, at 59-60.

195. Id. at 59.

196. Id.

197. Id.

198. Id.

199. Id. at 60.

200. Synopsis ofApplication, supra note 1 , at 60.

201. Id.

202. Janeway et AL., supra note 30, at 124.



2004] ENZO BIOCHEM V. GEN-PROBE 493

upon the location on the antigen to which it binds. Considering that proteins,

which can be conservatively substituted for one another, comprise an antibody,

the number ofpossible sequences that would bind to the antigen is astronomical.
Consequently, the structure or sequence of the antibody cannot be described

simply by knowing the antigen's sequence.

Applying written description case law to this example, the claim cannot

stand. First, the possession test cannot be met. The applicant did not make any
antibodies, nor did he conceive of any antibodies that could be described by a
method other than "any antibody, having a general antibody structure, which
functions in this way." One cannot merely claim to possess anything and
everything that works without being able to describe at least one structure or

sequence. With a claim of this scope, the applicant does not have a mental

picture of the structure and has not yet conceived the full invention covered by

the claims.
203

Second, no structure-function relationship is established.
204 The applicant

has not described any amino acids in the antibody that are complementary to and

that are responsible for the binding function of the antigen, assuming that the

antigen is a protein. Even ifthe antigen is not a protein, no structural information

can be surmised other than general concepts regarding polar attractions between

the antibody and antigen. In either case, no specific structure has been described.

Nor has any function been linked to any structure.
Considering the failure to meet the possession test and the lack ofa structure-

function relationship, such a broad antibody claim should not be permitted. It

simply does not describe the antibody with any particularity such that a skilled

person could visualize the invention. The claim is overly broad; any antibody

subsequently developed would be covered by the scope of this claim. Thus, it

does not preserve the public policy of allowing claims that are commensurate

with the scope of the invention. The applicant averring this claim is asserting
rights to any antibody that he may have discovered as well as any that will be
developed in the future. This type of protection is not in accordance with the

goals of the patent system.

C. Minimizing the Error ofEnzo II

In Enzo II, the Court ofAppeals for the Federal Circuit remanded the case to

the lower court to answer the questions offact: whether the hybridization claims

and the claims to non-deposited sequences of the '659 patent comply with the

written description requirement. To ensure an appropriate outcome, the lower

203. See Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed. Cir. 1991).

204. See Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1,

"Written Description" Requirement, 66 Fed. Reg. 1099, 1106 (Jan. 5, 2001) ("A biomolecule

sequence described only by a functional characteristic, without any known or disclosed correlation

between that function and the structure of the sequence, normally is not a sufficient identifying

characteristic for written description purposes, even when accompanied by a method of obtaining

the claimed sequence.").



494 INDIANA LAW REVIEW [Vol. 37:467

court needed to consider the technology associated with the Enzo case.
Unfortunately, "Enzo III" will not resolve these issues because the parties settled
the case out of court.

One major difference between Enzo and prior cases like Amgen, Fiers, and
Lilly is the technology. The prior cases involved relatively simple biotech issues
concerning descriptions of DNA or proteins within the scope of the claims.
Conversely, Enzo involved technology that is more complex. Enzo Biochem's
invention claimed DNA that hybridize to specific other DNA.205 Determining
whether that claim complies with the written description requirement demands
full understanding of the implications of hybridization—what structural
information can be inferred from hybridization under stringent conditions. The
science associated with hybridization is more technologically advanced than
merely determining whether the words "human insulin" adequately describe a
DNA sequence.206

Referring to the USPTO Guidelines and the Synopsis ofApplication ofthe
Guidelines, the Enzo court also discussed antibody technology.

207
Like

hybridization, the antibody field is more complex than the technology ofprevious

cases. In what may be regarded as dicta, the court addressed hybridization and
antibody technologies and then stated that it adopts the standards of the

Guidelines for determining compliance with the written description

requirement.

The complexity ofhybridization and antibody technologies has not been fully
considered and analyzed by the court. To ensure appropriate outcomes in future
cases with such complex technologies, the science relating to those technologies

should be thoroughly addressed. The court should consider factual assessments
controverting the examples in the Synopsis of Application,

209
and contrast

assessments in support thereof. Only then can the court accurately decide

whether deference to the Synopsis ofApplication is appropriate.

V. The Effect of Enzo II on Patent Practice and Biotechnology

A. A Post-Enzo Biotech Written Description Case: The TKT Case

Since Enzo, the Court ofAppeals for the Federal Circuit has decided another

biotech written description case, Amgen, Inc. v. Hoechst Marion Roussel, Inc.
210

205. U.S. Patent No. 4,900,659 (issued Feb. 13, 1990), Claims 1-3, at col. 27, 1. 29 to col. 28,

1.30.

206. Regents of Univ. of Cal. v. Eli Lilly & Co., 1 19 F.3d 1559, 1568 (Fed. Cir. 1997).
207. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).

208. Id.

209. See discussion supra Part IV.B.

210. 314 F.3d 1313 (Fed. Cir. 2003). To distinguish this case from Amgen, Inc. v. Chugai

Pharm. Co., 927 F.2d 1200 (Fed. Cir. 1991), the short citation for this case will be 'TAT." TKT
is used rather than Hoechst because most ofthe arguments revolve around Transkaryotic Therapies,

Inc.'s technology.



2004] ENZO BIOCHEM V. GEN-PROBE 495

This was a patent infringement case involving five patents, each being a
continuation

211
of the Amgen patent litigated in the 1991 case ofAmgen, Inc. v.

Chugai Pharmaceutical Co.
212

These patents broadly claimed compositions,

processes, or uses related to Amgen 's pioneering erythropoietin (EPO) product,
Epogen®. Epogen® was launched in 1 989,

213
and since that time, the product has

become a huge success, earning billions of dollars in sales. 214 When Hoechst
Marion Roussel and Transkaryotic Therapies (collectively "TKT") collaborated
to launch a competing product, HMR4396,215 Amgen filed a declaratory
judgment action against them,

216
alleging that HMR4396 infringed Amgen's

patents.
217

The main difference between Epogen® and HMR4396 is the production
technology. TKT's EPO product is produced through an innovative process
referred to as "endogenous" expression.

218
This process inserts a non-native

"promoter" upstream from the native EPO gene in human cells. This promoter
activates the gene to produce high amounts of EPO.219 Endogenous expression
was discovered approximately ten years after Amgen's patent priority date.220

Amgen's product is produced using "exogenous" expression.221 Amgen
introduces the EPO gene into Chinese hamster ovary (CHO) cells, a type of
mammalian cell, which use their own native processes to produce the human
EPO protein. Exogenously expressed EPO differs from native human EPO only
by the glycosylation pattern.

222

Amgen's patent claims did not specify endogenous or exogenous production,
but their patents exemplified only exogenous production.

223 TKT argued that the
Amgen patents did not meet the written description requirement because they

211. A "continuation" is a subsequently filed application having the same disclosure as the
previous application but introducing a new claim set or further right to prosecution. See U.S. Dep't

of Commerce, Manual of Patent Examining Procedure § 201.07 (Magdalen Y.C. Greenlief

ed., 8th ed. 2001). The continuations involved in the TKT litigation included U.S. Patent Nos.

5,955,422 (issued Sept. 21, 1999) (the '422 patent); 5,756,349 (issued May 26, 1998) (the '349

patent); 5,621,080 (issued Apr. 15, 1997) (the '080 patent); 5,618,698 (issued Apr. 8, 1997) (the

'698 patent); and 5,547,933 (issued Aug. 20, 1996) (the '933 patent). TKT, 314 F.3d at 1319-23.

212. 927 F.2d 1 200 (Fed. Cir. 1 99 1 ).

213. Epogen® Backgrounder, at http://www.amgen.com/product/epogen/epogenBackgrounder.

html (last visited Oct. 22, 2003).

214. Amgen, Inc. v. Hoechst Marion Roussel, Inc., 126 F. Supp. 2d 69, 77 (D. Mass. 2001).

215. Id. at 94.

216. TKT, 314F.3dat 1319.

217. Id. at 1324-25.

218. Id.

219. Mat 1325.
220. Id. at 1334.

221. Id. at 1321.

222. Glycosylation is the pattern of branched carbohydrate chains that bind to the protein

structure. Id. at 1321-22.

223. Id.



496 INDIANA LAW REVIEW [Vol. 37:467

failed to "sufficiently describe the use of all vertebrate and mammalian cells,"
and they excluded endogenous EPO DNA, both expressly and implicitly.224

As written description is a question of fact, the Court of Appeals for the
Federal Circuit examined the district court's finding for clear error.

225 The
District Court of Massachusetts rejected TKT's written description argument,
holding that TKT had proven Amgen's failure to meet the written description
requirement only by a preponderance of the evidence rather than by clear and

convincing evidence.
226 On appeal, TKT argued that it had indeed "clearly and

convincingly proven invalidity" under Lilly, Enzo II, and Gentry Gallery.
221

Judge Michel, writing for the majority, did not agree.
228

The TATcase provided the Court ofAppeals for the Federal Circuit a means
to discuss recent written description requirement cases. The court explained:

We held in Eli Lilly that the adequate written description of claimed
DNA requires a precise definition of the DNA sequence itself—not
merely a recitation of its function or a reference to a potential method for

isolating it. . . . More recently, in Enzo Biochem, we clarified that Eli
Lilly did not hold that all functional descriptions of genetic material

necessarily fail as a matter of law to meet the written description

requirement; rather the requirement may be satisfied if in the knowledge
ofthe art the disclosed function is sufficiently correlated to a particular,

known structure.229

The majority distinguished Lilly and Enzo II from TKT by explaining that
"the claim terms at issue here are not new or unknown biological materials that
ordinarily skilled artisans would easily miscomprehend."

230
Here, the terms

"vertebrate" and "mammalian" simply designate the types of cells used to

produce the EPO protein. In contrast, these terms in Lilly modified the
invention itself—the protein—an "undescribed, previously unknown DNA
sequence. . . ."

231 The TKTmajority agreed with the district court's holding that
the specification's description, which included two examples of vertebrate and

mammalian cells used, adequately supported claims to EPO produced by "the
genus vertebrate or mammalian cells."232

Moreover, the majority rejected TKT's argument that Gentry Gallery
233

requires essential elements ofan invention to be incorporated into patent claims.

224. Id. at 1331.

225. Id. at 1330.

226. Amgen, Inc. v. Hoechst Marion Roussel, Inc., 126 F. Supp. 2d 69, 101 (D. Mass. 2001 ).

227. r/Cr, 314 F.3dat 1331.

228. Id.

229. Id. at 1332 (citations omitted).

230. Id.

231. Id.

232. Id.

233. Gentry Gallery, Inc. v. Berkline Corp., 134 F.3d 1473 (Fed. Cir. 1998).



2004] ENZO BIOCHEM V. GEN-PROBE 497

TKT argued that Amgen's use of certain terms234 in the specification as well as
representations made during patent prosecution limited the scope of Amgen's
claims to exogenously produced EPO.235 TKT alleged that exogenous expression
was an essential element of Amgen's invention and thus should be required to
limit the claims.

236

The majority disagreed. It stressed that, despite popular opinion, Gentry
Gallery did not introduce an "essential elements" test but instead applied "the

settled principle that a broadly drafted claim must be fully supported by the
written description and drawings."

237
According to the court, Amgen's

statements, unlike Gentry's, did not indicate "that exogenous expression is the

only possible mode ofthe invention or that other methods were outside the stated
purpose ofthe invention."

238
Furthermore, the court "cannot invalidate a patent

for failure to describe a method ofproducing the claimed compositions that is not
itself claimed," especially considering that the other method was not developed
until ten years after the patent application was filed.239 Thus, the majority held
the district court was not clearly erroneous in its finding that Amgen's patents
satisfied the written description requirement.

240

The dissent, written by Judge Clevenger, strongly disagreed with the
majority's written description decision. Judge Clevenger asserted that the issue

is "whether Amgen's disclosure of one means of producing synthetic EPO in
mammalian cells, namely exogenous DNA expression, entitles it to claim all
EPO produced by mammalian cells in culture, or all cultured vertebrate cells that
produce EPO."241 Yet, the district court and the majority refused to consider this
issue because the asserted claims were directed to compositions, not processes.

242

Judge Clevenger emphasized that claim limitations that are essential to

patentability must comply with the written description requirement of § 1 12, first

paragraph.
243

Here, the majority allowed composition claims to stand with

modifiers such as "non-natural ly occurring" and "purified from mammalian cells
grown in culture" without requiring compliance. According to Judge Clevenger:

The majority holds that patentees are free to decorate their composition
claims with source and process limitations without any concern for

whether the full scope of those limitations is enabled or described, and

234. Terms included statements such as the following: the advantage of Amgen's invention

was "freedom from association with human proteins" and the invention was "uniquely

characterized" by exogenous expression. TKT, 314 F.3d at 1331.

235. Id. at 1331.

236. Id.

237. Id. at 1333.

238. Id.

239. Id. at 1334.

240. Id.

241

.

Id. at 1359 (Clevenger, J., dissenting).

242. Id. (Clevenger, J., dissenting).

243. Id. (Clevenger, J., dissenting).



498 INDIANA LAW REVIEW [Vol. 37:467

that these requirements of section 1 1 2 are waived so long as the patentee

succeeds in characterizing its claims as "product" claims. Competent
patent attorneys should be quick to take advantage of the majority's

broad exemption from the disclosure requirements by the appropriate
phraseology. Rather than endorse the district court's elevation of form

over substance, I would vacate its decision . . . and remand for further
consideration in light of the vast scope of the claims in suit for which

there appears to be insufficient . . . written description.
244

Furthermore, Judge Clevenger disagreed with the majority's opinion that

Lilly and Gentry Gallery did not apply to this case.
245 He asserted that by

dismissing Lilly, the majority "verges on confining [Eli] Lilly to its facts."
246

Gentry Gallery, he argued, is inescapably parallel: the claims recite elements

readily found in the specification but did not include limitations on the

"arrangement" of the elements. The Amgen patents did not include the
arrangement of "the non-human control sequences and coding DNA ... on an
exogenous expression vector in the cell."

247
According to Judge Clevenger, the

majority's holding allows claims to "become more resistant to written description

challenges the more broadly drafted they are."
248

B. Analysis o/TKT and the Effect ofEnzo on Written Description Law

The inflection point where the robust requirement for written descriptions
changed direction appears to be the reversal of Enzo I. Up to that point, much
dissension was noted among patent practitioners with respect to case law,
especially after the Lilly case.

249
Yet, the strong conflict ofopinions in the Court

of Appeals for the Federal Circuit concerning written description law did not

become apparent until the denial of the en banc hearing for Enzo I. 250 At that
time, written description law seems to have changed. The balance between
public disclosure and exclusivity for the inventor shifted from a position

emphasizing public disclosure to a position emphasizing inventors' needs.

From Vas-Cath through Lilly, the court stressed the importance ofdescribing
the full scope of the claims. This precedent required that the description be

sufficient to allow the ordinarily skilled artisan to recognize that the applicant

invented what was claimed.
251

Evidence of conception—a mental picture ofthe
invention—must be present.252 The invention must be described by more than

244. Id. at 1359-60 (Clevenger, J., dissenting).

245. Id. at 1360-61 (Clevenger, J., dissenting).

246. Id. at 1361 (Clevenger, J., dissenting).

247. Id. (Clevenger, J., dissenting).

248. Id. (Clevenger, J., dissenting).

249. See supra note 1 54.

250. See discussion supra Part III.C.

251. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991).

252. See Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed. Cir. 1991).



2004] ENZO BIOCHEM V. GEN-PROBE 499

mere function.
253 The description cannot be a simple wish or research plan, but

instead must be a description that has definite boundaries, such that the members
of the genus can be visualized or recognized.

254 By requiring that the
specification include a written description ofthe sequences deposited to comply
with the requirement,

255
Enzo I followed this line of precedent.

With the reversal ofEnzo I, written description law appears to have veered
away from precedent. Enzo II allowed incorporation by reference of three
deposited sequences to serve as written description ofthose species.

256
This does

not follow precedent because, without physically obtaining samples from the

depository and sequencing them, the skilled artisan would have no way to
visualize the boundaries. Enzo Biochem or the USPTO could not visualize the
boundaries either. The court's comment that the sequences were not obtainable
to Enzo Biochem is no justification for this exception to precedent. These
molecules were small enough that they could have been readily sequenced.

257
It

appears that the court made a decision to relax the written description
requirement. Then, by adopting the USPTO's standard for determining
compliance with the written description requirement in the Synopsis of
Application, the Enzo II court suggested that it may allow extremely broad claims
to stand—claims to compositions whose structures are not described anywhere
in the patent.

258
This is certainly not in accordance with precedent.

The Court of Appeals for the Federal Circuit confirmed this change in
philosophy toward the written description requirement in the TKT case.
Although the court stated, "A broadly drafted claim must be fully supported by
the written description and drawings," it allowed Amgen to have very broad
scope of its patent claims.

259
Despite limitations in the claims, the court granted

interpretations of the limitations that went beyond descriptions in the

specification itself. TKT challenged the court to apply precedent to Amgen's
patents, precedent that would require a robust description of the entire claimed

invention, limitations included. Yet, the court refused to apply the precedent.

By doing so, the court effectively limited the precedent to its facts, thereby
allowing broad scope of the claimed invention and contradicting the written

description requirement of cases like Fiers and Lilly.

TKTdemonstrates the derogation ofpublic policy associated with permitting

broad patent claims. Even though the method ofendogenous expression was not

developed until ten years after Amgen filed its patent application, the scope of
its claims were so broad that they covered all methods of expressing EPO in
mammalian and vertebrate cells. TKT's advancement ofthe technological field,

253. See Fiers v. Revel, 984 F.2d 1 164, 1 169 (Fed. Cir. 1993).

254. See Regents of Univ. of Cal. v. Eli Lilly & Co., 119F.3d 1559, 1568 (Fed. Cir. 1997).
255. Enzo Biochem, Inc. v. Gen-Probe, Inc., 285 F.3d 1013, 1023 (Fed. Cir.), vacated, 323

F.3d 956 (Fed. Cir. 2002).

256. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 965-6 (Fed. Cir. 2002).

257. See discussion supra Part IV. A.

258. Enzo, 323 F.3d at 967.

259. Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1333 (Fed. Cir. 2003).



500 INDIANA LAW REVIEW [Vol. 37:467

through the development of the endogenous expression method, was found to
infringe Amgen's patent.

260
That holding of infringement will prevent TKT's

product from being marketed, resulting in a lack ofcompetition which will likely
keep Epogen®'s price at its current level. Additionally, litigation is tremendously

expensive; Amgen may even have to raise its price to pay costs. Moreover, TKT
may have nothing more than litigation expenses and trial experience to show for
its advancement of the technology. Considering that Amgen never produced or
even conceived of producing EPO using the endogenous method, the negative
impact on the economic investment and subsequent fallout cannot be justified.

Conclusion

Patent protection of biotech inventions is essential to provide incentive for

investment and development. To date, biotech inventions have proven to be
extremely useful as medical diagnostics, pharmaceutical treatments and

prophylaxes, and much growth of the industry is expected to continue in the
future.

261

Yet, to ensure continued growth, patent protection must be provided that is
commensurate with the contribution of the invention to the art. The written
description requirement is one means of assurance. By strictly requiring written
description of the invention, the public is guaranteed that the inventor was in
possession of the invention when the patent application was filed. In effect, the
written description defines the scope ofthe invention—the metes and bounds that
will be given exclusivity. The scope should be neither too narrow nor too broad.

The USPTO Synopsis ofApplication ofthe Written Description Guidelines
represent very broad, relaxed interpretations ofthe law for biotech patent claims.

They allow the inventor to satisfy the written description requirement by
providing very little contribution to the skill of the art. Indeed, in the

hybridization and antibody examples, the inventor need not provide any

structural information for the actual invention.
262

Such broad scope is in direct

conflict with the public policies ofadvancing science, improving healthcare, and

promoting industrial growth. Enforcement of these overreaching claims would

be devastating to the field of biotechnology.

Cases such as Enzo II, which defers to the broad claim interpretation of the

Guidelines, and TKT, which seems to limit Lilly and Gentry Gallery to their facts,

evidence a change in the stringent requirement for written description. Rather

than allowing moderate claim scope that is proportional to contribution, the court

appears to be moving toward allowing broad, overreaching claims. This change
in direction will lead to even more confusion in an already unsettled area of

patent law, leaving the patent practitioner to guess how to satisfy the written
description requirement.

Nonetheless, litigation over the written description requirement continues.

260. Mat 1358.
261

.

Das, supra note 26, at 14.

262. See Synopsis ofApplication, supra note 1, at 35-37, 59-60.



2004] ENZO BIOCHEM V. GEN-PROBE 501

Hopefully, the courts will thoroughly consider the complexity of technology in

the current cases and reevaluate the Synopsis of Application of the Written
Description Guidelines. Results at the district court level for the Rochester

case
263

indicate a possible return to moderation ofclaim scope. Yet, the ultimate

standard for written description remains unresolved until future cases like Enzo
III and Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. 264 are decided.

263. Univ. of Rochester v. G.D. Searle & Co., Inc., 249 F. Supp. 2d 216 (W.D.N.Y. 2003).
See introductory discussion supra.

264. AriadAnnounces Filing ofLawsuitAgainst Eli Lilly Alleging Infringement ofPioneering

NF-KB Treatment-Method Patent, at http://media.corporate-ir.net/media_files/nsd/aria/releases/

062502-2.pdf.