In Re Gleave

United States Court of Appeals for the Federal Circuit

2008-1453
(Serial No. 10/346,493)

IN RE MARTIN GLEAVE and MAXIM SIGNAEVSKY

Marina T. Larson, Marina Larson & Associates, LLC, of Dillon, Colorado, argued
for appellants.

Mary L. Kelly, Associate Solicitor, Solicitor’s Office. United States Patent and
Trademark Office, of Arlington, Virginia, argued for the Director of the United States
Patent and Trademark Office. With her on the brief was Frances M. Lynch, Associate
Solicitor. Of counsel was Raymond T. Chen, Solicitor.

Appealed from: United States Patent and Trademark Office
Board of Patent Appeals and Interferences
 United States Court of Appeals for the Federal Circuit

2008-1453
(Serial No. 10/346,493)

IN RE MARTIN GLEAVE and MAXIM SIGNAEVSKY

Appeal from the United States Patent and Trademark Office, Board of Patent Appeals
and Interferences.

__________________________

DECIDED: March 26, 2009
__________________________

Before MICHEL, Chief Judge, PROST and MOORE, Circuit Judges.

PROST, Circuit Judge.

Martin Gleave and Maxim Signaevsky (collectively, “Gleave”) filed U.S. Patent

Application No. 10/346,493 (“’493 application”) on January 17, 2003. The examiner

rejected claims 1, 4, 15, and 18–21 as indefinite under 35 U.S.C. § 112, ¶ 2 and as

anticipated or obvious under 35 U.S.C. § 102(b)/103(a). The United States Patent and

Trademark Office Board of Patent Appeals and Interferences (“Board”) reversed the

examiner’s § 112, ¶ 2 rejection and affirmed the § 102(b)/103(a) rejection. Ex parte

Gleave, No. 2007-4154, 2008 WL 867799 (B.P.A.I. Mar. 31, 2008). Gleave appeals the

§ 102/103 rejections. For the reasons set forth below, we affirm.
 BACKGROUND

Gleave’s ’493 application is entitled “Bispecific Antisense Olignucleotides [sic]

that Inhibit IGFBP-2 and IGFBP-5 and Methods of Using Same.” 1 The claims are based

on the understanding that certain antisense oligodeoxynucleotides can simultaneously

bind to and prevent the translation of mRNA into two types of human Insulin-Dependent

Growth Factor Binding Protein (“IGFBP”). The application claims antisense

oligodeoxynucleotides, methods of making pharmaceutical compounds containing the

oligodeoxynucleotides, and methods of treating endocrine-regulated cancers by using

the oligodeoxynucleotides to prevent the formation of IGFBP-2 and IGFBP-5. The

examiner rejected claims 1, 4, 15, and 18–21, all of which were composition claims

directed to antisense oligodeoxynucleotides.

The Board selected claims 1 and 4 as representative. Claim 1 recites

[a] bispecific antisense oligodeoxynucleotide, wherein substantially all of
the oligodeoxynucleotide is complementary to a portion of a gene
encoding human IGFBP-2 and substantially all of the oligodeoxynucleotide
is also complementary to a gene encoding human IGFBP-5, and wherein
the oligodeoxynucleotide is of sufficient length to act as an antisense
inhibitor of human IGFBP-2 and human IGFBP-5.

1
We described antisense technology in greater detail in Enzo Biochem, Inc.
v. Calgene, Inc., 188 F.3d 1362 (Fed. Cir. 1999), and thus only give a brief overview for
purposes of this opinion. In double-stranded deoxyribonucleic acid (“DNA”), only
particular segments (called genes) actually encode proteins. Typically, this double-
stranded DNA is “transcribed” into messenger ribonucleic acid (“mRNA”), which is
complementary to one strand of the DNA. This mRNA then moves into the ribosome,
where the mRNA is “translated” into a series of amino acids. Together, these amino
acids form a single protein. Antisense technology is used to interrupt this process,
thereby preventing certain proteins from being synthesized by the cell. Short segments
of single-stranded DNA (called oligodeoxynucleotides) that are complementary to the
mRNA are introduced, and physically bind to the mRNA. This prevents the mRNA from
being translated into a protein. Some of these oligodeoxynucleotides are “bispecific,”
meaning that they can bind to mRNAs transcribed from two distinct genes and prevent
the formation of both proteins.

2008-1453 2
Claim 4 recites “[t]he antisense oligodeoxynucleotide according to claim 1, wherein the

oligodeoxynucleotide consists essentially of a series of bases as set forth in any of Seq.

ID. Nos. 3 through 7.” Those sequences range from eighteen to twenty-two DNA bases

in length. Before the examiner, Gleave elected Sequence No. 5, a twenty-base

oligodeoxynucleotide. The specification notes that the invention does not exclude

“minor modifications in sequence, such as the addition of one or two terminal bases, or

single base substitutions which might depart from perfect complementarity.”

The examiner initially rejected the claims over the published PCT application

00/78341 of Wraight et al. (“Wraight”). In Wraight, the applicants listed every fifteen-

base-long sense oligodeoxynucleotide in the IGFBP-2 gene. The list includes more

than 1400 sequences. Wraight also disclosed the general concepts that antisense

oligonucleotides are preferably between fifteen and twenty-five bases in length, and that

some antisense oligonucleotides may be bispecific (i.e., capable of inhibiting “an IGFBP

such as IGFBP-2 and/or IGFBP-3”). Finally, Wraight states that “[a]ntisense

oligonucleotides to IGFBP-2 may be selected from molecules capable of interacting with

one or more” of the sense oligonucleotides described in the long list.

The Board found that to anticipate claim 1, the prior art had to describe an

oligodeoxynucleotide of sufficient length to act as an antisense inhibitor to human

IGFBP-2 and IGFBP-5, and substantially all of the oligodeoxynucleotide had to be

complementary to a portion of the gene encoding human IGFBP-2 and complementary

to the gene encoding human IGFBP-5. The Board found that Wraight satisfied these

requirements and anticipated the claims. The Board also affirmed the § 103 rejection.

2008-1453 3
 The issue presented on appeal, therefore, is whether a reference that lists every

fifteen-base sense oligodeoxynucleotide in a known nucleic acid sequence anticipates

or renders obvious claims to specific antisense sequences having particular properties.

We have jurisdiction over the appeal under 28 U.S.C. § 1295(a)(4)(A).

DISCUSSION

As an initial matter, the parties disagree over the proper standard of review.

Under 35 U.S.C. § 102(b), a patent applicant cannot receive a patent if the invention

was “described in a printed publication in this or a foreign country . . . more than one

year prior to the date of the application for patent in the United States.” Gleave claims

that the issue at hand is “in essence” one of statutory construction (i.e., what a

reference must disclose to “describe” an invention under § 102(b)); thus, Gleave argues

we should review the Board’s decision de novo. 2 Yet Gleave has not unearthed for us

some previously hidden requirement for a reference to anticipate an invention under

§ 102(b).

A reference is anticipatory under § 102(b) when it satisfies particular

requirements. First, the reference must disclose each and every element of the claimed

invention, whether it does so explicitly or inherently. Eli Lilly & Co. v. Zenith Goldline

Pharms., Inc., 471 F.3d 1369, 1375 (Fed. Cir. 2006). While those elements must be

“arranged or combined in the same way as in the claim,” Net MoneyIN, Inc. v. VeriSign,

Inc., 545 F.3d 1359, 1370 (Fed. Cir. 2008), the reference need not satisfy an ipsissimis

2
The PTO argued that Gleave “waived review of the legal issue he now
asserts by failing to raise it before the Board.” We disagree. The entire thrust of
Gleave’s brief on appeal to the Board was the “significance” of Wraight’s disclosure in
an anticipation analysis. Gleave argued this position as early as his first office action
response on March 12, 2005.

2008-1453 4
verbis test, In re Bond, 910 F.2d 831, 832–33 (Fed. Cir. 1990). Second, the reference

must “enable one of ordinary skill in the art to make the invention without undue

experimentation.” Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, 1314 (Fed.

Cir. 2008); see In re LeGrice, 301 F.2d 929, 940–44 (CCPA 1962). As long as the

reference discloses all of the claim limitations and enables the “subject matter that falls

within the scope of the claims at issue,” the reference anticipates—no “actual creation

or reduction to practice” is required. Schering Corp. v. Geneva Pharms., Inc., 339 F.3d

1373, 1380–81 (Fed. Cir. 2003); see In re Donohue, 766 F.2d 531, 533 (Fed. Cir. 1985).

This is so despite the fact that the description provided in the anticipating reference

might not otherwise entitle its author to a patent. See Vas-Cath Inc. v. Mahurkar, 935

F.2d 1555, 1562 (Fed. Cir. 1991) (discussing the “distinction between a written

description adequate to support a claim under § 112 and a written description sufficient

to anticipate its subject matter under § 102(b)”).

As this summary makes clear, the outcome in this case depends largely on the

facts. After all, anticipation is a question of fact, including whether an element is

inherent in the prior art. Eli Lilly, 471 F.3d at 1375. And as with 35 U.S.C. § 112,

“[w]hether a prior art reference is enabling is a question of law based upon underlying

factual findings.” Minn. Mining & Mfg. Co. v. Chemque, Inc., 303 F.3d 1294, 1301 (Fed.

Cir. 2002). We review the Board’s factual determinations for substantial evidence. In re

Gartside, 203 F.3d 1305, 1315 (Fed. Cir. 2000). The Board’s legal conclusions, on the

other hand, we review de novo. In re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004).

A

Gleave frames the issue presented for review as “the meaning of the term

2008-1453 5
‘described’ in 35 U.S.C. § 102(b) and the type of disclosure that is therefore required for

a reference to be anticipatory.” Specifically, Gleave claims that “Wraight does not

describe any particular individual antisense species,” because Wraight merely gives the

public “ink, formed into strings of letters, without inventive thought and without placing

the public in possession of anything new. There is no guidance to make particular

selections, and no understanding of which of the targets would be useful, and what the

properties of the related antisense would be.”

We have at times framed the issue of enablement under § 102 as a question of

whether one of ordinary skill in the art would know how to “make and use” the invention

based on the reference’s disclosure. See, e.g., Impax Labs., Inc. v. Aventis Pharms.,

Inc., 468 F.3d 1366, 1381 (Fed. Cir. 2006) (“[A] prior art reference must be enabling so

that the claimed subject matter may be made or used by one skilled in the art.”); Bristol-

Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1374 (Fed. Cir. 2001) (“To

anticipate, the reference must also enable one of skill in the art to make and use the

claimed invention.”). Taken out of context, these formulations of our § 102 enablement

standard arguably support a use or utility requirement divorced from any “make”

requirement. A thorough reading of our case law, however, makes clear that a

reference need disclose no independent use or utility to anticipate a claim under § 102.

E.g., Novo Nordisk Pharms., Inc. v. Bio-Tech. Gen. Corp., 424 F.3d 1347, 1355 (Fed.

Cir. 2005) (“The standard for enablement of a prior art reference for purposes of

anticipation under [§] 102 differs from the enablement standard under 35 U.S.C.

§ 112.”); Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326 (Fed. Cir.

2005) (“[A] prior art reference need not demonstrate utility in order to serve as an

2008-1453 6
anticipating reference under [§] 102.”); In re Hafner, 410 F.2d 1403, 1405 (CCPA 1969)

(“[Section] 112 provides that the specification must enable one skilled in the art to ‘use’

the invention whereas § 102 makes no such requirement as to an anticipatory

disclosure.”).

The confusion stems from the fact that where a method claim is at issue, it is a

largely meaningless formulation of the standard to require a reference to disclose how

to “make” that method in order to anticipate. For method claims, the “make”

requirement becomes, in effect, a “use” requirement. The only way one can show that a

reference enables the method is to show that a person of ordinary skill would know how

to use—in other words, to practice or to carry out—the method in light of the reference.

This does not mean, however, that the prior art reference must demonstrate the

invention’s utility. For instance, in the context of a claimed method for treating a

disease, a prior art reference need not disclose “proof of efficacy” to anticipate the

claim. Impax Labs., 545 F.3d at 1315; Rasmusson, 413 F.3d at 1326. Gleave’s claims

are to compositions of matter—oligonucleotides—and therefore a reference satisfies the

enablement requirement of § 102(b) by showing that one of skill in the art would know

how to make the relevant sequences disclosed in Wraight. Thus, the fact that Wraight

provides “no understanding of which of the targets would be useful” is of no import,

because Gleave admits that it is well within the skill of an ordinary person in the art to

make any oligodeoxynucleotide sequence. See Appellant’s Br. 10. As such, Wraight is

an enabling disclosure sufficient to anticipate Gleave’s invention under § 102(b).

Gleave also points out that “[n]o example of an actual antisense oligonucleotide

complementary to a sequence on [Wraight’s] list is shown to have antisense activity.”

2008-1453 7
Id. at 4. We need not address any inherency issues, however, because the simple fact

is that Gleave’s composition claims do not require antisense activity either. The claims

at issue merely require the oligodeoxynucleotides to be “of sufficient length to act as an

antisense inhibitor of human IGFBP-2 and human IGFBP-5.” See Oral Arg. at 1:18,

available at http://oralarguments.cafc.uscourts.gov/mp3/2008-1453.mp3 (Judge Prost:

“I’m a little confused by this, and I guess turning to the language in claim 1, doesn’t it

just disclose an oligo ‘of sufficient length to act as an antisense inhibitor?’ And I’m not

seeing where the language requires that the oligo actually acts as an antisense

inhibitor.” Gleave’s counsel: “No, it doesn’t.”). As explained above, evidence as to

whether particular compounds work for their intended purpose is irrelevant to our

§ 102(b) analysis. Certainly where the claims themselves do not require a particular

activity, we have no call to require something more from the anticipating reference.

B

At its core, Gleave’s primary argument is rooted in policy:

Where the allegedly anticipatory disclosure is only a small part of a much
larger and exhaustive listing and there is no basis in the art for selecting
some individual members of the listing over others, what is actually
described and what is actually disclosed to the public is no more than the
generic concept underlying the list.

Appellant’s Br. 6. In other words, Gleave argues that we should collapse the distinction

between a list and a genus disclosure. See Oral Arg. at 4:42, available at

http://oralarguments.cafc.uscourts.gov/mp3/2008-1453.mp3 (Judge Moore: “I

understand what you’re saying—from a policy perspective, you’d like us to say when a

list gets long enough, you ought to treat them the same.” Gleave’s counsel: “No, I’m

not even saying when a list gets long enough. I’m saying when a list provides no more

2008-1453 8
information to an inve—to the public than the generic statement would.”) If we did, the

argument goes, then we would recognize that Wraight simply provides a “long winded

form of a statement that ‘you could make antisense that targets IGFBP-2.’”

Gleave also cites In re Wiggins for the proposition that a list of compounds,

“without any direction as to selection among the targets, is not a description of any one

of these targets.” Gleave urges us to find that Wiggins “clearly expressed the policy

concerns which this case exemplifies, that giving prior art effect to individual members

of lists of thousands of theoretically possible compounds would be contrary to the

purpose sought to be effectuated by the patent law.” Reply Br. 7–8 (citing In re

Wiggins, 488 F.2d 538, 543 (CCPA 1973) (quotations omitted)).

In Wiggins, the Court of Customs and Patent Appeals stated:

In our view, [the alleged anticipatory reference’s] listing of the compounds
by name constituted nothing more than speculation about their potential or
theoretical existence. The mere naming of a compound in a reference,
without more, cannot constitute a description of the compound, particularly
when, as in this case, the evidence of record suggests that a method
suitable for its preparation was not developed until a date later than that of
the reference.

If we were to hold otherwise, lists of thousands of theoretically
possible compounds could be generated and published which, assuming it
would be within the level of skill in the art to make them, would bar a
patent to the actual discoverer of a named compound no matter how
beneficial to mankind it might be.

488 F.2d at 543 (emphases added).

Gleave reads Wiggins to suggest that a description of a compound cannot be

anticipatory where it appears in a long list of other compounds. That conclusion,

however, ignores the facts at issue in that case. Contrary to Gleave’s representations,

no evidence existed that a person of ordinary skill in the art could make the compounds

2008-1453 9
disclosed in the alleged anticipatory reference at the time of disclosure. The reference,

published in 1957, mentioned by name two compounds that fell within the scope of

Wiggins’s claims. But the reference also noted that the synthesis of these compounds

had been unsuccessful; further, the only publication of record that disclosed a method of

making the compounds was not published until two years later. In short, the reference

was not an enabling reference—no person of ordinary skill in the art could make the

claimed invention in 1957. 3

The Wiggins court stated that “[t]he mere naming of a compound in a reference,

without more, cannot constitute a description of the compound.” 488 F.2d at 543. We

agree. The mere naming of a theoretical compound, without more, cannot constitute a

description under § 102(b). “Without more” is the key phrase, and read as a whole

Wiggins makes clear just what this something “more” is—a person of ordinary skill in the

art’s ability to make the claimed compound. See also Donohue, 766 F.2d at 533–34; In

re Samour, 571 F.2d 559, 562–64 (CCPA 1978); In re Brown, 329 F.2d 1006, 1009–10

(CCPA 1964) (discussing In re Von Bramer, 127 F.2d 149 (CCPA 1942)). This point is

underscored by the excerpt: not once, not twice, but three times the court pointed out

that its discussion was in the context of “potential or theoretical” compounds. That was

the issue presented to the court, and that was the issue it decided.

3
It is true that “[e]nablement of an anticipatory reference may be
demonstrated by a later reference.” Bristol-Myers Squibb, 246 F.3d at 1379. But in
Wiggins, our predecessor court did not elect to decide the case on this ground. 488
F.2d at 543 n.4 (“We do not mean to suggest that we have actually evaluated the
process taught by [the later reference] and concluded that it could be used to prepare
the claimed compounds. As this is irrelevant to our decision, we express no opinion on
this point.”).

2008-1453 10
 For the purposes of whether they are anticipatory, lists and genera are often

treated differently under our case law. Compare Perricone v. Medicis Pharm. Corp.,

432 F.3d 1368, 1376 (Fed. Cir. 2005) (rejecting “the notion that [a compound] cannot

anticipate because it appears without special emphasis in a longer list”) with Atofina v.

Great Lakes Chem. Corp., 441 F.3d 991, 999 (Fed. Cir. 2006) (“It is well established

that the disclosure of a genus in the prior art is not necessarily a disclosure of every

species that is a member of that genus.”). This distinction collapses when the class of

compounds that falls within the genus is so limited that a person of ordinary skill in the

art can “at once envisage each member of this limited class.” Eli Lilly, 471 F.3d at 1376.

In that limited circumstance, a reference describing the genus anticipates every species

within the genus. See Perricone, 432 F.3d at 1377. In this case, Gleave’s arguments

fail for two reasons. First, Wraight expressly lists every possible fifteen-base-long

oligodeoxynucleotide sequence in IGFBP-2, and under our precedent, this list

anticipates Gleave’s claims. Second, even if we were to accept Gleave’s invitation to

treat Wraight as equivalent to the statement that one “could make antisense that targets

IGFBP-2,” 4 which we decline to do, a person of ordinary skill in the art equipped with an

IGFBP sequence is admittedly capable of envisioning how to make any antisense

sequence. Thus, even if we were to adopt Gleave’s policy position, Gleave’s claims

would not be entitled to a patent over Wraight.

The rest of Gleave’s arguments fare no better. For instance, Gleave protests

that Wraight “does not show that sequences antisense to any of the sequences in this

4
We note that this is not the full extent of Wraight’s disclosure. See supra
at 3.

2008-1453 11
list were actually made and tested.” As we have already made clear, it is not

“necessary that an invention disclosed in a publication shall have actually been made in

order to satisfy the enablement requirement.” Donohue, 766 F.2d at 533. In light of the

foregoing, we agree with the Board’s conclusion that Gleave’s claims are invalid as

anticipated by Wraight.

CONCLUSION

In sum, “[t]he discovery of a new property or use of a previously known

composition, even when that property and use are unobvious from the prior art, can not

impart patentability to claims to the known composition.” In re Spada, 911 F.2d 705,

708 (Fed. Cir. 1990). The compositions described in the ’493 application are simply not

new—they were described in Wraight’s enabling disclosure. As we explained in In re

Schoenwald, Gleave’s contribution, at best, is “finding a use for the compound, not

discovering the compound itself.” 964 F.2d 1122, 1124 (Fed. Cir. 1992). If the use

Gleave discovered is new, he will be able to patent that method of use—“any more

would be a gratuity.” Id. Therefore, we affirm the Board’s rejection of claims 1, 4, 15,

and 18–21 of the ’493 application under § 102(b). We need not reach the § 103

obviousness rejection.

AFFIRMED

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