In Re Gleave
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
BACKGROUND
Gleave’s '493 application is entitled “Bis-pecific 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 oligodeoxynucleo-tides, and methods of treating endocrine-regulated cancers by using the oligodeoxy-nucleotides 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 oligodeoxynucleo-tide, wherein substantially all of the oli-godeoxynucleotide 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 anti-sense inhibitor of human IGFBP-2 and human IGFBP-5.
Claim 4 recites “[t]he antisense oligodeox-ynucleotide 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 anti-sense oligonucleotides are preferably between fifteen and twenty-five bases in length, and that some antisense oligonu-cleotides 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 Board found that to anticipate claim 1, the prior art had to describe an oligode-oxynueleotide of sufficient length to act as an antisense inhibitor to human IGFBP-2 and IGFBP-5, and substantially all of the oligodeoxynueleotide 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.
The issue presented on appeal, therefore, is whether a reference that lists every fifteen-base sense oligodeoxynueleotide 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
DISCUSSION
As an initial matter, the parties disagree over the proper standard of review. Under
A reference is anticipatory under
As this summary makes clear, the outcome in this case depends largely on the facts. After all, anticipation is a
A
Gleave frames the issue presented for review as “the meaning of the term ‘described’ in
We have at times framed the issue of enablement under
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.,
Gleave also points out that “[n]o example of an actual antisense oligonucleo-tide complementary to a sequence on [Wraight’s] list is shown to have antisense activity.”
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/mp 3/2008-1453.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
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 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,
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.
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 disclosed in the alleged anticipatory reference at the time of disclosure. The reference, published in 1967, 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.”
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.,
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 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,
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,
AFFIRMED
Notes
. We described antisense technology in greater detail in
Enzo Biochem, Inc. v. Calgene, Inc.,
. 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.
. It is true that "[e]nablement of an anticipatory reference may be demonstrated by a later reference.”
Bristol-Myers Squibb,
. We note that this is not the full extent of Wraighl's disclosure. See supra