NOTE: Pursuant to Fed. Cir. R. 47.6, this disposition is
not citable as precedent. It is a public record.
United States Court of Appeals for the Federal Circuit
05-1072
(Reexamination Nos. 90/005,147 and 90/005,326)
IN RE SIBIA NEUROSCIENCES, INC.
__________________________
DECIDED: November 29, 2005
__________________________
Before NEWMAN, MAYER, and DYK, Circuit Judges.
Opinion for the court filed PER CURIAM. Dissenting opinion filed by Circuit Judge
NEWMAN.
PER CURIAM.
Sibia Neurosciences, Inc. (“Sibia”) appeals the decision of the United States
Patent and Trademark Office, Board of Patent Appeals and Interferences (“board”), In
re Sibia Neurosciences, Inc., Nos. 90/005147 and 90/005326 (Jul. 30, 2004), affirming
the examiner’s rejection of claims 15-52 of U.S. Pat. No. 5,401,629 (“the ’629 patent”)
as obvious under 35 U.S.C. § 103. We affirm.
Obviousness is a legal determination based on underlying questions of fact. In
re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000). We review the board’s conclusions
of law de novo and affirm its findings of fact if they are supported by substantial
evidence. Id. Findings of fact in an obviousness determination include, inter alia, the
presence or absence of a motivation to combine references, id., and what a reference
teaches, Para-Ordnance Mfg., Inc. v. SGS Imps. Int’l, Inc., 73 F.3d 1085, 1088 (Fed.
Cir. 1995).
Sibia argues that the board erred in finding that U.S. Pat. No. 5,071,773
(“Evans”); U.S. Pat. No. 5,747,336 (“Bonner”); and Sassine-Corsi, et. al., “Induction of
proto-oncogene fos transcription through the adenylate cyclase pathway:
characterization of a c-AMP responsive element,” Genes & Development, Vol. 2 (1988)
(“Sassone-Corsi”), render claims 15-52 of the ’629 patent obvious. Those claims are
directed toward a method for using a reporter gene to identify compounds that modulate
the activity of G protein-coupled receptors (“GCPRs”). An increase in cyclic AMP
(cAMP) levels is an intermediate step between the GCPR and reporter gene activation.
Sibia argues that there is no motivation to combine the three references, that there is no
reasonable expectation of success, and that the references do not teach the elements
of the claim.
The board determined that the Bonner reference teaches a method for
measuring m1 muscarinic receptor activation by measuring changes in cAMP levels.
The difference between the Bonner reference and the ’629 patent is that Bonner
05-1072 2
measured cAMP levels and not the reporter gene product. The reference states that
“[t]he functional responses observed for one or more of the receptors include . . .
increases or decreases in cyclic AMP levels [which] could form the basis of a functional
assay for the screening.” Bonner, Col. 5, lines 22-64. Thus, it cannot be said that the
board’s finding as to what Bonner teaches was not supported by substantial evidence.
The board also determined that the Sassone-Corsi reference teaches treating
cells to increase levels of cAMP and then monitoring the effects of the cAMP levels on
promoters and reporter genes. The reference covers the steps in the ’629 patent
between increases in cAMP levels and reporter gene activation. Therefore, the fact that
the reference does not discuss GCPRs is irrelevant to its applicability to the step of the
’629 patent described.
The board further found that Evans shows the use of reporter genes to monitor
receptor activation in general, contrary to Sibia’s contention that the reference only
shows use of reporter genes to monitor activation of intracellular steroid hormone
receptors. The board recognized the difference between GCPRs and steroid hormone
receptors, but found that a person skilled in the art would not have considered the
difference significant in this context. Thus, substantial evidence supports the finding
that Evans provides a motivation to combine Bonner with Sassone-Corsi based on the
idea that steroid receptor activation increases reporter gene activity.
Additionally, only a reasonable, not absolute, expectation of success is
necessary to support an obviousness rejection. The board’s determination that there
was a reasonable expectation of success in light of Bonner, Sassone-Corsi, and Evans,
as well as the high level of skill in the art, was supported by substantial evidence.
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Lastly, secondary considerations of nonobviousness such as long-felt need and
commercial success do not overcome the examiner’s obviousness finding. Sibia failed
to present evidence that its claimed method in the ’629 patent met a long-felt need.
Further, Sibia’s declarations were directed toward the original claims 1-14, not the newly
narrowed claims 15-52, and failed to provide the required nexus for nonobviousness
based on commercial success. Therefore, substantial evidence supports the board’s
finding.
05-1072 4
NOTE: Pursuant to Fed. Cir. R. 47.6, this disposition
is not citable as precedent. It is a public record.
United States Court of Appeals for the Federal Circuit
05-1072
(Reexamination Nos. 90/005,147 and 90/005,326)
IN RE SIBIA NEUROSCIENCES, INC.
NEWMAN, Circuit Judge, dissenting.
I respectfully dissent. There is no suggestion or motivation in the prior art to make
the claimed combination, and no suggestion that, if made, the combination would be
successful to achieve the highly useful result that was achieved, for the first time, by these
inventors.
The invention is directed to the discovery of chemical/ biological compounds that
modulate the activity of a G protein-coupled receptor ("GPCR") on the surface of a cell.
The specification teaches that a compound binding to a cell surface GPCR induces a
complex cascade of events, including the production of cyclic adenosine monophosphate
("cAMP") and ultimately produces a change in reporter gene expression. The complexity of
this mechanism was oversimplified by the Board, leading the Board to combine, in perfect
hindsight, a reference showing that GPCR can cause changes in cAMP, and a reference
showing that cAMP can cause changes in reporter gene levels. From these references, the
Board adduced the claimed invention. The Board found no evidence of a motivation to
combine these references, or any suggestion of an expectation of success in achieving a
reliable screening method for compounds that affect GPCR activity.
No such motivation or suggestion can be found in the cited Bonner reference.
Bonner describes a particular GPCR receptor that causes changes in cAMP levels, and
speculates that such changes "could form the basis of a functional assay" for cAMP, by
"standard procedure." The panel majority overstates that Bonner taught any procedure or
"measured cAMP levels," for Bonner did neither. Sibia accurately points to the cAMP
measuring procedures then known, as "cumbersome," and the statements that such
procedures were expected to be replaced by methods that measured bioluminescence or
fluorescence indicate that Bonner thus teaches away, not toward, the reporter gene
approach of the Sibia invention.
The Sassone-Corsi reference, relied on by the Board as teaching that cAMP can
affect reporter genes, contains no suggestion that GPCR receptors can be affected and
activity screened with reference to receptor genes. Sassone-Corsi merely explores the
relationship between cAMP and reporter gene expression, without any suggestion to apply
this teaching to receptor signaling, or that such application would be successful. The
majority reasons that because Sassone-Corsi "covers the steps" between Bonner and the
Sibia invention, the fact that Sassone-Corsi does not discuss or mention GPCR is
"irrelevant." I cannot agree. It is highly relevant that Sassone-Corsi makes no mention of
05-1072 2
GPCR activity as related to reporter genes, and it is highly relevant that Bonner makes no
mention of possible use of reporter genes to indicate GPCR activity. No reference contains
any motivation or suggestion to combine these teachings; that comes only from PTO
hindsight using the Sibia disclosure as the template.
Sibia points out that Sassone is a mechanistic study in which cAMP is shown to be
responsive to extracellularly applied forskolin, and does not contain any suggestion that
receptor-mediated cAMP operating as a secondary messenger could be produced at a
sufficient level or be correctly localized so as to function as a signal and thereby be used in
a screening method for a large number of candidate molecules. That discovery came from
Sibia.
Finally, the Evans reference is clearly inapposite, for it relates to a completely
different receptor technology, that of an intracellular receptor. The Board found that this
difference is not "significant"; however, this conclusion is without support, as against Sibia's
overwhelming showing. The structural and functional differences between intracellular and
GPCR receptors are striking. The intracellular steroid receptors in Evans have a DNA
binding domain but no trans-membrane domain, whereas GPCRs have a trans-membrane
domain but no DNA binding domain. The intracellular steroid receptors localize and form a
complex in the nucleus or cytoplasm of the cell, whereas the GPCRs localize and form a
complex at the cell surface. The steroid receptors bind directly to the promoter of the
reporter gene being monitored, whereas the GPCRs induce a complex sequence of events
that ultimately results in a change in reporter gene expression -- any missing link in this
sequence may result in nonresponsiveness of the reporter gene. Sibia well demonstrated
that persons experienced in this field would recognize the large differences between the
05-1072 3
receptor studies in Evans and the cell surface receptor mechanisms of the claimed
invention, and the absence of predictable interchangeability of methodologies.
In this complex case of biological advance, the Board's decision is not supported by
substantial evidence, and should be reversed. From the panel majority's contrary holding, I
must respectfully dissent.
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