Sibia Neurosciences Inc. v. Cadus Pharmaceutical Corp.

Decision Date06 September 2000
Docket NumberPLAINTIFF-APPELLE,V,DEFENDANT-APPELLANT,No. 99-1381,99-1381
Citation225 F.3d 1349,55 USPQ2d 1927
Parties(Fed. Cir. 2000) SIBIA NEUROSCIENCES, INC.,CADUS PHARMACEUTICAL CORPORATION,
CourtU.S. Court of Appeals — Federal Circuit

Stephen P. Swinton, Cooley Godward Llp, of San Diego, California, argued for plaintiff-appellee. With him on the brief were Anthony M. Stiegler, J. Christopher Jaczko, Kent M. Walker, and Amy S. Hellenkamp.

Laura A. Coruzzi, Pennie & Edmonds Llp, of New York, New York, argued for defendant-appellant. With her on the brief was S. Leslie Misrock. Of counsel on the brief were Stanton T. Lawrence, III, Paul J. Zegger, and Carl P. Bretscher, Pennie & Edmonds Llp, of Washington, Dc.

Before Mayer, Chief Judge, Michel and Gajarsa, Circuit Judges.

Opinion for the court filed by Circuit Judge Gajarsa. Chief Judge Mayer dissents.

Cadus Pharmaceutical Corporation ("Cadus") appeals the judgment of the United States District Court for the Southern District of California entered after a jury verdict finding the patent claims at issue infringed and not invalid, and assessing damages of $18 million. Because we determine that the asserted claims are obvious as a matter of law, we reverse.

BACKGROUND

The identification of compounds that bind with particular cell surface proteins is useful in the search for new drugs. When such binding occurs, a cascade of biochemical events is activated within the cell in which a linkage, known as a signal transduction pathway, is formed between the cell surface protein and a gene in the cell's DNA. This linkage allows the cell to respond to signals from the external environment, which is critical for the cell to properly function. Compounds that activate this linkage often prove useful in pharmaceutical applications because many diseases stem from the malfunctioning of cellular communications.

In general, when a compound activates a signal transduction pathway, the cell responds by directing the production or non-production of a protein from a responsive gene in the DNA. Protein production involves two distinct processes-transcription and translation. Transcription refers to the process by which a strand of messenger RNA ("mRNA") is created by the expression of a gene. Translation refers to the process by which a corresponding protein (i.e., a sequence of amino acids) is created from the mRNA. Compounds that trigger or enhance transcription and translation are referred to as agonists, and compounds that block or decrease such activity are called antagonists. The displaying of agonist and antagonist activity is an indication that a compound has bound with the cell surface protein and has activated the signal transduction pathway.

SIBIA Neurosciences, Inc. ("SIBIA") is the owner of U.S. Patent No. 5,401,629 ("the '629 patent"), which is directed to a cell-based screening method useful for the identification of compounds that exhibit agonist and antagonist activity with respect to particular cell surface proteins. According to the patent, the claimed methods are particularly effective because they allow a scientist to rapidly and reliably screen large numbers of compounds for agonist and antagonist activity. See '629 patent, col. 1, ll. 45-50. Thus, the scientist could quickly develop a list of candidate compounds that merit further in-depth studies for therapeutic applications. See id. Claim 1, the only independent claim, reads as follows:

1. A method for identifying compounds that modulate cell surface protein-mediated activity by detecting intracellular transduction of a signal generated upon interaction of the compound with the cell surface protein, comprising:

comparing the amount of transcription of a reporter gene or the amount of reporter gene product expressed in a first recombinant cell in the presence of the compound with the amount of transcription or product in the absence of the compound, or with the amount of transcription or product in a second recombinant cell; and

selecting compounds that change the amount of transcription of a reporter gene or the amount of reporter gene product expressed in the first recombinant cell in the presence of the compound compared to the amount of transcription or product in the absence of the compound, or compared to the amount of transcription or product in the second recombinant cell, wherein:

the cell surface protein is a surface receptor or ion channel;

the first recombinant cell contains a reporter gene construct and expresses the cell surface protein;

the second recombinant cell is identical to the first recombinant cell, except that it does not express the cell surface protein; and

the reporter gene construct contains:

(a) a transcriptional control element that is responsive to the intracellular signal that is generated by the interaction of an agonist with the cell surface protein; and

(b) a reporter gene that encodes a detectable transcriptional or translational product and that is in operative association with the transcriptional control element.

See id., col. 13, l. 44 - col. 14, l. 12.

The methods claimed in the '629 patent utilize a recombinant cell that is exposed to various compounds in order to determine whether those compounds exhibit the desired activity. This recombinant cell, in addition to the host cell itself, has two basic components: a heterologous 1 cell surface protein and a reporter gene construct. The cell surface protein can be either an ion channel or a cell surface receptor. Ion channels are proteins that act as pores in the cell membrane and allow small inorganic ions to flow in or out of the cell. These ion channels open and close based on interaction with certain external compounds. Cell surface receptors, on the other hand, are proteins that span the external membrane of the cell and bind with particular molecules to commence a chain of intracellular reactions that transmit external signals to the DNA. As described above, cell surface proteins are physiologically important because they play a vital role in the stimulation of signal transduction pathways, and thus, the cell's ability to respond appropriately to stimuli from the external environment.

The second major component of the cell utilized in the '629 patent is the reporter gene construct, which consists of a transcriptional control element and a reporter gene. The transcriptional control element is a gene that reacts to the signal from the cell surface protein and regulates transcription of the reporter gene. The reporter gene, through the processes of transcription and translation, creates a corresponding protein, referred to as "reporter gene product." Both transcription of the reporter gene and translation to the reporter gene product can be measured.

In the claimed methods, this recombinant cell is used in a battery of assays, the goal of which is to determine if a given compound exhibits the desired binding activity with respect to a particular cell surface protein. The method of claim 1 contains two assays. In the first assay, referred to as the "compound/no compound assay," the recombinant cell is exposed to a test compound. The amount of reporter gene transcription, or reporter gene product expressed in that recombinant cell, is then compared to the amount of reporter gene transcription or reporter gene product expressed in a recombinant cell that was not exposed to the test compound. In the second assay, known as the "receptor/no receptor assay," two recombinant cells are exposed to a test compound. However, one of the recombinant cells has a cell surface protein, but the other does not. The amount of reporter gene transcription or reporter gene product expressed in both of these cells is then compared. Based on these measurements, the scientist is able to detect whether the compound has bound to the cell surface protein and modulated the signal transduction pathway. This, in turn, allows the scientist to determine whether the compound is a candidate for further study, or should be excluded from consideration.

SIBIA sued Cadus for infringement of the '629 patent. The court held a Markman hearing, see Markman v. Westview Instruments, Inc., 52 F.3d 967, 979, 34 USPQ2d 1321, 1329 (Fed. Cir. 1995) (en banc), aff'd, 517 U.S. 370 (1996), and issued an order construing numerous claim terms, including "identifying compounds," "cell," "recombinant cell," "comparing the amount," "identical" and "selecting compounds." Only the construction of "cell," "identifying compounds," and "selecting compounds" are relevant to this appeal. Before the district court, Cadus argued that because the claims use the term "cell" without modification, this term should refer to all cells, eukaryotic as well as prokaryotic. 2 Alternatively, Cadus argued that if "cell" should be limited to less than all cells, it should be limited to only mammalian cells, because the examples found in the written description of the patent only discuss mammalian cells. The court decided, however, that because the patentee describes the cells used in the claimed methods as "eukaryotic cells" in the written description, see '629 patent, col. 3, ll. 52-56, col. 4, ll. 9-11, a person of ordinary skill in the art would interpret cell as found in the claim language to mean only eukaryotic cells.

Also important to this appeal is the court's construction of the phrases "identifying compounds" and "selecting compounds." At the Markman hearing, the parties disagreed as to whether this claim language required the compounds to be unknown to interact with the particular cell surface protein prior to conducting the assays, or whether these terms include both compounds known and unknown to interact with the cell surface proteins. The court held that the ordinary meaning of "identifying compounds" is determining which compounds interact with a particular cell...

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2 books & journal articles
  • Secondary considerations: a structured framework for patent analysis.
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    • Albany Law Review Vol. 74 No. 1, September 2010
    • September 22, 2010
    ...and corroborates Whelan's conclusion. (123) 35 U.S.C. [section] 282 (2006). (124) SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1355-56 (Fed. Cir. 2000) ("While the presentation at trial of a reference that was not before the examiner does not change the presumption of val......
  • Ordinary creativity in patent law: the artist within the scientist.
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    ...& Wireless Internet Servs., Inc., 344 F.3d 1186, 1196 (Fed. Cir. 2003). (147.) See SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1356 (Fed. Cir. 2000) ("[I]n appropriate circumstances, a single prior art reference can render a claim obvious. However, there must be a sh......

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