Singh v. Brake

48 F. App'x 766
CourtCourt of Appeals for the Federal Circuit
DecidedOctober 16, 2002
DocketNo. 01-1621
StatusPublished

This text of 48 F. App'x 766 (Singh v. Brake) is published on Counsel Stack Legal Research, covering Court of Appeals for the Federal Circuit primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
Singh v. Brake, 48 F. App'x 766 (Fed. Cir. 2002).

Opinion

LOURIE, Circuit Judge.

Arjun Singh appeals from the remand decision of the United States Patent and Trademark Office Board of Patent Appeals and Interferences awarding judgment in an interference to Anthony Brake. Brake v. Singh, Inter. No. 102,728, Paper No. 199 (Bd. Pat.App. & Inter. June 19, 2001). Because the Board’s decision was supported by substantial evidence and was not contrary to law, we affirm.

BACKGROUND

This case arises out of an interference declared on November 12, 1991, involving a count corresponding to all thirty-seven claims of Brake’s U.S. Patent 4,870,008 (hereinafter “the Brake patent”) and claims 8 and 19-21 of Singh’s U.S. Application 07/552,719.

The Brake patent issued from U.S. Application 07/081,302, filed August 3, 1987, which was a continuation of, and was accorded the benefit of, U.S. Application 06/522,909 (hereinafter “Brake 2”), filed August 12, 1983, assigned to Chiron Corporation. Singh’s Application 07/552,719 was filed July 16, 1990, and was accorded the benefit of U.S. Application 06/506,098 (hereinafter “the Singh application”), filed June 20, 1983, and U.S. Application 06/488,323, filed April 25, 1983, both assigned to Genentech, Inc.

Because the earlier Singh application predated Brake 2, Singh was initially designated the senior party in the interference. However, Brake 2 was a continuation-in-part of U.S. Application 06/457,325 (hereinafter “Brake 1”), filed January 12, 1983, and Brake successfully moved for the benefit of the filing date of Brake 1 with respect to the count in the interference. Brake also successfully moved to attack the benefit accorded Singh of the April 25, [768]*7681983 filing date of U.S. Application 06/488,-323. Brake was then designated as the senior party.

The count, which is identical to claim 1 of Brake 2, reads as follows:

1. A DNA construct comprising a sequence of the following formula:

5’-L-S-Gene*-3’,
where:
L encodes a Saccharomyces alpha-factor leader sequence recognized by a yeast host for secretion;
S encodes a spacer sequence providing processing signals resulting in the enzymatic processing by said yeast host of a precursor polypeptide encoded by L-S-Gene* into the polypeptide encoded by Gene*, S containing the sequence 5-RJ-R2-3’ immediately adjacent to the sequence Gene*, Rj being a codon for lysine or arginine, R2 being codon for arginine, with the proviso that S not contain the sequence 5’-R3-R4-X-3’, where R3 =Ri, R4=R2, and X encodes a processing signal for dipeptidylaminopeptidase A; and Gene* encodes a polypeptide foreign to Saccharomyces.

Brake, Paper No. 199 at 6.

The DNA construct of the count thus includes three basic components: (1) a segment, “L,” which encodes an alpha-factor leader sequence;1 (2) a segment, “S,” which includes a first codon,2 R1( encoding either lysine or arginine, followed by a second codon, R2, encoding arginine; and (3) a gene, “Gene*,” which encodes a protein of interest, in particular, a polypeptide foreign to (i.e., not naturally produced by) Saccharomyces. See Brake patent, col. 2, ll. 11-16, 38-43.

After the DNA construct has been introduced into the yeast cell, e.g., via a plasmid vector, the cell “translates” the construct, producing a polypeptide having the sequence of amino acids encoded by the DNA. The sequence of the resulting polypeptide, like the DNA encoding it, is divided into three regions: the alpha-factor leader, the spacer sequence including either a lysine-arginine or an arginine-arginine two-amino acid block, and the amino acid sequence of the protein of interest (“gene product”).

According to the record in this case, the leader sequence functions to target the polypeptide for secretion from the yeast cell. During secretion, the yeast enzyme KEX-2 recognizes the lysine-arginine or arginine-arginine spacer sequence in the polypeptide and cleaves the polypeptide at the junction between the spacer and the gene product. As a result, the desired gene product is released into the extracellular medium, free of the leader and spacer portions of the polypeptide. See Brake, Paper No. 164 at 2. Because the yeast cell exports rather than retains the desired protein, protein purification is considerably simplified. See id.

The following is a statement of the facts as set forth in our earlier opinion in this case. Singh v. Brake, 222 F.3d 1362, 55 USPQ2d 1673 (Fed.Cir.2000). As we not[769]*769ed in that opinion, the factual context of Singh’s alleged conception of the claimed DNA construct is based on his statements to the PTO and other record evidence. Absent qualification, the facts set forth here are not disputed by the parties.

In the course of Singh’s attempts to design the claimed DNA construct in August 1982, he prepared plasmid p57, a circular DNA molecule containing the alpha-factor leader sequence and a spacer sequence directly adjacent to it. See Singh Decl. ¶ 21. During that same month, Singh incorporated the gene for human protein interferon D (“IFN-D”) into p57, thereby yielding plasmid p58. See id. In p58, the gene was also positioned adjacent to the spacer sequence, such that the leader, spacer, and gene sequences were all oriented in a fashion identical to the claimed construct. From September 6 to 11, 1982, Singh’s assistant, Dr. June Lugovoy, isolated the DNA segment from p58 containing the alpha-factor leader, spacer, and IFN-D sequence, and inserted that segment (hereinafter “the p60 DNA construct”) into yeast plasmid YEp9PT (“p60”). See id. ¶ 26. Plasmid p60 was then introduced into yeast cells to determine whether the p60 DNA construct would generate IFN-D. See id. ¶ 27.
On October 1, 1982, protein sequencing chemist Bill Kohr informed Singh that the IFN-D expressed by yeast cells transformed with p60 contained eight additional amino acids not normally present in natural IFN-D. See id. ¶ 33. On approximately that same date, Singh alleges that he conceived the claimed DNA construct, i.e., he devised a plan to redesign the p60 DNA construct in order to obtain the desired gene product, IFN-D, free of those additional amino acids. See id. ¶ 34. Specifically, Singh claims that he realized that he would need to remove eight unwanted codons (twenty-four nucleotides) from the p60 DNA construct, and that he planned to accomplish this deletion by use of a technique known as “loop deletion mutagenesis.”
On November 24, 1982, Singh wrote a laboratory notebook entry setting forth the undesired eight codons in the p60 DNA construct, as well as the twelve nucleotides on either side of that eight codon segment (the “flanking sequences”). See Singh Decl. ¶ 45. On that date, Singh also ordered a linear, 24-nucleotide sequence (a “24-mer”) that comprised the nucleotides of the flanking sequences.3 This order was canceled on the same day, and a notation in Singh’s laboratory notebook stated that Singh would perform the deletion experiment in a different way “without changing codons.” Id. On December 1, 1982, Singh ordered another 24-mer for the deletion experiment.

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