Genetics Inst. Llc v. Vaccines

• Citation: 99 U.S.P.Q.2d 1713,655 F.3d 1291
• Decision Date: 09 November 2011
• Docket Number: No. 2010–1264.,2010–1264.
• Parties: GENETICS INSTITUTE, LLC, Plaintiff–Appellant,v.NOVARTIS VACCINES AND DIAGNOSTICS, INC., Defendant–Appellee.
• Court: United States Courts of Appeals. United States Court of Appeals for the Federal Circuit

655 F.3d 1291

99 U.S.P.Q.2d 1713

GENETICS INSTITUTE, LLC, Plaintiff–Appellant,

v.NOVARTIS VACCINES AND DIAGNOSTICS, INC., Defendant–Appellee.

No. 2010–1264.

United States Court of Appeals, Federal Circuit.

Aug. 23, 2011.Rehearing En Banc Denied Nov. 9, 2011.

Bradford J. Badke, Ropes & Gray LLP, of New York, NY, argued for plaintiff-appellant. With him on the brief were Jeanne C. Curtis and Matthew A. Traupman. Of counsel was Christopher J. Harnett.George A. Riley, O'Melveny & Myers LLP, of San Francisco, CA, argued for defendant-appellee. With him on the brief was George C. Yu. Of counsel on the brief was John C. Kappos, of Newport Beach, CA. Also of counsel were Polaphat Veravanich, O'Melveny & Myers LLP, of Newport Beach, CA, and Mark S. Davies, Orrick, Herrington & Sutcliffe LLP, of Washington, DC.Before LOURIE, PLAGER, and DYK, Circuit Judges.Opinion for the court filed by Circuit Judge LOURIE. Opinion concurring-in-part and dissenting-in-part filed by Circuit Judge DYK.LOURIE, Circuit Judge.

Genetics Institute, LLC, (“Genetics”) appeals from the decision of the United States District Court for the District of Delaware dismissing its action under 35 U.S.C. § 291 for lack of an interference in fact between certain claims of its U.S. Patent 4,868,112 (the “'112 patent”) and certain claims of U.S. Patents 6,228,620 and 6,060,447 (the “'620 patent” and the “'447 patent”; collectively, the “Novartis patents”). Novartis asserts that the expiration of the '112 patent following the district court's entry of judgment renders us without jurisdiction over Genetics' appeal. Novartis also asserts that the district court lacked jurisdiction over certain claims of the '112 patent because its term extension under 35 U.S.C. § 156 applied only on a claim-by-claim basis. Because the district court did not err in dismissing Genetics' § 291 action for lack of an interference in fact, and because we disagree with Novartis's jurisdictional arguments, we affirm.

Background

I

The district court's opinion summarizes the science underlying the patented technology in this case, which relates to truncated forms of a protein called Factor VIII. Genetics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc., 687 F.Supp.2d 486, 490–92 (D.Del.2010). Factor VIII is an essential blood-clotting protein that circulates freely in the blood in an inactive state. Factor VIII becomes activated as part of a chain of reactions called the “blood-clotting cascade,” which causes the formation of a blood clot to stop bleeding from damaged blood vessels. Defects in the gene encoding Factor VIII result in hemophilia A, a genetic disorder associated with prolonged bleeding.

The human Factor VIII protein is stabilized in the bloodstream by binding to von Willebrand factor (“vWF”), a large blood protein that prevents the degradation of Factor VIII. Id. at 491. If Factor VIII is not able to form a complex with vWF, the half-life of Factor VIII in plasma is reduced about five-fold. Thus, while Factor VIII retains its procoagulant activity even without vWF binding, the association of Factor VIII with vWF is critical for the optimal regulation of blood coagulation. In addition, a Factor VIII protein that cannot bind vWF may cause unwanted clots in areas such as heart vessels because unbound Factor VIII can bind blood platelets even when no injury has been detected.

The full-length Factor VIII protein consists of 2,332 amino acid residues—the chemical building blocks of proteins. Id. The protein contains several regions, or “domains,” each of which folds into a three-dimensional structure independent of the others. Factor VIII contains the following domains: A1, A2, B, A3, C1, and C2. The Figure below depicts the locations of these domains in the full-length Factor VIII protein. See Br. of Pl.-Appellant at 9; see also Def.-Appellee Br. at 10–11. The “heavy chain” or “A domain” portion of the protein consists of amino acids 1 to 740 and contains the A1 and A2 domains as well as two acidic regions known as a1 and a2.¹ The B domain contains amino acids 741 to 1648. The “light chain” or “C domain” portion of the protein consists of amino acids 1649 to 2332. It contains a third acidic region, a3, as well as the A3, C1, and C2 domains. The a3 acidic region, of particular importance to the dispute in this case, contains amino acids 1649 to 1689. It is directly adjacent to the B domain.

Image 1 (4.36" X 1.15") Available for Offline Print

Treating patients with hemophilia A traditionally involved administering partially purified Factor VIII derived from porcine or human plasma. In the 1980s, however, human plasma sources had become contaminated with viruses, such as HIV and hepatitis, making treatment with plasma-derived Factor VIII dangerous. Recombinant Factor VIII, produced from DNA cloning, offered a safer and more abundant new source of therapeutic material. Scientists raced to clone Factor VIII successfully for the first time. Yet cloning Factor VIII proved to be an enormous technical undertaking, because the Factor VIII protein was nearly ten times larger than any protein previously cloned. The large size of the DNA sequence encoding the full-length Factor VIII protein also complicated the cloning process. Id. at 491–92.

Once the feat of cloning the full-length Factor VIII protein was achieved, researchers focused their efforts on finding a smaller, more easily cloned recombinant protein that mimicked the biological activity of Factor VIII in humans. Id. at 492. Those efforts formed the basis of the patents at issue in this appeal. As described below, scientists discovered that portions of the full-length Factor VIII protein were unnecessary for procoagulant activity, and they designed truncated Factor VIII proteins lacking these portions. Scientists further found that the a3 acidic region of Factor VIII is responsible for binding to vWF and is therefore critical to Factor VIII's performance.

II

The '112 patent is assigned to Genetics, a wholly owned subsidiary of Wyeth (which itself was recently acquired by Pfizer Inc.). Genetics, 687 F.Supp.2d at 489–90. The '112 patent, which issued on September 19, 1989, claims priority from an application filed April 12, 1985, and names John J. Toole, Jr., as the sole inventor. The '112 patent was set to expire on September 19, 2006, at the end of its seventeen-year term. In 2000, however, Genetics obtained a patent term extension under 35 U.S.C. § 156 based on the time consumed by testing and regulatory review of its commercial recombinant Factor VIII protein, ReFacto®. The United States Patent and Trademark Office (“PTO”) extended the term of the '112 patent to February 28, 2010.

At issue in this appeal are claims 1, 5, 9, and 10 of the '112 patent. These claim, respectively, a recombinant DNA whose expression results in a truncated Factor VIII protein; a host cell containing the recombinant DNA; a method of producing the truncated Factor VIII protein by culturing the host cells; and a truncated human Factor VIII protein.

The truncated Factor VIII protein of claims 1, 5, and 9 has the amino acid sequence for human Factor VIII protein except that, in the region between amino acid 740 and amino acid 1690, a number of amino acids are deleted; the size of the deletion ranges from at least 581 to all 949 amino acids in this region.² The region eligible for deletion encompasses the inactive B domain (amino acids 741 to 1648) and the a3 acidic region in the light chain (amino acids 1649 to 1689). Claim 10 claims a truncated Factor VIII protein having one of three specific deletions: between amino acids 981 to 1563; 759 to 1640; or 759 to 1675.³

Novartis Vaccines and Diagnostics, Inc., (“Novartis”) is the assignee of the '620 and '447 patents. Both of the Novartis patents claim priority from an application filed January 27, 1986.

At issue in the '620 patent are claims 68, 74, and 83. Claim 68 claims a nucleic acid expressing a truncated recombinant Factor VIII protein in which all or part of the B domain is deleted. The claimed recombinant protein retains the amino acids in the heavy chain (amino acids 1 to 740) and the light chain (amino acids 1649 to 2332, including the a3 acidic region) with the requirement that these retained portions have at least 90% sequence identity to the native human Factor VIII protein. The protein also optionally retains certain amino acids in the B domain: up to 10 amino acids contiguous to amino acid 740, and up to 10 amino acids contiguous to amino acid 1649.⁴ Claim 74 claims a host cell containing nucleic acid capable of expressing the truncated recombinant Factor VIII protein, and claim 83 claims a method of producing the truncated recombinant Factor VIII protein by culturing the host cell.

The only claim at issue in the '447 patent is claim 1, which claims a composition comprising Factor VIII proteins consisting essentially of two polypeptides: a first comprising an amino acid sequence of the heavy chain (A domain), and a second comprising an amino acid sequence of the light chain (C domain). At least 90% sequence identity with each region is required.⁵

III

On May 16, 2008, Genetics sued Novartis in the United States District Court for the District of Delaware to determine priority of invention under 35 U.S.C. § 291. Genetics alleged that an interference in fact existed between the following claims: (1) claim 1 of the '112 patent and claim 68 of the ' 620 patent; (2) claim 5 of the '112 patent and claim 74 of the '620 patent; (3) claim 9 of the '112 patent and claim 83 of the '620 patent; and (4) claims 9 and 10 of the '112 patent and claim 1 of the '447 patent. Genetics asserted that all three patents are directed to the same subject matter, viz., truncated Factor VIII proteins lacking all or part of the B domain while retaining procoagulant activity.

Novartis moved to dismiss, arguing that the court lacked subject matter jurisdiction because the extension of the '112...