743 F.Supp.2d 305
AVENTIS PHARMA S.A., and Sanofi–Aventis U.S., LLC, Plaintiffs,
v.
HOSPIRA, INC., Defendant.Aventis Pharma S.A., and Sanofi–Aventis U.S., LLC, Plaintiffs,
v.
Apotex, Inc., and Apotex Corp., Defendants.
C.A. Nos. 07–721–GMS
08–496–GMS.
United States District Court, D. Delaware.
Sept. 27, 2010.
[743 F.Supp.2d 313]
Steven J. Balick, Ashby & Geddes, Tiffany Geyer Lydon, Ashby & Geddes, Christopher N. Sipes, Pro Hac Vice, John G. Day, Ashby & Geddes, Kevin B. Collins, George F. Pappas, Pro Hac Vice, Lauren E. Maguire, Ashby & Geddes, Wilmington, DE, for Plaintiff.Richard K. Herrmann, Mary Matterer, Morris James LLP, Wilmington, DE, Imron T. Aly, Pro Hac Vice, James F. Hurst, Pro Hac Vice, Jovial Wong, Pro Hac Vice, Kathleen B. Barry, Pro Hac Vice, for Defendant Hospira Inc.Richard William Riley, Duane Morris LLP, Wilmington, DE, Anthony J. Fitzpatrick, Pro Hac Vice, Arthur Dresner, Pro Hac Vice, Elese E. Hanson, Pro Hac Vice, Laura A. Vogel, Pro Hac Vice, Matthew C. Mousley, Pro Hac Vice, Richard W. McLaren, Jr., Pro Hac, Vice, Richard T. Ruzich, Pro Hac Vice, Vincent L. Capuano, Pro Hac Vice, Ian Scott, Pro Hac Vice, Joseph M. Bennett-Paris, Pro Hac Vice, Kerry McTigue, Pro Hac Vice, for Defendant Apotex Inc.
In this consolidated patent infringement action, plaintiffs Aventis Pharma S.A. and Sanofi–Aventis U.S., LLC (collectively, “Sanofi” or “the plaintiffs”) allege that
[743 F.Supp.2d 314]
pharmaceutical products proposed by defendants Hospira, Inc. (“Hospira”) and Apotex, Inc. (“Apotex”) (collectively, “the defendants”) infringe the asserted claims of the patents-in-suit. (D.I. 1.) The court held a seven-day bench trial in this matter on October 26 through November 3, 2009. (D.I. 369–375.) Presently before the court are the parties' post-trial proposed findings of fact and conclusions of law concerning the validity and enforceability of the patents-in-suit and whether the defendants' proposed products infringe the patents-in-suit. (D.I. 378 & 383.)
Pursuant to Fed.R.Civ.P. 52(a), and after having considered the entire record in this case and the applicable law, the court concludes that: (A) claims 2 and 10 of the '561 Patent are invalid due to indefiniteness; (B) all asserted claims of the patents-in-suit are invalid due to obviousness; (C) the asserted claims are unenforceable due to inequitable conduct; (D) the asserted claims are not invalid due to double patenting; (E) the defendants' proposed products infringe asserted claims 2, 5, and 10 of the '561 Patent and. claim 33 of the '512 Patent; and (F) each of the parties Rule 52(c) motions are granted in part and denied in part. These findings of fact and conclusions of law are set forth in further detail below.
II. FINDINGS OF FACT 1A. The Parties1. Plaintiff Aventis Pharma S.A. is a French corporation with its principal place of business in Paris, France.
2. Plaintiff sanofi-aventis U.S., LLC is a Delaware corporation with its principal place of business in Bridgewater, New Jersey.
3. Aventis Pharma S.A. and sanofi-aventis U.S., LLC will be collectively referred to as “ Sanofi” or “ Plaintiffs.”
4. Rhone–Poulenc Rorer, SA is a predecessor in interest to Aventis Pharma SA.
5. Defendant Hospira, Inc. is a Delaware corporation with its principal place of business in Lake Forest, Illinois. Hospira and Maybe Pharma, will be collectively referred to as “ Hospira”.
6. Defendant Apotex, Inc. is a Canadian company with a principal place of business in Toronto, Ontario, Canada.
7. Defendant Apotex Corp. is a Delaware corporation with a principal place of business in Florida.
8. Apotex, Inc. and Apotex Corp. will be collectively referred to as “ Apotex”.
9. The Court has subject matter jurisdiction, as well as personal jurisdiction over all parties.
B. Background10. Taxanes are a group of chemotherapeutic agents which include the compounds paclitaxel and docetaxel.
11. Derived from a yew tree, i.e., taxus brevifolia, paclitaxel (also known by its commercial name “Taxol”) and docetaxel (which is also derived from a yew tree), are both hydrophobic antineoplastic agents
[743 F.Supp.2d 315]
demonstrating significant antitumor activity.
12. Docetaxel and paclitaxel work by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular function. Thus they are referred to as “anti-mitotic” drugs.
13. Taxanes interfere with cell division and thus preferentially disrupt the growth of cells, such as tumor cells, undergoing rapid cell division.
C. The Patents–in–Suit14. U.S. Application Number 07/930,392, from which U.S. Patent No. 5,714,512 B1 (the “'512 patent”) issued, was filed on August 23, 1993. The '512 patent issued on February 3, 1998 to Jean–Pierre Bastart, Thierry Depechez, and Jean–Louis Fabre.
15. U.S. Application Number 07/930,393, from which U.S. Patent No. 5,750,561 Bl (the “'561 patent”) issued, was filed on August 4, 1993. The ' 561 patent issued on May 12, 1998 to Jean–Pierre Bastart, Thierry Depechez, and Jean–Louis Fabre.
16. Both the '512 patent and '561 patent refer to French patent application FR 91 08527, which was filed on July 8, 1991.
17. Sanofi-aventis U.S. LLC is the current holder of approved New Drug Application (“NDA”) No. 020–449 for a docetaxel injection product, which has the proprietary name Taxotere®.
18. The FDA's Orange Book lists the following patents associated with NDA 20–449: the '512 patent, the '561 patent, U.S. Patent No. 4,814,470 (“'470 patent”), U.S. Patent No. 5,438,072, and U.S. Patent No. 5,698,582.
19. Sanofi sells a commercial version of a docetaxel formulation called Taxotere®. Taxotere® was first commercially available in the U.S. on or about May 14, 1996.
20. The first commercial version of Taxotere® used Formulation 2. That formulation was submitted in Sanofi's NDA 30–449. The label for this formulation stated that perfusions should be administered as soon as possible.
21. NDA 20–449 (for Taxotere®) was approved on May 14, 1996.
22. In 1997, Sanofi submitted a supplemental NDA or “sNDA” to the FDA with the same reference number, 20–449. This submission referred to what Sanofi called “Formulation 3” for Taxotere®. Formulation 3 was the same as Formulation 2 except that citric acid was added to the formulation.
23. Formulation 3 for Taxotere® was approved by the FDA in 1999. Taxotere® is currently commercially sold using Formulation 3.
24. Taxotere® is sold as a two-vial product. One vial is called a concentrate and the other is called a diluents. The concentrate vial has docetaxel, along with polysorbate 80, and residual amounts of ethanol. The diluent has water and ethanol.
25. The Taxotere® concentrate includes 40 mg/ml of docetaxel dissolved in polysorbate 80. The Taxotere® diluent includes 13% ethanol and the rest is water.
26. The concentrate vial and the diluents vial are then combined to form a “premix.” The premix is a solution that can be added to an IV bag to make a perfusion. According to the Taxotere® label, the premix is stable for up to 8 hours.
27. The premix can be diluted with 0.9% sodium chloride or 5% glucose solutions to prepare a perfusion for administration to patients. The recommended docetaxel concentrations in the perfusions are between 0.3 and 0.74 mg/ml. According to the Taxotere® label, the perfusion is stable for up to 4 hours.
28. Other than Taxotere®, there is not now and has never been another clinically
[743 F.Supp.2d 316]
tested or commercially available formulation of docetaxel in the U.S.
29. There is not now and has never been a clinically tested or commercially available formulation of paclitaxel in a formulation including polysorbate 80.
30. On July 3, 1992, applicants filed two applications under the Patent Cooperation Treaty (“PCT”). The first PCT application, PCT/FR/00624 (“PCT624”), entered the national phase in the United States in the priority chain leading to issuance of the '512 patent. The second PCT application, PCT/FR/00625 (“PCT625”), entered the national phase in the United States in the priority chain leading to issuance of the '561 patent. The specifications for PCT524 and PCT625 are not identical.
31. The application for the '512 Patent was filed on December 1995 and was assigned serial number 08/568, 760 (“the '760 Application”). The '760 Application was filed as a continuation-in-part application claiming priority through U.S. Patent Application Serial No. 08/398, 011 (“'011 Application”) back to French national application serial number 91 08527 (“FR527”). The application was originally filed with 35 claims and was assigned to a different examiner than the person that had examined and allowed the '011 Application.
32. On May 23, 1997, the PTO issued a Notice of Allowability of all pending claims on the '512 patent.
33. According to the '512 patent, the prior art formulation of paclitaxel caused “manifestations of alcohol poisoning during treatment.” According to the '512 patent, “the present invention provides compositions that make it possible either to reduce the ethanol concentrations greatly, or to eliminate Cremophor and ethanol completely from the perfusions.”
34. The specification of the '512 patent beings with the following introductory paragraph:
The present invention relates to compositions and especially pharmaceutical dosage forms containing therapeutic agents having antitumor and antileukemic activity. It relates more especially to compositions suitable for injection containing taxane derivatives, such as, in particular, taxol or one of its analogues or derivatives of the formula (1) [ILLUSTRATION SHOWN] in which R1 and R2 each represent a hydrogen atom or one of R1 and R2 represents a hydrogen atom and the other represents a hydroxyl, acyloxy, or acylcarbonylocy radical, or R2 represents a hydrogen atom and R1 forms a single bond together with the methyl carbon atom situated in the alpha position, so they...
