In a complaint filed June 14, 2016, Janssen Biotech Inc. seeks a preliminary injunction that would bar Celltrion and Hospira from selling the biosimilar version of Remicade® (infliximab) that received FDA approval April 2016, and also could impact the production of the Celltrion/Hospira products sold abroad. This complaint is separate from the pending biosimilar litigation and based on alleged actual infringement of a patent directed to specific cell culture media compositions used to produce infliximab.

The Patent At Issue

The patent at issue is U.S. Patent  7,598,083, directed to specific cell media compositions. Claim 1 recites:

1. A soluble composition, suitable for producing a final volume of cell culture media, wherein the composition comprises the following components in the following amounts per liter of the final volume of cell culture media:
anhydrous CaCl2, 5-200 mg; anhydrous MgCl2, 15-50 mg; anhydrous MgSO4, 20-80 mg; FeSO4.7H2O, 0.05-0.50 mg; Fe(NO3)3.9H2O, 0.01-0.08 mg; ZnSO4.7H2O, 0.40-1.20 mg; ferric ammonium citrate, 0.04-200 mg; KCl, 280-500 mg; NaCl, 5000-7500 mg; NaH2PO4.H2O, 30-100 mg; Na2HPO4, 30-100 mg; CuSO4.5H2O, 0.001-0.005 mg; CoCl2.6H2O, 0.001-0.10 mg; (NH4)6Mo7O24 4H2O, 0.001-0.005 mg; MnSO4.H2O, 0.000070-0.0080 mg; NiSO4.6H2O, 0.000025-0.0005 mg; Na2SeO3, 0.004-0.07 mg; Na2SiO3.9H.2O, 0.02-0.4 mg; SnCl2.2H2O, 0.000025-0.0005 mg; NH4VO3, 0.0001-0.0025 mg; D-Glucose, 500-8000 mg; sodium pyruvate, 0.0-1000 mg; sodium hypoxanthine, 0.0-20.0 mg; glycine, 0.0-150 mg; L-alanine, 0.0-150 mg; L-arginine.HCl, 200-5000 mg; L-asparagine.H2O, 40-250 mg; L-aspartic acid, 20-1000 mg; L-cysteine.HCl H2O, 25.0-250 mg; L-cystine.2HCl, 15-150 mg; L-glutamic acid, 0-1000 mg; L-histidine.HCl.H2O, 100-500 mg; L-isoleucine, 50-1000 mg; L-leucine, 50-1000 mg; L-lysine.HCl, 100-1000 mg; L-methionine, 50-500 mg; L-ornithine.HCl, 0-100 mg; L-phenylalanine, 25-1000 mg; L-proline, 0-1000 mg; L-serine, 50-500 mg; L-taurine, 0-1000 mg; L-threonine, 50-600 mg; L-tryptophan, 2-500 mg; L-tyrosine.2Na.2H2O, 25-250 mg; L-valine, 100-1000 mg; d-biotin, 0.04-1.0 mg; D-calcium pantothenate, 0.1-5.0 mg; choline chloride, 1-100 mg; folic acid, 1-10 mg; i-Inositol, 10-1000 mg; nicotinamide, 0.5-30 mg; p-aminobenzoic acid, 0.1-20 mg; riboflavin, 0.05-5.0 mg; thiamine.HCl, 0.5-20 mg; thymidine, 0-3.0 mg; vitamin B12, 0.05-5.0 mg; linoleic acid, 0.01-2.0 mg; DL-α-lipoic acid, 0.03-1.0 mg; pyridoxine.HCl, 0.5-30 mg; putrescine.2HCl, 0.025-0.25 mg; and ethanolamine.HCl, 2-100 mg.

Discovering The Alleged Infringement

According to the complaint, in proceedings surrounding the biosimilar litigation, “Celltrion and Hospira refused to provide information about the composition of the cell culture media used to make their biosimilar product and where the media was made.” However, “HyClone (a non-party to that action) eventually disclosed the composition of the media and that it was custom made for Celltrion in Logan, Utah.” As noted in the complaint, the court overseeing that action “granted Janssen’s motion to modify the protective order to permit the present action.”

The Alleged Infringement

According to the complaint, the claimed cell culture media were developed by “employees of Centocor (Janssen’s predecessor),” and originally manufactured by HyClone for Centocor “on a large scale for testing for biopharmaceutical production,” under a confidentiality agreement.

As told by Janssen, “Centocor decided not to use HyClone as its supplier for cell culture media for Remicade®,” but HyClone is now Celltrion’s supplier for cell culture media for Celltrion’s and Hospira’s biosimilar version of Remicade®.” According to the complaint, “[a]t least four of the same HyClone employees that worked on the cell culture media project for Centocor also worked on the development of Celltrion’s cell culture media.” However, “HyClone did not disclose to Centocor that it was collaborating with Celltrion or that its employees who worked on Centocor’s media were helping to develop media for Celltrion.” (Janssen also has sued HyClone for infringement of the ‘083 patent.)

The complaint asserts that “at least two of the cell culture media custom made by HyClone for Celltrion” infringe claims 1 and 2 of the ‘083 patent under the doctrine of equivalents. In particular, Janssen asserts:

  • By directing and controlling its agent HyClone’s development of the infringing media, and by participating in a contractual relationship pursuant to which HyClone continues to manufacture the infringing media, Celltrion has directly infringed and continues to directly infringe the 083 patent under 35 U.S.C. § 271(a).
  • By ordering the infringing custom-made cell culture media–in order to make and sell Defendants’ biosimilar infliximab products–Celltrion has induced and continues to induce the infringement of claims 1-2 of the 083 patent by HyClone, under the doctrine of equivalents, under 35 U.S.C. § 271(b).
  • Hospira actively induced the infringement by Celltrion and HyClone of the 083 patent under 35 U.S.C. § 271(b) by entering into one or more agreements with Celltrion to market and distribute a biological product made using infringing media. Hospira has ordered and sold its infliximab products outside of the United States, knowing that infringing media is made in the United States in order to make infliximab products.
  • Under contract with Celltrion, HyClone has manufactured and continues to manufacture the infringing custom-made media in the United States for Celltrion’s use in the manufacture and sale of a biological product that has been and continues to be sold by Celltrion and Hospira outside of the United States under the trade names Remsima and Inflectra respectively and that Hospira intends to sell in the United States under the trade name Inflectra.

According to the complaint, Celltrion and Hospira have sold infliximab products outside the U.S. (Remsima and Inflectra) since 2012. Thus, Janssen seeks actual damages for this past infringement (trebled) in addition to an injunction.

Is Janssen Concerned About The On Sale Bar?

The complaint notes that “Centocor retained HyClone to manufacture [the] new cell culture medium …. before the October 29, 2004 priority application for the 083 patent was filed.” Although the complaint asserts that this work was done under an “April 2013 confidentiality agreement between the two companies,” I can’t help but wonder if the contract manufacturing arrangement could give rise to an on sale bar if the Federal Circuit does not reach a different outcome on rehearing of The Medicines Company v. Hospira, Inc. Since Hospira was the alleged infringer in that case, I presume it will raise the issue if the facts might support invalidity on that basis.