Boehringer Ingelheim Animal Health v. Schering-Plough

• Decision Date: 06 October 1997
• Docket Number: No. CIV. 96-04047(HAA).,CIV. 96-04047(HAA).
• Citation: 984 F.Supp. 239
• Parties: BOEHRINGER INGELHEIM ANIMAL HEALTH, INC., Plaintiff, v. SCHERING-PLOUGH CORPORATION and Schering Corporation, Defendants.
• Court: U.S. District Court — District of New Jersey

984 F.Supp. 239

BOEHRINGER INGELHEIM ANIMAL HEALTH, INC., Plaintiff, v. SCHERING-PLOUGH CORPORATION and Schering Corporation, Defendants.

No. CIV. 96-04047(HAA).

United States District Court, D. New Jersey.

October 6, 1997.

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Jonathan A. Marshall, Jennifer Gordon, Scott D. Simpson, Pennie & Edmonds, New York, N.Y., H. Curtis Meanor, William Sandelands, Podvey, Sachs, Meanor, Catenacci, Hildner & Cocoziello, Newark, New Jersey, for Plaintiff.

Sidney David, Paul H. Konchanski, Lerner, David, Littenberg, Krumholz & Mentlik, Westfield, NJ, for Defendants.

OPINION

HARLOLD A. ACKERMAN, District Judge.

This matter comes before the court on plaintiff's motion for a preliminary injunction in its patent infringement action.¹ For the reasons detailed below, plaintiff's motion is DENIED.

I. Background

This patent litigation arises from two company's endeavors to develop a vaccine for a disease known as Porcine Reproductive Respiratory Syndrome ("PRRS")—"the most challenging infectious disease facing the [swine] industry today." Hays Declaration ¶ 6, Ex. 5 (copy of Schering letter to Swine Industry Professionals from Robert J. Young, Product Director, Large Animal Business Unit). This disease, PRRS, also known as Mystery Swine Disease ("MSD") and Swine Infertility and Respiratory Syndrome ("SIRS"), infects pigs and causes them to give birth to dead or sickly piglets. In addition, it causes reproductive failure, respiratory disease, and other symptoms such as anorexia, fever, dyspnea, and neurological impairment.

A. Basic Principles of Virology

Before one can begin to analyze the issues involved in this case, it is important to outline the some general principles of virology. Viruses, such as PRRS, are parasitic organisms that grow and multiply within "host cells." A virus depends on the host cell's "machinery" for survival and uses that machinery to reproduce. It will use this machinery to produce its own proteins and nucleic acids— the blueprint of all genetic information in living organisms. When a higher organism such as an animal or human is exposed to a virus and its cells become viral hosts, the animal or human develops a natural immunity. This immune response operates at two levels: first, at the initial stage of the infection before the virus has invaded the host and second, after the virus has invaded. When the virus stimulates certain specialized cells, these cells produce antibodies which prevent future infection. But this exposure still produces disease symptoms. Thus, the universal objective of virologists is to develop a vaccine which produces an immune response without the attending sickness.

There are two common types of vaccines— killed virus vaccines and modified-live virus vaccines. Both Boehringer and Schering's vaccines are derived from modified live viruses. A modified-live virus is made by obtaining a strain of the virus and putting it through the process of "attenuation." To "attenuate" a virus, like PRRS, means to repeatedly pass it through an appropriate in vitro culture system. In very crude terms, this means taking a tissue sample from a diseased animal and putting it into some kind of a vessel, like a bottle, with a host cell. When placed in a favorable medium, the tissue simple and cells interact in such a way as to facilitate the growth of the virus. That is the first passage. Then, the fluid or material containing the virus is transferred to another vessel with the host cell and passaged through a similar process. That is the second passage. Ultimately, the attenuation process alters the virus enough so that it produces the immune response and thereby protects against any subsequent infection without causing the disease. To be sufficiently attenuated, a virus may be passaged several times. The number of passages varies with each vaccine. For example, Schering has developed a PRRS vaccine which has been passaged ninety-four times.

B. Boehringer's Effort

In the early 1990's, Boehringer initiated an "extensive research program to study PRRS and develop a vaccine." Plaintiff's Br. at 4. First, Boehringer focused its energies on the task of "finding a suitable host cell" in which to grow and replicate the causative virus. See Gorcyca Declaration ¶ 12; Plaintiff's Br. at 4. In 1990, at the Conference of Research Workers in Annual Diseases, Joseph Harris, a Boehringer research assistance met Dr. James Collins and Dr. David Benfield, two scientists from the University of Minnesota and South Dakota State University scientist, respectively. Collins and Benfield had been working together on the cause of PRRS. They had successfully collected specimens from various organs of diseased pigs, reduced the organs to a tissue homogenate from which an inoculum could be prepared, and inoculated the inoculum into gnotobiotic pigs.² See Defendant's Br. at 5. As a result of their work, they could reproduce the symptoms of PRRS in the pigs. However, they were unable to observe CPE on cell lines. Id. at 6. CPE refers to "cytopathic effect" which the plaintiff has defined as a "change in the microscopic appearance of a cell after infection with a virus" or some observable effect shown on the simian cells. As the defendant has explained, this observable effect is the killing of inoculated cells. The court will elaborate on the significance of CPE below, (see infra, at 252), but for now, it is sufficient to know that one needs to observe CPE to be able to grow the virus on a cell line. Thus, Collins and Benfield could not grow the virus.

At some point, Boehringer agreed to work with Collins and Benfield on PRRS. Thereafter, Harris sent Collins a number of cell lines, but Collins did not try them. Collins sent his inoculum samples to Harris at the Boehringer lab so that Harris could try the inoculum on his own cell lines. On April 25, 1991, Harris observed CPE on the partial cell line derived from a monkey kidney, MA-104.

To confirm that it has been able to recover the PRRS virus, Boehringer need to perform what is known as "Koch's Postulates." In the instant case, this entailed sending the third passage of the virus to Benfield. Dr. Benfield took the viral agent recovered by Harris and introduced it into gnotobiotic pigs who then exhibited symptoms of the disease. Benfield took tissue samples from the diseased pigs and sent them back to Dr. Collins and then to Harris. Using the same method described above, Harris inoculated and incubated the sample and observed CPE. This satisfied Koch's Postulates and confirmed that Boehringer had been successful in recovering the PRRS virus.

After it "discovered that PRRS viruses could be grown and isolated on a full or partial sheet of simian monkey cells," specifically MA-104, Boehringer filed a patent application on August 26, 1991. On December 19, 1995 the Patent Office issued as Boehringer Patent No. 5,476,778 ("the '778 Patent"). The '778 Patent made the following five claims:

1. A method of growing and isolating swine infertility and respiratory syndrome virus, ATCC-VR2332, which comprises inoculating the virus on a full or partial sheet of simian cells in the presence of serum in a suitable growth medium and incubating the inoculated cell sheet at about 34°C. to 37°C. until CPE is observed.

2. The method as recited in claim 1 wherein the simian cell line is MA-104.

3. A method of attenuating swine infertility and respiratory syndrome virus, ATCC-VR2332, which comprises passaging the virus through simian cell line on maintenance medium in the presence of serum at ph about 7.6 about twenty-five time at about 35°-37°C without carbon dioxide, and then passaging the resulting virus through a simian cell line on maintenance medium in the presence of serum at ph about 7.6 about twelve times at about 31°C.

4. The method as recited in claim 3 wherein the simian cell line is MA-104.

5. The method as recited in claim 4 wherein the passages occur without CO_2.

In the instant action, only claims 1 and 2 are at issue. Notably, these two claims do not cover a vaccine. Rather, Boehringer believes that its patent covers a method which is instrumental in developing a vaccine for PRRS. After the patent issued, Boehringer obtained two licenses for modified-live vaccines —RespPRRS™ and RespPRRS/Repro™ —which prevent the respiratory form of PRRS. Boehringer alleges that these vaccines were made using patented methods at issue in this litigation.

C. Schering's Alleged Infringement

Like Boehringer, the defendant in this case Schering-Plough and Schering Corp. (collectively "Schering") was interested in the PRRS disease. In October 1991, Schering isolated its own strain of the PRRS virus using porcine alveolar macrophages as a host cell. Then, Schering created its "Master Seed Virus" by putting the virus through an attenuation process comprising ninety-four passages. It then developed a vaccine production process whereby it produced more of the virus using MA-104, a simian cell line, as a host cell line. According to the plaintiff, on August 20, 1996, Schering-Plough and Schering Corp. (collectively "Schering") "commenced sales of a swine vaccine for the prevention of PRRS that is made by a method that infringes the '778 Patent." Plaintiff's Br. at 1. As a result, the plaintiff alleges that Schering has infringed upon claims 1 and 2 of its '778 Patent, both literally and under the doctrine of equivalents.

II. Motion for Preliminary Injunction

A party seeking a preliminary injunction must establish four factors:

1. a reasonable likelihood of success on the merits

2. an irreparable harm

3. the balance of hardships tipping in its favor; and

4. a tolerable effect on the public interest.

Sofamor Danek Group v. DePuy-Motech, 74 F.3d 1216, 1219 (Fed.Cir.1996).

The court "must balance these factors against one another and against the extent of the relief sought." Id. The movant bears the burden of proving entitlement to...