UCB, Inc. v. Yeda Research & Dev. Co., 1:14cv1038(LMB/TCB).

• Court: United States District Courts. 4th Circuit. United States District Court (Eastern District of Virginia)
• Citation: 117 F.Supp.3d 755
• Docket Number: No. 1:14cv1038(LMB/TCB).,1:14cv1038(LMB/TCB).
• Parties: UCB, INC., Plaintiff/Counterclaim–Defendant, v. YEDA RESEARCH AND DEVELOPMENT CO., LTD., Defendant/Counterclaim–Plaintiff.
• Decision Date: 30 July 2015

117 F.Supp.3d 755

UCB, INC., Plaintiff/Counterclaim–Defendant,
v.
YEDA RESEARCH AND DEVELOPMENT CO., LTD., Defendant/Counterclaim–Plaintiff.

No. 1:14cv1038(LMB/TCB).

United States District Court, E.D. Virginia, Alexandria Division.

Signed July 30, 2015.

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Gregory N. Stillman, Wendy Cohen McGraw, Hunton & Williams, Norfolk, VA, Julie Margaret Peters, Hunton & Williams LLP, McLean, VA, for Plaintiff/Counterclaim–Defendant.

Syed Mohsin Reza, Mary Catherine Zinsner, Troutman Sanders, LLP, Tysons Corner, VA, for Defendant/Counterclaim–Plaintiff.

MEMORANDUM OPINION

LEONIE M. BRINKEMA, District Judge.

Plaintiff/Counterclaim–Defendant UCB, Inc. ("UCB") brought this declaratory judgment action seeking a declaration that its Cimzia® product, a humanized monoclonal antibody approved by the Food and Drug Administration ("FDA") for the treatment of rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis, and Crohn's disease, does not infringe defendant's patent and that the patent is invalid. Specifically, UCB argues that the defendant's patent does not cover humanized monoclonal antibodies like Cimzia®, Defendant/Counterclaim–Plaintiff Yeda Research and Development Co., Ltd. ("Yeda") owns United States Patent No. 6,090,923, titled "Murine Monoclonal Antibody Binding TNFα" (the "′ 923 Patent"). In its answer and counterclaim, Yeda alleges that the ′ 923 Patent is valid and that UCB infringes claims 1, 5, and 9 of the ′ 923 Patent by producing Cimzia®.

Before the Court are Yeda's Motion for Partial Summary Judgment, [Dkt. No. 83],¹ and UCB's Motion for Summary Judgment of Non–Infringement and Invalidity, [Dkt. No. 80], which focuses on the meaning of "monoclonal antibody" in the ′ 923 Patent. UCB argues that the term "monoclonal antibody," used in claims 1, 5, and 9 of the ′ 923 Patent, does not include humanized antibodies like Cimzia® because the technology to make humanized antibodies did not exist when the ′ 923 Patent was filed in December of 1984. Yeda responds that the plain meaning of "monoclonal antibody" is broad enough to include humanized antibodies. Although the parties raise numerous other arguments,

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deciding the meaning of "monoclonal antibody" resolves this action. For the reasons that follow, UCB's Motion for Summary Judgment will be granted in part and Yeda's Motion for Partial Summary Judgment will be denied as moot.

I. BACKGROUND

A. Monoclonal Antibodies

Humans and animals have immune systems which produce specialized cells called "antibodies" to attack viruses, bacteria, and other foreign invaders (also referred to as "antigens"). Plaintiffs Opening Brief in Support of Summary Judgment [Dkt. No. 81] ("UCB's MSJ Br.") at 3; Defendant Yeda's Opening Claim Construction Brief [Dkt. No. 88] ("Yeda's CC Br.") at 9. An antibody contains a "constant region" and a "variable region," also referred to as a "variable domain." Yeda's CC Br. at 9. An antibody genus consists of all antibodies with the same constant region. Id. Species within that genus have identical constant regions, but different variable regions. Id. The antibody genus relevant to the present civil action is the immunoglobulin ("IgG") antibody, as shown below:

Yeda's CC Br. Ex. 4 at 4. All antibodies in a given species have identical constant and variable regions. In addition, each antibody species is produced by a specialized immune cell called a "B-cell." Declaration of Dr. Scott A. Siegel [Dkt. No. 166] Ex. 1 ("Siegel Opening Report") ¶ 16. Each B-cell is only capable of making a single antibody species. Id

An antibody attacks an antigen by binding its variable region to the antigen. Yeda's CC Br. at 3. Multiple species of antibodies can bind to the same antigen, but each antibody will bind to the antigen in a different way. Id. at 8. For example, different species of antibodies may bind to different parts of the same antigen, to the same part of the antigen but in a different orientation, or bind more or less strongly to the antigen.Id. Binding location, binding orientation, and binding strength all contribute to how successfully an antibody can neutralize an antigen. Id. The variable region not only determines which antigen the antibody attacks, but also how effectively the antibody attacks that antigen. Id

To develop antibodies useful for treating human illnesses, scientists had to be able to produce large quantities of the particular antibody they sought to study. In 1975, two scientists developed a method which allowed researchers to study populations of homogenous antibodies. By fusing the B-cell for a particular antibody with benign tumor cells, researchers could create a single, hybrid cell, referred to as a "hybridoma,"² which would continuously produce clones of the antibody produced by the B-cell. Id.; Yeda's CC Br. Ex. 5 at 3–4; Yeda's CC Br. Ex. 6 at 3. The resulting

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homogenous antibody population is referred to as "monoclonal." Yeda's CC Br. Ex. 4 at 9. The B-cell provides the "blueprint" for the antibody to be created, while the tumor cell provides the ability for the hybridoma cells "to grow rapidly and continuously in the research laboratory, in a process development lab, or therapeutic manufacturing facility." Id . By December of 1984, the method of making monoclonal antibodies using hybridomas was well known. Yeda's CC Br. Ex. 5 at 4.

Initially, the cells used to make the hybridoma which created monoclonal antibodies came from mice.³ Using antibodies derived from non-human animals to treat humans presents complicated problems because these foreign substances often cause the human immune system to reject the substance, harming the patient and reducing the efficacy of the treatment. Declaration of Dr. James S. Huston [Dkt. No. 167] Ex. 1 ("Huston Opening Report") ¶ 51. To avoid rejection, it is desirable for the antibody to resemble a human antibody as closely as possible. Id.

During the 1980s, researchers began to use genetic engineering to create antibodies less likely to induce immune responses. Instead of being produced by a hybridoma, genetic engineering involved isolating the gene responsible for producing the antibody, altering the gene, and introducing that gene into a host cell capable of producing large amounts of the antibody. Id. ¶ 26. "Chimeric"⁴ monoclonal antibodies had a variable region from a mouse and a constant region from a human. Yeda's CC Br. Ex. 4 at 9. Because a chimeric antibody has a large human region, it is less likely to cause an immune response. See Huston Opening Report ¶ 51. Later, scientists developed "humanized" monoclonal antibodies, which are primarily human with only small portions of nonhuman material. Id. Because humanized monoclonal antibodies are closer to pure human antibodies than chimeric antibodies, there is an even further decreased chance that the human immune system will reject the antibody. Id. The image below shows the relative differences between mouse (murine), chimeric, humanized, and human antibodies:

Yeda's Supplemental Brief [Dkt. No. 217] ("Yeda's Supp. Br.") at 29.

B. Tumor Necrosis Factor

In 1975, scientists discovered that some animals, including humans, produced a

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substance that killed tumor cells. Yeda's CC Br. Ex. 3 at 6. That substance is now called "tumor necrosis factor" ("TNF"). Id. TNF became the target of intense research during the early 1980s as a possible cancer treatment due to its ability to destroy tumor cells. Id. at 6, 9; Declaration of Dr. Wayne A. Marasco [Dkt. No. 165] Ex. 1 ("Marasco Report") ¶ 65. To study TNF, researchers needed a method to purify it and to obtain enough of it to use in experiments. Yeda's CC Br. Ex. 5 at 4. The "most efficient and effective method" of purifying TNF was to use monoclonal antibodies. Id. There was considerable difficulty in purifying human TNF, however, because it only naturally occurred in the human body in very small amounts. Yeda's CC Br. Ex. 3 at 9.

High levels of TNF were also found to lead to serious medical conditions such as "sepsis, rheumatoid arthritis, and Crohn's disease." Marasco Report ¶ 64. As research continued into the late 1980s, scientists discovered that in addition to being used to purify TNF, "the antibodies themselves could serve as therapeutic agents." Yeda's CC Br. Ex. 5 at 4. Specifically, the antibodies could be used to reduce the levels of TNF in a person's body, thereby reducing the debilitating effects of those disorders. This realization, and subsequent research, eventually led to the development of Cimzia®, a humanized monoclonal antibody that functions by binding (and therefore neutralizing) TNF.⁵ UCB's MSJ Br. at 1.

C. The Claimed Invention

The application which would become the ′ 923 Patent was filed on December 12, 1985, claiming priority to an Israeli patent application filed on December 20, 1984. The ′ 923 Patent did not issue until July 18, 2000. The nearly fifteen-year pendency of that application led Yeda's own attorney to describe the ′ 923 Patent as a " 'submarine' patent"⁶ and used the "exceedingly...