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Genentech, Inc. v. Amgen Inc.

United States District Court, D. Delaware

June 17, 2019

AMGEN INC., Defendant.

          Michael P. Kelly, Daniel M. Silver, MCCARTER &ENGLISH, LLP, Wilmington, Delaware; Paul B. Gaffhey, David I. Berl, Thomas S. Fletcher, Teagan J. Gregory, Charles L. McCloud, Kathryn S. Kayali, Jonathan S. Sidhu, Benjamin Moskowitz, WILLIAMS & CONNOLLY LLP, Washington, D.C.; Daralyn J. Durie, Adam R. Brausa, Eric C. Wiener, Eneda Hoxha, DURIE TANGRI LLP, San Francisco, California. Counsel for Plaintiffs.

          Melanie K. Sharp, James L. Higgins, Michelle M. Ovanesian, YOUNG CONAWAY STARGATT & TAYLOR, LLP, Wilmington, Delaware; Siegmund Y. Gutman, PROSKAUER ROSE LLP, Los Angeles, California; Steven M. Bauer, Kimberly A. Mottley, Gourdin W. Sirles, PROSKAUER ROSE LLP, Boston, Massachusetts. Counsel for Defendant.



         Pending before me are competing proposed claim constructions in this consolidated patent infringement action brought pursuant to the Biologies Price Competition and Innovation Act ("BPCIA"), 42 U.S.C. § 262 by Plaintiffs Genentech, Inc. and City of Hope (collectively, "Genentech") against Defendant Amgen, Inc. ("Amgen"). Genentech has accused Amgen of infringing 26 patents.

         The parties initially asked me to construe the meaning often claim limitations in seven of the asserted patents. I reviewed the parties' claim construction briefing and held a Marbnan hearing that spanned two days. D.I. 340; D.I. 345. By the conclusion of the Marbnan hearing, only seven claim terms in six of the asserted patents remained in dispute.[1] I address in this Memorandum those disputed terms.

         The disputed terms appear in the following patents: U.S. Patent Nos. 8, 512, 983 ("the '983 patent"); 9, 441, 035 ("the '035 patent"); 8, 574, 869 ("the '869 patent"); 6, 884, 879 ("the '879 patent"); 7, 169, 901 ("the '901 patent"); and 7, 060, 269 ("the '269 patent"). D.I. 225; D.I. 325. These patents cover a wide range of complex technologies. Accordingly, I write primarily for the parties and, to a large degree, presume familiarity with the underlying technology. In general, however, the '983 patent, '035 patent, and '869 patent relate to various aspects of manufacturing proteins, particularly antibodies, using a cell culture process. D.I. 226 at 326, 381, 476. The '879 patent, '901 patent, and '269 patent disclose humanized and variant anti-VEGF antibodies and various uses of those antibodies. Mat 69, 157, 240.


         "It is a bedrock principle of patent law that the claims of a patent define the invention to which the patentee is entitled the right to exclude." Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005). "'[T]here is no magic formula or catechism for conducting claim construction.' Instead, the court is free to attach the appropriate weight to appropriate sources 'in light of the statutes and policies that inform patent law.'" SoftView LLC v. Applelnc, 2013 WL 4758195, at *1 (D. Del. Sept. 4, 2013) (quoting Phillips, 415 F.3d at 1324). Construing the claims in a patent is a question of law. Markman v. Westview Instruments, Inc., 52 F.3d 967, 977-78 (Fed. Cir. 1995), aff'd, 517 U.S. 370, 388-90 (1996).

         Unless a patentee acts as his own lexicographer by setting forth a special definition or disavows the full scope of a claim term, the words in a claim are to be given their ordinary and accustomed meaning. Thorner v. Sony Comput. Entm 't Am. LLC, 669 F.3d 1362, 1365 (Fed. Cir. 2012). "[T]he ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application." Phillips, 415 F.3d at 1313. A person of ordinary skill in the art ("POSITA") "is deemed to read the claim term not only in the context of the particular claim in which the disputed term appears, but in the context of the entire patent, including the specification." Id. at 1313. "[T]he specification is always highly relevant to the claim construction analysis. Usually, it is dispositive; it is the single best guide to the meaning of a disputed term." Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996).[2]

         The court may also consider extrinsic evidence, which "consists of all evidence external to the patent and prosecution history, including expert and inventor testimony, dictionaries, and learned treatises." Phillips, 415 F.3d at 1317. "Extrinsic evidence is to be used for the court's understanding of the patent, not for the purpose of varying or contradicting the terms of the claims." Markman, 52 F.3d at 981. "The construction that stays true to the claim language and most naturally aligns with the patent's description of the invention will be, in the end, the correct construction." Renishaw PLC v. Marposs Societa 'per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998).


         A. "a glutamine-free production culture medium" ('983 patent)

Genentech's Construction: "A production culture medium that is essentially free of glutamine" *

Amgen's Construction: "culture medium used in the production phase that does not contain glutamine when formulated" *

Court's Construction: "a culture medium used in the production phase that is not formulated or supplemented with glutamine"

         1. Background

         Claim 1 of the '983 patent, reformatted for clarity, teaches:

A process for producing a polypeptide in a mammalian host cell expressing said polypeptide,
comprising culturing the mammalian host cell in a production phase of the culture in a glutamine-free production culture medium containing asparagine, wherein the asparagine is added at a concentration in the range of 7.5 mM to 15 mM.

         '983 patent at 49:12-17 (emphasis added).

         Antibodies are polypeptides, manufactured by culturing genetically-engineered cells inside tanks called bioreactors. The cells in the bioreactor are suspended in a solution called a "cell culture medium," which supplies, among other things, various nutrients for the cells to consume. Cell culture media are comprised of "base media" (also sometimes called "basal media") and "feed media." Id. at 1:3 3-3 6. A base medium is the initial medium added to the bioreactor. Feed media are periodically added to the bioreactor to supplement (or replenish) the nutrients in the base medium. Base media and feed media are "formulated" (i.e., made or prepared).

         The amino acid glutamine is a nutrient frequently used in the formulation of base and feed media. Cells not only consume glutamine, they also produce their own glutamine. As a result, the concentration of glutamine in a cell culture medium is dynamic, as cells are continually consuming and adding to the glutamine in the cell culture medium and a manufacturer can also add glutamine at any time through feed media.

         2. Analysis

         Amgen argues that "a glutamine-free production culture medium" refers to a cell culture medium used in the production phase of antibodies that omits glutamine as an ingredient in the formulation of the culture medium's base media and/or feed media. Genentech takes the position that "a glutamine-free production culture medium" refers to the concentration of glutamine measured in the bioreactor at any point during the production phase. Because cells themselves can produce glutamine during the production phase, a glutamine-free culture medium would not exist in the production phase if "-free" means "the absence of glutamine" or "zero glutamine." Thus, not surprisingly, Genentech proposes that "glutamine-free" allow for some amount of glutamine and asks me to construe "-free" to mean "essentially free." D.I. 325 at 2.

         I find that Amgen's proposed construction better aligns with the patent's intrinsic evidence and I will construe the limitation similarly to, though not exactly, the way Amgen does. Specifically, I will construe "a glutamine-free production culture medium" to mean "a culture medium used in the production phase that is not formulated or supplemented with glutamine." My reasoning is threefold.

         First, the written description of the patent states that "the culture media of the present invention can be based [on] any of the media described in [certain prior art] provided that glutamine is omitted as an ingredient" '983 patent at 29:5-12 (emphasis added). The words "omitted" and "ingredient" connote preparing a formulation, not measuring a sample of a cell culture medium.

         Second, the patent links the term "glutamine-free" with media "formulated with" zero glutamine. It describes, for example, Figure 4 as presenting certain "[e]ffect[s] of asparagine under glutamine-free ... conditions" and the caption to Figure 4 is: "Cases formulated with 0mM Glutamine, 0mM or 5mM Glutamate, 10mM Aspartate." Id. at 4:59-60 and Figure 4 (emphasis added). Similarly, Figures 1 through 3 and Example 1 provide the results of a study designed to test the production of polypeptides in a production medium formulated with various concentrations of glutamine, including "0" glutamine. Id. at Figures 1-3; id. at 44:26-46:61. As noted above, because cells themselves produce glutamine, a cell culture medium (which, by definition, contains cells) cannot have "zero" glutamine. Only the base or feed media-which do not contain cells-can be said to have zero or an absence of glutamine.

         Third, during the prosecution history, both the Patent Examiner and Genetech used "glutamine-free" to describe media that omitted glutamine as an ingredient in their formulations. The Patent Examiner rejected claim 1 of the '983 patent as anticipated by Nagle, Tomei, and Kurano, because each of these references taught a "glutamine-free medium." D.I. 228 at 1044-48. In its response to the rejection, Genentech agreed that Nagle, Tomei, and Kurano each taught a "glutamine-free" culture medium.[3] Id. at 1060-65. As a result, how Nagle, Tomei, and Kurano defined a glutamine-free medium informs how Genentech and the Examiner understood the meaning of the term. See Am. Radio LLC v. Qualcomm Inc., 578 Fed.Appx. 975, 980 (Fed. Cir. 2014) (stating that prior "can often help to demonstrate how a disputed term is used by those skilled in the art" (quoting Vitronics, 90 F.3d at 1584)). A review of Nagle, Tomei, and Kurano shows that each of them taught the formulation of a cell culture medium that omits glutamine as an ingredient.

         Nagle states: "The primary intent of this paper was to present the formulation of a heat-stable chemically defined medium that supported increased populations of several cell lines." D.I. 326-8, J. A. 2526-2531, at 261 (emphasis added). The composition of the medium presented in Nagle "differ[ed] from that previously reported by the omission of glutamine." Id. at 260. Thus, Nagle's formulation of a cell culture medium differed from that previously reported precisely because it omitted glutamine as an ingredient.

         Tomei describes growing mammalian cells in a "glutamine-free ... chemically defined medium." D.I. 326-8, J.A. 2532-2537, at 2:8-12. "The composition of the particular medium used for [Tomei's] invention is shown in Table 1," which omits glutamine as one of the "components." Id. at 2:52-55, Table 1. Tomei further states that the composition set forth in Table 1 "does not necessarily represent a critical formulation because other formulations may also be used." Id. at 2:55-57. Accordingly, Tomei taught that a glutamine-free cell culture medium omitted glutamine as a component of the formulation.

         Lastly, Kurano "investigated whether the cells were able to grow on glutamine free medium or not." D.I. 326-5, J.A. 2110-2125, at 122. To conduct the investigation, Kurano compared a "medium A," which was a "standard MEM-a medium ... purchased from Gibco" to a "medium B," which was "prepared" using the "same components" as medium A "other than glucose, glutamine and asparagine." D.I. 228 at 1087-89 (emphasis added). Thus, Kurano described a glutamine-free cell culture medium as prepared without glutamine as a component.

         The repeated references in the prior art to the terms "components" and "formulations" makes clear that those skilled in the art at the time of the invention used the term "glutamine-free" to refer to a culture medium that was not formulated or supplemented with glutamine. Those references are consistent with the intrinsic evidence cited above, and accordingly, I will construe "a glutamine-free production culture medium" as "a culture medium used in the production phase that is not formulated or supplemented with glutamine."

         B. "wherein the cystine is at a concentration of from 1.25 mM to 2.5 mM" ('035 patent)

Genentech's construction: "Plain and ordinary meaning. The recited cystine concentration is the concentration of cystine in* the bioreactor."

Amgen's construction: "wherein the cystine is at a concentration of from 1.25 mM to 2.5 mM calculated when the cell culture medium is formulated"

Court's construction: "wherein the cystine is at a concentration of from 1.25 mM to 2.5 mM calculated when the cell culture medium is formulated"

         1. Background

         Claim 1 of the '035 patent, reformatted for clarity, recites:

A method of producing bevacizumab, or a fragment thereof,
comprising the step of culturing a Chinese hamster ovary (CHO) cell comprising a nucleic acid encoding bevacizumab or fragment ...

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