Opinion ID: 1038335
Heading Depth: 3
Heading Rank: 1

Heading: The Intrinsic Record

Text: The patentees refer to “beads” five times in the intrinsic record. All of those references appear in the written description, and four concern the use of beads in cell culturing. 7 In each and every one of those four references, the patentees clearly distinguish culturing with beads from culturing in three-dimensions. a. Beads “as opposed to” Three-Dimensional Cultures The patentees’ first use of the term “beads” comes during their discussion of the characteristics of the cells grown by methods known in the art. In a subsection titled “Conditioned Cell Media” that appears in the background section of the written description, the patentees state: Conditioned medium contains many of the origi- nal components of the medium, as well as a varie- ty of cellular metabolites and secreted proteins, including, for example, biologically active growth factors, inflammatory mediators and other extracellular proteins. Cell lines grown as a monolayer or on beads, as opposed to cells grown in three- dimensions, lack the cell-cell and cell-matrix interactions characteristic of whole tissue in vivo. ’494 patent col. 1 ll. 33–44 (emphasis added). [T]he . . . inventors would have understood that beads could be used in three-dimensional culture systems.”). 7 The fifth reference to beads appears in a section of the written description discussing the use of “[r]igid spherical beads suspended in a Newtonian fluid” as part of “formulations for dermal augmentation.” ’494 patent col. 26 ll. 35-50. Neither of the parties contends that reference is somehow relevant here. SKINMEDICA INC v. HISTOGEN INC 17 It is quite apparent from the use of the disjunctive phrase “as opposed to” that the patentees considered cells grown on beads to be different and distinct from cells grown in what they considered to be three-dimensions. The plain meaning of the disjunctive phrase, “as opposed to,” is “contrary or opposite to” or “standing in opposition, contrast, or conflict.” Oxford English Dictionary 867, vol. X (2d ed. 1989). SkinMedica, however, would like to limit the import of the disjunctive phrase by reading the passage as: “Cell lines grown as a monolayer or ‘on [the surface of the] beads,’ as opposed to cells grown in three-dimensions.” Appellant’s Br. 38 (alteration in original) (emphasis added). The addition of the phrase “the surface of the” is necessary, according to SkinMedica, to clarify that “the text is addressing only two-dimensional culturing” with beads. Id. That clarification is important in SkinMedica’s view because beads can be used to culture cells in both two- and three-dimensions, and the “specification’s mentions of beads simply emphasize that beads can be used for purely ‘two-dimensional’ culturing (i.e., a single layer of cells cultured on the surface of the beads) and when so used are not sufficient to practice the invention.” Id. We do not see any reason to add additional language to the passage—especially the phrase proposed by SkinMedica. The plain words selected by the inventors exhibit a clear intent to distinguish between threedimensional culturing and culturing in monolayer and on beads. Nowhere do the inventors indicate otherwise. Nor at any point—in the written description or in the entire prosecution history—do the inventors ever mention the “surface” of beads. And there is no indication in the specification or prosecution history that the inventors believed beads could be used for both two- and threedimensional culturing—as they used those terms in their patents. Rather, as the patentees stated to avoid prior art 18 SKINMEDICA INC v. HISTOGEN INC during prosecution, “conditioned medium obtained from . . . cells cultured in two-dimensions . . . [is] not identical, expressly or inherently” to “medium obtained from the same cells cultured in three-dimensions.” J.A. 101245–46 (emphasis added). The patentees clearly distinguished two-dimensional and three-dimensional cultures as distinct and different methods to culture cells with distinct and different results. The plain import of the phrase “[c]ell-line grown as a monolayer or on beads, as opposed to cells grown in threedimensions” is that, in context of the patents, cultures in which cells are grown on beads are distinct and different from cultures in which cells are grown in three- dimensions. In light of the specification and prosecution history, that means cells grown on beads are cells grown in a two-dimensional culture. b. Beads Produce Inferior Cell Culture Medium The second reference to beads made by the patentees immediately follows the first. Cell lines grown as a monolayer or on beads, as opposed to cells grown in three-dimensions, lack the cell-cell and cell-matrix interactions characteristic of whole tissue in vivo. Consequently, such cells secrete a variety of cellular metabolites although they do not necessarily secrete these metabolites and secreted proteins at levels that approach physiological levels. Conventional conditioned cell culture medium, medium cultured by cell-lines grown as a monolayer or on beads, is usually discarded or occasionally used in culture manipulations such as reducing cell densities. ’494 patent col. 1 ll. 33–44 (emphasis added). In that passage, the inventors unmistakably differentiate culturing on beads from culturing in three- dimensions by distinguishing the chemical composition of SKINMEDICA INC v. HISTOGEN INC 19 the medium conditioned by cells grown by each method. The patentees first mention why the “metabolites and secreted proteins” in medium conditioned by cells grown “as a monolayer or on beads” are different than those in medium conditioned by “cells grown in three-dimensions”: because the latter have “cell-cell and cell-matrix interactions characteristic of whole tissue in vivo.” Id. They then declare that the “conventional” medium conditioned by cells “grown as a monolayer or on beads” is “usually discarded.” Id. There is a logical and plain conclusion from the passage. It is that “cell-lines grown as a monolayer or on beads” are distinct from three-dimensional cultures because they produce “conventional” media with inferior chemical compositions. The prosecution history supports this conclusion. During prosecution of the ’494 patent, the patentees juxtaposed the chemical composition of the medium produced by three-dimensional cultures with the medium produced by “conventional” means to demonstrate that the medium used in their patents was part of a novel and patentable invention. To overcome an anticipation rejection, the patentees argued that “[c]ulturing cells in threedimensions results in the production of a conditioned medium having a different chemical composition than that of cells cultured by conventional means.” J.A. 101245 (first emphasis altered) (second emphasis added). They also explained that the two media were “not identical, expressly or inherently” and differed, in part, by the abundance of growth factors and other cell metabolites. J.A. 101245–46; see also J.A. 101284-91 (a declaration submitted by patentees’ expert during prosecution describing the differences between the media in specific detail). In its briefing on appeal, SkinMedica even acknowledges that “a key advantage of culturing in three dimensions” is the chemical composition of the medium conditioned by cells grown in such cultures. They agree 20 SKINMEDICA INC v. HISTOGEN INC with the district court that “cells cultured in three dimensions secrete growth factors and other proteins in [higher] ratios” and that the medium conditioned by them are accordingly “superior.” Appellant’s Br. 31 (internal quotation marks omitted). We therefore read the second reference to beads in the written description as another clear and unmistakable statement that bead cultures are not the three- dimensional cultures the inventors require in their claimed methods. 8 The inventors argued during prosecution that the chemical composition of the medium produced by cells cultured in three-dimensions was a novel and patentable aspect of their invention (an argument with which SkinMedica agrees), and they clearly stated in the written description that cultures of cells grown on beads do not produce such novel and patentable results (they are “usually discarded”). Such emphasis on a particular mode of operation, especially to avoid prior art, can operate as a disclaimer of the otherwise broad scope of a claim term. See SafeTCare Mfg., Inc. v. Tele-Made, Inc., 497 F.3d 1262, 1270 (Fed. Cir. 2007) (finding disclaimer when a feature was repeatedly emphasized in contradiction to another and that particular “attribute of the invention [was] important in distinguishing the invention over the prior art”). 8 The only reason presented by SkinMedica to read the second reference to beads differently is because they believe that “the advantages of three-dimensional culturing apply equally to bead-based three-dimensional culturing.” Appellant’s Br. 31. That belief, however, is premised on Dr. Salomon’s opinion, Doyle, and Seldon— evidence we find unpersuasive in light of the clear disclaimers in the written description. See discussion infra Section II(B)(2). SKINMEDICA INC v. HISTOGEN INC 21 c. Beads (i.e., Two-Dimensions) The third reference to beads made by the patentees occurs at the beginning of a section titled “Detailed Description of the Invention.” It states that: The present invention relates to novel composi- tions comprising any conditioned defined or undefined medium, cultured using any eukaryotic cell type or three-dimensional tissue construct and methods for using the compositions. The cells are cultured in monolayer, beads (i.e., two-dimensions) or, preferably, in three-dimensions. ’494 patent col. 7 ll. 24–29 (emphasis added). Here, the patentees once again list cell culture methods that can be used in their invention, 9 and once again, clearly differentiate between cells cultured using beads and those cultured in three-dimensions. They list methods for culturing cells, include beads and three- dimensions in that list, and use a disjunctive (“or”) as the coordinating conjunction that reveals the relationship of the members in the list. The disjunctive “or” plainly designates that a series describes alternatives. See Kustom Signals, Inc. v. Applied Concepts, Inc., 264 F.3d 1326, 1331 (Fed. Cir. 2001) (explaining that “or” designates alternatives); see also Oxford English Dictionary 882, vol. X (2nd ed. 1989) (defining “or” as a particle “coordinating two (or more) words, phrases, or clauses, between which there is an alternative”). In Thorner, we recognized that the “use of two terms as alternatives” functions as a redefintion of a term if that redefinition is “so clear that it equates to an explicit one.” 669 F.3d at 1368. The pa- 9 The “invention” referenced by the patentees here is that which they originally envisioned, one not restricted to use of conditioned medium formed by cells cultured in three-dimensions. 22 SKINMEDICA INC v. HISTOGEN INC tentees’ distinction between bead and three-dimensional cultures is that clear. They not only repeated such a disjunctive listing of culturing methods elsewhere in the specification, but also expressly chose to define beads as culturing in “two-dimensions”—a definition that places beads in stark contrast to another method immediately following it in the list, “three-dimensions.” And, unlike in their first reference to beads, the inventors here do not distinguish cells “grown” in three-dimensions from cells “grown” “on” beads; they broadly distinguish cells “cultured in” three-dimensions from cells “cultured in . . . beads.” Furthermore, we agree with the district court that the “phrase ‘beads (i.e, two-dimensions)’ explicitly define[s] beads as a two-dimensional culture method, despite that culturing cells in three-dimensions on beads was known in the art.” J.A. 22. A plain reading of that phrase indicates that the patentees considered beads a form of twodimensional culturing that was not akin to the threedimensional culturing used in their invention. In a specification, a patentee’s “use of ‘i.e.’ signals an intent to define the word to which it refers.” Edwards Lifesciences LLC v. Cook Inc., 582 F.3d 1322, 1334 (Fed. Cir. 2009); see also Abbott Labs. v. Novopharm Ltd., 323 F.3d 1324, 1330 (Fed. Cir. 2003) (holding that a patentee “explicitly defined” a term by using “i.e.” followed by an explanatory phrase). The inventors also used the phrase “i.e.” elsewhere in the specification (twelve other times in total) to introduce an explanation or definition of a word or phrase. See ’494 patent col. 1 l. 7; col. 7 l. 44; col. 8 l. 65; col. 10 l. 1; col. 15 l. 16; col. 18 l. 52; col. 19 l. 20; col. 20 l. 16; col. 22 l. 40; col. 26 l. 15; col. 27 l. 36; col. 30 l. 58. Based on the plain meaning of the term “i.e.” and the patentees’ consistent use of it throughout the specification, there is no reason to believe that the inventors did not intend for the abbreviation to signal an intent to define the word it followed when they stated “[t]he cells are cultured in . . . SKINMEDICA INC v. HISTOGEN INC 23 beads (i.e., two-dimensions) or, preferably, in threedimensions.” SkinMedica, however, argues that the inventors did not explicitly define beads as a two-dimensional culture method. It asserts that our cases indicate that the “mere use of ‘i.e.’ does not act as an express definition or limitation” and “must be read in the context of the patent as a whole.” Appellant’s Br. 41. Read in context, SkinMedica believes that the phrase “beads (i.e., two-dimensions)” merely represents the inventors’ recognition of the ability to use beads in both two- and three-dimensional cultures. To SkinMedica, the phrase simply clarifies culturing beads in two-dimensions is different from culturing beads in three-dimensions. Any other reading, in SkinMedica’s view, would be inconsistent with the ordinary meaning of three-dimensional cultures, which includes the use of beads. We agree with SkinMedica that our reading of “beads (i.e., two-dimensions)” is “inconsistent” with the ordinary meaning of three-dimensional culturing; but that result is inescapable in context of the entire specification. Read as a whole, the specification provides no distinction between culturing with beads in two- versus three-dimensions in the specification. We do not believe that the patentees used the phrase “beads (i.e., two-dimensions)” to signal that beads “can” be a two-dimensional culturing method. That is a not a natural reading. The inventors go to great lengths (in over twenty-five columns of text in the specification) to explain dozens upon dozens of different ways to culture cells in three-dimensions, yet do not mention beads once in any of them. See ’494 patent cols. 7–32. And in the only places where the inventors mention culturing with beads in the specification, they clearly distinguish such culturing from growing or culturing cells in three-dimensions. During prosecution, the patentees disclaimed medium conditioned by “conventional means” and taught in the written description that cells grown on 24 SKINMEDICA INC v. HISTOGEN INC beads produce such “conventional” medium. Reading “beads (i.e., two-dimensions)” as definitional comports with the plain language of the specification as a whole and the inventors clearly expressed intent to differentiate the use of beads from three-dimensional culturing. While that result might be “inconsistent” with the ordinary meaning of three-dimensional culturing, it is one that the intrinsic record here plainly demonstrates to be correct. In addition, the import we assign to the term “i.e.” here aligns with our case law. We have held—as dis- cussed above—that a “specification’s use of ‘i.e.’ signals an intent to define the word to which it refers.” Edwards Lifesciences, 582 F.3d at 1334. As SkinMedica correctly points out, such use of “i.e.” is not absolute. It identifies several cases in which we did not give “i.e.” its plain meaning and import. But the reasoning of those cases does not apply here. SkinMedica first points to Toshiba Corp. v. Imation Corp., 681 F.3d 1358 (Fed. Cir. 2012). In that case, which concerned DVD technology, we were unconvinced that a patentee’s use of the term “i.e.” clearly expressed an intent to define a term and affect a prosecution history disclaimer. A patentee had responded to an office action and when describing a figure had stated: “As illustrated in FIG. 2 . . . [disc number and side] information must be provided on each side of the disc—i.e., each recording plane—in order for the disc side identifier 3 to serve its purpose of identifying which side is being recorded/reproduced.” Id. at 1370 (emphasis added). We reasoned that the patentee’s statement did not limit the claim term “recording plane” to a “disc side.” Id. That was because the patentee was “merely explaining that, in the example in figure 2, a side of the disc constitutes a recording plane”—which did not mean “a recording plane is to be equated with a disc side in all instances.” Id. SKINMEDICA INC v. HISTOGEN INC 25 In contrast, the patentees here did not use the term “i.e.” to discuss how an aspect of one particular embodiment of their invention depicted in a figure satisfied a claim limitation. They were providing a list of different alternative methods by which cells could be cultured, and they used the term “i.e.” to describe how one of those methods did not satisfy a claim limitation. And, unlike in Toshiba, the definition that follows “i.e.” here directly contrasts the term it is defining with another listed alternative (two- versus three-dimensions). Moreover, we are not assigning definitional intent to “i.e.” in order to directly assign meaning to a claim term. “Two-dimensions” appears nowhere in the allowed claims. And we are not proposing that the definition of “twodimensions” (the term that follows “i.e.” here) be restricted to or defined as only “beads” (the word that precedes “i.e.”). We do the opposite: we read “beads” (the word that precedes “i.e.”) to be defined by “two-dimensions” (the term that follows “i.e.”). That is a natural interpretation of “i.e.” The other cases SkinMedica relies on are similarly distinguishable. In Dealertrack, Inc. v. Huber, we refused to read “i.e.” as showing intent to define because doing so would exclude multiple embodiments clearly discussed throughout the claims. 674 F.3d 1315, 1326 (Fed. Cir. 2012) (“The only way that the “i.e.” in this patent could be read definitionally is if it excluded from the claim scope the embodiments discussed throughout the claim where only a single funding source is selected. This is rarely, if ever, correct.” (internal quotation marks omitted)). Here, the use of beads is mentioned nowhere in the claims. And in Pfizer, Inc. v. Teva Pharmaceuticals, USA, Inc., we refused to limit a disputed claim term to a narrow definition introduced by “i.e.” in a patent specification because the specification expressly included a broader definition of the term in a different section that the “patentee clearly intended . . . to address the meaning of the same term.” 26 SKINMEDICA INC v. HISTOGEN INC 429 F.3d 1364, 1373 (Fed. Cir. 2005). Here, there is no other section of the specification in which the patentees have defined “beads” as being broader than “two- dimensions.” Thus, we give the term “i.e.” here its plain meaning— that it “signals an intent to define the word to which it refers.” Edwards Lifesciences, 582 F.3d at 1334. That reading comports with the inventors’ other uses of the abbreviation in the specification and with each and every other reference to culturing with beads. We therefore conclude that the patentees expressly defined culturing in beads as a two-dimensional culturing method. Because it is defined as two-dimensional, culturing in beads cannot be the three-dimensional culturing required by the claims. d. Cells Cultured in Beads or in Three-Dimensions The fourth reference to beads made by the patentees occurs in the same section as the third, “Detailed Description of the Invention,” but under the subheading, “The Cell Cultures.” There the patentees state: The cells may be cultured in any manner known in the art including in monolayer, beads or in three-dimensions and by any means . . . . ’494 patent col. 9 ll. 66–col. 10 l. 1. Once again, the patentees list cell culture methods that can be used in their originally-claimed invention, and again use the disjunctive “or” to differentiate between cells cultured using beads and those cultured in threedimensions. As we concluded from such evidence previously, the use of the disjunctive in context of the entire specification and prosecution history in evidence plainly evinces an intent of the inventors to classify culturing with beads as a non-three-dimensional cell culturing method. SKINMEDICA INC v. HISTOGEN INC 27 e. Conclusion From the Intrinsic Record In sum, although the inventors never explicitly redefined three-dimensional cultures to exclude the use of beads, their implicit disclaimer of culturing with beads here was even “so clear that it equates to an explicit one.” Thorner, 669 F.3d at 1368. Without fail, each time the inventors referenced culturing with beads in the specification, they unambiguously distinguished that culture method from culturing in three-dimensions. Every time they included beads in a list of methods for culturing cells, the inventors indicated that bead cultures were an alternative to three-dimensional cultures (by using the disjunctive “or”) or distinct from three-dimensional cultures (by using the disjunctive phrase “as opposed to”). The inventors also discussed beads in order to explain how the conditioned medium created from cells grown in threedimensions was chemically distinct and superior to the conventional conditioned medium created from cells grown on beads—a point of novelty the patentees relied upon during prosecution to avoid anticipatory prior art. And the patentees expressly defined culturing in beads as culturing cells in “two-dimensions,” which excludes that method from the three-dimensional culturing required by the claims. The patentees repeated and definitive statements clearly indicate that they disclaimed the ordinary meaning of “culturing . . . cells in three-dimensions.” See, e.g., Computer Docking Station Corp., 519 F.3d at 1374 (citing Watts, 232 F.3d at 882) (“[R]epeated and definitive remarks in the written description could restrict a claim limitation to a particular structure.”); Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1117 (Fed. Cir. 2004) (“All that is required is that the patent applicant set out the different meaning in the specification in a manner sufficient to give one of ordinary skill in the art notice of the change from ordinary meaning. Because the inquiry into the meaning of claim terms is an objective one, a patentee who notifies the public that 28 SKINMEDICA INC v. HISTOGEN INC claim terms are to be limited beyond their ordinary meaning to one of skill in the art will be bound by that notification, even where it may have been unintended.”); In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994) (“Where an inventor chooses to be his own lexicographer and to give terms uncommon meanings, he must set out his uncommon definition in some manner within the patent disclosure so as to give one of ordinary skill in the art notice of the change.” (internal quotation marks omitted)); see also Philips, 415 F.3d at 1312 (“reaffirm[ing] the “basic principles of claim construction outlined” in several cases, including Innova/Pure Water). Our holding comports with our cases in which we have found similar implicit disclaimers. For example, in Bell Atlantic, a patent holder argued for a plain meaning of the word “mode,” which would “encompass[] different methods of altering . . . transmission rates.” 262 F.3d at 1269 (emphasis added). We held, however, that the patentees redefined the broad term “mode” and excluded “rates” by “implication.” Id. at 1273. Even though the patentees did not provide an “explicit definition[]” of “mode” that excluded “rates,” we explained that they used “the claim term ‘throughout the entire patent specification, in a manner consistent with only a single meaning,’ one that was a ‘different and distinct concept[]’ than ‘rate.’” Id. at 1271 (quoting SciMed, 242 F.3d at 1344 and Vitronics, 90 F.3d at 1582). As we found, the patentees had consistently described transmission “mode” and transmission “rate” as possessing different characteristics and had distinguished between them repeatedly by explaining that either transmission “rate or mode” could be independently altered. Id. at 1271–73. Thus, because there was no “[v]aried use of [the] disputed term,” we held that the repeated explicit differentiation between the terms constituted a disclaimer. Id. at 1273 (quoting and distinguishing Johnson Worldwide Assocs. v. Zebco Corp., SKINMEDICA INC v. HISTOGEN INC 29 175 F.3d 985, 992 (Fed. Cir. 1999)) (internal quotation marks omitted). As in Bell Atlantic, the patentees in this case have, without express redefinition, disclaimed a potential embodiment from the ordinary scope of a claim term through clear, repeated, and consistent statements in the specification that describe how culturing with beads is different and distinct from culturing in three-dimensions. Like the Bell Atlantic inventors, the patentees here repeatedly used the disjunctive “or” in the specification to carve out a disclaimed embodiment (“beads”) from the ordinary meaning of a broad term (“culturing in threedimensions”). And like the Bell Atlantic inventors, they also describe how the characteristics of the disclaimed embodiment were different from those of the claimed feature (that culturing on beads produces chemically different and inferior conditioned medium). Furthermore, the patentees here have done even more than the inventors in Bell Atlantic to distinguish their disclaimed embodiment from the ordinary scope of a claim term. In addition to the disjunctive “or,” they used the unambiguous disjunctive phrase “as opposed to” when differentiating between bead and three-dimensional cultures. They also expressly defined culturing with beads as culturing cells in “two-dimensions”—a definition that plainly excludes culturing with beads from threedimensional cultures. Thus, the patentees here have affected an even clearer implicit redefinition of a term than the inventors in Bell Atlantic. We stated in Thorner that an “‘implied redefinition must be so clear that it equates to an explicit one.” 669 F.3d at 1368. The implicit redefinition here satisfies even that hurdle. We are left with “no question that the . . . patent specification uses the terms [“culturing with beads”] and [“culturing in three dimensions”] to 30 SKINMEDICA INC v. HISTOGEN INC refer to two different and distinct concepts.” Bell Atlantic, 262 F.3d at 1272. We also reached a similar result in SafeTCare. 497 F.3d 1262. In that case, we held that an inventor of an adjustable hospital bed disclaimed the full scope of the phrase, “pushing force on said plurality of deck sections.” 497 F.3d at 1270 (emphasis added). The patent holder had argued for a broad construction to cover any bed that adjusted through a directional force applied to a “deck section.” Id. at 1268-69. However, because the patentee “repeatedly emphasize[d]” in the written description that “the patented invention applies a pushing force . . . against a lift dog [a support member],” not the deck section, we limited the scope of the asserted claim to a pulling force exerted on a lift dog. Id. at 1270 (emphasis added). We felt additional comfort in reaching that result because the patentee had distinguished “conventional” adjustable bed frames in the written description by explaining: “[E]ach of the shafts . . . of bed lift motors [in the invention] . . . apply pushing forces against their respective lift dogs . . . . This is in contrast to conventional bed frames in which lift motors exert a pulling force against the frame.” Id. (emphasis added). Like the SafeTCare inventors, the inventors here affected a disclaimer by repeatedly emphasizing in the written description that culturing with beads is a method of culturing distinct from three-dimensional culturing—a point we have discussed extensively above. As we were in SafeTCare, we are reassured here of that disclaimer because the inventors distinguished their invention over the prior art by clearly differentiating between the medium produced by culturing with conventional means and the medium produced by culturing in three-dimensions. They did that not only in the specification—as the patentees in SafeTCare did—but also during prosecution to overcome anticipation and obviousness rejections. SKINMEDICA INC v. HISTOGEN INC 31 It is therefore clear from the intrinsic record that, although the inventors never explicitly redefined “culturing . . . cells in three-dimensions” to exclude the use beads, they affected a clear implicit disclaimer of culturing with beads from the scope of their claimed invention.