Opinion ID: 1038335
Heading Depth: 4
Heading Rank: 2

Heading: Doyle

Text: According to SkinMedica, the inventors also could not have disclaimed the use of beads because they stated in the written description that “cells may be cultured in any manner known in the art” and incorporated Doyle into the specification, 10 which “expressly discusses the use of beads to culture cells in three dimensions.” Appellant’s Br. 26–30. In other words, according to SkinMedica, the inventors stated that any three-dimensional culturing method would work with their invention and listed culturing with beads as such a three-dimensional culturing method by incorporating Doyle. That argument fails for several reasons. First, SkinMedica reads the phrase “cells may be cultured in any manner known in the art” out of context. The sentence from which SkinMedica plucked that phrase states that “[t]he 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. 2. That statement described the scope of the invention covered by the original proposed claims, which were written to include any culture method. Those claims were rejected. The patentees restricted them to a single method of culturing—three-dimensional culturing—in order to avoid prior art. Therefore, while the original proposed invention could have used cells cultured in any 10 The patentees stated in the written description that Doyle was “incorporated by reference . . . in [its] entirety.” ’494 patent col. 7 ll. 51-52. 34 SKINMEDICA INC v. HISTOGEN INC manner known in the art, the claimed invention is limited to cells cultured only in three-dimensions. Accordingly, it is impossible to know whether any discussion of beads in Doyle was intended to be an example of the culturing methods covered by the broad original claims (which covered two- and three-dimensional cultures) or the narrow final claims (which was restricted to threedimensional cultures). Second, Doyle does not “expressly discuss[] the use of beads to culture cells in three dimensions,” as claimed by SkinMedica. Appellant’s Br. 26 (emphasis added). SkinMedica identifies one paragraph in that voluminous reference to support its assertion. A common occurrence in microcarrier culture is the formation of large microcarrier aggregates in which the microcarriers are joined by cellular bridges. Microcarrier aggregates made up of as many as 10 or more microcarriers are not uncom- mon. Microcarrier bridging occurs mainly during the growth phase of the culture, with little addi- tional bridging occurring after cell growth has ceased (Borys & Papoutsakis 1992). This study also showed that there is an inverse relationship between the rate of microcarrier bridging and agitation intensity. Thus, it may be of interest to operate at higher agitation intensities during the growth phase of the culture to minimize microcar- rier aggregation, and to slow down the agitation as cell growth slows to minimize cell detachment during the later stages of the culture. In certain cases, such as to promote bead-to-bead transfer of cells to bare microcarriers, low agitation rates would be desirable during the culture growth phase. J.A. 100974. Nowhere does that portion of Doyle “expressly discuss” culturing with beads in “three dimenSKINMEDICA INC v. HISTOGEN INC 35 sions.” The phrase “three dimensions” does not even appear in the passage. 11 Third, even if we assume that the passage from Doyle discusses what one of ordinary skill in the art might understand to be three-dimensional culturing with beads, the inventors’ general citation of Doyle does not indicate any reliance on that particular passage to define “culturing in three-dimensions” and to abandon the otherwise clear disclaimer of beads in the specification. When discussing cell culture methods, the patentees make the following reference to Doyle: The cells may be cultured in any manner known in the art including in monolayer, beads or in three-dimensions and by any means . . . . Meth- ods of cell and tissue culturing are well known in the art, and are described, for example, in [Doyle], supra; Freshney (1987), Culture of Animal Cells: A Manual of Basic Techniques, infra. ’494 patent col. 10 ll. 2–6. It is clear from that passage that the inventors did not refer to Doyle in order to define what they meant by “three-dimensional culturing” in their patent. They did not indicate their reference to Doyle was for that purpose; nor did they even refer with any detailed particularity to the passages in Doyle that, according to SkinMedica, may 11 Histogen’s counsel stated at oral argument that Doyle does, in fact, reference culturing cells in threedimensions. He asserted, however, that the reference is in the index and points readers to sections of the book that do not discuss culturing cells with beads. Oral Argument available at http://www.cafc.uscourts.gov/oralargument-recordings/2012-1560/all 28:51-29:08. But the index of Doyle is not in the record. We therefore give no weight to counsel’s statements. 36 SKINMEDICA INC v. HISTOGEN INC have discussed three-dimensional culturing with beads. When the inventors wanted to use Doyle to explain the potential scope of terms they used, they did so specifically. See ’494 patent col. 20 ll. 21–26 (“[I]t may be necessary to further process the resulting supernatant. Such processing may include . . . the methods described in [Doyle], supra, pp 29 D:0.1-29D:0.4.”). But when describing cell culturing methods, the inventors generally referred to Doyle and another reference to support their assertion that many methods of cell culturing were well known in the art. 12 We see no reason for such a non-specific reference to trump the clear disclaimer in the specification of culturing with beads. See Advanced Display Sys., Inc. v. Kent State Univ., 212 F.3d 1272, 1282 (Fed. Cir. 2000) (discussing how a host document must “identify with detailed particularity what specific material it incorporates” to properly incorporate such material by reference). 13 12 That one of those methods known in the art could have been three-dimensional culturing with beads is of no import here. We assumed the patentees already knew that fact when we found a clear disclaimer in the specification. 13 The district court relied on our decision in Ad- vanced Display Systems to find that Doyle was not part of the intrinsic record because it was not incorporated with “detailed particularity.” J.A. 22. SkinMedica argues that was error. Appellant’s Br. 27-30. It is unnecessary for us to decide whether Doyle was incorporated into the specification with adequate particularity to become part of the intrinsic record. We conclude that the inventors’ reference to Doyle does not avoid a clear disclaimer of beads because it was not relied on by the inventors for an explicit or implicit definition of “culturing in three-dimensions” that included beads. The SKINMEDICA INC v. HISTOGEN INC 37 Therefore, because Doyle does not define culturing with beads as “three-dimensional” and the inventors did not refer to Doyle for the purpose of defining what they meant by three-dimensional culturing, it does not inform our analysis in this case.