Opinion ID: 1038335
Heading Depth: 3
Heading Rank: 2

Heading: Further Arguments Raised by SkinMedica

Text: SkinMedica asserts four additional reasons not to find a disclaimer of beads. First, it asserts that the inventors “expressly defin[ed] the term ‘three-dimensional framework,’” which is “used in ‘culturing . . . in three- dimensions,” to be “broad enough to include a threedimensional structure formed using beads.” Appellant’s Br. 26. Second, it stresses that the specification incorporated and referenced Doyle, “which expressly discusses the use of beads to culture cells in three dimensions.” Appellant’s Br. 26. Third, it claims that Seldon “expressly acknowledges that three-dimensional culturing with beads provides the same inherent advantages—i.e., mimicking an in vivo environment—as other three dimensional culturing.” Reply Br. 30. And, fourth, it asserts that Dr. Salomon “testified without contradiction that skilled practitioners understood that three-dimensional culturing could be performed using beads” and that “culturing using beads in three-dimensions produces the same benefits over two-dimensional culturing that the patents describe.” Appellant’s Br. 33. We take each argument in turn.
SkinMedica’s first argument, that the patentees defined “three-dimensional framework” broadly enough to encompass the use of beads, is straightforward, but unhelpful. SkinMedica’s argument is simple: “The inventors knew that beads could be used in three-dimensional culturing. Their definition of a three-dimensional framework broadly encompassed ‘any material and/or shape.’ Beads are of any material or shape. Therefore, the inven32 SKINMEDICA INC v. HISTOGEN INC tors intended that beads could be used in three- dimensional culturing.” See Appellant’s Br. 25-26. SkinMedica’s theory misses the mark. It focuses on the three-dimensional framework being “any material and/or shape” and ignores that the inventors expressly restricted the definition of a “three-dimensional framework” to a “three-dimensional scaffold.” The written description defines three-dimensional framework as: [A] three-dimensional scaffold composed of any material and/or shape that (a) allows cells to at- tach to it (or can be modified to allow cells to at- tach to it); and (b) allows cells to grow in more than one layer. ’494 patent col. 6 ll. 43–47 (emphasis added). Beads obviously are “any material and/or shape,” but that does not mean that they are also a “three- dimensional scaffold.” Without explaining how beads are a “three-dimensional scaffold,” SkinMedica’s reliance on the definition of “three-dimensional framework” is incomplete. If we were to simply ignore the scaffold restriction, any structure of any material and/or shape that allows for cell attachment and for cell growth in more than one layer would be swept into the definition. That could not have been the inventors’ understanding. For example, the patentees discuss in the written description that some “monolayer cultures . . . could grow to more than ten cells deep.” Id. at col. 2 ll. 40–41. Without the scaffold restriction, the structure used to grow those types of monolayer cultures would meet the definition of a threedimensional framework (cells attach and grow in more than one layer). See id. at col. 2 ll. 37–42. According to SkinMedica’s theory, those cultures would therefore be three-dimensional. But no one contends that a monolayer culture should qualify as three-dimensional. SKINMEDICA INC v. HISTOGEN INC 33 Because it is unclear how beads could be a three- dimensional scaffold, we are unconvinced by SkinMedica’s argument that the inventors broadly defined “threedimensional framework” to indicate their intent to include culturing with beads as a three-dimensional culturing method.
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.
SkinMedica argues that Seldon, an international patent application listed on the face of only the ’746 patent, “expressly acknowledges that three-dimensional culturing with beads provides the same inherent advantages—i.e., mimicking an in vivo environment—as other three- dimensional culturing.” Reply Br. 30. Specifically, SkinMedica asserts Seldon teaches that: Cells cultured in three dimensions using beads (i.e., cells that “formed attachments to both the bead surface and other cells” and “grew as bridges between . . . beads”)—as opposed to “cells attached as monolayers” on “the bead’s surface”—“were more reminiscent of that expected in vivo.” Reply Br. 30 (quoting Seldon). At oral argument though, Histogen contended that SkinMedica’s reliance on Seldon was improper because SkinMedica raised Seldon for the first time in its reply brief on appeal. Oral Argument available at http://www.cafc.uscourts.gov/oral-argumentrecordings/2012-1560/all 26:36-50. We agree. Advanced Display Systems detailed particularity requirement may, however, be a helpful framework for determining whether a patentee has clearly intended to rely on a portion of an incorporated document to effect or avoid a disclaimer. Cf. Helmsderfer, 527 F.3d at 1381. (discussing how patentees must “clearly express an intent” to disclaim the ordinary meaning of the words they use in a claim). 38 SKINMEDICA INC v. HISTOGEN INC Clearly, Seldon is not part of the intrinsic record we consider for claim construction. It was listed on the face of the ’746 patent as a reference cited during prosecution. But Seldon is not in evidence. It is not in the record on appeal and played no part in the proceedings below. Indeed, when referring to Seldon in its reply brief, SkinMedica could only cite to a publically available copy of the reference, not the record. See Reply Br. 30. Thus, Seldon is, at best, extrinsic evidence belatedly cited by SkinMedica in its reply brief. Even as extrinsic evidence, though, we decline to consider Seldon. Seldon is a technically-dense patent application. It has a fifty-one page written description and twenty-four claims directed at “hepatocytes in three dimensional support systems.” Seldon at 1. SkinMedica crafts a nuanced theory about cell culturing with beads by simply quoting a few short disjointed phrases from the lengthy reference. Yet it has provided no context for those quotes or any reasoning for its conclusions past the quotes themselves. And because it waited until its reply brief on appeal to first mention Seldon, neither the district court nor Histogen have had an opportunity to fully discuss the importance of the disclosures in the reference. “[E]xtrinsic evidence can shed useful light on the relevant art” during claim construction. Phillips, 415 F.3d 1317. However, SkinMedica’s tardiness has so shaded what light Seldon may have shed on the relevant art here that we cannot fairly consider it. We simply cannot decipher the import of the reference without adequate context. SkinMedica has waived its ability to rely on the reference for claim construction purposes on appeal. See Conoco Inc. v. Energy & Envtl. Int’l, L.C., 460 F.3d 1349, 1358-59 (Fed. Cir. 2006) (“[A] party may not introduce new claim construction arguments on appeal or alter the scope of the claim construction positions it took below.”); Harris Corp. v. Ericsson Inc., 417 F.3d 1241, 1251 (Fed. Cir. 2005) (“An SKINMEDICA INC v. HISTOGEN INC 39 appellate court retains case-by-case discretion over whether to apply waiver.”).
The district court afforded Dr. Salomon’s testimony “no weight” after finding that it was “inconsistent with the intrinsic patent record.” J.A. 23 n.5. SkinMedica, however, believes that Dr. Salomon’s testimony is relevant because of two points to which he testified “without contradiction”: (1) “skilled practitioners understood that three-dimensional culturing could be performed using beads” and (2) “culturing using beads in three-dimensions produces the same benefits over two-dimensional culturing that the patents describe—i.e., ‘exhibit[ing] cell-to-cell and cell-matrix interaction characteristic of whole tissue in vivo.’” Appellant’s Br. 33 (quoting J.A. 101615); see also Reply Br. 31. We agree with the district court. The first point from Dr. Salomon’s testimony highlighted by SkinMedica—that culturing with beads in three-dimensions was known in the art—simply confirms an assumption we already made during our analysis of the intrinsic record. When we determined that the inventors disclaimed culturing with beads, we assumed that culturing with beads in three-dimensions was known in the art. Dr. Salomon’s validation of our assumption is irrelevant. Dr. Salomon’s discussion of the benefits of culturing with beads is equally unhelpful here because it is conclusory and incomplete. SkinMedica asserts that Dr. Salomon testified that three-dimensional bead cultures can produce the same benefits of three-dimensional culturing described by the patents. To support that assertion, it points us to a single passage from Dr. Salomon’s testimony. Appellant’s Br. 33–34 (arguing that Dr. Salomon’s testimony is extrinsic evidence to show that “ordinary meaning applies”); see also Reply Br. 31. 40 SKINMEDICA INC v. HISTOGEN INC Q. In your opinion, Dr. Salomon, do fibroblasts that are cultured in three-dimensions on micro- carriers or beads, do they exhibit cell-to-cell and cell-matrix interactions characteristic of whole tissue in vivo. A. Yes. Q. And have you seen that? ... A. Yes. Q. And is that—is your opinion about that func- tional definition applied to three-dimensional use of beads consistent with what we saw in the Doyle reference . . . ? A. Yes. J.A. 101614–15 (emphasis added). While it does appear from that passage that Dr. Sa- lomon agreed that bead cultures can provide benefits similar to three-dimensional cultures, Dr. Salomon’s testimony consists exclusively of three conclusory affirmations elicited by leading questions posed by SkinMedica’s counsel. His testimony lacks any convincing detail explaining why or how cells in bead cultures exhibit the characteristics of whole tissue in vivo he claims they possess. Indeed, the patentees explained at length how the three-dimensional cultures used in their inventions have specific and valuable characteristics of tissue in vivo. For example, they described how their three-dimensional cultures can provide for: sustained long-term proliferation of cells; stimulation of cell growth and proliferation; provision of a greater surface area for protein attachment; regulation of cell differentiation; adequate spatial distribution of cellular elements; establishment of localized microenvironments; and greater potential for movement of migratory cells. See ’494 patent col. 1 ll. 37–40; col. 11 SKINMEDICA INC v. HISTOGEN INC 41 ll. 20–53; col. 14 ll. 20–36; J.A. 101245. But Dr. Salomon does not explain how culturing with beads provides for any of those important characteristics. He even fails to explain how culturing with beads provides for the sustained long-term proliferation of cells, the key characteristic of three-dimensional cultures that the patentees identified as distinguishing their invention from prior art—in both the specification and prosecution history. See discussion supra, Section I(A). Dr. Salomon’s oneword confirmations of directed conclusions in leading questions simply lack any helpful or informative detail regarding the benefits of culturing with beads. Moreover, while SkinMedica believes Dr. Salomon’s statements are “perfectly consistent with the intrinsic record,” Appellant’s Br. 34, they are not. The patentees plainly stated in the written description that: “Cell lines grown as a monolayer or on beads, as opposed to cells grown in three-dimensions, lack the cell-cell and cellmatrix interactions characteristic of whole tissue in vivo.” ’494 patent col. 1 ll. 37–40 (emphases added). Dr. Salomon, though, testified that “fibroblasts culture[ed] in three-dimensions on microcarriers or beads, . . . exhibit cell-to-cell and cell-matrix interactions characteristic of whole tissue in vivo.” J.A. 101614–15 (emphasis added). As the district court found, Dr. Salomon’s testimony is “inconsistent with the intrinsic patent record.” J.A. 23 n.5. In whole, Dr. Salomon’s opinions are unhelpful to our analysis here. They are conclusory and incomplete; they lack any substantive explanation tied to the intrinsic record; and they appear to conflict with the plain language of the written description. Without a more detailed explanation of how Dr. Salomon formed his conclusions and why they conflict with the plain language of the specification, we must agree with the district court that 42 SKINMEDICA INC v. HISTOGEN INC Dr. Salomon’s testimony deserves no weight. 14 See Phillips, 415 F.3d at 1318 (discussing how expert testimony “can suffer from bias that is not present in intrinsic evidence,” is “not useful” if based on “conclusory, unsupported assertions,” and should be “discount[ed]” if “clearly at odds with . . . the written record of the patent”); see also Bell Atl. Network Servs., 262 F.3d at 1269 (“[Extrinsic evidence] may not be used to vary, contradict, expand, or limit the claim language from how it is defined, even by implication, in the specification or file history.”); Vitronics, 90 F.3d at 1584 (“[W]here the patent documents are unambiguous, expert testimony regarding the meaning of a claim is entitled to no weight.”).