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Skinmedica, Inc v. Histogen Inc.; Histogen Aesthetics LLC; Gail K. Naughton

UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF CALIFORNIA


May 24, 2011

SKINMEDICA, INC.,
PLAINTIFF,
v.
HISTOGEN INC.; HISTOGEN AESTHETICS LLC; GAIL K. NAUGHTON, DEFENDANTS.

The opinion of the court was delivered by: Honorable Janis L. Sammartino United States District Judge

ORDER: CONSTRUING DISPUTED CLAIM TERMS OF UNITED STATES PATENT NOS. 6,372,494 AND 7,118,746 AND RELATED COUNTERCLAIMS

Pursuant to Markman v. Westview Instruments, Inc., 517 U.S. 370 (1996), the Court conducted a hearing on February 15 and 16, 2011 regarding the construction of disputed claim terms in United States Patent Nos. 6,372,494 (the '494 patent) and 7,118,746 (the '746 patent). Attorneys Stephen Swinton and Alexander Long appeared on behalf of Plaintiff SkinMedica, Inc. Plaintiff's expert, Dr. Daniel Salomon, also testified at the hearing. Attorneys Randall Kay, Lisa Haile, and Erin Gibson appeared on behalf of Defendants Histogen Inc., Histogen Aesthetics LLC, and Gail K. Naughton (collectively, Histogen). Upon careful consideration of the papers and counsel's oral arguments, the Court issues the following Order construing the disputed claim terms of the patents at issue in this case.

BACKGROUND

On January 22, 2009, SkinMedica filed this action alleging, inter alia, infringement of the '494 and '746 patents. (Doc. No. 1.) SkinMedica's operative complaint asserts claims for patent infringement, misappropriation of trade secrets, unfair competition, breach of contract, and imposition of constructive trust. (Doc. No. 31.) Histogen has filed counterclaims for a declaration of patent non-infringement and unfair competition. (Doc. No. 35.) And each side asserts various affirmative defenses to the other's claims. (Id.; Doc. No. 40.)

Generally, the '494 and '746 patents "describe and encompass 'novel conditioned cell culture medium compositions' and 'uses for these novel compositions.'" (Doc. No. 44 (SkinMedica's Claim Construction Brief (CCB)), at 9 (citing '494 Patent col.4 ll.40--44); accord Doc. No. 48 (Histogen's Responsive CCB), at 3 ("[T]he claims of the Asserted Patents are directed toward methods of making conditioned medium using a three-dimensional culture system . . . .").) "Cell culture medium is the liquid solution used to 'culture,' or, 'grow' cells in vitro, and typically includes various raw materials-e.g., amino acids, vitamins, sugars, etc.-that the cells need to grow and expand in number." (SkinMedica's CCB 9 (citing '494 Patent col.1 ll.21--26).) "Once the culture medium is incubated with cells, it becomes a 'spent' or 'conditioned' medium." (Id. (citing '494 Patent col.1 ll.30--32).) "The '494 and '746 patents are specifically directed to conditioned medium derived from cells cultured in three-dimensions." (Id.) Cells cultured in three dimensions "express an extracellular matrix of proteins, thus forming a living tissue." (Id. (citing '494 Patent col.6 ll.54--56).) Further, cells cultured in three dimensions secrete growth factors and other proteins in ratios higher than cells cultured in two-dimensional monolayers. (Id. (citing '494 Patent col.5 ll.1--4, col.6 ll.9--17).) Thus, conditioned medium derived from cells grown in three dimensions is superior to conditioned medium derived from cells grown in two dimensions. (See id.)

The independent claims of the '494 patent recite a method of making a composition, comprising "culturing fibroblast cells in three-dimensions . . . so that a conditioned medium is formed," "removing the conditioned medium from the cultured cells," and "combining the conditioned medium with a pharmaceutically acceptable carrier." '494 Patent col.32 ll.10--19, 33--49. The single independent claim of the '746 patent recites "[a] method of reducing deleterious effects to keratinocytes," comprising "administering to the keratinocytes a composition comprising conditioned cell medium that has previously supported the growth of mesenchymal cells cultured in three-dimensions on a non-living support . . . thereby reducing intracellular oxidation in the keratinocytes." '746 Patent col.40 ll.7--18.

LEGAL STANDARD

The Court construes the scope and meaning of disputed patent claims as a matter of law. Markman v. Westview Instruments, Inc., 517 U.S. 370, 388--90 (1996). Words of a claim are "generally given their ordinary and customary meaning." Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). This is the meaning the term would have to a person of ordinary skill in the art as of the effective filing date of the patent application. Phillips v. AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005). Because the inquiry into the meaning of claim terms is an objective one, the court looks to publicly available sources to show what a person would have understood the claim language to mean. Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1116 (Fed. Cir. 2004). Those sources include the claims, the specification, the prosecution history, and relevant extrinsic evidence. Id.

Claim construction begins with an analysis of the words of the claims themselves. See Scanner Techs. Corp. v. ICOS Vision Sys. Corp., 365 F.3d 1299, 1303 (Fed. Cir. 2004). In examining the claims, "the context in which a term is used can be highly instructive." Phillips, 415 F.3d at 1314. Moreover, "[o]ther claims of the patent in question, both asserted and unasserted can . . . be valuable sources of enlightenment as to the meaning of a claim term." Id. "Because claim terms are normally used consistently throughout the patent, the usage of a term in one claim can often illuminate the meaning of the same term in other claims." Id. Conversely, under the doctrine of claim differentiation, "'different words or phrases used in separate claims are presumed to indicate that the claims have different meanings and scope.'" Andersen Corp. v. Fiber Composites, LLC, 474 F.3d 1361, 1369 (Fed. Cir. 2007) (quoting Karlin Tech., Inc. v. Surgical Dynamics, Inc., 177 F.3d 968, 971--72 (Fed. Cir. 1999)).

"Importantly, the person of ordinary skill in the art 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." Phillips, 415 F.3d at 1313. "Usually, [the specification] is dispositive; it is the single best guide to the meaning of a disputed term." Vitronics, 90 F.3d at 1582; accord Phillips, 415 F.3d at 1317. The specification acts as a dictionary when it expressly or implicitly defines terms used in the claims. Vitronics, 90 F.3d at 1582. In doing so, the patentee may define a claim term in a manner inconsistent with its ordinary meaning. Metabolite Labs., Inc. v. Lab. Corp. of Am., 370 F.3d 1354, 1360 (Fed. Cir. 2004).

Patent claims ordinarily should be construed to encompass the preferred embodiments described in the specification, for "[a] claim construction that excludes a preferred embodiment . . . 'is rarely, if ever correct.'" SanDisk Corp. v. Memorex Prods., Inc., 415 F.3d 1278, 1285 (Fed. Cir. 2005). However, a court should not import limitations from the specification into the claims, Phillips, 415 F.3d at 1323, absent a specific reference in the claims themselves, Reinshaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1248 (Fed. Cir. 1998).

The prosecution history may also inform claim construction. Vitronics, 90 F.3d at 1582. "Like the specification, the prosecution history provides evidence of how the PTO and the inventor understood the patent." Phillips, 415 F.3d at 1317. It can be useful to show "how the inventor understood the invention and whether the inventor limited the invention in the course of prosecution, making the claim scope narrower than it would otherwise be." Id.

"In most situations, an analysis of the intrinsic evidence alone will resolve any ambiguity in a disputed claim term. In such circumstances, it is improper to rely on extrinsic evidence." Vitronics, 90 F.3d at 1583. But this is not a rule of admissibility, nor does it "prohibit courts from examining extrinsic evidence, even where the patent document is itself clear." Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1308 (Fed. Cir. 1999). The court is not "barred from considering any particular sources or required to analyze sources in any specific sequence, as long as those sources are not used to contradict claim meaning that is unambiguous in light of the intrinsic evidence." Phillips, 415 F.3d at 1324.

CONSTRUCTION

The '494 and '746 patents descend from the same application, and have similar specifications and claims. (See Histogen's Responsive CCB 3 ("The '746 patent is a continuation-in-part of the '494 patent . . . ."); '746 Patent, at [63].) Accordingly, the Court construes the patents together.

The parties dispute the meaning of over a dozen claim terms. (See generally Doc. No. 33 (Joint Claim Construction Chart).) However, because several of the disputed terms "are either identical or substantially the same across the two patents," the parties agree that "the Court need only address eight collective arguments."*fn1 (SkinMedica's CCB 11; see Histogen's Responsive CCB 8--23 (adopting SkinMedica's grouping of terms).) The Court addresses each argument in turn.

1. Dr. Salomon's Testimony

At the threshold, the Court notes that it admitted Dr. Salomon's testimony as to the meaning of the disputed claim terms over Defendants' objection. (See Doc. Nos. 146--147 (CC Hr'g Tr.), at 82--151; Doc. No. 140 (Order Overruling Defendants' Objections to Extrinsic Evidence).) Upon exhaustive review, however, the Court concludes that the intrinsic evidence of the disputed terms' meanings generally provides a sufficient basis from which to construe the terms. Accordingly, the Court declines to rely on Dr. Salomon's testimony except as specifically stated herein, where it is consistent with the intrinsic patent record. See Vitronics, 90 F.3d at 1584.

2. "culturing . . . cells in three-dimensions"

Claim language SkinMedica's proposed Histogen's proposed construction construction*fn2

"culturing fibroblast cells in Plain meaning, or "growing "growing fibroblast cells on a three-dimensions" fibroblast cells in three structure forming a porous dimensions" framework (as opposed to monolayers or beads) wherein the cells proliferate both on the surface of and into the pores of the framework, forming a three dimensional tissue"

"cultured in three- Plain meaning or "grown in "growing cells on a structure dimensions" three dimensions" forming a porous framework (as opposed to monolayers or beads) wherein the cells proliferate both on the surface of and into the pores of the framework, forming a three dimensional tissue" "culturing mesenchymal cells Plain meaning or "growing "growing mesenchymal cells in three-dimensions" mesenchymal cells in three on a structure forming a dimensions" porous framework (as opposed to monolayers or beads) wherein the cells proliferate both on the surface of and into the pores of the framework, forming a three dimensional tissue"

The term "culturing . . . cells in three-dimensions" is repeated in substantially the same form in claims 1 and 8 of the '494 patent, and claims 1 and 11 of the '746 patent. (Histogen's Responsive CCB 8.) "[T]he parties have agreed that this term has a common meaning across its various incarnations . . . ." (SkinMedica's CCB 12.) "The only difference is the scope of the tissue specific cells that are part of the culture . . . ." (Histogen's Responsive CCB 8.)

The parties agree that "'culturing' means 'growing' and that the terms 'three-dimensions' or 'three-dimensional' require no further elaboration or clarification." (SkinMedica's CCB 12.) Accordingly, the Court need only determine whether the inventors further limited the invention to specific embodiments described in the specification. (See, e.g., Doc. No. 43 (Histogen's CCB), at 6 ("[T]he claim construction issue for the Court's determination is what conditions, including structures, are encompassed by 'culturing . . . in three-dimensions' within the meaning of the [asserted] patent[s].").)

SkinMedica contends that "culturing . . . cells in three-dimensions" "has a plain meaning to a person of ordinary skill in the art taken in light of the patent record" (SkinMedica's CCB 12 (citing Doc. No. 44-1 (Salomon Decl. ISO SkinMedica's CCB) ¶ 16)) and encompasses any method of culturing cells known in the art (id. (citing '494 Patent col.9 l.66 to col.10 l.2)). According to SkinMedica, "culturing in three-dimensions" "does not involve any special structural or other functional features." (Id.)

Histogen seeks to narrow SkinMedica's proposed construction in two respects. The Court addresses each in turn.

A. "(as opposed to monolayers or beads)"

First, Histogen contends that the inventors acted as their own lexicographers by "clearly and unambiguously defining 'culturing . . . in three-dimensions'" to exclude "culturing 'in monolayer' or on 'beads (i.e. in two-dimensions).'" (Histogen's CCB 6; accord id. at 21--22.) According to Histogen, "[t]hroughout the specification[s], the . . . inventors consistently distinguish their invention of culturing cells in three-dimensions from growing cells in monolayer or on beads, which was explicitly carved out from their claimed invention . . . ." (Histogen's CCB 7; accord id. at 22.) "In every instance in which culturing cells on beads is described in the Asserted Patents' specifications, it its defined as culturing in two-dimensions and beads are distinguished from three-dimensional culture." (Histogen's Responsive CCB 9 (emphasis in original).)

The specifications contain four relevant references to beads:

(1) "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.37--40 (emphasis added);

(2) "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.44--47 (emphasis added);

(3) "The cells are cultured in monolayer, beads (i.e., two-dimensions) or, preferably, in three-dimensions," '494 Patent col.7 ll.28--29 (emphasis added); and

(4) "The cells may be cultured in any manner known in the art including in monolayer, beads[,] or in three-dimensions and by any means (i.e., culture dish, roller bottle, a continuous flow system, etc.)," '494 Patent col.9 l.66 to col.10 l.2.*fn3 From these references, Histogen concludes that the inventors defined culturing on beads as culturing in two dimensions. (Histogen's CCB 7--8; Histogen's Responsive CCB 10 ("The many phrases distinguishing and defining culturing on beads as culturing in two-dimensions 'as opposed to' culturing in three-dimensions were added to the '494 and '746 patent specifications, and should be given meaning.").) Accordingly, "[t]he intrinsic record compels a construction of 'culturing . . . in three dimensions' to require culturing . . . cells using a framework or structure other than . . . using beads." (Histogen's CCB 8.)

SkinMedica responds that nothing in the patent record "evidences a clear and unmistakable intention to narrow the plain language of 'culturing . . . cells in three-dimensions' to exclude the use of microcarrier beads in three dimensions." (SkinMedica's Responsive CCB 3.) SkinMedica points out that, during the '494 patent's prosecution, the inventors overcame a rejection as anticipated over prior art "by clarifying that the invention was directed to a conditioned medium derived from a cell culture grown in three-dimensions, as opposed to the monolayer (i.e., two-dimensional) cell culture" disclosed in the prior art. (Id. (citing id. Ex. 24, at 25).) But aside from "specifying that the cell culture used to condition the medium of the claimed invention must be three-dimensional," the inventors did not describe any "particular conditions, including structures" as either mandatory or outside the scope of the invention. (Id. at 4.)

Further, although SkinMedica concedes that the specification distinguishes "cells . . . cultured in three-dimensions" from cells grown in two dimensions "using beads," SkinMedica contends that "this is not the same as defining 'beads' used as the three-dimensional framework to be a two-dimensional cell culture." (Id. at 5 (emphasis in original).) According to SkinMedica, Histogen confuses "the composition of the framework with the dimensionality of the cell culture." (Id. (emphasis in original).) Thus, to adopt Histogen's proposed construction would contradict the broad definition of "three-dimensional framework" in the patents' specifications*fn4 and the understanding of persons of ordinary skill in the art. (Id. (citing, inter alia, Salomon Decl. ISO SkinMedica's CCB ¶¶ 11--12).)

Finally, SkinMedica contends that its proposed construction, which would include the use of beads, comports with the intrinsic patent record. (Id.) Specifically, Cell & Tissue Culture: Laboratory Procedures, which SkinMedica contends is incorporated into the patents by reference in its entirety, see '494 Patent col.7 ll.50--52; id. col.10 ll 2--4, describes how beads may be used to culture cells in three dimensions:

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 uncommon. . . . 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.

A. DOYLE ET AL., CELL & TISSUE CULTURE: LABORATORY PROCEDURES 8D:2.7 (1996), available at SkinMedica's CCB Ex. 7. Thus, according to SkinMedica, "culturing . . . cells in three-dimensions" is just as amenable to SkinMedica's proposed construction as it is to Histogen's, and there is not enough "clarity, deliberateness, and precision" in the reference "beads (i.e., two-dimensions)" to equate the term "beads" with "two-dimensions." (SkinMedica's Responsive CCB 7 (quoting Merck & Co., Inc. v. Teva Pharms. USA, Inc., 395 F.3d 1364, 1370 (Fed. Cir. 2005)).)

The Court agrees with Histogen that the inventors acted as their own lexicographers, defining "culturing . . . cells in three-dimensions" away from its ordinary meaning. In three of the four instances in which the specification mentions beads, the inventors distinguished culturing on beads from culturing in three dimensions by using the disjunctives "or" (see '494 Patent col.7 ll.28--29; id. col.9 l.66 to col.10 l.2) and "as opposed to" (id. col.1 ll.37--40). The fourth reference to beads defines medium cultured by cells grown on beads as "[c]onventional conditioned cell culture medium" and unequivocally teaches away from culturing on beads to create the claimed conditioned medium. (Id. col.1 ll.44--47 (stating that medium cultured by cells grown on beads is "usually discarded" or "occasionally used in culture manipulations such as reducing cell densities").) By consistently distinguishing culturing on beads from culturing in three dimensions, the inventors defined "culturing . . . cells in three-dimensions" by implication to exclude culturing on beads. See Bell Atl. Network Servs. v. Covad Commc'ns Grp., Inc., 262 F.3d 1258, 1271 (Fed. Cir. 2001) ("[W]hen a patentee uses a claim term throughout the entire specification, in a manner consistent with only a single meaning, he has defined that term 'by implication.'" (quoting Vitronics, 90 F.3d at 1582)).

That the inventors explicitly defined beads as a two-dimensional culture method further bolsters the Court's conclusion. Specifically, the phrase "beads (i.e., two-dimensions)" explicitly defines beads as a two-dimensional culture method, despite that culturing cells in three dimensions on beads was known in the art at the time the patent was filed. See Abbott Labs. v. Novopharm Ltd., 323 F.3d 1324, 1327, 1330 (Fed. Cir. 2003) (holding that specification explicitly defined the phrase "co-micronization of fenofibrate and a solid surfactant" by including the phrase "co-micronization of fenofibrate and a solid surfactant (i.e., the micronization of an intimate mixture of fenofibrate and a solid surfactant)" (emphasis added)).

The Court would reach a different conclusion if the intrinsic evidence disclosed even a single reference to culturing cells in three dimensions using beads. See, e.g., Pfizer, Inc. v. Teva Pharm, USA, Inc., 429 F.3d 1364, 1373--74 (Fed. Cir. 2005) (holding that specification did not explicitly define term "saccharides" by including the phrase "saccharides (i.e., sugars)" because specification indicated that a broader construction was appropriate). But contrary to SkinMedica's contention, the Court concludes that Doyle et al.-which SkinMedica relies on to support its construction-is not incorporated into the patents by reference in its entirety.

"When a document is 'incorporated by reference' into a host document, such as a patent, the referenced document becomes effectively part of the hose document as if it were explicitly contained therein." Telemac Cellular Corp. v. Topp Telecom, Inc., 247 F.3d 1316, 1329 (Fed. Cir. 2001). "To incorporate material by reference, the host document must identify with detailed particularity what specific material it incorporates and clearly indicate where that material is found in the various documents." Advanced Display Sys., Inc. v. Kent State Univ., 212 F.3d 1272, 1282 (Fed. Cir. 2000). "Whether and to what extent material has been incorporated by reference into a host document is a question of law." Id.

Under this standard, a general reference to a voluminous publication is not sufficient to incorporate by reference a specific portion of a host document. See Commonwealth Scientific & Indus. Research Org. v. Buffalo Tech. (USA), Inc., 542 F.3d 1363, 1372 (Fed. Cir. 2008) (holding that footnote citation to article did not constitute an incorporation by reference of "any or all" of the material set forth in the article). That is because such a reference does not identify with "detailed particularity" what "specific material" it incorporates into the host document. Advanced Display Sys., 212 F.3d at 1282. Nor does a general reference indicate "where" that material is found in the allegedly incorporated document. Id.

Here, SkinMedica contends that Doyle et al. is incorporated by reference "in its entirety," and thus, its discussion of beads as a three-dimensional culture method is part of the intrinsic patent record. (SkinMedica's Responsive CCB 7; see '494 Patent col.7 ll.42--52 ("Examples of cell media include . . . other media formulations readily apparent to those skilled in the art, including those found in . . . Cell & Tissue Culture: Laboratory Procedures . . . which [is] incorporated by reference herein in [its] entirety."); see also '494 Patent col.10 ll.2--4 ("Methods of cell and tissue culturing are well known in the art, and are described, for example, in Cell & Tissue Culture: Laboratory Procedures, supra . . . .").) However, there is nothing about the two references to Doyle et al. that appears to constitute an incorporation by reference of its discussion of beads as a three-dimensional culture method under the standard set forth in Advanced Display Systems. Specifically, the references do not identify the relevant discussion of culturing on beads with detailed particularity or indicate where it is found. Accordingly, because Doyle et al.'s discussion of beads as a three-dimensional culture method is not incorporated into the patents by reference, the intrinsic patent record does not compel a broader construction of "culturing . . . cells in three-dimensions."*fn5

B. "a structure forming a porous framework . . . wherein the cells proliferate both on the surface of and into the pores of the framework, forming a three dimensional tissue" Second, Histogen contends that the inventors further defined what type of three-dimensional frameworks could fall within the meaning of the '494 patent, namely, porous frameworks. (Histogen's CCB 8; Histogen's Responsive CCB 11 ("[A]ll references to the illustrative three-dimensional framework in the specifications are to a mesh or other porous framework.").) According to Histogen, "[t]he three-dimensional structure must allow the cells to proliferate both on the surface and into the pores of the framework, because . . . the living stromal tissue is formed when the cells 'substantially envelop the framework.'" (Histogen's CCB 9.)

SkinMedica responds that Histogen's proposed construction would inappropriately import limitations from the specification into the claims. (SkinMedica's CCB 12--14; SkinMedica's Responsive CCB 7--9.) According to SkinMedica, whereas Histogen's proposed construction "suggests that use of a mesh or similar porous framework is required," the patents' specifications "are explicit that such meshes are exemplary only." (SkinMedica's CCB 13 (emphasis in original).) Although the specifications state that "[t]he structure of the framework can include a mesh," '494 Patent col.6 ll.45--47 (emphasis added), they also make clear that "[a] number of different materials may be used to form the framework," id. col.11 ll.57--59, and that those materials "may be woven[,] braided, knitted, etc., into a mesh, for example, to form the tree-dimensional [sic] framework," id. col.12 ll.1--2.*fn6

The Court finds that a porous framework limitation has no place the claims. The Federal Circuit has repeatedly held that "a narrow disclosure in the specification does not necessarily limit broader claim language." Intamin Ltd. v. Magnetar Techs., Corp., 483 F.3d 1328, 1335 (Fed. Cir. 2007) (citing Phillips, 415 F.3d at 1323). Here, the overall context of the patents does not disavow the use of structures other than a mesh or porous framework. The references Histogen cites (see, e.g., Histogen's CCB 8--9 (citing, inter alia, '494 Patent col.10 ll.37--52)) do not expressly limit the entire invention but only describe a single embodiment.

Accordingly, the Court (1) CONSTRUES "culturing fibroblast cells in three-dimensions" to mean"growing fibroblast cells in three dimensions (excluding growing fibroblast cells in monolayers or on microcarrier beads)"; (2) CONSTRUES "cultured in three-dimensions" to mean "grown in three dimensions (excluding grown in monolayers or on microcarrier beads)"; and (3) CONSTRUES "culturing mesenchymal cells in three-dimensions" to mean "growing mesenchymal cells in three dimensions (excluding growing mesenchymal cells in monolayers or on microcarrier beads)."

3. "framework . . . formed into a three-dimensional structure"

Claim language SkinMedica's proposed Histogen's proposed construction construction

"framework . . . formed into a Plain meaning, or "a Framework: "a porous three-dimensional structure" three-dimensional structure structure, porous support, or composed of any material porous scaffold onto which and/or shape that (a) allows cells are innoculated" cells to attach to it (or can be modified to allow cells to A three-dimensional structure: attach to it); and (b) allows "a structure forming a mesh cells to grow in more than one or porous framework (as layer" opposed to monolayers or beads) wherein the cells proliferate both on the surface of and into the pores of the framework, forming three-dimensional tissue"

The term "framework composed of a biocompatible, non-living material formed into a three-dimensional structure" appears in independent claim 8 of the '494 patent. A slight variation of this term-"framework comprising a biocompatible, non-living material formed into a three-dimensional structure"-appears in dependent claims 6 and 19 of the '746 patent. "However, the parties agree that this variation does not alter the construction of the term, and therefore the 'framework' terms of both patents may be construed together." (SkinMedica's CCB 14 n.7.)

SkinMedica contends that the term "framework composed of a biocompatible, non-living material formed into a three-dimensional structure" has a plain meaning that is understood by one of skill in the art. (SkinMedica's CCB 14.) The specifications define "three-dimensional framework" to mean "a three-dimensional scaffold composed of any material and/or shape that (a) allows cells to attach to it (or can be modified to allow cells to attach to it); and (b) allows cells to grow in more than one layer. . . . The structure of the framework can include a mesh, a sponge[,] or can be formed into a hydrogel." '494 Patent col.6 ll.40--47; '746 Patent col.6 ll.48--55. According to SkinMedica, "[t]his definition makes clear that a 'framework composed of a biocompatible, non-living material formed into a three-dimensional structure' may be of any material and/or shape; therefore, at most, the definition suggests what the structure can include, not what it must include." (SkinMedica's CCB 15 (emphasis in original).)

Citing its proposed construction of "culturing . . . in three dimensions," Histogen contends that the inventors not only disclaimed growing cells on monolayers or beads, but also defined what three-dimensional frameworks fall within the meaning of the patents. (Histogen's CCB 16.) According to Histogen, during prosecution, the inventors "emphasized the importance of diffusion through the framework to the claimed invention." (Histogen's Responsive CCB 14 (citing Histogen's CCB Ex. G, at 84--89; id. Ex. N, at 208 ("[A]bility to diffuse through the structure appear[s] to affect the level of proteins found in the medium.")).) "The inventors intended to show that a mesh or other porous framework, onto which cells are inoculated, is required to distinguish from the prior art culture systems resulting in conditioned medium." (Histogen's CCB 16 (citing, inter alia, '494 Patent col.10 ll.49--52 ("Importantly, because openings in the mesh permit the exit of stromal cells in culture, confluent stromal cells do not exhibit contact inhibition, and the stromal cells continue to grow, divide, and remain functionally active.")).)

SkinMedica responds that the specifications demonstrate "that the use of a 'mesh or porous framework' is only exemplary, rather than mandatory." (SkinMedica's Responsive CCB 9.) Further, according to SkinMedica, the inclusion of the phrase "onto which cells are inoculated" in Histogen's proposed construction has the effect of excluding "polymerized hydrogels" that are expressly incorporated in the dependent claims as an alternate embodiment. (Id.) The patents contemplate that hydrogels may "harden into a matrix" only after they are mixed with "large numbers of the desired cell type." '494 Patent col.3 ll.20--22. Thus, cells cannot be inoculated "onto" a polymerized hydrogel.*fn7

The Court declines Histogen's invitation to import limitations from the specification into the claims. First, there is nothing in the claims, the specification, or the prosecution history that limits the framework to "a porous structure." At most, "a porous structure" is an exemplary embodiment. See '494 Patent col.10 ll.49--52; id. col.11 l.66 to col.12 l.2 ("Any of these materials may be woven, braided, knitted, etc., into a mesh, for example, to form the tree-dimensional [sic] framework.") (emphasis added). And as the Federal Circuit has made clear, the Court should not import a limitation from a specification into the claims absent a specific textual reference in the claims themselves. Reinshaw, 158 F.3d at 1248.

Second, Histogen's claim that the inventors distinguished their invention from the prior art based on the capacity for diffusion through the framework lacks merit. As discussed in greater detail infra, the principal distinction that the inventors drew during prosecution was between culturing cells in two dimensions and culturing cells in three dimensions. (See generally Histogen's CCB Ex. N, at 175--76, 206--10.) In fact, the portion of the prosecution history Histogen cites can be reasonably interpreted to refer to capacity for diffusion through the cell culture's three-dimensional structure, rather than the framework's.

Third, Histogen's proposed construction would exclude the use of frameworks composed of polymerized hydrogels because cells cannot be inoculated "onto" a polymerized hydrogel. Thus, insofar as it calls for a structure "onto which cells are inoculated," Histogen's construction would contravene the express language of dependent claim 9 of the '494 patent and dependent claim 19 of the '746 patent, which expressly incorporate polymerized hydrogels as an alternative embodiment.

Accordingly, the Court adopts SkinMedica's proposed construction and CONSTRUES "framework . . . formed into a three-dimensional structure" to mean "a three-dimensional structure composed of any material and/or shape that (a) allows cells to attach to it (or can be modified to allow cells to attach to it); and (b) allows cells to grow in more than one layer."

4. "substantially envelop" and "substantially enveloping"

Claim language SkinMedica's proposed construction "substantially enveloping" and "substantially Plain meaning, or "substantially enclosing, envelop" surrounding or covering"

The term "substantially enveloping" appears in claim 8 of the '494 patent, and the term "substantially envelop" appears in claims 6 and 19 of the '746 patent. The parties propose to give both terms the same construction. (See SkinMedica's CCB 16--17; Histogen's Responsive CCB 22--23.)

At the hearing, Histogen's counsel indicated that Histogen would agree to either plain meaning or SkinMedica's proposed construction. (CC Hr'g Tr. 281--82 ("The Court: So plain meaning or substantially enclosing, surrounding[,] or covereing. You're okay either way? [¶] Mr. Kay: Correct.").) In an abundance of caution, the Court adopts SkinMedica's proposed construction and CONSTRUES "substantially enveloping" and "substantially envelop" to mean "substantially enclosing, surrounding, or covering." See Power-One, Inc. v. Artesyn Techs., Inc., 599 F.3d 1343, 1348 (Fed. Cir. 2010) ("The terms, as construed by the court, must 'ensure that the jury fully understands the court's claim construction rulings and what the patentee covered by the claims.'" (quoting Sulzer Textil A.G. v. Picanol N.V., 358 F.3d 1356, 1366 (Fed. Cir. 2004)).

5. "conditioned medium" and "conditioned cell medium"

Claim language SkinMedica's proposed Histogen's proposed construction construction

"conditioned medium" and Plain meaning, or "a "a formulation containing "conditioned cell medium" formulation containing extracellular protein(s) and extracellular protein(s) and cellular metabolites, which cellular metabolites, which has previously supported the has previously supported the growth of cells having been growth of cells having been cultured on a cultured in three-dimensions" three-dimensional porous framework under normoxic conditions"

The term "conditioned medium" appears in independent claims 1 and 8 of the '494 patent, and dependent claim 11 of the '746 patent. The term "conditioned cell medium," appears in claims 1, 15, and 22 of the '746 patent, and the parties propose to construe it to have the same meaning as "conditioned medium."*fn8 (See Joint Claim Construction Chart 6--14, 26--30, 43--46.)

SkinMedica argues that "conditioned medium" and "conditioned cell medium" have a plain meaning to those of ordinary skill in the art, and thus require no construction. (SkinMedica's CCB 17 (citing '494 patent col.1 ll.30--32).) SkinMedica's proposed alternative construction "comports with the express definition" of conditioned medium and conditioned cell medium contained in the patents' specifications. (Id. (emphasis in original).) Specifically, the patents commonly define "conditioned media" and "conditioned cell media" to mean "a formulation containing extracellular protein(s) and cellular metabolites, which has previously supported the growth of any desired eukaryotic cell type, said cells having been cultured in either two or three dimensions." '494 Patent col.6 ll.25--30; '746 Patent col.6 ll.33--38.

Histogen seeks to narrow SkinMedica's proposed alternative construction in two respects. The Court addresses each in turn.

A. "three-dimensional porous mesh framework"

First, Histogen contends that the term only encompasses a conditioned medium "obtained from cells cultured on a three-dimensional porous structure." (Histogen's CCB 10.) According to Histogen, the inventors of the '494 and '746 patents argued during the patents' prosecution that "the 'ability to diffuse through the three-dimensional structure' made a patentable difference in the conditioned medium." (Histogen's Responsive CCB 13.)

During the '494 patent's prosecution, inventor Jonathan Mansbridge, Ph.D., submitted a declaration to the PTO describing the differences between conditioned medium obtained from cells cultured in two dimensions and that obtained from cells cultured in three dimensions. (See Histogen's CCB Ex. G ¶¶ 7--10.) Dr. Mansbridge described the results of experiments on two conditioned media:

These results demonstrate that the two conditioned media do not have the same composition and makeup factors and cytokines. Further, as described below, the level of factors secreted into the medium does not have direct correspondence to mRNA and protein production. Both protein processing steps and ability to diffuse through the three-dimensional structure appear to affect the levels of proteins found in the medium. (Id. ¶ 7 (emphasis added).)

As SkinMedica points out, however, the principal distinction that Dr. Mansbridge drew was between conditioned medium obtained from cells cultured in two dimensions and that obtained from cells cultured in three dimensions. (SkinMedica's Responsive CCB 12.) During the prosecution of the '746 patent, the inventors summarized Dr. Mansbridge's declaration:

The Declaration clearly demonstrates that the culturing of eukaryotic cells in three-dimensions results in the production of a conditioned medium having a different chemical composition and different biological activity than culture in two-dimensions and that these differences were unexpected and heretofore unknown prior to the filing of [the '494 application]. (Histogen's CCB Ex. N, at 176; see also id. Ex. G ¶ 10 ("This experiment demonstrates that the culturing of cells in three-dimensions results in the production of a conditioned medium that has an activity . . . that is different from the same cells cultured in two dimensions.").)

The Court rejects Histogen's attempt to limit the claims' reach to conditioned medium grown on a porous mesh framework. Dr. Mansbridge's declaration does not refer to the nature of the structure that the cells are cultured on. "Indeed, that declaration does not even mention the words 'mesh' or 'porous frameork.'" (SkinMedica's Responsive CCB 12 (emphasis in original).) In fact, the only reference to "structure"-the italicized portion of the declaration-can be reasonably interpreted to refer to the ability to diffuse through the cell culture's three-dimensional structure, rather than the framework's. Thus, there is no basis for the argument that the inventors distinguished their conditioned medium from the prior art based on the cell culture's ability to diffuse through a porous mesh framework. Rather, it was the observed difference between conditioned medium obtained from cells cultured in two dimensions and that obtained from cells cultured in three dimensions that distinguished the claimed conditioned medium from the prior art. (See Histogen's CCB Ex. N, at 175--76.)

B. "under normoxic conditions"

Second, Histogen contends that "the claimed 'conditioned medium' must be obtained from cells cultured under normoxic conditions."*fn9 (Histogen's CCB 11.) "Normoxic conditions were the commonly used tissue culture conditions at the time the '494 application was filed." (Id.) According to Histogen, other-than-normoxic conditions were "nascent technology" at the time the patent application was filed, and therefore, could not have been enabled without a specific textual reference.*fn10

(Id. at 11-12; Histogen's Responsive CCB 13--14; see Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1254 (Fed. Cir. 2004) ("Nascent technology . . . must be enabled with a 'specific and useful teaching.'" (quoting Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1368 (Fed. Cir. 1997))).

SkinMedica disagrees that other-than-normoxic conditions were nascent technology at the time the patent application was filed. (SkinMedica's Responsive CCB 13). SkinMedica points out that "[t]he patent specifications themselves discuss cell cultures grown by persons of ordinary skill in the art not only in 'normoxic conditions,' but also in 'hypoxic conditions' (less than normal oxygen) at the time the '494 patent was filed." (Id. (citing '494 Patent col.3 ll.45--51).) Further, one publication cited on the face of the '494 patent specifically addresses the effect of hypoxic conditions on cell cultures used to model avascular solid tumor growth. (See id. Ex. 26, at 91 ("The prevalence of hypoxic conditions in three-dimensional avascular solid tumour nodules will provide a strong selective force that will favour survival and proliferation of cells that are resistant to hypoxic stress.") (cited in '494 Patent, at [56]).)

The Court agrees with SkinMedica. The intrinsic evidence demonstrates that culturing cells under hypoxic conditions was known in the art at the time the patent application was filed. Thus, no disclosure was required to enable the claims for culturing cells under normoxic and hypoxic conditions. See Chiron, 363 F.3d at 1254 ("The law requires an enabling disclosure for nascent technology because a person of ordinary skill in the art has little or no knowledge independent from the patentee's instruction.").

Moreover, SkinMedica essentially proposes that the Court adopt the specification's definition verbatim, with the added limitation that the conditioned medium be obtained from cells cultured in three dimensions. And "[w]here . . . the patentee has clearly defined a claim term, that definition '[u]sually . . . is dispositive; it is the single best guide to the meaning of a disputed term.'" Jack Guttman, Inc. v. Kopykake Enters., Inc., 302 F.3d 1352, 1360 (Fed. Cir. 2002) (quoting Vitronics, 90 F.3d at 1582). Histogen's arguments for a contrary construction attempt to stretch the specification and the prosecution history beyond their outer limits.

Accordingly, the Court adopts SkinMedica's proposed construction and CONSTRUES "conditioned medium" and "conditioned cell medium" to mean "a formulation containing extracellular protein(s) and cellular metabolites, which has previously supported the growth of cells having been cultured in three-dimensions."

6. "pharmaceutically acceptable carrier" and "pharmaceutical carrier"

Claim language SkinMedica's proposed Histogen's proposed construction construction "pharmaceutically acceptable Plain meaning, or "solid or "a vehicle for internal carrier" and "pharmaceutical liquid diluents or administration" carrier" encapsulating substances that are suitable for administration to a human or lower animal"

The term "pharmaceutically acceptable carrier" appears in independent claims 1 and 8 of the '494 patent, and the term "pharmaceutical carrier" appears in dependent claims 2 and 11 of the '746 patent. "Although differing in phrasing, the parties agree that 'pharmaceutically acceptable carrier and 'pharmaceutical carrier' have a common meaning in the context of the '494 and '746 patents." (SkinMedica's CCB 18; see Histogen's Responsive CCB 15--18.)

SkinMedica contends that "the plain language of the claims, the specification[s], and the prosecution histories of the patents" all show that "pharmaceutically acceptable carrier" and "pharmaceutical carrier" should be given their plain meaning as understood by persons of ordinary skill in the art. (SkinMedica's CCB 18; see also Salomon Decl. ISO SkinMedica's CCB ¶ 20 (defining "pharmaceutically acceptable carrier," as understood by a person of ordinary skill in the art and citing extrinsic prior art references).) Contrary to Histogen's argument, SkinMedica contends that the patents' specifications make clear "that the use of a pharmaceutically acceptable carrier does not mandate the use of the claimed conditioned medium for internal administration only." (SkinMedica's CCB 19.) According to SkinMedica, "the specifications describe . . . examples involving a pharmaceutically acceptable carrier that are not strictly confined to 'internal administration, such as embodiments that 'include formulations of the conditioned media with a salve or ointment for topical applications.'" (Id. (quoting '494 Patent col.2 ll.32--36).)

Histogen contends that the inventors acted as their own lexicographers and implicitly defined "pharmaceutically acceptable carrier" and "pharmaceutical carrier" to have other than their ordinary meaning. (Histogen's CCB 12--14; 22--23; see Bell Atl., 262 F.3d at 1268 ("[T]he specification may define claim terms 'by implication' such that the meaning may be 'found or ascertained by a reading of the patent documents.'" (quoting Vitronics, 90 F.3d at 1582)).) According to Histogen, "[i]n every instance in which 'pharmaceutically acceptable carrier' is used in the specification, it refers to internal administration, as opposed to external use." (Id. (emphasis in original).) Histogen cites as an example the '494 patent's specification, wherein the inventors stated:

Once the cell medium of the invention is conditioned, it may be used in any state. Physical embodiments of the conditioned medium include, but are not limited to, liquid or solid, frozen, lyophilized[,] or dried into a powder. Additionally, the medium may be formulated with a pharmaceutically acceptable carrier as a vehicle for internal administration, applied directly to a food item or product, formulated with a salve or ointment for topical applications, or, for example, made into or added to surgical glue to accelerate healing of sutures following invasive procedures. '494 Patent col.5 ll.14--23 (emphasis added).*fn11 According to Histogen, the use of the word "or" in this passage evinces the inventors' intent to distinguish embodiments "formulated with a pharmaceutically acceptable carrier as a vehicle or internal administration," where internal administration is required, from other listed embodiments. (Histogen's CCB 13.)

Histogen's argument has some superficial appeal, but it does not withstand close scrutiny. Other than in the claims and the abstract, the patents' specifications each use the term "pharmaceutically acceptable carrier" four times. '494 Patent col.5 ll.14--23, col.24 ll.13--15, col.26 ll.13--31, col.26 ll.56--58; '746 Patent col.5 ll.26--32, col.27 ll.22--24, col.30 ll.20--22, col.30 ll. In each instance, the term refers to internal administration, as opposed to external use. But contrary to Histogen's assertion, the inventors did not use "pharmaceutically acceptable carrier" in a manner consistent with only a single meaning. (Histogen's Responsive CCB 13.) The term does not refer to a distinct concept, such that it would be illogical to construe it to have other than Histogen's proposed construction. See Bell Atl., 262 F.3d at 1271. Rather, the inventors used the term in a manner just as consistent with SkinMedica's proposed construction as with Histogen's.*fn12

Further, Histogen's proposed construction would exclude embodiments described in the specification. "A claim construction that excludes a preferred embodiment . . . 'is rarely, if ever correct.'" SanDisk., 415 F.3d at 1285 (quoting Vitronics, 90 F.3d at 1583); see Verizon Servs. Corp. v. Vonage Holdings Corp., 503 F.3d 1295, 1305 (Fed. Cir. 2007) ("We normally do not interpret claim terms in a way that excludes disclosed examples in the specification."). Although "a claim need not cover all embodiments," Intamin, 483 F.3d at 1337, the Federal Circuit "has cautioned against interpreting a claim term in a way that excludes disclosed embodiments, when that term has multiple ordinary meanings consistent with the intrinsic record," Helmsderfer v. Bobrick Washroom Equipment, Inc., 527 F.3d F.3d 1379, 1383 (Fed. Cir. 2008). But see Rolls-Royce, PLC v. United Techs. Corp., 603 F.3d 1325, 1334--35 (Fed. Cir. 2010) (construing claim to exclude alternative embodiment because "[a] claim construction that embraced both alternative embodiments would be unreasonable"); Helmsderfer, 527 F.3d at 1383 (construing claim to exclude preferred embodiment because construction "[left] open the possibility that claims not at issue . . . encompass[ed] omitted embodiments").

Both independent claims of the '494 patent require "combining the conditioned medium with a pharmaceutically acceptable carrier," '494 Patent col.32 ll.18--19, 46--48, which Histogen would have the Court construe to mean "combining with a vehicle for internal administration." Yet the patent's specification and prosecution history describe embodiments that are not limited to internal administration.*fn13 Histogen's proposed construction of "pharmaceutically acceptable carrier," which limits the term to internal administration, would exclude use of the claimed composition for the various topical applications described in the specification and prosecution history. SkinMedica's proposed construction, on the other hand, is consistent with the term's ordinary meaning (see Salomon Decl. ISO SkinMedica's CCB ¶ 20), is not inconsistent with the intrinsic record (see, e.g., '494 Patent col.5 ll.14--23; SkinMedica's CCB Ex. 4, at 105), and does not exclude the disclosed embodiments. See Helmsderfer, 527 F.3d at 1383.

Although SkinMedica derives its proposed construction from extrinsic prior art references (see SkinMedica's CCB 19 (citing Salomon Decl. ISO SkinMedica's CCB ¶ 20 (citing, inter alia, U.S. Patent No. 6,277,892, at col.10 ll.11--16 (filed Feb. 4, 1994))), these references illustrate what an ordinarily skilled artisan would understand "pharmaceutically acceptable carrier" to mean and are consistent with the intrinsic record. See Phillips, 415 F.3d at 1319. Accordingly, the Court adopts SkinMedica's proposed construction and CONSTRUES "pharmaceutically acceptable carrier" and "pharmaceutical carrier" to mean "solid or liquid diluents or encapsulating substances that are suitable for administration to a human or lower animal."

7. "cosmetic application"

Claim language SkinMedica's proposed Histogen's proposed construction construction "cosmetic application" Plain meaning, or "application "non-therapeutic internal use" as a preparation for beautifying, preserving or altering appearance"

The term "cosmetic application" appears in dependent claims 7 and 11 of the '494 patent. It does not appear in the '746 patent.

SkinMedica argues that "cosmetic application" "has a plain an ordinary meaning readily apparent to lay people, not just persons of ordinary skill in the art." (SkinMedica's CCB 20.) According to SkinMedica, the '494 patent's specification "demonstrates that the term 'cosmetic application' is used similarly in its ordinary manner." (Id. at 21 (citing '494 Patent col.25 ll.42--45 ("[T]he compositions . . . may be used in a hydrogel, injectable, cream, ointment, and may even be added to eye shadow, pancake makeup, compacts[,] or other cosmetics to fortify the skin topically.") (emphasis added)).) Thus, SkinMedica's proposed alternative construction incorporates the dictionary definition of "cosmetic." (Id. at 20--21 (citing id. Exs. 20--22 (defining "cosmetic")); see Phillips, 415 F.3d at 1318 ("[D]ictionaries and treatises can be useful in claim construction.").)

Citing its proposed construction of "pharmaceutically acceptable carrier," Histogen argues that "cosmetic application" must be construed to require internal use. (Histogen's CCB 14.) Otherwise, claims 7 and 11 "would be broader than or fail to limit claims 1 and 8," from which they depend. (Id.) Although Histogen recognizes that this construction would exclude embodiments described in the specification, Histogen submits that "the fact that the specification describes such embodiments does not support a broadening of the claim." (Id. at 15 (citing TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1373 (Fed. Cir. 2008)).) Histogen further notes that its proposed construction would not offend the plain meaning of "cosmetic" because the specification describes "formulations in the form of injectables or hydrogels[, which] may be used to eliminate wrinkles, frown lines, scarring[,] and to repair other skin conditions." (Histogen's Responsive CCB 19 (quoting '494 Patent col.5 ll.48--51).)

The conclusion supra that "pharmaceutically acceptable carrier" has a broader meaning than "a vehicle for internal administration" takes most of the wind out of Histogen's sails. Unless claims 1 and 8 are limited to internal use, Histogen has provided no reason to limit claims 7 and 11 to internal use.

Further, the authority Histogen cites for the proposition that "the patent need not encompass all disclosed embodiments" is inapposite. TIP Sys., 529 F.3d at 1373. In that case, the district court's claim construction excluded an alternative embodiment disclosed in the specification. Id. at 1372--73. The Federal Circuit observed that "to construe the claim term to encompass the alternative embodiment . . . would contradict the language of the claims." Thus, the court concluded that the district court did not err in construing the claim to exclude the alternative embodiment. Id. at 1373 (citing, inter alia, Schoenhaus v. Genesco, Inc., 440 F.3d 1354, 1359 (Fed. Cir. 2006) ("[W]here a patent specification includes a description lacking a feature, but the claim recites that feature, the language of the claim controls.")).

Here, there is no such conflict between the language of the claims and SkinMedica's proposed construction. To construe "cosmetic application" to include topical applications is consistent with the language of the independent claims, which are not facially limited to internal uses. At most, SkinMedica's proposed construction of "cosmetic application" would contradict the Histogen's proposed construction of "pharmaceutically acceptable carrier," which the Court rejected supra.

Accordingly, the Court adopts SkinMedica's proposed construction and CONSTRUES "cosmetic application" to mean "application as a preparation for beautifying, preserving or altering appearance."

8. "mesenchymal cells"

Claim language Agreed-upon construction "mesenchymal cells" "cells of mesenchymal lineage"

The term "mesenchymal cells" appears in claim 1 of the '746 patent. It does not appear in the '494 patent.

At the hearing, the parties indicated that they reached an agreement as to the meaning of "mesenchymal cells." (CC Hr'g Tr. 333 ("Mr. Long: . . . I think both parties are willing to agree that mesenchymal cells should be interpreted as cells of mesenchymal lineage, period.").) Accordingly, the Court adopts the parties' agreed-upon construction and CONSTRUES "mesenchymal cells" to mean "cells of mesenchymal lineage."

9. "reducing intracellular oxidation in the keratinocytes"

Claim language SkinMedica's proposed Histogen's proposed construction construction "reducing intracellular Plain meaning, or "reducing "reducing oxidation due to the oxidation in the oxidation inside the presence of antioxidant keratinocytes" keratinocyte cells" activity in the conditioned cell medium"

The term "reducing intracellular oxidation in the keratinocytes" appears in claim 1 of the '746 patent. It does not appear in the '494 patent.

Histogen contends that "[i]n order for the conditioned medium to reduce intracellular oxidation in the keratinocytes, it must contain factors that have antioxidant activity." (Histogen's CCB 21.) In support of this contention, Histogen cites section 7 of the specification, '746 Patent col.38 ll.7--44, wherein the inventors describe the effect of antioxidant activity of keratinocytes, see, e.g., id. col.38 ll.35--39 ("Human keratinocytes exposed to Applicants' conditioned cell medium exhibited a statistically significant (p<0.0003) 50%="" reduction="" in="" intracellular="" oxidation="" compared="" to="" the="" same="" cells="" incubated="" in="" the="" presence="" of="" serum-free="" or="" serum-containing="" medium.")="" (citation="" omitted).="" (histogen's="" ccb="" 21.)="" further,="" histogen="" contends="" that,="" during="" the="" '746="" patent's="" prosecution,="" the="" "inventors="" distinguished="" their="" invention="" based="" upon="" antioxidant="" activity="" in="" the="" conditioned="" medium."="" (histogen's="" responsive="" ccb="" 21="" (citing="" histogen's="" ccb="" ex.="" n,="" at="" 177).)="" according="" to="" histogen,="" to="" overcome="" a="" rejection="" for="" lack="" of="" enablement,="" the="" inventors="" "argued="" that="" their="" invention="" was="" enabled="" because="" 'it="" was="" known="" in="" the="" art="" at="" the="" time="" of="" the="" filing="" of="" the="" subject="" application="" that="" mesenchymal="" cells="" from="" a="" large="" number="" of="" tissues="" produce="" antioxidants.'"="" (id.="" at="" 21--22="" (quoting="" histogen's="" ccb="" ex.="" n,="" at="" 177);="" see="" southwall="" techs.="" v.="" cardinal="" ig="" co.,="">54 F.3d 1570, 1576 (Fed. Cir. 1995) ("Arguments and amendments made during the prosecution of a patent application and other aspects of the prosecution history . . . must be examined to determine the meaning of terms in the claims.").)

SkinMedica responds that Histogen attempts to improperly "read limitations from embodiments described in the patent specification into the claims without . . . any textual reference to those limitations in the plain language of the claims, or . . . 'words or expressions of manifest exclusion or restriction, which is necessary to further narrow the claim language.'" (SkinMedica's CCB 23 (quoting Linear Tech. Corp. v. Int'l Trade Comm'n, 566 F.3d 1049, 1058 (Fed. Cir. 2009)); see also SkinMedica's Responsive CCB 22.) According to SkinMedica, although the '746 patent's specification "discuss[es] a reason for the conditioned medium's capacity for 'reducing intracellular oxidation in the keratinocytes,' the plain language of the claims is not limited to any particular reason for reduced oxidation." (SkinMedica's CCB 23.) "As such, it is improper to import such a reason-e.g., the presence of antioxidant activity-into the claims." (Id. at 23--24.)

The claim itself does not expressly indicate how the conditioned medium-through antioxidant activity, for example-reduces intracellular oxidation in the keratinocytes. In order to properly determine the meaning of this phrase, the Court must consider it in light of the entire patent. See Phillips, 415 F.3d at 1321 ("Properly viewed, the 'ordinary meaning' of a claim term is its meaning to the ordinary artisan after reading the entire patent.").

Here, the specification only describes one mechanism by which the conditioned medium reduces intracellular oxidation in the keratinocytes, namely, antioxidant activity. See '746 Patent col.7 l.65 to col.8 l.4 ("FIG. 5 is a graph representing the anti-oxidant activity in the conditioned cell medium . . . on human epidermal keratinocytes in culture. A statistically significant (p<0.003) reduction="" in="" intracellular="" oxidation="" of="" approximately="" 50%="" was="" noted="" in="" human="" keratinocytes="" exposed="" to="" the="" conditioned="" medium="" .="" .="" .="" .");="" col.28="" l.64="" to="" col.29="" l.6="" ("[i]n="" another="" embodiment,="" the="" medium="" of="" the="" invention="" is="" used="" to="" reduce="" cell="" aging="" and="" inhibit="" the="" activity="" of="" the="" factors="" which="" cause="" skin="" cancer.="" that="" the="" conditioned="" medium="" has="" antioxidant="" activity="" is="" shown="" in="" section="" 7.1.="" .="" .="" .="" applicants="" have="" discovered="" that="" a="" statistically="" significant=""><0.003) intracellular="" oxidation="" of="" approximately="" 50%="" was="" noted="" in="" human="" keratinocytes="" exposed="" to="" applicants'="" conditioned="" medium.");="" id.="" col.38="" ll.7--44="" (describing="" "[t]he="" antioxidant="" activity="" of="" the="" three-dimensional="" conditioned="" medium"="" and="" its="" effect="" on="" human="" keratinocytes).="" accordingly,="" an="" ordinarily="" skilled="" artisan="" reading="" the="" claim="" in="" light="" of="" the="" specification="" would="" understand="" that,="" to="" the="" extent="" the="" conditioned="" medium="" reduces="" intracellular="" oxidation="" in="" the="" keratinocytes,="" it="" does="" so="" by="" virtue="" of="" the="" presence="" of="" antioxidant="" activity.="" cf.="" bell="" atl.,="" 262="" f.3d="" at="" 1271="" (quoting="" vitronics,="" 90="" f.3d="" at="">

Contrary to SkinMedica's argument, by limiting the claim to antioxidant-activity-induced reduction of intracellular oxidation, the Court does not impermissibly import a limitation from a preferred embodiment into the claim. Rather, the portions of the prosecution history that describe the conditioned medium of the invention as having antioxidant activity refer to the invention as a whole, as opposed to a specific embodiment. See '746 Patent col.7 l.65 to col.8 l.4 (referring to antioxidant activity "in the conditioned cell medium"); id. col.28 ll.66--67 ("[T]he conditioned medium has antioxidant activity . . . ."); id. col.29 ll.8--9 ("[T]he conditioned medium of the invention has strong antioxidant acitivty." (emphasis added)); id. col.38 ll.7--44 (describing "[t]he antioxidant activity of the three-dimensional conditioned medium"). Repeated references in the specification to the invention as a whole can limit a claim, provided that the specification as a whole and prosecution history do not warrant a contrary result. See Netcraft Corp. v. Ebay, Inc., 549 F.3d 1394, 1398 (Fed. Cir. 2008).

Here, the prosecution history supports limiting the claim to reducing intracellular oxidation in the keratinocytes due to antioxidant activity in the conditioned medium. To overcome a rejection for lack of enablement, the inventors asserted that "[t]he invention . . . increases the amount of antioxidant generated during the culture of mesenchymal cells thereby providing a medium that can be used in reducing intracellular oxidation." (Histogen's CCB Ex. N, at 177.) The inventors emphasized that "most mesenchymal cells are capable of generating anti-oxidant molecules," and accordingly, "no undue experimentation is required for implementing the claimed method [of inhibiting or reversing deleterious effects to keratinocytes, where the effects are induced by intracellular oxidation,] in conjunction with mesenchymal cells."*fn14 (Id. at 178.) Thus, as in the specification, the inventors made clear during prosecution that it was the invention's antioxidant activity, and not some other mechanism, that had the effect of reducing intracellular oxidation in the keratinocytes.

Because the specification only describes one mechanism by which the invention reduces intracellular oxidation in the keratinocytes, the Court concludes that the claim only extends to reducing oxidation via that mechanism. See Netword, LLC v. Centraal Corp., 242 F.3d 1347, 1352 (Fed. Cir. 2001) ("Although the specification need not present every embodiment or permutation of the invention and the claims are not limited to the preferred embodiment of the invention, neither do the claims enlarge what is patented beyond what the inventor has described as the invention." (citation omitted)). Accordingly, the Court CONSTRUES "reducing intracellular oxidation in the keratinocytes" to mean "reducing intracellular oxidation in the keratinocytes due to the presence of antioxidant activity in the conditioned medium."

CONCLUSION

In summary, and for the reasons stated herein, the Court construes the disputed claim terms of the '494 and '746 patents as follows:

Claim language Court's construction "culturing fibroblast cells in "growing fibroblast cells in three dimensions three-dimensions" (excluding growing fibroblast cells in monolayers or on microcarrier beads)" "cultured in three-dimensions" "grown in three dimensions (excluding grown in monolayers or on microcarrier beads)" "culturing mesenchymal cells in "growing mesenchymal cells in three three-dimensions" dimensions (excluding growing mesenchymal cells in monolayers or on microcarrier beads)" "framework . . . formed into a "a three-dimensional structure composed of three-dimensional structure" any material and/or shape that (a) allows cells to attach to it (or can be modified to allow cells to attach to it); and (b) allows cells to grow in more than one layer" "substantially enveloping" and "substantially "substantially enclosing, surrounding, or envelop" covering" "conditioned medium" and "conditioned cell "a formulation containing extracellular medium" protein(s) and cellular metabolites, which has previously supported the growth of cells having been cultured in three-dimensions" "pharmaceutically acceptable carrier" and "solid or liquid diluents or encapsulating "pharmaceutical carrier" substances that are suitable for administration to a human or lower animal" "cosmetic application" "application as a preparation for beautifying, preserving or altering appearance" "mesenchymal cells" "cells of mesenchymal lineage" "reducing intracellular oxidation in the "reducing intracellular oxidation in the keratinocytes" keratinocytes due to the presence of antioxidant activity in the conditioned medium"

IT IS SO ORDERED.


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