Opinion ID: 625949
Heading Depth: 3
Heading Rank: 1

Heading: A method to increase expression of a gene in a

Text: mammalian cell comprising inserting into the mammalian cell an isolated DNA enhancer con- sisting of DNA from the upstream region of the major immediate early (IE) gene of human cy- tomegalovirus (HCMV) and a heterologous gene that is to be expressed, wherein the DNA from the upstream region of the IE gene of HCMV is the only HCMV material to which the mammalian cell is exposed. ’522 patent col.2 l.63 – col.3 l.3 (emphases added). 2 In the district court, the parties disputed the meanings of “isolated DNA enhancer” and “DNA from the upstream region of the major immediate early (IE) gene of human cytomegalovirus (HCMV).” In resolving those issues, the district court construed “isolated DNA enhancer” to mean 2 Claim 2 depends from claim 1, imposing further limitations on the DNA that can constitute the isolated DNA enhancer recited in claim 1. See ’522 patent col.3 ll.4–8. Because we agree with the district court that Appellees do not infringe claim 1, we need not separately address claim 2. SANOFI-AVENTIS v. GENENTECH 6 a DNA sequence, separated by human interven- tion from the promoter DNA in its original source, that (1) strongly stimulates transcription of a linked gene, (2) functions independent of orientation, and (3) functions even if located long dis- tances upstream or downstream relative to the initiation site of the linked gene. Claim Construction Order, 2010 WL 2525118, at  (emphases added). The district court next construed “DNA from the upstream region of the major immediate early (IE) gene of human cytomegalovirus (HCMV)” as “DNA from the region that is upstream of the transcription start site of the major IE gene of HCMV.” Id. at . On the issue of infringement, the district court held that Appellees did not infringe the ’522 patent because, inter alia, Appellees do not practice the step of “inserting” an isolated DNA enhancer into a mammalian cell. Final Judgment, 2011 WL 839411, at –6. 1. Claim Construction
On appeal, Sanofi argues that the district court erred by defining “isolated DNA enhancer” to require the enhancer to be “separated . . . from the promoter DNA in its original source.” Claim Construction Order, 2010 WL 2525118, at . Sanofi argues that the claimed “isolated DNA enhancer” can include the native HCMV promoter but concedes that it need not, pointing out that the ’522 patent’s specification teaches that the HCMV enhancer can be used with or without the HCMV IE promoter. See ’522 patent col.2 ll.6–10, 43–56. Appellees respond that Sanofi disclaimed enhancer fragments that include the HCMV IE promoter during prosecution and that the 7 SANOFI-AVENTIS v. GENENTECH disclosure excludes the promoter from its discussion of enhancer-active elements. We agree with the district court that the intrinsic evidence does not support Sanofi’s construction. We have held that an otherwise broadly defined term can be narrowed during prosecution through arguments made to distinguish prior art. Phillips v. AWH Corp., 415 F.3d 1303, 1317 (Fed. Cir. 2005) (en banc). In this case, the applicants made such a disclaimer during prosecution of U.S. Patent Application No. 07/170,140—an ancestor of the application that eventually issued as the ’522 patent—to overcome obviousness rejections against thenpending claims that recited an “isolated enhancer.” Specifically, the examiner had cited two references (Thomsen and Jahn) that disclose HCMV-derived DNA sequences encompassing the HCMV IE enhancer and promoter regions. In a response dated March 14, 1988, the applicants distinguished the cited art, as follows: [N]either of these primary references teaches the preparation of an isolated enhancer region as de- fined by the pending claims. . . . Thomsen et al. expressly discusses promoter sequences . . . . [Jahn] isolates and characterizes a variety of clones and illustrates several maps. The refer- ence does not appear to isolate an enhancer se- quence . . . . J.A. 806–07 (emphasis in original). Thus, the applicants distinguished their isolated enhancer from the cited references, and such statements amount to “a clear and unmistakable disavowal of scope during prosecution” of the ’522 patent. Purdue Pharma L.P. v. Endo Pharms. Inc., 438 F.3d 1123, 1136 (Fed. Cir. SANOFI-AVENTIS v. GENENTECH 8 2006); see also Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 997–98 (Fed. Cir. 2006). Because Thomsen and Jahn disclose the entire HCMV IE regulatory region, including the claimed enhancer sequences, the applicants cast those references as general disclosures that failed to describe or isolate the HCMV enhancer from its native context within the surrounding viral sequences. Moreover, the applicants underscored the presence of HCMV IE promoter sequences in Thomsen to distinguish that reference from the “isolated enhancer” recited in the pending claims. Hence, their claims must be interpreted to refer to the enhancer separated from the promoter, and we agree with the district court that the term “isolated DNA enhancer” requires an enhancer separated from the promoter DNA in its original source.
In addition, Sanofi alleges error in the construction of the term “DNA from the upstream region of the major immediate early (IE) gene of human cytomegalovirus (HCMV),” which the district court interpreted to mean “DNA from the region that is upstream of the transcription start site of the major IE gene of HCMV.” Claim Construction Order, 2010 WL 2525118, at  (emphasis added). Sanofi contends that the term “DNA from the upstream region of the major immediate early (IE) gene of human cytomegalovirus (HCMV)” should be construed to mean “DNA from upstream of the translation start site of the major IE gene of HCMV.” According to Sanofi, the specification discloses the use of HCMV enhancers including portions of viral DNA extending beyond the transcription start site to the HCMV splice donor site at +120 or the downstream PstI site at approximately +930. See ’522 patent col.2 ll.6–10, 44–56. To include those features, Sanofi argues, the claimed “upstream region of the major 9 SANOFI-AVENTIS v. GENENTECH immediate early (IE) gene” must encompass the transcribed, but untranslated, region spanning the transcription and translation start sites of the HCMV IE gene at +1 and approximately +950, respectively. We disagree. A diagram of the HCMV IE gene, adapted from figure 1a of the ’522 patent and marked to emphasize relevant points of reference, is shown below: Claim 1 recites the method of using an isolated DNA enhancer that consists of “DNA from the upstream region of the [HCMV IE gene],” and the specification uses consistent language in describing the HCMV enhancer’s position as “located in the upstream region of the [HCMV IE gene].” Id. [57] (emphasis added); see also id. col.1 ll.14– 17. But the specification describes the location of the +120 splice donor site differently, with the key phrase “upstream region” notably absent. Rather, the specification describes the +120 splice donor sequence as the “splice donor consensus sequence of the IE gene.” Id. col.2 ll.8–9 (emphasis added). Thus, while the +120 splice donor site is indeed part of the IE gene, the specification reserves the “upstream region” label from its discussion of the splice donor site, indicating that the claim term “DNA from the upstream region of the [HCMV IE gene]” specifies a distinct portion of the broader IE gene that excludes SANOFI-AVENTIS v. GENENTECH 10 the splice donor site (+120), the downstream PstI site (+930), and the translation start site (+950). 3 We therefore reject Sanofi’s contention that the downstream end of the “upstream region” recited in claim 1 extends to the translation start site of the IE gene, and we affirm the construction adopted by the district court.