ISIS Pharmaceuticals, Inc. v. Santaris Pharma A/S Corp. et al, No. 3:2011cv02214 - Document 53 (S.D. Cal. 2012)
Court Description: ORDER Denying Defendants' 17 Motion for Summary Judgment without prejudice. The parties shall be permitted 120 days following the entry of this Order to conduct limited discovery related to the issues raised by Santaris's Safe Harbor motion. The Court grants Santaris leave to re-file a motion for summary judgment pursuant to § 271(e)(1) within 30 days following the close of the limited discovery period. Signed by Judge Barry Ted Moskowitz on 9/18/2012. (rlu)
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ISIS Pharmaceuticals, Inc. v. Santaris Pharma A/S Corp. et al Doc. 53 1 2 3 4 5 6 7 8 UNITED STATES DISTRICT COURT 9 SOUTHERN DISTRICT OF CALIFORNIA 10 11 ISIS PHARMACEUTICALS, INC., a Delaware Corporation, Case No. 11cv02214 BTM (KSC) ORDER DENYING DEFENDANTS’ MOTION FOR SUMMARY JUDGMENT WITHOUT PREJUDICE 12 Plaintiff, v. 13 14 15 SANTARIS PHARMA A/S CORP., a Delaware Corporation, and SANTARIS PHARMA A/S, a Danish Corporation, Defendants. 16 17 Plaintiff Isis Pharmaceuticals, Inc. (“Isis” or “Plaintiff”) alleges that Defendants Santaris 18 Pharma A/S Corp. and Santaris Pharma A/S (collectively, “Santaris” or “Defendants”) have 19 infringed upon two of Isis’s patents. Pending before the Court is Defendants’ motion for 20 summary judgment, in which Defendants argue that their activities are protected by the “Safe 21 Harbor” provision of 35 U.S.C. § 271(e)(1) (the “Safe Harbor”). 22 I. BACKGROUND 23 24 25 The two patents at issue in this litigation provide for a form of biotechnology called 26 antisense molecules. This background section provides an overview of antisense technology 27 generally, the two relevant patents, and Plaintiff’s specific infringement claims. 28 // 1 11cv02214 BTM (KSC) Dockets.Justia.com 1 a. Overview of antisense technology 2 3 Proteins, fundamental molecules found in all living cells, are primary actors within a 4 cell. They perform a variety of essential functions such as catalyzing chemical reactions, 5 communicating between cells, and providing structural support. The overproduction or 6 abnormal production of proteins can cause disease. One method for treating a disease 7 caused by the overproduction of a certain “target” protein is to create an “antisense” molecule 8 that interrupts the cellular process of creating that protein. 9 The cellular process of creating proteins begins with genetic information (“genes”) 10 stored in DNA and proceeds in two stages: transcription and translation. 11 transcription, the gene for a particular protein is copied from a strand of DNA to a molecule 12 called messenger RNA (“mRNA”). During translation, cellular machinery converts the 13 information on the mRNA into proteins. During 14 Antisense molecules—typically a type of a nucleic acid that is similar to DNA and 15 mRNA molecules, but much shorter—are able to interrupt the genesis of the target protein 16 at the translation stage by binding to the mRNA molecules containing the genetic information 17 for that protein. Once bound to an mRNA molecule, the antisense molecule can obstruct the 18 chemical process that translates the mRNA into a protein. The two biotechnology patents 19 at issue in this litigation relate to antisense technology. 20 21 b. The ‘199 Patent 22 23 U.S. Patent No. 6,326,199, “Gapped 2’ Modified Oligonucleotides” (the “‘199 Patent”), 24 claims, in independent claim 1, a method of enhancing an antisense molecule by creating 25 structural features (a) enabling the antisense molecule to resist degradation before it reaches 26 its target mRNA; (b) enhancing “binding affinity” (the strength of the chemical bond between 27 the antisense molecule and the target mRNA); and (c) activating an enzyme called Rnase 28 H that, once activated, severs the target mRNA, preventing translation into the target protein. 2 11cv02214 BTM (KSC) 1 See Cplt. ¶¶ 19-21; ‘199 Patent Col. 31, ll. 39-49. Many of the dependent claims claim 2 methods of modifying the molecule described in Claim 1 in additional ways. 3 Independent claim 11 claims a method of “modifying a sequence-specific ribo-nucleic 4 acid” (i.e., a target mRNA or other type of RNA) using a molecule having the properties 5 claimed in claim 1. (‘199 Patent Col. 33, ll. 3-15.) In other words, claim 11 claims the 6 method of using the antisense molecule described in claim 1 to affect the function of its 7 target. 8 9 c. The ‘500 Patent 10 11 U.S. Patent No. 6,066,500, “Antisense Modulation of Beta Catenin Expression” (the 12 ‘500 Patent”), is directed toward antisense technology that is designed specifically to inhibit 13 the expression of a protein called Beta catenin. Beta catenin has been implicated in the 14 development of several types of cancer, including cancer of the colon and of the skin. 15 Independent claims 1 and 3 claim an antisense molecule of a particular size that hybridizes 16 with the mRNA molecule responsible for generating Beta catenin, and thereby “inhibits the 17 expression of Beta catenin.” (Col. 65, ll. 53-54.) Many of the dependent claims claim a more 18 specific type of molecule that meets the qualifications of the molecule described in claims 1 19 and 3. 20 Claims 11 and 20 claim a “method of inhibiting the expression of human Beta catenin 21 in human cells or tissues comprising contacting said cells or tissues in vitro with the 22 antisense compound of [claims 1 and 3] so that expression of Beta catenin is inhibited.” (Col. 23 66, ll. 56-59; Col. 68, ll. 3-6.) 24 25 d. Isis’s infringement claims 26 27 Plaintiff has alleged that Defendants have used molecules claimed by the ‘199 Patent, 28 and the method of contacting cells with those molecules also claimed in the ‘199 Patent, to 3 11cv02214 BTM (KSC) 1 “identify [gene] targets and/or to screen gapmer . . . antisense molecules for activity inhibiting 2 a target. Santaris further sells and offers for sale in the United States the patented methods 3 of the ‘199 Patent.” (Cplt. ¶ 24.) Plaintiff further alleges that “Santaris has offered for sale 4 and sold antisense compounds that inhibit Beta catenin production in violation of the ‘500 5 Patent.” (Id. ¶ 26.) 6 Plaintiff alleges four specific agreements between Santaris and pharmaceutical 7 companies based in the United States that form the basis of these infringement contentions: 8 January 4, 2011 announced agreement with Pfizer, Inc. Plaintiff alleges that Pfizer 9 paid Santaris “$14 million for access to Santaris Pharma A/S Locked Nucleic Acid (LNA) 10 Drug Platform to develop RNA-targeted drugs.” (Id. ¶ 37 (quoting Cplt. Ex. 3, 4 Jan. 2011 11 Press Release).) Pfizer also allegedly “agreed to pay milestones to Santaris upon the 12 identification of up to ten gene targets and the discovery of lead antisense LNA molecule 13 candidates.” (Id.) This agreement allegedly infringes the ‘199 Patent by “[o]ffering for sale 14 and selling the process of using gapmers to reduce target RNA for target validation 15 purposes; and/or [o]ffering for sale and selling the process of screening and identifying 16 gapmer compounds to identify drug candidates for drug development.” (Id. ¶ 39.) 17 July 27, 2006 announced agreement with Enzon Pharmaceuticals, Inc. Plaintiff 18 alleges that Santaris “sold two antisense gapmer molecules and targets to Enzon for $6 19 million” (id. ¶ 41), and that, pursuant to the agreement, “Enzon nominated six additional 20 targets for which Santaris agreed to identify LNA gapmer compounds that inhibit the 21 nominated targets using Isis’[s] methods patented in the ‘199 Patent and compositions 22 covered in the ‘500 Patent” (id. ¶ 42). 23 August 24, 2009 announced agreement with Shire PLC. Pursuant to this agreement, 24 Santaris allegedly receives significant upfront payments, milestone payments and royalties 25 for providing access to Santaris’s LNA technology and exclusivity for three targets and an 26 additional two targets to be nominated by Shire in the future. (Id. (citing Cplt. Ex. 6, 24 Aug. 27 2009 Press Release).) Plaintiff alleges that this agreement infringes on the ‘199 Patent by 28 “[o]ffering for sale and selling the process of using gapmers to identify and reduce target 4 11cv02214 BTM (KSC) 1 RNA for further drug discovery; and/or [o]ffering for sale and selling the process of screening 2 and identifying gapmer candidates to identify drug candidates for drug development.” (Id. 3 ¶ 48.) 4 December 19, 2007 announced agreement with GlaxoSmithKline. Plaintiff alleges 5 that, pursuant to this agreement, “Santaris would receive approximately $8 million as an 6 upfront payment, milestone payments, and royalties for providing access to Santaris’ LNA 7 technology and exclusivity for four targets.” (Id. ¶ 50.) Plaintiff alleges that this transaction 8 infringed upon the ‘199 Patent in the exact same manner as the August 4, 2009 agreement 9 with Shire PLC, described in the preceding paragraph. (Id. ¶ 52.) 10 11 II. STANDARD 12 13 Summary judgment is appropriate under Rule 56 of the Federal Rules of Civil 14 Procedure if the moving party demonstrates the absence of a genuine issue of material fact 15 and entitlement to judgment as a matter of law. Celotex Corp. v. Catrett, 477 U.S. 317, 322 16 (1986). A fact is material when, under the governing substantive law, it could affect the 17 outcome of the case. Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248 (1986); Freeman 18 v. Arpaio, 125 F.3d 732, 735 (9th Cir. 1997). A dispute is genuine if a reasonable jury could 19 return a verdict for the nonmoving party. Anderson, 477 U.S. at 248. 20 A party seeking summary judgment always bears the initial burden of establishing the 21 absence of a genuine issue of material fact. Celotex, 477 U.S. at 323. Once the moving 22 party establishes the absence of genuine issues of material fact, the burden shifts to the 23 nonmoving party to set forth facts showing that a genuine issue of disputed fact remains. 24 Celotex, 477 U.S. at 314. The nonmoving party cannot oppose a properly supported 25 summary judgment motion by “rest[ing] on mere allegations or denials of his pleadings.” 26 Anderson, 477 U.S. at 256. When ruling on a summary judgment motion, the court must 27 view all inferences drawn from the underlying facts in the light most favorable to the 28 nonmoving party. Matsushita Elec. Indus. Co. v. Zenith Radio Corp., 475 U.S. 574, 587 5 11cv02214 BTM (KSC) 1 (1986). 2 3 III. DISCUSSION 4 5 Section 271(e)(1)’s “Safe Harbor” provides: 6 It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention . . . solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs[.] 7 8 35 U.S.C. § 271(e)(1). The Supreme Court has interpreted this statutory language to 9 “provide[] a wide berth for the use of patented drugs in activities related to the federal 10 regulatory process.” Merck KGaA v. Integra Lifesciences I, Ltd, 545 U.S. 193, 202 (2005); 11 see also Momenta Pharmaceuticals, Inc. v. Amphastar Pharmaceuticals, Inc., --- F.3d ---, 12 2012 WL 3140303, at *6 (Fed. Cir. 2012) (“Congress could not have been clearer in its 13 choice of words: as long as the use of the patented invention is solely for uses ‘reasonably 14 related’ to developing and submitting information pursuant to ‘a Federal law’ regulating the 15 manufacture, use, or sale of drugs, it is not ‘an act of infringement.’). 16 In Merck, the Supreme Court clarified the scope of the Safe Harbor as it applies to 17 patents for biological compounds: 18 19 20 21 22 At least where a drugmaker has a reasonable basis for believing that a patented compound may work, through a particular biological process, to produce a particular physiological effect, and uses the compound in research that, if successful, would be appropriate to include in a submission to the FDA, the use is “reasonably related” to the “development and submission for information . . . under federal law.” Id. at 207 (citing 35 U.S.C. § 271(e)(1)) (alterations in original) (emphasis added). 23 The Safe Harbor does not apply, however, when a biological compound is used to 24 perform “basic scientific research” or as a “research tool.” “Basic scientific research” is 25 performed when the researcher “lacks the intent to develop a particular drug or a reasonable 26 belief that the compound will cause the sort of physiological effect the researcher intends to 27 induce.” Id. at 205-06. 28 “Research tools” are patented inventions that are “used in the development of . . . 6 11cv02214 BTM (KSC) 1 regulatory submissions, but [are] not [themselves] subject to the [regulatory] approval 2 process.” Proveris Scientific Corp. v. Innovasystems, Inc., 536 F.3d 1256, 1265 (Fed. Cir. 3 2008). For example, in PSN Illinois, LLC v. Abbott Laboratories, No. 09 C 5879, 2011 WL 4 4442825, at *4-6 (N.D. Ill. Sept. 20, 2011), the Court found that the defendants’ use of a 5 patented protein receptor was a “research tool,” where the receptor was used only to perform 6 tests on other drug candidates that did not themselves incorporate the patented invention. 7 “They were using a patented invention to develop their own patentable product. . . . 271(e)(1) 8 offers no protection for such activity.” Id. at *6. 9 Plaintiff has alleged in its complaint, and maintains in its opposition to Santaris’s 10 motion for summary judgment, that Santaris used and/or sold infringing compounds, 11 methods, and processes both to conduct basic scientific research and as research tools. 12 Against these allegations, and in support of its motion, Santaris presents only the declaration 13 of one of its officers, Dr. Henrik Ørum, which states that Santaris does not begin using the 14 antisense technology allegedly covered by the ‘199 and ‘500 Patents unless and until “a 15 therapeutic target has been identified by someone else, and Santaris is sufficiently satisfied 16 that it may achieve a therapeutic effect against a human disease by modulating the identified 17 target with . . . antisense drugs.” (Ørum Decl. ¶ 20.) 18 Dr. Ørum’s declaration provides a broad overview of the process of generating a 19 “library” of antisense drug candidates tailored to the “therapeutic target,” performing in vitro 20 and in vivo tests to “to identify the most effective drug candidates[,]” and transmitting the 21 information gained during this process and/or samples of the antisense drug candidates 22 themselves to Santaris’s “partners.” (Id. ¶ 22-35). The declaration concludes that if one of 23 Santaris’s pharmaceutical company partners “wish[es] to obtain FDA approval” for an 24 antisense drug generated through this process, “[t]he data and results that Santaris has 25 generated throughout the design and development process are used for purposes of 26 submission to the FDA” (id. at ¶ 37). On the basis of these representations, Santaris argues 27 that all of its activities fall within the Safe Harbor: 28 [A]ll of Santaris’s activities are undertaken with the express purpose and intent of developing a specific LNA antisense drug to treat an identified condition after 7 11cv02214 BTM (KSC) 1 2 3 a reasonable basis has been established and demonstrated that the activity of the RNA molecule of interest may be modulated to bring about the desired physiological effect. (Def. Br. at 13.) 4 At the outset, the Court finds that the facts introduced by Santaris by way of the 5 declaration of one of its officers falls short of the evidentiary burden placed on an accused 6 infringer claiming exemption from infringement under § 271(e)(1). On remand from the 7 Supreme Court’s decision in Merck, the Federal Circuit noted that “the variety of 8 experimental activity that may apply to any specific biologic or physiologic investigation 9 reinforces the fact-dependency of the inquiry.” Integra Lifesciences I, Ltd. v. Merck KgaA, 10 496 F.3d 1334, 1347 (Fed. Cir. 2007) (emphasis added). In that case, the Federal Circuit 11 determined that the defendants’ uses of the infringing biological compound were “reasonably 12 related” to the development and submission of information to the FDA only after a detailed 13 review of the purpose of each of sixteen enumerated categories of accused experiments in 14 light of “extensive” trial testimony regarding “how and why all of these experiments were 15 performed,” the type of information generated by each experiment, and the type of 16 information called for the by the specific FDA regulations at issue. Id. at 1343-44. The 17 record before this Court stands in stark contrast to the record before the Federal Circuit in 18 Integra. The Ørum declaration describes in general terms a process that could fall within the 19 Safe Harbor. But even taking as true everything in the Ørum Declaration, the Court would 20 decline to resolve Santaris’s claim to the Safe Harbor exemption without a more specific 21 analysis of Santaris’s uses of the allegedly infringing compounds, methods, and processes. 22 Moreover, the Court declines to grant summary judgment in favor of Santaris on all claims 23 at this early stage in the litigation solely on the basis of the Ørum Declaration, without first 24 providing an opportunity for Isis at least to conduct limited discovery and depose Dr. Ørum. 25 The Court also finds that Isis has called into question Santaris’s claim that “Santaris 26 does not perform any antisense technology work until a therapeutic target has been identified 27 by someone else[.]” (Ørum Decl. ¶ 20.) First, Isis points to language in a press release 28 covering one of the allegedly infringing sales between Santaris and a pharmaceutical 8 11cv02214 BTM (KSC) 1 company suggesting that Santaris did not know, at the time it licensed antisense technology 2 to the pharmaceutical company, which mRNA molecules the pharmaceutical company 3 intended to target. See Gaede Decl. Ex. 11, 27 Jul. 2006 Press Release (“Enzon will make 4 an initial up-front payment of $8 million to Santaris Pharma, followed by an additional $3 5 million upon the successful identification of certain LNA targets.”) (emphasis added). 6 Second, Isis has introduced a sworn declaration of Dr. Ørum provided to the U.S. 7 Patent and Trademark Office in December 2009 during the reexamination of one of 8 Santaris’s patents, in which Dr. Ørum states: 9 The majority of our collaborators have taken broad licenses to our proprietary LNA [“locked nucleic acid”—a type of antisense molecule] platform in order to discover, develop, and commercialize new LNA-based drugs against RNA targets associated with disease. 10 11 12 (Gaede Decl. Ex. 23, 20 Dec. 2009 Second Declaration of Henrik Ørum Under 37 C.F.R. § 13 1.132, ¶ 3 (emphasis added).) This same declaration specifically references Santaris’s 14 agreements forming the basis of the alleged infringing acts in this lawsuit. To the extent 15 Santaris is selling and/or licensing infringing “platform” technology so that another company 16 can “discover and develop” drug candidates—rather than developing and/or licensing/selling 17 specific drug candidates itself—Santaris could be using or selling patented technology to 18 perform “basic scientific research.” Merck, 545 U.S. at 207. 19 // 20 // 21 // 22 // 23 // 24 // 25 // 26 // 27 // 28 // 9 11cv02214 BTM (KSC) 1 IV. CONCLUSION 2 3 For all these reasons, the Court DENIES Santaris’s motion for summary judgment 4 without prejudice at this time. The parties shall be permitted 120 days following the entry of 5 this Order to conduct limited discovery related to the issues raised by Santaris’s Safe Harbor 6 motion. The Court grants Santaris leave to re-file a motion for summary judgment pursuant 7 to § 271(e)(1) within 30 days following the close of the limited discovery period. 8 9 IT IS SO ORDERED. 10 Dated: September 18, 2012 11 HONORABLE BARRY TED MOSKOWITZ United States District Judge 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 10 11cv02214 BTM (KSC)
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