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GlaxoSmithKline LLC v. Glenmark Pharmaceuticals Inc.

United States District Court, D. Delaware

May 2, 2017




         In these two related actions filed by Plaintiffs GlaxoSmithKline LLC and SmithKline Beecham (Cork) Limited (collectively, "GSK" or "Plaintiffs") against Defendant Glenmark Pharmaceuticals Inc., USA ("Glenmark") and Teva Pharmaceuticals USA, Inc. ("Teva") (collectively, "Defendants"), GSK alleges induced infringement of United States Patent No. RE40, 000 (the "Asserted Patent" or the "'000 patent"). Presently before the Court is Defendants' motion for summary judgment of invalidity (the "Motion").[1] (Civil Action No. 14-877-LPS- CJB (hereinafter "Glenmark Action"), D.I. 214; Civil Action No. 14-878-LPS-CJB (hereinafter "Teva Action"), D.I. 248)[2] The Court recommends that Defendants' Motion be DENIED.

         I. BACKGROUND

         A. The Parties

         GSK manufactures and sells the drug carvedilol under the trade name COREG®. (D.I. 60 at ¶¶ 8, 22) Plaintiff SmithKline Beecham (Cork) Limited is the owner, by assignment, of the '000 patent, which relates to methods of administering carvedilol; Plaintiff Glaxo SmithKline LLC is the patent's exclusive licensee. (Id. at ¶¶ 37-38; see also '000 Patent)

         Defendants are engaged in the business of developing, manufacturing, and distributing generic versions of branded drug products throughout the United States. (See, e.g., Glenmark Action, D.I. 61 at ¶ 47; Teva Action, D.I. 60 at ¶ 47; D.I. 105 at ¶ 47)

         B. Discovery of Carvedilol as a Treatment for Congestive Heart Failure

         Congestive heart failure (or "CHF"), which has been construed by the Court to mean "a condition that occurs as a result of impaired pumping capability of the heart and is associated with abnormal retention of water and sodium[J" (D.I. 165 at 43), affects over 5 million people in the United States, (D.I. 298 (hereinafter, "McCann Decl. Vol. I"), ex. 2 at ¶ 23). Symptoms of CHF include dyspnea (breathlessness), poor exercise intolerance, fatigue and edema (swelling of the legs). (D.I. 253 (hereinafter, "Rosendorff Decl."), ex. A at ¶ 28; McCann Decl. Vol. I, ex. 2 at ¶ 24) Historically, approximately half of the people that developed CHF died within 5 years of diagnosis. (See '000 patent, col. l:55-57;[3] McCann Decl. Vol. I, ex. 2 at ¶ 23) Before 1997, the only treatments approved by the United States Food and Drug Administration ("FDA") for heart failure were diuretics, certain angiotensin converting enzyme ("ACE") inhibitors and digoxin/digitalis. (McCann Decl. Vol. I, ex. 2 at ¶ 25) These drugs were used to treat the symptoms of heart failure. (Id.) Controlled clinical trials also demonstrated that ACE inhibitors reduced the risk of mortality from heart failure by about 20%. (Id.)

         Carvedilol has been a known beta blocker since at least 1978. (U.S. Patent No. 4, 503, 067; see also McCann Decl. Vol. I, ex. 2 at ¶ 29) Beta blockers are compounds that prevent stimulation of the adrenergic receptors responsible for increased heart rate and contractility, and thus they can cause the heart to pump slower or with less force. (McCann Decl. Vol. I, ex. 2 at ¶ 27) Historically, beta blockers were contraindicated in the treatment of CHF because of the medical community's "widely-held concern" that this type of drug would further reduce the diseased and/or damaged heart's ability to pump blood through the body. (Id. at ¶¶ 27-28; see also D.I. 299 (hereinafter, "McCann Decl. Vol. IT), ex. 53 at 50, 55 (Glenmark's expert Sean C. Beinart, M.D. noting that when he was in medical school in the "mid-'90s" he was taught "capital letters, beta blockers are contraindicated [for CHF]"); '000 patent, col. 3:56- 60) For example, guidelines published in 1993 regarding the treatment of high blood pressure indicated that beta blockers were "[r]elatively or [a]bsolutely [c]ontraindicated" in patients with cardiac failure. (McCann Decl. Vol. I, ex. 3 at Table 8; see also GSK's Anticipation and Obviousness Presentation, Slide PDX-104)

         Nevertheless, dating back to the mid-1970s, groups were studying the effectiveness of beta blockers to treat patients with CHF. In 1975, a group of Swedish researchers hypothesized that beta blockers could "influence the progression of congestive cardiomyopathy and prolong life in these patients[, ]" (D.I. 264 (hereinafter, "Riley Decl. Vol. I"), ex. 3 at 1034-35), and by 1979, they published their first clinical trial which "suggested that [beta blockers] prolong[] survival in patients with congestive cardiomyopathy[, ]" (id., ex. 4 at 1374-75; cf. ex. 5 at ¶ 269). A study published in 1994 by Japanese physicians noted that "[e]vidence for the effectiveness of long-term [beta blockers] in the treatment of heart failure has been increasingly accumulated" and concluded that the survival rate in patients with dilated cardiomyopathy was significantly improved by beta-blocker therapy. (Id., ex. 6 at 355-58)

         As to carvedilol, in particular, the prior art included studies showing that it improved hemodynamics and symptoms in patients with CHF. (See, e.g., id., ex. 5 at ¶¶ 245-47, 293, 302; Rosendorff Deck, ex. A at ¶¶ 147-52, 156-58) For instance, an abstract published in early 1993 described a study of carvedilol in 54 patients with CHF due to either idiopathic or ischemic dilated cardiomyopathy; the abstract concluded that "[c]arvedilol is well tolerated and improves both symptoms and cardiac function in [such patients]." (Riley Decl. Vol. I, ex. 7; see also Rosendorff Deck, ex. A at ¶ 156) That same year, a researcher from Australia, Dr. David T. Kelly, published an article that (1) described recent studies that "have demonstrated symptomatic improvement with carvedilol in patients with heart failure" and (2) summarized a planned "multicentre trial" (which was known as the "ANZ pilot study" and was conducted by another physician, Dr. Norman Sharpe) "to evaluate [the drug's] efficacy and safety" (hereinafter, the "Kelly reference" or "Kelly"). (Riley Decl. Vol. I, ex. 8 (hereinafter, "Kelly");[4] see also D.I. 297 at 13, 17n.12)

         In the late 1980s, meanwhile, the named inventors of the '000 patent (Mary Ann Lukas-Laskey, Robert Ruffolo, Jr., and Neil Howard Shusterman of GSK's predecessor and Gisbert Sponer and Klaus Strein of Boehringer Mannheim Pharmaceuticals Corporation) were investigating the possible uses of carvedilol (then in development as a drug to treat hypertension) to treat different diseases. (McCann Decl. Vol. I, ex. 2 at ¶ 30; '000 patent, col. 3:15-36) They pursued promising research suggesting that carvedilol could be used to successfully treat CHF, receiving approval from the FDA to initiate a clinical trial in 1992. (McCann Decl. Vol. I, ex. 2 at ¶ 30) According to Dr. Ruffolo, the reaction from his colleagues was very negative, due to concerns that a beta blocker like carvedilol would actually hasten the death of those with CHF. (McCann Decl. Vol. II, ex. 81 at GSK00983250) One colleague told him that he was '"going to kill a lot of people with that drug[.]'" (Id.) GSK's Chief Executive Officer received a letter protesting the studies of carvedilol in CHF patients as resembling '"the studies done by the Nazi scientists in the death camps of World War II[.]'" (Id.; see also McCann Decl. Vol. I, ex. 4 at 86) In light of these concerns, GSK established a Data and Safety Monitoring Board ("DSMB") to monitor the trial and to stop it if carvedilol, in fact, was killing patients. (McCann Decl. Vol. I, ex. 4 at 87)

         In February 1995, the DSMB did indeed terminate the clinical trial early, but based on the finding of a significant effect of carvedilol on survival in CHF patients. (Id.; see also id., ex. 2 at ¶ 33; id., ex. 6; id., ex. 7; id., ex. 8 at 329-30) The trial revealed that patients treated with carvedilol had an approximately 65% lower risk of death than those given placebo. (Id., ex. 11 at GSK00776812; see also id., ex. 8 at 243-44; '000 patent, col. 3:60-64) In light of this data, the DSMB believed that it would be "'unethical'" to maintain a placebo arm of the study. (McCann Decl. Vol. I., ex. 6-7; see also id., ex. 4 at 87) The results of the clinical trial were published in The New England Journal of Medicine. (Id., ex. 11)

         In November 1995, GSK sought FDA approval of carvedilol to reduce the risk of mortality caused by heart failure. (Id., ex. 13 at ¶ 34) The FDA initially rejected GSK's application, but after receiving additional confirmatory data and analysis, in May 1997, the FDA ultimately approved carvedilol as the first beta blocker for the treatment of CHF, as an adjunctive therapy. (Id. at ¶¶ 34-35; see also D.I. 297 at 5-6) The next month, GSK launched COREG. (McCann Decl. Vol. I, ex. 14 at ¶ 10)

         By 2004, the FDA had approved COREG for three indications:

1.1 Heart Failure: COREG® is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization...
1.2 Left Ventricular Dysfunction Following Myocardial Infarction: COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of <40% (with or without symptomatic heart failure)...
1.3 Hypertension: COREG is indicated for the management of essential hypertension []. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics[.]

(D.I. 60, ex. F at 1160) In 2006-2007 (and prior to the entry into the market of Defendants' generic carvedilol in September 2007), sales of COREG peaked at approximately $1.6 billion per year. (See McCann Decl. Vol. II, ex. 82 at GSK00983295; see also D.I. 297 at 6) And by 2007, treatment guidelines specifically recommended carvedilol for treatment of heart failure. (McCann Decl. Vol. I, ex. 13 at ¶ 50) Dr. Ruffolo and Dr. Lukas have received a number of awards for their work in developing the invention claimed in the '000 patent. (Id. at ¶¶ 381-83; McCann Decl. Vol. II, ex. 82)

         C. '000 Patent

         In June 1995, the inventors filed a patent application directed to a method of using carvedilol to decrease the risk of mortality caused by CHF; the patent issued in June 1998 as U.S. Patent No. 5, 760, 069 (the '"069 patent"), entitled "Method of Treatment for Decreasing Mortality Resulting from Congestive Heart Failure." (See '000 patent) The FDA published the '069 patent in the "Approved Drug Products with Therapeutic Equivalence Evaluations" publication (the "Orange Book") as covering COREG for use in decreasing mortality caused by CHF. (See McCann Decl. Vol. I, ex. 15)

         In November 2003, GSK requested a reissue of the '069 patent, and on January 8, 2008, that patent reissued as the '000 patent. ('000 patent) In February 2008, GSK replaced the '069 patent in the Orange Book with the '000 patent, and it identified "Decreasing Mortality Caused By Congestive Heart Failure" as the method of use covered by the '000 patent that should be included as the "use code" in that publication. (McCann Decl. Vol. I, ex. 16 at GSK00592204, GSK00592217)

         The '000 patent contains 9 method claims directed to methods of decreasing mortality caused by CHF in a patient in need thereof by administering carvedilol in a manner recited in the claims. ('000 patent) GSK asserts all but claim 5 against Defendants in these actions. (D.I. 249 at 3) Claim 1 is the only independent claim of the '000 patent, and it reads:

1. A method of decreasing mortality caused by congestive heart failure in a patient in need thereof which comprises administering a therapeutically acceptable amount of carvedilol in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of an angiotensin converting enzyme inhibitor (ACE), a diuretic, and digoxin,
wherein the administering comprises administering to said patient daily maintenance dosages for a maintenance period to decrease a risk of mortality caused by congestive heart failure, and said maintenance period is greater than six months.

('000 patent, col. 8:30-40 (emphasis in original)) The italicized portion of the claim is the portion that was added during the reissue proceeding.

         The limitations "decreasing mortality caused by congestive heart failure" and "to decrease a risk of mortality caused by congestive heart failure" will be referred to herein as the "decreasing mortality limitations." The Court has construed the decreasing mortality limitations as claim limitations that mean '" attempting] to reduce the probability that a patient will die as a result of congestive heart failure.'" (D.I. 165 at 43-44; see also D.I. 290 at 6-7)

         D. Procedural History

         On July 3, 2014, GSK commenced these actions. (Glenmark Action, D.I. 1; Teva Action, D.I. 1) GSK alleges that Defendants induce infringement of the '000 patent by making, offering to sell, selling, importing, and otherwise promoting and distributing generic carvedilol tablets. (Glenmark Action, D.I. 59, 175; Teva Action, D.I. 60, 211) On October 16, 2014, Chief Judge Leonard P. Stark referred these cases to the Court to hear and resolve all pretrial matters, up to and including the resolution of case-dispositive motions. (Glenmark Action, D.I. 16; Teva Action, D.I. 18) After a Markman hearing, (Glenmark Action, D.I. 118; Teva Action, D.I. 147), the Court issued a Report and Recommendation on claim construction on June 3, 2016, (Glenmark Action, D.I. 133; Teva Action, D.I. 165). Chief Judge Stark overruled objections to that Report and Recommendation on February 17, 2017 as to all but one term ("maintenance dosages"). (Glenmark Action, D.I. 251; Teva Action, D.I. 290)

         Briefing on the instant Motion was completed on March 3, 2017, (D.I. 313), and the Court held oral argument on the Motion (and various other summary judgment and Daubert motions filed in the case) on March 24, 2017, (D.I. 335 (hereinafter, "Tr.")). A 5-day trial is set to begin in the Teva Action on June 12, 2017. (D.I. 38, 329)


         A. Summary Judgment

         A grant of summary judgment is appropriate where "the movant shows that there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law." Fed.R.Civ.P. 56(a). The moving party bears the burden of demonstrating the absence of a genuine issue of material fact. See Matsushita Elec. Indus. Co., Ltd. v. Zenith Radio Corp., 475 U.S. 574, 585-86 & n.10 (1986). If the moving party meets this burden, the nonmovant must then "come forward with specific facts showing that there is a genuine issue for trial." Id. at 587 (emphasis in original) (internal quotation marks and citation omitted). If the nonmoving party fails to make a sufficient showing on an essential element of its case with respect to which it has the burden of proof, the moving party is entitled to judgment as a matter of law. Celotex Corp. v. Catrett, 477 U.S. 317, 322-23 (1986). During this process, the Court will "draw all reasonable inferences in favor of the nonmoving party, and it may not make credibility determinations or weigh the evidence." Reeves v. Sanderson Plumbing Prods., Inc., 530 U.S. 133, 150 (2000).

         However, in order to defeat a motion for summary judgment, the nonmoving party must "do more than simply show that there is some metaphysical doubt as to the material facts." Matsushita, 475 U.S. at 586; see also Podobnik v. U.S. Postal Serv., 409 F.3d 584, 594 (3d Cir. 2005) (party opposing summary judgment "must present more than just bare assertions, conclusory allegations or suspicions to show the existence of a genuine issue") (internal quotation marks and citation omitted). The "mere existence of some alleged factual dispute between the parties will not defeat an otherwise properly supported motion for summary judgment; the requirement is that there be no genuine issue of material fact." Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 247-48 (1986) (emphasis in original). Disputes over facts that could alter the outcome are "material, " and a factual dispute is genuine only where "the evidence is such that a reasonable jury could return a verdict for the nonmoving party." Id. at 248. "If the evidence is merely colorable, ... or is not significantly probative, ... summary judgment may be granted." Id. at 249-50 (internal citations omitted). A party asserting that a fact cannot be-or, alternatively, is-genuinely disputed'must support the assertion either by citing to "particular parts of materials in the record, including depositions, documents, electronically stored information, affidavits or declarations, stipulations (including those made for purposes of the motion only), admissions, interrogatory answers, or other materials"; or by "showing that the materials cited do not establish the absence or presence of a genuine dispute, or that an adverse party cannot produce admissible evidence to support the fact." Fed.R.Civ.P. 56(c)(1)(A) & (B).

         B. Invalidity

         A patent granted by the United States Patent and Trademark Office (the "PTO") is presumed to be valid. 35 U.S.C. § 282(a); Microsoft Corp. v. i4i Ltd. P'ship, 131 S.Ct. 2238, 2245-46 (2011). The rationale underlying this presumption of validity is that "the PTO, in its expertise, has approved the claim[.]" KSR Int'l Co. v. Teleflex lnc, 550 U.S. 398, 426 (2007). The burden of proving invalidity rests with the patent challenger at all times, who, when disputed questions of fact arise, must establish a patent's invalidity by clear and convincing evidence in order to prevail. Microsoft Corp., 131 S.Ct. at 2245-49; see also Id. at 2253 (Breyer, J., concurring). Clear and convincing evidence places within the mind of the fact finder "an abiding conviction that the truth of [the] factual contentions are highly probable." Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009) (quoting Colorado v. New Mexico, 467 U.S. 310, 316 (1984)). When a defendant attempts to rely on prior art that was before the patent examiner during prosecution in challenging the validity of a patent, its burden is "especially difficult[.]" Glaxo Grp Ltd. v. Apotex, Inc., 376 F.3d 1339, 1348 (Fed. Cir. 2004) (citation omitted).

         C. Anticipation

         A claim is anticipated under 35 U.S.C. § 102(a) or (b) if:

(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for patent, or
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of the application for patent in the United States ....

35 U.S.C. § 102.[5] A patent claim is anticipated if each and every limitation is found, either expressly or inherently, in a single prior art reference. In re Gleave, 560 F.3d 1331, 1334 (Fed. Cir. 2009) (citing Eli Lilly & Co. v. Zenith Goldline Pharms., Inc., 477 F.3d 1369, 1375 (Fed. Cir. 2006)); Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1321-22 (Fed. Cir. 2003). This test mirrors, to some extent, the test for infringement, and "it is axiomatic that that which would literally infringe if later anticipates if earlier." Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1378 (Fed. Cir. 2001). In order to anticipate, however, a reference must enable one of skill in the art to make and use the invention without undue experimentation, In re Gleave, 560 F.3d at 1334 (citing Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, 1314 (Fed. Cir. 2008)), and must also "show all of the limitations of the claims arranged or combined in the same way as recited in the claims[, ]" Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1370 (Fed. Cir. 2008).

         Anticipation is a question of fact. Smith Kline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1343 (Fed. Cir. 2005). If there are no genuine disputes underlying the anticipation inquiry, then the issue is ripe for judgment as a matter of law. Id.


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;With this Motion, Defendants move for summary judgment on the ground that the asserted claims of the &#39;000 patent (i.e., all claims except for claim 5) are invalid because: (1) claims 1-3 and 6-9 are anticipated by Kelly; and (2) claims 4, 6 and 7 are obvious based on Kelly in combination with other ...

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