Medical

January 15, 2015

Indiana Trade Secret Law: Federal Prosecutors Drop All Charges Against Scientists Accused of Theft of Lilly Trade Secrets

Indianapolis, Indiana – All federal criminal charges against Guoqing Cao and Shuyu Li, who were formerly employed by Eli Lilly and Company (“Lilly”), were recently dropped by federal prosecutors, who stated that “additional information” had been received that altered “the investigative facts initially relied upon by the government” in its case against Cao and Li.

This federal indictment was brought in 2013 in the Southern District of Indiana. Defendants Cao and Li, two doctoral-level scientists, were charged with multiple counts of theft. At issue was intellectual property belonging to Indiana-based Lilly valued at $55 million. Counts one through three of the indictment, as well as counts five through ten, were listed as theft of trade secrets and aiding and abetting. Count four alleged conspiracy to commit theft of trade secrets.

In the initial proceedings, the United States maintained that Defendants were traitors who had conveyed “American trade secrets” – specifically, “crown jewels” in the form of many millions worth of intellectual property belonging to Lilly – to Jiangsu Hengrui Medicine Co., Ltd., a company located in Shanghai, China.

January 13, 2015

Indiana Patent Litigation: Federal Circuit Overturns Trial Court’s Award of Enhanced Damages for Patent Infringement

By Overhauser Law Offices, LLC

Washington, D.C. – The U.S. Court of Appeals for the Federal Circuit ruled on the patent infringement litigation between Zimmer of Warsaw, Indiana and Stryker of Kalamazoo, Michigan. The Federal Circuit upheld the jury’s finding that Zimmer had infringed three of Stryker’s patents but overturned the decision of the Western District of Michigan to triple the damage award, reducing the award from $228 million to $70 million, and vacated the district court’s award of attorneys’ fees.

Stryker and Zimmer are the two principal participants in the market for orthopedic pulsed lavage devices. A modern, orthopedic pulsed lavage device is a combination spray-gun and suction-tube, used by medical professionals to clean wounds and tissue during surgery.

In 2010, Stryker Corp, Stryker Puerto Rico, Ltd. and Stryker Sales Corp. (collectively, “Stryker”), sued Zimmer, Inc., Zimmer Surgical, Inc. and Zimmer Orthopaedic Surgical Products of Warsaw, Indiana (collectively, “Zimmer”) alleging that Zimmer’s line of Pulsavac Plus pulsed lavage devices infringed three of Stryker’s patents – U.S. Patent No. 6,022,329 (“the ‘329 patent”), U.S. Patent No. 7,144,383 (“the ‘383 patent”) and U.S. Patent No. 6,179,807 (“the ‘807 patent”). A jury awarded $70 million in damages and the district court increased that figure by approximately $2.4 million to reflect sales made by Zimmer during a time period that had not been considered by the jury.

Stryker also moved for enhanced damages under 35 U.S.C. § 284, alleging willful patent infringement by Zimmer. Under § 284, “the court may increase the damages up to three times the amount found or assessed” at trial. For this determination, the court referred to Read Corp. v. Portec, Inc.. In Read, the Federal Circuit had held that the “paramount determination in deciding to grant enhancement and the amount thereof is the egregiousness of the defendant’s conduct based on all the facts and circumstances.” In evaluating the egregiousness of the defendant’s conduct, courts typically rely on the nine Read factors, which are:

1. whether the infringer deliberately copied the patentee’s ideas or design;

2. whether the infringer investigated the scope of the patent and formed a good faith belief that it was invalid or not infringed;

3. the infringer’s conduct during litigation;

4. the infringer’s size and financial condition;

5. closeness of the case;

6. duration of the infringing conduct;

7. remedial actions, if any, taken by the infringer;

8. the infringer’s motivation for harm; and

9. whether the infringer attempted to conceal its misconduct.

The district court found that all nine Read factors favored substantial enhancement of the jury’s award and trebled both the jury’s award of $70 million and the court’s award of supplemental damages.

In the current opinion, the Federal Circuit affirmed the jury’s findings that Stryker’s patents were valid and had been infringed by Zimmer, as well as the jury’s award of damages to Stryker but reversed the district court’s judgment that Zimmer’s infringement was willful.

To establish willfulness, the patentee has the burden of showing “by clear and convincing evidence that the infringer acted despite an objectively high likelihood that its actions constituted infringement of a valid patent.” If and only if the patentee establishes this “threshold objective standard” does the inquiry then proceed to the question of whether the objectively defined risk was either known or so obvious that it should have been known to a party accused of patent infringement.

The Federal Circuit noted that the district court had failed to undertake the required objective assessment of Zimmer’s specific defenses to Stryker’s claims. The Federal Circuit then considered the question of objective recklessness, which “will not be found where the accused infringer’s position is susceptible to a reasonable conclusion of no infringement.” The court held that the objective standard showed that Zimmer had presented reasonable defenses to all of the asserted claims of Stryker’s patents. Consequently, Zimmer was found not to have acted recklessly and the decision to award enhanced damages was reversed.

Because the appellate court reversed the trial court’s determination that the infringement of the patents had been willful – and because district court’s award of attorneys’ fees was based on that determination – the Federal Circuit vacated district court’s finding that the case was exceptional as well as the award of attorneys’ fees and remanded the issue to the trial court for further consideration.

January 2, 2015

Indiana Patent Litigation: Eli Lilly Sues Sandoz Inc. Alleging Infringement of Patented ALIMTA

By Overhauser Law Offices, LLC

Indianapolis, Indiana – In conjunction with co-counsel, an Indiana patent attorney for Eli Lilly and Company of Indianapolis, Indiana sued in the Southern District of Indiana alleging infringement by Sandoz Inc. of Princeton, New Jersey of ALIMTA®, Patent No. 7,772,209, which was issued by the U.S. Patent Office.

ALIMTA, which is licensed to Lilly, is a chemotherapy agent used for the treatment of various types of cancer. ALIMTA is composed of the pharmaceutical chemical pemetrexed disodium. It is indicated, in combination with cisplatin, (a) for the treatment of patients with malignant pleural mesothelioma, or (b) for the initial treatment of locally advanced or metastatic nonsquamous non-small cell lung cancer. ALIMTA also is indicated as a single agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy. Additionally, ALIMTA is indicated for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. One or more claims of the ‘209 patent cover a method of administering pemetrexed disodium to a patient in need thereof that also involves administration of folic acid and vitamin B12.

This Indiana patent infringement lawsuit arises out of the filing by Defendant of an Abbreviated New Drug Application (“ANDA”) with the U.S. Food and Drug Administration (“FDA”) seeking approval to manufacture and sell generic versions of ALIMTA prior to the expiration of the ‘209 patent. Defendant filed as a part of that ANDA a certification of the type described in Section 505(j)(2)(A)(vii)(IV) of the Food, Drug and Cosmetic Act, 21 U.S.C. § 55(j)(2)(A)(vii)(IV), with respect to the patent-in-suit, asserting that the claims of the patent-in-suit are invalid, unenforceable, and/or not infringed by the manufacture, use, offer for sale, or sale of Defendant’s ANDA products.

In its complaint, filed by an Indiana patent lawyer, Lilly states that Defendant intends to engage in the manufacture, use, offer for sale, sale, marketing, distribution, and/or importation of Defendant’s ANDA products and the proposed labeling therefor immediately and imminently upon approval of the ANDA i.e., prior to the expiration of the patent-in-suit. Lilly asserts that Defendant’s actions constitute and/or will constitute infringement of the patent-in-suit, active inducement of infringement of the patent-in-suit, and contribution to the infringement by others of the patent-in-suit.

The complaint lists a single claim: Infringement of U.S. Patent No. 7,772,209. Lilly asks the court for the following relief:

(a) A judgment that Sandoz has infringed the ‘209 patent and/or will infringe, actively induce infringement of, and/or contribute to infringement by others of the ‘209 patent;

(b) A judgment ordering that the effective date of any FDA approval for Sandoz to make, use, offer for sale, sell, market, distribute, or import Sandoz’s ANDA Products, or any product the use of which infringes the ‘209 patent, be not earlier than the expiration date of the ‘209 patent, inclusive of any extension(s) and additional period(s) of exclusivity;

(c) A preliminary and permanent injunction enjoining Sandoz, and all persons acting in concert with Sandoz, from making, using, selling, offering for sale, marketing, distributing, or importing Sandoz’s ANDA Products, or any product the use of which infringes the ‘209 patent, or the inducement of or contribution to any of the foregoing, prior to the expiration date of the ‘209 patent, inclusive of any extension(s) and additional period(s) of exclusivity;

(d) A judgment declaring that making, using, selling, offering for sale, marketing, distributing, or importing of Sandoz’s ANDA Products, or any product the use of which infringes the ‘209 patent, prior to the expiration date of the ‘209 patent, infringes, will infringe, will actively induce infringement of, and/or will contribute to the infringement by other of the ‘209 patent;

(e) A declaration that this is an exceptional case and an award of attorneys’ fees pursuant to 35 U.S.C. § 285; and

(f) An award of Lilly’s costs and expenses in this action.

October 23, 2014

Indiana Patent Litigation: Lilly Sues Alleging Infringement of ALIMTA

By Overhauser Law Offices, LLC

Indianapolis, Indiana – An Indiana patent attorney for Eli Lilly and Company of Indianapolis, Indiana (“Lilly”) and The Trustees of Princeton University of Princeton, New Jersey (“Princeton”) filed a patent infringement complaint in the Southern District of Indiana alleging that Nang Kuang Pharmaceutical Co., Ltd. of Tainan City, Taiwan and CANDA NK-2, LLC of Waco, Texas infringed and/or will infringe ALIMTA®, U.S. Patent Nos. 5,344,932 (“the ‘932 patent”) and 7,772,209 (“the ‘209 patent”; collectively, “the patents-in-suit”), which have been issued by the U.S. Patent Office.

ALIMTA, which is licensed to Lilly, is a chemotherapy agent used for the treatment of various types of cancer. ALIMTA is composed of the pharmaceutical chemical pemetrexed disodium. It is indicated, in combination with cisplatin, (a) for the treatment of patients with malignant pleural mesothelioma, or (b) for the initial treatment of locally advanced or metastatic nonsquamous non-small cell lung cancer. ALIMTA also is indicated as a single agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy. Additionally, ALIMTA is indicated for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. One or more claims of the ‘209 patent cover a method of administering pemetrexed disodium to a patient in need thereof that also involves administration of folic acid and vitamin B12. The ‘932 patent, titled “N-(pyrrolo(2,3-d)pyrimidin-3-ylacyl)-Glutamic Acid Derivatives,” along with the ‘209 patent, have been listed in connection with ALIMTA in the FDA’s publication Approved Drug Products with Therapeutic Equivalence Evaluations.

This Indiana patent infringement lawsuit arises out of the filing by Defendant Nang Kuang of an Abbreviated New Drug Application (“ANDA”) with the U.S. Food and Drug Administration (“FDA”) seeking approval to manufacture and sell generic versions of ALIMTA prior to the expiration of the ‘932 and ‘209 patents. Nang Kuang filed as a part of that ANDA a certification of the type described in Section 505(j)(2)(A)(vii)(IV) of the Food, Drug and Cosmetic Act, 21 U.S.C. § 55(j)(2)(A)(vii)(IV), with respect to the patents-in-suit, asserting that the claims of the patents-in-suit are invalid, unenforceable, and/or not infringed by the manufacture, use, offer for sale, or sale of Defendants’ ANDA products.

In their complaint, filed by an Indiana patent lawyer, Lilly and Princeton state that Defendants intend to engage in the manufacture, use, offer for sale, sale, marketing, distribution, and/or importation of Defendants’ ANDA products and the proposed labeling therefor immediately and imminently upon approval of the ANDA i.e., prior to the expiration of the patents-in-suit. Plaintiffs asserts that Defendants’ actions constitute and/or will constitute infringement of the patents-in-suit, active inducement of infringement of the patents-in-suit, and contribution to the infringement by others of the patents-in-suit.

The complaint, filed by an Indiana patent lawyer, lists the following claims:

Count I: Infringement of U.S. Patent No. 5,344,932
Count II: Infringement of U.S. Patent No. 7,772,209

Lilly and Princeton ask the court for:

(a) A judgment that Defendants have infringed the ‘932 patent and/or will infringe and/or actively induce infringement of the ‘932 patent;

(b) A judgment ordering that the effective date of any FDA approval for Defendants to make, use, offer for sale, sell, market, distribute, or import Defendants’ ANDA Products, or any product the use of which infringes the ‘932 patent, be not earlier than the expiration date of the ‘932 patent, inclusive of any extension(s) and additional period(s) of exclusivity;

(c) A preliminary and permanent injunction enjoining Defendants, and all persons acting in concert with Defendants, from making, using, selling, offering for sale, marketing, distributing, or importing Defendants’ ANDA Products, or any product the use of which infringes the ‘932 patent, or the inducement of any of the foregoing, prior to the expiration date of the ‘932 patent, inclusive of any extension(s) and additional period(s) of exclusivity;

(d) A judgment declaring that making, using, selling, offering for sale, marketing, distributing, or importing of Defendants’ ANDA Products, or any product the use of which infringes the ‘932 patent, prior to the expiration date of the ‘932 patent, infringes, will infringe and/or will actively induce infringement of the ‘932 patent;

(e) A judgment that Defendants have infringed the ‘209 patent and/or will infringe, actively induce infringement of, and/or contribute to infringement by others of the ‘209 patent;

(f) A judgment ordering that the effective date of any FDA approval for Defendants to make, use, offer for sale, sell, market, distribute, or import Defendants’ ANDA Products, or any product the use of which infringes the ‘209 patent, be not earlier than the expiration date of the ‘209 patent, inclusive of any extension(s) and additional period(s) of exclusivity;

(g) A preliminary and permanent injunction enjoining Defendants, and all persons acting in concert with Defendants, from making, using, selling, offering for sale, marketing, distributing, or importing Defendants’ ANDA Products, or any product the use of which infringes the ‘209 patent, or the inducement of or contribution to any of the foregoing, prior to the expiration date of the ‘209 patent, inclusive of any extension(s) and additional period(s) of exclusivity;

(h) A judgment declaring that making, using, selling, offering for sale, marketing, distributing, or importing of Defendants’ ANDA Products, or any product the use of which infringes the ‘209 patent, prior to the expiration date of the ‘209 patent, infringes, will infringe, will actively induce infringement of, and/or will contribute to the infringement by others of the ‘209 patent;

(i) A declaration that this is an exceptional case and an award of attorneys’ fees pursuant to 35 U.S.C. § 285; and

(j) An award of Plaintiffs’ costs and expenses in the action.

Practice Tip #1: This summer, Lilly succeeded in defending the ‘209 method-of-use patent in before District Judge Tanya Walton Pratt in the Southern District of Indiana. The court found, inter alia, that the patent did not fail for “obviousness.”

Practice Tip #2: Obviousness is a legal conclusion based on underlying factual findings. Such findings include: 1) the scope and content of the prior art; 2) the differences between the claims and the prior art; 3) the level of ordinary skill in the art; and 4) objective considerations of non-obviousness such as commercial success and satisfaction of a long-felt need. Moreover, it is insufficient that prior art merely includes separate references to the subject matter of a subsequent patent claim. Instead, obviousness requires the additional showing that a person of ordinary skill in the art of the subject matter would have combined those elements of the prior art.

August 14, 2014

Indiana Patent Infringement Lawsuit: CeraMedic Sues DePuy Orthopaedics

By Overhauser Law Offices, LLC

South Bend, Indiana – In conjunction with New York intellectual property co-counsel,

biolox picture.jpg

Indiana patent attorneys for CeraMedic LLC of Plano, Texas sued in the Northern District of Indiana alleging that DePuy Orthopaedics, Inc. of Warsaw, Indiana (“DePuy”) infringed “Sintered AL₂O₃ Material, Process for Its Production and Use of the Material,” Patent No. 6,066,584 (the “‘584 patent”), which has been issued by the U.S. Patent Office.

The ‘584 patent relates to the field of ceramics and concerns sintered Al₂O₃ compositions and methods for the use of such material as medical implants or tool material. It was issued in May 2000 to Fraunhofer-Gesellschaft zur Förderung der Angewandten Forschung e.V., Germany (“Fraunhofer”), Europe’s largest application-oriented research organization. CeraMedic states that Fraunhofer, the assignee of over 1,500 U.S. patents, assigned ownership of the ‘584 patent to CeraMedic in early 2014.

CeraMedic indicates that non-party CeramTec GmbH (“CeramTec”) developed and manufactures BIOLOX Delta, an aluminum oxide matrix composite ceramic consisting of approximately 82% alumina (Al₂O₃), 17% zirconia (ZrO₂), and other trace elements.

CeraMedic then states that Defendant DePuy “designs, develops, manufactures, offers for sale, sells, uses, distributes, and markets hip implants, many of which include” CeramTec’s BIOLOX Delta and that such actions constitute infringement of the ‘584 patent. DePuy is accused of infringing the ‘584 patent directly, literally, and/or by equivalents.

The complaint, filed by New York patent attorneys in conjunction with Indiana patent lawyers, lists a single count: infringement of the ‘584 patent. CeraMedic asks the court for a judgment against DePuy determining that DePuy has infringed and continues to infringe one or more claims of the ‘584 patent; enjoining DePuy and its agents from further infringing the ‘584 patent; ordering DePuy to account for and pay to CeraMedic all damages suffered by CeraMedic as a consequence of DePuy’s alleged infringement of the ‘584 patent, together with interest and costs; trebling or otherwise increasing CeraMedic’s damages under 35 U.S.C. § 284 upon a finding that the asserted infringement by DePuy of the ‘584 patent was deliberate and willful; and declaring that this case is exceptional and awarding to CeraMedic its costs and attorneys’ fees in accordance with 35 U.S.C. § 285.

Practice Tip: DePuy Orthopaedics Inc. has been involved in similar Indiana patent infringement litigation before. See, e.g.:

• Howmedica Osteonics Corp. and Stryker Ireland Ltd. Sues DePuy Orthopaedics Inc.

for Patent Infringement of a Surgical Implant Used in Hip Replacement Procedures

• Orthopaedic Hospital Seeks Injunction and Damages for Patent Infringement

August 13, 2014

Indiana Patent and Trade Dress Litigation: Polymer Technology Systems Asserts Patent and Trade Dress Infringement of Its Cholesterol Testing Technology

By Overhauser Law Offices, LLC

Indianapolis, Indiana – Indiana patent attorneys for Polymer Technology Systems, Inc. (“PTS”) of Indianapolis, Indiana filed an intellectual property lawsuit in the Southern District of Indiana alleging that Jant Pharmacal Corporation of Encino, California (“Jant”) Infopia America LLC of Titusville, Florida (“Infopia USA”) and Infopia Co., Ltd. of Kyunggi, Korea (“Infopia

Korea”) infringed “Method for determining HDL concentration from whole blood or plasma,” Patent No. 7,087,397, which was issued by the U.S. Patent Office. PTS has also accused Defendants of federal unfair competition under the Lanham Act.

PTS develops, manufactures and sells point-of-care diagnostic products for the human healthcare market. At issue in this Indiana litigation is PTS’s “CardioChek® Multi-Analyte Strip,” a hand-held, point-of-care testing system that can test for total cholesterol, high-density lipoproteins (HDL) and triglycerides with a single drop of blood. In August 2006, Patent No. 7,087,397 (“the ‘397 Patent”) was issued to PTS. PTS indicates that this patent includes a significant portion of the technology embodied in this Indiana invention.

Defendant Infopia Korea has also developed a test strip that tests for total cholesterol, high-density lipoproteins and triglycerides. This system is branded as the LipidPlus Lipid Profile Test Strip. PTS contends that Infopia Korea imports the LipidPlus testing strip into the United States and that Defendants Infopia USA and Jant offer and sell the LipidPlus product in the U.S. market.

PTS alleges that much of the technology incorporated into the LipidPlus testing strip is copied from PTS’s CardioChek product. It contends that the copied aspects include the concept of the testing strip itself, the analytes selected for analysis, the structure of the strip and the chemistries used. PTS also contends that Defendants have copied the trade dress of PTS’s CardioChek testing strip. PTS further accuses Defendants of offering the LipidPlus testing strip at a price that is both extremely low and below cost.

In its complaint, filed by Indiana trade-dress and patent lawyers, PTS alleges the following:

• Count I: Patent Infringement of the ‘397 Patent

• Count II: Violation of the Lanham Act, 15 U.S.C. 1125(a)

PTS asks the court:

• for a judgment that the ‘397 Patent is valid and enforceable;

• for a judgment of direct or indirect infringement, or inducement to infringe, by Defendants;

• to declare that Defendants have unfairly competed with PTS by infringing and misappropriating PTS’s trade dress;

• for an award to PTS of lost profits and a reasonable royalty for Defendants’ acts of patent infringement and trade-dress infringement;

• to treble the award of damages pursuant to a finding of willful, intentional and deliberate infringement;

• for an injunction prohibiting Defendants from engaging in acts of infringement or unfair competition; and

• for a declaration that the case is exceptional and an award of attorneys’ fees.

Practice Tip: The United States Supreme Court addressed the elements required for trade dress to be protected in Two Pesos, Inc. v. Taco Cabana, Inc., 505 U.S. 763 (1992). In Two Pesos, the Court held that, to establish a cause of action for trade dress infringement, a plaintiff must establish that (a) the design is non-functional; (b) the design is inherently distinctive or distinctive by virtue of having acquired secondary meaning; and (c) there is a likelihood of confusion.

July 30, 2014

Indiana Trade Secret Law: Removing Allegation of Theft of Trade Secrets Results in Defendants’ Release from “Lockdown”

By Overhauser Law Offices, LLC

Indianapolis, Indiana – In 2013, a federal indictment including counts of theft of trade secrets belonging to Eli Lilly and Company (“Lilly”) was presented to the Southern District of Indiana. On the basis of this indictment, the court ordered Defendants Guoqing Cao and Shuyu Li, formerly employed by Eli Lilly and Company, to be detained at housing provided by Volunteers of America – Indiana (“VOA”), pending their criminal trial. When the 2013 indictment was superseded by a second indictment that did not include counts for the theft of trade secrets, the court granted Defendants’ request to be released to home detention.

On August 14, 2013, Defendants Cao and Li, two doctoral-level scientists formerly employed by Lilly, were charged with multiple counts of theft. At issue was intellectual property belonging to Lilly valued at $55 million. Counts one through three of the indictment, as well as counts five through ten, were listed as theft of trade secrets and aiding and abetting. Count four alleged conspiracy to commit theft of trade secrets.

In the initial proceedings, the United States maintained that the Defendants were traitors who had conveyed “American trade secrets” – specifically, “crown jewels” in the form of many millions worth of intellectual property belonging to Lilly – to Jiangsu Hengrui Medicine Co., Ltd., a company located in Shanghai, China. These arguments strongly impacted the court’s decision to order “lockdown” detention at the VOA.

A second indictment was later filed by the United States. Under the new indictment, the Defendants faced no charges of trade-secret theft. Instead, they were charged with one count each of wire fraud, aiding and abetting, and conspiracy to commit wire fraud. Based on the absence of allegations relating to trade-secret theft in the subsequent indictment, the Defendants asked the court to modify the terms of their detention.

The court was persuaded that such a change was warranted. It noted that there was “a difference between allegations of ‘theft of trade secrets’ and disclosure of ‘Lilly Property.'” It further stated that the earlier allegation – that Lilly’s “crown jewel” secrets had been stolen and provided to China – had been a critical factor in justifying the Defendants’ incarceration.

When the allegations of trade secret misappropriation were removed, the court found that those justifications were no longer applicable: “No longer are the Defendants accused of stealing ‘trade secrets’–those words are found nowhere in the superseding indictment” and released the Defendants from lockdown to the less-restrictive conditions of home detention.

Practice Tip #1: Nine Lilly trade secrets pertaining to pharmaceuticals under development for cardiovascular disease, diabetes and cancer were at issue in this Indiana criminal prosecution for theft of intellectual property.

Practice Tip #2: Defendants’ home detention restricts individuals to their residence at all times except for employment; education; religious services; medical, substance abuse, or mental health treatment; attorney visits; court appearances; court-ordered obligations; or other activities approved in advance by the pretrial services office or supervising officer. Defendants were also ordered not to access or use any internet-enabled device with the exception of utilizing email to communicate with counsel.

July 24, 2014

Lilly Successful in Defending Alimta Method-of-Use Patent

By Overhauser Law Offices, LLC

Indianapolis, Indiana – In conjunction with co-counsel, an Indiana patent attorney for Eli Lilly of Indianapolis, Indiana prevailed in the Southern District of Indiana on claims of patent infringement. At issue was Lilly’s patent on the use of Alimta® in conjunction with specific vitamins. District Judge Tanya Walton Pratt concluded that Defendants Teva Parenteral Medicines, Inc. of Irvine, California; APP Pharmaceuticals, LLC of Schaumburg, Illinois; Pliva Hrvatska D.O.O. of Zagreb, Croatia; Teva Pharmaceuticals USA Inc. of North Wales, Pennsylvania; and Barr Laboratories, Inc. of Montvale, New Jersey failed to prove invalidity of U.S. Patent No. 7,772,209 (the “‘209 Patent”) and entered judgment in favor of Lilly.

Lilly sells the drug Alimta (“pemetrexed”), a chemotherapy drug, to treat various types of lung cancer, including mesothelioma. However, certain side effects were troublesome, including treatment-related hematologic and gastrointestinal toxicity. Deaths among some patients were attributed to treatment with pemetrexed. In response to this concern, Lilly took the unusual step of mandating supplementation of the pemetrexed protocol with two vitamins – folic acid and vitamin B₁₂. The patentability of that idea was the focus of a patent challenge – this litigation – by five manufacturers of generic drugs.

Lilly’s ‘209 Patent describes a method of using an antifolate, pemetrexed, with vitamins. Antifolates are a type of chemotherapy drug used to treat certain types of cancer. They work by competing with folates, a class of essential nutrients that includes folic acid. By interfering with the action of folates, antifolates thereby deprive cancer cells of the DNA precursors they need to proliferate.

The generic challengers contended in part that the patent on the combined therapy is invalid, arguing that someone knowledgeable about both nutrition and medicine could have easily concluded that supplementation with B₁₂ and folate might alleviate certain side effects of pemetrexed.

Lilly, in contrast, argued that the vitamin regimen was not only counterintuitive when it was proposed, it was called “crazy” by a leading cancer doctor before testing showed its benefits.

Lilly prevailed. The court found that Defendants failed to show by clear and convincing evidence that the asserted claims of the ‘209 Patent were invalid for obviousness, obviousness-type double patenting, inadequate description or lack of enablement. Thus, the ‘209 Patent is valid and enforceable.

The ‘209 Patent is presumed to be valid under 35 U.S.C. § 282. Defendants, as the parties challenging the validity of the ‘209 Patent, bore the burden of proving invalidity by clear and convincing evidence.

Defendants’ first contention was that the ‘209 Patent was obvious. To prove obviousness, they would have to show by clear and convincing evidence that the differences between the claims and the prior art at the time the invention were such that, considered as a whole, the claims would have been obvious to a person of ordinary skill in the art (“POSA”) in that subject matter.

Obviousness is a legal conclusion based on underlying factual findings. Such findings include: 1) the scope and content of the prior art; (2) the differences between the claims and the prior art; (2) the level of ordinary skill in the art; and (4) objective considerations of non-obviousness such as commercial success and satisfaction of a long-felt need. Moreover, it is insufficient that prior art merely includes separate references to the subject matter of a subsequent patent claim. Instead, obviousness requires the additional showing that a POSA would have combined those elements of the prior art. Thus, Defendants in this case bore the burden of proving that a POSA would have had reason to (1) administer folic acid pretreatment with pemetrexed, (2) administer vitamin B₁₂ pretreatment with pemetrexed, and (3) administer each of them according to the doses and schedules indicated in the ‘209 Patent.

The court first found that folic pretreatment with pemetrexed was not obvious. Among its findings were that the prior studies on mice would not have led a POSA to consider such supplementation. There would have been considerable difficulty in comparing studies on the combined treatment in mice with effects likely to be observed in humans, given the differences between humans and mice. One substantial difference was that mice have much higher requirements for folic acid. As an additional confounding factor, the studies on mice given low-folate diets were only possible because the mice were also given an antibiotic to prevent bacteria in the intestines of the mice from making folic acid that would otherwise raise a mouse’s level of folic acid.

These and other differences would have represented substantial obstacles in making the leap from the prior state of understanding of vitamin supplementation with antifolates to the claims of the ‘209 Patent. The court thus held that a POSA reviewing the prior art, instead of concluding that the supplementation was useful, would have likely concluded that supplementation decreased the efficacy of the drug. Consequently, those prior studies would have resulted in a “teaching away” from the claimed invention by discouraging a POSA from pursuing vitamin supplementation in conjunction with pemetrexed.

The court concluded that, likewise, vitamin B₁₂ pretreatment with pemetrexed was not obvious and that, as of June 1999, a POSA would have expected that vitamin B₁₂ would counteract the efficacy of antifolates. Instead, the court held that the benefit of using B₁₂ in conjunction with pemetrexed was not discovered until late 1999, when a mathematician for Lilly ran an extensive statistical analysis of data from patients in the worldwide, phase-III pemetrexed trial.

The court next held that the doses and schedules within the claims asserted by Lilly were not obvious. The vitamin dosing regimens attempted in the prior art, which contained folic acid only, reduced the efficacy of pemetrexed as compared to unsupplemented trials. However, the regimen in the ‘209 Patent actually improved the efficacy of the drug over unsupplemented clinical trials. While normally a change in temperature, concentration or both would be an unpatentable modification, patentability may be found if the results of such a change are “unexpectedly good.” The court held that the changes resulting from the methods described in the ‘209 Patent fell within this exception to the general rule.

The scheduling of the pretreatment with the vitamin supplementation was also deemed non-obvious by Judge Walton Pratt, as prior studies had shown that administration of folic acid one week prior to the administration of lometrexol (another chemotherapy agent) reduced the efficacy of the drug and was a cause of concern for oncologists. Based upon the results of that study, a POSA would have not have anticipated a likelihood of success with pretreatment with vitamins.

In its evaluation of non-obviousness, the court last considered secondary indicia of non-obviousness of the asserted claims of the ‘209 Patent. These indicia include the commercial success of the invention at issue and its satisfaction of a long-felt need; skepticism or disbelief before the invention; failure of others and evidence of unexpected properties. It found these indicia supported a conclusion of non-obviousness.

Finally, the court held that the claims at issue were not invalid for obviousness-type double patenting, concluding that the claims asserted in the ‘209 Patent were patentably distinct from Lilly’s U.S. Patent No. 5,217,974 (the “‘974 Patent”). The court included in its reasoning that the ‘974 Patent discloses, inter alia, the use of a much greater amount of folic acid, does not reference pemetrexed and includes nothing about pretreating with vitamin B₁₂.

Consequently, the court found that the asserted claims of the ‘209 Patent were valid and enforceable, and entered judgment in favor of Lilly and against Defendants.

Practice Tip #1:

Patent-infringement litigation between brand-name manufacturers and generic-drug makers is common. In a typical lawsuit, a company that wishes to sell a generic version of a brand-name drug, usually a widely used drug, will try to invalidate the patent on the drug, in the hopes that it could then offer the same drug in generic form.

This litigation was different from traditional patent litigation. The original patent on Alimta, administered as a stand-alone treatment, protects only Alimta’s active ingredient. That patent will expire in 2017. However, the focus of the current litigation was on the combination treatment – a “method-of-use patent” – that involves both Alimta and the vitamin regimen.

Practice Tip #2:

Because the ‘209 Patent was upheld, the period of exclusivity for Alimta, in conjunction with the vitamin supplementation, now expires in 2022. In 2013, Lilly earned revenues of $2.7 billion from global sales of Alimta. Thus, the extra five years of patent protection may result in additional revenues in excess of $10 billion for Lilly.

July 17, 2014

Indiana Patent Litigation: Lilly Brings Another Defendant into Effient Patent Infringement Litigation

By Overhauser Law Offices, LLC

Indianapolis, Indiana – In conjunction with co-counsel from Washington, D.C., an Indiana patent attorney for Eli Lilly and Company of Indianapolis, Indiana; Daiichi Sankyo Co., Ltd of Tokyo, Japan; Daiichi Sankyo, Inc. of Parsippany, New Jersey; and Ube Industries, Ltd. of Yamaguchi, Japan sued in the Southern District of Indiana alleging that First Time US Generics LLC of Broomall, Pennsylvania infringed Effient® products, Patent Nos. 8,404,703 and 8,569,325 which have been issued by the U.S. Patent Office.

This is a civil action for patent infringement. It arises out of the filing by Defendant First Time US Generics LLC (“FTUG”) of an Abbreviated New Drug Application (“ANDA”) with the United States Food and Drug Administration (“FDA”) seeking approval to manufacture and sell generic versions of two of Lilly’s pharmaceutical products, Effient® 5mg and Effient® 10mg tablets, prior to the expiration of Daiichi Sankyo’s and Ube’s U.S. patents, which purportedly cover methods of using Effient® products. Plaintiffs assert that Lilly holds an exclusive license to these products. DSI currently co-promotes Effient® products in the United States with Lilly.

Effient® products were approved by the FDA for the reduction of thrombotic cardiovascular events in certain patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI, or angioplasty). The instructions accompanying Effient® products state that patients taking Effient® products should also take aspirin. The use of Effient® products in combination with aspirin for the reduction of thrombotic cardiovascular events in patients with ACS who are to be managed with PCI is covered by the claims of the ‘703 and ‘325 patents.

FTUG has submitted an Abbreviated New Drug Application (the “FTUG ANDA”) to the FDA pursuant to 21 U.S.C. § 355(j), seeking approval to market a generic version of Lilly’s product for oral administration (the “FTUG Products”) in the United States.

Plaintiffs assert that FTUG will knowingly include with the FTUG Products instructions for use that substantially copy the instructions for Effient® products, including instructions for administering the FTUG Products with aspirin as claimed in the ‘703 and ‘325 patents. Moreover, Plaintiffs contend that FTUG knows that the instructions that will accompany the FTUG Products will induce and/or contribute to others using the FTUG Products in the manner set forth in the instructions. Plaintiffs also contend that FTUG specifically intends that health care providers, and/or patients will use the FTUG Products in accordance with the instructions provided by FTUG to directly infringe one or more claims of the ‘703 and ‘325 patents. FTUG therefore will actively induce and/or contribute to infringement of the ‘703 and ‘325 patents, state Plaintiffs.

In the complaint, the Indiana patent lawyer for Plaintiffs listed the following counts:

• Count I: Infringement of U.S. Patent No. 8,404,703
• Count II: Declaratory Judgment of Infringement of U.S. Patent No. 8,404,703
• Count III: Infringement of U.S. Patent No. 8,569,325
• Count IV: Declaratory Judgment of Infringement of U.S. Patent No. 8,569,325

Plaintiffs ask the court for judgment:

A. That FTUG has infringed or will infringe, after the FTUG ANDA is approved, one or more claims of the ‘703 patent;
B. That FTUG has infringed or will infringe, after the FTUG ANDA is approved, one or more claims of the ‘325 patent;
C. That, pursuant to 35 U.S.C. § 271(e)(4)(B), FTUG and its agents be permanently enjoined from making, using, selling or offering to sell either or both of the FTUG Products within the United States, or importing either or both of the FTUG Products into the United States prior to the expiration of the ‘703 and ‘325 patents;
D. That, pursuant to 35 U.S.C. § 271(e)(4)(A), the effective date of any approval of the FTUG ANDA under § 505(j) of the Federal Food, Drug and Cosmetic Act (21 U.S.C. § 355(j)) shall not be earlier than the latest of the expiration dates of the ‘703 and ‘325 patents, including any extensions;
E. If FTUG commercially makes, uses, sells or offers to sell either or both of the FTUG Products within the United States, or imports either or both of the FTUG Products into the United States, prior to the expiration of either of the ‘703 and ‘325 patents, including any extensions, that Plaintiffs will be awarded monetary damages for those infringing acts to the fullest extent allowed by law and be awarded prejudgment interest based on those monetary damages;
F. That this case be deemed exceptional under 35 U.S.C. § 285
G. Declaring that the ‘703 patent remains valid and enforceable;
H. Declaring that the ‘325 patent remains valid and enforceable; and
I. That Plaintiffs be awarded reasonable attorney’s fees, costs and expenses.

Practice Tip:

In March 2014, Lilly et al. filed a 101-page complaint making similar accusations against more than thirty defendants: Accord Healthcare, Inc. USA; Accord Healthcare, Inc.; Intas Pharmaceuticals Ltd.; Amneal Pharmaceuticals LLC; Amneal Pharmaceuticals of New York, LLC; Amneal Pharmaceuticals Co. India Pvt. Ltd.; Aurobindo Pharma Limited; Aurobindo Pharma USA Inc.; Dr. Reddy’s Laboratories, Ltd; Dr. Reddy’s Laboratories, Inc.; Glenmark Generics Inc., USA; Glenmark Generics Ltd.; Glenmark Pharmaceuticals Ltd.; Hetero USA Inc.; Hetero Labs Limited; Hetero Labs Limited Unit V; Hetero Drugs Ltd.; Mylan Pharmaceuticals Inc.; Mylan Inc.; Mylan Laboratories Limited; Par Pharmaceutical Companies, Inc.; Par Pharmaceutical, Inc.; Sun Pharma Global FZE; Caraco Pharmaceutical Laboratories, Ltd.; Sun Pharma Global Inc.; Sun Pharmaceutical Industries, Ltd.; Teva Pharmaceuticals USA, Inc.; Teva Pharmaceutical Industries, Ltd.; Watson Laboratories, Inc.; Actavis plc; Actavis, Inc.; Actavis Pharma, Inc.; Zydus Pharmaceuticals USA, Inc.; and Cadila Healthcare Ltd. d/b/a Zydus Cadila.

FTUG is the latest of addition to Lilly’s list of defendants in the Effient litigation. In contrast to the March complaint against 30-plus mostly unrelated defendants, FTUG, as well as the other subsequent unrelated defendants, have been added via separate complaints alleging patent infringement.

July 14, 2014

Indiana Patent Litigation: HEC Pharm Added to Effient Patent Infringement Litigation

By Overhauser Law Offices, LLC

Indianapolis, Indiana – An Indiana patent attorney for Eli Lilly and Company of Indianapolis, Indiana; Daiichi Sankyo Co., Ltd of Tokyo, Japan; Daiichi Sankyo, Inc. of Parsippany, New Jersey; and Ube Industries, Ltd. of Yamaguchi, Japan sued in the Southern District of Indiana alleging that HEC Pharm Co., Ltd. of China and HEC Pharm USA Inc. of Princeton, New Jersey (collectively, “HEC Pharm”) infringed Lilly’s patented Effient® product, Patent No. 8,404,703, which has been issued by the United States Patent Office.

This lawsuit adds another defendant, HEC Pharm, to Lilly’s Indiana patent litigation regarding Effient. In these Effient patent-defense lawsuits, Lilly et al. allege infringement of certain patents related to the pharmaceutical Effient. At issue in the litigation against HEC Pharm is only one of the Effient-related patents, 8,404,703 “Medicinal Compositions Containing Aspirin,” (the “‘703 patent”).

This complaint asserts patent infringement arising out of the filing by HEC Pharm of an Abbreviated New Drug Applications (“ANDA”) with the United States Food and Drug Administration (“FDA”) seeking approval to manufacture and sell generic versions of two pharmaceutical products – Effient 5mg and Effient 10mg tablets – prior to the expiration of the ‘703 patent. These patents cover a method of using Effient products for which Lilly claims an exclusively license.

Effient products were approved by the FDA for the reduction of thrombotic cardiovascular events in certain patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI, or angioplasty). Effient products contain prasugrel hydrochloride, which is also known as 5-[(1RS)-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate hydrochloride.

The instructions accompanying Effient products state that patients taking Effient products should also take aspirin. The use of Effient products in combination with aspirin for the reduction of thrombotic cardiovascular events in patients with ACS who are to be managed with PCI is allegedly covered by the claims of the ‘703 patent.

HEC Pharm is accused of planning to infringe the patents-in-suit by including with its products instructions for use that substantially copy the instructions for Effient products, including instructions for administering HEC Pharm’s products with aspirin as claimed in the ‘703 patent.

Plaintiffs contend that HEC Pharm knows that the instructions that HEC Pharm intends to include with its products will induce and/or contribute to others using those products in the allegedly infringing manner set forth in the instructions. Moreover, Lilly et al. also contend that HEC Pharm specifically intends for health care providers, and/or patients to use HEC Pharm’s products in accordance with the instructions provided by HEC Pharm and that such use will directly infringe one or more claims of the ‘703 patent. Thus, state Plaintiffs, HEC Pharm’s actions will actively induce and/or contribute to infringement of the ‘703 patent.

The complaint, filed by an Indiana patent lawyer, lists two counts:

• Count I: Infringement of U.S. Patent No. 8,404,703
• Count II: Declaratory Judgment of Infringement of U.S. Patent No. 8,404,703

Plaintiffs ask the court for judgment:

• That HEC Pharm has infringed the ‘703 patent and/or will infringe, actively induce infringement of, and/or contribute to infringement by others of one or more claims of the ‘703 patent;
• That, pursuant to 35 U.S.C. § 271(e)(4)(B), HEC Pharm be permanently enjoined from making, using, selling or offering to sell any of its accused products within the United States, or, where applicable, importing accused products into the United States prior to the expiration of the ‘703 patent;
• That, pursuant to 35 U.S.C. § 271(e)(4)(A), the effective date of any approval of the HEC Pharm ANDA under § 505(j) of the Federal Food, Drug and Cosmetic Act (21 U.S.C. § 355(j)) shall not be earlier than the later of the expiration dates of the ‘703 patent, including any extensions;
• If HEC Pharm commercially makes, uses, sells or offers to sell any accused product within the United States, or, where applicable, imports any accused product into the United States, prior to the expiration of either of the ‘703 patent, including any extensions, that Plaintiffs be awarded monetary damages for those infringing acts to the fullest extent allowed by law and be awarded prejudgment interest based on those monetary damages;
• That the case be deemed exceptional under 35 U.S.C. § 285;
• That the ‘703 patent remains valid and enforceable;
• That Plaintiffs be awarded reasonable attorney’s fees, costs and expenses.

Practice Tip #1: The Effient litigation also involves Patent No. 5,288,726, “Tetrahydrothienopyridine Derivatives, Furo and Pyrrolo Analogs Thereof and Their Preparation and Uses for Inhibiting Blood Platelet Aggregation,” and Patent No. 8,569,325, “Method of Treatment with Coadministration of Aspirin and Prasugrel.”

Practice Tip #2: The FDA’s ANDA process for generic drugs has been abbreviated such that, in general, the generic drug seeking approval does not require pre-clinical (animal and in vitro) testing. Instead, the process focuses on establishing that the product is bioequivalent to the “innovator” drug that has already undergone the full approval process.

The statute that created the abbreviated process, however, had also created some interesting jurisdictional issues with respect to declaratory judgments. For an interesting look at some of the issues, see here
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