Presenting a live 90-minute webinar with interactive Q&A Labeling and Induced Infringement in Pharma Patent Litigation and Protecting IP Rights THURSDAY, JULY 13, 2017 1pm Eastern 12pm Central 11am Mountain 10am Pacific Today s faculty features: Thomas L. Irving, Partner, Finnegan Henderson Farabow Garrett & Dunner, Washington, D.C. Barbara R. Rudolph, Ph.D., Partner, Finnegan Henderson Farabow Garrett & Dunner, Washington, D.C. The audio portion of the conference may be accessed via the telephone or by using your computer's speakers. Please refer to the instructions emailed to registrants for additional information. If you have any questions, please contact Customer Service at 1-800-926-7926 ext. 10.
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Outline I. Implications of Lilly for induced infringement II. Other Federal Circuit induced infringement decisions post- Commil A. Takeda Pharma U.S.A. v. Hikma Am Inc. (Fed. Cir. May 6, 2015) B. Braintree Labs Inc. v. Breckenridge Pharm. Inc. (Fed. Cir. May 5, 2017) III. How do Novo v. Caraco and use codes fit in? IV. Strategic considerations of label language for induced infringement 5
Induced Infringement 6
35 U.S.C. 271 a) Except as otherwise provided in this title, whoever without authority makes, uses, offers to sell, or sells any patented invention, within the United States, or imports into the United States any patented invention during the term of the patent therefor, infringes the patent. b) Whoever actively induces infringement of a patent shall be liable as an infringer. 7 7
Inducement: Basic Requirements To prove induced infringement, the patent owner must show that: (i) there is direct infringement; (ii) the accused infringer induced the infringement; and (iii) the accused infringer knew or should have known that its actions would induce actual infringement. The required knowledge/scienter can be satisfied by either (i) actual knowledge of a patent or (ii) willful blindness to the existence of a patent. Global-Tech Appliances, Inc. v. SEB S.A., 131 S. Ct. 2060, 2068 (2011). 8 8 8
Induced Infringement Global-Tech Appliances, Inc. v. SEB S.A., 131 S.Ct. 2060 (May 31, 2011) Holding: [I]nduced infringement under 271(b) requires knowledge that the induced acts constitute patent infringement.... Deliberate indifference to a known risk that a patent exists is not the appropriate standard under 271(b) but Supreme Court nevertheless affirmed the judgment of the Court of Appeals because the evidence supported a finding of Pentalpha s knowledge under the doctrine of willful blindness. 9 9
Global-Tech v. SEB Supreme Court: Induced Infringement Elements of willful blindness: (1) defendant must subjectively believe that there is a high probability that a fact exists; (2) defendant must take deliberate actions to avoid learning of that fact 10 10
Induced Infringement: Intent Commil USA, LLC v. Cisco Systems, Inc., 135 S.Ct. 752 (U.S. Dec. 5, 2014) Held: A reasonable belief of noninfringement is a defense to claims of inducement, but a good faith belief that a patent is invalid is not a defense to a charge of induced or contributory infringement. 11 11
Induced Infringement Hatch Waxman Act cases First prong of Global-Tech is easily shown by the patents listed in the Orange Book and the generic manufacturer s paragraph IV certification. Second prong of specific intent to induce infringement may be proven by the instructions and information in a drug label. 12 12
Induced Infringement Limelight Networks, Inc. v. Akamai Techs., Inc., 134 S. Ct. 2111 (2014) Supreme Court: Liability for induced infringement can only be found if the patent has been directly infringed, meaning directly infringed by a single party. Found no reason to interpret the statutory requirements for induced and direct infringement differently. 13 13
Divided Infringement 14
Divided Infringement Infringement of a method claim where its steps are performed by more than one actor. Supreme Court A defendant may not be liable for infringing a patent under 271(b) when no one has directly infringed the patent under 271(a) or any other statutory provision. Acknowledged that a would-be infringer could evade liability by dividing performance of a method patent's steps with another whom the defendant neither directs nor controls. 15 15
Divided Infringement Akamai Techs., Inc. v. Limelight Networks, Inc., 797 F.3d 1020 (Fed. Cir. 2015) Federal Circuit: In cases of divided infringement, one entity could be liable for direct infringement under two circumstances: Entity directs or controls another entity s performance. Acts through agency or contractual relationship Conditions participation in an activity or receipt of a benefit upon performance of a step or steps of a patented method and establishes the manner or timing of that performance Entities form a joint enterprise. 16 16
Divided Infringement Akamai Techs., Inc. v. Limelight Networks, Inc., 797 F.3d 1020 (Fed. Cir. 2015) Entity directs or controls another entity s performance Key concept: third party s actions are attributed to the alleged infringer such that the alleged infringer becomes the single actor chargeable with direct infringement. 17 17
Divided Infringement Eli Lilly & Co. v. Teva Parenteral Medicines, Inc., 845 F.3d 1357 (Fed. Cir. 2017) Claim 12. An improved method for administering pemetrexed disodium to a patient in need of chemotherapeutic treatment, wherein the improvement comprises: a) administration of folic acid prior to the first administration of pemetrexed disodium; b) administration of vitamin B12, prior to the first administration of pemetrexed disodium; and c) administration of pemetrexed disodium. 18 18
Eli Lilly & Co. v. Teva Parenteral Medicines Teva Supplies the pemetrexed Patient Self-administers folic acid Physician Administers B12 & pemetrexed 19 19
Divided Infringement Eli Lilly & Co. v. Teva Parenteral Medicines District Court: Claims valid and infringed. No single actor performs all steps of the asserted claims -- actions of both physicians and patients are required. But all steps of the asserted claims are attributable to physicians. Defendants liable for inducing that infringement. 20 20
Divided Infringement Eli Lilly & Co. v. Teva Parenteral Medicines Federal Circuit: Affirmed. Single actor who directly infringes: Product labeling and testimony provide sufficient evidence that physicians condition patient participation in an activity or receipt of a benefit (pemetrexed treatment) on folic acid administration and also establish the manner or timing of performance. 21 21
Eli Lilly v. Teva Parenteral Divided Infringement Physician Prescribing Information: Instruct patients to initiate folic acid 400 [mg] to 1000 [mg] orally once daily beginning 7 days before the first dose of [pemetrexed] Instruct patients on the need for folic acid and vitamin B12 supplementation to reduce treatmentrelated hematologic and gastrointestinal toxicity 22 22
Eli Lilly v. Teva Parenteral Divided Infringement Patient Information: To lower your chances of side effects of [pemetrexed], you must also take folic acid prior to and during your treatment with [pemetrexed]. 23 It is very important to take folic acid and vitamin B12 during your treatment with [pemetrexed] to lower your chances of harmful side effects. You must start taking 400 1000 micrograms of folic acid every day for at least 5 days out of the 7 days before your first dose of [pemetrexed] 23
Eli Lilly v. Teva Parenteral Divided Infringement Single actor who directly infringes: Did physicians direct or control their patients administration of folic acid? Condition the patient s participation: Based on the product labeling, taking folic acid in the manner specified is a condition of the patient s participation in pemetrexed treatment. Manner and timing of performance: Physicians would prescribe an exact dose of folic acid and direct that it be ingested daily. The performance of all steps of the asserted claims were attributable to physicians. 24 24
Induced Divided Infringement Eli Lilly v. Teva Parenteral Intent to induce: Must show Teva has specific intent to induce. [T]he intent for inducement must be with respect to the actions of the underlying direct infringer, here physicians. The label must encourage, recommend, or promote infringement. For purposes of inducement, it is irrelevant that some users may ignore the warnings in the proposed label. In this case, [t]he instructions are unambiguous on their face and encourage or recommend infringement. 25 25
Induced Infringement: Method of Use Patents 26
35 U.S.C. 271(e)(2) 35 U.S.C. 271(e)(2) It shall be an act of infringement to submit [ ] an application under section 505(j) of the [FDA Act] or described in section 505(b)(2) of that Act for a drug claimed in a patent or the use of which is claimed in a patent... if the purpose of such submission is to obtain approval under such Act to engage in the commercial manufacture, use or sale of a drug... claimed in a patent before the expiration of such patent. Requirement 1: an application: directed to an FDA approved use Requirement 2: a patent claiming a use of the drug 27 27
Method of Use Patents A viable Hatch-Waxman Act claim of inducement of method claims Accused use must be an approved use. Accused use must also be a claimed use. 28 28
Method of Use Patents Takeda Pharmaceuticals U.S.A., Inc. v. West-ward Pharmaceutical Corp., 785 F.3d 625 (Fed. Cir. 2015) Takeda patents cover several methods of administering colchicine products but not colchicine itself. Hikma did not file a Para. IV certification with respect to Takeda s patents because it did not seek FDA approval of Mitigare for a use covered by Takeda s patents. Federal Circuit: No preliminary injunction to stop West-Ward from continuing its launch of Mitigare and from launching an authorized generic version of Mitigare. 29 29
Takeda v. West-ward Method of Use Patents Label language: [i]f you have a gout flare while taking [Mitigare], tell your healthcare provider. Takeda argued that statement induced infringement because, in the case of the patient taking Mitigare for prophylaxis, the physician would likely tell the patient to use the Mitigare product to treat the acute flare. DC: Instruction insufficient to establish induced infringement. 30 30
Takeda v. West-ward Method of Use Patents Federal Circuit: Agreed. Instructions need to evidence an intent to encourage infringement. Mere knowledge of off-label infringing uses of Mitigare s product would not establish inducement. The label must encourage, recommend, or promote infringement. The mere existence of direct infringement by physicians, while necessary to find liability for induced infringement, is not sufficient for inducement. 31 31
Section 4.2a Instructions FDA revised the instructions on identifying labeling information regarding method of use claims. Form Section October 2010 November 2013 Form FDA 3542 Method of Use (4.2a) Specify the part of the approved drug labeling that is claimed by the patent. Identify the precise words of the approval labeling that describe with specificity the patented method of use. Align the method of use patent claims with direct, verbatim text in the proposed or final drug labeling? Focus on label as a whole supports concept of looking beyond the Indications and Usage section for approved methods 32 32
METHOD OF USE 3542 (11/13) 4.2b USE CODE 33 33
Section 4.2b If the answer to 4.2 is "Yes," also provide the information on the indication or method of use for the Orange Book "Use Code" description. Use: (Submit the description of the approved indication or method of use that you propose FDA include as the "Use Code" in the Orange Book, using no more than 240 total characters including spaces.) 34 34
Section 4.2b Instructions Section 4.2b Information and Instructions The answer to this question will be what FDA uses to create a use-code for Orange Book publication. The use code designates a method of use patent that claims an approved method of using a drug product. Each approved method of use claimed by the patent should be separately and specifically identified in this section and the use code created should contain adequate detail to assist 505(b)(2) and ANDA applicants in determining whether a listed method of use patent claims a method of use for which the 505(b)(2) or ANDA applicant is not seeking approval. Use a maximum of 240 characters for each use code. 35 35
USE CODES U-279: METHOD OF USE OF THE APPROVED PRODUCT U-308: CLAIMS A SOLID ORAL FORMULATION INCLUDING TABLETS AND GRANULES OF OLANZAPINE USEFUL FOR TREATING ANY NUMBER OF LISTED CONDITIONS, INCLUDING SPECIFIC PSYCHOLES, EMPLOYING OLANZAPINE AS PER THE INDICATIONS OF THIS NDA U-362: USE OF APPROVED FORMULATIONS TO TREAT ALL APPROVED DISEASE INDICATIONS 36 36
The Prandin Case Prandin (repaglinide) was originally approved as an adjunct to diet and exercise to improve glycemic control in adults with Type 2 Diabetes Mellitus (1) alone, (2) in combination with metformin, and (3) in combination with thiazolidinediones (TZDs). In 2004, Novo submitted the 358 patent to FDA with the following use codes: U-546: USE OF REPAGLINIDE IN COMBINATION WITH METFORMIN TO LOWER BLOOD GLUCOSE In 2005, Caraco submitted an ANDA for repaglinide with a section viii statement carving out the metformin combination use. 37 37
FDA In 2008, at FDA s request, Novo adopted the indication statement: PRANDIN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Novo then revised its use code to track the new indication: U-968: A METHOD FOR IMPROVING GLYCEMIC CONTROL IN ADULTS WITH TYPE 2 DIABETES MELLITUS This forced FDA to disallow Caraco s section viii statement, because the use code now read entirely on the indication statement. Caraco immediately sought relief in the courts, claiming the use code was unlawful. 38 38
District Court Caraco brought a counterclaim in its patent suit with Novo In a patent infringement action against the ANDA applicant, the applicant may assert a counterclaim seeking an order requiring the holder to correct or delete the patent information submitted by the holder... on the ground that the patent does not claim either (aa) the drug for which the application was approved; or (bb) an approved method of using the drug. 21 USC 355(j)(5)(C)(ii) (emphasis added) District Court granted Caraco s motion and ordered Novo to amend its use code. Novo appealed to the Federal Circuit. Does patent information include use codes? 39 39
Federal Circuit April 2010, the Federal Circuit reversed and later declined en banc review: Patent Information is a term of art under 21 USC 355(b)(1), referring to the patent number and date of expiration only. Caraco s real complaint was with FDA, whose actions in 2008 prompted the use code change. This court recognizes that a broad use code covering all uses of a pharmaceutical could require generic manufacturers to prove specifically that their use will not overlap with and infringe the patented use. This proof, under Hatch-Waxman procedures, will take the form of a Paragraph IV lawsuit. In the context, the generic may provide proof that their use will not cause infringement of the patented use... Thus, the Act again facilitates efficient resolution of disputes concerning potential overlapping of protected and unprotected uses. (emphasis added). 40 40
Supreme Court Supreme Court held that a generic drug manufacturer may employ the counterclaim provision of the Hatch-Waxman Act to force correction of a use code that inaccurately describes the brand s patent as covering a particular method of using a drug. Dicta in Caraco regarding content of use code Footnote 7: Novo claims that a use code may sweep more broadly than the patent. But that is incorrect. 41 41
More From Caraco From the concurrence FDA s guidance as to what is required of brand manufacturers in use codes remarkably opaque. Novo argued that the regulations permit a brand manufacturer to submit for publication in the Orange Book a description of either the patented method of use or the indication (which refers to what a drug does ) [The regulations and the form] at the least suggest (as Novo thought) that a method of use here is distinct from an indication and that either suffices as a use code. For the reasons explained by the Court, Novo is mistaken. But the company can hardly be faulted for so thinking. 42 42
Final Rules: Use Codes For Method Of Use Patents Goal: Address overbroad or ambiguous use codes that may delay approval of generic drugs Use Code must: describe only the specific approved method of use claimed by the patent for which a claim of infringement could reasonably be asserted identify with specificity the section(s) and subsection(s) of the approved labeling that describes the method(s) of use claimed by the patent Contents of patent submission Before approval - identify the patent, method, and labeling sections Upon and after approval - same, plus description of use For Final Rules, see 81 Fed. Reg. 69580-69658 (Oct. 6, 2016). 43 43
Scope Of The Use Code FDA s Guiding Principles: 1. Claimed use is broader than approved indication Use code must describe only the specific patented method of use described in the approved label 2. Claimed use is narrower than approved indication Use code must describe only the specific approved method claimed by the patent 3. Claimed use is co-extensive with approved indication Use code must describe only the specific approved method of use claimed by the patent 44 44
Use Code Submission No duty for current NDA holders to resubmit patent information for all currently listed patents. But others can submit a patent listing dispute. NDA holders required to submit new patent information only prospectively, after December 5, 2016. 45 45
Skinny Labeling Is Allowed From FDA response to RAPAMUNE Citizen Petition 46 46
Why Do We Care? Better to force para. IV than allow section 8. 30-month stay. Notice to NDA holder. Downside of improper use code Generics request change at FDA. Generics present counterclaim under Caraco. Possible patent misuse / antitrust suit if branded loses ANDA lawsuit? 47 47
Rapamune FDA approved snda related to cyclosporine withdrawal procedures in patients at low to moderate risk for rejection. 3 years of marketing exclusivity. Label: Indications and Usage It is recommended that Rapamune be used initially in a regimen with cyclosporine and corticosteroids. In patients at low to moderate immunologic risk cyclosporine should be withdrawn 2 to 4 months after transplantation.... Wyeth filed Citizen s Petition requesting FDA to refrain from approving generic versions of Rapamune before expiration of exclusivity period. FDA agreed. 48 48
FDA Response * * * 49 49
Approved indication: Farxiga An adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Patent claim: A method of treating Type II diabetes in a mammal comprising administering to the mammal a therapeutically-effective amount of the pharmaceutical composition according to claim 1. Use code: TREATMENT OF TYPE 2 DIABETES MELLITUS 50 50
Dalvance Approved indication: Usage: 51 51
Patent claim: Dalvance A method for treating a bacterial infection in a human in need thereof, the method comprising: administering initial and subsequent therapeutically effective doses of dalbavancin in a pharmaceutically acceptable carrier to the patient, wherein each dose is separated by five to ten days and wherein the amount of the initial dose is about 100 mg to about 5000 mg, and wherein the amount of the initial dose is at least about two times the amount of dalbavancin contained in the subsequent dose. Use code: TREATMENT OF BACTERIAL INFECTIONS USING A TWO-DOSE REGIMEN OF DALBAVANCIN. 52 52
Approved Indication: Zontivity Reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). ZONTIVITY has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization (UCR). Patent claim: A method of treating thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, myocardial infarction, glomerulonephritis, thrombotic stroke, thromboembolic stroke, peripheral vascular diseases, or cerebral ischemia comprising administering. Use code: REDUCTION OF THROMBOTIC CARDIOVASCULAR EVENTS 53 53
Approved Indication: Relistor RELISTOR is indicated for the treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Patent claim: 11. A method comprising the steps of: (i) providing a packaged composition, substantially free from tungsten, comprising a unit dosage of a liquid composition comprising 8 mg or 12 mg of a compound of formula III-1 in 0.4 ml or 0.6 ml water, and a compound of formula II-1 wherein the compound of formula II-1 is present in an amount of less than about 190 ppm; and (ii) administering the unit dosage to a subject via subcutaneous injection. Use code: TREATMENT OF OPIOID-INDUCED CONSTIPATION 54 54
Vimpat 55 55
Patent claim: Vimpat 11. A method of treating central nervous system disorders in an animal comprising administering to said animal in need thereof an anticonvulsant effective amount of a compound according to any one of claims 1-9. Use codes: METHOD OF TREATING, AS MONOTHERAPY OR ADJUNCTIVE THERAPY, PARTIAL-ONSET SEIZURES IN A PATIENT WITH EPILEPSY AGED 17 YEARS AND OLDER METHOD OF TREATING, AS INTITIAL LOADING DOSE FOR MONOTHERAPY OR ADJUNCTIVE THERAPY, PARITAL ONSET- SEIZURES IN A PATIENT WITH EPILEPSY AGED 17 YEARS OR OLDER 56 56
Hypothetical Example Indicated Use: Drug X for treating disease A. Patented Use: A method for causing pharmacologic effect. Expert: Drug X treats disease A via pharmacologic effect. 57 57
Hypothetical Example Indicated Use: Drug X for treating disease A. Patented Use: A method for treating class of diseases. Expert: Disease A is member of patented class. 58 58
Label Construction Example What evidence determines the scope of the approved use? Under Bayer, the label, taken in its entirety, [must] recommend or suggest to a physician that [the drug] is safe and effective for inducing the claimed [effect]. 59 59
Summary Impact of recent decisions on label language. Strategic considerations to keep in mind when labeling drugs. 60 60
Drafting and Prosecution Tips for Pharma Patents Coordinate patent, regulatory and clinical personnel early. Maintain consistency between claims and likely or actual label language. Maintain the coordination referenced above throughout the U.S. patent prosecution and label negotiation with FDA. 61 61
Drafting and Prosecution Tips for Pharma Patents Consider drafting claims so that one party infringes claims (e.g., one party performs all recited steps). Consider obtaining a noninfringement opinion to show good-faith belief of noninfringement. Opinion of counsel concluding that the patent in question is invalid will not be relevant to induced infringement allegation. Consider explicitly pleading indirect infringement and knowledge of the patent prior to the complaint. 62 62
Thank You! Contact Information: tom.irving@finnegan.com barbara.rudolph@finnegan.com 63 63