Labeling and Induced Infringement in Pharma Patent...

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Presenting a live 90-minute webinar with interactive Q&A

Labeling and Induced Infringement

in Pharma Patent Litigation and

Protecting IP Rights

Today’s faculty features:

1pm Eastern | 12pm Central | 11am Mountain | 10am Pacific

THURSDAY, JULY 13, 2017

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.

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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

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Induced Infringement

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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.

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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).

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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.”


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Global-Tech v. SEB

• Supreme Court:

– 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


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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.

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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.

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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.

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Divided Infringement

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• 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.

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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.

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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.

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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.

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Eli Lilly & Co. v. Teva Parenteral Medicines

Physician Administers B12 & pemetrexed

Patient

Self-administers folic acid

Teva

Supplies the pemetrexed

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• 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 .

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• 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.”

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Eli Lilly v. Teva Parenteral

– 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 treatment-

related hematologic and gastrointestinal toxicity”

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– 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].’’

• “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]”

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• 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.

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Induced Divided Infringement


• 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.”

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Induced Infringement: Method of Use

Patents

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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

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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.

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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.

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Takeda v. West-ward

• 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.

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Takeda v. West-ward

• 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.

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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”

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METHOD OF USE

4.2b USE CODE

3542 (11/13)

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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.) _____________________________

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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.’”

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“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

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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.

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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.

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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?

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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).

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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.

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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.

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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).

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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

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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.

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“Skinny Labeling” Is Allowed

From FDA response to RAPAMUNE Citizen Petition

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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?

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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.

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FDA Response

* * *

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Farxiga®

• Approved indication:

– 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

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Dalvance®

• Approved indication:

• Usage:

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Dalvance®

• Patent claim:

– 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.

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Zontivity®

• Approved Indication:

– 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

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Relistor®

• Approved Indication:

– 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

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Vimpat®

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Vimpat®

• Patent claim:

– 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

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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.

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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.

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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].”

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Impact of recent decisions on label language.

Strategic considerations to keep in mind when

labeling drugs.

Summary

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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.

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• 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.

Drafting and Prosecution Tips for Pharma Patents

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Thank You!

Contact Information: [email protected]

[email protected]

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