hedge fund ipr challenges to pharma patents: strategies to...

Hedge Fund IPR Challenges to Pharma

Patents: Strategies to Strengthen

Patents to Withstand Attack

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THURSDAY, MAY 28, 2015

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

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.

Amanda Murphy, Ph.D. Associate, Finnegan Henderson Farabow Garrett & Dunner, Washington, D.C.

Rekha Bensal, Sr. Director of IP, Principia Biopharma, So. San Francisco, CA

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These materials have been prepared solely for educational and entertainment

purposes to contribute to the understanding of U.S. intellectual property law.

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5

IPR Filings Have Risen Quickly

As of May 14, 2015. Source: http://www.uspto.gov/sites/default/files/documents/0514015_aia_stat_graph.pdf

6 PGRs filed so far; 2 settled prior to institution decision, 4 institution decision pending.

Tota

l AIA

Post-

Gra

nt

Fili

ngs P

er

Month

?

IPR: 2,894

CBM: 344

PGR: 6

DER: 11

Total: 3,255

Oct. 2012

Oct. 2013

Oct. 2014 Filings approximately doubled from Oct. 2013 to Oct. 2014

6

IPR Petitions by Technology

FY15 filings as of April 9, 2015. Source: http://www.uspto.gov/sites/default/files/documents/040915_aia_stat_graph.pdf

7

IPR Petitions by Technology (May 14, 2015)

FY15 filings as of May 14, 2015. Source: http://www.uspto.gov/sites/default/files/documents/051415_aia_stat_graph.pdf

Bio/Pharma petitions

rising?

8

Bio/Pharma IPR Petitions

7.8%

8.3%

8.4%

8.3%

7.5%

7.6%

7.7%

7.8%

7.9%

8.0%

8.1%

8.2%

8.3%

8.4%

8.5%

Bio/Pharma (TC1600)

9-Apr

23-Apr

7-May

21-May

FY15 filings as of April 9, 2015. Source: http://www.uspto.gov/sites/default/files/documents/040915_aia_stat_graph.pdf FY15 filings as of April 23, 2015. Source: http://www.uspto.gov/sites/default/files/documents/042315_aia_stat_graph.pdf FY15 filings as of May 7, 2015. Source: http://www.uspto.gov/sites/default/files/documents/050715_aia_stat_graph.pdf FY15 filings as of May 14, 2015. Source: http://www.uspto.gov/sites/default/files/documents/051415_aia_stat_graph.pdf

9

http://www.uspto.gov/sites/default/files/documents/042315_aia_stat_graph.pdf

http://www.uspto.gov/sites/default/files/documents/042315_aia_stat_graph.pdf

Petition Grant Rate is High!

Granted, 68% 1227/1800

Joinder, 7% 121/1800

Denied, 25% 452/1800

Decisions Whether to Institute (1800 Petitions)

Granted + joinder = 75%

As of May 14, 2015. Source: http://www.uspto.gov/sites/default/files/documents/051415_aia_stat_graph.pdf

10

Grant Rate Higher for Pharma/Chem/Bio IPR Petitions

Settled/ terminated

before decision, 9

Petition denied: 50

Petition partially

denied: 31

Instituted: 106

Pending: 136

Instituted on at least one challenged claim: 73% (137/187))

187 institution

decisions

Of 332 IPR petitions filed relating to TC1600 and TC1700, institution decisions

as of May 7, 2015. Source: Finnegan research.

11

And If IPR Instituted, Cancellation Rate is High!

As of April 1, 2015. Source: Finnegan research, with thanks to Dan Klodowski, Kai Rajan, Elliot Cook, and Joe Schaffner.

“Mixed outcome”: some instituted claims survived, some did not.

196 72.06%

44 16.18%

32 11.76%

IPR Results by Case

No Instituted or Substitute Claims Survived

Mixed Outcome

All Instituted Claims Survived

12

And If IPR Instituted, Cancellation Rate is High!

As of April 1, 2015. Source: Finnegan research, with thanks to Dan Klodowski, Kai Rajan, Elliot Cook, and Joe Schaffner.

2949 73.50%

792 19.74%

271 6.75%

IPR Results by Claim

Instituted Claims Cancelled by PTAB

Instituted Claims Survived

Instituted Claims Conceded by Owner

80% of claims do

not survive!

13

Pharma/Chem/Bio IPR Case Outcomes in Terminated IPRs (137 Cases)

Adverse judgment: 8

8%

Mixed (some unpatentable, some

survived): 15 15%

All challenged claims unpatentable: 59

57%

All challenged claims survived: 13

13%

Settlement/ Terminated:

8 8%

Of 137 instituted IPRs filed relating to TC1600 and TC1700, as of May 7, 2015, 34 remain pending. 103 are terminated.

Source: Finnegan research.

14

Pharma/Chem/Bio IPR Case Outcomes in FWDs on the Merits (87 Decisions)

Mixed: 17% (15)

All challenged claims

unpatentable: 68% (59)

All challenged claims survived:

15% (13)

Of 87 instituted IPRs filed relating to TC1600 and TC1700, as of May 7, 2015, terminated on the merits.

Source: Finnegan research.

15

Pharma/Chem/Bio “Mixed” Results

Closer Look at the 15 “Mixed” Results By Claim: Most Claims Still Cancelled

Unpatentable: 68%

186/253

Survived: 32% 67/253

16

Why Petition for IPR?

Leverage for settlement

Lower burden of proof

Avoid or stay litigation

Faster resolution

•PTAB written decision within 12-18 months

•Appeal directly to Federal Circuit if losing party has Article III judicial standing

Lower cost

• Limited discovery and no live testimony

At present, general unavailability of Patent Owner amendment to

avoid cited prior art

To become an authorized generic and avoid Hatch-

Waxman Regime

Force forfeiture of 1st-

filer’s 180-day exclusivity

Any other reason?

17

New Threat

IPR PETITIONER PATENT OWNER

PATENT # SUBJECT MATTER CLAIMS PRODUCT FILED NOTES

IPR2015-00720

Coalition for Affordable Drugs, LLC

Acorda Therapeutics, Inc.

8,663,685 Sustained release aminopyridine composition

1-8 Ampyra® (MS)

(corr) 3/5/2015

Current H-W litigation

IPR2015-00817

Coalition for Affordable Drugs, LLC

Acorda Therapeutics, Inc.

8,007,826 Sustained release aminopyridine composition

1–3, 5–8, 10–41

(corr) 3/25/2015

IPR2015-00988

Coalition for Affordable Drugs, II, LLC

Shire, Inc. 6,773,720 Mesalazine controlled release oral pharmaceutical compositions

1-4 Lialda® (ulcerative colitis)

4/1/2015 Upheld as valid in district court litigation (2013)

IPR2015-01086

Coalition For Affordable Drugs, V, LLC

Biogen IDEC 8,759,393 Utilization of dialkylfumarates

1-13 Tecfidera® (MS)

4/22/2015

IPR2015-01136

Coalition For Affordable Drugs, V, LLC

Biogen MA Inc. 8,399,514 Treatment of MS 1-20 5/1/2015

18

http://www.killerbassbaits.com/

New Threat


PATENT #

SUBJECT MATTER

CLAIMS PRODUCT FILED NOTES

IPR2015-01018

Coalition for Affordable Drugs, III, LLC

Jazz Pharms., Inc.

7,895,059 Sensitive drug distribution system and method

1-16 Xyrem® (narolepsy)

4/6/2015

IPR2015-01076

Coalition for Affordable Drugs, IV, LLC

Pharmacyclics, Inc.

8,754,090 Use of inhibitors of bruton's tyrosine kinase (Btk)

1-2 Imbruvica® (cancer)

4/20/2015

IPR2015-00990


NPS Pharms., Inc.

7,056,886 GLP-2 formulations 46-52 and 61-75

Gattex® (SBS)

4/1/2015 Same patent as -01093, same art

IPR2015-01093


NPS Pharms., Inc.

7,056,886 GLP-2 formulations 1-45 Gattex® (SBS)

4/23/2015 Same patent as -00990, same art

IPR2015-01241

Coalition for Affordable Drugs, VII, LLC

Pozen, Inc. 6,926,907 Pharmaceutical compositions for the coordinated delivery of NSAIDs

1-23 Vimovo® 5/21/2015

19


New Threat


PATENT # SUBJECT MATTER Claims Product FILED

IPR2015-01092

Coalition For Affordable Drugs, VI, LLC

Celgene Corp. 6,045,501 Methods for delivering a drug to a patient while preventing the exposure of a foetus or other contraindicated individual to the drug

1-10 Thalomid® Revlimid®

4/23/2015

IPR2015-01102

Coalition for Affordable Drugs, VI, LLC

Celgene Corp. 6,315,720 Methods for delivering a drug to a patient while avoiding the occurrence of an adverse side effect known or suspected of being caused by the drug

1-32 Pomalyst® Revlimid®

4/23/2015

IPR2015-01103




4/23/2015

IPR2015-01096




4/23/2015

IPR2015-01169


Celgene Corp. 5,635,517

Method of reducing TNFα levels with amino substituted 2-(2,6-dioxopiperidin-3-yl)-1-oxo-and 1,3-dioxoisoindolines


5/7/2015

20


New Threat


PATENT #

SUBJECT MATTER

Claims Product FILED NOTES

IPR2015-00858

Ferrum Ferro Capital LLC

Allergan Sales, LLC

7,030,149 Combination of brimonidine timolol for topical ophthalmic use

4 Combigan® 3/9/2015 Upheld as valid in district court litigation (2013)

21


Ferrum Ferro Capital LLC v. Allergan Sales, LLC, IPR2015-00858

• U.S. Pat. No. 7,030,149: Combination of brimonidine timolol for topical

ophthalmic use.

• Issued April 18, 2006

• 4 claims

• 2 independent claims

• Only claim 4 challenged.

― Claim 4: A method of reducing the number of daily topical ophthalmic doses

of brimondine administered topically to an eye of a person in need thereof

for the treatment of glaucoma or ocular hypertension from 3 to 2 times a

day without loss of efficacy, wherein the concentration of brimonidine is

0.2% by weight, said method comprising administering said 0.2% brimonidine

by weight and 0.5% timolol by weight in a single composition.

22


• Drug – Combigan®

• Used to treat glaucoma or ocular hypertension.

• INDICATIONS AND USAGE – COMBIGAN® (brimonidine tartrate/timolol

maleate ophthalmic solution) 0.2%/0.5% is an alpha-adrenergic receptor

agonist with a beta-adrenergic receptor inhibitor indicated for the

reduction of elevated intraocular pressure (IOP) in patients with glaucoma

or ocular hypertension who require adjunctive or replacement therapy

due to inadequately controlled IOP; the IOP-lowering of COMBIGAN® dosed

twice a day was slightly less than that seen with the concomitant

administration of 0.5% timolol maleate ophthalmic solution dosed twice a

day and 0.2% brimonidine tartrate ophthalmic solution dosed three times

per day.

23


• Orange Book patents listed – Combigan (all OB-listed patents are in same

family)

• 7030149 expiration Apr 19, 2022 U – 849

• 7320976 expiration Apr 19, 2022 U - 849

• 7323463 expiration Jan 19, 2023

• 7642258 expiration Apr 19, 2022 U - 1024

• 8133890 expiration Apr 19, 2022 U - 1235

• 8354409 expiration Apr 19, 2022 U - 1371

• 8748425 expiration Apr 19, 2022 U - 1524

A delisting request

indicated on the OB

24


• Patent holder – Allergan, Inc., a global, multi-specialty health

care company.

• March 17, 2015: Actavis (NYSE:ACT) completed the acquisition

of Allergan, creating a $23 billion diversified global

pharmaceutical company and a leader in a new industry model

- Growth Pharma.

25


• Related litigation listed in the Ferrum petition:

• Allergan, Inc. v. Sandoz Inc., Case No. 2:09-cv-00097 (E.D. Tex)

• Allergan, Inc. v. High-Tech Pharmacal Co., Case No. 2:09-cv-00182

(E.D. Tex) and Allergan, Inc. v. Alcon Labs, Inc., Case No. 2:09-cv-

00348 (E.D. Tex)

• Allergan, Inc. v. Apotex Inc., Case No. 2:10—cv-00200 (E.D. Tex)

• Allergan, Inc. v. Watson Labs, Inc., Case No. 2:10-cv-00344 (E.D.

Tex)

26


• Previous litigation

• Allergan v. Sandoz, 726 F.3d 1286 (Fed. Cir. 2013)(PROST,

O’Malley, Dyk)(Dyk concurring-in-part and dissenting-in-part), pet.

for cert. denied, 134 S.Ct. 1764 (U.S., 2014)

• Sandoz asserted reference taught fixed combinations of alpha2-

agonists and beta-blockers for the treatment of glaucoma.

• At the time of the invention, both timolol and brimonidine were

commercially available drugs used for opthamalic conditions,

available in claimed concentrations, contained the preservative BAK,

and it was known that the serial administration of brimonidine and

timolol reduced intraocular pressure greater than either timolol or

brimonidine alone.

• Another reference “expressly provided a motivation to formulate

fixed combinations of alpha2-agonists and beta blockers, including

timolol, in order to increase patient compliance.”

27



• Allergan v. Sandoz, 726 F.3d 1286 (Fed. Cir. 2013)(con’t)

• Fed. Cir.: Majority held claim 4 of the ‘149 patent not invalid under

§103.

― No clear and convincing evidence of obviousness relating to reducing the

daily number of doses of brimonidine from 3 to 2 times a day without loss

of efficacy.

― Record firmly established “that when brimonidine is dosed twice per day

as opposed to three times per day, there is a loss of efficacy in the

afternoon—the so called, afternoon trough. Sandoz has failed to point to

evidence in the prior art that would allow us to conclude that the addition

of timolol to brimonidine dosed twice per day would eliminate the

afternoon trough issue.”

― Claims 1-3 summary judgment of non-infringement; no judgment on

validity.

28



• Allergan v. Sandoz, 726 F.3d 1286 (Fed. Cir. 2013)(con’t)

• Dissent: Would have held claim 4 invalid.

― “The majority’s outcome appears to rest, therefore, on the

notion that claim 4 was not obvious because it claims the result

of twice-a-day doing—avoiding ‘a loss of efficacy in the

afternoon.’ …. Avoiding a ‘loss of efficacy’ is not a separate step,

but rather a result of the claimed method…. We should

recognize in this case … that ‘[n]ewly discovered results of

known processes directed to the same purpose are not

patentable.’”

29


• Petitioner – Ferrum Ferro Capital, LLC

• Ferrum Ferro Capital, LLC is a privately-held venture focused on innovation,

application, and monetization.

• Led by Kevin Barnes

• U.S. 7,030,149

• Challenged patentability of one claim (claim 4)

• Claim 4 of the ‘149 patent. A method of reducing the number of daily

topical ophthalmic doses of brimondine administered topically to an

eye of a person in need thereof for the treatment of glaucoma or

ocular hypertension from 3 to 2 times a day without loss of efficacy,

wherein the concentration of brimonidine is 0.2% by weight, said

method comprising administering said 0.2% brimonidine by weight and

0.5% timolol by weight in a single composition.

• Challenged on one ground (§103 ).

30


• Note that claims 1-3 of the ‘149 patent were adjudged to be not

infringed in the Federal Circuit appeal.

• Unchallenged Claim 1 of the ‘149 patent: A method of treating

glaucoma or ocular hypertension by topical administration of about

0.2% brimonidine by weight to an eye of a person in need thereof,

said improvement comprising topically administering to said eye, in a

single composition, about 0.2% brimonidine by weight and about 0.5%

timolol by weight twice a day; as the sole active agents; wherein said

method is as effective as administration of 0.5% timolol twice a day

and 0.2% brimonidine three time a day to said eye, wherein the two

compounds are administered in separate compositions.

• Claim 2 depends from claim 1 and adds the limitation that the composition further

comprises from 0.001% to 0.01% benzalkonium chloride.

• Claim 3 depends from claim 2 and adds the limitation that the composition further

comprises about 0.005% benzalkonium chloride.

31


• Obviousness ground asserted based on DeSantis in view of Timmermans, and further in view of Larsson

and/or Stewart.

• DeSantis and Larsson were both before the Federal Circuit. • According to Ferrum, “[t]he Federal Circuit already determined that the fixed combination of 0.5%

brimonidine and 0.2% timolol for glaucoma treatment would have been obvious when it invalidated the

composition claims of the related ’463 Patent. The Federal Circuit’s reasoning applies equally to method

claim 4 of the ’149 Patent.”

• DeSantis teaches the use of alpha-2 agonists and beta-blockers in fixed combinations for treatment of

glaucoma; discloses the beta-blocker timolol. • Provides motivation to combine the active ingredients into a fixed combination to increase patient

compliance through a simpler dosage regimen.

• Timmermans discloses alpha-2 agonists; discloses brimonidine.

• Larsson teaches twice daily serial administration of 0.2% brimonidine followed by 0.5% timolol after a five

minute period.

• Stewart also teaches twice daily serial administration of brimonidine and timolol, as well as no difference

in intraocular pressure effects of the twice daily dosing when compared to three times a day dosing.

• Before the ’149 Patent, there were three pharmaceutically acceptable alpha-2 agonists: clonidine,

apraclonidine, and brimonidine. • Of these three, brimonidine was favored for long-term treatment (as required for glaucoma)

32


• IPR Petition (con’t)

• Argument: Federal Circuit decision regarding the validity of claim

4 turned on the construction of “loss of efficacy,” but in this

proceeding, “broadest reasonable interpretation” (BRI) applies.

• Federal Circuit majority held “loss of efficacy” term was a claim

limitation.

• Federal Circuit dissent held “loss of efficacy” was not a claim

limitation – since the dissent’s view is the broader of the two, it

should apply here.

33


• IPR Petition (con’t)

• “Loss of efficacy” is merely an intended result.

• Expert declaration attests that POSITA would understand the term to be an intended result, not a step of the

claimed process.

• It would have been obvious to combine 0.5% brimonidine and 0.2% timolol in a fixed

combination for twice daily use in glaucoma treatment, and it would have been

obvious to dose the fixed combination twice daily.

• POSITA would be motivated to combine the two APIs in a fixed combination to

achieve better patient compliance.

• Objective evidence does not overcome prima facie case of obviousness. • Federal Circuit found long-felt need to be conclusory and without support;

• Federal Circuit rejected evidence of unexpected result of no loss of efficacy with twice daily

dosing. ― Objective evidence of an unexpected result tied to “without loss of efficacy” “is not a relevant

secondary consideration.”

34


• Status of IPR2015-00858

• Petition accorded filing date of March 9, 2015.

• No POPR filed yet (due no later than June 9, 2015).

• No institution decision yet (due no later than Sept. 9,

2015).

• No other IPR challenge

35

Coalition For Affordable Drugs III LLC v. Jazz Pharms., Inc.,

IPR2015-01018

• Petition filed April 6, 2015

• Claims 1-16 of U.S. Pat. No. 7,895,059

• Claim 1. A computerized method of distributing a prescription drug under exclusive control of an exclusive

central pharmacy, the method comprising:

• receiving in a computer processor all prescription requests, for any and all patients being prescribed the

prescription drug, only at the exclusive central pharmacy from any and all medical doctors allowed to

prescribe the prescription drug, the prescription requests containing information identifying patients,

the prescription drug, and various credentials of the any and all medical doctors;

• requiring entering of the information into an exclusive computer database associated with the exclusive

central pharmacy for analysis of potential abuse situations, such that all prescriptions for the

prescription drug are processed only by the exclusive central pharmacy using only the exclusive

computer database;

• checking with the computer processor the credentials of the any and all doctors to determine the

eligibility of the doctors to prescribe the prescription drug; confirming with a patient that educational

material has been received and/or read prior to shipping the prescription drug;

• checking the exclusive computer database for potential abuse of the prescription drug; mailing or

sending by courier the prescription drug to the patient only if no potential abuse is found by the patient

to whom the prescription drug is prescribed and the doctor prescribing the prescription drug;

• confirming receipt by the patient of the prescription drug; and generating with the computer processor

periodic reports via the exclusive computer database to evaluate potential diversion patterns.

36


IPR2015-01018

• Total Revenue 2014: $1172.9 M

• Net Income 2014: $527.6 M

• Key Products and Revenue: • XYREM® (sodium 4-hydroxy butyrate)

• Used to treat excessive daytime sleep and cataplexy associated with narcolepsy


• Schedule III drug

• Erwinaze®/Erwinase®

• Used to treat acute lymphoblastic leukemia (ALL)


• Defitelio®(defibrotide)

• Used to treat severe hepatic veno-occlusive disease (VOD) in patients over one

month of age undergoing hematopoietic stem cell transplantation (HSCT)

therapy

• Total Revenue 2014: $73.4M

• Patent Estate: 17 patents covering XYREM®

• Patents Listed in Orange Book: 15

37


IPR2015-01018

• Orange Book listings

38

Appl No Prod No Patent No Patent Expiration

Drug Substance Claim

Drug Product Claim

Patent Use Code

Delist Requested

N021196 001 6780889 Jul 4, 2020 Y

N021196 001 7262219 Jul 4, 2020 Y

N021196 001 7668730 Jun 16, 2024 U - 1110

N021196 001 7765106 Jun 16, 2024 U - 1069

N021196 001 7765107 Jun 16, 2024 U - 1070

N021196 001 7851506 Dec 22, 2019 U - 1101

N021196 001 7851506 Dec 22, 2019 U - 1102

N021196 001 7895059 Dec 17, 2022 U - 1110

N021196 001 8263650 Dec 22, 2019 Y U - 1101

N021196 001 8263650 Dec 22, 2019 Y U - 1102

N021196 001 8324275 Dec 22, 2019 U - 1101

N021196 001 8324275 Dec 22, 2019 U - 1102

N021196 001 8457988 Dec 17, 2022 U - 1110

N021196 001 8589182 Dec 17, 2022 U - 1110

N021196 001 8731963 Dec 17, 2022 U - 1110

N021196 001 8772306 Mar 15, 2033 U - 1532

N021196 001 8859619 Dec 22, 2019 Y

N021196 001 8952062 Dec 22, 2019 U - 1101

N021196 001 8952062 Dec 22, 2019 U - 1102

Yellow: Pharmaceutical composition, method of treatment patents. Last patent expires July 2020

Pink: Restricted distribution system for Xyrem. Six of these are being challenged by one or more ANDA filers in district court and in

IPR. Were also challenged under CBM but institution was denied by PTAB for failure to show the claims were CBM.

Green: A method of treatment with Xyrem when patent is also taking valproate.

at issue in this IPR and

in DC litigation with ANDA filers

http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=021196&TABLE1=OB_Rx




















IPR2015-01018

39

Patent No

Patent Expiration

Other PTAB challenges of Patent at Issue in IPR2015-01018

District court challenges of Patent at Issue in IPR2015-01018

Notes

7895059 Dec 17,

2022 Par (IPR2015-00548), filed April 1, 2015

Watson Labs, Ranbaxy Labs., Amneal

Pharma, Par Parma, Roxanne Labs. Continuation of 7,668,730

Patent No

Patent Expiration

Other OB-listed patents: PTAB challenges

Other OB-listed patents: District court challenges

Notes

8457988 Dec 17,

2022 Par (IPR2015-00551) filed Jan. 8, 2015 Yes

Div of 13/013,680, abandoned, which is cont of patent

7,895,059 which is cont of 7,668,730

8589182 Dec 17,

2022

Amneal /Par (IPR2015-00545) filed Jan. 8, 2015

Yes

Cont. of 13/013,680, abandoned, which is cont of

patent 7,895,059 which is cont of 7,668,730

8731963 Dec 17,

2022

Cont. of 13/013,680, abandoned, which is cont of

patent 7,895,059 which is cont of 7,668,730

7668730 Jun 16, 2024

Amneal/Par (IPR2015-00554) filed Jan. 8, 2015

Yes

7765106 Jun 16, 2024

Amneal/Par (IPR2015-00546) filed Jan. 8, 2015

Yes Div of 7,668,730

7765107 Jun 16, 2024

Amneal/Par (IPR2015-00547)

filed Jan. 8, 2015 Yes Div of 7,668,730


IPR2015-01018

• Asserted references:

• U.S. Published Application No. 2004/0176985 to Lilly et al.

(“Lilly”) (§102(e) reference)

• Published transcript of an FDA Drug Advisory Committee

Meeting relating to Xyrem® (“the DAC Transcript”) (§102(b)

reference)

• U.S. Patent No. 6,587,829 (“Camarda”) (§102(b) reference)

• Published Preliminary Clinical Safety Review of the NDA for

Xyrem® (the “CSR”) (§102(b) reference)

40


IPR2015-01018

• Two grounds asserted, both §103.

• Claims 1-6, 9 and 12-14 obviousness over combination of Lilly in view of

the DAC Transcript and Camarda, because a POSITA would be motivated to

combine the teachings of these references to arrive at a method for

reducing the abuse of drug products such as Xyrem® and thus improve the

healthcare system while reducing healthcare costs.

• Lilly discloses a computerized system to assist pharmacies to distribute prescription drugs to

patients; store and obtain various types of data, including comparing new prescription to

medical history; desirable to reduce misure/abused prescriptions.

• DAC transcript discloses risk management program under which product, such as Xyrem®,

made available through a central pharmacy and shipped directly to patient at home via a

closed loop distribution system, with checks to determine if the physician is eligible to

prescribe Xyrem® and education about the risks and the appropriate use of the drug after the

first prescription is filled.

• Camarada teaches predicting which patients are most likely to fail to comply with their

prescription; report patient data to pharmacy.

41


IPR2015-01018

• Two grounds asserted, both §103 (con’t)

• Claims 7-8, 10-11 and 15-16 obviousness over combination of

above three references, in combination with the Preliminary

Clinical safety Review (CSR) reference which was part of FDA’s

approval process for Xyrem®

• CSR discloses that a patient’s prescription of Xyrem® may be shipped

to another pharmacy for patient’s pick up, rather than shipping it

directly to the patient.

42

Coalition Filed 5 IPRs Against Celgene


PATENT # SUBJECT MATTER Claims Product FILED

IPR2015-01092 Coalition For Affordable Drugs, VI, LLC

Celgene Corp. 6,045,501 Methods for delivering a drug to a patient while preventing the exposure of a foetus or other contraindicated individual to the drug

1-10 Thalomid® Revlimid®

4/23/2015

IPR2015-01102 Coalition for Affordable Drugs, VI, LLC



4/23/2015




4/23/2015




4/23/2015


Celgene Corp. 5,635,517

Method of reducing TNFα levels with amino substituted 2-(2,6-dioxopiperidin-3-yl)-1-oxo-and 1,3-dioxoisoindolines


5/7/2015

43


Celgene Corp.

• Celgene: major global biopharmaceutical corporation.

• Total Revenue 2014: $7,670.4 M

• Net Income 2014: $1,999.9 M

• Products and Revenue: • ABRAXANE® (paclitaxel protein-bound particles for injectable suspension) (albumin-bound)

― Used to treat breast cancer, pancreatic cancer, and non-small cell lung cancer

― Total Revenue 2014: $848.2 M

• ISTODAX® (romidespsin)

― Used to treat cutaneous T-cell lymphoma and peripheral T-cell lymphoma


• OTEZLA® (apremilast)

― Used to treat psoriatic arthritis and psoriasis

― Total Revenue 2014: $69.8M

• POMALYST® (pomalidomide)

― Used to treat multiple myeloma and systemic sclerosis


• REVLIMID® (lenalidomide)

― Used to treat hematological malignancies (multiple myeloma and myelodysplastic syndromes)

― Total Revenue 2014: $4,980.0 M

• THALOMID® (thalidomide)

― Used to treat multiple myeloma and erythema nodosum leprosum


• VIDAZA® (azacitidine - pyrimidine nucleoside analog)

― Used to treat myelodysplastic syndromes


44

Orange-Book Listed Patents for POMALYST® (pomalidomide)

use of pomalidomide to inhibit the secretion of

pro-inflammation cytokines, including tumor

necrosis factor alpha

use of pomalidomide while preventing the

exposure of a fetus or other contraindicated

individual to pomalidomide

use of pomalidomide while preventing the exposure of a fetus or other contraindicated individual

to pomalidomide

45

Orange-Book Listed Patents for REVLIMID® (lenalidomide)

use of lenalidomide to inhibit the secretion of pro-

inflammatory cytokines, including tumor necrosis

factor alpha

use of lenalidomide while preventing the exposure of a

fetus or other contraindicated individual to lenalomide

use of lenalidomide while preventing the exposure of a

fetus or other contraindicated individual to lenalomide

46

Orange-Book Listed Patents for THALOMID® (thalidomide)

approval for marketing only under a special restriction program approved by FDA

called “System for Thalidomide Education and

Prescribing Safety”

use in combination with dexamethasone is indicated for the treatment of patients

with newly diagnosed multiple myeloma

use in combination with dexamethasone is indicated for the treatment of patients

with newly diagnosed multiple myeloma

method for delivering a drug to a patient in need of

the drug, while avoiding the

occurrence of an adverse side effect

known or suspected of being caused by

said drug

47

Coalition For Affordable Drugs VI LLC v. Celgene Corp.,

IPR2015-01092

• U.S. Pat. No. 6,045,501

• Claim 1. A method for delivering a teratogenic drug to patients in need of the

drug while avoiding the delivery of said drug to a foetus comprising:

• a. registering in a computer readable storage medium prescribers who are qualified to

prescribe said drug;

• b. registering in said medium pharmacies to fill prescriptions for said drug;

• c. registering said patients in said medium, including information concerning the ability

of female patients to become pregnant and the ability of male patients to impregnate

females;

• d. retrieving from said medium information identifying a subpopulation of said female

patients who are capable of becoming pregnant and male patients who are capable of

impregnating females;

• e. providing to the subpopulation, counseling information concerning the risks attendant

to fetal exposure to said drug;

• f. determining whether patients comprising said subpopulation are pregnant; and

• g. in response to a determination of non-pregnancy for said patients, authorizing said

registered pharmacies to fill prescriptions from said registered prescribers for said non-

pregnant registered patients.

• Patent expires: Aug. 28, 2018.

48


IPR2015-01092

• 2 Grounds asserted, both §103.

• Petition combines references that discuss the importance of

monitoring and counseling patients regarding the risks of pregnancy

while taking teratogenic drugs, such as thalidomide, with references

teaching such computer-based programs for other drugs.

• Petition argues keeping records in a computer readable storage

medium would have been obvious to a person of ordinary skill in the

art, as a matter of routine optimization.

• None of asserted references was before the Examiner during

prosecution.

49


IPR2015-01092

• Related litigation

• Celgene Corp. v. Lannett Holdings, Inc., 2-15-cv-00697 (NJD) (filed

January 30, 2015) - pending (Briefing on Motion to Dismiss for Lack of

Jurisdiction and Improper Venue).

• Celgene Corp. v. Natco Pharma Ltd., 2-10-cv-05197 (NJD) (filed October

8, 2010) - Current status: Order regarding infringement entered May 7,

2014.

• Celgene Corp. v. Barr Labs., Inc., 2-08-cv-03357 (NJD) (filed July 3, 2008);

Celgene Corp. v. Barr Labs., Inc., 2-07-cv-05485 (NJD) (filed November 14,

2007); Celgene Corp. v. Barr Labs., Inc., 2-07-cv-04050 (NJD) (filed

August 23, 2007); Celgene Corp. v. Barr Labs., Inc., 2-07-cv-00287 (NJD)

(filed January 18, 2007) - cases consolidated and dismissed w/out

prejudice on May 26, 2010.

50


IPR2015-01102, -01103, -01096

• U.S. Pat. No. 6,315,720

• Claim 1. In a method for delivering a drug to a patient in need of the drug, while avoiding

the occurrence of an adverse side effect known or suspected of being caused by said drug,

wherein said method is of the type in which prescriptions for said drug are filled only

after a computer readable storage medium has been consulted to assure that the

prescriber is registered in said medium and qualified to prescribe said drug, that the

pharmacy is registered in said medium and qualified to fill the prescription for said drug,

and the patient is registered in said medium and approved to receive said drug, the

improvement comprising: • a. defining a plurality of patient risk groups based upon a predefined set of risk parameters for said

drug;

• b. defining a set of information to be obtained from said patient, which information is probative of

the risk that said adverse side effect is likely to occur if said drug is taken by said patient;

• c. in response to said information set, assigning said patient to at least one of said risk groups and

entering said risk group assignment in said medium;

• d. based upon said information and said risk group assignment, determining whether the risk that

said adverse side effect is likely to occur is acceptable; and

• e. upon a determination that said risk is acceptable, generating a prescription approval code to be

retrieved by said pharmacy before said prescription is filled.

• Patent expires: Oct. 23, 2020.

51


IPR2015-01102, -01103, -01096

• -01096 Petition

• Challenges all 32 claims

• 2 Grounds: §102 and §103.

• §102: Petition cites discussion in Thalidomide Package Insert of the

special restricted distribution program approved by the FDA, and

argues the claimed step of generating a prescription approval code is

inherent in the system disclosed in the Package Insert.

• §103: Petition argues that if the step of generating a prescription

approval code is not inherent in the Package Insert, it is obvious over

the teachings of another cited reference.

52


IPR2015-01102, -01103, -01096

• -01102 Petition

• Challenges all 32 claims.

• 1 ground: §103

• Essentially combines the arguments of -01092 and -01096 Petitions.

• -01103 Petition

• Challenges all 32 claims.

• 1 ground: §103

• Essentially combines the arguments of -01092 and -01096 Petitions.

53


IPR2015-01102, -01103, -01096

• Related litigation (same as for U.S. Pat. No. 6,045,501 at issue in IPR2015-

01092)

• Celgene Corp. v. Lannett Holdings, Inc., 2-15-cv-00697 (NJD) (filed January 30,

2015) - pending (Briefing on Motion to Dismiss for Lack of Jurisdiction and

Improper Venue).

• Celgene Corp. v. Natco Pharma Ltd., 2-10-cv-05197 (NJD) (filed October 8, 2010)

- Current status: Order Regarding Infringement entered May 7, 2014

• Celgene Corp. v. Barr Labs., Inc., 2-08-cv-03357 (NJD) (filed July 3, 2008);

Celgene Corp. v. Barr Labs., Inc., 2-07-cv-05485 (NJD) (filed November 14,

2007); Celgene Corp. v. Barr Labs., Inc., 2-07-cv-04050 (NJD) (filed August 23,

2007); Celgene Corp. v. Barr Labs., Inc., 2-07-cv-00287 (NJD) (filed January 18,

2007) - cases consolidated and dismissed w/out prejudice on May 26, 2010.

54


IPR2015-01169

• U.S. Pat. No. 5,635,517

• Claim 1: The method of reducing undesirable levels of TNFα in a mammal

which comprises administering thereto an effective amount of a compound of

the formula:

• in which in said compound one of X and Y is C=O and the other of X and Y is C=O

or CH2.

• Patent expires:

• October 4, 2019 for drug substance claims relating to lenalidomide.

• July 24, 2016 for all other claims.

55


IPR2015-01169

• 3 grounds asserted, all §103.

• Ground 1: Petition argues it would have been obvious to use the claimed

thalidomide analogs for reducing TNFα production because the cited

references show that the parent molecule (thalidomide) and other analogs

have that property.

• Ground 2: Petition argues that the cited combination of references shows

a direct link between structure and function among thalidomide analogs,

and establishes an expectation that structurally similar analogs of

thalidomide will behave like their parent compounds.

• Ground 3: Petition argues that two of the cited references establish a

“lead compound” and the remaining references provide motivation to

make the claimed modifications, which were known to maintain the anti-

inflammatory activity of thalidomide and to increase solubility.

• Asserted references – one considered during prosecution.

56


IPR2015-01169

• Related litigation

• Celgene Corp. v. Natco Pharma Ltd., 2-12-cv-04571 (NJD) (filed

July 20, 2012) – pending.

• Celgene Corp. v. Natco Pharma Ltd., 2-10-cv-05197 (NJD) (filed

October 8, 2010) – pending.

57

What Can Innovative Pharma Do Today To Strengthen Their

Patents To Enhance The Chance Of Survival In IPR,

Irrespective Of The Identity Of The Petitioner

58

Reminder of Standards Unfavorable to Patent Owner

ISSUE PGR/CBM PGR/IPR DISTRICT COURT

Burden of proof Preponderance of the

evidence Clear and convincing

evidence

Presumption of Validity?

No Yes

Claim construction Broadest reasonable Interpretation (BRI)*

Phillips/Markman framework: analyze claims, specification,

and prosecution history to determine how claims would

be understood by one of ordinary skill in the art

Decision maker Patent Trial and

Appeal Board (APJs) District court judge or jury

* and no attempt to preserve patentability; also not bound to follow district court’s construction, if it exists.

59

25% of the Institution Decisions Have Been Denials

Patent Owner’s best outcome is a denial

60

http://borderlessnewsandviews.com/2012/05/the-parasitic-economy/

Institution Decision Non-Appealable

• 35 U.S.C. § 314(d): NO APPEAL.—The

determination by the Director whether

to institute an inter partes review

under this section shall be final and

nonappealable.

61

Federal Circuit Treatment So Far

• In re Cuozzo Speed Technologies, LLC, 778 F.3d 1271 (Fed. Cir. 2015)

• No jurisdiction to review PTAB’s IPR institution decision (See 35 U.S.C. § 314(d)).

• Affirm PTAB’s Final Written Decision in full (all instituted claims unpatentable as obvious)

• No error in PTAB’s application of BRI claim construction standard;

• No error in obviousness determination; and

• No error in denial of Cuozzo’s motion to amend.

― Lack of written description support;

― Improper broadening

62 62

http://vignette1.wikia.nocookie.net/prettylittleliars/images/e/ee/Thumbs_up.jpeg/revision/latest?cb=20150129232017

Federal Circuit Using Rule 36 Affirmances for PTAB Appeals Note: Affirmance Rate is 100%

• Rule 36 non-precedential decisions affirming PTAB decisions:

• Softview LLC v. Kyocera Corp., No. 2014-1599, 592 Fed.Appx. 949 (Fed. Cir. Feb. 9, 2015) (same) (IPR2013-00004)

(joined)


(joined)


(joined)


(joined)

• Board Of Trustees Of The University Of Illinois v. Micron Technology, Inc., No. 2014-1509, __Fed. Appx. __ (Fed. Cir.

March 12, 2015) (same) (IPR2013-00005)


March 12, 2015) (same) (IPR2013-00006)


March 12, 2015) (same) (IPR2013-00008) • Clearlamp, LLC v. LKQ Corp., 594 Fed.Appx. 687 (Fed. Cir. Feb. 18, 2015)

• In re Zillow, Inc., --Fed. Appx. __ (Fed. Cir. March 12, 2015)

• Helferich Patent Licensing, LLC v. CBS Interactive, Inc., --Fed. Appx. __ (Fed. Cir. April 8, 2015)

• Also written decisions affirming PTAB decisions: • In re Cuozzo Speed Technologies, LLC, 778 F.3d 1271 (Fed. Cir. 2015)

• Belden Inc. v. Berk-Tek LLC, 2015 WL 1781484 (Fed. Cir. Apr. 17, 2015) (affirmed in written decision) (IPR2013-

00058)(non-precedential)

• Belden Inc. v. Berk-Tek LLC, 2015 WL 1781484 (Fed. Cir. Apr. 17, 2015) (affirmed in written decision) (IPR2013-

00069)(non-precedential)

63

What Are Some Examples Of The Bases Of These Denials?

• Failure to name real-party-in-interest as required by 35 U.S.C. §312(a)(2) and 37 C.F.R. §42.8(b)(1). • Very fact-dependent. • This is one area where we are seeing motions for additional discovery granted.

• Time-barred under 35 U.S.C. §315(b)

• Same or substantially the same prior art/arguments under 35 U.S.C. §325(d)

• “Same or substantially the same prior art or arguments” during prosecution • “Same or substantially the same prior art or arguments” in another IPR petition

• Claim construction

• Insufficient evidence to meet threshold for institution

• 35 U.S.C. §314(a): “shows that there is a reasonable likelihood that the petitioner would prevail with respect to at least 1 of the claims challenged in the petition.”

• Objective evidence of nonobviousness

• Reference is not prior art

64

Filing POPR Is Optional, But More Petitions Denied When POPR Filed:

Sample from Pharma/Chem IPR Petitions

POPR filed in denied petition,

47

No POPR filed in denied

petition, 3

POPR filed in partially

denied petition, 25

No POPR filed in

partially denied

petition, 6

In 94% (47/50) of cases where petition denied, POPR was filed.

In 81% (25/31) of cases where petition partially denied, POPR was filed.

“Partially denied” indicates institution on fewer than all claims challenged in the petition.

Source: Finnegan research. As of May 13, 2015.

65

Filing POPR Is Optional, But More Petitions Denied When POPR Filed:

Sample from Pharma/Chem IPR Petitions

Source: Finnegan research. As of May 13, 2015. “Denied-in-Part” indicates institution on fewer than all claims challenged in the petition.

73 50%

25 17%

47 33%

POPR Filed (145 cases)

Instituted Denied-in-Part Denied

33 79%

6 14%

3 7%

POPR Not Filed (42 cases)

Instituted Denied-in-Part Denied

66

Use the POPR to Tell PTAB Why Petition Should Be Denied

• Do not make PTAB figure it out.

• PTAB just does not have time.

• PTAB looking for the concise, compelling

argument.

67

“Front-load” to Maximize Chance of Success at Institution Stage

• Institution decision is substantive

• Don’t hold back arguments:

• Actavis, Inc. v. Research Corporation Technologies, Inc., IPR2014-

01126, Paper 21 (PTAB Jan. 9, 2015):

• “Therefore, based on the record before us, we determine that Petitioner has

not provided competent evidence to qualify the LeGall thesis as a “printed

publication” under § 102(b). Petitioner may have recognized this deficiency.

Indeed, in a footnote, Petitioner states that it “reserves the right to

supplement this Petition with additional evidence that the LeGall thesis was

accessible to a POSA well before” the critical date. Pet. 36 n. 3. But a party

may only submit supplemental information after a trial has been instituted

(37 C.F.R. § 42.123) while we must decide whether to institute a trial based

on “the information presented in the petition” (35 U.S.C. § 314(a)). Because

the Petition and the accompanying evidence are insufficient to qualify the

LeGall thesis as a § 102(b) prior art, we deny the Petition regarding this ground.

(emphasis added)

68

Suggestions

• Claim construction is critical.

• If the Patent Owner has not made it clear in

specification and claims, it could be a tough go for

the Patent Owner.

• Lack of specification definition/claim clarity

could force PTAB to rely on dictionary

definitions.

69

Take-Away

• Drafting and prosecution

• Define terms judiciously, considering dual objectives of

patentability and proving infringement.

• Once defined, use terms consistently.

• Lay basis for Patent Owner’s desired claim construction, both

at PTAB and in district court litigation, and enhance chances

of PTAB denial of institution.

• Probably want range of claims from broad to narrow, but

consider what limits you want on broad claims so that the

broadest reasonable interpretation (BRI) is not unreasonable.

• Rely on such a specification in POPR when attacking

Petitioner’s proposed BRI! 70

Practitioner Drafting And Prosecution Tools To Strengthen Potentially Important Patent Applications

and Increase Chances of IPR Denial

o Build up specification and file history during drafting and

prosecution.

Patent Owners cannot present newly-generated declaration

evidence in a Patent Owner's Preliminary Response (POPR);

Solidify novelty, non-obviousness, enablement, and written

description positions.

Consider declarations during prosecution, but be mindful of

inequitable conduct attacks in litigation.

71

Declarations to Provide Foundation for Denial

• Declarations need to be as solid as possible. PTAB has found that defective declarations relied on for patentability during prosecution can form an independent basis for instituting an IPR.

• K-40 Electronics, LLC v. Escort, Inc., IPR2013-00203, Paper 6 (PTAB Aug. 29, 2013)

― Board reviewed a § 1.131 declaration from the prosecution, found it

deficient, and reapplied the prior art the declaration had antedated, instituting the IPR.

― Case also had live testimony from inventor at oral hearing. ― One might want declarations from the inventor during prosecution that

can then by referred to by the Patent Owner in the optional Preliminary Response to try to ward off institution.

• Therasense always a consideration with declarations.

72

Thank You!

Contact Information:

Tom Irving

[email protected]

202.408.4082

Barbara Rudolph, Ph.D.

[email protected]

202.408.4346

Amanda Murphy, Ph.D.

[email protected]

202.408.4114

Rekha Bensal

[email protected]

650.416.7711

73

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