future pharmaceutical trends - patent & pipeline –

2011 Express Scripts, Inc.All Rights Reserved

Future Pharmaceutical Trends- Patent & Pipeline –

Chris Peterson, PharmDAimee Tharaldson, PharmD


• Patent Expiration Overview: 2011-2013

• Traditional Pipeline Highlights• Specialty Pipeline Overview

Objectives

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Objectives

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Patent Expiration Landscape

200120022003200420052006200720082009201020112012201320142015

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Patent Expiration LandscapeNext 5 Years

2011 2012 2013 2014 2015$0

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Patent Expiration LandscapeNext 5 Years

2011 2012 2013 2014 2015$0

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LipitorZyprexaLevaquinConcerta

PlavixSeroquelSingulairDiovanActos

Lexapro

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CymbaltaOxyContinNiaspan

NexiumCelebrexActonel

AbilifyGleevec

Namenda

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Patent Expirations: 2011

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Drug Manufacturer

Patent Sales (US)

Taxotere Sanofi Mar 15 $1,200 Xalatan Pfizer Mar 22 $711 Concerta* J&J May 01 $1,437 Femara Novartis Jun 03 $682 Nasacort AQ* Sanofi Jun 15 $244 Levaquin J&J Jun 20 $1,523 Arixtra GSK Expired $340Uroxatral Sanofi Jul 18 $248 Combivir* ViiV 4Q2011 $328 Zyprexa Lilly Oct 23 $2,958 Solodyn (45, 90, 135)* Medicis Nov 01 $667 Lipitor* Pfizer Nov 30 $7,245

* Settlement Agreement



8

Drug Manufacturer

Patent Sales (US)

Taxotere Sanofi Mar 15 $1,200 Xalatan Pfizer Mar 22 $711 Concerta* J&J May 01 $1,437 Femara Novartis Jun 03 $682 Nasacort AQ* Sanofi Jun 15 $244 Levaquin J&J Jun 20 $1,523 Arixtra GSK Expired $340Uroxatral Sanofi Jul 18 $248 Combivir* ViiV 4Q2011 $328 Zyprexa Lilly Oct 23 $2,958 Solodyn (45, 90, 135)* Medicis Nov 01 $667 Lipitor* Pfizer Nov 30 $7,245




9

Drug Manufacturer

Patent Sales (US)

Avandia* GSK 1Q2012 $342 Lexapro* Forest Mar-14 $2,812 Seroquel AstraZeneca Mar-26 $5,172 Avapro BMS Mar-30 $486 Provigil* Cephalon Apr-01 $1,133 Plavix BMS May-17 $6,130 Clarinex* Merck Jul-01 $248 Tricor* Abbott Jul-01 $1,345 Singulair Merck Aug-03 $4,073 Actos* Takeda Aug-17 $3,535 Xopenex neb* Sunovion Aug-20 $545 Geodon Pfizer Sep-01 $1,281 Diovan Novartis Sep-21 $3,533 Detrol Pfizer Sep-25 $790 Atacand AstraZeneca Dec-04 $199

* Settlement Agreements



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Drug Manufacturer

Patent Sales (US)





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Drug Manufacturer

Patent Sales (US)





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Drug Manufacturer

Patent Sales (US)





13

Drug Manufacturer

Patent Sales (US)





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Drug Manufacturer

Patent Sales (US)

Propecia* Merck Jan-01 $154 Opana ER* Endo Jan-01 $369 Reclast Novartis Mar-02 $405 Zometa Novartis Mar-02 $768 Valcyte Genentech Mar-15 $289 OxyContin Purdue Apr-16 $3,085 Zomig AstraZeneca May-14 $200 AcipHex Eisai May-18 $1,055 Temodar Merck Aug-11 $389 Advicor* Abbott Sep-20 $111 Niaspan* Abbott Sep-20 $1,129 Cymbalta Lilly Dec-11 $3,153



Patent Expirations: 2013Drug Manufacture

rPatent Sales

(US)Propecia* Merck Jan-01 $154 Opana ER* Endo Jan-01 $369 Reclast Novartis Mar-02 $405 Zometa Novartis Mar-02 $768 Valcyte Genentech Mar-15 $289 OxyContin Purdue Apr-16 $3,085 Zomig AstraZeneca May-14 $200 AcipHex Eisai May-18 $1,055 Temodar Merck Aug-11 $389 Advicor* Abbott Sep-20 $111 Niaspan* Abbott Sep-20 $1,129 Cymbalta Lilly Dec-11 $3,153


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Objectives

16


Cardiovascular PipelineXarelto (rivaroxaban – Bayer/J&J)

Indication: Stroke/systemic embolism in a-fib.Route: Oral (once daily)Comments: Approved July 1, 2011. Also under

FDA Review for a-fib indication (Nov. 5, 2011).

Eliquis (apixaban – BMS/Pfizer)Indication: Stroke/systemic embolism in a-fib.Route: Oral (twice daily)Comments: Submission of NDA by the end of

2011 with FDA approval in 2012. 17


FDA Action Dates: Cardiovascular

Drug Manufacturer Use Action Date

Simvastatin/sitagliptin Merck DM/Lipids Oct 17Xarelto (rivaroxaban) Bayer/J&J A-Fib (new indication) Nov 5Azilsartan/chlorthalidone Takeda Hypertension Dec 23Eliquis (apixaban) BMS/Pfizer A-Fib 2012ethyl icosapentate (AMR101)

Amarin hypertriglyceridemia

2012

Kynamro (mipomersen) Genzyme/ISIS Hyperlipidemia 2012

18


Diabetes Pipeline Dapagliflozin (AstraZeneca/BMS)

Indication: Type 2 diabetesRoute: Oral (two times daily)Comments: FDA Ad Board held on July 19. FDA

action date is October 28, 2011.

Bydureon (exenatide LAR – Amylin/Lilly)Indication: Type 2 diabetesRoute: subcutaneous injection (once weekly)Comments: “Complete response” received in

March 2011. FDA action date is January 28, 2012. 19


Diabetes Pipeline Insulin Degludec (Novo-Nordisk)

Indication: DiabetesRoute: Subcutaneous injection (three times

weekly)Comments: Long-acting basil insulin.

Submission planned by the end of 2011.

20


FDA Action Dates: Diabetes


Simvastatin/sitagliptin Merck T2DM/Lipids Oct 17Dapagliflozin BMS/AZ Diabetes Oct 28Janumet XR Merck Type 2 diabetes Nov 11

Alogliptin Takeda Type 2 diabetes Jan 26Alogliptin/pioglitazone Takeda Type 2 diabetes Jan 26Bydureon Lilly/Amylin Type 2 diabetes Jan 28Insulin decludec Novo Nordisk Diabetes 2012Pioglitazone/sitagliptin Merck Type 2 diabetes 2012

21


Respiratory Pipeline Eklira (aclidinium – Forest)

Indication: COPDRoute: Inhalation (twice daily)Comments: FDA Action date is Apr 30, 2012.

Glycopyrronium (NVA237 – Novartis) Indication: COPDRoute: Inhalation (once daily)Comments: NDA submission planned by the

end of 2011.

22


FDA Action Dates: Respiratory


Dymista Meda Allergic Rhinitis Feb 4Omnaris HFA Nasal Sunovion Allergic rhinitis Apr 06Eklira Forest COPD Apr 30QNaze Teva Allergic Rhinitis May 24glycopyrronium (NVA237)

Novartis COPD 2012

23


CNS Pipeline Opana ER (oxymorphone e.r. –

Endo)Indication: Chronic painRoute: Oral (Twice daily)Comments: “Tamper resistant” formulation.

FDA Action date is Dec 13, 2011.

Remoxy (oxycodone e.r. – Pfizer) Indication: Chronic painRoute: Oral (Twice daily)Comments: “Tamper resistant” formulation.

Complete response issued in in June.24


CNS Pipeline Levomilnacipran (Forest)

Indication: DepressionRoute: Oral (once daily)Comments: Isomer of milnacipran (Savella).

NDA by expected “early 2012”.

25


CNS Pipeline Levadex (dihydroergotamine - MAP)

Indication: Acute migraineRoute: InhalationComments: Asthma-sized inhaler device. FDA

Action date is Mar 26, 2012.

26


FDA Action Dates: CNSDrug Manufacturer Use Action DateOnfi Lundbeck Seizures 4th QuarterCPI-300 IntelGenx Depression Nov 13Opana E.R. (TR) Endo Pain Dec 13Fentanyl SL Spray Insys Pain Jan 4Adasuve Alexza Agitation Feb 4Levadex MAP Migraine Mar 26MoxDuo QRxPharma Pain May 11IPX066 Impax Parkinson’s

disease2012

Levomilnacipran Forest Depression 2012Telcagepant Merck Migraine 2012

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FDA Action Dates: OtherDrug Manufacture

r Use Action Date

Saflutan Merck Glaucoma 4Q2011Alendronate, effervescent

EffRx Osteoporosis Nov 11

Bio-T Gel Teva HRT Nov 14Plan B One Step (OTC) Teva Contraceptive Dec 7Anturol Antarex Overactive

Bladder Dec 8

Civanex Winston Osteoarthritis Dec 31Ivermectin Cream Topaz Head Lice Feb 7Prochieve Watson Preterm Birth Feb 26Avanafil Vivus Erectile

dysfunctionApr 30

Linaclotide Forest Chronic Constipation

Jun 9

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Objectives

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FDA New Drug Approvals

2008 2009 2010 2011 (YTD)02468

1012141618

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Traditional SpecialtySource: U.S. Food and Drug Administration


Specialty Trend Continues to Dwarf Traditional

PMPY

2010 2011 2012 2013$0

$200

$400

$600

$800

$1,000

Annual Trend

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2010 2011 2012 20130%

5%

10%

15%

20%

25%

30%

Source: Express Scripts’ Drug Trend Report data and Forecasting

Specialty Traditional


Top Specialty Therapy Classes

#5 Growth De-ficiency

#4 Anticoagulants

#3 Cancer

#2 Multiple Sclerosis

#1 Inflammatory Conditions

$0 $10 $20 $30 $40

$6

$7Total PMPY = $130

PMPY

2010 PMPY

$22

$30

$37

Source: Express Scripts’ Drug Trend Report data


Therapy Class Review• Inflammatory Conditions• Multiple Sclerosis• Cancer• Hepatitis C• Cystic Fibrosis• Other Drugs to Watch

33


Inflammatory ConditionsPipeline Trends

• Oral biologics will compete with injectables

• More therapies for gout?• “Biobetters” on the horizon

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Inflammatory ConditionsPipeline

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Drug (Manufacturer) Indication Route

Approval

Orencia* (BMS) RA (new SQ) SQ ApprovedHumira* (Abbott) Ulcerative

ColitisSQ Feb 2012

Apremilast (Celgene) Psoriasis, PA Oral 2012Tofacitinib (Pfizer) RA, Psoriasis Oral 2012Arcalyst* (Regeneron) Gout SQ 2012Ilaris* (Novartis) Gout SQ 2012Benlysta* (HGS / GSK) Lupus (new

SQ)SQ 2013

Fostamatinib (Rigel / AZ)

RA Oral 2013

INCB-28050 (Incyte / Lilly)

RA Oral 2013

RA = Rheumatoid Arthritis; PA = Psoriatic Arthritis*Already on the market for another indication or different route


Oral BiologicsApremilast (Celgene)

Indication: Psoriasis, Psoriatic ArthritisRoute: Oral (twice daily)Comments: Inhibits inflammatory cytokines;

Approval in 2012 for psoriasis

Tofacitinib (Pfizer)Indication: Rheumatoid Arthritis, PsoriasisRoute: Oral (twice daily)Comments: Inhibits JAK; Approval in 2012 for

RA

36

RA = Rheumatoid ArthritisJAK = Janus Kinase


GoutIlaris (canakinumab - Novartis)

Indication: Treatment and prevention of acute gout

Route: SQ InjectionComments: Negative Ad Board, CRL in August

Arcalyst (rilonacept - Regeneron)Indication: Treatment and prevention of acute

goutRoute: SQ InjectionComments: Approval in 2012?

- Both already on market for CAPS - 37

CRL = Complete Response Letter; CAPS = Cryopyrin-Associated Periodic Syndromes


Multiple Sclerosis Pipeline Trends

• More oral disease-modifying drugs• May see combination use of MS

drugs• Expanded MS use for currently

marketed drugs

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Multiple Sclerosis Pipeline

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Drug Manufacturer Route ApprovalBG-12 Biogen Idec Oral 2012Laquinimod Teva / Active

BiotechOral 2012

Lemtrada* Genzyme IV 2012Teriflunomide Sanofi Oral 2012Zenapax* Biogen Idec /

AbbottSQ 2012

Tovaxin Opexa SQ 2013Peg-Avonex Biogen Idec IM 2014*Already on the market for another indication


Oral Disease-Modifying Drugs for MS

Dimethyl Fumarate (BG-12 – Biogen Idec)Indication: Relapsing Remitting Multiple

SclerosisRoute: Oral (two times daily)Comments: Approval in 2012; G.I./flushing

issues

Laquinimod (Teva / Active Biotech)Indication: Relapsing Remitting Multiple

SclerosisRoute: Oral (once daily)Comments: Approval in 2012; May liver

enzymes40


Currently Marketed Drugs Expand into MS

Lemtrada (alemtuzumab - Genzyme)Indication: Relapsing Remitting Multiple

SclerosisRoute: IV Infusion (5 then 3 days per year)Comments: Approved for CLL; ITP and

infection risk

Zenapax (daclizumab – Biogen Idec/Abbott)Indication: Relapsing Remitting Multiple

SclerosisRoute: SQ Injection (once monthly)Comments: Approved for transplant; Infection

and liver toxicity risk41

CLL = Chronic Lymphocytic Leukemia; ITP = Immune Thrombocytopenic Purpura


Cancer Pipeline Trends• Cancer treated as a chronic

condition– Oral drugs– Targeted therapies

• Niche or orphan cancer types • Pharmacogenomics plays a role

42


2011 Cancer Drug Approvals

43

Drug (Manufacturer) Indication Route

Approval

Yervoy (Bristol Myers Squibb)

Malignant Melanoma

IV March 25th

Sylatron (Merck) Melanoma SQ March 29th

Caprelsa (AstraZeneca) Thyroid Cancer Oral April 6th

Zytiga (Centocor) Prostate Cancer Oral April 28th

Zelboraf (Genentech) Malignant Melanoma

Oral August 17th

Adcetris (Seattle Genetics)

HL and ALCL IV August 19th

Xalkori (Pfizer) Lung Cancer (NSCLC)

Oral August 26th

HL = Hodgkin’s Lymphoma; ALCL = Anaplastic Large Cell Lymphoma;NSCLC = Non-Small Cell Lung Cancer


PharmacogenomicsZalboraf (vemurafenib – Genentech)

Indication: Malignant MelanomaRoute: Oral (twice daily)Comments: For patients with BRAF mutation;

Approved Aug. 17th

Xalkori (crizotinib - Pfizer)Indication: Non-Small Cell Lung CancerRoute: Oral (twice daily)Comments: For patients with ALK mutation;

Approved Aug. 26th

44


Cancer Pipeline- 2011 –

Erwinaze (crisantaspase – EUSA)Indication: Acute Lymphoblastic LeukemiaRoute: IM (every other day)Comments: Cell growth inhibitor; Approval in

2011

Ruxolitinib (Incyte)Indication: MyelofibrosisRoute: Oral (twice daily)Comments: JAK inhibitor; FDA action: Dec 3rd

45

JAK = Janus Kinase


Cancer Pipeline- 2012 -

Drug Use Route

Axitinib (Pfizer)

Kidney Cancer

Oral

Biovax ID (Biovest)

Lymphoma (NHL)

SQ

Bositinib (Pfizer)

Leukemia (CML)

Oral

Brivanib (Bristol-Myers)

Liver Cancer

Oral

Cabozantinib (Exelixis)

Thyroid Cancer

Oral

Carfilzomib (Onyx)

Multiple Myeloma

IV

Herceptin (Genentech)

Breast Cancer (SQ)

SQ

Lucanix (NovaRx)

Lung Cancer (NSCLC)

Inj.

Drug Use Route

NeuVax Vaccine (Apthera)

Breast Cancer

Inj.

Omapro (Cephalon)

Leukemia (CML)

SQ

Perifosine (Keryx)

Multiple Myeloma

Oral

Regorafenib (Bayer)

Kidney Cancer

Oral

Ridaforolimus (Merck)

Bone Sarcomas

Oral

Talacteroferrin alfa (Agennix)

Lung Cancer (NSCLC)

Oral

Tivozanib (Aveo)

Kidney Cancer

Oral

Vismodegib (Genentech)

Basal Cell Carcinoma

Oral46

NHL = Non-Hodgkin’s Lymphoma; CML = Chronic Myeloid Leukemia; NSCLC = Non-Small Cell Lung Cancer



Drug Use Route

Axitinib (Pfizer)

Kidney Cancer

Oral

Biovax ID (Biovest)

Lymphoma (NHL)

SQ

Bositinib (Pfizer)

Leukemia (CML)

Oral


Liver Cancer

Oral


Thyroid Cancer

Oral

Carfilzomib (Onyx)

Multiple Myeloma

IV


Breast Cancer (SQ)

SQ

Lucanix (NovaRx)

Lung Cancer (NSCLC)

Inj.

Drug Use Route


Breast Cancer

Inj.

Omapro (Cephalon)

Leukemia (CML)

SQ

Perifosine (Keryx)

Multiple Myeloma

Oral

Regorafenib (Bayer)

Kidney Cancer

Oral


Bone Sarcomas

Oral


Lung Cancer (NSCLC)

Oral

Tivozanib (Aveo)

Kidney Cancer

Oral



Oral47




Drug Use Route

Axitinib (Pfizer)

Kidney Cancer

Oral

Biovax ID (Biovest)

Lymphoma (NHL)

SQ

Bositinib (Pfizer)

Leukemia (CML)

Oral


Liver Cancer

Oral


Thyroid Cancer

Oral

Carfilzomib (Onyx)

Multiple Myeloma

IV


Breast Cancer (SQ)

SQ

Lucanix (NovaRx)

Lung Cancer (NSCLC)

Inj.

Drug Use Route


Breast Cancer

Inj.

Omapro (Cephalon)

Leukemia (CML)

SQ

Perifosine (Keryx)

Multiple Myeloma

Oral

Regorafenib (Bayer)

Kidney Cancer

Oral


Bone Sarcomas

Oral


Lung Cancer (NSCLC)

Oral

Tivozanib (Aveo)

Kidney Cancer

Oral



Oral48



Oral Drugs for CancerAxitinib (Pfizer)

Indication: Renal Cell CarcinomaRoute: Oral (twice daily)Comments: Angiogenesis inhibitor; FDA

approval expected in April 2012

Ridaforolimus (Merck)Indication: Soft-Tissue and Bone SarcomasRoute: Oral (once daily x 5 days each week)Comments: mTOR inhibitor; Approval in April

2012

49


Hepatitis C Pipeline Trends

• Oral protease inhibitors hit the market• Watch for more direct acting antivirals• Novel interferons in 2-3 years

50


Hepatitis C Pipeline- Protease Inhibitors -

51

Drug Manufacturer Dosing* ApprovalVictrelis (boceprevir)

Merck TID May 13th

Incivek (telaprevir)

Vertex TID May 23rd

ABT-450 Abbott QD 2013TMC-435 Tibotec (J&J) /

MedivirQD 2013

ACH-1652 Achillion QD 2014BI-201335 Boehringer

IngelheimQD 2014

Vaniprivir Merck BID / QD 2014BMS-650032 Bristol-Myers Squibb BID / QD 2015Danoprevir InterMune /

GenentechTID / BID 2015

* TID = Three Times Daily; BID = Twice Daily; QD = Once Daily

Approved


Hepatitis C Pipeline- Polymerase Inhibitors -

52

Drug Manufacturer Dosing* ApprovalIDX-184 Idenix QD 2013mericitabine Roche BID 2014ANA-598 Anadys BID 2014Filibuvir Pfizer TID / BID 2014PSI-7997 Pharmasset QD 2014VX-222 Vertex BID 2014

* QD = Once Daily; BID = Twice Daily; TID = Three Times Daily


Hepatitis C Pipeline- Novel Interferons -

53

Drug Manufacturer Route Approval

Locteron Biolex SQ 2013Peg-Interferon Lambda

Bristol-Myers Squibb

SQ 2013

IFN-Alpha-2b XL Flamel Technologies

SQ 2014

Interferon Omega Boehringer Ingelheim

Implant 2014


Cystic Fibrosis Pipeline Trends

New drugs to:• Increase mucus clearance• Treat underlying disease• Fight lung infections

54


Cystic Fibrosis Pipeline

55


Ataluren PTC Therapeutics Oral 2012Aeroquin Mpex Inhaled 2012Arikase Transave Inhaled 2012Bronchitol Pharmaxis Inhaled 2012VX-770 Vertex Oral 2012



56



- Increase Mucus Clearance -



57



- Treat Underlying Disease -



58



- Fight Infections -


Other Drugs to Watch

59

Drug (Manufacturer)

Indication Route Approval

Soliris (Alexion) aHUS IV 10/07/11Iluvien (Alimera) DME Intra-

vitreal11/12/11

Eyela (Regeneron) AMD Intra-vitreal

11/18/11

rFactor XIII (Novo N.) FXIII Deficiency

IV 12/23/11

Velcade (Millenium) Multiple Myeloma

SQ 01/23/12

Corlux (Corcept) Cushing Disease

Oral 02/17/12

Peginesatide (Affymax)

Anemia IV/SQ 03/27/12

aHUS = Atypical Hemolytic Uremic Syndrome; DME = Diabetic Macular Edema; AMD = Age-related Macular Degeneration



60

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12






61

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12






62

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12






63

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12






64

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12






65

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12






66

Drug (Manufacturer)



vitreal11/12/11


11/18/11


IV 12/23/11


SQ 01/23/12


Oral 02/17/12





Questions?

67

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