UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`AKORN, INC.
`
`
`Petitioner
`
`V.
`
`
`
`
`
`
`SEN] U PHARMACEUTICAL CO., LTD.
`
`
`
`
`MITSUBISHI CHEMICAL CORPORATION
`
`
`
`Patent Owner
`
`
`
`
`Case IPR2015-01205
`
`
`Patent 6, 1 14,319
`
`
`
`
`
`
`
`
`DECLARATION OF DIANE PANG REGARDING AUTHENTICATION OF
`
`
`
`
`OMNIPREDTM (PREDNISOLONE ACETATE OPHTHALMIC
`
`
`SUSPENSION) LABEL
`
`
`
`
`
`
`
`
`
`
`
`
`
`SENJU-MITSUBISHI 2081
`
`

`
`
`
`
`IPR2015-01205
`
`
`
`
`
`U.S. Patent No. 6,114,319
`
`
`
`
`
`Declaration of Diane Pang
`
`
`
`
`
`
`Exhibits Referenced In This Declaration
`
`
`
`
`
`T
`
`A
`
`
`
`
`
`
`
`
`
`Printout of “omnipred” search results from
`
`
`“Drus I FDA” database
`
`
`
`
`
`
` Label for Omnipredm (prednisolone acetate ophthalmic
`
`susension
`
`
`
`
`
`

`
`
`
`IPR2015—01205
`
`
`
`
`
`U.S. Patent No. 6,114,319
`
`
`
`
`
`Declaration of Diane Pang
`
`
`1.
`
`
`2.
`
`
`
`
`
`
`
`
`
`
`
`
`I, Diane Pang, am an attorney at O’Melveny & Myers LLP.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Exhibit A is a true and correct copy of the search results for
`
`
`
`
`
`
`
`
`
`
`
`
`
`“omnipred” that I obtained from the “Drugs@FDA” database on June 22, 2016.
`
`
`3.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Exhibit B is a true and correct copy of the Omnipredm (prednisolone
`
`
`
`
`
`
`
`
`
`
`
`acetate ophthalmic suspension) Label that I obtained from the “Drugs@FDA”
`
`
`
`
`
`
`database on June 22, 2016.
`
`
`4.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`I declare under penalty of perjury under the laws of the United States
`
`
`
`
`
`
`that the foregoing is true and correct. This declaration is executed this 22"“ day of
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`June, 2016, at Newp_qrt Beach, California.
`
`
`
`
`
`
`
`
`
`

`
`Exhibit A
`
`
`
`

`
`|'Jn.lgs@i-‘DA: FDA Approved Drug Products
`
`
`
`
`
`
`
`
`|“li ilii i". H I
`
`
`
`:1 ll) '—.‘.'. -1..
`
`
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`q)
`l Pr,
`film] _=m«_'i 5-“i.
`‘ flijl M3 Y-_1:;r' lii:~a‘th
`
`
`
`
`
`
`
`A lo I lndo:
`
`
`
`
`
`
`iollow FDA
`
`
`
`
`in fspanol
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Medical Devices Radiation-Emitting Products Veccinee, Blood a. Biologic:
`
`
`
`
`
`
`
`
`
`
`
`
`
`Animel&Ve1erlnery Cosmetics
`
`
`
`
`
`Tobacco Product:
`
`
`
`
`0 FDA Home 0 Drug Dalabases 0 Drugs@FDA
`
`
`
`
`
`
`
`
`
`DIega@lM
`
`FDA Approved Drug Products
`
`
`
`
`
`
`Slarl Over
`
`
`
`
`
`
`Drug Details
`
`Drug Neme(e)
`
`
`FDA Application No.
`
`
`
`Active lngredlentiei
`
`
`
`Company
`
`
`Original Approval or Tentative Approval Deie
`
`
`
`
`
`
`
`
`Chemical Type
`
`
`Review cl eeelfioeiion
`
`
`
`FAQ |
`
`
`instructions | Glossary | Coniaci Ue
`
`
`
`
`
`Id_.
`
`9 Email Link
`
`
`
`
`OMNIPHED
`
`(RDA) 017459
`
`
`PFIEDNISOLONE ACETATE
`
`
`
`ALCON
`
`
`
`July 10. 1973
`
`
`
`5 New formulation or new manufacturer
`
`
`
`
`
`
`
`5 Standard review drug
`
`
`
`
`
`0 Therepeutlc Equivalents
`
`
`I Approval l-iieiory, Lenere, Reviews. end Related Documents
`
`
`
`
`
`
`
`
`0 Label Infonnetion
`
`
`
`Products on Applicefion (NDA) #011459
`
`
`
`
`
`CHOU! on I COIl.l|'I'|I‘I HOIUOI’ I0 l‘I-I001 {HO IIDII:
`
`
`
`
`
`
`
`
`
`
`
` AcflveIngredients
`
`
`
`
`
`
`
`
`
`
`
`DoeegeForrriiflome
`
`
`
`
`
`
`
`
`
`1 SUSPENSIONIDFIOPSDPHTHALMIC
`
`
`
`
`Back to Top | Back to Previous Page | Back to Drugs@FDA Home
`
`
`
`
`
`
`
`
`
`
`
`
`
`rlteling
`
`Statue
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DMNIPRED
`
`
`PHEDNISOLONE ACETATE
`
`
`Disclaimer
`
`
`FDNCenter for Drug Evaluation and Research
`
`
`
`
`
`Office of Communications
`
`
`
`Division oi Online Communications
`
`
`
`
`U pdaie Frequency: Daily
`
`
`
`
`
`
`Halo: If you need help accessing information in different file formats, see lnstmcilons for Downloading Viewers and Players.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Accessibility
`
`
`
`
`Contact FDA
`
`
`
`
`
`Careers
`
`
`FDA Basics
`
`
`
`FOIA
`
`
`No FEAR Act
`
`
`
`
`i
`
`
`
`sure Map
`
`
`
`Transparency
`
`
`website Policies
`
`
`
`
`
`
`
`
`U.S. Food and Drug Administration
`10903 New Hampshire Avenue
`
`
`
`
`Silver Spring. MD 20993
`
`
`
`
`Ph. 1-B8B~|NFO-FDA (1—B8B-463-6332)
`
`
`
`
`
`
`
`
`
`Conlacl FDA
`
`
`
`cernialrleilon Producie
`
`
`Advisory Commmeee
`
`
`Science I fleeeerch
`
`
`Regulatory Information
`
`
`Seieiy
`
`
`hnp::‘.'w\.vw..1ocessdatu,fda.guv/scriptsicdenicirugsalfdaiindcx.cfm'?t'uscac1ion=Search.DrugDe1aiis[6.’22i’).0I6 2: 16:32 PM]
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`¢ U.S.Dcparh11a1t of Hulfll I. Hurnen Sc-vloee
`
`
`
`
`
`
`
`
`

`
`Dru3s@FDA: FDA Approved Drug ?rochIcls
`
`
`
`
`
`
`
`
`
`
`
`Forflavnrnmont
`
`
`
`
`f
`
`
`
`ForPrIu
`
`
`
`
`
`
`
`
`
`
`
`|m“‘EEm'"m
`
`
`
`Tnlnlng and continuing Education
`
`
`
`
`Impoenuwcamplunco
`
`Shh I LDCII Olficlfll
`
`
`
`conaumorl
`
`
`Industry
`
`Hum Protoulomls
`
`
`FDA Arulllvu
`
`
`
`hnp:lfwww.Iccessd.In.fda.govfscI'ipIsIodu.'drugn!fdIlindex.cfm?fuseaction=Seuch.Dn1gDeuils[6J22l2Ol6 2:16:32 PM]
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`
`
`Exhibit B
`
`

`
`NDA 1 7-469/S-040
`
`
`
`
`
`Page 3
`
`
`
`
`
`
`
`0mnipred'““ (prednisolone acetate ophthalmic suspension)
`
`
`
`
`
`
`
`
`
`
`DESCRIPTION: 0mnipred"' (prednisolone acetate ophthalmic suspension) is an adrenocortical
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`steroid product prepared as sterile ophthalmic suspension. The active ingredient is represented by the
`chemical structure:
`
`
`
`CHEMICAL STRUCTURE
`
`
`
`
`
`
`
`
`
`Established name:
`
`
`
`
`Chemical name:
`
`
`Prednisolone Acetate
`
`
`
`
`
`
`
`
`
`
`Pregna—1,4-diene-3,20-dione,21-(acetyloxy)-1 1,17-dihydroxy-,(l 1B)-.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Each mL contains: Active: prednisolone acetate 1.0%. Preservative: benzalkonium chloride 0.01%.
`
`
`
`
`
`
`
`
`
`
`Vehicle: hypromellose. Inactives: dibasic sodium phosphate, polysorbate 80, edetate disodium,
`
`
`
`
`
`
`
`
`
`
`
`
`glycerin, citric acid and/or sodium hydroxide (to adjust pH), purified water.
`
`
`
`
`
`
`
`
`
`
`
`
`CLINICAL PHARMACOLOGY: Corticosteroids inhibit the inflammatory response to a variety of
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary
`
`
`
`
`
`
`
`
`
`
`dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`and scar formation associated with inflammation. There is no generally accepted explanation for the
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the
`
`
`
`
`
`
`
`
`
`
`
`
`
`induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is
`
`
`
`
`
`
`
`released from membrane phospholipids by phospholipase A2.
`
`
`
`
`
`
`
`
`
`
`Corticosteroids are capable of producing a rise in intraocular pressure.
`
`
`
`
`
`
`
`
`
`
`
`
`INDICATIONS AND USAGE: Steroid responsive inflammatory conditions of the palpebral and
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`bulbar conjunctiva, cornea, and anterior segment of the globe such as allergic conjunctivitis, acne
`
`
`
`
`
`
`
`
`
`
`
`rosacea, superficial punctate keratitis, herpes zoster keratitis, iritis, cyclitis, selected infective
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`conjunctivitides, when the inherent hazard of steroid use is accepted to obtain an advisable diminution
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`in edema and inflammation; corneal injury from chemical, radiation, or thermal burns, or penetration
`
`
`
`of foreign bodies.
`
`
`
`
`
`
`
`
`
`CONTRAINDICATIONS: 0mnipredTM (prednisolone acetate ophthalmic suspension) is
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and
`
`
`
`
`
`
`
`
`
`
`
`
`fungal diseases of ocular structures. 0mnipredT'“ (prednisolone acetate ophthalmic suspension) is also
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of
`
`
`
`

`
`NDA 1 7-469/S-040
`
`
`
`
`
`Page 4
`
`
`
`
`
`
`
`
`
`this preparation and to other corticosteroids.
`
`
`
`
`
`
`
`
`
`
`
`
` S: FOR TOPICAL OPHTHALMIC USE ONLY. Prolonged use of corticosteroids may
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in
`
`
`
`
`
`
`
`
`
`
`
`
`
`posterior subcapsular cataract formation. Prolonged use may also suppress the host immune response
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`and thus increase the hazard of secondary ocular infections. Various ocular diseases and long-term use
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation. Acute purulent
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`infections of the eye may be masked or activity enhanced by the presence 0
`teroid medication.
`o
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`If this product is used for 10 days or longer, intraocular pressure should b
`monitored even
`
`
`ou h it ma be
`icult m c 1
`ren and unCOOpf;Eil:tE_pi;£i(3_rl1C_S. Steroids should be used with caution
`1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`in the presence of glaucoma.
`
`
`
`
`
`
`intraocular pressure should be checked fiequently.
`
`
`
`o
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The use of steroids after cataract surgery may delay healing and increase the incidence of bleb
`
`fonnation.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is
`recommended.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Corticosteroids are not effective in mustard gas keratitis and Sjt5gren’s keratoconjunctivitis.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`PRECAUTIONS: General: The initial prescription and renewal of the medication order should be
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`made by a physician only after examination of the patient with the aid of magnification, such as slit
`
`
`
`
`
`
`
`
`
`
`
`
`
`lamp biomicroscopy and, where appropriate, fluorescein staining. If signs and symptoms fail to
`
`
`
`
`
`
`
`
`
`
`improve after two days, the patient should be re-evaluated.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`As fungal infections of the cornea are particularly prone to develop coincidentally with long-term local
`
`
`
`
`
`
`
`
`
`
`
`
`corticosteroid applications, fungal invasion should be suspected in any persistent corneal ulceration
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`If this product is used for 10 days or longer, intraocular pressure should be monitored (SEE
`
` S).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Information for Patients: If inflammation or pain persists longer than 48 hours or becomes
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`aggravated, the patient should be advised to discontinue use of the medication and consult a physician.
`
`

`
`NDA 17-469/S-040
`
`
`
`
`
`Page 5
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`This product is sterile when packaged. To prevent contamination, care should be taken to avoid
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`touching the bottle tip to eyelids or to any other surface. The use of this bottle by more than one person
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`may spread infection. Keep bottle tightly closed when not in use. Keep out of the reach of children.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility: No studies have been conducted in animals
`
`
`
`
`
`
`
`
`
`
`or in humans to evaluate the potential of these effects.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Pregnancy: Teratogenic effects. Pregnancy Category C. Prednisolone has been shown to be
`
`
`
`
`
`
`
`
`
`
`
`
`teratogenic in mice when given in doses 1-10 times the human dose.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Dexamethasone, hydrocortisone and prednisolone were ocularly applied to both eyes of pregnant mice
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`five times per day on days 10 through 13 of gestation. A significant increase in the incidence of cleft
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`palate was observed in the fetuses of the treated mice. There are no adequate and well controlled
`
`
`
`
`
`
`
`
`
`
`
`studies in pregnant women. 0mnipred'““ (prednisolone acetate ophthalmic suspension) should be used
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`during pregnancy only if the potential benefitjustifies the potential risk to the fetus.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Nursing Mothers: It is not known whether topical administration of corticosteroids could result in
`
`
`
`
`
`
`
`
`
`
`
`sufficient systemic absorption to produce detectable quantities in human milk. Systemically
`
`
`
`
`
`
`
`
`
`
`
`
`administered corticosteroids appear in human milk and could suppress growth, interfere with
`
`
`
`
`
`
`
`
`
`
`
`
`
`endogenous corticosteroid production, or cause other untoward effects. Because of the potential for
`
`
`
`
`
`
`
`
`
`
`
`
`
`serious adverse reactions in nursing infants from prednisolone acetate, a decision should be made
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`whether to discontinue nursing or to discontinue the drug, taking into account the importance of the
`
`
`
`
`drug to the mother.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly
`
`
`
`and younger patients.
`
`
`
`
`
`
`
`
`
`
`
`
`
`ADVERSE REACTIONS: Adverse reactions include, in decreasing order of frequency, elevation of
`
`
`
`
`
`
`
`
`
`
`
`
`
`intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage,
`
`
`
`
`
`
`
`
`posterior subcapsular cataract formation, and delayed wound healing.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Although systemic effects are extremely uncommon, there have been rare occurrences of systemic
`
`
`
`
`
`
`hypercorticoidism after use of topical steroids.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Corticosteroid-containing preparations have also been reported to cause acute anterior uveitis and
`
`
`
`
`
`
`
`
`
`
`perforation of the globe. Keratitis, conjunctivitis, corneal ulcers, mydriasis, conjunctiva] hyperemia,
`
`
`
`

`
`NDA l7-469/S-040
`
`
`
`
`
`Page 6
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`loss of accommodation and ptosis have occasionally been reported following local use of
`corticosteroids.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The development of secondary ocular infection (bacterial, fungal and viral) has occurred. Fungal and
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`viral infections of the cornea are particularly prone to develop coincidentally with long-tenn
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`applications of steroid. The possibility of fungal invasion should be considered in any persistent
`
`
`
`
`
`
`
`
`
`
`corneal ulceration where steroid treatment has been used (SEE WARNINGS).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DOSAGE AND ADMINISTRATION: SHAKE WELL BEFORE USING. Two drops topically in
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`the eye(s) four times daily. In cases of bacterial infections, concomitant use of anti-infective agents is
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`mandatory. Care should be taken not to discontinue therapy prematurely. If signs and symptoms fail to
`
`
`
`
`
`
`
`
`
`
`
`
`improve after two days, the patient should be re-evaluated (SEE PRECAUTIONS).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The closing of OmnipredT" suspension may be reduced, but care should be taken not to discontinue
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`therapy prematurely. In chronic conditions, withdrawal of treatment should be carried out by gradually
`
`
`
`
`
`decreasing the fiequency of applications.
`
`
`
`
`
`
`
`
`
`
`
`
`
`HOW SUPPLIED: OmnipredTM (prednisolone acetate ophthalmic suspension) is supplied in a white,
`
`
`
`
`
`
`
`
`
`
`
`
`
`round low density polyethylene DROP-TAlNER® dispenser with a natural low density polyethylene
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`dispensing plug and pink polypropylene cap. Tamper evidence is provided with a shrink band around
`
`
`
`
`
`
`
`
`the closure and neck area of the package.
`'
`
`
`
`Omnipred“'s suspension:
`
`
`
`5 mL NDC 0065-06378-27
`
`
`
`
`10 ml. NDC 0065-06378-25
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`STORAGE: STORE at 8° - 24°C (46° - 75°F) in an UPRIGHT position.
`
`
`Rx Only
`
`
`
`
`ALCON LABORATORIES, INC.
`
`
`
`
`
`Fort Worth, Texas 76134 USA
`
`Printed in USA
`
`
`
`
`
`©2006 Alcon, Inc.
`
`Revised: June 2006
`
`
`
`9001774-0706