Department of Health and Human Services
`Food and Drug Administration
`
`Form Awrevsdi OMB No. 0910-0513
`Expiration Date: 101'31l2016
`See OMB Statement on Page 3.
`
`PATENT INFORMATION SUBMITTED UPON AND
`
`AFTER APPROVAL OF AN NDA OR SUPPLEMENT
`
`For Each Patent That Claims a Drug Substance
`(Active ingredient), Drug Product (Formulation or
`Composition} and/or Method of Use
`
`ACTIVE INGREDIENTiS}
`treprostinil
`
`STRENGTHS)
`0.6 mglmL
`
`Inhalation solution
`
`July 30, 200
`
`This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) within thirty [30} days after
`approval of an NBA or supplement or within thirty {30) days of issuance of a patent as required by 21 CFR 314.53{c}(2}(ii) at the
`address provided in 21 CFR 314.53(d)(4). To expedite review of tfis patent declaration form, you may submit an additional copy of
`this declaration form to the Center for Drug Evaluation and Research “Orange Book" staff.
`
`If additional space is required for any narrative answer (i.e., one that does
`For hand-written or typewriter versions of this report:
`not require a “Yes' or "No' response), please attach an additional page referencing the question number.
`
`FDA will not list patent information if you file an incomplete patent (federation or the patent declaration indicates the patent
`is not eligible for listing.
`
`For each patent submitted for the approved NBA or supplement referenced above. you must submit all the information
`described below. if you are not submitting analr patents for this NBA or supplement, complete above section and sections 5
`and 6.
`
`1. GENERAL
`3. United States Patent Number
`
`9.358.240
`d.
`ame o atent 0 her
`United Therapeutics Corporation
`
`ent or representative who restdes or maln-
`a. Name o
`Isms a Steps of EGsrness wIIEIn the United States author-
`ized to receive notice of patent codification under seclion
`
`b. Issue Data at Patent
`
`c. Expiration Date of Patent
`
`June 7, 2016
`- dress fol Patent Owner}
`55 T.W. Alexander Drive
`
`May 5. 2028
`
`' capstan
`Research Triangle Park, North Carolina
`' ZIP Code
`' FAX Number filavarlable)
`27709
`(919)313-1293
`' Tetephone Number
`' E-Mail Address (if available)
`(919) 435-8350
`rmauthe@unither.com
`A -dress (at agent or representative named in 1.9.)
`
`505mm and till2llB) or the Federal Food, Drug, and
`Cosmetic Act and 21 CFR 314.52 and 314.95 (if patent
`owner or NDA applicantlholder does not reside or have a
`place of business within the United States)
`
`.
`
`i
`.
`C“? 51319
`
`' ZIP Code
`
`' FAX Number {it available)
`
`' Telephone Number
`
`' E-Mail Address {it available)
`
`
`
`. st e patent re renne- above a patent t at as oeen su-mitted prevnsly -r the
`approved NDA or supplement referenced above?
`I
`is patent re erenoe- an '
`.
`date a new expiration date?
`
`or Isting, Is
`
`eexpiratlon
`
`'
`
`FORM FDA 3542 (11:13}
`
`Page 1
`N MIIMK kn It“ 1 ”I I “iv-6‘10
`If}-
`
`UNITED THERAPEUTICS, EX. 2016
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR201T—01621
`Page 1 of4
`
`

`

`For the patent referenced above, provide the following information on each patent that claims the drug substance. drug
`product. or method of use that is the subject of the approved NBA or supplement. FDA will not list patent information i!
`you file an incomplete patent declaration or the patent declaration indicates the patent is not eligible for listing. FDA will
`consider an incomplete patent declaration to be a declaration that does not include a response to all the questions
`contained within each section below applicable to the patent referenced above.
`
`2. Drug Substance {Active Ingredient}
`2.1 Does the patent claim the drug substance that is the active ingredient in the dmg product
`described in the approved NDA or supplement?
`
`2.2 Does the patent claim a drug substance that is a different poiymorph of the active
`ingredient described in the NBA?
`
`2.3 It the answer to question 2.2 is “Yes.“ do you oertily that. as of the date of this declaration. you have test data
`demonstrating that a drug product containing the polymorph will perform the same as the dmg product
`
`described in the NBA? The type oftest data required is described at 21 CFR 314.53(h). D Yes
`2.4 Specify the polymorphic formts) claimed by the patent for which you have the test results described in 2.3.
`
`2.5 Does the patent claim only a metabolite of the approved active ingredient? (Complete the intormation in
`section 4 below if the patent claims an approved method of using the approved drug product to administer
`the metabolite.)
`
`[I Yes
`
`2.8 Does the patent claim only an intermediate?
`
`2.7 If the patent relerenced in 2.1 is a product-by-process patent. is the product claimed in the
`patent novel? (An answer is required only if the patent is a pmduct-by-prooess patent.)
`
`
`
`FDA will not list the patent in the Orange Book as claiming the drug substance it:
`. the answers to 2.1 and 2.2 are "No." or,
`the answer to 2.2 is “Yes“ and the answer to 2.3 is ”No." or,
`the answer to 2.3 is “Yes“ and there is no response to 2.4. or.
`the answer to 2.5 or 2.6 Is "Yes."
`the answer to 2.? is ”No."
`
`3. Drug Product {CompositioniFonnutatlon}
`3.1 Does the patent claim the approved drug product as defined in 21 CFR 314.3?
`
`3.2 Does the patent claim only an intermediate?
`
`3.3 If the patent relerenced in 3.1 is a product-by-process patent. is the product claimed in the
`patent novel? (An answer is required only it the patent is a pmduct-by-prooess patent.)
`FDA will not list the patent in the Orange Book as claiming the drug product If:
`' the answer to question 3.1 is "No." or.
`' the answer to question 3.2 is "Yes.“ or.
`. the answer to question 3.3 is “No."
`4. Method of Use
`
`Sponsors must submit the information in section 4 for each approved method of using the approved drug product claimed by the patent.
`For each approved method of use claimed by the patent, provide the following inbrn'ration:
`4.1 Does the patent claim one or more approved methods of using the approved drug product?
`
`Yes
`
`D No
`
`4.2 Patent Claim Numberls) {as tieredrh the patent)
`1_g
`4.2a It the answer to 4.2 is
`
`Does (Do) the patent claimle) reterenced in 4.2 claim an
`|:| No
`Yes
`approved method of use of the approved drug product?
`Use: (Submit indication ormethad of use inlarmalrbn as identified specifically in the approved labeling.)
`
`“Yes? identify the U99
`“‘“h 599m" ”$33“?
`me app'med la
`"‘9 or
`the drug product.
`
`Tyvaso is a prostacyclin vasodilator indicated for the treatment of pulmonary
`arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Tyvaso is intended
`for oral inhalation using the Tyvaso Inhalation System. which consists of an ultrasonic.
`.
`.
`.
`.
`pulsed delivery dewce and Its accessories.
`
`FORM FDA 3542 {11i13}
`
`Page 2
`
`UNITED THERAPEUTICS. EX. 2016
`WATSON LABORATORIES V. UNITED THERAPEUTICS. IPR2017-D1621
`Page 2 0M
`
`

`

`4.2b If the answer to 4.2 is
`'Yas.‘ also provide the
`
`Use: (Submit the description of the approved indication or method of use that you propose FDA include as
`the ”Use Code'in the Orange Boolr. using no more than 240 total characters including Spaces.)
`
`'"formai'm 0" “‘9
`indication or method of
`use for the Orange Book
`“Use Code” description.
`
`Method of treating pulmonary hypertension by administering treprostinil or a salt thereof by
`.
`.
`.
`.
`Inhalation usin a detrice
`9
`
`FDR wlll not list the patent in the Orange Book as clalmlng the method of use if:
`' the answerte question 4.1 or 4.2 is ”No,“ or
`' itthe answer to 4.2 is "Yes“ and the information requested in 4.2a and 4.2b is not provided in full.
`
`5. No Relevant Patents
`
`For this MBA or supplement. there are no relevant patents that claim the approved drug substance (active
`ingredient) or the approved drug product (formulation or composition) or approved method{s) of use with
`respect to which a claim of patent intringement could reasonably be asserted ifa person not licensed by the
`owner of the patent engaged in the manufacture. use. or sale of the dmg product.
`
`6. Declaration Certification
`
`
`6.1 The undersigned declares that this is an accurate and complete submission of patent information for the NBA or
`supplement approved under section 505 of the Federal Food, Drug. and Cosmetic Act. This time-sensitive patent
`information is submitted pursuant to 21 CFR 314.53. fattest that tam familiar with 21‘ CFR 314.53 and this submission
`complies with the requirements of the regulation. l verify under penalty of perjury that the foregoing is true and
`correct.
`
`Warning: A willfully and knowingly false statement Is a criminal offense under 18 U.S.C. 1001'.
`Authorized Signature of NBA ApplicantlHolder or Patent Owner (Attorney. Agent. Representative or
`Date Signed
`other Authorized Official) (Provide information below)
`Dig‘talv signed by manhofiunnhor com
`DN m=rrnmre®uni
`.m.
`'
`Dan zoicmee OEDGOI 04W
`rma Ulhe@un ltheLoom m—Wmvzcmm
`
`06i08i’201 6
`
`NOTE: ItinlgiI an NBA applicantlholder may submit this declaration directliiI to the FDA. A patent owner who is not the NDA applicantl holder
`is authorized to sign the declaration but may not submit it directly to FDA. 21 CFR 314.531c)(4) and (dim.
`
`Cheok applicable box and provide information below.
`
`x NOA ApptioanUHolder
`
`l
`
`_ NOR Applicant'slHolder‘s Attomev. Agent (Representative) or other
`Authorized O‘Hicial
`
`7 Patent Owner
`
`' Name
`
`§_- Patent Owner's Attomev. Agent (Representative) or Other Authorized
`Official
`
`
`
`Rex Mauthe, Vice President. RegulatOry Affairs. United Therapeutics Corp
`' Address
`' CityiState
`55 T.W. Alexander Drive
`Research Triangle Park. North Carolina
`
`i ZIP Code
`27709
`i Fifi-Number '(if'avaiiafiiej'
`(919) 3134298
`
`' Telephone Number
`(919) 485-8350
`' E-Mail Address fifevailable)
`rmauthe@unither.oom
`
`This section applies only lo mquinmtmlLs of the Paperwork Reduction Aclol 1995.
`“DO NOT SEND YOI‘R COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW'.‘
`
`'l'hc butdcn timic for this collection of information is cslilmlod to average 5 hours per I‘cspmlsc. including the lime to
`review instructions. search csisling data sources. gather and maintain the data needed and. complclc and review the
`collection of inl'onnntinn. Send comments regarding [his burden estimate or any other uspccl ol'this information collection.
`including suggeslions for reducing this burden. to:
`Department of Health and Human Scn'icci:
`lined and Drug hdniinistratimi
`Office of Chief Inlbrn'lalion Olliccr
`Paperwork Reduction Act [PRA] Staff
`PR.-lStofl{‘rkfdn.iiiiLngv
`
`":lli ugc'nqv hilly not conduct or .rpmimi‘.
`amt n pit-ram! f.‘ rial required to l‘lik'llmli'l't! to, (l
`colic-chm: (Jinfemlulmn unit-Ex it dri‘pii'ujr: u
`ciri'rt'ntlr valid (ll-{B innrrlwi'. "
`
`FORM FDA 3542 {11l13}
`
`Page 3
`
`UNITED THERAPEUTICS, EX. 2016
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR201T—D1621
`Page 3 of4
`
`

`

`INFORMATION AND INSTRUCTIONS FOR FORM 3542
`
`PATENT INFORMATION SUBMITTED UPON AND AFTER
`APPROVAL OF AN NDA OR SUPPLEMENT
`
`General Information
`
`2. Drug Substance (Active Ingredient)
`
`Complete all items in this section ifthe patent claims the drug
`substance that is the subject of the approved NDA or supplement.
`
`2'4) Name the Pmymmphic mm 0m“: drug idmfificd by 1h“
`palcnl.
`
`2.5) A patent for a metabolite oflhe approved active ingredient
`may not be listed. It'the patent claims an approved method
`of using the approved drug product to administer the
`
`metabolite. the patent may be listed as a method ofuse_ _ _
`
`
`Palm depending on the responses I“ scum“ 4 ofthts [mm-
`
`2.?) Answer this question only it" the patent is a product—
`
`process patent.
`.
`.
`.
`3' Drug Product (Composttiont'Formulatton)
`Complete all items in this section it'the patent claims the drug
`product that is the subject ot'the approved NDA or suppltnnent.
`33) An answer to this question is required only il‘the referenced
`patent is a product-by-process patent.
`
`4. Method of Use
`Complete all items in this section if the potent claims one or more
`tttcthods of use of the drug product that is the subject ol'the
`approved NDA or supplement.
`
`4.2)
`
`4.2
`
`.
`_
`For each approved use at the drug claimed by the Patent
`identity by number the claim[s) in the patent that claim the
`approved use ol'the drug. An applicant may list together
`multiple patent claim numbers and information for each
`approved method «(use if applicable litrwsvcr. cath‘
`“Rpm“? method “I "3'3 must be separately ltsted wtthm
`thls socllun ofthc form.
`th t
`ll be]'
`d t'th
`ldcnt'
`th
`'.
`a) descrilicy “Riggs-1:: 1h:patsiiiflrnfi‘eihtii ofliiiie. a
`4.2b} 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 ol‘ use patent that claims an appnwed
`ntcthod of using a drug product. Each approved tnethod 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 ofuse
`patent claims a method close for which the 505(b)(2) or
`ANDA applicant is not seeking approval. Use a maximum of
`240 Characters I'Ol‘ saith "use code."
`5. No Relevant Patents
`
`describes the authorized signature.
`
`' To submit patent information to the agency the appropriate
`patcnt declaration tbrrn must be used. 'l'wo t'onns are available
`for patent submissions. 'llte approval status of your New Dmg
`Application will dctentiine which form you should use.
`
`Form 3542a should be used when submitting patent information
`with original NDA submissions. NDA amendments and NBA
`supplements prior to approval.
`
`_
`v
`v
`i
`‘\
`\
`\ \
`v
`-
`3
`I
`Iorm 542 should bt. used after NDA or \llpplLl‘llLl‘ll approval
`This form is to be submitted within 30 days after approval of an
`application. This form should also be used to submit patent
`infonnation relating to an approved supplement under 2] Cl-‘R
`3 l4.53(d) to change the fonnulation, add a new indication or
`other condition ofuse. chain c the strcn th. or to make an other
`patented change regarding the drug. dnigg product. or any 3'
`method of use. Form 3542 is also to ht: used for patents issued
`alter dmg approval. Patents issued atler drug approval are
`required to be submitted within 30 days ofpatcnt issuance For
`the patent to be considered ”timely tiled."
`
`' Only intbrmation front form 3542 will be used tor Orange Book
`publication purposes.
`
`' Forms 5'10"” be submitted as described in 2' CFR 314-53-
`Sending an additional copy ot‘fonn 3542 to the Orange Book
`Stal'fwill expedite patent publication in the Orange Book. The
`Orange Book Staffaddress [as of April 200?) is: Orange Bmk
`Stall‘. Ollicc ofGencric Drugs OGDEHFD-olfl. 1620 Standish
`Place, Rockville, MD 20851
`
`' the receipt date is the date that the patent intitrmulion is date
`stamped in the central document rootn. Patents are considered
`listed on thc date received.
`
`' Additional copies ot‘ these Tomts may be downloaded from the
`Internet at:
`ittrprfx‘tt'u'wfdtagotchimestrift"mechaicesxfifqfiimrsf
`qufiumchrml.
`.
`'
`hr“ Sectltlll
`Complete all items in this section.
`
`1. General Section
`
`Complete all items in this section with reference to the patent
`.
`.
`'lsuli'
`let include patent expiration date. including any llatch-Waxnutn
`patent extension already granted. Do not include any
`applicable pediatric exclusivity. The agency will include
`pediatric esclusivilies where applicable upon publication.
`
`Id] include full address ofpatcnt corner. 11' patent owner resides
`outside the US. indicate the country in the zip code block.
`
`lc} Answer this question ifapplicablc. lt‘patcnl ovmcr and NDA
`applicantt’holdcr reside in the United States. leave space
`blank.
`
`Complete this section only il‘applicablc.
`
`6' Declaratlon Cet'tll'teatlttn
`Ctm‘tplete all items in this section.
`6.2} Authorized signature. Check one of the four boxcs that best
`
`FORM FDA 3542 (11:13)
`
`Page 4
`
`UNITED THERAPEUTICS, EX. 2016
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR201T—01621
`Page 4 0M
`
`