CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`
`22-3 87
`
`ADMINISTRATIVE and CORRESPONDENCE
`
`DOCUMENTS
`
`

`

`Food and Drug Administration
`
`PATENT INFORMATION SUBMITTED WITH THE FlLlNG
`OF AN NDA, AMENDMENT, OR SUPPLEMENT
`
` Department of Health and Human Services
`
`
`
`
`Form Approved: OMB No. 0910-0513
`
`
`Expiration Date: 7/31/10
`See OMB Statement on Page 3.
`
`
`NDA NUMBER
`
`22387
`
`
`
`NAME OF APPLICANT/NDA HOLDER
`
`
`
`For Each Patent That Claims 3‘ Drug Substance
`
`United Therapeutics Corp
`(Active ingredient), Drug Product (Formulation and Composition)
`
`
`and/or Method of Use
`
`
`
`
`The following is provided in accordance with Section 505(
`b} and (c) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`
`
`TYVASO (Proposed)
`
`
`
`ACTIVE lNGREDlENTtS)
`STRENGTH(S)
`
`
`
`treprostinil sodium
`0.6 nag/ml
`
`
`
`
`
` DOSAGE FORM
`
`
`inhalation Solution
`
`
`
` This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application,
`
`amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53(d)(4).
`
`
`
`Within thirty (30) days after approval of an NDA or supplement, or within thirty (30) days of issuance ota new patent, a new patent
`
`
`declaration must be submitted pursuant to 21 CFR 314.53(c)(2)(ii) with all of the required information based on the approved NDA or
`
`
`
`supplement. The information submitted in the declaration form Submitted upon or after approval will be the only information relied
`upon by FDA for listing a patent in the Orange Book.
`
`
`
`' For hand-written or typewriter versions (only) of this report: lfadditional space is required for any narrative answer(i.e., one that
`3 does not require a “Yes“ or "No" response). please attach an addltional page referencing the question number.
`
`
` FDA will not list patent information if you submit an incomplete patent declaration or the patent declaration indicates the
`
`patent is not eligible for listing.
`.
`
`For each patent submitted for the pending NDA, amendment, or supplement referenced above, you must submit all the
`information described below. if you are not submitting any patents for this pending NDA, amendment, or supplement,
`complete above section and sections 5 and 6.
`1. GENERAL
`
`a. United States Patent Number
`b. issue Date of Patent
`' c. Expiration Date of Patent
`
`5,153,222
`-
`Oct. 06, 1992
`Oct. l6, 3014
`d. Name of Patent Owner
`Address {ofPatent Owner)
`.
`_
`.
`.,
`.
`1735 Connecticut Avenue, NW
`Third Floor
`United Therapeutics Corporation
`
`City/State
`Washington. DC
`
`ZIP Code
`”
`i
`'
`l FAX Number(il’available)
`2.0009
`-.
`_ ‘ (202‘) 483-4005
`Telephone Number
`E-Mail Address (ifavallable)
`
`(202) 483—7000
`e. Name of agent or representative who resides or maintains Address (ofagent 07 representative named in 1.9.)
`a place of business within the United States authorized to
`, Not Applicable
`receive notice of patent certification under section 505(b)(3)
`and (j)(2)(B) of the Federal Food, Drug, and Cosmetic Act ~7—-
`and 21 CFR 314.52 and 314.95 (it patent owner or NDA
`C'W’Sta‘e
`applicant/holder does not reside or have a place of
`
`_...__m
`business within the United States)
`ElP'Code
`--
`FAX Number (if available)
`as
`’
`
`I E—Mail Address (ifavailable) '
`Telephone Number
`
`is the patent referenced above a patent that has been submitted previailsiy‘i‘aiifié‘"""""""
`H
`f.
`approved NDA or supplement referenced above? Z] No [:1 Yes
`
`
`if the patent referenced above has been submitted previously for listing, is the expiration
`_
`date a new expiration date?
`E] No
`FORM FDA 3542a (7707)
`
`
`
`._
`
`
`
`9.
`
`[I Yes
`
`Page 1
`USC erphirs (SOD-554090
`ET:
`
`

`

`
`
`For the patentreferenced ab0ve, provide the following information on the dru
`use that is the subject of the pending NDA, amendment, or supplement.
`
`2. Drug Substance (Active ingredient»)
`
`
` 2.1 Does the patent claim the drug substance that is the active ingredient in the drug product
`described in the pending NDA, amendment, or supplement?
`[:3 Yes
`No
`
`
`
`
`
`2.2 Does the patent claim a drug substance that is a different polymorph ot the active
`_
`
`
`D Yes
`ingredient described in the pending NDA. amendment, or supplement?
`[fig] No
`
`
` 2.3 if the answer to question 2.2 is "Yes," do you certify that. as oi the date of this declaration. you have test
`
`data demonstrating that a drug product containing the polymorph will perform the same as the drug product
`
`
`E} No
`D Yes
`described in the NBA? The type of test data required is described at 7.1 CFR 314.53lb).
`
`
`aulls described in 2.3.
`
`
`
`D Yes
`
`
`
`
`2.5 Does the patent claim only a metabolite of the active ingredient pending in the NbA or supplement?
`(Complete the information in section 4 below it the patent claims a pending method of using the pending
`drug product to administer the metabolite)
`5‘ Yes
`Z! No
`
`
`2.6 Does the patent claim only an intermediate?
`Z} No
`
`
`2.7 it the patent referenced in 2.1 is a product-by-process patent. is the product claimed inthe
`_
`
`patent novel? (An answer is required only if the patent is a product-by-process patent.)
`CI Yes
`t] No
`W...
`
`
`
`
`3. Drug Product (Compositioanon-nuiation)
`. 3.1 Does the patent claim the drug product. as defined in 21 CFR 314.3, in the pending NDA. anteridrne-nt,"
`
`
`or supplement?
`:I No
`C] Yes
`
`
`
`3.2 Does the patent claim only an intermediate?
`
`
`
` 3.3 lithe patent referenced in 3.1 is a product~hy-process patent, is the product claimed in the
`
`patent novel? (An answer is required only if the patent is a product-by--process patent.)
`[:1 Yes
`'2] No
`
` 4. Method of Use
`
`
`
`
`4.1 Does the patent claim one or more methods of use for which approval is being sought in
`the pending NDA, amendment, or supplement?
`E! Yes
`E] No
`
`
`
`l Does (Do) the patent clalm(s) referenced in 4.2 claim a
`4.2 Patent Claim Number(s) (as listed in the patent)
`pending method of use for which approval is being sought
`
`D No
`Q] Yes
`1 Md 2
`in the pending NDA, amendment, or supplement?
`
`
`
`
`4.2a if the answer to 4.2 is
`Use: (Submitindicalion or'melhod of use information as identified specifically in the proposed labeling.)
`"Yes." identify with speci-
`
`
`ficity the use with refer-
`~
`TYVASO 15 indicated for the treatment ofpulmonary arterial hypertension in patients with NYHA Class Ill
`
`‘-‘ symptoms.
`
`ence to the proposed
`
`
`.
`.
`.
`,
`i
`_
`.
`‘
`labeling for the drug
`,
`I
`.
`‘
`
`product.
`T‘r VASO is intended tor oral inhalation use With an ultrasonic pulsaled Optlneb-u' nebullzcr.
`
`
`
`. 5.. No Relevant Patents
`
`
`
`
`
`For this pending NDA, amendment. or supplement, there are no relevant patents that claim the drug substance (active ingredient),
`i
`drug product (formulation or composition) or method(s) of use, for which the applicant is seeking approval and with respect to which i
`[:7 Yes
`
`
`a claim of patent infringement could reasonably be asserted it a person not licensed by the owner of the patent engaged in the
`i
`
`manufacture, use, or sale of the drug product.
`
`
`FORM FDA 3542a (7/07)
`
`Page 2
`
`

`

`
`6. Deciaration Certification
`
`6.1 The undersigned declares that this is an accurate and complete submission ofpatent information for the NDA,
`
`
`amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-
`
`. sensitive patent information is submitted pursuant to 21 CFR 314.53. l attest that] am familiar with 21 CFR 314.53 and
`
`
`this submission complies with the requirements of the regulation I 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 US. C. 1007.
`
`
`
`6.2 Authorized Signature of NDA ApplicantJHolder or Patent Owner (Allomey, Agent, Representative or
`Date Signed
`othfl’m‘orized Official) (Provide Information below)
`
`)4; ”(54%.7/4fxflx/
`/ :5 vinegezlza/
`E
`'
`-
`,/j
`,
`r
`I
`k
`
`NOTE: Only an NDA applicant/holder may submit this declaratlon directly to the FDA. A patent owner who is not the NDA applicant]
`
`holder is authorized to slgn the declaration but may not submit it directly to FDA. 21 CPR 314.53(c)(4) and (10(4).
`
`
`Check applicable box and provide information below.
`
`
`
`
`
`
`
`
`
`
`
`
`
`CI Patent Owner
`._.
`
`Name
`
`-.. .,
`
`__'L_
`
`[:1 Patent Owner’s Attorney, Agent (Represenlalive) or Other Authorized
`Official
`
`
`
`
`El NDA Applicant/Holder
`{:1 NDA Applicant’s/Holder's Attorney, Agent (Representative) or other
`Authorized Official
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`ZIP Code
`Telephone N'meer
`
`
`27709
`(919) 485—8350
`'
`
`
`
`("FAX Number (if available)
`__.. E-Mail Address (ifavailob/e)
`
`
`
`
`
`'
`(919) 3134298
`i dbuncc@uni1hei‘.com
`
`
`
`
`Dean Bunce, Senior Vice President Regulatory Affairs and Compliance, United Tlicrapouiics Corp
`Address
`_[Clly/State
`'~
`.
`One Park Drive, Suite 400
`Research Triangle Park, North Carolina
`
`— --—
`
`
`
`
`
`including the lime. for reviewing
`The public i'eponing burden for this collection of information has been estimated to average 20 hours per response,
`inslruclions, searching existing data sources, gathering and maintaining the dam needed, and completing and reviewing the collection of lnfonnmion. Scnd
`comments regarding this burden estimate or any other aspect of this colleclion of information, including suggestions for reducing this burden to:
`Food and Drug Administration
`CDER (l-lFD-007)
`5600 Fishers Lane
`Rockville, MD 20857
`
`An agency may not conduct or sponsor. and a person is nor required In reg-pond to, a collection of
`information unless it displays a currently valid OMB caulml number.
`
`FORM FDA 3542a (7/07)
`
`‘
`
`Page 3
`
`

`

`Department of Health and Human Services
`Food and Drug Administration
`
`PATIENT INFORMATION SUBMITTED WITH THE FILING
`OF AN NDA, AMENDMENT, 0R SUPPLEMENT
`
`DOSAGE FORM
`
`Inhalation Solution
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Form Approved: OMB No. 0910—0513
`Expiration Date: 7/31/10
`See OMB Statement on Page 3.
`
`
`
`NDA NUMBER
`
`
`22387
`
`
`NAME OF APPLICANT/NDA HOLDER
`
`
`
`For Each Patent That Claims a Drug Substance
`
`{Active Ingredient), Drug Product (Formulation and Composition)
`United Therapeutics Corp
`
`
`
`and/or Method of Use
`
`
`The following is provided in accordance with Section 505(b) and (c) of the Federal Food, Drug, and Cosmetic Act.
`
`
`TRADE NAME (OR PROPos‘éb‘rnKb'E NAME)
`TYVASO (Proposed)
`
`
`
`
`ACTIVE lNGREDlENT(S)
`STRENGTHiS)
`trepi‘ostinil sodium
`0.6. mg/ml
`
`
`
`This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application,
`amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 3t4.53(d)(4).
`Within thirty (30) days after approval of an NDA or Supplement, or within thirty (30) days of issuance of a new patent, a new patent
`declaration must be submitted pursuant to 21 CFR 314.53(c)(2)(ii) with all of the required information based on the approved NDA or
`supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied
`upon by FDA for listing a patent in the Orange Book.
`
`
`For handwritten or typewriter versions (only) of this report: Ifadditional space is required for any narrative answer (i.e.. one that
`
`
`
`does not require a "Yes" or "No" response). please attach an additional page referencing the question number.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`. 1. GENERAL
`
`
`a. United States Patent Number
`6,756,033
`d. Name of Patent Owner
`United Therapeutics Corporation
`
`
`
`
`
`
`
`
`"""""*M'
`
`
`
`
`
`
`FAX Number (i/ available)
`
`Z] No
`fl Yes
`
`
`
`
`
`
`b. issue Date of Patent
`c. Expiration Date of Patent
`*—
`Jun. 29, 2004
`Nov. 13,2018
`
`
`Address (ofPatent Owner)
`1735 Connecticut Avenue, NW
`Third Floor
`
`City/state
`"
`Washington, DC
`
`
`ZIP Code
`"
`‘ FAX Number (llava/Iable)
`"
`
`
`202) 483—4005
`20009
`
`
`Telephone Number '
`avian Address (i/avai/able)
`' _
`
`
`(202) 483~7000
`
`
`e. Name of a rant or re resentative who resides or maintains i Address (ofagent or representative named in 1.9.)
`
`a place of business within the United States authorized to
`Not Applicable
`
`receive notice of patentcertification under section 505(b)(3)
`
`and (j)(2)(B) of the Federal Food. Drug, and Cosmetic Act
`,
`—-
`and 21 CFR 314.52 and 314.95 (if patent owner or NDA
`C'tV/S’a'e
`
`applicant/holder does not reside or have a place of
`
`
`“"""'
`"W
`"m‘
`‘ ZIP Code-m “
`
`1 Telephoneuhiumber
`E—Mail Address-(ifavaihable)
`l
`
`is the patent referenced above a patent that has been submitted previously for the
`
`
`
`approved NDA or supplement referenced above?
`”ET-If the patent referenced above has been submitted previously for listing, is the expiration
`
`
`
`,2) No
`Yes
`date a new expiration date?
`
`FORM FDA 3542a (7/07)
`'
`‘
`'
`’
`Pagei
`('St' Graphics (3U!) ~H3.l(lon
`BF
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`13%:
`
`business within the United States)
`
`l.
`
`

`

`For the patentreferenced above, provide the following information on the drug substance, drug product and/or method of
`use that is the subject of the pending NDA, amendment, or supplement,
`
`2. Drug Substance (Active ingredient)
`
`2.1 Does the patent claim the drug substance that is the active ingredient in the drug product
`described in the pending NDA. amendment. or supplement?
`CI Yes
`
`2.2 Does the patent claim a drug substange that is a different polymorph of the active
`Ingredient described in the pending NDA, amendment, or supplement?
`[3 Yes
`
`2.3 If the answer to question 2.2 is "Yes," do you certify that. as olthc date of this declaration, you have test
`data demonstrating that a drug product containing the polymorph will perform the same as the drug product
`[3 Yes
`described in the NDA? The type of test data required ls described at 21 CFR 314.53(b),
`
`2.4 Specify the polymorphic form(s) claimed by the patent for which you have the test results described in 2.3.
`
`“an—R
`2.5 Does the patent claim only a metabolite of the active ingredient pending in the MBA or supplement?
`(Complete the information in section 4 below if the patent claims a pending method of using the pending
`drug product to administer the metabolite.)
`2.6 Does the patent claim only an intermediate?
`
`
`[:1 Yes
`
`
`
`[:| Yes
`
`2A7 If the patent referenced in 2.1 is a product-by~process patent, is the product claimed in the
`D Yes
`patent novel? (An answer is required only if the patent is a product-by~process patent.)
`
` 3. Drug Product (Composition/FormulationI
`
` 3.1 Does the patent claim the drug product, as defined in 21 CFR 314.3. in the pending NDA. amendment,
`or supplement?
`
` 3.2 Does the patent claim only an intermediate?
`
`
`
`C] Yes
`
`
`
`
`3.3 If the patent referenced in 3.1 is a product-by-process patent. is the product claimed—in the
`patent novel? (An answer'ls required only if the patent is a product—by—prncess patent.)
`
`
`4. Method of Use
`
`
`
`
`Sponsors must submit the information in section 4 for
`each method of using the pending drug product for which approval [5 being
`sought that is claimed by the patent. For each pending method of use claimed by the patent, provide the following information:
`
`4.1 Does the patent claim one or more methods of use for which approval is being sought in
`
`the pending NDA, amendment. or supplement?
`m Yes
`DNO
`42 Patent Claim Number(s) {as listed in the patent)
`Does (Do) the patent claim(s) referenced in 4.2 claim a
`
`pending method of use to: which approval is being sought
`
`in the pending NDA, amendment. or supplement?
`1"3 and 5
`BNO
`
`
`
`Use: (Submitind/‘cation ormethod of use information as idenh
`4.2a It the answer to 4.2 is
`lied specifically in the proposed labeling.)
`
`"Yes," identify with speci—
`ficity the use with refer—
`TYVASO is indicated for the treatment of pulmonary arterial hypertension in patients with NYHA Class III \
`
`ence to the proposed
`»/ symptoms.
`
`labellng for the drug
`
`product.
`
`
`
`TYVASO is_intcndcd for oral inhalation use with an ultrasonic. pulsated Optineb-ir iicbulizei.
`
` E 5. No Relevant Patents
`
`
`For this pending NDA, amendment, or supplement, there are no relevant patents that claim the drug substance (active ingredient .
`!—
`drug product (formulation or composlllon) or method(s) of use. for which the applicant is seeking approval and with respect to which
`
`a claim of patent infringement could reasonably be asserted it a person not licensed by the owner of the patent engaged in the
`
`manufacture, use. or sale of the drug product.
`
`
`FORM FDA 3542a (7/07)
`Page 2
`
`[:3 Yes
`
`El Yes
`
`11(4)
`
`

`

`
`6. Declaration Certification.
`6.1 The undersigned declares that this is an accurate and complete submission of patent information for the NDA,
`amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act. This time-
`sensitive patent information is submitted pursuant to 21 CFR 314.53. [attest that I am familiar with 21 CFR 314.53 and
`this submission complies with the requirements of the regulation. I 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.
`
`. Date Signed
`/.7 W»! 5W"?
`
`».)
`
`:
`
`
`
`. 6.2 Authorizefgpalure of NDA Applicani/Holder or Palent Owner (Attorney. Agent, Representative or
`'
`other A.
`on‘ze Official) (Provide Information below)
`/a
`
`Vr’fiicvlt (“L/Lavggfio—
`
`NOTE: Only an NDA applicant/holder may submit this declaration directly to the FDA. A parent owner who is not the NDA applicant]
`holder is authorized to sign the declaration but may not submit it directly lo FDA. 21 CPR 314.53(c)(4) and (d)(4).
`
`I Check applicable box and provide information below.
`.,
`*W'i—
`El NDA Applicant/Holder
`I
`
`
`--_
`__-_
`[:i NDA Applicant's/Holder‘s Attorney, Agent (Representative) or other
`Authorized Official
`
`1:] Patent Owner
`
`Name
`
`E} PatantOwner’s Attorney, Agent (Represenlative) or Other Authorized
`Official
`
`
`Dean Bunce, Senior Vice President Regulatory Affairs and Compliance, United Therapeutics Corp
`Address
`City/Stale
`One Park Drive, Suite.- 400
`Research Triangle Park, North Carolina.
`
`‘
`
`l ZIP Code
`' 27709
`FAX Number (Fa-Jaimie)
`(919) 313-1298
`
`'
`
`"
`
`’
`
`Telephone Number
`(919) 485-8350
`E-Mail Address (iiavailab/e)
`I dbunce@unilhcr.com
`
`including the lime for reviewing
`The public reponing burden for this collection of infonnation has been estimated to average 20 hours per response,
`instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send
`comments regarding this burden estimate or any olhuij aspect of [his collection ol'inl'omintion, including suggestions For reducing this burden to:
`Food and Drug AdminieraLion
`CDER (HFD~OI')7)
`5600 Fishers Lane
`Rnokville, MD 20857
`
`An agency may not conduct or sponsor, and a person is not required to respond in, a collectinn of
`information unless it displays a currently valid OMB comm] number.
`
`FORM FDA 3542a (7107)
`
`_
`
`Page 3
`
`

`

`Department of Health and Human Services
`Food and Drug Administration
`
`Form Approved: OMB No. 0910-0513
`
`Expiration Date: 7/31/10
`
`See OMB Statemenl on Page 3.
`
`PATENT lNFORMATlON SUBl’VllTTED WlTH‘THE FlLlNG
` NDA NUMBER
`22387
`OF AN NDA, AMENDMENT, OR SUPPLEMENT
`
`
`NAME OF APPLlCANT/NDA HOLDER
`
`
`United Therapeutics Corp
`
`
`
`
`
`
`For Each Patent That Claims 6 Drug Substance
`(Active ingredient), Drug Product (Formulation and Composition)
`and/or Method of Use
`
`The following is provided in accordance with Section 505(1)} and (c) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`TYVASO (Proposed)
`
`ACTIVE lNGREDlENTlS)
`V treproslinil sodium
`
`‘
`
`STRENGTH(8)
`0.6 rug/ml
`
`
`
`' DOSAGE FORM
`Inhalation Solution
`
`This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application,
`amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53(d)(4).
`Within thirty (30) days after approval of an NDA or supplement. or within thirty (30) days of issuance of a new patent, a new patent
`declaration must be submitted pursuant to 21 CFR 314,53(c)(2)(ii) with all of the required information based on the approved NDA or
`supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied
`upon by FDA for listing a patent in the Orange Book.
`
`For hand‘written or typewritcrverslons (only) of this report: lfadditional space is required for any narrative answer (i.e.. one that
`does not require a "Yes“or "No" response), please attach an additional page referencing the question number.
`
`FDA will not list patent information if you submit an incomplete patent declaration or the patent declaration indicates the
`patent is not eligible for listing.
`
`
`For each patent submitted for the pending NDA, amendment, or supplement referenced above, you musl submit all the
`information described below. If you are not submitting any patents for this pending NDA, amendment, or supplement,
`complete above section and sections 5 and 6.
` 1». GENERAL
`0. Expiration Date of Patent
`. a. United States Patent Number
`b. Issue Date ol Patent
`
`Jul. 20, 2004 .6,765,117 Oct. 24, 2017
`
`
`
`d. Name of Patent Owner
`Address (ofPalenl Owner)
`
`1735 Connecticut Avenue, NW
`United Therapeutics Corporation
`Third Floor
`City/Stale
`
`
`
`2::
`its
`_
`
`ZlP~Code
`,1 FAX Number {if available)
`
`20009
`i (2034334005
`
`Telephone Number
`E-Mail Address (ifavailable)
`
`(202) 483—7000
`er Name of agent or representative who resides or maintains ; Address (ofagentor representative named in 1e.)
`21 place of-business within the United States authorized to
`' Not Applicable
`receive notice of patent codification under section 505(b)(8)
`and (j)(2)(l3) of the Federal Food, Drug, and Cosmetic Act
`_-—-
`and 21 CFR 314.52 and 314.95 (if patent owner or NDA
`Olly/State
`
`applicant/holder does not reside or have a place or
`business within the United States)
`l
`| FAX Number(if available)
`[13‘5"
`
`
`’
`
`ZIP Code
`
`
`
`TeEp-honfie Number
`
`
`“
`
`E-Mail Address (ifavailable)
`
`)
`
`f.
`
`Is the patent referenced above a patent that has been submitted previously for the
`
`approved NDA or supplement referenced above?
`if the patent referenced above has been submitted previously for listing, is the expiration
`date a new expiration date?
`FORM FDA 3542a (7/07)
`
`9.
`
`v
`I: Yes
`
`C Yes
`
`
`
`E No
`
`E No
`
`Page 1
`PSI? Graphics pen 24.1402")
`EF
`
`

`

`For the patentreferenced above, provide the following information on the drug substance, drug product and/or method of
`use that is the subject of the pending NDA, amendment, or supplement.
`
`2. Drug Substance (Active Ingredient)
`
`2.1 Does the patent claim the drug substance that is the active ingredient in the drug product
`
`(2] Yesdescribed in the pending NDA, amendment, or supplement? C] No
`2.2 Does the patent claim a drug substance that is adifiereiit polymorph of the active
`
`
`D Yes'ingredient described in the pending NDA. amendment, or supplement? 2 No
`2.3 if the answer to question 2.2 is "Yes," do you certify that, as of the date of thistleclaration, you have test
`.-
`data demonstrating that a drug product containing the polymorph will perform the same as the drug product
`
`2 No
`L] Yes
`described in the NBA? The type oftest data required is described at21 CFR 314.53(b).
`"2.4 Specify the polymorphic form(sj 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 active ingredient pending in the NDA or supplement?
`(Complete the information in section 4 below if the patent claims a pending method of using the pending
`
`drug product to administer the metabolite.)
`D Yes
`2} No
`2.6 Does the patent claim only an intermediate?
`
`
`1:] Yes
`
`2) No
`
`2.7 It the patent referenced in 2.1 is a product—by—process patent, is the product claimed ”REE—
`patent novel? (An answer is required only it'the patent is a product-by-process patent.)
`
`Yes
`
`
`
`:1 No
`
`' 3. Drug Product (Compositiart/Formulation),
`
`3.1 Does the patent claim the drug product, as defined in 21 CFR 314.3. in the pending NDA, amendment,
`‘
`C] Yes
`'2] No
`or supplement?
`
`3.2 Does the patent claim only an intermediate?
`
`
`D Yes
`
`El No
`
`3.3 it the patent referenced in 3.1 is a product—by—process patent, is the product claimedin‘the"”m_——_m
`patent novel? (An answer is required only if the patent is a product-by-process patent.)
`
`[:1 Yes
`
`Z] No
`
`_ 4. Method of Use
`
`Sponsors must submit the information in section 4 for each method of using the pending drug product for which approval is being
`sought that Is claimed by the patent. For each pending method of use claimed by the patent, provide the following information:
`4.1 Does the patent claim one or more methods of use for which approval is being sought in
`
`the pending NDA, amendment. or supplement? E) No El Yes
`4.2 Patent Claim Number(s) {as listed in the patent)
`[ Does (Do) the patent claim(s) referencedin42 claim a
`'
`pending method of use {or which approval is being sought
`
`NO‘ applicable
`
` E] Yesin the pending NDA. amendment. or supplement? E! No
`4.2a if the answer to 4.2 is
`Use: (Subrnitindication ormethod of use information as identified specifically in the proposed labeling.)
`"Yes." identity with speci-
`ficity the use with refer-
`ence to the proposed
`labeling for the drug
`product.
`
`
`
`_, 5. No Relevant Patents
`
`For this pending NDA, amendment, or supplement, there are no relevant patents that claim the drug substance (active ingredient).
`drug product (formulation or composition) or method(s) of use, for which the applicant is seeking approval and with respect to which
`a claim of patent infringement could reasonably be asserted it a person not licensed by the owner at the patent engaged in the
`manufacture, use. or sale of the drug product.
`
`[:3 Yes
`
`FORM FDA 3542a (7/07)
`
`‘
`
`_
`
`Page 2
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`[:l NDA Applicant's/Holder‘s Attorney. Agent (Representative) or other
`[a NDA Applicant/Holder
`Authorized Official
`
`U Patent Owner
`CI Patent Owner’s Attorney, Agent (Representative) or OtherAuthorized
`
`Official
`
`r
`
`
`
`
`
`
`
`
`Dean Bunce, Senior Vice President Regulatory Affairs and Compliance, United ’l"herapeulics Corp
`Address
`"
`[ City/State
`
`One Park Drive, Suite 4-00
`1 Research Triangle Park, North Carolina
`
`Name
`
`
`
`
`‘ 6. Oeclarafion Certification
`
`6-1 The undersigned declares that this is an accurate and complete submission of patent information for the NDA,
`
`
`amendment, or supplement pending under section 505 of the Federal Food, Drug, and Cosmetic Act, This time-
`
`
`sensitive patent Information is submitted pursuant to 21 CFR 314.53, I attest that I am familiar with 21 CFR 314.53 and
`
`this submission complies with the requirements of the regulation. I verify under penalty ofperjury that the foregoing is
`true and correct.
`
`
` Date Signed
`
`
`/ 3’ monetary
`
`
`NOTE: Only an NDA applicant/holder may suomit this declaration directly to the FDA. A patent owner who is not the NDA applicant]
`
`holder is authorized to slgn the declaration but may not submit it directly to FDA. 21 CFR 314.53ic)(4) and (00(4).
`
`Check applicable box and provide information below.
`
`
`
`
`Warning: A willfully and knowingly false statement is a criminal offense under 18' U.S,C, 1001.
`
` 6.2 Authorized Signature of NDA Applicant/Holder or Patent Owner (Attorney, Agent, Representative or
`other mind Official) (Provide information below)
` ewe {item—w
`
`
`
`
`ZIP Code
`..
`‘
`I
`-
`I
`Telephone Number”
`
`
`
`27709
`(919) 485-8350
`
`
`FAX Numberfil available)
`,_-.
`(919) 313-1293
`
`
`
`
`
`
`The public reporting burden for this collection of information has been estimated to average 20 hours per response,
`including the time for reviewing
`
`
`instructions, searching, existing data sources, gathering and maintaining the dam needed, and completing and reviewing the collection of infornmtion. Send
`
`comments regarding this burden estimate or any other aspect of this collection ofinfonnaiion. including suggestions for reducing this burden lo:
`Food and Drug Administration
`CDER (HFDOO'D
`5600 Fishers Lane
`Rockvillc, MD 20857
`
`
`
`
`
`
`
`An agency may not conduct or sponsor, and 0 person ix not required (0 )‘r?.<pv.7iid lo, a collection 9/
`infommn‘rm unless ir dilrplays (( currently valid OMB control mini/mi:
`
`
`
`
`
`
`FORM FDA 3542a (7/07)
`'
`'
`'
`Page 3
`
`

`

`Fm” App'oved: OMB N“ 0910‘0513
`Department of Health and Human Services
`99833;?272333;#7062151; 3‘
`Food and Drug Administration
`
`PATENT iNFORMATION SUBMITTED WITH THE FILING NDA NUMBER
`
`OF AN NDA, AMENDMENT, 0R SUPPLEMENT
`22387
`NAME OF- APPLICANT/NBA HOLDER
`
`For Each Patent That Claims a Drug Substance
`(Active Ingredient), Drug Product (Formulation and Composition)
`and/or Method of Use
`
`united Therapeutics C0”)
`
`
`
`
`
`The following is provided in accordance with Section 505(1)) and (c) of the Federal Food, Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`
`TYVASO (Proposed)
`
`ACTlVE |NGREDlENT(S)
`h'eprostinil sodium
`
`DOSAGE FORM
`
`Inhalation Solution
`
`STRENGTH(S)
`0.6 mg/ml
`
`This patent declaration form is required to be submitted to the Food and Drug Administration (FDA) with an NDA application,
`amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53(d)(4).
`Within thirty (30) days after approval of an NDA or supplement. or within thirty (30) days of issuance ofa new patent, a new patent
`declaration must be submitted pursuant to 21 CFR 314.53(C)(2)(ii) with all of the required information based on the approved NDA or
`supplement The information submitted in the declaration form submitted upon or after approval will be the only information relied
`upon by FDA for listing a patent in the Orange Bookl
`
`For hand-written or typewriter versions (only) of this report: if additional space is required for any narrative answer (i.e., one that
`does not require a “Yes“ or“No“ response), please attach an additional page referencing the question number.
`
`FDA will not list patent information if you submit an incomplete patent declaration or the patent declaration indicates the
`patent is not eligible for listing.
`
`For each patent submitted for the pending NDA, amendment. or supplement referenced above, you must submit all the
`information described below. If you are not submitting any patents for this pending NDA, amendment, or supplement,
`complete above section and sections 5 and 6.
`
`, 1. GENERAL
`
`
`
`at United States Patent Number
`b. Issue Date oiFaTeTit
`c. Expiration Date of Patent
`
`6,521,212
`Feb. 18, 2003
`Nov 13, 20l8
`_...
`cl. Name of Patent Owner
`Address (of Patent Owner)
`United Therapeutics Corporation
`:gilirgfcmm Avenue, N'W
`
`rCiiyiStaie
`7_____
`_
`Washington, DC
`
`
`"271566216—T"
`FAX NumberT/T available)
`
`20009
`(202) 483-4005
`; Téie—phone Nuniber
`E-Mail Addre—s—svlifma-vailab/e)
`”—
`
`(202) 433~7ooo
`6. Name of agent or representative who resides or maintains Address (ofagent or representative named in 1e.)
`a place of business within the United States authorized to
`Not Applicable
`receive notice of patentcertlficalion under section 505(b)(3)
`
`and (j)(2)(B) of the Federal Food, Drug, and Cosmetic Act f———»——~~
`-~-~~
`and 21 CFR 314.52 and 314.95 (it patent owner or NDA
`City/State
`applicant/holder does not reside or have a place of
`business within the United States)
`it?
`
`EFZTCode
`....______ FAX Number (ifavailable)
`
`
`5 Telephone Number
`
`"mlimEiMaii Address (ifavailable)
`l
`
`f.
`
`15 the patent referenced above a patent that has been submitted previously for the
`__
`approved NDA or Supplement referenced above?
`L_] Yes
`Z] No
`
`.9. lithe patent referenced above has been submitted previously for listing, is the expiration
`date a new expiration date?
`
`1:) Yes
`
`W No
`
`FORM FDA 3542a (7/07)
`
`Page 1
`rscoraphicstmuuzdum)
`EF
`
`

`

`
`For the patent referenced above, provide the following information on the drug substance, drug product and/or method of
`
`use that is the subject of the pending NDA, amendment, or supplement.
`2. Drug Substance (Active ingredient)
`2.1 Does the patent claim the drug substance that is the active ingredient in the drug product
`
`described in the pending NDA, amendment, or supplement? [2} No D Yes
`2.2 Does the patent claim a drug substance that is a different polymorph oi the active
`[,2] No
`C] Yes
`ingredient described in the pending NDA, amendment, or supplement?
`
`
`2.3 It the answer to question 2.2 is "Yes," do you certily that, as ofthe date of this declaration, you have test
`data demonstrating that a drug product containing the polymorph will perform the same as the drug product
`
`
`[2] No “2.4 gpecify the polymorphic formic) claimed by the patent for which you have the test re