Morris Corporate Center III
`400 Interpaee Parkway
`Paralppanv, M 0?054
`T852.261.?OGO
`F 862.261.?001
`www.wutson.com
`
`June 29, 2016
`
`G} .
`
`Watson
`
`Via FedEx®
`
`General Counsel
`
`United Therapeutics Corporation
`55 TW Alexander Drive
`
`Research Triangle Park, NC 27709
`
`General Counsel
`
`United Therapeutics CorpOi-ation
`[735 Connecticut Ave, NW" #2
`Washington, DC 20009
`
`General Counsel
`
`United Therapeutics Corporation
`1040 Spring Street
`Silver Spring, IVID 20910
`
`Foley& Lardner
`Stephen B, Maebius
`3000 K Street, N.W., Suite 600
`Washington, DC 20007-5109
`
`HIGHLY CON FI DENT [AL
`
`Re: Notification of Certification for US. Patent Nos. 9,339,507 and 9,358,240 Pursuant
`to § 5050)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act
`
`Dear Madam or Sir:
`
`Pursuant to §505fj)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act and 21
`CPR. :5; 314,95, Watson Laboratories, Inc. (“Watson") hereby provides notice ofthe following
`information to United Therapeutics Corporation (“United Therapeutics”), as the apparent holder
`of approved New Drug Application (“NBA") No. 02238? for Tyvaso® (treprostinil) Inhalation
`Solution, 0.6 trig/m1 according to the records of the US. Food and Drug Administration (“FDA“)
`and record owner of US. Patent Nos. 9,339,50? (“the ‘507 patent“) and 9,358,240 (“the ‘240
`patent) as indicated on the face of the patents.
`
`As a courtesy, Watson is also providing a copy of this Notice Letter and Detailed
`Statement to Foley & Lardner, cr‘o Stephen B. Maebius, as the correspondent for the ‘50? and
`‘240 patents as indicated on the face ofthe patents.
`
`-1_
`
`UNITED THERAPEUTICS, EX. 201B
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`

`United Therapeutics Corporation
`Page 2
`
`Pursuant to 21 CPR. §3l4.95(e), Watson requested from FDA permission to
`send this notice by means other than registered or certified mail. Specifically, Watson requested
`that it be allowed to send this notice by FedEx®. FDA granted Watson‘s request.
`
`Pursuant to 21 U.S.C. § 355G)(2)(B)(iv)(l) and 21 C.F.R. § 314.95(c)(l),
`1.
`we advise you that FDA has received a Patent Amendment
`to Abbreviated New Drug
`Application (“ANDA”) from Watson for Treprostinil Inhalation Solution, 0.6 mg/ml. The
`ANDA contains the required bioavailability andfor bioequivalence data and/or bioequivalence
`waiver. The Patent Amendment was submitted under 21 U.S.C. § 3SSU)(1) and (2)(A), and
`contains Paragraph IV certifications
`to obtain approval
`to engage in the commercial
`manufacture, use or sale of Treprostinil Inhalation Solution, 0.6 mg/ml before the expiration of
`US. Patent Nos. 9,339,502 and 9,358,240 which are listed in the Patent and Exclusivity
`Information Addendum of FDA’s publication, Approved Drug Product‘s with Therapeutic
`Equivalence Evaluations (commonly known as the “Orange Book“).
`
`to 21 C.F.R. § 314.95(c)(2), we advise you that FDA has
`Pursuant
`II.
`assigned Watson’s ANDA the number 208172.
`
`Pursuant to 21 CPR. § 314.95(c)(3), we advise you that the established
`III.
`name of the drug product that
`is the subject of Watson’s ANDA is Treprostinil Inhalation
`Solution, 0.6 mgfrnl.
`
`the active
`to 21 C.F.R. § 314.95(c)(4), we advise you that
`Pursuant
`IV.
`ingredient in the proposed drug product is treprostinil; the strength of the proposed drug product
`is 0.6 mg/ml of treprostinil; and the dosage form of the proposed drug product is inhalation
`solution.
`
`the patents
`Pursuant to 21 C.F.R. § 314.95(e)(5), we advise you that
`V.
`alleged to be invalid, unenforceable, andi’or not infringed in the Paragraph IV certifications are
`US. Patent Nos. 9,339,50? and 9,358,240 which are listed in the Orange Book in connection
`with United Therapeutics’ approved NDA No. 022387 for Tyvasofi. According to information
`published in the Orange Book, the patents will expire as follows:
`
` U.S. PATENT NO.
`9,339,507 March 10, 2028
`
`
`
`EXPIRATION DATE
`
`
`
`9,358,240 May 5, 2028
`
`V1. Watson alleges, and has certified to FDA, that in Watson’s opinion and to
`the best of its knowledge, LLS. Patent Nos. 9,339,507 and 9,358,240 are invalid, unenforceable,
`andfor will not be infringed by the commercial manufacture, use or sale of the drug product
`described in Watson’s ANDA. Therefore, pursuant to 21 U.S.C. § 3550)(2){B)(iv)(ll) and 21
`C.F.R.
`§ 314.95(c)(6), Watson’s detailed statement of the legal and factual basis for the
`Paragraph IV certifications set forth in Watson‘s Patent Amendment is attached hereto and made
`
`UNITED THERAPEUTICS, EX. 2018
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`

`United Therapeutics Corporation
`Page 3
`
`a part hereof.
`
`Pursuant to 21 U.S.C. § 355(j)(5)(C), this notice letter includes an Offer of
`VII.
`Confidential Access to Application. As required by §355(j)(5)(C)(i)(III), Watson offers to
`provide confidential access to certain information from its ANDA No. 208172 for the sole and
`exclusive purpose of determining whether
`an
`infringement
`action
`referred
`to
`in
`§ 3550)(5)(B)(iii) can be brought.
`
`Confidential Access to Watson’s ANDA No. 208172 shall be govemed by the
`Stipulated Protective Order, entered in Civil Action No. 3:15-cv-05723.
`
`Section 3550)(5)(C)(i)(lll} provides that any request for access that United Therapeutics
`makes under this Offer of Confidential Access “shall be considered acceptance of the offer of
`confidential access with the restrictions as to persons entitled to access, and on the use and
`disposition of any information accessed, contained in [this] offer of confidential access” and that
`the “restrictions and other terms of [this] offer ofconiidential access shall be considered terms of
`an enforceable contract.” Thus,
`to the extent
`that United Therapeutics requests access to
`Confidential Watson information,
`it necessarily accepts the terms and restricticms outlined
`above.
`
`By providing this Offer of Confidential Access to Application, Watson maintains the
`right and ability to bring and maintain a Declaratory Judgment action under 28 U.S.C. § 2201 et‘
`seq, pursuant to 21 U.S.C. § 3550)(5)(C).
`
`Very truly yours,
`
`Watson Laboratories, Inc.
`
` Joyce Anne
`
`e gaudio
`Executive Director, Regulatory Affairs
`
`Enclosure: Watson ’3 Detailed Factual and Legal Basis for Its Paragraph IV Certifications that
`US. Patent Nos. 9339.507 and 9.358.240 are Invalid, Uneaforceable and/or Not
`Infringed by the Treproslr’nil Product Described in Watson ’3 AND/l No. 208172
`
`UNITED THERAPEUTICS, EX. 2018
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`

`ENCLOSURE
`
`Watson’s Detailed Factual and Legal Basis for Its Paragraph IV Certifications that US.
`Patent Nos. 9,399,507 and 9,358,240 Are Invalid, Unenforceable andfor Not Infringed by
`the Treprostinil Product Described in Watson’s ANDA No. 208172
`
`I.
`
`Introduction
`
`Pursuant to § 505(j)(2)(B)(iv)(II) of the Federal Food, Drug, and Cosmetic Act and 21
`C.F.R. § 314.95(c)(6), this document is the detailed factual and legal basis for the Paragraph IV
`certifications of Watson Laboratories, Inc. (“Watson”) that, in its opinion and to the best of its
`knowledge, US. Patent Nos. 9,3 39,5 07 (“the ‘507 patent”) and 9,358,240 (“the ‘240 patent”) are
`invalid, unenforceable andlor will not be infringed by the commercial manufacture, use or sale of
`the Treprostinil product described in Watson’s ANDA No. 208172. Watson specifically reserves
`the right to raise any additional defenses should litigation ensue.
`
`II.
`
`Watson’s ANDA Products
`
`The product that is the subject ol'Watson’s ANDA No. 208172 (“Watson ANDA
`Product” or “Watson ANDA formulation”) is a generic version of Tyvaso® (treprostinil)
`Inhalation Solution, 0.6 mg/ml. Watson’s ANDA Product is an inhalation solution containing as
`the active pharmaceutical ingredient treprostinil. The strength of Watson’s ANDA Product is 0.6
`mg/ml. Watson will market the Watson ANDA Product for the currently approved indication for
`the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise
`ability.
`
`III.
`
`The Orange Book Listed Patents
`
`11.5. PATENT N0.
`
`EXPIRATION oars
`
`'
`
` 9,339,507
`
`March 10, 2028
`
`9,358,240
`
`May 5, 2028
`
`IV.
`
`Legal Principles
`
`A.
`
`Claim Constructitm
`
`A court must first construe claims before determining whether they are valid or infringed.
`Amazon.com, Inc. v. Barnesandnobiecom, Inc, 239 F.3d 1343, 1351 (Fed. Cir. 2001); Markman
`v. Wes-Mew instruments, Inc, 52 F.3d 967, 976. 926 n. 7 (Fed. Cir. .1995) (en bane). Claims
`must be construed the same way for determining validity and infringement. Amazon. com, 239
`F.3d at 1351.
`
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`The claim construction inquiry begins in all cases with the actual words of the claims.
`Phillips v. AWH Corp. 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en bane). Claim terms are to be
`given their ordinary and customary meanings as they would have been understood by a person of
`ordinary skill in the art in the context of the patent at the time of the invention, 126., as of the
`effective filing date of the patent application.
`Id. at 1312—14. To properly interpret claim terms,
`the “intrinsic” record, including the claims, the specification, and the prosecution history must be
`considered.
`Id. at 1314—24. The claims must be read “in view of“ and “so as to be consistent
`
`with” the specification, which is the “single best guide to the meaning of a disputed term." Id. at
`1315—1316. The importance of the specification in claim construction derives from its statutory
`role of providing a “full” and “exact” description of the claimed invention.
`Id. at 1316.
`
`B.
`
`Infringement
`
`To literally infringe a United States Letters Patent, an accused product or process must
`meet each and every limitation of the patent claim exactly, including any functional limitations.
`See Coming Glass Works v. Sunritomo Elec. U.S./1., Inc... 868 F.2d I251, 1258 (Fed. Cir. 1989).
`Any dcviation from the claim precludes a finding ol‘literal infringement. See, e.g.. Cole v.
`Kimberthlark Corp, 102 F.3d 524, 532 (Fed. Cir. 1996).
`
`first, the claims must be
`An analysis of literal infringement requires two inquiries:
`construed to resolve their proper scope and meaning; and second, it must be determined whether
`the accused product or process falls exactly within the scope of the properly construed claims.
`See Marketa», 52 F.3d at 976; see also Novo Nordisk ofN. A m, inc. v. Genentech, Inc, 77 F.3d
`1364, 1368 (Fed. Cir. 1996). The first inquiry is a legal question for the court; the second
`inquiry is a factual determination for the fact-finder. See Markman. 52 F.3d at 976—80.
`
`Infringement may also be found under the doctrine of equivalents if the accused product
`or method includes features that are equivalent to each claimed element. Warner—Jenkinson C0.,
`Inc. v. H1710}? Davis Chem. Co., 520 U.S. 17, 21, 40 (1997). The determination of equivalency is
`an objective inquiry applied on an element-by-clement basis taking into account the role of each
`claim element in the context of the claim.
`Id. at 29, 40.
`
`Id.
`The Supreme Court has not mandated any specific approach to evaluate equivalency.
`at 39-40. Among the recognized approaches that may be applied include the function-way-result
`test and the insubstantial differences test. 1d. at 25, 36, 39-40.
`
`There are a number of limitations on the application of the doctrine of equivalents. For
`example, the doctrine of equivalents cannot be applied so as to effectively eliminate a Claim
`limitation in its entirety.
`Id. at 29. Moreover, limitations may not be afforded a scope of
`equivalency that effectively results in a claim that does not patentably distinguish the prior art.
`Sec, 9.3., Wi'z'son Sporting Goods Co. 1:. David Geoffrey if: Assam, 904 F.2d 677, 683 (Fed. Cir.
`1990), overruled on other grounds by Cardinal Chem. Co. v. Morton In: '2, 508 U.S. 83 (1993).
`Additionally, prosecution history estoppel operates to prevent recapture, through the doctrine of
`eq uivalents, of coverage of subject matter that was relinquished by amendment or argument
`during prosecution- Feslo Corp. v. Shoketsu Kinzoku Kogyo Kabnshi‘ki Co, Ltd, 535 U.S. T22,
`733-34 (2002).
`
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`Although the sale of an apparatus to perform a patented method or process is not a direct
`infringement of a method or process claim, such a sale may nevertheless constitute an active
`inducement of infringement under 35 U.S.C. § 271(b) andfor a contributory infringement under
`35 U.S.C. § 271(c). See Joy Techs, inc. v. Fiah. inc, 6 F.3d 770, 774 (Fed. Cir. 1993).
`“Liability for either active inducement of infringement or for contributory infringement is
`dependent upon the existence of direct infringement." iii; see also CR. Bard, inc. 1:. Advanced
`Cardiovascular Sys.. Inc, 91 1 F.2d 670, 673 (Fed. Cir. 1990).
`
`lnducement of infringement is actively and knowingly aiding and abetting another’s
`direct infringement ofa patent claim. See id. at 675; DSU Med. Corp. v. JMS Co, Ltd, 471 F.3d
`1293, 1306 (Fed. Cir. 2006).
`.ln order to find induced infringement, a patentee must show (i)
`direct infringement, either literally or under the doctrine of equivalents, (ii) that the alleged
`indirect in fringer actually intended to cause another to directly infringe, (iii) that the alleged
`indirect infringer knew of the allegedly infringed patents, and (iv) that the alleged indirect
`infringer knew or should have known that its actions would lead to actual infringement. See 35
`U.S.C. § 271(b) (201 1);.ree aiso DSUMed. Corp, 471 F.3d at 130-4705.
`
`Contributory infringement is knowingly making andior selling a product for use in
`practicing a patented method or process, when that product is Specifically designed for use in
`infringement of the patented method or process and has no substantial non-infringing uses. See
`Preemption Devices, Inc. v. Minn. Mining d: Mfg. Co, 803 F.2d 1 170, 1174 (Fed. Cir. 1986).
`
`C.
`
`Invalidity
`
`A patent may be proven invalid by a showing of clear and convincing evidence.
`Microsofi‘ Corp. v.
`i-a'i Lid. P'snip, 131 S.Ct. 2238, 2251 (2011).
`
`1.
`
`Anticipation
`
`One basis for establishing invalidity is anticipation by the prior art. The general test for
`anticipation requires that each and every limitation recited in a claim must be found in one item
`of prior art, either expressly or inherently, and arranged in the item of prior art in the same way
`as it is claimed, so that the disclosure effectively puts the public in possession of the invention.
`Silicon Graphics. inc. v. ATI Technologies, Inc, 607 F.3d 784, 796-97 (Fed. Cir. 2010). A
`reference will be considered anticipatory if “it discloses the claimed invention ‘such that a skilled
`artisan could take its teachings in combination with his own knowledge of the particular art and
`be in possession of the invention.” In re Graves, 69 F.3d 1147, 1152, 36 U.S.P.Q.2d 1697 (Fed.
`Cir. 1995).
`
`The law of anticipation does not require that a prior art reference explicitly disclose
`information that is inevitably present based on the express disclosure of the reference. Thus,
`“[a]n anticipatory reference
`need not duplicate word for word what
`is in the claims.
`Anticipation can occur when a claimed limitation is ‘inherent’ or otherwise implicit in the
`relevant reference.” Standard Havens Products, inc. v. Gencor industries, inc, 953 F.2d 1360,
`1369 (Fed. Cir. 1991).
`In addition, “products of identical chemical composition cannot have
`mutually exclusive properties.” in re Spada, 91] F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed.
`Cir. 1990). A chemical composition and its properties are inseparable.
`id. Therefore, if the
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`prior art teaches the identical chemical structure, the properties applicant discloses andfor claims
`are necessarily present. Id.
`
`Inherent anticipation does not require that a person of ordinary skill in the art at
`the time would have recognized the inherent disclosure. Abbott Laboratories v. Baxter
`Pharmaceuticai Products, Inc, 471 F.3d 1363, 1367—68 (Fed. Cir. 2006). Thus, with respect to
`claims to chemical compositions, the discovery of inherent properties of prior compositions that
`were unknown or unrecognized prior to the alleged invention does not impart patentable novelty
`on the chemical composition. Titanium Marat: Corp. ofAmer't'ca v. Banner, 778 F.2d TIS, "£82
`(Fed. Cir. 1985) (“it is immaterial, on the issue of novelty, what inherent properties the alloys
`have or whether these applicants discovered certain inherent properties”).
`
`Further, a party may rely on extrinsic evidence to show a feature not explicitly disclosed
`in a prior art reference is inherently disclosed in that reference. The Federal Circuit has
`explained:
`
`recourse to extrinsic evidence is proper to determine whether a
`feature, while not explicitly discussed, is necessarily present in a
`reference. The evidence must make clear that the missing feature
`is necessarily present, and that it would be so recognized by
`persons of skill in the relevant art.
`
`Telemoe Cellular Corp. v. Topp Telecom, Inc, 247 F.3d 1316, 1328 (Fed. Cir.
`2001).
`
`As such, a party asserting inherent anticipation may reference extrinsic evidence beyond the
`disclosure of the inherently anticipating reference to establish that an inherent feature or property
`is necessarily present.
`
`2.
`
`Obviousness
`
`A patent claim is invalid in view of one or a combination ofmultiple prior art references
`if “the differences between the subject matter sought to be patented and the prior art are such that
`the subject matter as a whole would have been obvious at the time the invention was made to a
`person having ordinary skill in the art to which said subject matter pertains.” 35 U.S.C. § 103(a)i
`(201 1).
`In determining obviou sness, the following four factors must be considered: (1 ) the scope
`and content of the prior art; (2) any differences between the prior art and the claims at issue; (3)
`the level of ordinary skill in the pertinent art; and, (4) any secondary considerations evidencing
`nonobviousness, such as commercial success, copying, long felt but unsolved needs, failures of
`others, unexpected results, etc. See KSR Int ’1' Co. v. Teleflex Inc, 550 U.S. 398, 406 (2007)
`(citing Graham 12. John Deere Co. ofKonsos City, 383 US. 1, 17—18 (1966)).
`
`In KSR, the US. Supreme Court confirmed that, in evaluating obviousness, “an
`expansive and flexible” approach is to be taken, 112., “rigid and mandatory formulas” are
`
`' 35 U.S.C. 103(a) in its form prior to March 16, 2013 is applicable to the Orange Book Patents,
`since the filing date of the earliest applications for which the Orange Book Patents are entitled to
`priority falls before March 16, 2013.
`
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`

`improper. 1d. at 415, 419. More specifically, the Court stated that “[t]he combination of familiar
`elements according to known methods is likely to be obvious when it does no more than yield
`predictable results.” Id. at 416. Additionally, it is likely obvious to: (1) substitute one known
`element for another in a known structure to yield no more than a predictable result, (2) arrange
`old elements with each performing its same known function to yield no more than one would
`expect from the arrangement, (3) make a predictable variation in a known work, when there are
`design incentives or other market forces prompting the variation (either in the same or a different
`field) and a person of ordinary skill could have implemented the variation, and (4) use a known
`technique for improving one device to improve similar devices in the same way, if such use of
`the technique would be recognized by and within the capability of a. person ofordinary skill in
`the art.
`Id. at 416—417.
`in these situations, a court must ask “whether the improvement is more
`than the predictable use of prior art elements according to their established functions." Id. at
`41?.
`
`Relevant factors in determining the level of ordinary skill in the art include the
`educational level of active workers in the field, the type of problems encountered in the art, prior
`art solutions to such problems, the rapidity of innovations in the art, and the sophistication of the
`technology. See In re GPAC Inc, 57 F.3d 1573, 1579 (Fed. Cir. 1995).
`
`In order for evidence of Secondary considerations of non -obviousness to be given
`substantial weight, the patentec must demonstrate that there is a nexus between such evidence
`and the merits of the claimed invention. Ormco Corp. v. Align Tech. Inc, 463 F.3d 1299, 131 i—
`13 (Fed- Cir. 2006).
`In other words, such evidence must arise from the claimed invention, rather
`than from extrinsic influences such as unclaimed features, prior art features, marketing activities,
`FDA requirements, etc.
`id.
`
`V.
`
`Factual and Legal Basis for Watson’s Certification
`
`A.
`
`U.S. Patent No. 9,339,507 (“the ‘507 patent”); Treprostinil Administration by
`Inhalation
`
`US. Patent No. 9,339,507 (“the ‘507 patent”) to Olschewski et a1. issued May 1?, 2016.
`The ‘507 patent is entitled “Treprostinil Administration by Inhalation," and is assigned on its
`face to United Therapeutics Corporation. The application that became the ‘507 patent was filed
`with the USPTO on May 11, 2012 and assigned U.S. Patent Application No. 13f469,854 (“the
`‘507 patent application”).
`
`1.
`
`The Claims of the ‘50? Patent
`
`The claims of the ‘507 patent read as follows:
`
`1. A kit for treating pulmonary hypertension compri sing:
`(i) a formulation comprising 200 to 1000 ugiml treprostinil or a
`pharmaceutically acceptable salt thereof;
`(ii) a pulsed ultrasonic nebulizer comprising an opto-acoustical
`trigger, configured to
`(a) aerosolizc a fixed amount of treprostinil per pulse,
`
`and
`
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`

`(b) deliver by inhalation a therapeutically effective
`single event dose of said formulation,
`said single event dose comprising 15 pg to 90 pg treprostinil or a
`pharmaceutical] y acceptable salt thereof delivered in l to 18 breaths; and
`(iii) instructions for using the pulsed ultrasonic nebulizer with
`the formulation to treat a patient with pulmonary hypertension by
`delivering [5 pg to 90 pg treprostinil or a pharmaceutically acceptable
`salt thereof in l to 18 breaths to the patient in the single event dose.
`
`2. The kit of claim l. wherein the formulation comprises 600 [,1le of
`the treprostinil or its pharmaceutical ly acceptable salt thereof.
`
`3. The kit of claim I , further comprising instructions for the human not
`to repeat the single event dose for a period of at least 3 hours.
`
`4. The kit of claim 1. wherein the single event dose produces a peak
`plaSma concentration of treprostinil about l0—l 5 minutes after the single
`event dose.
`
`5. The kit of claim 1, wherein the fixed amount of treprostinil or its
`phannaceutically salt for each breath inhaled by the human comprises at
`least 5 ng of trepmstinil or its phannaceutically acceptable salt.
`
`6. The kit of claim 2, wherein the fixed amount of treprostinil or its
`phannaceutically salt for each breath inhaled by the human comprises at
`least 5 ng of treprostinil or its pharmaceutically acceptable salt.
`
`1. The kit of claim I. wherein the single event dose is inhaled in 3 to 18
`breaths by the human.
`
`3. The kit ofclaim 6, wherein the single event dose is inhaled in 3 to 13
`breaths by the human.
`
`9. The kit ofclaim 6, further comprising instructions for the human not
`to repeat the single event dose for a period of at least 3 hours.
`
`‘507 patent at l8:l 2-52.
`
`B.
`
`U.S. Patent No. 9,358,240; Treprostinil Administration by Inhalation
`
`U.S. Patent No. 9,358,240 (“the ‘240 patent”) to Olschewski et al- issued June 7, 2016.
`The ‘240 patent is entitled “Treprostinil Administration by Inhalation,” and is assigned on its
`face to United Therapeutics Corporation. The application that became the ‘240 patent was filed
`with the USPTO on November l2, 2009 and assigned U.S. Patent Application No. 1259 l ,200
`(“the ‘240 patent application”). The ‘240 patent application was a continuation of U.S. Patent
`Application No.
`1 11748305 (“the ‘205 application”), filed on May 14, 2007 and now abandoned.
`The ‘205 application claimed priority to U.S. Provisional Application No. 60800916, filed on
`May [5, 2006.
`
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`l.
`
`The Claims of the ‘240 Patent
`
`The claims of the ‘240 patent read as follows:
`
`1. A method of treating pulmonary hypertension comprising:
`administering by inhalation to a human suffering from
`pulmonary hypertension a therapeutically effective single event dose of a
`formulation comprising fi'om 200 to 1000 ug/ml of treprostinil or a
`pharmaceutically acceptable salt thereof
`with a pulsed ultrasonic nebulizer that aerosolizes a fixed
`amount of treprostinil or a pharmaceutically acceptable salt thereof per
`pulse,
`
`said pulsed ultrasonic nebulizer comprising an opto-acoustical
`trigger which allows said human to synchronize each breath to each
`pulse,
`
`said therapeutically effective single event dose comprising from
`15 pg to 90 pg of treprostinil or a pharmaceutically acceptable salt
`thereof delivered in l to 18 breaths.
`
`2. The method of claim 1, wherein the formulation comprises 600 ug/ml
`of the treprostinil or its pharmaceutically acceptable salt thereof.
`
`3. The method of claim I, wherein the single event dose is not repeated
`for a period of at least 3 hours.
`
`4. The method of claim 1, wherein the single event dose produces a peak
`plasma concentration of treprostinil about 10—l 5 minutes after the single
`event dose.
`
`5. The method of claim 1, wherein the fixed amount of treprostinil or its
`pharmaceutical Iy salt for each breath inhaled by the human comprises at
`least 5 ug of treprostinil or its pharmaceutically acceptable salt.
`
`(1. The method of claim 2, wherein the fixed amount of treprostinil or its
`pharmaceutically salt for each breath inhaled by the hutnan comprises at
`least 5 ug of treprostinil or its pharmaceutically acceptable salt.
`
`7. The method of claim 1, wherein the single event dose is inhaled in 3-
`18 breaths by the human.
`
`8. The method of claim 6, wherein the single event dose is inhaled in 3-
`18 breaths by the human.
`
`9. The method of claim 6, wherein the single event dose is not repeated
`for a period of at least 3 bonus.
`
`‘240 patent at 13:2-37.
`
`UNITED THERAPEUTICS, EX. 2018
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR2017-D1621
`Page 10 of 41
`
`

`

`C.
`
`Claim Construction
`
`The claims ofthe ‘50? and ‘240 patents are to be accorded their usual and ordinary
`meanings to one of ordinary skill in the art as informed by the Specification and file history.
`
`D.
`
`Non-Infringement Analysis
`
`1.
`
`The ‘50? Patent
`
`(:1)
`
`Watson‘s ANDA Product Does Not Directly or Indirectly
`lnfringe the Claims of the ‘50? Patent.
`
`Claim 1
`
`is the sole independent claim of the ‘507 patent and reads as follows:
`
`1 . A kit for treating pulmonary hypertension comprising:
`(i) a formulation comprising 200 to 1000 ug/ml treprostinil or a
`pharmaceutically acceptable salt thereof;
`(ii) a pulsed ultrasonic nebulizer comprising an opto-acoustical
`trigger, configured to
`(a) aerosolize a fixed amount of treprostinil per pulse,
`
`and
`
`(b) deliver by inhalation a therapeutically effective
`single event dose of said formulation,
`said single event dose comprising 15 pg to 90 pg treprostinil or a
`p'hannaceutically acceptable salt thereof delivered in l to 18 breaths; and
`(iii) instructions for using the pulsed ultrasonic nebulizer with
`the formulation to treat a patient with pulmonary hypertension by
`delivering 15 pg to 90 pg treprostinil or a pharmaceutically acceptable
`salt thereof in 1 to 18 breaths to the patient in the single event dose.
`
`‘507 patent at 18:12-28.
`
`The Watson ANDA Product does not literally infringe claim 1 of the ‘507 patent because
`the Watson ANDA Product is an ampoule comprising a treprostinil formulation for inhalation
`and not a kit comprising: (i) a formulation comprising 200 to lOOOug/ml treprostinil; (ii) a pulsed
`ultrasonic nebulizer; and (iii) instructions for using the pulsed ultrasonic nebulizer with the
`formulation.
`
`Further, claim 1 cannot be expanded under the doctrine of equivalents to encompass the
`Watson ANDA Product based on claim vitiation. That is, if claim 1 was expanded to include the
`Watson ANDA Product, then the entire element of claim 1 requiring a kit comprising a pulsed
`ultrasonic nebulizcr would be vitiated. Such an interpretation under the doctrine of equivalents
`is improper. See Asyst Techs, Inc. v. Emirak, Inc, 402 F.3d 1188, 1195 (Fed. Cir. 2005);
`Freedman Seating Co. v. Am. Scaring Ca, 420 F.3d 1350, 1358 (Fed. Cir. 2005).
`
`Claims 2-9 of the ‘507 patent depend, either directly or indirectly, from claim 1 and
`thereby incorporate all the limitations of claim '1. Sec 35 U.S.C. § 1 12, 1] 4 (providing in relevant
`part “A claim in dependent form shall be construed to incorporate by reference all the limitations
`
`8
`
`UNITED THERAPEUTICS, EX. 201B
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR2017-D1621
`Page 11 of 41
`
`

`

`of the claim to which it refers”). See also Monsanto Co. v. Syngenta Seeds, inc. 503 F.3d 1352,
`1358 (Fed. Cir. 2007) (“Instead, claim 4, like its predecessor claim, as attested by the prosecution
`history, is in dependent form and incorporates the limits of the overarching independent claim.“
`id. ); Wotverine Work? Wide, Inc. v. Nike, Inc, 33 F.3d 1192, 1199 (Fed. Cir. 1994) (“It is axiomatic
`that dependent claims cannot be found infringed unless the claims from which they depend have
`been found to have been infringed.” id. (internal citations and quotations omitted». Therefore, the
`Watson ANDA Product cannot infringe claims 2-9 of the ‘50? patent, either literally or under the
`doctrine of equivalents, for the reasons discussed above regarding claim .1 of the ‘507 patent.
`
`The manufacture, sale, or distribution of the Watson ANDA Product
`
`is not an act of
`
`infringement of the ‘507 patent under a theory of induced infringement andlor
`indirect
`contributory infringement, because the use of the Watson ANDA Product with a pulsed
`ultrasonic nebulizer does not directly infringe the claims of the ‘507 patent.
`
`It is well-settled law that indirect infringement cannot occur without an act of direct
`infringement. See Limelight Networks, Inc. v. Akamai Technologies, Inc, 134 S.Ct. 2111, 2118-
`19 (20M) (“[l]n this case, performance of all the claimed steps cannot be attributed to a single
`person, so direct
`infringement never occurred. Limelight cannot be liable for
`inducing
`infringement that never came to pass”); Kendal Co. v. Progressive Medical Technoiogy, 85
`F.3d. 1570, 1573 (Fed. Cir. 1996)-
`It
`is also well-settled law that the replacement of an
`unpatented part of a claimed multi-part invention is the lawful right of the owner to repair his
`property. Aro Mfg. Co. v. Convertible Top Replacement Co, 365 U.S. 336 (1961); Kendal, 85
`F.3d at 153’4. Sec aiso Special Equipment Co. v. Coe, 324 U.S. 370 (I925) (the unpatented part
`of a combination patent may be appropriated by anyone).
`
`In the present situation, a patient will initially obtain the TYVASO® kit from United
`Therapeutics, the owner of the ‘ 507 patent. The TYVA SO® kit includes a Nebu-Tec OPTIN FIRE
`ultrasonic inhaler, instructions for using the inhaler, and an initial supply of ampoules containing
`600 ug/mL of treprostinil. The patent owner is aware that the initial supply of ampoules that are
`included with the kit will be used by the patient and additional ampoules will be required to
`continue to use the kit. See TYVASO® Prescribing information at p. 3 (2.4 Administration), 12
`(i 6 How Supplied/Storage and Handling).
`Therefore,
`the patient
`legally obtained the
`'I'YVASO® kit along with the right to obtain replacement ampoules in order to continue to use
`the TYVASO® kit.
`
`The ‘507 patent only claims a treprostinil formulation in combination with a kit that
`includes a nebulizer and instructions, and does not claim a treprostinil
`formulation alone.
`Indeed,
`the ‘507 patent could not claim only a formulation containing 200-1000pgimL of
`treprostinil because formulations containing this range of treprostinil for use in nebuiizers were
`known in the art well before the filing date ofthe ‘507 patent. See generally Cloutier et al., US.
`Patent No. 6,521,212 (“Cloutier”) at 5:22-29 (disclosing an inhalation formulation comprising
`500 ugme of treprostinil).
`
`Because the Watson ANDA Product is an unpatcnted and known diSposable pan of the
`kit recited in the claims of the ‘507 patent. a patient is permitted to obtain