Morris Corporate Center III
`400 Interpace Parkwav
`Parsippany, N13205::
`T862.261.?w0
`F 862.261.?001
`www.wutson.corr
`
`June 29, 201 6
`
`watso n
`
`Via FedEx®
`
`General Counsel
`
`United Therapeutics Corporation
`55 TW Alexander Drive
`
`Research Triangle Park, NC 27709
`
`General Counsel
`
`United Therapeutics Corporation
`1735 Connecticut Ave, N.W., #2
`Washington, DC 20009
`
`General Counsel
`
`United Therapeutics Corporation
`1040 Spring Street
`Silver Spring, MD 20910
`
`Foley& Lardner
`Stephen B. Maebius
`3000 K Street, N.W., Suite 600
`Washington, DC 20007-5109
`
`HIGHLY CONFIDENTIAL
`
`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 §505(j)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act and 21
`C.F.R. § 314.95, Watson Laboratories, Inc. (“Watson") hereby provides notice of the following
`information to United Therapeutics Corporation (“United Therapeutics”), as the apparent holder
`of approved New Drug Application (“NBA") No. 022387 for Tyvaso® (treprostinil) Inhalation
`Solution, 0.6 mg/ml according to the records of the US. Food and Drug Administration (“FDA“)
`and record owner of U.S. Patent Nos. 9,339,503’ (“the ‘50?f 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, ci’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
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR2017-D1622
`Page 1 of 41
`
`

`

`United Therapeutics Corporation
`Page 2
`
`Pursuant to 21 CPR. §314.95(c), 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 11.5.0. § 355(j)(2)(B)(iv)(I) 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 biocquivalence
`waiver. The Patent Amendment was submitted under 21 U.S.C. § 3550)(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 mgfml before the expiration of
`U.S. Patent Nos. 9,339,507 and 9,358,240 which are listed in the Patent and Exclusivity
`Information Addendum of FDA’S publication, Approved Drug Products 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
`[1.
`assigned Watson’s ANDA the number 208172.
`
`Pursuant to 21 CPR. § 3]4.95(c){3), we advise you that the established
`[11.
`name of the drug product that
`is the subject of Watson’s ANDA is Treprostinil Inhalation
`Solution, 0.6 mg/ml.
`
`the active
`§ 314.95(c)(4), we advise you that
`to 21 C.F.R.
`Pursuant
`IV.
`ingredient in the proposed drug product is treprostinil; the strength of the proposed drug product
`is 0.6 mgfml of treprostinil; and the dosage form of the proposed drug product is inhalation
`solution.
`
`the patents
`Pursuant to 21 CPR. § 314.95(c)(5), we advise you that
`V.
`alleged to be invalid, unenforceable, andz’or not infringed in the Paragraph IV certifications are
`U.S. Patent Nos. 9,339,507 and 9,358,240 which are listed in the Orange Book in connection
`with United Therapeutics‘ approved NDA No. 022387 for Tyvasom. According to information
`published in the Orange Book, the patents will expire as follows:
`
`U.S. PATENT NO.
`
`EXPIRATION DATE
`
`March 10, 2028
`
`9,339,507
`
`
`
`9,358,240 May 5,2028
`
`VI. Watson alleges, and has certified to FDA, that in Watson’s opinion and to
`the best ofits knowledge, U.S. Patent Nos. 9,339,507 and 9,358,240 are invalid, unenforceable,
`andr'or will not be infringed by the commercial manufacture, use or sale of the drug product
`described in Watson’s ANDA. Therefore, pursuant to 2] 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 2i U.S.C. § 3SSfj)(5)(C), this notice letter includes an Offer of
`VII.
`Confidential Access to Application. As required by §355(j)(5)(C)(i)(Ill), 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 governed by the
`Stipulated Protective Order, entered in Civil Action No. 3:15-cv-05723.
`
`Section 3550)(5){C)(i)(III) 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 of confidential access shall be considered terms of
`an enforceable contrac .” Thus,
`to the extent
`that United Therapeutics requests access to
`Confidential Watson Information,
`it necessarily accepts the terms and restrictions 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 at
`set}, 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 1V Certifications that
`US. Patent Nos. 9,339,507 and 9,358,240 are Invalid. Unenforceable and/or Not
`Infringed by the Treprostr'm't Product Described in Watson ’3 ANDA No. 208172
`
`UNITED THERAPEUTICS, EX. 2018
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR2017-D1622
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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 audior Not Infringed by
`the Treprostinil Product Described in Watson’s ANDA No. 208172
`
`I.
`
`Introduction
`
`Pursuant to § 5050)(2)(B)(iv)(ll) of the Federal Food, Drug, and Cosmetic Act and 21
`C.F.R. § 3 l4.95(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. 9,33 9,507 (“the ‘50? patent”) and 9,358,240 (“the ‘240 patent”) are
`invalid, unenforceable andtor 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.
`
`1].
`
`Watson ’5 ANDA Prod u cts
`
`The product that is the subject of 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
`m g/ml. Watson will market the Watson ANDA Product for the currently approved indication for
`the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise
`ability.
`
`Ill.
`
`The Orange Book Listed Patents
`
`[1.8. PATENT NO.
`
`March 10, 2028
`
`EXPIRATION DATE 9,339,507
`
`9,353,240
`
`May 5, 2028
`
`IV.
`
`Legal Principles
`
`A.
`
`Claim Coustruction
`
`A court must first construe claims before determining whether they are valid or infringed.
`Amazon.com, Inc. v. Barnesandnoblecom, Inc, 239 F.3d 1343, 1351 (Fed. Cir. 2001); Markman
`v. Westview Instruments, Inc, 52 F.3d 967, 976, 976 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, 122., 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 ofthe specification in claim construction derives from its statutory
`role of providing a “full” and “exact” description of the claimed invention.
`Id. at 13 16.
`
`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 Gtass Works 12. Sumfromo EIeo. USA, Inc, 868 F.2d 1251, 1258 (Fed. Cir. 1989).
`Any deviation from the claim precludes a finding of literal infringement. See, e.g.. Cole v.
`Kimberly-Ciork Corp, 102 F.3d 524, 532 (Fed. Cir. I996).
`
`first, the claims must be
`An analysis ofliteral 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 Markman, 52 F.3d at 976; see also Navo Nordisk ofN. Arm, Inc. v. Genenrech, Inc, 77 F.3d
`[364, 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 Markmon, 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. Womer-Jenkinson C0.,
`Inc. v. Hilton Davis Chem. Co., 520 US. 1?, 21, 40 (l 997). The determination of equivalency is
`an objective inquiry applied on an element-by-element basis taking into account the role of each
`claim element in the context ofthe 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-resuit
`test and the insubstantial differences test.
`Id. 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.
`See. e.g.. Wilson Sporting Goods Co. 1:. David Geoflrey & Assocs., 904 F.2d 67?, 683 (Fed. Cir.
`1990), overruled on other grounds by Cardinal Chem. Co. v. Morton Inr‘t, 508 [1.5. 83 (1993).
`Additionally, prosecution history estoppel operates to prevent recapture, through the doctrine of
`equivalents, of coverage of subject matter that was relinquished by amendment or argument
`during prosecution. Fesro Corp. v. Shaketsn Kimoku Kogyo Krtbushikt’ Co, Ltd. 535 U.S. 722,
`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 ofinfringement under 35 U.S.C. § 271(1)) andIor a contributory infringement under
`35 U.S.C. § 271(c). See Joy Techs, Inc. v. Fiakr. 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 ofdirect in fringement." Id; see oIso C. R. Bard. Inc. v. Advanced
`Cardiovascular Sys. Inc., 91 1 F.2d 670, 673 (Fed. Cir. 1990).
`
`Inducement of infringement is actively and knowingly aiding and abetting another’s
`direct infringement of a patent claim. See id at 6?5; DSUMed. Corp. v. JMS Co, Ltd, 47] F.3d
`1293, 1306 (Fed. Cir. 2006).
`in order to find induced infringement, a patentce must show (1)
`direct infringement, either literally or under the doctrine of equivalents, (ii) that the alleged
`indirect infringer actually intended to cause another to directly infiinge, (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) (2011); see also DSU Med. Corp, 471 F.3d at 1304—05.
`
`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 & Mfg. (30., 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.
`Microsofl Corp. 12. Mi Ltd. P'ship, 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.
`SiIicon Graphics, Inc. v. ATI Technologies, Inc, 60'? 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 ofthe invention.” In re Graves, 69 F.3d 1147, 1152, 36 U.S.P.Q.2d 169? (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,
`
`In addition, “products of identical chemical composition cannot have
`1369 (Fed. Cir. 1991).
`mutually exclusive properties.” In re Spada, 911 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
`Phamtaceutr'oai Products, Inc, 4?I F.3d I363, 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 Metats Corp. of/tmerr‘ca v. Banner, 778 F.2d 775, 782
`(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.
`
`Telemac Cellular Corp. v. Topp Telecom. Inc, 247 F.3d 13l6, 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 of multiple 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)]
`(20] I).
`In determining obviousness, 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 In: ’1 Co. v. Teieflex Inc, 550 U.S. 393, 406 (2007)
`(citing Graham v. John Deere Co. ofKansas City, 383 US. 1, 17—18 (1966)).
`
`In KSR, the US. Supreme Court confirmed that, in evaluating obviousuess, “an
`expansive and flexible" approach is to be taken, i.e., “rigid and mandatory formulas” are
`
`' 35 U.S.C. 103(a) in its form prior to March l6, 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. 20} 3.
`
`4
`
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`

`Id. at 415, 419. More specifically, the Court stated that “[t]he combination of familiar
`improper.
`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: (I) 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 ofa person of ordinary 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 GPAClnc., 57 F.3d 1573, 1579 (Fed. Cir. 1995).
`
`In order for evidence of secondary considerations of non-obviousness to be given
`substantial weight, the patentee mu st demonstrate that there is a nexus between such evidence
`and the merits of the claimed invention. Ornico Corp. v. Align Tech. Inc, 463 F.3d 1299, 131 l—
`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.
`
`US. 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. 13/469,854 (“the
`‘507 patent applicatioa”).
`
`l.
`
`The Claims ofthe ‘51]?I Patent
`
`The claims of the ‘507 patent read as follows:
`
`1. A kit for treating pulmonary hypertension comprising:
`(i) a formulation comprising 200 to 1000 ugl’ml treprostinil or a
`pharmaceutically acceptable salt thereof;
`(ii) a pulsed ultrasonic nebulizer comprising an opto-acoustical
`trigger, configured to
`(a) aerosol ize a fixed amount of trcprostinil 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
`pharmaceutically acceptable salt thereof delivered in l to l8 breaths; and
`(iii) instructions for using the pulsed ultrasonic nebulizcr with
`the formulation to treat a patient with pulmonary hypeitension by
`delivering 15 pg to 90 ng 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 1. wherein the formulation comprises 600 pg/ml of
`the n'eprostinil or its pharmaceutically acceptable salt thereof.
`
`3. The kit of claim 1, 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— 15 minutes after the single
`event dose.
`
`5. The kit of claim 1. wherein the fixed amount oftrcprostinil or its
`phannaceutically salt for each breath inhaled by the human comprises at
`least 5 ng of treprostini] or its pharmaceutically 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.
`
`?. The kit of claim 1, wherein the single event dose is inhaled in 3 to 18
`breaths by the human.
`
`8. The kit of claim 6, wherein the single event dose is inhaled in 3 to 18
`breaths by the human.
`
`9. The kit of claim 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 ”3:12-52.
`
`B.
`
`US. Patent No. 9.358.240; Trap rostinil Administration by Inhalation
`
`US. Patent No. 9,358,240 (“the ‘240 patent”) to Olschewski et at. 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 [ISI’TO on November 12, 200.9 and assigned US. Patent Application No. 125912.00
`(“the ‘240 patent application”). The ‘240 patent application was a continuation of US. Patent
`Application No. 11l748,205 (“the ‘205 application”), filed on May 14, 200? and now abandoned.
`The ‘205 application claimed priority to US. Provisional Application No. 6022800316, filed on
`May 15, 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 from 200 to 1000 pg/ml of treprogtinil or a
`pharmaceutically acceptable salt thereof
`with a pulsed ultrasonic nebulizer that aerosolizes a fixed
`amount of treprostinil or a phannaceutically 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
`l5 pg to 90 pg of treprostinil or a pharmaceutically acceptable salt
`thereof delivered in l to 13 breaths.
`
`2. The method of claim 1, wherein the formulation comprises 600 pgfml
`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-] 5 minutes afier the single
`event dose.
`
`5. The method of claim 1, wherein the fixed amount of treprostinil or its
`pharmaceutically salt for each breath inhaled by the human comprises at
`least 5 pg of treprostinil or its phannaccutically acceptable salt.
`
`6. The method of claim 2, wherein the fixed amount ot‘treprostinil or its
`pharmaceutically salt for each breath inhaled by the human comprises at
`least 5 pg of treprostinil or its pharmaceutically acceptable salt.
`
`’7. The method of claim l, wherein the single event dose is inhaled in 3-
`18 breaths by the human.
`
`3. 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 hours.
`
`‘240 patent at 18:2-37.
`
`UNITED THERAPEUTICS, EX. 2018
`WATSON LABORATORIES V. UNITED THERAPEUTICS, IPR2017-D1622
`Page 10 of 41
`
`

`

`C.
`
`Claim Construction
`
`The claims of the ‘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 tile history.
`
`D.
`
`Non-Infringement Analysis
`
`I.
`
`The ‘50? Patent
`
`(a)
`
`Watson‘s ANDA Product Does Not Directly or Indirectly
`lufringe the Claims of the ‘50? Patent.
`
`Claim I
`
`is the sole independent claim ofthe ‘507 patent and reads as follows:
`
`I. A kit for treating pulmonary hypertension comprising:
`(i) a formulation comprising 200 to 1000 ug/rnl treprostinil or a
`pharmaceutically acceptable salt thereof;
`(ii) a pulsed ultrasonic nebulizer comprising an opto-acoustica]
`trigger, configured to
`(a) aerosolize a fixed amount of treproslinil 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 ug treprostinil or a
`pharmaceutically acceptable salt thereof delivered in 1 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 ug treprosrinil or a phannaceutically acceptable
`salt thereof in l 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 lOOOpg/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 nebulizer 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. Searing Ca. 420 F.3d 1350, 1358 (Fed. Cir. 2005}.
`
`Claims 2-9 of the ‘50?l patent depend, either directly or indirectly, from claim l and
`thereby incorporate all the limitations ofclaim 1. See 35 U.S.C. § 112, 11 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-D1622
`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); Wolverine World Wide, inc. v. Nike, Inc, 38 F.3d 1192, 1199 (Fed. Cir. 1.994) (“it is axiomatic
`that dependent claims cannot be found infringed unless the claims from which they depend have
`been tbund to have been infringed.” Id. (internal citations and quotations omitted». Therefore, the
`Watson ANDA Product cannot infringe claims 2-9 ofthe ‘507 patent, either literally or under the
`doctrine of equivalents, for the reasons discussed above regarding claim ] 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 and/or
`indirect
`contributory infi-ingement, because the use of the Watson ANDA Product with a pulsed
`ultrasonic nebulizer does not directly infringe the claims of the ‘507 patent.
`
`is well-settled law that indirect infringement cannot occur without an act of direct
`It
`infringement. See Limelight Networks, Inc. v. Akamoi Technologies. Inc, 134 S.Ct. 21 l l, 21 18-
`19 (2014) (“[I]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 Teehnoiogt, 85
`F.3d. 1570, 1573 (Fed. Cir. 1996).
`It
`is 21150 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. Ara Mfg. Co.
`1:. Convertible Top Replacement Co., 365 US. 336 (1961); Kendal, 85
`F.3d at 1574. See also Special Equipment Co. v. Coe, 324 US. 370 (I 925) (the unpatented part
`of a combination patent may be appropriated by anyone).
`
`initially obtain the TYVASO€to kit from United
`In the present situation, a patient will
`Therapeutics, the owner of the ‘507 patent. The TYVASO‘m kit includes a Nebu-Tec OP’l‘lNEB®
`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‘R‘ kit along with the right to obtain replacement ampoules in order to continue to use
`the TYVASO” kit.
`
`The ‘50? 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 ZOO-lOOOpgimL of
`treprostinil because formulations containing this range of treprostinil for use in nebulizcrs were
`known in the art well before the filing date of the ‘507 patent. See generoiijz Cloutier et 31., U.S.
`Patent No. 6,521,212 (“Cloutier”) at 5:22-29 (disclosing an inhalation formulation comprising
`500 ug/mL oftreprostinil).
`
`Because the Watson ANDA Product is an unpatcnted and known disposable part of the
`kit recited in the claims of the ‘507 patent. a patient
`is permitted to obtain the unpateuted
`arnpoules fro