Morris Corporate Center In
`400 Interpace Parkway
`Pa rsipparw, NJ 0?054
`T 862.261.7000
`F 862.261.2001
`www.watson.corn
`
`June 12,2015
`
`Watson
`
`Via FedEx®
`
`General Counsel
`
`United Therapeutics Corporation
`PO. Box 14185
`55 T.W. 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
`1 104 Spring Street
`Silver Spring, MD 20910
`
`Foley& Lardner
`Stephen B. Meabius
`300 K Street, N.W., Suite 600
`Washington, DC 20007—5109
`
`HIGHLY CONFIDENTIAL
`
`Re: Notification of Certification for US. Patent Nos. 6,521,212; 6,736,033; and 8,497,393
`Pursuant to § 505(j)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act
`
`Dear Madam or Sir:
`
`to §505(j)(2)(B)(iv) of the Federal Food, Drug, and Cosmetic Act and 21
`Pursuant
`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 (“NDA”) No. 022387 for Twaso® Inhalation Solution, 0.6
`Ing/rnl according to the records of the US. Food and Drug Administration (“FDA”) and record
`owner of US. Patent Nos. 6,521,212 (“the ‘212 patent“); 6,756,033 (“the ‘033 patent“); and
`8,497,393 (“the ‘393 patent) according to the records of the US. Patent and Trademark Office
`(“PTO“) anda’or as indicated on the face of the patents.
`
`UNITED THERAPEUTICS, EX. 2013
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR2017—D1622
`Page 1 of 30
`
`

`

`United Therapeutics Corporation
`Page 2
`
`As a courtesy, Watson is also providing a copy of this Notice Letter and Detailed
`Statement to Foley & Lardner, cfo Stephen B. Meabius, as the correspondent for the “212, ‘033,
`and “393 patents according to the records of the PTO and70r as indicated on the face of the
`patents.
`
`Pursuant to 21 C.F.R. §3l4.95(e), Watson requested and received 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. Consequently, the operative date for determining the start of the 45-day clock under 21
`U.S.C. § 355(1')(5)(B)(iii) began from the receipt ofthis notice, as sent via FedEx®.
`
`Pursuant to 21 U.S.C. § 3550)(2)(B)(iv)(l) and 21 CPR. §3l4.95(c)(l),
`1.
`we advise you that FDA has received an Abbreviated New Drug Application (“ANDA”) from
`Watson for Treprostinil Inhalation Solution, 0.6 mgfml. The ANDA contains the required
`bioavailability andi’or bioequivalence data andlor bioequivalence waiver. The ANDA 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 nag/ml before the expiration of U.S. Patent Nos. 6,521,212; 6,756,033; and
`8,497,393 which are listed in the Patent and Exclusivity Information Addendum of FDA’s
`publication, Approved Drug Products with Therapeutic Equivalence Evahtations (commonly
`known as the “Orange Book").
`
`to 21 C.F.R.
`Pursuant
`II.
`assigned Watson’s ANDA the number 208172.
`
`§ 314.95(c)(2), we advise you that FDA has
`
`Pursuant to 21 CPR. § 314.95(c)(3}, we advise you that the established
`111.
`name of the drug product that
`is the subject of Watson’s ANDA is Treprostinil Inhalation
`Solution, 0.6 rag/ml.
`
`the active
`to 21 C.F.R. § 314.9S(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
`to 21 C.F.R. § 314.95(c)(5), we advise you that
`Pursuant
`V.
`alleged to be invalid, unenforceable, andi’or not infringed in the Paragraph IV certifications are
`U.S. Patent Nos. 6,521,212; 6,756,033; and 8,497,393 which are listed in the Orange Book in
`connection with United Therapeutics‘ approved NDA No. 022387 for Tyvaso®. According to
`information published in the Orange Book, the patents will expire as follows:
`
`U.S. PATENT NO.
`
`EXPIRATION DATE
`
`
`
`.
`6,521,212
`November 13, 2018
`
`
`
`6,756,033
`November 13, 2013
`
`8,497,393
`December 15, 2028
`
`
`UNITED THERAPEUTICS, EX. 2013
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR2017—D1622
`Page 2 of 30
`
`

`

`United Therapeutics Corporation
`Page 3
`
`V1. Watson alleges, and has certified to FDA, that in Watson‘s opinion and to
`the best of its knowledge, U.S. Patent Nos. 6,521,212; 6,756,033; and 8,497,393 are invalid,
`unenforceable, andi’or 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.
`§ 355(j)(2)(B)(iv)(II) and 21 C.F.R. § 314.95(c)(6), Watson’s detailed statement ofthe legal and
`factual basis for the Paragraph 1V certifications set forth in Watson’s ANDA is attached hereto
`and made 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.
`
`Section 3550)(5)(C)(i)(lll) allows Watson to impose restrictions “as to persons
`entitled to access, and on the use and disposition of any information accessed, as would apply
`had a protective order been entered for the purpose of protecting trade secrets and other
`confidential business information.” That provision also grants Watson the right to redact its
`ANDA in response to a request for Confidential Access under this offer.
`
`As permitted by statute, Watson imposes the following terms and restrictions on
`its Offer of Confidential Access:
`
`(1)
`
`(2)
`
`(3)
`
`Watson will permit confidential access to certain information from its proprietary
`ANDA No. 208172 to attorneys from one outside law firm representing United
`Therapeutics, provided however that such attorneys do not engage, formally or
`informally,
`in any patent prosecution for United Therapeutics or any FDA
`counseling, litigation or other work before or involving FDA. Such information
`(hereinafter, “Confidential Watson Information“) shall be marked with the legend
`“CONFIDENTIAL.”
`
`The attorneys from the outside law firm representing United Therapeutics shall
`not disclose any Confidential Watson Information to any other person or entity,
`including employees of United Therapeutics, outside scientific consultants, andfor
`other outside counsel retained by United Therapeutics, without the prior written
`consent of Watson.
`
`As provided by §355(j)(5)(C)(i)(III), the outside law firm representing United
`Therapeutics shall make use of the Confidential Watson Information for the sole
`and exclusive purpose of determining whether
`an action referred to in
`§3550)(5)(B)(iii) can be brought — and for no other purpose. By way of
`example only, the Confidential Watson Information shall not be used to prepare
`or prosecute any future or pending patent application by United Therapeutics; in
`connection with any filing to, or communication with, FDA relating to Watson’s
`ANDA No. 208179; or in connection with any submission to, or communication
`with, the United States Phannacopeia or any similar organization. The outside
`law firm representing United Therapeutics agrees to take all measures necessary
`
`UNITED THERAPEUTICS, EX. 2013
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201T—D1622
`Page 3 of 30
`
`

`

`United Therapeutics Corporation
`Page 4
`
`to prevent unauthorized disclosure or use of the Confidential Watson lnfonnation,
`and that all Confidential Watson Information shall be kept confidential and not
`disclosed in any manner inconsistent with this Offer of Confidential Access.
`
`The Confidential Watson Information disclosed is, and remains, the property of
`Watson. By providing the Confidential Watson Information, Watson does not
`grant United Therapeutics andfor their outside law firm any interest in or license
`for the Confidential Watson lnfonnation.
`
`The outside law firm representing United Therapeutics shall, within thirty-five
`(35) days from the date that it first receives the Confidential Watson Information,
`return to Watson all Confidential Watson Information and any copies thereof
`Said outside law firm shall return all Confidential Watson Information before any
`infringement suit is filed by United Therapeutics, if suit is commenced before this
`35-day period-expires.
`In the event that United Therapeutics opts to file suit, none
`of the information contained in or obtained from any Confidential Watson
`Information that Watson provides shall be included in any publicly-available
`complaint or other pleading.
`
`Nothing in this Offer of Confidential Access shall be construed as an admission
`by Watson regarding the validity, enforceability, andfor infringement of any US.
`patent. Further, nothing herein shall be construed as an agreement or admission
`by Watson with respect to the competency, relevance, or materiality of any such
`Confidential Watson Information, document, or thing. The fact that Watson
`provides Confidential Watson lnfonnation upon request of United Therapeutics
`shall not be constnied as an admission by Watson that such Confidential Watson
`lnfonnation is relevant to the disposition of any issue relating to any alleged
`infi-ingement of or to the validity or enforceability of US. Patent Nos. 6,521,212;
`6,756,033; and 8,497,393.
`
`The attorneys from the outside law firm representing United Therapeutics shall
`acknowledge in writing their receipt of a copy of these terms and restrictions prior
`to production of any Confidential Watson Information.
`Such written
`acknowledgement shall be provided to Watson.
`
`This Offer of Confidential Access shall be governed by the laws of the State of
`New Jersey.
`
`(4)
`
`(5)
`
`(6)
`
`(7")
`
`(8)
`
`Section 355(j)(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 contract." Thus,
`to the extent
`that United Therapeutics requests access to
`Confidential Watson information,
`it necessarily accepts the terms and restrictions outlined
`above. Written notice requesting access under this Offer of Confidential Access should be made
`to:
`
`UNITED THERAPEUTICS, EX. 2013
`WATSON LABORATORIES V. UNITED THERAPEUTICS, |PR201T—D1622
`Page 4 of 30
`
`

`

`United Therapeutics Corporation
`Page 5
`
`Brian Anderson, Esq.
`Morris Corporate Center III
`400 Interpace Parkway
`Parsippany, NJ 07054
`(862) 261~8406
`brian.andersonfaactaviscom
`
`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 er
`seq, pursuant to 21 U.S.C. § 355(j)(5)(C).
`
`Very truly yours,
`
`Watson Laboratories, Inc.
`
`By:
`
`glfimggha:
`
`’Qf
`
`Joyce Anne De gaudio
`Executive Director, Regulatory Affairs
`
`Enclosure: Watson ’3 Detailed Focma! and Legel’ Basis for Its Paragraph 1 V Certifications that
`US. Patent Nos. 6,521,2f2: 6, 756. 033: and 8,497,393 are Irrvoh'd, Unenforceable
`and/or No! Infi't'trged by the Treprosn'm? Product Described in Watson ’5 AND/I No.
`208} 72
`
`UNITED THERAPEUTICS, EX. 2013
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`Page 5 of 30
`
`

`

`ENCLOSURE
`
`Watson’s’ Detailed Factual and Legal Basis for Its Paragraph IV Certifications that U.S.
`Patent Nos. 6,521,212; 6,756,033; and 8,497,393 Are Invalid, Unenforceable andz’or Not
`Infringed by the Treprostinil Product Described in Watson’s ANDA No. 208172
`
`I.
`
`Introduction
`
`Pursuant to § 5050)(2)(B)(iv)(11) of the Federal Food, Drug, and Cosmetic Act and 21
`CPR. § 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. 6,521,212 (“the ‘212 patent"); 6,756,033 (“the ‘033 patent“); and
`8,497,393 (“the ‘393 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.
`
`II.
`
`Watson’s ANDA Products
`
`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 myml. 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 pulmonaiy arterial hypertension (PAH) (WHO Group 1) to improve exercise
`ability.
`
`III.
`
`The Orange Book Listed Patents
`
`I vs. PATENT NO.
`
`EXPIRATION DATE
`
`
`
`6,521,212 November 13, 2018
`
`December 15, 2028
`
`6,756,033
`
`8,497,393
`
`November 13, 2018
`
`IV.
`
`Legal Principles
`
`A.
`
`Claim Construction
`
`A court must first construe claims before determining whether they are valid or infringed.
`Amazon.com. Inc. v. Barnesnndnobfe. com. Inc, 239 F.3d 1343, 1351 (Fed. Cir. 2001); Markmon
`v. Wesm'cw Instruments, Inc, 52 F.3d 967, 976, 976 n. 7 (Fed. Cir. 1995) (en bane). Claims
`
`UNITED THERAPEUTICS, EX. 2013
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`

`

`must be construed the same way for determining validity and infringement. Amazoncom, 23.9
`F.3d at 1351.
`
`The claim construction inquiry begins in all cases with the actual words of the claims.
`Pfit'h‘i'ps v. AW?! Corp, 415 F.3d 1303, 1312 (Fed. Cir. 2005} (on bone). 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, 1.6., as of the
`effective filing date ofthe 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.“ 1d. at
`1315—1316. The importance ofthe specification in claim construction derives from its statutory
`role ofproviding a “full” and “exact“ description ofthe 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 Corning Glass Works v. Sumitomo Efec. U.S.A.. Inc, 868 F.2d 1251, 1258 (Fed. Cir. 1989).
`Any deviation from the claim precludes a finding ofliteral infringement. See, e.g., Cote v.
`Kimberly-Clark 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 Mor‘kmnn, 52 F.3d at 976; see also Novo Nordisfc ofN. Am, Inc. v. Genentech. Inc, 7'? 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 Marianas, 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-Jenki‘nson Co.,
`Inc. v. Hifron Dow‘s Chem. Co., 520 U.S. 17, 21, 40 (199?). The determination ofequivalency is
`an objective inquiry applied on an element-by-element basis taking into account the role of each
`claim element in the context of the claim. Id. at 29, 40.
`
`The Supreme Court has not mandated any specific approach to evaluate equivalency. Id.
`at 39-40. Among the recognized approaches that may be applied include the function-way-result
`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.,
`tfi'fson Sporting Goods Co. v. David Geoffrey & Assocs., 904 F.2d 677, 633 (Fed. Cir.
`1990), overruled on other grounds by Carolina! Chem. Co. v. Morton Int’f, 508 US. 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
`
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`

`during prosecution. Festo Corp. v. Sizoketsn Kiiizoktt Kogyo Knbtrsiiiki Co.. Ltd, 535 U.S. 722,
`733—34 {2002).
`
`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. § 2?l(b) andfor a contributory infringement under
`35 U.S.C. § 2?1(c). See Joy Techs, Inc. v. Flatt. Inc, 6 F.3d 770, 7?4 (Fed. Cir. 1993).
`“Liability for either active inducement of infringement or for contributory infringement is
`dependent upon the existence of direct infringement.” Id; see also CR. Bord, Inc. v. Advanced
`Cordiovoscnianys.. Inc, 911 F.2d 670, 6?3 (Fed. Cir. 1990).
`
`Inducement'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).
`In 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 infringer 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 toactual infringement. See 35
`U.S.C. § 271(b) (2011); see also DSU Med. Corp, 471 F.3d at 1304—05.
`
`Contributo1y infringement is knowingly making andfor 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. Co, 803 F.2d 1170, l 174 (Fed. Cir. 1986).
`
`C.
`
`Invalidity
`
`A patent may be proven invalid by a showing of clear and convincing evidence.
`Microsofl Corp. v. i4i Ltd. P’ship, 131 S.Ct. 2238, 2251 (2011).
`
`I.
`
`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—9? (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 an and
`be in possession of the invention.” in re Groves, 69 F.3d 1 147, 1152, 36 U.S.P.Q.2d 1697r (Fed.
`Cir. 1995).
`
`The law of anticipation does not require that a prior alt reference explicitly disclose
`infonnation that is inevitably present based in 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. Gen-cor Industries. Inc, 953 F.2d 1360,
`1369 (Fed. Cir. 1991).
`In addition, “products of identical chemical composition cannot have
`3
`
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`

`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
`prior art teaches the identical chemical structure, the prOperties applicant discloses andior claims
`are necessarily present. 7d.
`
`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
`Phai'maceaiicai 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 Metals Corp. of/imerica 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 Ceiiiifar Caip. v, Topp Teiecom, 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 preperty
`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)I
`(201 1). In determining obviousness, the following four factors must be considered: (1) the scope
`and content of the prior an; (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 [mi '7 Co. v. Teieflex Inc, 550 U.S. 398, 406 (2007)
`(citing Graham v. John Deere Co. ofKansas City, 383 U.S. 1, 17—18 (1966)).
`
`' 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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`

`In KSR, the U.S. Supreme Court confirmed that, in evaluating obviousness, “an
`expansive and flexible” approach is to be taken, i.e., “rigid and mandatory formulas” are
`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: (l) 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 fi'om 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 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 GPACInc., 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 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, 1311—
`13 (Fed. Cir. 2006).
`In other words, such evidence must ari se 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. 6,521,212; Method for Treating Peripheral Vascular Disease
`by Administering Benzindene Prostaglandins by Inhalation
`
`U.S. Patent No. 6,521,212 (“the ‘212 patent") to Cloutier et a1. issued February 18, 2003.
`The ‘212 patent is entitled “Method for Treating Peripheral Vascular Disease by Administering
`Benzindene Prostaglandins by Inhalation,“ and is assigned on its face and according to the PTO
`Assignment database to United Therapeutics Corporation. The application which became the
`‘212 patent was filed with the USPTO on March 15, 2000 and assigned U.S. Patent Application
`No. 095255-171 (“the ‘212 patent application"). The ‘212 patent application claimed priority to
`U.S. Provisional Patent Application No. 601124399, filed on March 18, 1999.
`
`l.
`
`The Claims of the ‘212 Patent
`
`The claims of the ‘212 patent, as amended by the Certificate of Correction, read as
`follows:
`
`I. A method of treating peripheral vascular disease comprising
`
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`

`administering to a mammal in need thereof by inhalation a
`formulation comprising a therapeutically effective amount ofa
`benzindene prostaglandin.
`
`2. The method of claim 1, wherein said benzindene prostaglandin
`is inhaled in an aerosolized form.
`
`3. The method of claim 2, wherein said benzindene prostaglandin
`is UT-l 5.
`
`4. The method of claim 3, wherein said aerosolized form comprises
`droplets less than 10 micrometers in diameter, said droplets
`comprising said UT-l 5 in a suitable pharmacologically-
`acceptable liquid carrier.
`
`5. The method of claim 1, wherein the mammal is a human.
`
`6. A method for treating pulmonary hypertension in a mammal
`comprising delivering to said mammal an effective amount of
`UT-l 5 or its pharmaceutically acceptable salt or ester by
`inhalation.
`
`'7. The method ofelaim 6, wherein said UT-lS is inhaled in an
`aerosolized form.
`
`'
`
`8. The method of claim 7, wherein said aerosolized form comprises
`droplets less than 10 micrometers in diameter, said droplets
`comprising UT-15 in a Suitable pharmacological]y—acceptable
`liquid carrier.
`
`9. The method of claim 6, wherein said UT—lS is inhaled in powder
`form comprising particles less than 10 micrometers in diameter.
`
`10. The method of claim 1, wherein the formulation comprises a
`sustained release form of a benzindene prostaglandin [sic].
`
`i l. The method of claim 6, wherein said UT} 5 is a sustained
`release form.
`
`12. The method of claim 1, wherein said aerosolized administration
`of benzindene prostaglandin has no effect on heart rate.
`
`(‘212 patent at col. 13,1. 26,to col. 14,1.29.)
`
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`B.
`
`U.S. Patent No. 6,756,033; Method for Delivering Benzindene Prostaglandins
`by Inhalation
`
`US. Patent No. 6,756,033 (“the ‘033 patent") to Clouticr ct a]. issued June 29, 2004. The
`‘033 patent is entitled “Method for Delivering Benzindene Prostaglandins by Inhalation,” and is
`assigned on its face to United Therapeutics Corporation. The application which became the “033
`patent was filed with the USPTO on August 6, 2002 as a continuation ofthe ‘2] 2 patent
`application and assigned US. Patent Application No. 10f212,144 (“the ‘033 patent application”).
`
`1.
`
`The Claims of the ‘033 Patent
`
`The claims of the ‘033 patent, as amended by the Certificate of Correction, read as
`follows:
`
`1. A method of delivering to a mammal in need thereof a
`therapeutically effective amount of a benzindene prostaglandin
`comprising administering to the mammal by inhalation a
`formulation comprising droplets measuring less than 10
`micrometers in diameter, wherein said droplets comprise a
`therapeutically effective amount of the benzindene
`prostaglandin.
`
`2. The method of claim 11 wherein said formulation comprises
`droplets less than 10 micrometers in diameter, said droplets
`comprising said benzindene prostaglandin is 9-deoxy-2',9-alpha-
`methane-3 -oxa-4, 5,6-trinor3 ,7-{1 ‘3 '-interphenylene)—l 3,14-
`dihydro-prostaglandin F] in a suitable pharmacologically-
`acceptable liquid carrier.
`
`3. The method of claim 1, wherein the mammal is a human.
`
`4. The method of claim 1, wherein the formulation comprises a
`sustained release form of the benzindene prostaglandin.
`
`5. The method of claim 1, wherein the administering of benzindene
`prostaglandin has no effect on heart rate.
`
`6. A method of delivering to a mammal in need thereofa
`therapeutically effective amount of a benzindenc prostaglandin
`comprising administering to the mammal by inhalation a powder
`formulation comprising particles measuring less than 10
`micrometers in diameter, wherein said particles comprise a
`therapeutically effective amount of the benzindene
`prostaglandin.
`
`7. The method of claim 6, wherein the benzindene prostaglandin is
`UT—] 5
`
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`

`8. The method of claim 6, wherein the mammal is a human.
`
`9‘ The method of claim 6, wherein the formulation comprises a
`sustained release form ofthe benzindene prostaglandin.
`
`10. The method of claim 6, wherein the administering ofthe
`benzindene prostaglandin has no effect on heart rate.
`
`(“033 patent at col. 13,1. 2Sto col. 14,1. 29.)
`
`C.
`
`US. Patent No. 8,497,393; Process to Prepare Treprostinil, the Active
`Ingredient in Remodulin®
`
`US. Patent No. 8,497,393 (“the ‘393 patent”) to Batra et al. issued July 30, 2013. The
`‘393 patent is entitled “Process to Prepare Treprostinil, the Active Ingredient in Remodulin,” and
`is assigned on its face to United Therapeutics Corporation. The “393 patent application was filed
`on July 13, 2012 as a continuation ofU.S. Patent Application No. 121’3343’31, filed on December
`15, 2008, now US. Patent No. 8,242,305. The ‘393 patent further claims priority to Provisional
`Application No. 61/014,232, filed on December 17', 2007.
`
`1.
`
`The Claims of the ‘393 Patent
`
`The ‘393 patent issued on July 20, 2013 with the following twenty-two claims:
`
`1. A product comprising a compound of formula I
`H
`YI_fi—fi ‘R‘r
`u. L .
`OH
`
`H
`
`otcnzmoon
`
`(II
`
`or a pharmaceutically acceptable salt thereof, wherein said
`product is prepared by a process comprising
`(a) alkylating a compound of structure 11 with an
`alkylating agent to produce a compound of formula
`III,
`
`Yl_fi_fi_R7
`M:
`I-I
`
`H
`
`H
`
`1111
`
`Utmzucu
`
`um
`
`Yrfi—fi—R’
`OH
`
`H
`
`“
`
`OH
`
`wherein
`
`w = 1,