`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`Commissioner for Patents
`United States Patent and Trademark Office
`Washington, D.C. 20231
`www.USPTO.gov
`
`Leslie Morioka
`Patent Department
`White & Case LLP
`1155 Avenue of the Americas
`New York, NY 10036-2787
`
`In Re: Patent Term Extension
`Application for
`US. Patent No. 5,674,860
`
`.
`
`Ad LED
`SAN 09 201Lf
`
`DENIAL OF PATENT TERM EXTENSION APPLICATION
`. UNDER 35 U.S.C. 156 FOR U.S. PATENT No.5,674,860
`
`Thisis in responseto the application for extension of the patent term of U.S. Patent No.
`5,674,860 (the ‘860 patent) under 35 U.S.C. § 156 filed in the United States Patent and Trademark
`Office (USPTO)on September 19, 2006. The patent term extension application (PTE Application)
`wasfiled by AstraZeneca AB (Applicant) the ownerofrecord of the patent. Extension was sought
`based upon the premarket review under § 505 of the Federal Food, Drug, and Cosmetic Act
`(FFDCA)for a human drug product known by the tradename SYMBICORT®andhavingthe active
`ingredients budesonide and formoterol fumarate dihydrate. The application indicated that
`SYMBICORT®had been approved for commercial use and sale by the Food and Drug
`Administration (FDA) on July 21, 2006.
`
`A determination has been madethat the ‘860 patent is NOTeligible for patent term
`extension based uponthe regulatory review period of SYMBICORT®. Therefore, Applicant’s PTE
`application is DENIED.
`
`PROCEDURAL BACKGROUND
`
`(1)
`
`(2)
`
`(3)
`
`(4)
`
`On October 7, 1997, the USPTO issued the ‘860 patent to Christer C.G. Carlin et al. It is
`assigned to AstraZeneca AB.
`.
`
`On July 21, 2006, FDA approved New Drug Application (NDA) No. 21-929, thereby
`' granting permission for commercial marketing or use of SYMBICORT®(budesonide and
`formoterol fumarate dihydrate). Applicant received notice of this approval at 4:36 PM on
`July 21, 2006 (after the close of business).
`
`On September 19, 2006, Applicant filed a PTE Application under § 156 to extend the term
`of the ‘860 patent based on FDAregulatory review of SYMBICORT®.
`
`On June 20, 2007, pursuant to the Memorandum of Understanding Between the USPTO and
`the FDA, see 52 Fed. Reg. 17830, May 12, 1987, the USPTO requested assistance from the
`FDA (USPTOLetter to FDA) in determining eligibility of the ‘860 patent for patent term
`extension based on the regulatory review period of SYMBICORT®. The USPTOindicated
`in its letter that “[s]ince budesonide and formoterol [fumarate dihydrate] have been
`previously approved individually, their use in a combination product does not appear to
`comply with 35 U.S.C. § 156(a)(5)(A), i.e., the approval of SYMBICORT® would not
`
`]
`
`Complex Ex. 1013
`Complex Ex. 1013
`
`1
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`

`

`U.S. Patent No. 5,674,860
`Page 2
`appear to'constitute the first permitted commercial marketing or use of the product as
`required by 35 U.S.C. § 156(a)(5)(A).”
`
`(5)
`
`On December6, 2007, the FDA communicated their findings to the USPTO (FDALetter).
`The FDAindicated that SYMBICORT®(budesonide and formoterol fumarate dihydrate)
`had been subject to regulatory review under NDA 21-929 in accordance with section 505 of
`the FFDCA,and confirmed that NDA 21-929 did not representthe first permitted
`commercial marketing or use ofthe active ingredients of SYMBICORT®(budesonide and
`formoterol fumarate dihydrate).
`
`(6)
`
`On June 13, 2008, the USPTO dismissed Applicant’s request for extension of the term of the
`*860 patent filed under the provisions of 35 U.S.C. § 156(d)(1).
`
`(7)|On December 16, 2008, Applicantfiled a Response to the Notice of Final Determination of
`June 13, 2008 (Reconsideration Request I) pursuant to the provisions of 37 C.F.R. § 1.750.
`
`(8)
`
`On June 24, 2011, Applicant filed an additional Response to the Notice of Final
`Determination of June 13, 2008 (Reconsideration Request II) to address the timeliness issue
`in light ofthe district court decision in The Medicines Company v. Kappos, 3731 F.Supp. 2d
`470 «.D. Va. 2010).
`
`DECISION
`
`The USPTOhasconsidered the arguments made by Applicant in its Reconsideration
`- Request and-finds the arguments regarding compliance with 35 U.S.C. § 156(a)(5)(A)to be
`unpersuasive. With respect to the arguments regarding the failure to comply with the timing
`requirementforfiling an application in 35 U.S.C. § 156(d)(1), the USPTO finds the arguments in
`the Reconsideration RequestII to be persuasivein light of the amendments to § 156(d)(1) and the
`district court decision in The Medicines Company v. Kappos, 731 F.Supp. 2d 470 (E.D. VA. 2010)
`as discussed below. Thus, the USPTO will address Applicant's arguments regarding compliance
`with 35 U.S.C. 156(a)(5)(A) in turn.
`
`A.
`
`Approval of NDA 21-929 for SYMBICORTon July 21, 2006 at 4:36 PM Meansthe
`PTE Application Submitted on September 19, 2006 is Timely
`
`The time period for submission of an application for patent term extensionis set by statute.
`Thestatute provides, “such an application may only be submitted within the sixty-day period
`beginning on the date the product received permission underthe provision of law under which the
`applicable regulatory review period occurred ...
`.” 35 U.S.C. § 156(d)(1) (emphasis added). Thus,
`day oneofthe sixty-day period starts on the date the product receives permission for commercial
`marketing or use.
`
`Asoriginally determined in the USPTO communication to FDA of June 20, 2007, the
`
`2
`
`

`

`U.S. Patent No. 5,674,860
`
`Page 3
`
`present PTE application wasfiled on day 61 when counting day oneofthe sixty-day period as the:
`date the product was approved. However, the words, “beginning on the date” were at issue in The
`Medicines Company v. Kappos from 2010. Theruling of the district court was codified in section
`37 of the Leahy-Smith America Invents Act which added the following sentence to the patent term
`extension provisions of § 156:
`
`For purposesof determining the date on which a productreceives
`permission under the second sentenceofthis paragraph,if such
`permission is transmitted after 4:30 P.M., Eastern Time,on a business
`day, or is transmitted on a day that is not a business day, the product
`shall be deemed to receive such permission on the next businessday.
`For purposesof the preceding sentence, the term “business day” means
`any Monday, Tuesday, Wednesday, Thursday,or Friday, excluding any
`legal holiday undersection 6103oftitle 5.
`
`35 U.S.C.§ 156(d).
`
`In their Reconsideration RequestII, Applicant argued that the USPTO,in their
`determination from 2007, erroneously applied the calendar day interpretation. Since the
`USPTO’s initial determination of June 2007, the district court determined that the term
`“date”as used in § 156(d)(1) means business day. Moreover, the Leahy-Smith America
`Invents Act of 2011 revised 35 U.S.C. § 156(d)(1) by adding language regarding how to
`determinethestart the count of the sixty-day periodset forth in 35 U.S.C. 156(d)(1)
`whenthe approval of the regulated product is received after the regulating agency’s
`- Close of business. Because Applicant received their approval-after 4:30-PM on July 21,-
`2006, the date whichtriggers the sixty-day period of § 156(d)(1) is July 22, 2006.
`Thus, the PTE application filed.on September 19, 2006 is considered timely.
`
`B. Permission For Commercial Marketing Or Use of SYMBICORT® Is Not The First
`Permitted Commercial Marketing Or Use As Required By 35 U.S.C. 156(a)(5)(A)
`
`In order for the regulatory review of a drug productto give rise to patent term extension for a
`patent claiming such product undertheprovisions of 35 U.S.C: § 156, the permission for the
`commercial marketing or use of the product mustbe thefirst permitted commercial marketing or use
`- of the productunderthe provision of law under whichthe regulatory review period occurred. Here,
`the permission for commercial marketing or use of eachof the active ingredients of SYMBICORT®
`doesnot constitute the first permitted commercial marketing or use of either budesonide or
`formoterol fumarate dihydrate. Thus, Applicant’s PTE application must be denied.
`
`3
`
`

`

`U.S. Patent No. 5,674,860
`
`Page 4
`
`1.
`
`Section 156(f) recites that an active ingredient of a new drugis, “as a single
`entity or in combination with anotheractive ingredient”
`
`Applicant argues that because the drug product SYMBICORT®is a synergistic combination
`of budesonide and formoterol fumarate dihydrate, it constitutes a single active ingredient.
`Reconsideration RequestI at 1. Applicant asserts that the USPTO’s reliance on Jn re Alcon, 13
`USPQ2d 1115 (Comm’s Pat. & Trademarks 1989)is in error because the holding in Jn re Alconis
`inconsistent with Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392 (Fed. Cir. 1990). Applicant
`further argues that the A/con decision by the Commissioner wasbased on a faulty interpretation of
`the legislative history of 35 U.S.C. § 156(a)(5)(A). Reconsideration Requestat 1.
`
`First, Applicant’s analysis of the language of section 156(f) is flawed. Applicant glosses over
`the clear language of section 156(f) which providesthat the active ingredient of a new drug mayexist
`as a single entity or in combination with another active ingredient. When Congress provided a
`definition of “product” for purposes of determining which kinds of products, when subject to a
`regulatory review period and claimedin a patent, would giverise to patent term extension,the
`definition indicated that a new drug hadeither an active ingredient as a single entity or multiple
`active ingredients which are in combination with one another. See § 156(f)(2)(A). The language of
`section 156(f) recites that the term “product,” means “a drug product,” which in turn, means “the
`active ingredient of a new drug .
`.
`. as a single entity or in combination with anotheractive
`ingredient.” Applying the statutory language here, a drug product, SYMBICORT®,meansthe active
`ingredient (budesonide) of a “new drug” in combination with anotheractive ingredient (formoterol
`fumarate). There is no escapingthe plain language that the statute contemplates an active ingredient
`as a single entity in a new drug or an active ingredient in combination with anotheractive ingredient
`' inanew drug. To conclude that a single active ingredient can be a combination of two or more
`active ingredients would render superfluous the statutory language “or in combination with another
`active ingredient.
`
`Second, contrary to Applicant’s reading of the Commissioner’s decision in Jn re Alcon, the
`decision did notlimit patent term extension to situations where FDA granted permission for
`marketing or use of “New Chemical Entities,” as that term is defined, for purposes of exclusivity, in
`21 U.S.C. 355(c)(3)(E)(ii) and 21 U.S.C. 355(j)(5)(F)(ii) and its implementing regulation at 21
`C.F.R. 318.108. Rather, the A/con decision discusses that the data available to Congressat the time
`of the passage of the Drug Price Competition and Patent TermRestoration Act of 1984 (Hatch-
`Waxman Act) related to the costs and patent coverage of what wasreferred to as new molecular
`entities..
`
`Alcon involved an extension application for a patent based on the regulatory review of
`Tobradex, a combination product of tobramycin and dexamethasone. Since only tobramycin was
`claimed in the patent, the Commissioner held that the permission for commercial marketing or use of
`tobramycin mustconstitute the first permitted commercial marketing or use in the Tobradex product
`in orderto giverise to eligibility for extension of Alcon’s patent. Although dexamethasonehad not
`been approvedpriorto the approval of Tobradex, because the Alcon patent didn’t claim
`dexamethasone, compliance with 35 U.S.C. 156(a)(5)(A) regarding dexamethasone wasirrelevant.
`
`4
`
`

`

`U.S. Patent No. 5,674,860
`
`Page 5
`
`Accordingly, because the approval of the combination productdid not constitute the first permitted
`commercial marketing or use of tobramycin which wasthe only componentof the combination
`product which wasclaimed in Alcon’s patent, the approval of Torbradex did not constitute the first
`permitted commercial marketing or use requirement of 35 U.S.C. 156(a)(5)(A) and extension was
`denied.
`
`Applicant further opines that the USPTO’s interpretation ofJn re Alcon is inconsistent with
`Glaxo Operations UK Ltd. v. Quigg. Althoughthe court in Glaxo indicated that patent term
`extension was not limited to “new chemicalentities” as that term is used in 21 C.F.R. 314.108, the
`issue in Glaxo did not address combination products. Glaxo addressed a separate question,i.e.,
`whetherthe active ingredient in a drug productis: (i) the underlying active chemical moiety, or(ii)
`the formulation of that active moiety, e.g., as a salt or ester, as it actually exists in the approved drug
`product. The case confirmedthat the active ingredient is not the underlying chemical moiety, but the
`actual formulation of that moiety as it appears in the approved drug product. Here, the USPTO has
`considered the actual formulation of budesnoide as an active ingredient in combination with
`formoterol fumarate dihydrate as an active ingredient.
`
`Additionally, Applicant indicates that the USPTO doesnot dispute the synergistic effect of
`SYMBICORT®. Reconsideration Request I at 1. Such statementis true, but unavailing. While such
`properties and information regarding synergy are perhaps relevant for patentability purposes, there is
`no basis in 35 U.S.C. 156 for considering whether a drug product containing two active ingredients
`acts synergistically to achieve a specific pharmacological effect. Rather, the relevant inquiry for
`purposesof section 156 is whether the drug productrepresents the first commercial marketing or use
`of that product. When a drug product contains two active ingredients,at least one of those
`ingredients must constitute the first permitted commercial marketingoruse as requiredby35 U.S.C.
`§ 156(a)(5)(A). Budesonide wasfirst approved for commercial marketing or use in the drug
`products Entocort EC, Pulmicort and Rhinocort. For example, Rhinocort was approved on February
`14, 1994. Formoterol fumarate dihydrate wasfirst approved for commercial marketing or use in the
`drug product Foradil. Foradil was approved on February 16, 2001. Because both budesonide and
`formoterol fumarate dihydrate had been previously approved, neither can constitute the first
`permitted commercial marketing or use for compliance with§ 156(a)(5)(A).
`
`.
`
`2.
`
`Determining Compliance with 35 U.S.C. 156(a)(5)(A) Requires Analysis
`Of A Product On An Active Ingredient-By-Active Ingredient Basis
`
`Applicant argues that the USPTO haserroneouslyrelied on the Federal Circuit’s decisionin
`Arnold P’ship v. Dudas, 262 F.3d 1338 (Fed. Cir. 2004). Reconsideration Request I at 1-2
`Applicant also claims support for the argument that SYMBICORT®is a drug with a single active
`ingredient by reference to MPEP 2751 and states that this section of the MPEP supportstreating a
`combination of two active ingredients as a single active ingredient where synergy can be shown.
`Reconsideration RequestI at 2.
`
`Applicant acknowledgesthat“the active ingredients of the Approved Product have each been
`separately approved for marketing or use by the U.S. Food and Drug Administration.” PTE
`
`5
`
`

`

`U.S. Patent No. 5,674,860
`
`Page 6
`
`application at 5 (emphasis added). Applicant’s characterization of the active ingredients of
`SYMBICORT®in their PTE Application directly tracks the presentation of arguments in Arnold
`P’ship. Specifically, the district court noted, footnote 1:
`
`Hydrocodonebitartrate is a cough suppressant, while ibuprofenis a’
`pain reliever. PHYSICIANS DESK REFERENCE GENERICS 1441,
`1489 (1st ed. 1995). In plaintiff's application for extension of the '252
`patent, which comprises a binding part of the administrative record
`below,plaintiff clearly identified hydrocodonebitartrate and ibuprofen
`as discrete active ingredients. Aff. of Joseph E. Topmiller, Esq. in
`Supp.of Pl.'s Mot. for Summ. J. and Opp. to Def.'s Mot. for Summ.J.
`at A36, A38. In its pleadings, however,plaintiff characterizes these
`chemicals as the "therapeutic agents" of Vicoprofen. Plaintiff is bound
`by its admissions in the administrative process. . .
`.
`
`See Arnold P’ship v. Rogan, 246 F. Supp. 460, 462 (E.D. Va. 2003) (emphasis
`added).
`
`Here, Applicant admits that both active ingredients, plural, have been previously
`approved. PTE application at 5. Furthermore, Applicant identified in their application materials
`that “the two active ingredients of SYMBICORT®are shown to have a pharmacological
`interaction which produced unexpectedly beneficial results.” PTE Application at 5 (Emphasis
`added). Clearly, Applicant is indicating that there are two discrete active ingredients in the
`SYMBICORT® product. The same argument regarding a combination of two active ingredients
`_ showing.a pharmacological interaction was raised by the plaintiff in Avanir Pharm. v. Kappos,
`No. 12-69, (E.D. Va. March 21, 2012). On March 21, 2012,the district court stated its findings
`and conclusions pursuant to Fed. R.Civ.P. 52(a) orally in open court. Motions Hearing Tr. 1-73.
`There the district court stated, “additionally in light of the Federal Circuit’s discussion of synergy
`in Arnold Partnership v. Dudas.. . .I do think that that is dicta, but I can consider it. And I do not
`see pharmacologicalinteraction as a term distinction in the extension statute. There is no
`reference to pharmacological interaction in 35 U.S.C. 156.” Transcript of Motions Hearing at 66,
`Avanir Pharm. v. Kappos, No. 12-69 (E.D. Va. March 21, 2012). Just as in Avanir, the applicant
`here is asserting that the intended use of the co-administered two active ingredients means that
`the drug productis a single active ingredient, rather than the two separate anddistinct active
`ingredients. Because the patent term extension statute does not include any provisions:to consider
`any physiological effect of a drug product, synergy, or pharmacologicalinteraction, relying on
`such properties would be improper.
`
`Contrary to Applicant’s arguments, the Federal Circuit’s decision in Arnold Partnership
`v. Dudas, 262 F.3d 1338 (Fed. Cir. 2004) is directly and succinctly on point. The facts here are
`analogousto those in Arnold Partnership. Like the active ingredients ibuprofen and
`hydrocodonebitartrate in the combination product VICOPROFEN®in Arnold Partnership,
`budesonide and formoterol fumarate dihydrate each have been previously granted permission for
`commercial marketing oruse prior to the approval of SYMBICORT®.Asa result, the use of
`
`6
`
`

`

`US. Patent No. 5,674,860 -
`
`Page 7.
`
`budesonide and formoterol fumarate dihydrate in the product SYMBICORT® doesnotconstitute
`the first permitted commercial marketing or use of the SYMBICORT®asrequired by 35 U.S.C.
`§ 156(a)(5)(A), just as the use of ibuprofen and hydrocodonebitartrate in the combination
`product VICOPROFEN®did not constitute the first permitted commercial marketing of
`VICOPROFEN®in Arnold Partnership. See id. at 1342-43.
`
`Applicant’s reliance on MPEP§ 2751 is likewise misplaced. The statement in the MPEP
`pointed to by Applicant does not require that the USPTOtreat an alleged synergistic combination
`drug product with twoactive ingredients as a single active ingredient madeupofthe twoactive
`ingredients for patent term extension purposes. Rather, MPEP § 2751 merely explains that a
`product having two active ingredients, without synergy, will not be treated as a single active
`ingredient. Contrary to Applicant’s arguments, the MPEPis not authority for the converse.
`Furthermore, this section ofthe MPEPhasnot been updatedto reflect the clarityin law provided
`by Arnold Partnership v. Dudas.
`
`Asdiscussed supra, just as each active ingredient in VICOPROFEN®,considered in
`Arnold Partnership, was foundto be a discrete substance incorporatedinto a single dosage form,
`the sameis said for SYMBICORT®,each active ingredient described by Applicant is a discrete
`active ingredient contained in a single dosage form. Therefore, the ’860 patentis not entitled to a
`patent term extension.
`|
`
`7
`
`

`

`U.S. Patent No. 5,674,860
`
`——
`
`Cc.
`
`Conclusion
`
`Page 8
`
`Because the approval of SYMBICORT®fails to comply with the requirementof section
`156(a)(5)(A), the application for patent term extension under 35 U.S.C. 156(d)(1) is denied.
`
`This is considered a final agency decision.
`
`Anycorrespondence with respectto this matter should be submitted via the USPTO"s EFS-WEb
`
`System and should be addressedas follows:
`
`By mail:
`
`Mail Stop Hatch-Waxman PTE
`Commissionerfor Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Telephoneinquiries related to this determination should be directed to Mary C.Till,
`Senior Legal Advisor, at (571) 272-7755.
`
`beelGr—
`
`Brian E. Hanlon
`’ Director
`Office of Patent Legal Administration
`United States Patent and Trademark Office
`
`cc:
`
`Office of Regulatory Policy
`Food and Drug Administration
`10903 New Hampshire Ave., Bldg. 51, Rm. 6222
`Silver Spring, MD 20993-0002
`
`Re:
`
`SYMBICORT®
`(budesonide and formoterol
`fumarate dihydrate)
`
`Docket No. FDA-2007-E-0440
`
`Attention: Beverly Friedman
`
`8
`
`