Filed on behalf of Petitioner COALITION FOR AFFORDABLE DRUGS X LLC
`
`
`By: Jeffrey D. Blake, Esq.
` MERCHANT & GOULD P.C.
`
`191 Peachtree Street N.E., Suite 4300
` Atlanta, GA 30303
`
`jblake@merchantgould.com
` Main Telephone: (404) 954-5100
` Main Facsimile: (404) 954-5099
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`COALITION FOR AFFORDABLE DRUGS X LLC,
`Petitioner,
`
`v.
`
`ANACOR PHARMACEUTICALS, INC.,
`Patent Owner.
`___________________
`Case No.: Unassigned
`Patent No.: 7,582,621
`________________________________________________________
`
`
`
`
`
`PETITION FOR INTER PARTES REVIEW OF PATENT NO. 7,582,621
`
`
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION......................................................................................... 1
`
`MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1) ....................... 4
`
`I.
`
`II.
`
`A. Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1) .................................... 4
`
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2) ............................................. 5
`
`C. Lead And Back-Up Counsel Under 37 C.F.R. §§ 42.8(b)(3) & 42.10(a) ..... 5
`
`D. Service Information Under 37 C.F.R. § 42.8(b)(4) ....................................... 6
`
`III.
`
`IV.
`
`PAYMENT OF FEES UNDER 37 C.F.R. § 42.103 .................................... 6
`
`REQUIREMENTS FOR IPR UNDER 37 C.F.R. § 42.104 ......................... 6
`
`A. Grounds For Standing Under 37 C.F.R. § 42.104(a) .................................... 6
`
`B.
`
`Identification Of Challenge Under 37 C.F.R. § 42.104(b) And Relief
`Requested ...................................................................................................... 7
`
`1. Claims For Which IPR Is Requested Under 37 C.F.R. § 42.104(b)(1) ..... 7
`
`2.
`
`Specific Art And Statutory Grounds On Which The Challenge Is
`Based Under 37 C.F.R. § 42.104(b)(2) ...................................................... 7
`
`3. The Construction Of The Challenged Claims Under 37 C.F.R. §
`42.104(b)(3) ................................................................................................ 9
`
`4. How The Construed Claims Are Unpatentable Under 37 C.F.R. §
`42.104(b)(4) ................................................................................................ 9
`
`5.
`
`Supporting Evidence Under 37 C.F.R. § 42.104(b)(5) .............................. 9
`
`V.
`
`SUMMARY OF THE ’621 PATENT ........................................................10
`
`A. Lineage Of The ’621 Patent ........................................................................10
`
`B. Description Of The Alleged Invention Of The ’621 Patent ........................10
`
`C. Construction Of Key Terms In The ’621 Claims ........................................11
`ii
`
`
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`D. Summary Of The Original Prosecution Of The ’621 Patent .......................13
`
`E. The State Of The Art ...................................................................................15
`
`VI.
`
`
`PETITIONER HAS A REASONABLE LIKELIHOOD OF
`PREVAILING .............................................................................................21
`
`A. Each Reference Relied On For Grounds 1-3 Is Prior Art ...........................23
`
`B. A Person Of Ordinary Skill In The Art .......................................................23
`
`C. Ground 1: Claims 1-12 Are Obvious Over Austin In View Of Brehove ....23
`
`1. Claims 1-12 Generally Recite Methods Of Treating Onychomycosis
`In Humans With 5-Fluoro Benzoxaborole ...............................................24
`
`2. Austin Discloses 5-Fluoro Benzoxaborole As An Anti-Fungal Agent ....27
`
`3. Brehove Discloses The Topical Application Of Boron-Based
`Compounds To Treat Onychomycosis .....................................................29
`
`4.
`
`Summary: Claims 1-12 Are Obvious Over Austin And Brehove ............31
`
`D. Ground 2: Claims 1-12 Are Obvious Over Austin In View Of Freeman ...43
`
`1. Claims 1-12 Generally Recite Methods Of Treating Onychomycosis
`In Humans With 5-Fluoro Benzoxaborole ...............................................43
`
`2. Austin Discloses 5-Fluoro Benzoxaborole As An Anti-Fungal Agent ....43
`
`3. Freeman Discloses The Topical Application Of Boron-Based
`Compounds To Treat Onychomycosis .....................................................43
`
`4.
`
`Summary: Claims 1-12 Are Obvious Over Austin And Freeman ...........45
`
`E. Ground 3: Claim 9 Is Obvious Over Austin In View Of Freeman
`
`And Sun .......................................................................................................56
`
`1. Claim 9 Recites A Method Of Treating Onychomycosis In Humans
`Via Application Of 5-Fluoro Benzoxaborole To The Skin
`Surrounding A Nail ..................................................................................56
`
`
`
`iii
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`2. Austin Discloses 5-Fluoro Benzoxaborole As An Anti-Fungal Agent
`And Freeman Discloses The Topical Application Of Boron-Based
`Compounds To Treat Onychomycosis .....................................................57
`
`3.
`
`Sun Discloses The Anti-Fungal Treatment Of Nails Via Topical
`Application To The Skin Surrounding The Nail ......................................57
`
`4.
`
`Summary: Claim 9 Is Obvious Over Austin, Freeman, And Sun ............57
`
`VII.
`
`CONCLUSION ...........................................................................................59
`
`
`
`iv
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`TABLE OF AUTHORITIES
`
`
`Cases
`
`Graham v. John Deere Co.,
`
`383 U.S. 1 (1966) ........................................................................................... 22
`
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007)........................................................................... 22, 38, 51
`
`Statutes & Other Authorities
`
`35 U.S.C. § 102(b) ............................................................................................... 8, 23
`
`35 U.S.C. § 103(a) ......................................................................................... 8, 13, 21
`
`35 U.S.C. § 112 .................................................................................................. 13, 14
`
`35 U.S.C. §§ 311-319................................................................................................. 1
`
`35 U.S.C. § 315(e)(1) ................................................................................................. 7
`
`37 C.F.R. § 42.6(e) ................................................................................................... 60
`
`37 C.F.R. § 42.8(a)(1) ................................................................................................ 4
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 4
`
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 5
`
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 5
`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 6
`
`37 C.F.R. § 42.10(a) ................................................................................................... 5
`
`37 C.F.R. § 42.10(b) .................................................................................................. 6
`
`34 C.F.R. § 42.15(a)(1-2) ........................................................................................... 6
`
`
`
`v
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`37 C.F.R. § 42.63(a) ............................................................................................. 9, 10
`
`37 C.F.R. § 42.100 et seq ........................................................................................... 1
`
`37 C.F.R. § 42.100(b) ................................................................................................ 9
`
`37 C.F.R. § 42.102(a)(2) ............................................................................................ 7
`
`37 C.F.R. § 42.103 ..................................................................................................... 6
`
`37 C.F.R. § 42.104 ..................................................................................................... 6
`
`37 C.F.R. § 42.104(a) ................................................................................................. 6
`
`37 C.F.R. § 42.104(b) ................................................................................................ 7
`
`37 C.F.R. § 42.104(b)(1) ............................................................................................ 7
`
`37 C.F.R. § 42.104(b)(2) ............................................................................................ 7
`
`37 C.F.R. § 42.104(b)(3) ............................................................................................ 9
`
`37 C.F.R. § 42.104(b)(4) ...................................................................................... 9, 21
`
`37 C.F.R. § 42.104(b)(5) ............................................................................................ 9
`
`
`
`vi
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`Coalition For Affordable Drugs X LLC (“Petitioner” or “CFAD”)
`
`respectfully submits this Petition for Inter Partes Review (“IPR”) of claims 1-12 of
`
`U.S. Patent No. 7,582,621 (“the ’621 Patent”) (Ex. 1001) pursuant to 35 U.S.C. §§
`
`311-319 and 37 C.F.R. § 42.100 et seq.
`
`I.
`
`
`INTRODUCTION
`
`The ’621 Patent is directed to methods of treating fungal infections,
`
`including ungual and/or periungual infections that affect the hoof, nail, or claw
`
`(onychomycosis) with a specific boron-based compound: 1,3-dihydro-5-fluoro-1-
`
`hydroxy-2, 1-benzoxaborole, referred to herein as 5-fluoro benzoxaborole. Its
`
`chemical structure is:
`
`OH
`B
`
`O
`
`
`
`F
`
`The claims of the ’621 Patent should be invalidated as obvious. The exact
`
`claimed compound was disclosed in WO 1995/033754 to Austin et al. (“Austin”)
`
`as a preferred compound for use as a fungicide. Moreover, Austin explicitly tests
`
`the efficacy of the claimed compound against Candida albicans, which is one of
`
`the fungal pathogens that cause onychomycosis.
`
`During prosecution, the Examiner rejected the pending claims over U.S.
`
`
`
`1
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`Patent No. 5,880,188 to Austin et al.1 in view of a definition of “fungicide” found
`
`on a general interest, non-scientific internet website called Answers.com, which
`
`defined a fungicide in broad terms of pharmaceutical uses, as well as agricultural
`
`uses. The Patent Owner overcame this rejection by arguing that Answers.com
`
`taught away from human treatment because the same Internet entry stated that
`
`some fungicides were harmful to humans. The Examiner accepted this argument
`
`and allowed the claims to issue.
`
`While the Patent Owner’s “teaching away” argument may have persuaded
`
`the Examiner, it cannot withstand scrutiny in this forum. The fallacy of the
`
`argument is exposed in view of how drugs are developed in the pharmaceutical
`
`industry. Drug candidates are screened through routine experimentation to
`
`determine efficacy and safety before application to humans, thus avoiding the
`
`safety fears that the Patent Owner argued to the Examiner. Even more telling,
`
`however, is that U.S. Patent Pub. No. 2002/0165121 to Brehove (“Brehove”)
`
`disclosed a pre-existing boron-based industrial fungicide to create a topical
`
`pharmaceutical to successfully treat onychomycosis in humans and WO
`
`
`1 U.S. Patent No. 5,880,188 is related to WO 1995/033754, which Petitioner relies
`
`on in this Petition because the abstract of WO 1995/033754 specifically identifies
`
`the compound of claims 1-12 as a preferred compound.
`
`
`
`2
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`2003/009689 to Freeman et al. (“Freeman”) also disclosed additional boron-based
`
`fungicides for treating onychomycosis in humans.
`
`Claims 1-12 of the ’621 Patent are obvious against this real-world backdrop.
`
`A person of ordinary skill in the art (“POSITA”) would have known that the
`
`preferred industrial fungicide disclosed in Austin was effective against Candida
`
`albicans (a known cause of onychomycosis). Accordingly, the Austin fungicide
`
`would have been an obvious candidate for potential therapeutic use in humans to
`
`treat onychomycosis in view of: (1) Brehove, which discloses a similar boron-
`
`based fungicide that suppresses Candida albicans and safely treats onychomycosis
`
`in humans; or (2) Freeman, which discloses additional boron-based fungicides that
`
`effectively suppress species of Candida and Trichophyton rubrum (a known cause
`
`of onychomycosis); or (3) Freeman and Sun, which discloses a method for topical
`
`treatment of onychomycosis, including topical administration to the nail and the
`
`surrounding skin. Therefore, Petitioner asserts three grounds for invalidity: (1)
`
`claims 1-12 are obvious over Austin in view of Brehove; (2) claims 1-12 are
`
`obvious over Austin in view of Freeman; and (3) claim 9 is obvious over Austin in
`
`view of Freeman and Sun.
`
`
`
`
`
`
`
`
`
`3
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1)
`A. Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(1)
`Petitioner certifies that CFAD, Hayman Credes Master Fund, L.P.
`
`(“Credes”), Hayman Orange Fund SPC – Portfolio A (“HOF”), Hayman Capital
`
`Master Fund, L.P. (“HCMF”), Hayman Capital Management, L.P. (“HCM”),
`
`Hayman Offshore Management, Inc. (“HOM”), Hayman Investments, L.L.C.
`
`(“HI”), nXn Partners, LLC (“nXnP”), IP Navigation Group, LLC (“IPNav”), J.
`
`Kyle Bass, and Erich Spangenberg are the real parties-in-interest (collectively,
`
`“RPI”). The RPI certifies the following information:
`
`CFAD is a wholly owned subsidiary of Credes. Credes is a limited
`
`partnership. HOF is a segregated portfolio company. HCMF is a limited
`
`partnership. HCM is the general partner and investment manager of Credes and
`
`HCMF. HCM is the investment manager of HOF. HOM is the administrative
`
`general partner of Credes and HCMF. HI is the general partner of HCM. J. Kyle
`
`Bass is the sole member of HI and sole shareholder of HOM. CFAD, Credes, HOF,
`
`and HCMF act, directly or indirectly, through HCM as the general partner and/or
`
`investment manager of Credes, HOF and HCMF. nXnP is a paid consultant to
`
`HCM. Erich Spangenberg is the Manager and majority member of nXnP. IPNav is
`
`a paid consultant to nXnP. Erich Spangenberg is the Manager and majority
`
`member of IPNav.
`
`
`
`4
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`Other than HCM and J. Kyle Bass in his capacity as the Chief Investment
`
`Officer of HCM and nXnP, and Erich Spangenberg in his capacity as the
`
`Manager/CEO of nXnP, no other person (including any investor, limited partner,
`
`or member or any other person in any of CFAD, Credes, HOF, HCMF, HCM,
`
`HOM, HI, nXnP, or IPNav) has authority to direct or control (i) the timing of,
`
`filing of, content of, or any decisions or other activities relating to this Petition or
`
`(ii) any timing, future filings, content of, or any decisions or other activities
`
`relating to the future proceedings related to this Petition. All of the costs associated
`
`with this Petition will be borne by HCM, CFAD, Credes, HOF and/or HCMF.
`
`B. Related Matters Under 37 C.F.R. § 42.8(b)(2)
`Petitioner is aware of a concurrently filed “First” Petition and a concurrently
`
`filed “Second” Petition for Inter Partes Review of U.S. Patent No. 7,767,657,
`
`which is a continuation-in-part of the ’621 Patent (Case Nos. Unassigned).
`
`C. Lead And Back-Up Counsel Under 37 C.F.R. §§ 42.8(b)(3) &
`
`42.10(a)
`
`
`Lead Counsel
`Jeffrey D. Blake, Esq.
`Reg. No. 53,214
`Merchant & Gould PC
`191 Peachtree Street N.E., Suite 4300
`Atlanta, GA 30303
`Main Telephone: (404) 954-5100
`Main Facsimile: (404) 954-5099
`jblake@merchantgould.com
`
`Back-Up Counsel
`Kathleen E. Ott, Esq.
`Reg. No. 64,038
`Peter A. Gergely, Esq.
`(Pro Hac Vice)
`Ryan James Fletcher, Ph.D., Esq.
`(Pro Hac Vice)
`Merchant & Gould PC
`1801 California Street, Suite 3300
`Denver, CO 80202
`
`
`
`5
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`Main Telephone: (303) 357-1670
`Main Facsimile: (303) 357-1950
`kott@merchantgould.com
`pgergely@merchantgould.com
`rfletcher@merchantgould.com
`
`Brent E. Routman, Esq.
`(Pro Hac Vice)
`Merchant & Gould PC
`3200 IDS Center
`80 South Eighth Street
`Minneapolis, MN 55402
`Main Telephone: (612) 332-5300
`Main Facsimile: (612) 322-9081
`broutman@merchantgould.com
`
`
`
`
`
`Pursuant to 37 C.F.R. § 42.10(b), a Power of Attorney is provided herewith.
`
`Service Information Under 37 C.F.R. § 42.8(b)(4)
`
`D.
`Service information for lead and back-up counsel is provided above in the
`
`designation of lead and back-up counsel. Petitioner also consents to electronic
`
`service by e-mail at KerydinIPR@merchantgould.com.
`
`III. PAYMENT OF FEES UNDER 37 C.F.R. § 42.103
`Payment of $23,000 for the fees set forth in 37 C.F.R. § 42.15(a)(1-2)
`
`accompanies this Petition. The USPTO is authorized to charge Deposit Account
`
`No. 13-2725 for any additional fees that may be due for this Petition.
`
`IV. REQUIREMENTS FOR IPR UNDER 37 C.F.R. § 42.104
`A. Grounds For Standing Under 37 C.F.R. § 42.104(a)
`Petitioner hereby certifies that the ’621 Patent is available for IPR and that
`
`
`
`6
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`neither Petitioner nor any RPI is barred or estopped from requesting IPR of the
`
`’621 Patent because: (1) neither Petitioner nor any RPI are the patent owner; (2)
`
`neither Petitioner nor any RPI has filed a civil action challenging the validity of a
`
`claim in the ’621 Patent; (3) neither Petitioner nor any RPI has been served with a
`
`complaint alleging infringement of the patent; (4) the estoppel provisions of 35
`
`U.S.C. § 315(e)(1) do not prohibit this IPR; and (5) the patent is not described in §
`
`3(n)(1) of the Leahy-Smith America Invents Act and so is available for IPR
`
`pursuant to 37 C.F.R. § 42.102(a)(2).
`
`B.
`
`
`Identification Of Challenge Under 37 C.F.R. § 42.104(b) And
`Relief Requested
`
`Petitioner requests the cancellation of claims 1-12 of the ’621 Patent as
`
`unpatentable over the prior art for the reasons given herein.
`
`1.
`
`
`Claims For Which IPR Is Requested Under 37 C.F.R. §
`42.104(b)(1)
`
`Petitioner requests IPR of claims 1-12 of the ’621 Patent.
`
`2.
`
`
`Specific Art And Statutory Grounds On Which The Challenge
`Is Based Under 37 C.F.R. § 42.104(b)(2)
`
`IPR of the ’621 Patent is requested in view of the following four
`
`publications: (1) WO 1995/033754 to Austin et al. (“Austin”) (Ex. 1002); (2) U.S.
`
`Patent Pub. No. 2002/0165121 to Brehove (“Brehove”) (Ex. 1003); (3) WO
`
`2003/009689 to Freeman et al. (“Freeman”) (Ex. 1004); and (4) U.S. Patent No.
`
`
`
`7
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`6,042,845 to Sun et al. (“Sun”) (Ex. 1005). None of Austin, Brehove, Freeman, or
`
`Sun was made of record during prosecution of the ’621 Patent.
`
`Each of the publications listed above is available as prior art against the ’621
`
`Patent under pre-AIA 35 U.S.C. § 102(b) because each was published more than
`
`one year before February 16, 2005, the filing date of the provisional application to
`
`which the ’621 Patent claims priority. Specifically, (1) Austin was published on
`
`December 14, 1995; (2) Brehove was published on November 7, 2002; (3)
`
`Freeman was published on February 6, 2003; and (4) Sun was published March 28,
`
`2000.
`
`The following combinations of the above-listed publications render claims
`
`1-12 of the ’621 Patent obvious under pre-AIA 35 U.S.C. § 103(a):
`
`Ground Claim Nos.
`1
`1-12
`
`2
`
`3
`
`1-12
`
`9
`
`Proposed Statutory Rejections
`Claims 1-12 of the ’621 Patent are obvious under 35
`U.S.C. §103(a) over Austin in view of Brehove.
`Claims 1-12 of the ’621 Patent are obvious under 35
`U.S.C. §103(a) over Austin in view of Freeman
`Claim 9 of the ’621 Patent is obvious under 35 U.S.C.
`§103(a) over Austin in view of Freeman and Sun
`
`Copies of Austin, Brehove, Freeman, and Sun are filed herewith. The above
`
`
`
`
`grounds for unpatentability are supported by the Declaration of Stephen Kahl,
`
`Ph.D. (“Kahl Decl.”) (Ex. 1006) and the Declaration of S. Narasimha Murthy,
`
`Ph.D. (“Murthy Decl.”) (Ex. 1008), which are both filed herewith.
`
`
`
`8
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`3.
`
`
`The Construction Of The Challenged Claims Under 37 C.F.R. §
`42.104(b)(3)
`
`The terms of the ’621 Patent claims are to be given their broadest reasonable
`
`interpretation in light of the specification, as understood by a person of ordinary
`
`skill in the art. See 37 C.F.R. § 42.100(b). Petitioner submits, for purposes of the
`
`IPR only, the constructions given in Section V.C. below. Any claim terms not
`
`discussed herein should be given their “ordinary meaning” under the “broadest
`
`reasonable construction” standard of § 42.100(b).
`
`4.
`
`
`How The Construed Claims Are Unpatentable Under 37 C.F.R.
`§ 42.104(b)(4)
`
`A detailed explanation of how construed claims 1-12 of the ’621 Patent are
`
`unpatentable on the statutory grounds identified above, including the identification
`
`of where each element of claims 1-12 are found in prior art publications, is set
`
`forth below in Section VI.
`
`5.
`
`Supporting Evidence Under 37 C.F.R. § 42.104(b)(5)
`
`The exhibit numbers of the supporting evidence relied upon to support
`
`Petitioner’s challenge as to claims 1-12 of the ’621 Patent and the relevance of the
`
`evidence to the unpatentability arguments raised, including the specific portions of
`
`the evidence that support Petitioner’s challenge, are set forth in Section VI. Exhibit
`
`1006 is a Declaration of Stephen Kahl, Ph.D. under 37 C.F.R. § 42.63(a) attesting
`
`to, among other issues, the safety of boron-based compounds and that it would
`
`
`
`9
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`have been obvious to try 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole to
`
`treat onychomycosis. Exhibit 1008 is a Declaration of S. Narasimha Murthy, Ph.D.
`
`under 37 C.F.R. § 42.63(a) attesting to, among other issues, the obviousness of
`
`claims 1-12, reasons for combining the references relied upon in this Petition, and
`
`the reasons and motivations to pharmaceutically formulate and topically apply the
`
`compounds discussed herein.
`
`V.
`
`SUMMARY OF THE ’621 PATENT
`A. Lineage Of The ’621 Patent
`The ’621 Patent, entitled “Boron-Containing Small Molecules,” issued
`
`September 1, 2009, from U.S. Patent Application No. 11/357,687 (“the ’687
`
`Application”) filed February 16, 2006, claiming priority to U.S. Provisional
`
`Application No. 60/654,060, filed February 16, 2005. (Ex. 1001.)
`
`B. Description Of The Alleged Invention Of The ’621 Patent
`The ’621 Patent is directed to boron-based heterocyclic compounds for
`
`treating fungal infections, and in particular, topical treatment of onychomycosis
`
`and other cutaneous fungal infections. (Ex. 1001, Abstract.) In the background, the
`
`’621 Patent cites problems with prior art treatment methods and compounds, such
`
`as adverse effects related to long-term oral administration of antifungals (id. at Col.
`
`1:28-44), issues with surgical removal of all or part of the nail (id. at Col. 1:46-52),
`
`
`
`10
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`and issues with topical treatments, including maintaining nail contact and nail
`
`penetration (id. at Col. 1:53-67, Col. 2:12-25).
`
`The ’621 Patent claims administration of 1,3-dihydro-5-fluoro-l-hydroxy-
`
`2,1-benzoxaborole (“C10 compound”), or a pharmaceutically acceptable salt
`
`thereof, sufficient to treat an infection. (Id. at Col. 67:34-38.) Preparation and
`
`analytical data regarding the C10 compound is described with reference to
`
`Examples 5-7 (id. at Cols. 55:59-57:18), Example 16, antifungal activity (id. at
`
`Cols. 59:42-60:42), Example 17, solubility, stability (id. at Cols. 60:44-62:29),
`
`Examples 18-20, nail penetration (id. at Cols. 62:31-67:32), and Figures 1B, 2A-4,
`
`6-7. The ’621 Patent admits that formulation of pharmaceutically effective carriers,
`
`as well as pharmaceutically acceptable additives and penetration enhancers, were
`
`known in the art. (Id. at Col. 11:3-57.)
`
`C. Construction Of Key Terms In The ’621 Claims
`Claims 1, 11, and 12 of the ’621 Patent recite the following compound: “1,3-
`
`
`
`dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole.” 1,3-dihydro-5-fluoro-1-hydroxy-
`
`2,1-benzoxaborole is disclosed in Austin as 5-fluoro-1,3 dihydro-1-hydroxy-2,1-
`
`benzoxaborole. (Ex. 1008 at ¶¶ 39-40, 61, 79.) The compound of Independent
`
`claims 1, 11, and 12 has the following structure:
`
`
`
`11
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`F
`
`OH
`B
`
`O
`
`
`
`(Id. at ¶ 79.) The ’621 Patent discloses this structure at column 32, lines 10-25 as
`
`Compound I with a formula of C7H6BFO2 and a molecular weight of 151.93
`
`Daltons. (Ex. 1001 at Col. 32:10-25; Ex. 1008 at ¶ 80.)
`
`
`
`Claims 1, 11, and 12 of the ’621 Patent recite a “therapeutically effective
`
`amount” of the claimed compound. Therapeutically effective amount means “an
`
`amount of the claimed compound needed to reach the desired therapeutic result.”
`
`(Ex. 1008 at ¶ 81.) This is consistent with how the ’621 Patent defines
`
`“therapeutically effective amount.” (Ex. 1001 at Col. 9:53-58.)
`
`
`
`Claim 3 recites the term “dermatological diseases.” Dermatological diseases
`
`is a broad term that means “diseases of the hair, nail, or skin.” (Ex. 1008 at ¶ 82.)
`
`This is consistent with the ’621 Patent’s use of “dermatological diseases” when
`
`giving some examples of dermatological diseases of the nail. (Ex. 1001 at Col.
`
`29:33-44.)
`
`
`
`Claim 3 recites the term “tinea pedis.” Tinea pedis means and is commonly
`
`referred to as athlete’s foot. (Ex. 1008 at ¶ 83.) This is consistent with the ’621
`
`Patent’s use of tinea pedis. (Ex. 1001 at Col. 29:51-57.)
`
`Claim 6 recites the term “tinea unguium.” Tinea unguium is “onychomycosis
`12
`
`
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`caused by a dermatophyte.” (Ex. 1008 at ¶ 84.) This is consistent with how the ’621
`
`Patent defines tinea unguium. (Ex. 1001 at Col. 28:24-25.)
`
`Summary Of The Original Prosecution Of The ’621 Patent
`
`D.
`The ’621 Patent was filed on February 16, 2006, as U.S. Application No.
`
`11/357,687 with 39 claims. (Ex. 1010 at pp. 99-111.) In response to a restriction
`
`requirement, Applicants elected claims 27-31 (and new claims 40-42), canceled
`
`claims 1-26 and 32-39, and made a species election of 1,3-dihydro-5-fluoro-1-
`
`hydroxy-2,1-benzoxaborole. (Ex. 1011.) Applicants further amended claim 27
`
`(issued claim 1) to recite “1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a
`
`pharmaceutically acceptable salt thereof or a prodrug thereof.” (Id. at 3.)
`
`In an Office Action dated August 26, 2008, all pending claims were rejected
`
`based on 35 U.S.C. § 112, first paragraph, because Applicants claimed “‘treating or
`
`preventing infection’ without limitation” (Ex. 1012 at p. 5), and “the prodrug of the
`
`instant compound” (id. at p. 7). The claims were further rejected under 35 U.S.C. §
`
`103(a) over Austin et al. (U.S. Patent No. 5,880,188) in view of a definition for
`
`fungicide (Answers.com), which provided that a fungicide can be used for the
`
`agricultural or pharmaceutical industries. (Id. at pp. 11-12.) The Examiner noted
`
`that while “the level of skill in the art is high,” due to the unpredictable nature of
`
`the pharmaceutical art, the specification failed to provide sufficient support for the
`
`broad use of the pharmaceutical compound to treat or prevent infection, or for
`
`
`
`13
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`formulation of a prodrug thereof, and would result in exhaustive search or undue
`
`experimentation by one of skill in the art. (Id. at pp. 3-10.)
`
`In response to the rejections under section 112, first paragraph, Applicants
`
`did not refute that the level of skill in the art was high, but amended claim 27
`
`without argument, deleting the phrases “or preventing” and “or a prodrug thereof”
`
`and adding the phrase “sufficient to treat said infection.” (Ex. 1013 at p. 2.) In fact,
`
`during prosecution of a related continuation-in-part application (U.S. Application
`
`No. 11/505,591), Applicants responded to a similar statement by the Examiner as
`
`follows: “As stated by the Examiner, the level of skill in the chemical arts is high.
`
`In view of this finding, Applicants submit that the specification, coupled with the
`
`knowledge generally known in the art, is sufficient to enable practice of the full
`
`scope of the rejected claim.” (Ex. 1015 at p. 8.)
`
`In response to the obviousness rejections, Applicants argued that “one of
`
`skill in the art would not presumptively consider a compound to be suitable for
`
`administration to an animal, especially a human, merely because a compound has
`
`been shown to have antifungal effects in paint or aviation fuel.” (Ex. 1013 at p. 6.)
`
`Moreover, applicants argued that the secondary reference (Answers.com) cited by
`
`the Examiner did not provide motivation and, in fact, taught away from using the
`
`claimed compound to treat human infection by stating that “some fungicides are
`
`dangerous to human health.” (Id.)
`
`
`
`14
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`The Examiner accepted Applicants arguments and a Notice of Allowance
`
`issued on April 22, 2009. (Ex. 1014.) The ’621 Patent issued on September 1,
`
`2009. (Ex. 1001.) After issuance, the Patent Owner filed petitions to extend the
`
`patent term adjustment from 267 days to 464 days (Ex. 1016), which was granted
`
`(Ex. 1017), and to remove Carolyn Bellinger-Kawahara and Kirk Maples as
`
`inventors (Ex. 1018), which was also granted. (Ex. 1019.)
`
`The State Of The Art
`
`E.
`Fungicides have been simultaneously disclosed for both industrial and
`
`
`
`pharmaceutical use for more than half a century. The cross-application of
`
`fungicides for both industrial and pharmaceutical uses, including use with humans,
`
`is neither new nor discouraged. Some representative examples from the past half
`
`century include:
`
`▪ U.S. Patent No. 2,831,866 to W.A. Freeman et al. (Ex. 1020) disclosed
`
`pyridyl-4-nitrosopyrazoles for treating fungal infections, e.g., resulting from
`
`Trichophyton rubrum, in plants and humans. (Id. at Col. 1:19-42.)
`
`▪ U.S. Patent No. 3,093,659 to Bell et al. (Ex. 1021) disclosed fungicides for
`
`industrial applications as well as for clinical applications, e.g., treating
`
`fungal infections caused by Trichophyton rubrum and Candida albicans,
`
`without irritating effects. (Id. at Cols. 2:65-3:19.)
`
`▪ U.S. Patent No. 3,297,525 to Grier (Ex. 1022) disclosed heterocyclic
`
`15
`
`
`
`
`
`
`
`
`
`

`

`Petition For Inter Partes Review
`Patent No. 7,582,621
`
`
`compounds for clinical treatment of fungal infections, e.g., caused by
`
`Candida albicans and Trichophyton rubrum, as well as for industrial
`
`applications, such as fungicidal additives for paints and other coating
`
`compositions and organic films. (Id. at Col. 1:18-26, Col.4:20-46, Col.
`
`13:32-38, Col. 18:1-45.)
`
`
`
`▪ U.S. Patent No. 3,370,957 to Wagner et al. (Ex. 1023) disclosed the use of
`
`heterocyclic compounds as effective fungicidal agents for industrial
`
`applications, e.g., paint, leather, plastics, and fuel, as well as for medical
`
`therapies to treat, for example, mycotic infections such as onychomycosis
`
`caused by Trichophyton rubrum. (Id. at Col. 1:28-32, Col. 3:25-38, Cols.
`
`3:74-4:36, Col. 9:11-24, Col. 13:3-15, 64-70.)
`
`▪ U.S. Patent No. 4,202,894 to Pfiffner (Ex. 1026) disclosed morpholine
`
`compounds for use as effective fungicides in agricultural and pharmaceutical
`
`applications, including the disclosure that certain compounds were effective
`
`against Candida albicans and trichophytes. (Id. at Cols. 16:24-17:8, Col.
`
`18:42-43, Table III.)
`
`▪ U.S. Patent No. 4,822,822 to Arita et al. (Ex. 1029) disclosed benzylamine
`
`derivatives as agricultural, industrial and therapeutic fu