U.S. Patent No.: 8,859,623
`Paper No. ___
`Petition for Post-Grant Review
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________________
`
`Altaire Pharmaceuticals, Inc.
`
`Petitioner
`
`v.
`
`Paragon Bioteck, Inc.
`
`Patent Owner
`
`U.S. Patent No. 8,859,623
`Issue Date: October 14, 2014
`Entitled: METHODS AND COMPOSITIONS OF STABLE PHENYLEPHRINE
`FORMULATIONS
`
`____________________
`
`Post-Grant Review No.: Unassigned
`____________________
`
`PETITION FOR POST-GRANT REVIEW
`
`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`TABLE OF CONTENTS
`
`Page No.
`
`I.
`
`MANDATORY NOTICES................................................................................................III
`
`II.
`
`III.
`
`IV.
`
`V.
`
`VI.
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`Real Party-In-Interest Pursuant to 37 C.F.R. § 42.8(b)(1).................................1
`
`Related Matters Pursuant to 37 C.F.R. § 42.8(b)(2)...........................................1
`
`Lead and Back-Up Counsel Pursuant to 37 C.F.R. § 42.8(b)(3)........................1
`
`Service Information Pursuant to 37 C.F.R. § 42.8(b)(4) ....................................2
`
`Payment of Fees Under 37 C.F.R. §§ 42.15(b) and 42.203.................................2
`
`GROUNDS FOR STANDING............................................................................................2
`
`TIMING ...............................................................................................................................3
`
`STATEMENT OF PRECISE RELIEF REQUESTED........................................................3
`
`A.
`
`B.
`
`Identification of Claims Challenged and Relief Sought .....................................3
`
`Statutory Grounds and Prior Art Relied Upon for Each Ground ....................3
`
`SPECIFIC CLAIMS AND GROUNDS FOR RELIEF.......................................................3
`
`STATEMENT OF REASONS FOR THE RELIEF REQUESTED....................................4
`
`A.
`
`B.
`
`C.
`
`D.
`
`Brief Summary of Reasons for Relief Requested................................................4
`
`The ’623 Patent ....................................................................................................13
`
`1.
`Prosecution History of the ’623 Patent ......................................................15
`One of Ordinal Skill in the Art at the Time of the Alleged Invention.............30
`
`Claim Interpretation of the ’623 Patent.............................................................31
`
`1.
`2.
`
`3.
`
`4.
`
`“chiral purity” and “initial chiral purity”...................................................31
`“wherein the chiral purity of R-phenylephrine hydrochloride is at least
`95% of the initial chiral purity after 6 months” .........................................32
`“administering the composition into an eye of an individual in need
`thereof, wherein the composition is stored between -10 to 10 degree
`Celsius prior to administration”.................................................................32
`“allowed to be” ..........................................................................................33
`
`i
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`E.
`
`Specific Identification of Where Each Element of the Claims is Disclosed in
`Prior Art Patents and Printed Publications ......................................................33
`
`1.
`
`2.
`
`Claims 1-13 of the ’623 patent are invalid under 35 U.S.C. § 102 as
`lacking novelty over Altaire’s Product, or, in the alternative, invalid under
`35 U.S.C. § 103 as obvious in view of Altaire’s Product and the
`knowledge of one of ordinary skill in the art.............................................33
`Claims 1-13 of the ’623 patent are invalid under 35 U.S.C. § 102, or in the
`alternative, 35 U.S.C. § 103 as anticipated or rendered obvious in view of
`Altaire’s Package Insert, or alternatively, in view of common knowledge
`in the art or, alternatively or in addition, in view of U.S. Patent No.
`3,966,749 and in further view of Syn-Tech’s Commercially Available
`product. ......................................................................................................45
`Claims 1-13 of the ’623 patent are invalid under 35 U.S.C. § 103 as being
`obvious in view of Applicants’ Admitted Prior Art (“AAPA”), Altaire’s
`Package Insert, and/or the common knowledge in the art or, alternatively
`or in addition, in view of U.S. Patent No. 3,966,749.................................57
`Claims 1-13 of the ’623 patent are invalid under 35 U.S.C. § 112(b) for
`failing to particularly point out and distinctly claim the subject matter
`which the joint inventors regard as the invention ......................................66
`VII. CONCLUSION .....................................................................................................................68
`
`3.
`
`4.
`
`ii
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`
`In re Cuozzo Speed Techs., LLC, 2014-130, 778 F.3d 1271 (Fed. Cir. Feb. 4, 2015)...................31
`
`Markman v. Westview Instruments, 517 U.S. 370 (U.S. 1996) .....................................................69
`
`Nautilus, Inc. v Biosig Instruments, Inc., 134 S. Ct. 2120 (U.S. 2014) .........................................69
`
`STATUTES
`
`35 U.S.C. § 102................................................................................................................3, 4, 34, 46
`
`35 U.S.C. § 102(a)(1)...........................................................................................................3, 37, 46
`
`35 U.S.C. § 103...................................................................................................................... passim
`
`35 U.S.C. § 112..................................................................................................................41, 42, 52
`
`35 U.S.C. § 112(b) ...............................................................................................................4, 67, 69
`
`35 U.S.C. §§ 321-328 ......................................................................................................................3
`
`35 U.S.C. § 322(a)(3).......................................................................................................................3
`
`35 USC §§ 102 and 103...................................................................................................................3
`
`REGULATIONS
`
`37 C.F.R. § 42.8(b)(1)......................................................................................................................1
`
`37 C.F.R. § 42.8(b)(2)......................................................................................................................1
`
`37 C.F.R. § 42.8(b)(3)......................................................................................................................1
`
`37 C.F.R. § 42.8(b)(4)......................................................................................................................2
`
`37 C.F.R. § 42.10(b) ........................................................................................................................1
`
`37 C.F.R. §§ 42.15(b) and 42.203....................................................................................................2
`
`37 C.F.R. §§ 42.200-42.224.............................................................................................................3
`
`37 C.F.R. § 42.200(b) ..............................................................................................................31, 32
`
`iii
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`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`37 C.F.R. § 42.202(a).......................................................................................................................3
`
`37 C.F.R. § 42.204(a).......................................................................................................................2
`
`37 C.F.R. § 42.204(b) ......................................................................................................................3
`
`37 CFR 1.75(e)...............................................................................................................................58
`
`iv
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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`LISTING OF EXHIBITS
`
`Exhibit 1001:
`
`U.S. Patent No. 8,859,623 (Issued Oct. 14, 2014)
`
`Exhibit 1002:
`
`Prosecution and Transaction History of U.S. Patent No.
`8,859,623
`
`Exhibit 1003:
`
`Sawaya Declaration
`
`Exhibit 1004:
`
`Altafrin 2.5% Product Label (Rev. 08/05)
`
`Exhibit 1005:
`
`Altafrin 10% Product Label (Rev. 11/04)
`
`Exhibit 1006:
`
`NEOFRIN 2.5% Lot 12402 Product Images (10/12)
`
`Exhibit 1007:
`
`OCuSOFT, Inc. Invoice (10/12)
`
`Exhibit 1008:
`
`Phenylephrine Hydrochloride Ophthalmic Solution, USP 10%
`Product Images (Expiration 12/13)
`
`Exhibit 1009:
`
`Hub Pharmaceuticals Invoice (10/12)
`
`Exhibit 1010:
`
`FDA Information Request (12/12)
`
`Exhibit 1011:
`
`U.S. Patent No. 3,966,749 (Issued Jun. 29, 1976)
`
`Exhibit 1012:
`
`Identification Study for the Racemic(-) Form of
`Phenylephrine Hydrochloride in Phenylephrine
`Hydrochloride Ophthalmic Solution, USP 2.5% and 10%
`(STU0328) (2/13)
`
`Exhibit 1013:
`
`Paragon Bioteck, Inc. Purchase Order # 4009 (4/13)
`
`Exhibit 1014:
`
`Paragon Bioteck, Inc. Purchase Order # 4010 (7/13)
`
`Exhibit 1015:
`
`Exhibit 1016:
`
`Akorn Phenylephrine 2.5% (Lot 091281) and 10 % (Lot
`081431) Chromatograms
`
`Altaire Pharmaceuticals, Inc. Phenylephrine 2.5% (Lots
`11302, 11577, 11578) and 10 % (Lots 11323, 11581, 11582)
`
`v
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`Chromatograms
`
`Exhibit 1017:
`
`Exhibit 1018:
`
`Exhibit 1019:
`
`Exhibit 1020:
`
`Altaire Pharmaceuticals, Inc. Phenylephrine 2.5% (Lot
`15040) Elevated Temperature Storage Chromatograms
`
`Altaire Pharmaceuticals, Inc. Phenylephrine Product Insert
`(8/10)
`
`Summary of Chiral Purity Testing by HPLC of Phenylephrine
`HCl Ophthalmic Solution USP (2.5% and 10%) (4/15)
`
`Drug Substances used in the Manufacture of Phenylephrine
`HCL Ophthalmic Solution (4/15)
`
`vi
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`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`I. MANDATORY NOTICES
`
`A.
`
`Real Party-In-Interest Pursuant to 37 C.F.R. § 42.8(b)(1)
`
`Altaire Pharmaceuticals, Inc. (“Altaire” or “Petitioner”) having its
`
`principal place of business at 311 West Lane, Aquebogue, NY, 11931 is the real
`
`party-in-interest.
`
`B.
`
`Related Matters Pursuant to 37 C.F.R. § 42.8(b)(2)
`
`Records of the U.S. Patent and Trademark Office (“PTO”) indicate that
`
`U.S. Patent No. 8,859,623 (“the ’623 patent”) (Exhibit 1001), assigned on its face
`
`to Paragon Bioteck, Inc. (“Paragon”), issued October 14, 2014, from U.S. Patent
`
`Application No. 14/080,771 (“the ’771 application”),1 filed November 14, 2013,
`
`which is the ’623 patent’s earliest effective filing date. The issues of validity,
`
`enforceability or infringement of the ’623 patent are not involved in any Civil
`
`Action.
`
`C.
`
`Lead and Back-Up Counsel Pursuant to 37 C.F.R. § 42.8(b)(3)
`
`Petitioner designates Dipu A. Doshi (Reg. No. 60,073) as Lead Counsel
`
`and Edward A. Meilman (Reg. No. 24,735) and Jonathan W.S. England (Reg. No.
`
`71,223) as Backup Counsel. Pursuant to 37 C.F.R. § 42.10(b), a Power of
`
`Attorney accompanies this Petition.
`
`1 The complete File History of the ’623 patent is attached as Exhibit 1002.
`
`1
`
`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`D.
`
`Service Information Pursuant to 37 C.F.R. § 42.8(b)(4)
`
`Lead counsel for Petitioner may be served by electronic mail or mail at:
`
`Dipu A. Doshi (Reg. No. 60,073)
`DICKSTEIN SHAPIRO LLP
`1825 Eye Street NW
`Washington, DC 20006
`Tel (202) 420-2604
`Fax (202) 420-2201
`doshid@dicksteinshapiro.com
`meilmane@dicksteinshapiro.com
`englandj@dicksteinshapiro.com
`
`E.
`
`Payment of Fees Under 37 C.F.R. §§ 42.15(b) and 42.203
`
`The required fees are submitted herewith. If additional fees are owed
`
`during this proceeding, the PTO is authorized to charge Deposit Account No. 04-
`
`1073.
`
`II. GROUNDS FOR STANDING
`
`Pursuant to 37 C.F.R. § 42.204(a), Petitioner certifies that the ’623 patent
`
`is available for post grant review and that it is not barred or estopped from
`
`requesting post grant review challenging the patent claims on the grounds set forth
`
`herein. Petitioner is not the owner or assignee of the ’623 patent, nor has it filed a
`
`civil action challenging the validity of the patent against same.
`
`2
`
`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`III. TIMING
`
`The ’623 patent issued October 14, 2014. Pursuant to 37 C.F.R. §
`
`42.202(a), this Petition is being filed within nine months of the issue date of the
`
`’623 patent.
`
`IV. STATEMENT OF PRECISE RELIEF REQUESTED
`
`A.
`
`Identification of Claims Challenged and Relief Sought
`
`Pursuant to 37 C.F.R. § 42.204(b), Petitioner respectfully requests post-
`
`grant review of claims 1-13 of the ’623 patent under 35 U.S.C. §§ 321-328 and 37
`
`C.F.R. §§ 42.200-42.224, and the cancellation of those claims as being
`
`unpatentable under 35 USC §§ 102, 103, 112.
`
`B.
`
`Statutory Grounds and Prior Art Relied Upon for Each Ground
`
`It is more likely than not that at least one of claims 1-13 of the ’623
`
`patent will be found unpatentable based upon the following prior art and
`
`arguments. Each printed publication and sale set forth in the Listing of Exhibits
`
`and/or discussed herein constitutes prior art against the ’623 patent under 35
`
`U.S.C. § 102(a)(1) and is submitted under 35 U.S.C. § 322(a)(3).
`
`V. SPECIFIC CLAIMS AND GROUNDS FOR RELIEF
`Ground 1
`
`Claims 1-13 of the ’623 patent are invalid under 35
`
`U.S.C. § 102 as lacking novelty over Altaire’s Product, or, in the alternative,
`
`invalid under 35 U.S.C. § 103 as obvious in view of Altaire’s Product and the
`
`knowledge of one of ordinary skill in the art.
`
`3
`
`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`Ground 2
`
`Claims 1-13 of the ’623 patent are invalid under 35
`
`U.S.C. § 102, or in the alternative, 35 U.S.C. § 103 as anticipated or rendered
`
`obvious in view of Altaire’s Package Insert, or alternatively, in view of common
`
`knowledge in the art or, alternatively or in addition, in view of U.S. Patent No.
`
`3,966,749 and in further view of Syn-Tech’s Commercially Available product.
`
`Ground 3
`
`Claims 1-13 of the ’623 patent are invalid under 35
`
`U.S.C. § 103 as being obvious in view of Applicants’ Admitted Prior Art
`
`(“AAPA”), Altaire’s Commercial Product, and/or the common knowledge in the
`
`art or, alternatively or in addition, in view of U.S. Patent No. 3,966,749.
`
`Ground 4
`
`Claims 1-13 of the ’623 patent are invalid under 35
`
`U.S.C. § 112(b) for failing to particularly point out and distinctly claim the subject
`
`matter which the joint inventors regard as the invention.
`
`VI. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`
`A.
`
`Brief Summary of Reasons for Relief Requested
`
`The sole independent claim of the ’623 patent recites a method of
`
`applying a known ophthalmic composition to achieve a known result with the
`
`alleged “improvement comprising storing the composition between -10 to 10° C.”
`
`The ’623 specification likewise describes “a composition comprising at least 95%
`
`R-phenylephrine hydrochloride and an aqueous buffer for substantially
`
`maintaining [the] chiral purity of R-phenylephrine hydrochloride for at least 6
`
`4
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`

`

`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
`
`months, the improvement comprising storing the composition between -10 to 10
`
`degree Celsius.” (Exhibit 1001 (the ’623 patent) at 3:6-122).
`
`When filed, the application claimed only the composition per se, and the
`
`Examiner rejected the claims as obvious. The claims were allowed only after
`
`applicants amended the claims to read as method of use claims and after applicants
`
`relied on a Declaration purportedly finding surprising results. In the Notice of
`
`Allowance, the Examiner stated that the “Applicant’s Declaration filed 19 March
`
`2014 provides evidence that the chiral purity of R-phenylephrine is maintained
`
`after 6 months of storage at -10 to 10 °C, but is not maintained when the
`
`composition is stored at room temperature (20 to 25 degrees Celsius).” (Exhibit
`
`1002 (the ’623 File History) at 164 of 167). The Examiner further noted that while
`
`the cited prior art teaches an ophthalmic solution of R-phenylephrine
`
`hydrochloride, it: 1) suggested storage at 20 to 25 ºC.; 2) failed to disclose storage
`
`at -10 to 10 °C; and 3) failed to disclose the degree of chirality of the R-
`
`phenylephrine hydrochloride composition. (See id.). Thus, the Examiner
`
`determined the Declaration established the nonobviousness of claims 1–13 of the
`
`’623 patent. (See id.).
`
`2 The notation of “X:Y” refers to the column number or page number (X) and line
`
`number(s) of the column or page (Y), respectively. Thus, “2:53-65” refers to
`
`column 2, lines 53-65 of the ’623 patent.
`
`5
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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`The Examiner, however, was not made aware that; prior to the effective
`
`filing date of the ’623 patent, it was well known to the public to store a
`
`composition of substantially pure, buffered, R-phenylephrine hydrochloride in the
`
`range between -10 and 10º C.
`
`For example, Altaire manufactured and sold the products that are the
`
`subject of the ’623 patent (Phenylephrine HCl Ophthalmic Solution 2.5% and
`
`Phenylephrine HCl Ophthalmic Solution 10%) for various customers, for at least 8
`
`years prior to the ’623 patent’s filing date. (See Exhibit 1003, ¶ 2). Altaire’s
`
`products have consistently had a label instructing storage in a refrigerator “at 2°-8°
`
`C (36°-46° F).” (See Exhibit 1003, ¶ 2; see, e.g., Exhibits 1004 and 1005 (excerpts
`
`reproduced and annotated below)).3
`
`3 Exhibits 1004 and 1005 are dated as approved for print in September 2005 and
`
`December 2004, respectively.
`
`6
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`Labels like those depicted above were provided on Altaire’s
`
`Phenylephrine Hydrochloride Ophthalmic Solution sold and distributed over one
`
`year prior to the ’623 patent’s filing. (See Exhibit 1003, ¶ 3; see, e.g., Exhibit 1006
`
`at 1 of 3 and 3 of 3 (reproduced and annotated below).
`
`The above depicted product (Lot # 11578 (see id. at 2 of 3)) was sold and
`
`distributed over a year prior to the ’623 patent’s earliest filing date. (See Exhibit
`
`1007). Lot # 11578 was manufactured in December 2011 as a 2.5% Phenylephrine
`
`Hydrochloride Ophthalmic Solution. (See Exhibit 1003, ¶ 4). Lot #11578 had an
`
`7
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`expiration date of December 2013, which means that it would maintain its chirality
`
`for application to the eye when stored at 2°-8° C low temperature storage until that
`
`date. (See Exhibit 1003, ¶ 4; Exhibit 1006 at 2 of 3 (noting a date of “12/13”
`
`indicating its expiration date)).
`
`Altaire also sold and distributed a 10% Phenylephrine Hydrochloride
`
`Ophthalmic Solution. (See Exhibit 1003, ¶ 5; see, e.g., Exhibit 1008 at 1 of 3 and 3
`
`of 3 (reproduced below)).
`
`Lot # 11581 (see id. at 2 of 3)) was sold and distributed over a year prior
`
`to the ’623 patent’s earliest filing date. (See Exhibit 1003, ¶ 6; Exhibit 1009). Lot
`
`# 11581 was manufactured in January 2012 and had an expiration date of
`
`8
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`December 2013, which means that it would maintain its chirality for application to
`
`the eye when stored at 2°-8° C low temperature storage until that date. (See
`
`Exhibit 1003, ¶ 6; Exhibit 1008 at 2 of 3 (noting a date of “12/13” indicating its
`
`expiration date).). After years of selling its Phenylephrine Hydrochloride
`
`Ophthalmic Solution, Altaire was approached by Paragon’s CEO, Mr. Patrick
`
`Witham, to enter into an agreement dated May 15, 2011 (“Agreement”) whereby
`
`Altaire would provide the Chemistry, Manufacturing and Controls (or CMC)
`
`sections regarding Altaire’s Phenylephrine HCl Ophthalmic Solution product for
`
`the limited purposes of supporting a New Drug Application (or NDA) to be
`
`submitted by Paragon to the Federal Food & Drug Administration (“FDA”). (See
`
`Exhibit 1003, ¶ 7). As part of the Agreement, Altaire’s CMC sections were
`
`provided for the limited purposes of obtaining the NDAs contemplated by the
`
`Agreement; the Altaire information was not to be used for any other purpose; and
`
`it was the specific intent of the parties that the Altaire information is the
`
`proprietary and confidential information of Altaire. (See Exhibit 1003, ¶ 8).
`
`Also, as part of the Agreement, Altaire would be Paragon’s exclusive
`
`manufacturer and supplier, and Paragon would purchase Altaire’s phenylephrine
`
`hydrochloride ophthalmic solution at a recited price and be its exclusive
`
`distributor. (Id. at ¶ 9). Paragon submitted its NDA on September 21, 2012. (Id.).
`
`In a December 2012 Information Request, the FDA requested that the NDA
`
`9
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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`sponsor “[c]onsider adding a chiral purity test to the drug product specification or
`
`provide a justification for not doing so.” (See Exhibit 1010 at 2 of 4). In February
`
`2013, Altaire performed a study to assess the chiral purity of its products after low
`
`temperature (2° C to 8° C) storage. (Exhibit 1003, ¶ 10; Exhibit 1012 at 1 of 9).
`
`Since Altaire manufactured two products – containing 2.5% (Altaire formula #
`
`A0358) and 10% (Altaire formula # A0359) – Altaire subjected one lot of each
`
`formulation to chiral purity testing. (Exhibit 1003, ¶ 10). Lot # 11578 (2.5%
`
`formula # A0358) and 11582 (10% formula # A0359)4, manufactured in December
`
`2011 and January 2012, respectively, and stored under refrigeration (2 C to 8 C)
`
`were tested in Altaire’s cGLP laboratories, and found to have had a chiral purity of
`
`101.5% and 97.8%, respectively. (See Exhibit 1003, ¶ 10; Exhibit 1012 at 8 of 9
`
`(showing that the 2.5% formula A0358 had a chiral purity percentage of 101.5 and
`
`that the 10% formula A0359 had a chiral purity percentage of 97.8)).
`
`The chiral purity of the samples was tested by obtaining their specific
`
`rotation. (See Exhibit 1012 at 3 of 9). Lot # 11578 was found to have a specific
`
`rotation of -47.0. (See id. at 7 of 9). Lot # 11578’s specific rotation was divided
`
`by a control, which had a specific rotation of -46.3, and found to have a chiral
`
`4 Lot # 11582 and lot # 11581 are the same formulation, i.e., A0359. (Exhibit
`
`1003, fn 2.
`
`10
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`

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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`purity of 101.5%. (See id. at 8 of 9). Lot # 11582 was found to have a specific
`
`rotation of -45.5°. (See id.). Lot # 11582’s specific rotation was divided by a
`
`control, which had a specific rotation of -46.5°, and found to have a chiral purity of
`
`97.8%. (See Exhibit 1003, ¶ 11; see also Exhibit 1012 at 8 of 9).
`
`Prior to FDA requested testing, Altaire sold and distributed 6,024 units of
`
`Lot # 11578 of its 2.5% Phenylephrine Hydrochloride Ophthalmic Solution to
`
`OcuSoft, Inc. (Rosenberg, Texas) on October 18, 2012 – more than 1 year prior to
`
`the ’623 patent’s filing date. (See Exhibit 1007). Similarly, Altaire sold and
`
`distributed 3996 units of Lot # 11581 – the same formulation as Lot # 11582 – of
`
`its 10% Phenylephrine Hydrochloride Ophthalmic Solution to Hub
`
`Pharmaceuticals (Livonia, Michigan) on October 16, 2012 – more than 1 year prior
`
`to the ’623 patent’s filing date. (See Exhibit 1009).
`
`The chiral purity of these two formulations was provided to Paragon,
`
`which submitted a supplementary NDA filing with the FDA. (Exhibit 1003, ¶ 13).
`
`On March 21, 2013, the FDA granted Paragon’s NDA. (Id.) On or about April 10,
`
`2013, Altaire received a purchase order from Paragon, signed by Patrick Witham,
`
`for the FDA approved phenylephrine hydrochloride ophthalmic solution. (See
`
`Exhibit 1013 (Paragon Bioteck Purchase Order dated April 10, 2013)). Paragon
`
`issued a second purchase order on or about July 25, 2013 to Altaire for the FDA
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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`approved phenylephrine hydrochloride ophthalmic solution. (See Exhibit 1014
`
`(Paragon Bioteck Purchase Order dated July 25, 2013)).
`
`On November 14, 2013, Paragon filed the ’711 application naming
`
`Patrick H. Witham, Sailaja Machiraju and Lauren Mackensie-Clark Bluett as joint
`
`inventors. (See Exhibit 1001). On October 14, 2014, the ’623 patent issued. (Id.).
`
`To Altaire’s surprise, Example 1 of the ’623 patent claimed Altaire’s confidential
`
`and proprietary formulation of its Phenylephrine Hydrochloride Ophthalmic
`
`Solution, including product subject to chiral testing.5 (See Exhibit 1003, ¶ 15).
`
`Paragon listed the ’623 patent in the “Orange Book” in connection with
`
`the NDA discussed above, which encompasses Altaire’s Phenylephrine
`
`Hydrochloride Ophthalmic Solution that was previously sold and distributed to
`
`third parties years prior to the ’623 patent’s filing. (See Exhibit 1003, ¶ 16).
`
`Despite knowledge of Altaire’s prior sales and distribution of its
`
`Phenylephrine Hydrochloride Ophthalmic Solution – including as a response to a
`
`purchase order signed by one of the named joint inventors (see Exhibit 1013) – ,
`
`Paragon withheld this material information from the U.S. Patent & Trademark
`
`Office (“PTO”).6
`
`5 The ’771 application did not publish prior to the ’623 patent’s issuance.
`
`6 This petition does not consider whether the patent is unenforceable as a result of
`
`any inequitable conduct committed during prosecution of the application that
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`U.S. Patent No. 8,859,623
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`As explained in greater detail below, had the Examiner been made aware
`
`of Altaire’s prior sales and distribution of Phenylephrine Hydrochloride
`
`Ophthalmic Solution, and the literature describing the uses of and storage
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`conditions for Altaire’s products, the ’623 patent would not have issued. Paragon
`
`has improperly taken from the public that which was already publicly available.
`
`Thus, Petitioner respectfully submits that the Patent & Trial Appeal Board institute
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`Post Grant Review of claims 1-13 of the ’623 patent.
`
`B.
`
`The ’623 Patent
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`U.S. Patent No. 8,859,623 (“the ’623 patent”) is assigned on its face to
`
`Paragon Bioteck, Inc. (“Paragon”), issued October 14, 2014, from U.S. Patent
`
`Application No. 14/080,771 (“the ’771 application”), filed November 14, 2013,
`
`and does not claim any priority earlier than the filing date of the application.
`
`(Exhibit 1001).
`
`The Abstract of the ’623 patent states the patent is directed towards
`
`methods and compositions of stabilizing phenylephrine formations. According to
`
`the ’623 patent, it was “known in the art that Phenylephrine Hydrochloride solution
`
`should be stored protected from light.” (Exhibit 1001 at 2:53-54). “The benzylic
`
`hydrogen is acidic and can be deprotonated easily. The hydroxyl group may be
`
`issued as the ’623 patent for either the omission of material information or material
`
`misrepresentations to the PTO regarding the March 14, 2014 Witham Declaration.
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`U.S. Patent No. 8,859,623
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`oxidized to form a carbonyl moiety conjugated with phenyl group, especially with
`
`help of the adjacent basic amino group.” (Id. at 2:54-58). The ’623 patent
`
`continues:
`
`Thus, it is known in the art that a Phenylephrine
`Hydrochloride solution should be stored protected from light.
`For example, an insert from a commercially available
`Phenylephrine Hydrochloride Ophthalmic Solution provides
`that the solution should be stored at 20° to 25° C. (USP
`controlled room temperature) and keep container tightly
`closed. Do not use if solution is brown or contains precipitate.
`(AKORN Package Insert)
`
`(Id. at 2:58-65).
`
`According to the ’623 patent, “[h]owever, a solution under such
`
`condition often turns brown over time despite carefully keeping container tightly
`
`closed at 20° to 25° C. (USP controlled room temperature). Those packages
`
`containing the brown solution cannot be used and thus create waste.” (Id. at 2:66-
`
`3:3). “The present invention provides the improvement to overcome such
`
`instability problem.” (Id. at 23:4-5). As detailed below, however, the ’623 patent
`
`fails to provide any alleged improvement to overcome any instability problems;
`
`instead, the ’623 patent conflates the perceived instability problem with that of
`
`chiral purity without having any factual basis to do so.
`
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`U.S. Patent No. 8,859,623
`Petition for Post Grant Review
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`1.
`
`Prosecution History of the ’623 Patent
`
`The originally filed claims of the ’711 application had only one
`
`independent claim which recited:
`
`1. A composition comprising at least 95% R-phenylephrine
`hydrochloride and an aqueous buffer for substantially
`maintaining chiral purity of R-phenylephrine hydrochloride
`for at least 6 months, the improvement comprising storing the
`composition between -10 and 10 degrees Celsius.
`
`(Exhibit 1002 at 23 of 617).
`
`The Examiner rejected the originally filed claims as obvious under
`
`Section 103 over El-Shibini, et al. The Stability of Phenylephrine—Part 3: The
`
`racemisation reaction, Arzneimittelforschung. Sep. 1969;19(9):1613-4 (“Shibini”)
`
`(said to show a buffered solution of L-phenylephrine) in view of Valle US
`
`4,260,600 (said to show the R-enantiomer was the therapeutic form of the
`
`compound). (See Exhibit 1002 at 85-87 of 617). The Examiner pointed out that
`
`“[w]hile Shibinia [sic] does not expressly teach storing the composition between -
`
`10 to 10 degrees Celsius (claim 1) or 2 to 8 degrees Celsius (claim 2), it is noted
`
`that said limitation is a process limitation,” which is not given patentable
`
`consideration for a product claim. (Id. at 86 of 617).
`
`The applicants responded by pointing out that Shibini did not relate to an
`
`ophthalmic composition, that Valle related to treating depression, that neither
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`U.S. Patent No. 8,859,623
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`taught the chiral purity being claimed, and submitted a comparative Declaration by
`
`Patrick Witham. (Id. at 100-101 of 617).
`
`The Examiner maintained the rejection because the response and the
`
`accompanying Declaration argued limitations that did not relate to the claimed
`
`composition, but instead, related to the method of storage. (See id. at 122-125 of
`
`617).
`
`In an attempt to overcome the Examiner’s rejection based upon
`
`obviousness, the applicants amended the claims to recite a method of using the
`
`composition, and relied on the assertion in paragraph 7 of the Witham Declaration
`
`that:
`
`(1) Paragon surprisingly discovered that S-Phenylephrine
`dilated the eye only slightly more than that was untreated, and
`it is important that an eye drop containing Phenylephrine
`hydrochloride used for dilation of the pupil contains
`predominantly the R-isomer in order to maintain maximum
`efficacy of the ophthalmic solution; (2) current R-
`Phenylephrine hydrochloride eye products explicitly specify
`storage at 20 to 25 degree Celsius (hereinafter "room
`temperature storage"); and (3) chiral chromatogram of R-
`Phenylephrine hydrochloride product of high chiral purity and
`subject to low temperature storage shows surprisingly better
`R-Phenylephrine preservation, when compared to chiral
`chromatogram of a commercially available R-Phenylephrine
`
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`U.S. Patent No. 8,859,623
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`hydrochloride product and subject to room temperature
`storage.
`
`(Id. at 136-138, 142-143 of 617).
`
`The Witham Declaration purports to compare a room temperature-stored
`
`formulation identified as that described in an Akorn package insert with a low
`
`temperature-stored formulation. (Id. at 109-110 of 617). Neither the initial chiral
`
`purity of the Akorn formulation nor a chromatogram of the initial formulation was
`
`disclosed. (See id.).
`
`The chromatogram of the Akorn formulation set forth at the top of
`
`Exhibit 3 of the Witham Declaration shows two unresolved “peaks” having
`
`retention times of 5.222 minutes and 5.481 minutes, respectively, and being
`
`completely eluted at about 5.9 minutes. (See Exhibit 1002 at 113 of 617
`
`(reproduced below)).
`
`Exhibit 3 of Witham Declaration:
`
`(Id.).
`
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`U.S. Patent No. 8,859,623
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`Both of these unresolved peaks fall squarely within the range of retention
`
`time applicable to the R-phenylephrine hydrochloride (5.1-5.5 minutes) and are
`
`prior to the retention time applicable to the S-phenylephrine hydrochloride (6.3-6.4
`
`minutes). (Exhibit 1001 at 2:23-34; see also id., Fig. 4 (showing a chromatogram
`
`of the S-Form of phenylephrine hydrochloride) (reproduced below)).
`
`Figure 4 of the ’623 patent:
`
`(Exhibit 1001 at Fig. 4).
`
`Since there is no peak at 6.3-6.4 minutes for the Akorn formulation
`
`(Exhibit 3 of the Witham Declaration), the composition does not contain any S-
`
`phenylephrine, and consequently the chiral purity of the R-phenylephrine in the
`
`Akorn formulation after storage at room temperature is essentially 100%. (Exhibit
`
`1003, ¶ 18; see also Exhi