`Filed: May 31, 2016
`
`
`
`Filed on behalf of Dr. Reddy’s Laboratories, Ltd.
`and Dr. Reddy’s Laboratories, Inc.
`
`By:
`
`Jeffery B. Arnold
`jarnold@cantorcolburn.com
`Cantor Colburn LLP
`1180 Peachtree Street, Suite 2050
`Atlanta, Georgia 30309
`Telephone: (404) 607-9991
`Facsimile: (404) 607-9981
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,603,514
`
`DR. REDDY’S LABORATORIES, LTD. AND DR. REDDY’S
`LABORATORIES, INC.,
`Petitioners,
`
`v.
`
`MONOSOL RX, LLC,
`Patent Owner.
`
`
`
`
`
`
`
`
`
`
`
`
`Patent No. 8,603,514
`Issue Date: December 10, 2013
`Title: UNIFORM FILMS FOR RAPID DISSOLVE DOSAGE FORM
`INCORPORATING TASTE-MASKING COMPOSITIONS
`Inter Partes Review No. IPR2016-XXXXX
`
`
`
`
`
`
`
`
`
`I.
`II.
`
`V.
`
`TABLE OF CONTENTS
`
`
`Page
`INTRODUCTION ........................................................................................... 1
`BACKGROUND ............................................................................................. 1
`A.
`Brief Overview of the ‘514 Patent ........................................................ 1
`B.
`Brief Overview of the Prosecution History ........................................... 1
`III. GROUNDS FOR STANDING ........................................................................ 8
`IV. MANDATORY NOTICES UNDER 37 C.F.R. §42.8 .................................... 8
`A.
`Real Party-In-Interest (§ 42.8(b)(1)) ..................................................... 8
`B.
`Related Proceedings (§ 42.8(b)(2)) ....................................................... 8
`C.
`Lead and Backup Counsel (§ 42.8(b)(3)) ............................................10
`D.
`Service Information (§ 42.8(b)(4)) ......................................................11
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`IDENTIFICATION OF THE CHALLENGE (§ 42.104(b)) .........................11
`VI. LEVEL OF ORDINARY SKILL IN THE ART ...........................................12
`VII. THE CHALLENGED CLAIMS OF THE ‘514 PATENT ............................13
`VIII. CLAIM CONSTRUCTION ..........................................................................14
`IX. TECHNOLOGY TUTORIAL .......................................................................15
`A.
`Polymers ..............................................................................................15
`B.
`Particles ...............................................................................................18
`C.
`Role of Viscosity .................................................................................18
`D. Drying of Suspensions ........................................................................21
`E.
`Role of Uniformity in Drug Formulations ..........................................22
`
`
`
`-i-
`
`
`
`X.
`
`Films ....................................................................................................23
`F.
`Flavoring of Pharmaceutical Formulations ..........................................23
`G.
`SCOPE AND CONTENT OF THE PRIOR ART .........................................24
`A. WO 00/42992 (“Chen”) (Ex. 1005) ....................................................24
`B.
`U.S. Patent No. 7,067,116 (“Bess”) (Ex. 1004) ..................................25
`C.
`CA 2,274,910 (“Cremer”) (Ex. 1006) .................................................26
`XI. DETAILED EXPLANATION OF THE GROUNDS FOR
`UNPATENTABILITY ..................................................................................27
`A. Ground 1: The Challenged Claims of the ‘514 Patent are
`Invalid Under 35 U.S.C. § 103(a) as Being Obvious Over Bess
`in View of Chen ..................................................................................27
`1. Claim Chart: Bess in View of Chen ..................................39
`Ground 2: The Challenged Claims of the ‘514 Patent are
`Invalid Under 35 U.S.C. § 103(a) as Being Obvious Over Chen
`in View of Cremer ...............................................................................50
`1. Claim Chart: Chen in View of Cremer ................................52
`XII. CONCLUSION ..............................................................................................62
`
`
`B.
`
`
`
`
`
`-ii-
`
`
`
`PETITIONERS’ EXHIBIT LIST
`
`Exhibit No.
`
`Reference
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`U.S. Patent No. 8,603,514 (filed July 10, 2007)
`
`File History, U.S. Patent No. 8,603,514
`
`Expert Declaration of Metin Çelik, Ph.D., Relating to U.S. Patent
`No. 8,603,514
`
`U.S. Patent No. 7,067,116 (filed Mar. 23, 2000) (“Bess”)
`
`WO 00/42992 (published July 27, 2000) (“Chen”)
`
`CA 2,274,910 (published June 25, 1998) (“Cremer”)
`
`File History of Reexam No. 95/002,170
`
`Alfred Martin, Physical Pharmacy (4th ed. 1993) (“Physical
`Pharmacy”)
` [Intentionally Left Blank]
`
`Trial Transcript, Reckitt Benckiser Inc. v. Watson Labs., Inc., CA
`No. 14-1574-RGA (Nov. 3-4, 2015) (“Trial Tr.”)
`
`U.S. Patent No. 6,221,402 (issued April 24, 2001)
`
`C.S. Fuller et al., Interactions in poly(ethylene oxide)—
`hydroxypropyl methylcellulose blends, 42 Polymer 9583 (2001)
`
`Leon Lachman et al, The Theory and Practice of Industrial
`Pharmacy (1986) (“The Theory and Practice of Industrial
`Pharmacy”)
`
`J. Thuro Carstensen, Theory of Pharmaceutical Systems Volume
`II: Heterogenous Systems (1973) (“Theory of Pharmaceutical
`Systems”)
`
`-iii-
`
`
`
`
`
`
`
`
`
`Exhibit No.
`
`Reference
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`Remington’s Pharmaceutical Sciences (Alfonso R. Gennaro, ed.,
`18th ed., 1990)
`
`Mixing in the Process Industries (N. Harnby et al., eds., 2nd ed.,
`1997)
`
`Sevim Kaya & Ahmet Kaya, Microwave drying effects on
`properties of whey protein isolate edible films, 43 Journal of Food
`Engineering 91 (2000)
`
`X.Z. Shu et al., Novel pH-sensitive citrate cross-linked chitosan
`film for drug controlled release, 212 International Journal of
`Pharmaceutics 19 (2001)
`
`T.J. Bowser & L.R. Wilhelm, Modeling Simultaneous Shrinkage
`and Heat and Mass Transfer of a Thin, Nonporous Film During
`Drying, Vol. 60 No. 4 Journal of Food Science 753 (Nov. 4, 1995)
`
`U.S. Patent No. 6,596,298 (filed September 14, 1999)
`
`U.S. Patent No. 6,099,865 (filed June 11, 1999)
`
`U.S. Patent No. 5,166,233 (filed January 31, 1990)
`
`Jian-Hwa Guo & Horst Zerbe, Water Soluble Film for Oral
`Administration, The 24th International Symposium on Controlled
`Release of Bioactive Materials 227 (1997) (“Guo”)
`
`J.P. Cassidy et al., Controlled buccal delivery of buprenorphine,
`25 Journal of Controlled Release 21 (1993)
`
`U.S. Patent No. 4,849,246 (issued July 18, 1989)
`
`U.S. Patent No. 5,393,528 (filed June 1, 1993)
`
`U.S. Patent No. 5,948,430 (filed August 1, 1997) (“Zerbe”)
`
`U.S. Patent No. 5,629,003 (filed September 2, 1994)
`
`
`
`
`
`-iv-
`
`
`
`Exhibit No.
`
`Reference
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`EP No. 0,090,560 (published May 3, 1989) (“Mitra”)
`
`Appellant’s Appeal Brief Regarding U.S. Patent 7,824,588,
`Reexamination Control 95/001,753
`Arlene Weintraub, It's On The Tip Of Your Tongue, Bloomberg
`(July 30, 2006), http://www.bloomberg.com/bw/stories/20060730/
`itsonthetipofyourtongue
`
`U.S. Patent No. 6,552,024 (filed Nov. 5, 1999)
`
`WO 2001/70194 (published September 27, 2001)
`
`1034
`
`Curriculum Vitae of Metin Çelik, Ph.D.
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`Materials Considered by Metin Çelik, Ph.D.
`
`S. Le Person, et al., Near Infrared Drying of Pharmaceutical Thin
`Films: Experimental Analysis of Internal Mass Transport, 37
`Chemical Engineering & Processing 257 (1998) (“Le Person”)
`Decision on Appeal Regarding U.S. Patent 7,666,337, Appeal 2014-
`00893
`
`Decision on Appeal Regarding U.S. Patent 7,824,588, Appeal 2014-
`000547
`
`Decision on Appeal Regarding U.S. Patent 7,897,080, Appeal 2014-
`007671
`
`Patent Owner’s Preliminary Response in IPR2016-00281 of U.S.
`Patent 8,603,514
`
`
`
`-v-
`
`
`
`I.
`
`INTRODUCTION
`
`Under 35 U.S.C. § 311, § 6 of the Leahy-Smith America Invents Act
`
`(“AIA”), and 37 C.F.R. Part 42, Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s
`
`Laboratories, Inc. (“Petitioner”) respectfully requests inter partes review of claims
`
`1-3, 9, 15, 62- 65, 69-73, and 75 of U.S. Patent No. 8,603,514 (“the ’514 patent”),
`
`which is assigned to Monosol RX, LLC (“Monosol” or “Patent Owner”). This
`
`petition and supporting exhibits demonstrate there is a reasonable likelihood that
`
`claims 1-3, 9, 15, 62-65, 69-73, and 75 of the ’514 patent are unpatentable over the
`
`prior art and should be canceled.
`
`II.
`
`BACKGROUND
`
`A. Brief Overview of the ‘514 Patent
`
`The ’514 patent is entitled “Uniform Films for Rapid Dissolve Dosage Form
`
`Incorporating Taste-Masking Compositions.” (Ex. 1001.) The patent is directed to
`
`rapidly dissolving, thin-film drug delivery compositions for the oral administration
`
`of active pharmaceutical components. (Id. at Abstract.) In general, the patent
`
`describes the manufacture of uniform pharmaceutical film drug products using
`
`techniques and ingredients that were well known to those of ordinary skill in the art.
`
`(See Ex. 1003, Metin Çelik Decl. at ¶¶ 26-37, 48-49.)
`
`B.
`
`Brief Overview of the Prosecution History
`
`The application that matured into the ’514 patent was filed July 10, 2007 as
`
`
`
`-1-
`
`
`
`Application No. 11/775,484 (“the ‘484 application”) and claims priority to several
`
`applications. (Exs. 1001, 1002.) The ’514 patent issued on December 10, 2013, and
`
`names Robert K. Yang, Richard C. Fuisz, Garry L. Myers, and Joseph M. Fuisz as
`
`inventors. (Id.)
`
`The ‘484 application is a continuation-in-part of application No. 10/768,809
`
`(“the ‘809 application”), filed on January 30, 2004 and published on December 23,
`
`2004. The ‘809 application is a continuation-in-part of applications Nos.
`
`PCT/US02/32575 (“the ‘575 PCT application”); PCT/US02/32594 (“the ‘594 PCT
`
`application”); and PCT/US02/32542 (“the ‘542 PCT application”), all filed on
`
`October 11, 2002. The ‘809 application issued as U.S. Patent No. 7,357,891. The
`
`‘484 application is also a continuation-in-part of application No. 10/856,176 (“the
`
`‘176 application”), filed on May 28, 2004 and published on February 17, 2005,
`
`which itself is a continuation-in-part of the ‘809 application. The ‘176 application
`
`issued as U.S. Patent No. 7,666,337.
`
`The ‘514 patent also claims priority to provisional applications Nos.
`
`60/328,868 (“the ‘868 application”), filed on October 12, 2001; 60/386,937 (“the
`
`‘937 application”), filed on June 7, 2002; 60/414,276 ( “the ‘276 application”), filed
`
`on September 27, 2002; 60/443,741 (“the ‘741 application”), filed on January 30,
`
`2003; and 60/473,902 (“the ’902 application”), filed on May 28, 2003.
`
`On September 9, 2010, the Examiner rejected many of the claims in the ‘484
`
`
`
`-2-
`
`
`
`application as anticipated under 35 U.S.C. §102(e) by U.S. Patent 7,067,116 (Ex.
`
`1004, “Bess”). (Ex. 1002, ’514 File History, September 9, 2010, Non-Final
`
`Rejection at 3-6.) The Examiner stated that Bess “discloses fast dissolving orally
`
`consumable solid film [sic] containing a taste masking agent and a
`
`pharmaceutically active agent . . .” (Id. at 4.) The Examiner also rejected the
`
`majority of the claims as obvious, under §103, over Ex. 1005, WO2000/42992
`
`(“Chen”) in view of U.S. Patent No. 5,653,993 (“Ghanta”). (Id. at 6-8.) According
`
`to the Examiner, “Chen discloses a water-soluble hydrocolloid; mucosal surface
`
`coated forming film, having an effective dose of an active agent.” (Id. at 6.) The
`
`Examiner also stated that active agents “can be encapsulated in a material that is
`
`different than the hydrocolloid. Encapsulation is additionally utilized to achieve
`
`masking of taste of active agents that are bitter.” (Id. at 7.)
`
`On December 9, 2010, Applicants amended several claims to recite the
`
`limitation: “wherein the uniformity is determined by the composition having a
`
`variation of drug content of less than 10% per film unit.” (’514 File History, Ex.
`
`1002, December 9, 2010 Amendment and Response at 2-9.) Applicants also argued
`
`that none of the cited references taught films where the dosing is uniform. (Id. at
`
`11-17.)
`
`On February 2, 2011, the Examiner issued a Final Rejection of all the claims,
`
`maintained the previous rejections, and asserted that Applicants had the burden of
`
`
`
`-3-
`
`
`
`showing that the prior art did not achieve uniformity. (’514 File History, Ex. 1002,
`
`February 2, 2011 Final Rejection at 2-10.) The Examiner suggested that “Applicant
`
`provide evidence that the film does not have a different drug variation than that
`
`claims [sic] in the instant claims.” (Id. at 12.)
`
`On April 4, 2011, Applicants submitted an Amendment After Final
`
`Rejection. Applicants amended several claims, including by adding a limitation that
`
`the matrix have “a viscosity sufficient to aid in substantially maintaining non- self-
`
`aggregating uniformity of the active in the matrix.” (‘514 File History, Ex. 1002,
`
`April 4, 2011 Amendment and Response at 2, 5.) Applicants argued that none of the
`
`cited prior art demonstrated uniformity. (Id. at 12-18.) Applicants further argued
`
`that because Bess uses “‘conventional’ drying techniques, i.e. air- dried or dried
`
`under warm air[,] . . . [u]niform distribution of actives within the final film would
`
`not be expected with Bess’s process.” (Id. at 15.) Applicants again asserted that
`
`Chen merely mixes the taste modifying agents without recognizing the problems of
`
`attaining uniformity and asserted that Chen does not disclose “using the specific
`
`controlled, bottom-drying methods presently claimed.” (Id. at 17-18.)
`
`On June 1, 2011, Applicants filed a Request for Continued Examination, in
`
`which they incorporated their previous amendments. (‘514 File History, Ex. 1002,
`
`June 1, 2011 Request for Continued Examination at 1-2.) On June 19, 2012, the
`
`Examiner issued a non-final rejection of all the claims over the same references
`
`
`
`-4-
`
`
`
`discussed above. (‘514 File History, June 19, 2012 Non-Final Rejection, Ex. 1002
`
`at 2-13.) On December 19, 2012, Applicants responded with minor amendments to
`
`the claims and largely reiterated their previous argument that the burden was on the
`
`Examiner to demonstrate inherency. (Id., December 19, 2012 Amendment and
`
`Response at 1-16.)
`
`On March 13, 2013, the Examiner issued a Final Rejection. (Id., March 13,
`
`2013 Final Rejection at 2-10.) However, the Examiner indicated that certain claims
`
`would be allowed if written in independent form. (Id. at 2.) The Examiner
`
`maintained the rejection over Bess and the rejection over the combination of Chen
`
`and Ghanta, again reiterating that the burden was on Applicants to show the lack of
`
`uniformity in these references. (Id. at 2-10.)
`
`On May 10, 2013, Applicants filed a Response After Final Action.
`
`Applicants added new claims and amended other claims, which eventually became
`
`the final, issued claims. (Id., May 10, 2013 Amendment and Response After Final
`
`Action at 2-19.) Applicants referenced a May 1, 2013 interview in which they
`
`persuaded the Examiner that Bess and Chen did not obtain uniform formulations.
`
`(Id., May 10, 2013 Amendment and Response After Final Action at 20-21.) In the
`
`Interview Summary, Applicants stated:
`
`During the Interview, 2 exhibits were discussed: 1) the Declaration
`under 35 U.S.C. § 1.132 of B. Arlie Bogue dated March 13, 2013
`demonstrating the uniformity of the Applicants’ drug delivery
`
`
`
`-5-
`
`
`
`compositions both within single lots and across lots and 2) a sheet
`based on Figure 5 of the Chen reference demonstrating that Chen’s
`compositions vary by greater than 10% from a desired amount of
`active. . . . The Bogue declaration was submitted in Reexamination
`No. 95/002,170.
`(Id.) The Bogue Declaration was not filed in the ‘484 file history, but there are
`
`three substantially similar declarations found in the File History of Reexam No.
`
`95/002,170 (the “‘170 Reexam”). (See ’170 Reexam, Ex. 1007 at 5-6.)1
`
`
`
`On June 14, 2013, the Examiner issued a Notice of Allowance. (‘514 File
`
`History, Ex. 1002, June 14, 2013 Notice of Allowance at 1-4.) On June 18, 2013,
`
`Applicants filed an Amendment after Notice of Allowance, correcting the
`
`dependencies of the to-be issued claims. (Id., June 18, 2013 Amendment After
`
`Notice of Allowance at 2-16.) Applicants also offered a “detailed interview
`
`summary.” (Id. at 18-20.) There, Applicants stated:
`
`As shown in Figure 5 of Chen, which shows the release profiles of
`four actives from exemplary films, in many instances the amount of
`active released from Chen’s films is greater than 110% of the
`expected amount.
`
`
`1 Reexam No. 95/002,170 was a reexamination of U.S. Patent No. 7,897,080 (“the
`‘080 patent”), involving some of the same prior art as the prosecution of the ‘514
`patent, including Chen (Ex. 1005). It was filed September 10, 2012. It terminated in
`the amendment or cancellation of several claims of the ‘080 patent in an office
`action on September 3, 2003.
`
`
`
`
`-6-
`
`
`
`
`(Id. at 18-19.) Applicants also argued that Bess “is devoid of any teaching of the
`
`
`
`active content uniformity of its compositions.” (Id. at 19.)
`
`On August 1, 2013, Applicants also briefly summarized the May 1, 2013
`
`interview. Applicants’ summary states:
`
`Applicants presented arguments regarding the teachings of Bess
`[Bess] and Chen. After reviewing Figure 5 of Chen and the
`Declaration, it was determined that neither Bess nor Chen inherently
`result in a film having a uniformity in which the individual dosage
`unit does not vary by more than 10% of the desired amount of the
`active. All pending claims appear allowable over the prior art.
`(Id. at 1.) The claims under consideration ultimately issued. (Ex. 1002, November
`
`20, 2013 Issue Notification at 1.)
`
`
`
`-7-
`
`
`
`III.
`
`GROUNDS FOR STANDING
`
`Pursuant to 37 C.F.R. § 42.104(a), Petitioner hereby certifies that the ’514
`
`patent is available for Inter Partes review and that the Petitioner is not barred or
`
`estopped from requesting Inter Partes review challenging the claims of the ’514
`
`patent on the grounds identified herein.
`
`IV.
`
`MANDATORY NOTICES UNDER 37 C.F.R. §42.8
`
`A. Real Party-In-Interest (§ 42.8(b)(1))
`
`The real parties-in-interest are Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s
`
`Laboratories, Inc. (“Dr. Reddy’s” or “Petitioner”).
`
`B. Related Proceedings (§ 42.8(b)(2))
`
`The following proceedings may affect or be affected by a decision in this
`
`proceeding:
`
`Related Proceeding
`Reckitt Benckiser Pharmaceuticals Inc. v.
`Par Pharmaceutical, Inc. et al.
`
`Reckitt Benckiser Pharmaceuticals Inc.
`v. Watson Laboratories, Inc. et al.
`Reckitt Benckiser Pharmaceuticals Inc. v.
`Alvogen Pine Brook, Inc.et al.
`
`Jurisdiction
`Case No.
`1-13-cv-01461-RGA U.S. District
`Court District of
`Delaware
`(Wilmington)
`(“DED”)
`1-13-cv-01674-RGA DED
`
`1-13-cv-02003-RGA DED
`
`
`
`-8-
`
`
`
`Reckitt Benckiser Pharmaceuticals Inc.
`v. Par Pharmaceutical, Inc. et al.
`Reckitt Benckiser Pharmaceuticals Inc. v.
`Teva Pharmaceuticals USA, Inc.
`Reckitt Benckiser Pharmaceuticals Inc.
`et al. v Par Pharmaceutical Inc. et al.
`Reckitt Benckiser Pharmaceuticals Inc.
`et al. v. Watson Laboratories Inc. et al.
`Reckitt Benckiser Pharmaceuticals Inc.
`v. Alvogen Pine Brook, Inc.
`Indivior Inc. et al v. Mylan Technologies
`Inc. et al.
`Indivior Inc. et al v. Sandoz Inc.
`RGA Indivior Inc. et al. v. Teva
`Pharmaceuticals USA, Inc.
`Indivior Inc. et al v. Mylan Technologies
`Inc. et al.
`
`BioDelivery Sciences International, Inc.
`v.Reckitt Benckiser Pharmaceuticals Inc.
`BioDelivery Sciences International, Inc.
`v.Reckitt Benckiser Pharmaceuticals Inc.
`Teva Pharmaceuticals USA, Inc. v.
`
`1-14-cv-00422-RGA DED
`
`1-14-cv-01451-RGA DED
`
`1-14-cv-01573-RGA DED
`
`1-14-cv-01574-RGA DED
`
`1-15-cv-00477-RGA DED
`
`1-15-cv-01016-RGA DED
`
`1-15-cv-01051-RGA DED
`1-16-cv-00178-RGA DED
`
`1-15-cv-00209-IMK United States
`District
`Court/Northern
`District of West
`Virginia
`(Clarksburg)
`USPTO/PTAB
`
`IPR2014-00325
`
`IPR2014-00998
`
`UPSTO/PTAB
`
`IPR2016-00280
`
`UPSTO/PTAB
`
`
`
`-9-
`
`
`
`Indivior UK Limited
`
`The following administrative proceedings may affect or be affected by a
`
`decision in this proceeding: Petitioner is aware of at least one currently-pending
`
`U.S. patent application that claims the benefit of the ‘514 Patent: U.S. Patent
`
`Application Serial No. 14/572,173 filed on December 16, 2014, which is pending.
`
`C. Lead and Backup Counsel (§ 42.8(b)(3))
`
`Lead Counsel
`
`Back-Up Counsel
`
`Jeffery B. Arnold
`USPTO Reg. No. 39,540
`Cantor Colburn LLP
`1180 Peachtree Street, Suite 2050
`Atlanta, Georgia 30309
`Telephone: (404) 607-9991
`Facsimile: (404) 607 9981
`jarnold@cantorcolburn.com
`
`
`Leslie-Anne Maxwell, Ph.D.
`USPTO Reg. No. 44,778
`Cantor Colburn LLP
`20 Church Street, 22nd Floor
`Hartford, Connecticut 06103
`Telephone: (860) 286-2929
`Facsimile: (860) 286-0115
`amaxwell@cantorcolburn.com
`
`Peter R. Hagerty
`USPTO Reg. No. 42,618
`Cantor Colburn LLP
`1180 Peachtree Street, Suite
`2050
`Atlanta, Georgia 30309
`Telephone: (404) 607-9991
`
`
`
`-10-
`
`
`
`Facsimile: (404) 607-9981
`phagerty@cantorcolburn.com
`
`Andrew C. Ryan
`USPTO Reg. No. 43,070
`Cantor Colburn LLP
`20 Church Street, 22nd Floor
`Hartford, Connecticut 06103
`Telephone: (860) 286-2929
`Facsimile: (860) 286-0115
`ryan@cantorcolburn.com
`
`
`
`D.
`
`Service Information (§ 42.8(b)(4))
`
`Please direct all correspondence to counsel at the contact information above.
`
`Petitioner consents to service by electronic mail.
`
`V.
`
`
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`IDENTIFICATION OF THE CHALLENGE (§ 42.104(b))
`
`Petitioner challenges claims 1-3, 9, 15, 62-65, 69-73, and 75 of the ’514
`
`patent (“the Challenged Claims”), and requests review of those claims under 35
`
`U.S.C. § 311 and AIA § 6. Petitioner challenges these claims on the following
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`grounds:
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`Ground
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`Claims
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`Description
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`1
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`2
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`1-3, 9, 15, 62-65, 69-73 and 75 Obvious under 103 over Bess2 in
`view of Chen3
`1-3, 9, 15, 62-65, 69-73 and 75 Obvious under 103 over Chen in
`view of Cremer4
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`To support these grounds of unpatentability, this Petition is accompanied by
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`the declaration of Dr. Metin Çelik (“Çelik Decl.,” Ex. 1003).
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`The Grounds raised in this petition are meaningfully distinct. Ground 1
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`presents obviousness of claims 1-3, 9, 15, 62-65, 69-73, and 75 based upon Bess in
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`view of Chen. Ground 2 differs from Ground 1 in asserting obviousness of claims
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`1-3, 9, 15, 62-65, 69-73, and 75 based upon Chen in view of Cremer. This ground is
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`not cumulative of Ground 1 as Bess teaches a hydrated polymer gel film and
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`Cremer teaches a film with a mucoadhesive layer that includes a water-soluble, film
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`forming polymer.
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`VI.
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`LEVEL OF ORDINARY SKILL IN THE ART
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`A person of ordinary skill in the art related to the ’514 patent would have a
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`Master’s Degree, Ph.D., or their equivalent in pharmaceutics or pharmaceutical
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`sciences or a related field, and several years of experience in developing and
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`formulating dosage forms for drugs. (See Ex. 1003, Çelik Decl. at ¶ 45.)
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`2 Ex. 1004
`3 Ex. 1005
`4 Ex. 1006
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`VII.
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`THE CHALLENGED CLAIMS OF THE ‘514 PATENT
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`
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`Petitioner challenges claims 1-3, 9, 15, 62-65, 69-73 and 75 of the ‘514
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`patent. Independent claims 1 and 62 are illustrative:
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`1.
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`A drug delivery composition comprising:
`(i) a cast film comprising a flowable water-soluble or water
`swellable film-forming matrix comprising one or more substantially
`water soluble or water swellable polymers; and a desired amount of at
`least one active;
`wherein said matrix has a viscosity sufficient to aid in
`substantially maintaining non-self-aggregating uniformity of the
`active in the matrix;
`(ii) a particulate active substantially uniformly stationed in the
`matrix; and
`(iii) a taste-masking agent coated or intimately associated with
`said particulate to provide taste-masking of the active; wherein the
`combined particulate and taste-masking agent have a particle size of
`200 microns or less and said flowable water-soluble or water
`swellable film-forming matrix is capable of being dried without loss
`of substantial uniformity in the stationing of said particulate active
`therein; and wherein the uniformity subsequent to casting and drying
`of the matrix is measured by substantially equally sized individual
`unit doses which do not vary by more than 10% of said desired
`amount of said at least one active.
`62. A drug delivery composition comprising:
`(i) a cast film comprising a flowable water-soluble or water
`swellable film-forming matrix comprising one or more substantially
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`water soluble or water swellable polymers; and a desired amount of at
`least one active;
`wherein said matrix has a viscosity sufficient to aid in
`substantially maintaining non-self-aggregating uniformity of the
`active in the matrix;
`(ii) a particulate active substantially uniformly stationed in the
`matrix; and
`(iii) a taste-masking agent selected from the group consisting of
`flavors, sweeteners, flavor enhancers, and combinations thereof to
`provide taste-masking of the active; wherein the particulate active has
`a particle size of 200 microns or less and said flowable water-soluble
`or water swellable film-forming matrix is capable of being dried
`without loss of substantial uniformity in the stationing of said
`particulate active therein; and wherein the uniformity subsequent to
`casting and drying of the matrix is measured by substantially equally
`sized individual unit doses which do not vary by more than 10% of
`said desired amount of said at least one active.
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`(Ex. 1001 at 67:34-56; 73:48-74.9) Dependent claims 2-3, 9, 15, 63-65, 69-73, and
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`75 of the ‘514 patent relate to particulate size, drug content, taste-masking agents,
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`etc.
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`VIII.
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`CLAIM CONSTRUCTION
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`A claim subject to Inter Partes Review receives the broadest reasonable
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`construction or interpretation in light of the specification of the patent in which it
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`appears because, among other reasons, the patent owner has an opportunity to
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`amend the claims, which is the case here. 37 C.F.R. § 42.100(b); In re Cuozzo
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`Speed Techs., LLC, 793 F. 3d 1268 (Fed. Cir. 2015). For purposes of this
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`proceeding only, one claim term warrants a specific construction: “dried without
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`the loss of substantial uniformity.” (’514 Patent, Ex. 1001, at claims 1 and 62).
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`In a co-pending litigation, Patent Owner’s expert witness on validity of the ’514
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`patent, Dr. Langer, testified that the claims were not limited to any particular form
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`of drying, or any particular drying parameters.5 For these reasons, under the
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`broadest reasonable interpretation standard, “dried without the loss of substantial
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`uniformity” should be construed at least as broadly as Patent Owner’s proposed
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`construction in the district court, i.e., “any method of drying.” A viable opportunity
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`to amend is present should Patent Owner desire a narrower interpretation.
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`IX.
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`TECHNOLOGY TUTORIAL
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`A.
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`Polymers
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`In the pharmaceutical industry, polymers are used for various purposes, such
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`as coating, thickening, binding, controlled release, taste-masking, solubility
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`enhancement and packaging. (Ex. 1008, Physical Pharmacy, 4th ed., 1993, at 557;
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`Ex. 1003, Çelik Decl. at ¶ 55.) A polymer is made of many repeating chemical units
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`which are termed “monomers.” These monomers are polymerized to one another
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`5 “Q. Now, the claim -- in none of the claims you looked at specifies parameters for
`drying, is that correct, it does not specify? A. Not parameters.” (Reckitt Benckiser
`Pharmaceuticals Inc. v. Watson Laboratories, Inc., CA No. 14-1574-RGA, Trial
`Tr., Ex. 1010 at 556:10-14.)
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`using well-known methods, such as “addition” or “chain reaction” polymerization
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`and “condensation” or “stepwise” techniques. (Id.) Polymers can be depicted by the
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`chemical structure of their monomers. As an example, the structure for
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`polyvinylpyrrolidone is depicted below:
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`(a monomer unit of polyvinylpyrrolidone). In this figure, “n” refers to the number
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`of monomer units that make up the polymer. (Id.)
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`The molecular weight and composition of a polymer may vary depending on
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`the number of monomers or the chemical structures of the monomers. (Ex. 1008.
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`Physical Pharmacy, at 557-558; Ex. 1003, Çelik Decl. at ¶ 60.) These changes result
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`in polymers with different properties, including flexibility, solubility, and/or
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`viscosity. Viscosity can be adjusted by changing the concentration of the polymer
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`and/or using polymers of different average molecular weights. (Ex. 1008, Physical
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`Pharmacy, at 565-566; Ex. 1003, Çelik Decl. at ¶ 60.)
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`Another method of obtaining a polymer composition with different properties
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`such as flexibility, solubility and/or viscosity, is to create a multiple- polymer
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`system using polymers with different properties. (Physical Pharmacy, at 565-566
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`Ex. 1003, Çelik Decl. at ¶ 43.) For example, a single polymer system may contain a
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`highly water-soluble polymer, such as hydroxypropyl methylcellulose, while a two
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`polymer system may contain both a water-soluble polymer, such as hydroxypropyl
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`methylcellulose, and a water-insoluble polymer, such as ethylcellulose6. (Id)
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`Other polymers are well known for their use as taste-masking agents in drug
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`formulations. These include acrylic polymers, such as a butyl methacrylate/(2-
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`dimethylaminoethyl), methacrylate/methyl methacrylate copolymer and
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`polyvinylacetal diethylaminoacetate. (See, e.g., Ex. 1011, U. S. Pat. No. 6,221,402,
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`entitled “Rapidly releasing and taste-masking pharmaceutical dosage form,” at
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`4:24-41.)
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`Some polymers are well known for use in film compositions, including cast
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`films. These include polyethylene oxide, which is water-swellable, and hydrophilic
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`cellulosic polymers, such as hydroxypropyl methylcellulose, methylcellulose, and
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`hydroxypropylcellulose, which are water-soluble. (Ex. 1012, Fuller, Interactions in
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`poly(ethylene oxide)—hydroxypropyl methylcellulose blends, Polymer,
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`6 Some examples of water-soluble polymers include methylcellulose,
`hydroxypropyl methylcellulose, hydroxypropylcellulose, polyethylene glycol
`(PEG), polyvinyl pyrrolidone (PVP), carboxymethyl cellulose, cellulose acetate
`phthalate and sodium carboxymethylcellulose. (Id.) Some examples of water-
`insoluble polymers include ethyl cellulose, starch, carboxymethyl starch, and
`cross-linked povidone. These water-insoluble polymers can absorb water and are
`typically used for their gelling or thickening properties. (Id.) Gums that are
`naturally occurring polymers from plants or animals, can be used for the same
`purpose. (Ex. 1008. Physical Pharmacy, at 557; Ex. 1003, Çelik Decl. at ¶ 62.)
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`42(2001):9583-9592, 2001, at 9583-9584; Ex. 1003, Çelik Decl. at ¶ 64.)
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`B.
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`Particles
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`Particles are solid materials which, in pharmaceutical formulations, generally
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`range in size from 0.0005 to 0.01 millimeters. (Ex. 1008, Physical Pharmacy, at
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`423; Ex. 1003, Çelik Decl. at ¶ 65.) Typically, particles in a mixture are not all of a
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`uniform size, so particle size is expressed as an average distribution. Methods used
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`to determine the particle size distribution include sieving, microscopy, and
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`sedimentation. (Ex. 1008, Physical Pharmacy, at 430-434; Ex. 1003, Çelik Decl. at
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`¶ 65.) The particle size can be changed by simply milling the particles using a
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`number of different techniques. (Ex. 1013, The Theory and Practice of Industrial
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`Pharmacy, 3rd ed. 1986 at 654; Ex. 1003, Çelik Decl. at ¶ 65.)
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`C. Role of Viscosity
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`Viscosity is “an expression of the resistance of a fluid to flow; the higher the
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`viscosity, the greater the resistance.” (Ex. 1008, Physical Pharmacy, at 453; Ex.
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`1003, Çelik Decl. at ¶ 66.) The unit of measure for viscosity is centipoise (cps). (Ex.
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`1013, The Theory and Practice of Industrial Pharmacy, at 124; Ex. 1003, Çelik
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`Decl. at ¶ 49.) For reference, the viscosity of water is 1 cps, motor oil is 400 cps,
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`and sour cream is 100,000 cps. Viscosity is important to the physical stability of
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`suspensions and, thus, the uniformity of those suspensions. (Ex. 1003, Çelik Decl.
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`at ¶ 66.)
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