Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 1 of 52 PageID #:4985
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF
`ILLINOIS EASTERN DIVISION
`
`
`
`
`
`
`
`
`
`C.A. No. 1:16-cv-00651
`C.A. No. 1:17-cv-07903
`(Consolidated)
`
`Hon. Rebecca R. Pallmeyer
`
`
`
`FRESENIUS KABI’S OPENING POST-TRIAL BRIEF
`
`
`
`
`v.
`
`FRESENIUS KABI USA, LLC,
`
`
`Plaintiff,
`
`Defendant.
`
`
`HOSPIRA, INC.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 2 of 52 PageID #:4986
`
`TABLE OF CONTENTS
`
`INTRODUCTION .............................................................................................................. 1
`BACKGROUND ................................................................................................................ 2
`A.
`The Farmos Invention and the IND ........................................................................ 2
`B.
`State of the Art As of the Priority Date ................................................................... 3
`1.
`U.S. Patent No. 4,910,214........................................................................... 3
`2.
`Precedex Concentrate Product .................................................................... 3
`3.
`Dexdomitor ................................................................................................. 4
`4.
`Dexmed Chemistry ..................................................................................... 4
`Precedex Line Extension......................................................................................... 5
`C.
`Asserted Claims of the ’049 and ’106 Patents ........................................................ 6
`D.
`Claim Construction ................................................................................................. 6
`E.
`THE CLAIMS OF THE ASSERTED PATENTS WERE OBVIOUS IN
`VIEW OF THE PUBLISHED PRIOR ART AND POSA KNOWLEDGE ....................... 7
`A.
`Person of Ordinary Skill in the Art ......................................................................... 8
`B.
`The Compositions of the Asserted Claims—A Ready-To-Use,
`Sealed Glass Container, with 4 µg/mL Dexmed—Were Obvious ......................... 9
`1.
`Precedex Concentrate and Knowledge of a POSA ..................................... 9
`2.
`Precedex Concentrate and Dexdomitor .................................................... 13
`The pH Limitation of Claim 8 of the ’049 Patent Was Obvious .......................... 14
`The “About 2%” Limitation of Claim 6 of the ’106 Patent Was
`Obvious ................................................................................................................. 15
`1.
`The “About 2%” Limitation Is an Inherent Property of the
`Obvious Prior Art Combination ................................................................ 16
`Reasonable Expectation of Success .......................................................... 19
`2.
`THE DEXMED IND RENDERS THE ASSERTED CLAIMS OBVIOUS .................... 21
`A.
`The Dexmed IND Is Prior Art Because of Lack of Inventorship ......................... 22
`1.
`Farmos Conceived of the “Subject Matter Sought to be
`Patented” ................................................................................................... 23
`The Dexmed IND was communicated to Hospira .................................... 25
`2.
`The IND Is Prior Art Under the On-Sale Bar ....................................................... 25
`1.
`The Dexmed IND Was Subject to a Commercial Sale ............................. 26
`2.
`The Dexmed IND Product was ready for patenting .................................. 31
`
`C.
`D.
`
`B.
`
`i
`
`I.
`II.
`
`III.
`
`IV.
`
`
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 3 of 52 PageID #:4987
`
`2.
`
`V.
`
`VI.
`
`C.
`
`B.
`
`The Dexmed IND and Precedex Concentrate Renders the Asserted
`Claims Obvious ..................................................................................................... 33
`1.
`The Dexmed IND Renders the pH 2-10 Limitation Obvious
`to a POSA ................................................................................................. 34
`The Dexmed IND Renders the About 2% Limitation
`Obvious to a POSA ................................................................................... 34
`HOSPIRA PRESENTED NO EVIDENCE OF SECONDARY
`CONSIDERATIONS ........................................................................................................ 36
`CLAIM 6 OF THE ’106 PATENT IS NOT ENABLED .................................................. 37
`A.
`The Patent Does Not Teach How to Attain the 2% Limitation If
`That Stability Is Not Inherent for Type I Glass With a Coated
`Stopper .................................................................................................................. 37
`A POSA Would Require Undue Experimentation To Determine
`The Full Scope Of Claimed Compositions That Achieve The 2%
`Limitation. ............................................................................................................. 38
`VII. CONCLUSION ................................................................................................................. 39
`
`
`PROPOSED FINDINGS OF FACT AND CONCLUSIONS OF LAW
`
`FINDINGS OF FACT....................................................................................................... 40
`A.
`Obviousness .......................................................................................................... 40
`1.
`Level of Skill in the Art ............................................................................ 40
`2.
`Scope and Content of the Prior Art ........................................................... 40
`3.
`Differences Between the Prior Art and Claims ......................................... 42
`Enablement ........................................................................................................... 42
`B.
`CONCLUSIONS OF LAW .............................................................................................. 43
`A.
`Claim Construction ............................................................................................... 43
`B.
`Obviousness .......................................................................................................... 43
`C.
`Enablement ........................................................................................................... 44
`
`
`
`ii
`
`I.
`
`II.
`
`
`
`
`
`
`
`
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 4 of 52 PageID #:4988
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`Cases
`
`Adaptix, Inc. v. Alcatel-Lucent, Inc.,
`No. 6:12-cv-22, 2015 WL 12712287 (E.D. Tex. Jun. 26, 2015) .............................................. 25
`Alcon Research, Ltd. v. Apotex Inc.,
`687 F.3d 1362 (Fed. Cir. 2012) .......................................................................................... 16, 17
`Allen Eng’g Corp. v. Bartell Indus., Inc.,
`299 F.3d 1336 (Fed. Cir. 2002) ................................................................................................ 31
`Alloc, Inc. v. Pergo, Inc.,
`No. 02-cv-736, 2008 WL 1968301 (E.D. Wis. May 1, 2008) .................................................. 25
`ALZA Corp. v. Andrx Pharms.,
`603 F.3d 935 (Fed. Cir. 2009) ............................................................................................ 38, 39
`Apotex Corp. v. Istituto Biologico Chemioterapico S.P.A.,
`No. 02-C-5345, 2003 WL 21780965 (N.D. Ill. July 30, 2003) ................................................ 28
`Apotex, Inc. v. Cephalon, Inc.,
`No. 06-cv-2768, 2011 WL 6090696 (E.D. Pa. Nov. 7, 2011) .................................................. 25
`Atlanta Attachment Co. v. Leggett & Platt, Inc.,
`516 F.3d 1361 (Fed. Cir. 2008) .......................................................................................... 30, 31
`Burroughs Wellcome Co. v. Barr Labs., Inc.,
`40 F.3d 1223 (Fed. Cir. 1994) .................................................................................................. 22
`Continental Can Co. USA, Inc. v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991) ................................................................................................ 17
`Corona Cord Tire Co. v. Dovan Chem. Corp.,
`276 U.S. 358 (1928) .................................................................................................................. 31
`Dippin’ Dots, Inc. v. Mosey,
`476 F.3d 1337 (Fed. Cir. 2007). ............................................................................................... 26
`Enzo Biochem, Inc. v. Gen-Probe, Inc.,
`424 F.3d 1276 (Fed. Cir. 2005) ................................................................................................ 26
`Ferag AG v. Quipp Inc.,
`45 F.3d 1562 (Fed. Cir. 1995) ............................................................................................ 26, 30
`Gambro Lundia AB v. Baxter Healthcare Corp.,
`110 F.3d 1573 (Fed. Cir. 1997) ................................................................................................ 22
`Graham v. John Deere Co.,
`383 U.S. 1 (1966). ....................................................................................................................... 7
`
`
`
`iii
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 5 of 52 PageID #:4989
`
`Helsinn Healthcare S.A. v. Teva Pharm. USA, Inc.,
`855 F.3d 1356 (Fed. Cir. 2017) .................................................................................... 26, 31, 32
`Hoosier Energy Rural Elec. Co-op., Inc. v. Amoco Tax Leasing IV Corp.,
`34 F.3d 1310 (7th Cir. 1994) .................................................................................................... 28
`Hospira, Inc. v. Amneal Pharm., LLC,
`285 F. Supp. 3d 776 (D. Del. 2018) .......................................................................................... 18
`Hybritech, Inc. v. Monoclonal Antibodies, Inc.,
`802 F.2d 1367 (Fed. Cir. 1986) ................................................................................................ 22
`In re Carlson,
`983 F.2d 1032 (Fed. Cir. 1993) .................................................................................................. 8
`In re Caveney,
`761 F.2d 671 (Fed. Cir. 1985) .................................................................................................. 26
`In re Cuozzo Speed Techs., LLC,
`793 F.3d 1268 (Fed. Cir. 2015) .................................................................................................. 8
`In re Dybel,
`524 F.2d 1393 (C.C.P.A. 1975) ................................................................................................ 30
`In re Hamilton,
`882 F.2d 1576 (Fed. Cir. 1989) ................................................................................................ 31
`In re Hyatt,
`708 F.2d 712 (Fed. Cir. 1983) .................................................................................................. 38
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) ................................................................................................ 17
`In re Klein,
`987 F.2d 1569 (Fed. Cir. 1993) .................................................................................................. 8
`In re Kollar,
`286 F.3d 1326 (Fed. Cir. 2002) ................................................................................................ 29
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) ................................................................................................ 17
`In re Wands,
`858 F.3d 731 (Fed. Cir. 1988) .................................................................................................. 38
`J.A. LaPorte, Inc. v. Norfolk Dredging Co.,
`787 F.2d 1577 (Fed. Cir. 1986) ................................................................................................ 26
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007) .................................................................................................................... 7
`Law Debenture Tr. Co. of New York v. Maverick Tube Corp.,
`595 F.3d 458 (2d Cir. 2010) ..................................................................................................... 28
`Liebel-Flarsheim Co. v. Merad, Inc.,
`481 F.3d 1371 (Fed. Cir. 2007) ................................................................................................ 39
`
`
`
`iv
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 6 of 52 PageID #:4990
`
`Medicines Co. v. Hospira, Inc.,
`827 F.3d 1363 (Fed. Cir. 2016) (en banc) ................................................................................ 26
`Merck & Co., Inc. v. Teva Pharms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) ................................................................................................ 36
`Minton v. Nat’l Ass’n of Securities Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) ................................................................................................ 28
`Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co.,
`878 F.3d 1336 (Fed. Cir. 2018) ................................................................................................ 17
`OddzOn Prods., Inc. v. Just Toys, Inc.,
`122 F.3d 1396 (Fed. Cir. 1997) .......................................................................................... 22, 23
`Par Pharm., Inc. v. TWi Pharm., Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ............................................................................................ 7, 16
`Pfaff v. Wells Elecs., Inc.,
`525 U.S. 55 (1998) .............................................................................................................. 26, 31
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) .................................................................................................. 8
`Schering Corp. v. Geneva Pharm.,
`339 F.3d 1373 (Fed. Cir. 2003) ................................................................................................ 17
`Sciele Pharma Inc. v. Lupin Ltd.,
`684 F.3d 1253 (Fed. Cir. 2012) .................................................................................................. 7
`Sundance, Inc. v. DeMonte Fabricating Ltd.,
`550 F.3d 1356 (Fed. Cir. 2008) ................................................................................................ 35
`Telemac Cellular Corp. v. Topp Telecom, Inc.,
`247 F.3d 1316 (Fed. Cir. 2001) ................................................................................................ 17
`Trustees of Boston Univ. v. Everlight Elecs. Co.,
`--- F.3d ---, 2018 WL 3554627 (Fed. Cir. Jul 25, 2018) ........................................................... 39
`Wyeth & Cordis Corp. v. Abbott Labs.,
`720 F.3d 1380 (Fed. Cir. 2013) ................................................................................................ 37
`
`Statutes and Regulation
`
`26 C.F.R. § 1.482-1(b) .................................................................................................................. 34
`35 U.S.C. § 102(b) .................................................................................................................. 23, 29
`35 U.S.C. § 102(f) .................................................................................................................. passim
`35 U.S.C. § 103 ................................................................................................................... 7, 23, 29
`35 U.S.C. § 112 ............................................................................................................................. 41
`
`
`
`
`
`v
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 7 of 52 PageID #:4991
`
`I.
`
`INTRODUCTION
`
`Fresenius Kabi, largely through the unrebutted testimony of formulation expert Dr. James
`
`Kipp, showed that the 1999 Precedex Concentrate already made obvious what Hospira patented in
`
`2012. The Concentrate formulation contained dexmedetomidine (“dexmed”) and normal saline,
`
`packaged in Type I glass with a coated rubber stopper. It came in a 100 microgram/milliliter
`
`(µg/mL) concentration and, because it was a concentrate, had to be diluted to 4 µg/mL by adding
`
`more saline. Hospira’s supposed invention was to make a “Premix” product, which came already
`
`diluted with the additional saline to a 4 µg/mL concentration, so a hospital could save that step.
`
`Hospira still used the same old formulation of dexmed and normal saline, packaged in the same
`
`old Type I glass with a coated rubber stopper. Even the prior art veterinary product, Dexdomitor,
`
`used the same old approach of dexmed and saline, with Type I glass and a coated rubber stopper.
`
`Hospira did not change the formula or add special steps to make the Premix or to obtain the pH
`
`and stability properties associated with it. It just sold the same product in a bigger bottle.
`
`Hospira ended up rebutting very little at the five-day trial regarding the invalidity of its two
`
`still-asserted claims, claim 8 of the ’049 patent and claim 6 of the ’106 patent. Hospira’s
`
`formulation expert, Dr. Robert Linhardt, only postulated about potential oxidation, but he provided
`
`no opinion about the extreme conditions under which a POSA would expect to see oxidation nor
`
`any actual data showing oxidation. Neither he nor anyone else rebutted Fresenius Kabi’s evidence
`
`that a POSA would be motivated to make a premix product at 4 µg/mL, that a POSA would have
`
`a reasonable expectation of success by using the tried-and-true formulation of dexmed and normal
`
`saline packaged in the prior art sealed glass container, and that nothing more was needed to obtain
`
`the pH limitation of the ’049 patent or the stability limitation of the ’106 patent. Indeed, Hospira’s
`
`principal focus at trial was disputing whether the 1989 IND for dexmed was prior art under the on-
`
`sale bar—ignoring Farmos’s prior invention—but the claims are invalid with or without the IND.
`
`
`
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 8 of 52 PageID #:4992
`
`Hospira also did not respond to the enablement issue. The ’106 patent discloses one
`
`embodiment for room temperature stability: the obvious copy of the prior art using Type I glass
`
`with a coated rubber stopper. If the “about 2%” property of claim 6 is not inherent to that obvious
`
`combination, then the patent specification does not teach how to obtain it. In addition, claim 6 is
`
`not enabled to its full scope because it covers any “sealed glass container,” without any teaching
`
`to meet the “about 2%” limitation.
`
`In summary, claim 8 of the ’049 patent is invalid as obvious because the pH limitation of
`
`that claim was disclosed or expected in view of the combination of either (a) Precedex Concentrate
`
`and POSA knowledge, (b) Precedex Concentrate and Dexdomitor, or (c) Precedex Concentrate
`
`and IND. Claim 6 of the ’106 patent is invalid as obvious in view of the same prior art
`
`combinations, because the stability limitation of that claim was either inherent or expected.
`
`Claim 6 is additionally invalid as it is not enabled to its full scope.
`
`II.
`
`BACKGROUND
`
`A.
`
`The Farmos Invention and the IND
`
`Dexmed is an old drug that was developed in the late 1980s by Farmos. In July 1988,
`
`Farmos applied for a patent covering dexmed as an injectable drug that can be used for sedation.
`
`JTX-134. In March 1989, Farmos filed an IND (Investigational New Drug application) for
`
`dexmed. JTX-35. The IND provided all of the details needed to administer dexmed to humans
`
`for clinical trials. JTX-35.223-277. The IND included formulation details, glass ampule container
`
`specifications, animal studies, and summaries of completed and ongoing human trials. JTX-35.13-
`
`62, 243-246, 277. An ampule is a sealed glass container that has glass on all sides, whereas a vial
`
`is sealed with a stopper. Trial Tr. 258:7-24 (Kipp); Tata-Venkata Dep Tr. 277:16-21. In 1994
`
`Orion transferred the IND to Abbott. JTX-110.41-42.
`
`
`
`2
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 9 of 52 PageID #:4993
`
`B.
`
`State of the Art As of the Priority Date
`
`The parties agree that the priority date is January 4, 2012. Trial Tr. 251:18-252:13.
`
`The asserted patents do not relate to a new drug, or a new use, or a new formulation, or
`
`even a new container type. Rather, Farmos’s U.S. Patent No. 4,910,214 (“the ’214 patent”) already
`
`covered dexmed and its use as a sedative. And two commercial products, Precedex Concentrate
`
`and Dexdomitor, already used the dexmed and normal saline formulation, packaged in a Type I
`
`glass container with a coated rubber stopper. Even the prior art was old by 2012, the priority date
`
`for Hospira’s asserted patents.
`
`1.
`
`U.S. Patent No. 4,910,214
`
`Farmos obtained the ’214 patent in 1990, which disclosed and claimed the dexmed
`
`compound in particular. JTX-134.14; Trial Tr. 253:9-20 (Kipp). The ’214 patent also disclosed
`
`and claimed the use of dexmed for sedation, which is the same use it has to this day. JTX-134.4;
`
`Trial Tr. 254:2-6 (Kipp).
`
`2.
`
`Precedex Concentrate Product
`
`The FDA approved Precedex Concentrate in 1999. JTX-15.2; Tr. 264:19-20 (Kipp). The
`
`Precedex Concentrate product was a 100 µg/mL dexmed HCl formulation with “sodium chloride
`
`in water” (normal saline), supplied in “2 mL clear glass vials and 2 mL clear glass ampules.” JTX-
`
`15.14; Trial Tr. 268:17-24 (Kipp). Precedex Concentrate used a “Type I glass container with
`
`Teflon-coated stoppers.” Trial Tr. 288:17-20 (Kipp); id. 154:17-19 (Roychowdhury). The
`
`Precedex Concentrate label instructed users to dilute the 2 mL dexmed/normal saline with 48 mL
`
`of more normal saline to a final diluted concentration of 4 µg/mL dexmed. JTX-15.13; Trial Tr.
`
`265:23-266:3 (Kipp); id. 485:4-16 (Maile). Following those instructions resulted in a total final
`
`solution with 200 µg of dexmed in 50 mL of normal saline. Trial Tr. 266:19-24 (Kipp). That is
`
`identical to one of the three sizes of today’s commercial Precedex Premix. Id. 266:25-267:5
`
`
`
`3
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 10 of 52 PageID #:4994
`
`(Kipp); id. 137:6-22 (Roychowdhury).
`
`The Precedex Concentrate label also expressly disclosed that the dexmed-in-saline
`
`formulation has a pH of 4.5 to 7. JTX-15.2; Trial Tr. 271:3-7 (Kipp); id. 485:17-486:3 (Maile).
`
`“And other than using dexmedetomidine in normal saline,” nothing else is required to obtain that
`
`pH. Trial Tr. 271:8-11 (Kipp); JTX-15.2.
`
`The Precedex Concentrate label also provides substantial information about the dexmed
`
`molecule and its stability. The label disclosed the chemical structure for dexmed, and reported its
`
`“partition coefficient in octonal:water at pH 7.4 is 2.89,” which indicates that the molecule is
`
`lipophilic. JTX-15.2. The label specifically states that Precedex Concentrate is “preservative-free
`
`and contains no additives or chemical stabilizers.” JTX-15.2; Trial Tr. 270:1-17 (Kipp).
`
`3.
`
`Dexdomitor
`
`Orion launched Dexdomitor, a commercial veterinary product with ready-to-use dexmed
`
`HCl. In 2002, The European Medicines Evaluation Agency (EMEA) published the Dexdomitor
`
`Label. DTX 288; Trial Tr. 284:21-285:4 (Kipp). Dexdomitor has 500 µg/mL dexmed HCl as a
`
`salt (of which 420 µg is dexmed itself) stored in a 10 mL Type I glass vial sealed with a coated
`
`rubber stopper. DTX 288_0001-02; Trial Tr. 286:6-17, 287:2-6 (Kipp). The Dexdomitor Label
`
`reported a shelf life of two years. DTX 288_0001, 05; Trial Tr. 286:18-21 (Kipp). It further
`
`expressly discussed stability test results that “all parameters remained essentially unchanged at all
`
`storage conditions” and that “no difference between inverted and upright containers could be
`
`noted.” DTX 288_0005; Trial Tr. 287:21-288:12 (Kipp). These disclosures would inform a POSA
`
`that the dexmed and saline formulation is very stable in Type I glass with a coated stopper. DTX
`
`288_0005; Trial Tr. 287:9-15, 288:13-16 (Kipp).
`
`4.
`
`Dexmed Chemistry
`
`A POSA would know from dexmed’s chemistry that it is very stable, because of its
`
`
`
`4
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 11 of 52 PageID #:4995
`
`signature properties. As both Dr. Kipp and Dr. Linhardt explained, dexmed has “aromatic rings”
`
`with the “magic number” of 6 pi electrons, which a POSA would immediately recognize as
`
`imparting special stability. Trial Tr. 319:22-326:10 (Kipp); id. 818:4-18, 819:11-15 (Linhardt).
`
`A POSA would not expect stability to be an issue for this chemical compound, particularly for
`
`
`
`the short time frame of only 5 months.
`
`C.
`
`Precedex Line Extension
`
`In 2004, Abbott transferred dexmed and its IND to Hospira. JTX-109. In 2006, dexmed
`
`was Hospira’s only branded product, so it held meetings to determine what to do: the ’214 patent
`
`on dexmed was set to expire in 2013, which would open the door for generic dexmed products.
`
`JTX-72.4; DTX 90_0005; Trial Tr. 208:19-21, 222:3-12, 222:17-23 (Cedergren). Hospira
`
`discussed Life Cycle Management strategies, and quickly recognized—within months—that it
`
`could sell a premix version of the concentrate, so long as it used glass containers, just as had
`
`already been done. Trial Tr. 148:5-15, 151:21-25, 152:2-8 (Roychowdhury). Still, Hospira did
`
`not need to rush to the Patent Office, as it had until 2013 to see if it could get plastic containers to
`
`work or come up with other ideas. Hospira tasked two scientists, Drs. Roychowdhury and
`
`Cedergren, with the job but neither of them could get plastic containers to work. Trial Tr. 212:20-
`
`213:13, 215:10-13
`
`(Cedergren); 151:18-25, 152:2-11
`
`(Roychowdhury)
`
`(discussing
`
`DTX 413_0001). Years after both left the company, and just before the ’214 patent was about to
`
`expire, Hospira resigned itself to obtain patents for a “ready to use” 4 µg/mL product in a “sealed
`
`glass container.” JTX-1; JTX-2; Trial Tr. 131:10-14, 136:19-138:10 (Roychowdhury); id. 199:15-
`5
`
`
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 12 of 52 PageID #:4996
`
`200:4, 213:5-17 (Cedergren). Hospira’s timing of its patent filings and the Precedex Premix
`
`launch are classic life-cycle management, aimed not at patenting inventions but rather inventing
`
`patents. See DTX 90_0005 (“Protect market from generic competition when patent expires”).
`
`D.
`
`Asserted Claims of the ’049 and ’106 Patents
`
`During the course of litigation, Hospira dropped all but two claims, and asserted at trial
`
`only claim 8 of the ’049 patent and claim 6 of the ’106 patent. Both patents share the same patent
`
`specification text and the same priority date. A summary of the two asserted claims is below:
`
`Claim 8 of the ’049 patent
`
`Claim 6 of the ’106 patent
`
`Ready-to-use liquid pharmaceutical
`composition for parenteral administration to a
`subject, comprising
`
`Ready-to-use liquid pharmaceutical
`composition for parenteral administration to a
`subject, comprising
`
`dexmedetomidine or a pharmaceutically
`acceptable salt thereof
`
`dexmedetomidine or a pharmaceutically
`acceptable salt thereof
`
`at a concentration of about 4 µg/mL
`
`at a concentration of about 4 µg/mL
`
`disposed within a sealed glass container
`
`disposed within a sealed glass container
`
`wherein the composition has a pH of about 2
`to about 10
`
`wherein the composition when stored in the
`glass container for at least five months
`exhibits no more than about 2% decrease in
`the concentration of dexmedetomidine
`
`E.
`
`Claim Construction
`
`The terms “ready to use,” “sealed glass container,” “dexmedetomidine,” “subject,” and
`
`“patient” have already been construed.1 Claim Const. Order, Dkt. No. 69 at 17; Jt. Claim Const.
`
`Chart, Dkt. No. 63 at 3.
`
`
`1 The Court also construed the term “intensive care unit,” and the parties agreed to constructions
`of “patient” and “effective amount,” but these terms appears only in a method-of-use patent that
`Hospira no longer asserts against Fresenius Kabi.
`
`
`
`6
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 13 of 52 PageID #:4997
`
`Claim Term
`
`“ready to use”
`
`Construction
`
`“formulated to be suitable for administration to a patient
`without dilution or reconstitution”
`
`“sealed glass container”
`
`no construction necessary
`
`“dexmedetomidine”
`
`“substantially pure, optically active dextrorotary
`stereoisomer of medetomidine, as a free base or
`pharmaceutically acceptable salt”
`
`“subject”
`
`“a human, a non-human mammal or a non-human animal”
`
`III. THE CLAIMS OF THE ASSERTED PATENTS WERE OBVIOUS IN VIEW OF
`THE PUBLISHED PRIOR ART AND POSA KNOWLEDGE
`
`Inventions are invalid as obvious under 35 U.S.C. § 103 when “the differences between
`
`the subject matter sought to be patented and the prior art are such that the subject matter as a whole
`
`would have been obvious at the time the invention was made to a [POSA] to which such subject
`
`matter pertains.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 406 (2007). The following inquiries
`
`are pertinent to resolving obviousness: (1) the scope and content of the prior art; (2) the level of
`
`ordinary skill in the art; (3) the difference between the prior art and the claims at issues; and (4) if
`
`offered by the patent owner, objective evidence of secondary considerations. Graham v. John
`
`Deere Co., 383 U.S. 1, 17-18 (1966). Obviousness must be shown by clear and convincing
`
`evidence. Sciele Pharma Inc. v. Lupin Ltd., 684 F.3d 1253, 1260 (Fed. Cir. 2012). But “there is
`
`no heightened or added burden that applies to invalidity defenses that are based upon references
`
`that were before the Patent Office.” Id.
`
`Obviousness may be based on combining references, or combining a reference with the
`
`knowledge of a POSA, so long as there is a motivation to combine and a reasonable expectation
`
`of success. Par Pharm., Inc. v. TWi Pharm., Inc., 773 F.3d 1186, 1193, 1196-97 (Fed. Cir. 2014).
`
`In addition, “inherency may supply a missing claim limitation in an obviousness analysis.” Id. at
`
`
`
`7
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 14 of 52 PageID #:4998
`
`1195-96. In other words, “an obvious formulation cannot become nonobvious simply by
`
`administering it to a patient and claiming the resulting serum concentration.” Santarus, Inc. v. Par
`
`Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012).
`
`Thus, for an otherwise obvious combination that tacks on a resulting property in the claim,
`
`the property is also obvious if either (1) the property is inherent with the combination or (2) there
`
`is a reasonable expectation of success to obtain the property. Id.
`
`A broad claim is invalid if any one embodiment that it covers is obvious. Where a “claim
`
`covers plural alternative embodiments,” obviousness “is proper if the prior art demonstrates the
`
`obviousness of any one of them . . . .” In re Klein, 987 F.2d 1569, 1570 (Fed. Cir. 1993). “It is a
`
`long-established rule that claims which are broad enough to read on obvious subject matter are un-
`
`patentable even though they also read on nonobvious subject matter.” In re Cuozzo Speed Techs.,
`
`LLC, 793 F.3d 1268, 1281 (Fed. Cir. 2015) (internal qutations omitted).
`
`Applying this legal background, this section of the brief addresses two issues. First, would
`
`a POSA find the composition combination obvious that is common to both claims: 4 µg/mL
`
`dexmed in a ready-to-use, sealed glass container? Second, if so, then do the pH and stability
`
`limitations add anything to that obvious composition to make them patentable?
`
`A.
`
`Person of Ordinary Skill in the Art
`
`A person of ordinary skill in the art (POSA) is a hypothetical person who is presumed to
`
`be aware of all pertinent art, and has the requisite education and experience. In re Carlson, 983
`
`F.2d 1032, 1038 (Fed. Cir. 1992). A POSA would be “someone with an advanced degree, either
`
`a Ph.D. or a master’s degree in a pharmaceutically related science,” and some years of experience.
`
`Trial Tr. 250:3-20. Dr. Kipp was recognized as an expert in the area of formulation science and
`
`formulation chemistry, and testified about obviousness and enablement from the point of view of
`
`a POSA. Id. 243:22-24. Hospira does not dispute Fresenius Kabi’s POSA definition and its expert,
`8
`
`
`
`

`

`Case: 1:16-cv-00651 Document #: 134 Filed: 07/31/18 Page 15 of 52 PageID #:4999
`
`Dr. Linhardt, applied Dr. Kipp’s POSA definition. Id. 810:5-10 (Linhardt).
`
`B.
`
`The C