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`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________________________
`
`TWI PHARMACEUTICALS, INC.,
`Petitioner,
`v.
`MERCK SERONO S.A.,
`Patent Owner.
`________________________________________________
`Case IPR2023-00049
`U.S. Patent 7,713,947
`________________________________________________
`
`PATENT OWNER’S RESPONSE
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`IPR2023-00049
`U.S. Patent 7,713,947
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`TABLE OF CONTENTS
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`I.
`
`II.
`
`INTRODUCTION ........................................................................................... 1
`
`STATE OF THE ART ..................................................................................... 3
`
`A. MS ......................................................................................................... 3
`
`1. MS Treatment as of 2004 ............................................................ 4
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`2. MS Outcome Measures ............................................................... 4
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`3.
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`Cladribine .................................................................................... 5
`
`B.
`
`Alleged Prior Art ................................................................................... 6
`
`1.
`
`2.
`
`Bodor (Ex. 1029)......................................................................... 6
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`Rice (Ex. 1008) ........................................................................... 6
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`III.
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`’947 PATENT .................................................................................................. 7
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`IV. POSA ............................................................................................................... 7
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`V.
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`CLAIM CONSTRUCTION ............................................................................ 8
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`VI. BODOR’S REGIMEN IS NOT “BY ANOTHER” ........................................ 8
`
`A.
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`Petitioner fails to meet its burden to show Bodor’s regimen is
`“by another” .......................................................................................... 9
`
`B.
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`Bodor’s regimen is not “by another” .................................................. 11
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`VII. THE CHALLENGED CLAIMS ARE PATENTABLE ............................... 16
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`A. Ground I – Bodor Does Not Anticipate .............................................. 17
`
`1.
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`2.
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`Petitioner Misinterprets Anticipation Jurisprudence ................ 17
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`Bodor Does Not Disclose All Claim Limitations ..................... 19
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`
`
`i
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`
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`Ground II – Claims Are Non-Obvious Over Bodor and a
`POSA’s Knowledge ............................................................................ 36
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`B.
`
`1.
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`Bodor Does Not Disclose Or Suggest All Claim
`Limitations ................................................................................ 36
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`2.
`
`No Motivation Or Reasonable Expectation of Success ............ 37
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`C.
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`Ground III – Claims Are Non-Obvious Over Bodor and Rice ........... 51
`
`1.
`
`2.
`
`Bodor and Rice Fail to Disclose or Suggest All Claim
`Limitations ................................................................................ 51
`
`No Motivation or Reasonable Expectation of Success in
`Combining Bodor and Rice ...................................................... 52
`
`VIII. OBJECTIVE INDICIA SUPPORT NONOBVIOUSNESS OF THE
`CLAIMS ........................................................................................................ 57
`
`A.
`
`B.
`
`C.
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`Skepticism Of Others .......................................................................... 57
`
`Unexpected Results ............................................................................. 59
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`Satisfaction of a Long-Felt, Unmet Need ........................................... 61
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`D. Nexus ................................................................................................... 63
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`IX. CONCLUSION .............................................................................................. 65
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`
`ii
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`
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`TABLE OF AUTHORITIES
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`IPR2023-00049
`U.S. Patent 7,713,947
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` Page(s)
`
`Federal Cases
`Acoustic Tech., Inc. v. Itron Networked Sols., Inc.,
`949 F.3d 1366 (Fed. Cir. 2020) .......................................................................... 17
`Akamai Techs., Inc. v. Cable & Wireless Internet Servs., Inc.,
`344 F.3d 1186 (Fed. Cir. 2003) .......................................................................... 18
`Dayco Prods., Inc. v. Total Containment, Inc.,
`329 F.3d 1358 (Fed. Cir. 2003) .......................................................................... 22
`In re DeBaun,
`687 F.2d 459 (C.C.P.A. 1982) ........................................................................ 8, 16
`Duncan Parking Techs., Inc. v. IPS Grp., Inc.,
`914 F.3d 1347 (Fed. Cir. 2019) .......................................................................... 10
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`800 F.3d 1375 (Fed. Cir. 2015) .......................................................................... 10
`
`Eli Lilly & Co. v. L.A. Biomedical Rsch. Inst. at Harbor-UCLA Med.
`Ctr.,
`849 F.3d 1073 (Fed. Cir. 2017) .......................................................................... 18
`Ex parte McNutt,
`No. 2009-3451, 2009 WL 3044465 (B.P.A.I. Sept. 22, 2009) ..................... 18, 24
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) .......................................................................... 56
`In re Land,
`368 F.2d 866 (C.C.P.A. 1966) .............................................................................. 9
`Neptune Generics, LLC v. Eli Lilly & Co.,
`921 F.3d 1372 (Fed. Cir. 2019) .......................................................................... 59
`Quanergy Sys., Inc. v. Velodyne Lidar USA, Inc.,
`24 F.4th 1406 (Fed. Cir. 2022) ........................................................................... 63
`
`
`
`iii
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`Rambus Inc. v. Rea,
`731 F.3d 1248 (Fed. Cir. 2013) .......................................................................... 63
`Riverwood Int’l Corp. v. R.A. Jones & Co.,
`324 F.3d 1346 (Fed. Cir. 2003) .................................................................... 10, 11
`Takeda Chem. Indus. v. Alphapharm Pty.,
`492 F.3d 1350, 1359 (Fed. Cir. 2007) ................................................................ 56
`Unigene Lab’ys, Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) .......................................................................... 50
`Verdegaal Bros. v. Union Oil Co. of Cal.,
`814 F.2d 628 (Fed. Cir. 1987) ...................................................................... 17, 20
`Volvo Penta of the Americas, LLC v. Brunswick Corp.,
`81 F.4th 1202 (Fed. Cir. 2023) ........................................................................... 57
`WBIP, LLC v. Kohler Co.,
`829 F.3d 1317 (Fed. Cir. 2016) .......................................................................... 57
`Federal Statutes
`35 U.S.C. § 102(a) ..................................................................................................... 9
`35 U.S.C. § 102(b) ..................................................................................................... 8
`35 U.S.C. § 102(e) ..................................................................................................... 9
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`
`
`iv
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`
`
`INTRODUCTION
`By 2004, a person of ordinary skill in the art (“POSA”) did not expect
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`IPR2023-00049
`U.S. Patent 7,713,947
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`I.
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`cladribine to be of clinical benefit in treating multiple sclerosis (“MS”), much less
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`with any durability and without dangerous side effects. Ex. 2010, 45, 67; Ex.
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`2011, 753; Ex. 2012, 341; Ex. 2013, III/3. Several studies had reported that
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`cladribine was not clinically effective, had inconsistent outcome measure results,
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`or raised significant safety concerns. See, e.g., Ex. 1008, 1153; Ex. 1018, 432; Ex.
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`2014, 34; Ex. 1016, 43-44. Nonetheless, the ’947 patent’s inventors persisted in
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`designing a dosing regimen for cladribine, ultimately discovering the claimed
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`novel and unique dosing regimen, which is unexpectedly not just effective and
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`safe during treatment, but also capable of sustained benefits for almost 11 years
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`after treatment. See Ex. 2015, 719, 728.
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`Each of Petitioner’s invalidity grounds fails.
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`The centerpiece of Petitioner’s evidence is Dr. Greenberg’s declaration, but
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`his opinion that the challenged claims are allegedly anticipated and/or obvious
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`should be given little weight at least because it is unsupported by the record. Other
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`than ipse dixit statements, Dr. Greenberg’s declaration fails to demonstrate that the
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`challenged claims are anticipated by Bodor, or obvious over Bodor in view of the
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`common knowledge or Rice.
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`1
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`Bodor discloses in passing a dosing regimen confidentially shared by the
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`inventors of the ʼ947 patent to the Bodor PCT’s assignee, IVAX, under a joint
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`research program between IVAX and Serono.1 Because Bodor’s dosing regimen
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`was attributable to the ʼ947 patent inventors and not “by another,” it is not prior art
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`against the ʼ947 patent. But even if Bodor were prior art, Bodor does not teach or
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`suggest the claimed weight-based dosing or maintenance period, nor would a
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`POSA have inferred those features from Bodor. Moreover, there is nothing that
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`would have motivated a POSA to modify the teachings of Bodor to arrive at the
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`claimed regimens. Nor would a POSA have viewed Bodor’s regimen as effective:
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`Bodor discloses no efficacy results for its regimen.
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`The addition of Rice does not remedy Bodor’s deficiencies. Not only does
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`Rice fail to disclose or suggest the claimed cladribine-free or maintenance periods,
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`but Rice also reports “clinical efficacy was not shown” in its study. Ex. 1008,
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`1153. Dr. Rice later questioned the initially reported MRI results and looked to
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`more clinically relevant MRI results, which he concluded were “clinically
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`unimportant.” Ex. 2016, 44. Petitioner fails to show that a POSA would have
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`1 “Serono” herein collectively refers to Patent Owner, its predecessors, and
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`affiliates.
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`2
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`been motivated to combine Bodor with Rice, much less with a reasonable
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`expectation of success.
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`Hindsight also infects Petitioner’s contention that “fine tuning” dosages
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`would yield the claimed regimen. The complex and variable nature of MS and its
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`slowly evolving disability over years ensures that the treatment effects of any
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`disease modifying agent (“DMA”) dosing schedule can only be assessed over a
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`long period of time. A POSA would have understood that it would require years to
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`evaluate how changes made to an MS drug’s dose and/or dosing schedule would
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`impact clinical outcomes, and “fine tuning” a dosing regimen would be anything
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`but “predictabl[e].” See Pet. 46.
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`Patent Owner (“PO”) respectfully requests that the Board uphold the
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`challenged claims.
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`II.
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`STATE OF THE ART
`A. MS
`In MS, the body’s immune system attacks the central nervous system,
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`causing destruction of myelin insulating nerve fibers. Ex. 1001, 1:24-26; Ex. 2019,
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`¶¶43-44; Ex. 2017, 18; Ex. 2018, 131.
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`3
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`
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`1. MS Treatment as of 2004
`MS clinical subtypes include relapsing remitting MS (“RRMS”) and
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`secondary progressive MS (“SPMS”), among others. Ex. 1001, 1:47-50; Ex. 2019,
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`¶¶45-50.
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`By 2004, FDA had approved DMAs for MS; all were injectables—none was
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`approved for oral administration—and none was dosed by bodyweight. Ex. 1020,
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`12; Ex. 1021, 3; Ex. 1023, 17; Ex. 1022, 19; Ex. 1017, 29; Ex. 1019, 10; Ex. 2058,
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`911; Ex. 2019, ¶¶51-57.
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`By 2004, all FDA-approved MS drugs were dosed continuously to maintain
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`the pharmacologic and clinical effects of the drug—none were administered in a
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`“cyclical” manner. See Ex. 2020, 9; Ex. 2021, 571, 573; Ex. 2022, 1879, 1883; Ex.
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`1022, 2-3; Ex. 2059, 1126; Ex. 2060, 1; Ex. 2019, ¶¶58-70. That is, they were
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`dosed “continuously without an intended interruption in dosing, because clinical
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`efficacy is tightly linked to the period of dosing.” Ex. 2023, 1923.
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`2. MS Outcome Measures
`The mainstay for assessing MS treatment efficacy is clinical outcome
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`variables such as relapse rate and physical disability status, while MRI outcomes
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`can be indicative of disease activity. Ex. 2019, ¶¶71-74; Ex. 2013, III/4. The most
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`widely used measure of physical disability is the Kurtzke Expanded Disability
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`Status Scale (“EDSS”), which measures disability status based on neurologic
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`4
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`examination of functional systems throughout the body. Ex. 2024, 1445-49; Ex.
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`1018, 425-426; Ex. 2019, ¶71.
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`When assessing MS treatment efficacy, a POSA would have understood that
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`outcome measures should be considered collectively, not individually. Ex. 2019,
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`¶72-73. For example, MS studies have shown a dissociation between MRI effects
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`and clinical outcomes. See, e.g., Ex. 1008, 1145; Ex. 2014, 34. A POSA would
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`have understood that “[a]n important principle when interpreting clinical trial data
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`is that of coherence,”2 i.e., all outcomes align to confirm treatment efficacy. Ex.
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`2013, III/4; Ex. 2019, ¶73.
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`3.
`Cladribine
`Clinical studies on cladribine through 2004 left skilled artisans skeptical
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`about cladribine’s utility for treating MS due to (1) reported lack of clinical
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`efficacy and (2) safety concerns arising from cladribine’s lymphocytotoxic
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`activity. Ex. 2019, ¶¶75-86. For example, skilled artisans characterized pre-2004
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`trials on cladribine as “unsuccessful,” Ex. 2013, III/3, showing cladribine “not to
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`be of benefit,” Ex. 2010, 45, and “show[ing]…unconvincing clinical benefit.” Ex.
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`2012, 341; see also infra VIII.A.
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`2 Hereinafter, all emphasis is added unless otherwise noted.
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`5
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`A POSA also would have understood that cladribine posed significant long-
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`term safety concerns due to its lymphocytotoxic activity. Ex. 2019, ¶¶84-85.
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`Further, “[r]epeated treatment raises long-term toxicity issues.” Ex. 1016, 43-44.
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`B. Alleged Prior Art
`1.
`Bodor (Ex. 1029)
`U.S. Patent No. 7,888,328 (“Bodor”) claims priority to a PCT application
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`(Ex. 1007; “Bodor PCT”) filed in March 2004, teaching and claiming cladribine
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`formulations. Ex. 1029, 3:25-4:17. Although the invention in Bodor is clearly
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`directed to cladribine formulations, Petitioner focuses on a 7-line dosing regimen,
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`which teaches neither weight-based dosing nor a maintenance period. Id., 13:19-
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`25; Ex. 2019, ¶¶87-88. What it does disclose, however, is the work of the ’947
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`patent inventors. Infra VI; Ex. 2053, ¶53; Ex. 2055, ¶¶25-29.
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`2.
`Rice (Ex. 1008)
`Rice is a publication disclosing a clinical trial in progressive MS patients
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`with a total (subcutaneous) cladribine dose of 0.7 or 2.1 mg/kg. Ex. 1008, 1146.
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`The primary efficacy outcome measure was mean change in EDSS score and
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`secondary clinical outcomes were mean change in Scripps Neurologic Rating Scale
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`(SNRS) score and time to progression of MS. Id. Rice reported “clinical efficacy
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`was not shown in this trial.” Id., 1153. Rice also reported effects based on MRI,
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`which were not designated as outcome measures. See Ex. 2019, ¶¶89-92.
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`6
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`
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`’947 PATENT
`Claims 36, 38-39, and 41-48 of the ’947 patent (“challenged claims”) are
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`III.
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`directed to an oral MS dosing regimen comprising (i) an about 2-4 month induction
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`period having a total cladribine dose of about 1.7-3.5 mg/kg; (ii) an about 8-10
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`month cladribine-free period; (iii) an about 2-4 month maintenance period having a
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`total cladribine dose of about 1.7 mg/kg; and (iv) a cladribine-free period. Ex.
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`1001, 19:13-30; Ex. 2019, ¶¶93-94.
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`The claimed dosing regimen overcame the challenges and drawbacks of
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`earlier cladribine clinical studies and provides a safe and effective method for
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`treating MS, now FDA-approved as MAVENCLAD®. Ex. 2019, ¶¶95-98; Ex.
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`2026, 416; Ex. 2027, 1-2; Ex. 2028, 1594; Ex. 2043, 1; infra VIII.B.
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`IV. POSA
`A POSA would have an M.D. with at least two years of experience treating
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`neurological conditions, with a focus on autoimmune disorders including but not
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`limited to multiple sclerosis, and prescribing immunotherapies to treat such
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`neurological conditions. Ex. 2019, ¶30. A POSA would also be part of a team
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`including individuals with experience in investigation of the pharmacokinetics and
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`pharmacodynamics of drugs, pharmaceutical drug development, and clinical trial
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`design. Id.
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`7
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`Under either this or Petitioner’s definition, the claims are valid for the
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`reasons stated herein, and Dr. Fred Lublin qualifies as a POSA. Ex. 2019, ¶¶1-17,
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`30-33.
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`V. CLAIM CONSTRUCTION
`PO agrees with Petitioner that all terms in the challenged claims should be
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`given their plain and ordinary meaning, which provides that the total doses of
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`cladribine during the maintenance and induction periods can be the same. See Pet.
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`1-2, 25.
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`PO disagrees with Petitioner’s mischaracterization of the prosecution
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`history; there is no “disclaimer by unmistakable disavowal of scope” with respect
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`to the total maintenance period. Id., 15-16 n.2; see Ex. 1003, 405-423; Ex. 1004,
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`121-131, 152-158, 166-167.
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`VI. BODOR’S REGIMEN IS NOT “BY ANOTHER”
`It is black letter law that “an [inventor’s] own work…may not be used
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`against” them unless it was published over a year before their application.3 In re
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`DeBaun, 687 F.2d 459, 462 (C.C.P.A. 1982). But that is what Petitioner seeks
`
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`3 Bodor or Bodor PCT was not published more than a year before the December
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`22, 2004 filing date of the ’947 patent priority applications, U.S. 60/638,669 and
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`EP04106909, and is not prior art under pre-AIA 35 U.S.C. § 102(b).
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`8
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`here: Bodor includes the work of named inventors of the ’947 patent, which
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`IVAX, the original assignee of Bodor PCT, obtained through a joint research
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`agreement between IVAX and Serono. The dosing regimen in Bodor, which
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`Petitioner cited to challenge the claims, was solely the work of the inventors of the
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`’947 patent, and not the work of Bodor’s inventors, Drs. Bodor or Dandiker.
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`Consequently, it is not prior art “by another” under pre-AIA 35 U.S.C. § 102(a) or
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`(e), and all Petitioner’s grounds fail.
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`A.
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`Petitioner fails to meet its burden to show Bodor’s regimen is “by
`another”
`A disclosure is not prior art under pre-AIA Section 102(a) or (e) unless it is
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`“by another.”4 The Federal Circuit has established a three-step framework for
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`making the “by another” determination:
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`[T]he Board must (1) determine what portions of the reference patent
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`were relied on as prior art to anticipate the claim limitations at issue,
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`(2) evaluate the degree to which those portions were conceived “by
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`4 The relevant part of Section 102(a) requires knowledge or use “by others.” A
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`patent disclosure that is not “by another” under Section 102(e) is likewise not
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`knowledge or use “by others” under Section 102(a). In re Land, 368 F.2d 866,
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`877-79 (C.C.P.A. 1966).
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`another,” and (3) decide whether that other person’s contribution is
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`significant enough, when measured against the full anticipating
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`disclosure, to render him a joint inventor of the applied portions of the
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`reference patent.
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`Duncan Parking Techs., Inc. v. IPS Grp., Inc., 914 F.3d 1347, 1358 (Fed. Cir.
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`2019).
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`Petitioner bears the burden of proving any alleged prior art disclosure is “by
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`another” and “that burden never shifts to the patentee.” Dynamic Drinkware, LLC
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`v. Nat’l Graphics, Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015). Petitioner thus must
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`prove the regimen upon which Petitioner relies is attributable to Drs. Bodor or
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`Dandiker, not the inventors of the ’947 patent. Riverwood Int’l Corp. v. R.A. Jones
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`& Co., 324 F.3d 1346, 1356 (Fed. Cir. 2003). If the inventors of the challenged
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`patent communicated their ideas to someone else, mere publication of the
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`inventor’s ideas by the recipient in a publication is not “by another.” For example,
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`in In re Mathews, two coworkers told each other about their inventions and each
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`filed separate patent applications including descriptions of the other’s invention.
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`408 F.2d 1393, 1394-95 (C.C.P.A. 1969). The Court of Customs and Patent
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`Appeals held that the disclosure of Mathews’s invention in his coworker’s
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`application was not prior art “by another” because it merely reflected Mathews’s
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`10
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`own work communicated to his coworker, not the coworker’s independent work.
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`Id., 1395-96.
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`Under step 1 of Duncan, Petitioner’s grounds each rely upon 7 lines of
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`Bodor to allegedly disclose the treatment regimen and dosage in the challenged
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`claims. Pet. 45-47.
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`Turning to Duncan step 2, Petitioner offers no argument that these 7 lines in
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`Bodor were “by another.” Indeed, as described infra VI.B., Bodor’s inventors did
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`not invent any dosing regimen at all.
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`The analysis should end here. Petitioner’s grounds fail because Petitioner
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`failed to prove Bodor’s regimen is prior art.
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`B.
`Bodor’s regimen is not “by another”
`Even if Petitioner had satisfied step 2 of Duncan, the evidence demonstrates
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`that Bodor’s disclosure was first developed by the ’947 patent inventors who
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`communicated it to IVAX before February 2004. The cited disclosure in Bodor
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`states:
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`
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`[F]or the treatment of multiple sclerosis, 10 mg of
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`cladribine in the instant complex cladribine-cyclodextrin
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`complex in the instant solid dosage form would be
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`administered once per day for a period of five to seven
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`days in the first month, repeated for another period of five
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`11
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`to seven days in the second month, followed by ten months
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`of no treatment.
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`Ex. 1029, 13:19-25.
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`Both of Bodor’s inventors—Drs. Bodor and Dandiker—declare they did not
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`invent this regimen. Ex. 2054, ¶27; Ex. 2055, ¶25. One of the ’947 inventors,
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`Dr. Munafo, explains that he and his co-inventors developed this regimen and
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`communicated it to IVAX before the effective filing date of the Bodor PCT. Ex.
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`2053, ¶¶17-54. This is corroborated by contemporaneous documents showing
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`communications from Serono to IVAX.
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`Serono and the original assignee of the Bodor PCT (IVAX) entered into a
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`joint research agreement in October 2002 to develop oral cladribine for treating
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`MS. Ex. 2048, 19-22; Ex. 2055, ¶14; Ex. 2054, ¶18; Ex. 2053, ¶23; Ex. 2030; Ex.
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`2031, 22, 137; Ex. 2032. Under the agreement, IVAX would “develop an oral
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`dosage formulation of [cladribine] in tablet or capsule form suitable for use in
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`clinical trials and for commercial sale.” Ex. 2048, 19. Serono agreed to “conduct
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`clinical trials” to determine “the dose, safety, and/or efficacy” of IVAX’s oral
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`tablets or capsules, “obtain necessary health authority approvals, and market the
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`final product.” Id., 2, 17-18.
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`Under this agreement, IVAX and Serono regularly and confidentially
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`exchanged substantial information about their work, including via emails and
`12
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`meetings, Ex. 2054, ¶29; Ex. 2055, ¶¶15-18; Ex. 2053, ¶¶27-32; Ex. 2048, which
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`included Dr. Dandiker, a named inventor of Bodor, and others at IVAX. Ex. 2053,
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`¶¶27-32; Ex. 2055, ¶¶15-18; Ex. 2049; Ex. 2050.
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`On December 17, 2003, a Serono employee emailed a Briefing Document
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`containing a clinical trial design invented by the Serono inventors, including Drs.
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`Munafo and Lopez-Bresnahan, disclosing the regimen later added to Bodor, to Dr.
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`Dandiker and IVAX. Ex. 2049; Ex. 2053, ¶¶29, 39-48; Ex. 2055, ¶¶18, 28. This
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`Briefing Document explained that Serono’s study would include three treatment
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`groups including “high/low/placebo,” i.e., 2.1/0.7/0 mg/kg, where in the “low”
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`dose group, patients would receive daily 10 mg oral cladribine tablets for 5
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`consecutive days in each of the first 2 months. Ex. 2049, 47-48; Ex. 2053, ¶¶41,
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`43-46; Ex. 2055, ¶28. At this rate, patients would have received the low dose over
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`two months, one-third as many months as the high dose, which was three-times
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`larger. Ex. 2053, ¶44; Ex. 2055, ¶28; Ex. 2049, 47-49. This is consistent with an
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`August 2003 meeting in Amsterdam, where Dr. Lopez-Bresnahan explained to
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`IVAX that patients receiving the low dose would receive oral cladribine for 5
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`consecutive days per month for 2 months. Ex. 2050, 4; Ex. 2053, ¶¶35-38.
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`Patients would receive another dose starting after month 12, leaving a 10-month
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`cladribine-free period after the first 2 months. Ex. 2049, 48-49; Ex. 2053, ¶¶45-46;
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`Ex. 2055, ¶28.
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`The Briefing Document says the “duration of treatment” was 6 months for
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`all patients, and that “low dose patients receive placebo to fill out high dose
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`cycles” to maintain “double blind.” Ex. 2049, 47-49; Ex. 2053, ¶¶42-43. As Dr.
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`Munafo explains, after two-months of treatment, patients in the low dose arm
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`would receive 4 months of placebos to total 6 months of treatment, thus concealing
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`which patients received which doses, followed by 6 months with no “treatment.”
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`Ex. 2053, ¶¶42-44; Ex. 2055, ¶28; Ex. 2050, 4; Ex. 2049, 47-49. Consequently,
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`low dose patients would receive 5-days of cladribine for 2 months, followed by 4
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`months of placebos and another 6 months with no “treatment.” Ex. 2053, ¶¶43-44;
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`Ex. 2055, ¶28.
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`According to Dr. Munafo, Serono also communicated to IVAX an
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`alternative dosing regimen of daily oral cladribine tablets for 5 days per month for
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`6-months followed by an 18-month cladribine-free period, which was also
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`thereafter disclosed in Bodor. Ex. 2053, ¶¶36-38, 51; Ex. 1029, 13:25-30.
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`As Dr. Munafo further explains, the Serono inventors’ “Study Design” was
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`in draft form, and they discussed with IVAX the possibility of adjusting certain
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`parameters, including dosing 10 mg cladribine tablets for 6 or 7 days/month. Ex.
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`2053, ¶47. Thus, Serono communicated to IVAX the same dosing regimen later
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`disclosed in Bodor—daily 10 mg oral cladribine tablets for 5-7 days per month for
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`2-months followed by a 10-month cladribine-free period. Ex. 2053, ¶53; Ex. 2049,
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`47-49.
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`Drs. Bodor and Dandiker corroborate that the cited regimen is attributable to
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`the Serono inventors. The testimony of Drs. Munafo, Bodor, and Dandiker
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`confirm the IVAX/Serono joint research agreement under which IVAX would
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`develop an oral cladribine formulation while Serono would design dosing regimens
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`and conduct clinical trials. Ex. 2053, ¶¶23-29; Ex. 2054, ¶¶11-18, 19-21, 23-26,
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`28; Ex. 2055, ¶¶12-19, 21-24; Ex. 2041, 65:10-19. Drs. Bodor and Dandiker
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`confirm that, consistent with the agreement, neither they nor anyone else on their
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`team at IVAX developed, researched, or invented any cladribine dosing regimen
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`for treating MS. Ex. 2054, ¶27, 30; Ex. 2055, ¶25.5
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`Instead, Dr. Dandiker recalls receiving the August 2003 presentation and
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`December 2003 Briefing Document from Serono and believes the Serono inventors
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`disclosed the Bodor regimen to him and others at IVAX. Ex. 2055, ¶¶16-18, 27-
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`29. Dr. Bodor agrees it is “highly likely” the Serono inventors communicated the
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`dosing regimen to IVAX. Ex. 2054, ¶29. That Serono communicated Bodor’s
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`5 Neither Drs. Bodor nor Dandiker were aware of the two IVAX provisional
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`applications cited in the Bodor PCT, both of which were later abandoned. Ex.
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`1007, 23:24-29; Ex. 2055, ¶20; Ex. 2054, ¶22; Ex. 2047 10; Ex. 2072, 3.
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`regimen to IVAX is further corroborated by the fact that before Serono disclosed
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`its August 2003 presentation and December 2003 Briefing Document to IVAX,
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`Bodor’s first two provisional applications, U.S. Nos. 60/458,922 (filed March 28,
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`2003) and 60/484,756 (filed July 2, 2003), did not contain such dosing regimen;
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`while after Serono’s disclosures, Bodor’s third provisional application, U.S. No.
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`60/541,247 (filed February 4, 2004), did contain this dosing regimen. Ex. 2044;
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`Ex. 2045; Ex. 2046, 20:6-10.
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`The Board need not reach step 3 of Duncan, because there is no evidence
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`that Drs. Bodor or Dandiker made any contribution to the regimen in Bodor on
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`which Petitioner relies, significant or not; instead, both state that they did not
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`invent any dosing regimen.
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`The total evidence demonstrates the ’947 patent inventors invented the
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`regimen described in Bodor. Ex. 1029, 22:20-26:32; Ex. 1007, 40-53; Ex. 2029,
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`22:16-27:15. This work cannot be used against the ’947 patent. In re DeBaun,
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`687 F.2d at 462. Petitioner’s grounds fail because the portion of Bodor on which
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`Petitioner relies is not “by another.”
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`VII. THE CHALLENGED CLAIMS ARE PATENTABLE
`Even if Bodor were prior art, each of Petitioner’s Grounds fails.
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`A. Ground I – Bodor Does Not Anticipate
`1.
`Petitioner Misinterprets Anticipation Jurisprudence
` “A claim is anticipated only if each and every element as set forth in the
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`claim is found, either expressly or inherently described, in a single prior art
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`reference.” Verdegaal Bros. v. Union Oil Co. of Cal., 814 F.2d 628, 631 (Fed. Cir.
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`1987).
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`Petitioner does not and cannot argue that every claim limitation is expressly
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`disclosed in Bodor. See, e.g., Ex. 1005, ¶117 (“Bodor is silent on exactly what
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`parameters would apply to the dosing regimen of the maintenance phase.”). Nor
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`does Petitioner show that the missing limitations are inherent, i.e., necessarily
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`present. Instead, Petitioner argues that anticipation can be established where a
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`POSA “would ‘reasonably understand or infer’ from a prior art reference that
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`every claim limitation is disclosed in that single reference,” suggesting that a
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`reasonable “inference” that a claim limitation is present is sufficient to show
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`anticipation. Pet. 29 (quoting Acoustic Tech., Inc. v. Itron Networked Sols., Inc.,
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`949 F.3d 1366, 1373 (Fed. Cir. 2020)). But Petitioner’s reliance on Acoustic
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`Technology is misplaced. In Acoustic Technology, the court found anticipation
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`only after relying on expert testimony that the prior art’s disclosure of “radio wave
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`communication was the same as” the claimed limitation. 949 F.3d at 1374.
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`Moreover, the decision on which Acoustic Technology relies, Akamai
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`Technologies, clearly frames the “reasonably understand or infer” query in the
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`context of an inherency analysis, which requires that a missing limitation be
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`necessarily present. See Akamai Techs., Inc. v. Cable & Wireless Internet Servs.,
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`Inc., 344 F.3d 1186, 1192 (Fed. Cir. 2003). Likewise, the Board in Ex parte
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`McNutt explained that “the Examiner must establish that one skilled in the art
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`would reasonably understand or infer from the prior art teaching that the claim
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`limitation is necessarily present.” No. 2009-3451, 2009 WL 3044465 at *5
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`(B.P.A.I. Sept. 22, 2009) (quotations omitted). The Board reversed an anticipation
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`rejection after finding “[t]he Examiner…did not provide evidence that [the missing
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`claim limitation] would necessarily be inferred or understood by the skilled
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`worker upon reading the [prior art].” Id. Thus, Petitioner’s anticipation analysis
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`misses a crucial requirement: a POSA must reasonably understand or infer from a
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`reference that the missing limitation is necessarily present.
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`Petitioner’s arguments regarding what a POSA “would reasonably
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`understand or infer” thus are facially deficient for showing anticipation and
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`amount, at best, to a single reference obviousness argument. See Eli Lilly & Co. v.
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`L.A. Biomedical Rsch. Inst. at Harbor-UCLA Med. Ctr., 849 F.3d 1073, 1074-75
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`(Fed. Cir. 2017). For example, Petitioner’s declarant acknowledges Bodor doesn’t
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`expressly teach the claimed maintenance period, “Bodor is silent on exactly what
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`parameters would apply to the dosing regimen of the maintenance phase,” but
`18
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`argues that Bodor “instead instructs practitioners to apply whatever regi
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