United States Patent and Trademark Office
`Before the Patent Trial and Appeal Board
`
`MYLAN PHARMACEUTICALS INC.,
`SAWAI USA, INC., AND
`SAWAI PHARMACEUTICAL CO., LTD.,
`Petitioners
`v.
`BIOGEN MA, INC.,
`Patent Owner
`
`Case IPR2018-01403*
`Patent No. 8,399,514
`*Case IPR2019-00789 has been joined with this proceeding.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`
`Before the Patent Trial and Appeal Board
`
`MYLAN PHARMACEUTICALS INC.,
`SAWAI USA, INC., AND
`SAWAI PHARMACEUTICAL CO., LTD.,
`Petitioners
`v.
`BIOGEN MA, INC.,
`Patent Owner
`
`Case IPR2018-01403*
`Patent No. 8,399,514
`*Case IPR2019-00789 has been joined with this proceeding.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`
`
`Prior Art Timeline
`
`1990
`Nieboer discloses
`treatment of psoriasis with
`DMF monotherapy vs. Fumaderm,
`both at a dose of 480 mg/day DMF,
`finding no difference in efficacy
`[Ex.1017]
`
`1994
`ICH provides guidance
`to determine administration
`of appropriate doses
`[Ex.1011]
`
`2005
`Biogen discloses
`Kappos Phase II study protocol
`using BG-12 (DMF monotherapy)
`at doses of 120, 360, and 720 mg/day
`to treat MS and that dose reduction
`will be allowed
`[Ex.1010]
`
`Jan. 2006
`Biogen announces
`Kappos Phase II study
`met its primary endpoint
`[Ex.1005]
`
`2004
`Schimrigk reports efficacy of
`360 mg/day and 720 mg/day DMF
`(dosed as Fumaderm) to treat MS
`[Ex.1006]
`
`
`
`1990 1992
`
`1994
`
`2003
`
`2004
`
`1992
`Kolbach discloses
`480 mg/day (psoriasis)
`[Ex.1117]
`
`2005
`Results reported of Biogen’s
`Phase II study using BG-12
`(DMF monotherapy) at doses of
`120, 360, and 720 mg/day
`to treat psoriasis
`[Ex. 1118]
`
`2005
`
`2007
`
`2006
`WO ᾽342 discloses dose
`of 480 mg/day DMF to
`treat autoimmune
`diseases such as MS
`[Ex.1008]
`2006
`2006
`Kappos 2006 reports
`BG-12 (DMF monotherapy)
`reduced Gd+ lesions
`in a “dose-dependent manner”
`in Kappos Phase II study
`[Ex.1007]
`
`2/8/2007
`Critical
`Date
`
`2003
`Joshi recognizes
`gastrointestinal irritations and side effects
`associated with administration of DMF
`[Ex.1009]
`
`2006
`Kappos presents Phase II results
`disclosing marked imbalance
`in mean baseline Gd+ lesions for
`360 mg/day DMF patients;
`GI adverse events were
`highest with 720 mg/day dose
`[Ex.1046]
`
`2005
`Fumaderm Label warns
`not to exceed a dose
`of 720 mg/day DMF
`[Ex.1020]
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`2
`
`
`
`DMF Dosing Disclosed in the Prior Art
`
`Fumaderm
`DMF monotherapy
`
`᾽514 Patent
`Ex. 1001
`(MS)
`
`800
`
`700
`
`600
`
`500
`
`400
`
`300
`
`200
`
`100
`
`DMF (mg/day)
`
`0
`
`3
`
`Nieboer
`1990
`Ex. 1017
`(psoriasis)
`
`Schimrigk 2004
`Ex. 1006
`(MS)
`
`Phase II
`Ex. 1118
`(psoriasis)
`
`Kappos
`Phase II
`Ex. 1006
`(MS)
`PRIOR ART STUDIES
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`
`
`Prior Art Points to 480 mg/day DMF Dosing to Treat MS
`
`Prior Art
`
`Nieboer 1990
`(Ex.1017)
`
`Regimen
`Conclusion
`480 mg/day DMF vs.
`• Discloses that there is no difference between treatment with DMF vs.
`480 mg/day DMF
`Fumaderm at a dose of 480 mg/day DMF in patients with psoriasis. Id. at
`2, 6.
`(Fumaderm)
`240 mg/day DMF vs.
`“Apparently a dosage of 480 mg of DMFAE per day is necessary to
`480 mg/day DMF
`achieve a satisfactory improvement in approximately 50% of the
`patients.” Id. at 2.
`(Fumaderm)
`120, 360, 720 mg/day DMF
`• Dose ranging study of 120, 360, 720 mg/day DMF to treat psoriasis. Id. at
`(BG-12)
`6-7.
`
`•
`
`Kolbach 1992
`(Ex.1117)
`Drugs 2005
`(Ex.1118)
`Schimrigk 2004
`360 mg/day and 720 mg/day
`Abstract
`DMF (Fumaderm)
`(Ex.1006)
`
`Clinical Trials
`(Ex.1010)
`January 2006
`Press Release
`(Ex.1005)
`Kappos 2006
`(Ex.1007)
`
`Kappos 2006
`Presentation
`(Ex.1046)
`
`120, 360, 720 mg/day DMF
`(BG-12)
`
`120, 360, 720 mg/day DMF
`(BG-12)
`
`120, 360, 720 mg/day DMF
`(BG-12)
`
`120, 360, 720 mg/day DMF
`(BG-12)
`
`WO ᾽342
`(Ex.1008)
`
`480 mg/day DMF
`
`• Suggests range of 360 mg/day to 720 mg/day doses of DMF are effective
`in treating MS. Id. at 5.
`
`•
`
`•
`
`•
`
`“Dose reduction will be allowed for subjects who are unable to tolerate
`investigational drug.” Id. at 2.
`“Phase II study designed to evaluate the efficacy and safety of BG-12, an
`oral fumarate, in patients with relapsing-remitting multiple sclerosis (MS)
`met its primary endpoint.” Id. at 1.
`“BG00012 significantly reduces brain lesion activity, in a dose-dependent
`manner, as measured by MRI in patients with RRMS.” Id. at 27.
`• Discloses an over three-fold difference in mean baseline Gd+ lesions in
`360 mg/day DMF group v. placebo. Id. at 17.
`• 720 mg/day dose produced highest number of GI serious adverse events
`and adverse events, and highest discontinuation rate. Id. at 18, 24, 25.
`• Discloses 480 mg/day DMF to treat autoimmune diseases and lists MS.
`Id. at 10:8-9, 38:13-29, 41:1-3.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`4
`
`
`
`Administration of 480 mg/day DMF to Treat MS
`Was Obvious
`
`The Problem
`
`• Fumarates such as DMF were known to cause side effects such as gastrointestinal problems and
`flushing
`
`The Motivation
`
`• GI and flushing side effects seen with 720 mg/day DMF (dosed as Fumaderm or BG-12)
`• Patients prefer less frequent dosing
`• 480 mg/day DMF within the range of efficacious DMF doses to treat MS (360 and 720 mg/day)
`• Prior art taught dose of 480 mg/day DMF to treat psoriasis, an autoimmune disease with an
`immunopathologic pathway similar to MS
`
`The Solution
`
`• Follow prior art to less frequent 480 mg/day BID dosing while reducing side effects and increasing
`compliance to optimize the dose
`
`Prior Art
`
`The Grounds
`
`• 480 mg/day DMF in immunologically similar disease psoriasis [Exs. 1017]
`• 360 mg/day and 720 mg/day DMF (Fumaderm) in MS [Ex. 1006]
`• 120, 360, 720 mg/day DMF (BG-12) in psoriasis and MS [Exs. 1118, 1007]
`• January 2006 Press Release [Ex. 1005] + Schimrigk 2004 Abstract [Ex. 1006]
`• Kappos 2006 [Ex. 1007] + Schimrigk 2004 Abstract [Ex. 1006]
`• Kappos 2006 [Ex. 1007] + WO ᾽342 [Ex. 1008]
`• Kappos 2006 [Ex. 1007], Clinical Trials [Ex. 1010], Joshi ᾽999 [Ex. 1009], ICH Guidelines [Ex. 1011]
`• Magnitude of effect from 480 mg/day DMF dose in DEFINE/CONFIRM trials was not unexpected
`• No nexus for commercial success due to disincentives from Biogen’s existing and potential patent
`rights and extensive marketing for Tecfidera
`• Any commercial success was fueled by factors beyond the claims of the ᾽514 patent
`• The ᾽514 patent claims satisfied no long-felt but unmet need
`• No nexus between industry praise and the ᾽514 patent claims
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Alleged Secondary
`Considerations
`
`5
`
`
`
`The Claimed DMF Dosing Regimen
`
`What is claimed is:
`1. A method of treating a subject in need of treatment for
`multiple sclerosis comprising orally administering to the subject in
`need thereof a pharmaceutical composition consisting essentially of
`(a) a therapeutically effective amount of dimethyl fumarate,
`monomethyl fumarate, or a combination thereof, and (b) one or
`more pharmaceutically acceptable excipients, wherein the
`therapeutically effective amount of dimethyl fumarate, monomethyl
`fumarate, or a combination thereof is about 480 mg per day.
`
`Ex.1001, claim 1.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`6
`
`
`
`Grounds Asserted
`
`GROUND 1
`January 2006 Press Release [Ex. 1005]
`+ Schimrigk 2004 Abstract [Ex. 1006]
`
`GROUND 2
`Kappos 2006 [Ex. 1007]
`+ Schimrigk 2004 Abstract [Ex. 1006]
`
`GROUND 3
`Kappos 2006 [Ex. 1007]
`+ WO ᾽342 [Ex. 1008]
`
`GROUND 4
`Kappos 2006 [Ex. 1007]
`+ Clinical Trials [Ex. 1010]
`+ Joshi ᾽999 [Ex. 1009]
`+ ICH Guidelines [Ex. 1011]
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`7
`
`
`
`The Board’s Previous Findings
`
`Kappos 2006 “teaches
`both the effectiveness of
`720 mg/day dose and that
`DMF is a result-effective
`variable.” Id. at 26.
`Joshi ᾽999 reports side
`effects with fumarate
`treatment. Id.
`Clinical Trials allows for
`dose reduction. Id. at 12.
`ICH “presents general
`guidance to those
`developing new drugs or
`drug treatments in
`determining appropriate
`and acceptable drug
`doses.” Id.
`
`IPR2015-01993, Final Written Decision, Paper 63 at 25–26.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`8
`
`
`
`January 2006 Press Release
`
`Confirms DMF Monotherapy Effectively Treats MS
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`9
`
`Ex.1005, 1.
`
`
`
`Schimrigk 2004
`
` 360 and 720
`mg/day DMF
`(Fumaderm) to
`treat MS
` 6-week baseline
` First treatment
`(18-weeks):
`titrated to 720
`mg/day DMF
` 4-week wash-out
` Second treatment
`(at least 42-
`weeks):
`titrated to 360
`mg/day DMF
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`10
`
`Ex.1006, 4–5.
`
`
`
`Schimrigk 2004: Dosing Was Effective
`
`Ex.1006, 5.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`11
`
`
`
`Nieboer 1990
`
` Demonstrates
`therapeutic
`efficacy of
`480 mg/day
`DMF
`monotherapy in
`psoriasis
` No efficacy
`difference in
`treatment of
`psoriasis with
`480 mg/day
`DMF dosed as
`a monotherapy
`or as
`Fumaderm
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`12
`
`Ex.1017, 2.
`
`
`
`Kolbach 1992
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`13
`
`Ex.1117, 2.
`
`
`
`Drugs 2005
`
` Doses tested were
`120, 360, and 720
`mg/day DMF (BG-12)
` Dose-dependent
`effect was observed
`with BG-12
`
`14
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Ex.1118, 6–7.
`
`
`
`POSAs Investigated Using DMF to Treat MS
`
`Ex.1006, 4–5.
`
`Ex.1012, 5.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`15
`
`
`
`Schimrigk 2006
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Ex.1018, 4.
`
`16
`
`
`
`Kappos 2005
`
` MS treatment
`with DMF
`(BG-12)
` Doses to be
`tested were
`120, 360, and
`720 mg/day
`DMF
`
`Ex.1015, 2.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`17
`
`
`
`Kappos 2006: DMF Reduced Gd+ Lesions in a
`“Dose-Dependent Manner”
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`18
`
`Ex.1007, 27.
`
`
`
`Kappos 2006 Presentation
`
`Ex.1046, 8, 20.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`19
`
`
`
`Difference in Mean Baseline Gd+ Lesions
`in the 360 mg/day Group
`
`Ex.1046, 17.
`
`Ex.1121 ¶ 151.
`
` A POSA would understand the substantially higher number of mean
`baseline Gd+ lesions in the 360 mg/day group compared to placebo meant
`these patients were experiencing higher baseline disease activity.
` The mean baseline Gd+ lesions directly relate to the primary endpoint of
`the Kappos Phase II study and therefore required correction.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`Petition, Paper 2, 46.
`
`20
`
`
`
`Kappos 2006 Presentation: Relapse Efficacy
`
`Higher Annualized Relapse Rate (0.78) for 360 mg/day Group
`
`Ex.1046, 23; Ex. 1121 ¶ 153.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`21
`
`
`
`Correction for the Substantial Imbalance in
`Mean Baseline Gd+ Lesions
`
`Correction
`indicates the
`efficacy of the
`360 mg/day
`group was
`similar to 720
`mg/day group
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`22
`
`Ex.1003 ¶ 173; Ex.1121 ¶ 155.
`
`
`
`Correction for the Substantial Imbalance in
`Mean Baseline Gd+ Lesions
`
`Correction
`indicates the
`efficacy of the
`360 mg/day
`group was
`similar to 720
`mg/day group
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`23
`
`Ex.1003 ¶ 175; Ex.1121 ¶ 156.
`.
`
`
`
`Motivation to Decrease Dose From 720 mg/day DMF
`to Reduce Side Effects
`
` DMF’s side effects were well-known. See, e.g., Exs. 1019, 1026, 1028.
` The Board previously found motivation to decrease 720 mg/day DMF
`dose based on side effects. IPR2015-01993, Final Written Decision,
`Paper 63, 26.
` Gastrointestinal side effects were highest in 720 mg/day DMF treatment
`group in Kappos Phase II study. Ex. 1046, 25; see also Ex. 1121 ¶ 226.
` A POSA would not be discouraged from dosing lower than 720 mg/day
`based on the Kappos Phase II study data.
` Kappos Phase II study was a 6-month dose-ranging study that was
`not powered to detect an effect on relapse rate and is very different
`than a much longer 2-year phase III trial.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`24
`
`Petition, Paper 2, 33, 37–38;
`Petitioner’s Reply, Paper 68, 2–4, 10–11.
`
`
`
`May 2006 Press Release
`
`Ex.1016, 1.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`25
`
`
`
`Clinical Trials
`
`Ex.1010, 1–2.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`26
`
`
`
`WO ᾽342 Discloses Treating Autoimmune Diseases Such as
`MS with a Dose of 480 mg/day DMF (BID)
`
`Ex. 1008, 10:13–14, 38:18–19, 41:1–3.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`27
`
`
`
`The Board Found WO ᾽342 Language Is
`Indicative of Obviousness
`
`Interference No. 106,023, Decision – Motions, Paper 813, 23–24.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`28
`
`
`
`Patent Owner’s Arguments Are
`Inconsistent with Evidence
`
` Fumaderm: A POSA would not believe the MEF
`salts in Fumaderm were functionally “active.”
` Schimrigk study: A POSA would rely on the
`results of the Schimrigk study as suggesting
`efficacy of 360 mg/day and 720 mg/day DMF to
`treat MS.
` Psoriasis studies: A wealth of prior art, including
`Biogen’s studies, connected treatment and
`dosing with DMF in psoriasis to treatment and
`dosing with DMF in MS.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`29
`
`Petitioner’s Reply, Paper 68, 4–7.
`
`
`
`DMF and Fumaderm
`
` “[T]reatment of psoriasis with FAC-EC [Fumaderm] does not result in a better
`therapeutic result compared to DMFAE-EC monotherapy.” Ex. 1017 (Nieboer
`1990) at 6.
` “It was concluded that the main active ingredient of Fumaderm® is DMF.”
`Ex. 1019 (Mrowietz 2005) at 2.
` “[T]here is cumulating evidence that dimethylfumarate (DMF), the main
`ingredient of [Fumaderm®], is the active compound.” Ex. 1027 (Ormerod
`2004) at 1.
` “DMF, which is metabolized to monomethylfumarate (MMF), is apparently
`the most potent antipsoriatic substance in [Fumaderm].” Ex. 1021 (Ockenfels
`1998) at 4.
` “The most effective fumarate metabolite of [Fumaderm] is
`monomethylfumarate (MMF), which is formed in the circulation by
`hydrolysis of DMF.” Ex. 1023 (de Jong 1996) at 1.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`30
`
`
`
`Schimrigk Study Reliability
`
`Biogen Referred to the Schimrigk Study in Connection with
`the Kappos Phase II Study
`
`Ex. 1034, 1.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`31
`
`
`
`Schimrigk Study Reliability
`
`Biogen Referred to the Schimrigk Study
`
`Ex. 1046, 11.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`32
`
`
`
`The Link Between Psoriasis and MS Treatment
`
` “Since the inflammatory processes involved in multiple sclerosis (MS) are
`thought to be similar to those of psoriasis, fumaric acid therapy may also be
`effective in treating MS.” Ex. 1014 (Schimrigk 2005) at 3.
` “Given the involvement of immune-mediated responses and predominance of
`the Th1 cytokine profile in both psoriasis and MS, the objective of this study
`was to determine if oral fumarate therapy is effective in patients suffering
`from relapsing remitting MS (RRMS).” Ex. 1012 (Schimrigk 2004 Poster) at
`4.
` “Commonalities exist between MS and psoriasis in terms of immune function
`changes that may explain the efficacy of FAE in both psoriasis and MS.” Ex.
`1018 (Schimrigk 2006) at 6.
` “Because several other inflammatory diseases, such as . . . multiple sclerosis,
`follow similar immunological pathways of T-cell activation, psoriasis can be
`regarded as a vi[a]ble disease model.” Ex. 1019 (Mrowietz 2005) at 2.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`33
`
`
`
`DMF Studies in Psoriasis/
`DMF Studies in MS
`
`“In summary, the putative immunomodulatory effects, the psoriasis efficacy of
`FUMADERM®, and the efficacy data in the pilot MS study of BG00012 support
`a proof of concept study in MS.” Mylan Ex. 1010 (Clinical Trials) p.2 (emphases
`added).
`
`Biogen Refers to
`Psoriasis Studies
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`34
`
`Ex. 1046, 11.
`
`
`
`DMF Doses Tested in Psoriasis/
`DMF Doses Tested in MS
`
`Biogen’s Psoriasis
`Phase II Study
`(Dose of DMF)*
`
`Biogen’s MS
`Phase II Study
`(Dose of DMF)**
`
`120 mg/day
`
`120 mg/day
`
`360 mg/day
`
`360 mg/day
`
`720 mg/day
`
`720 mg/day
`
`*Mylan Ex. 1118 (Drugs 2005), 6–7.
`**Mylan Ex. 1006 (Kappos 2006), 1.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`35
`
`Ex.1121 ¶ 217.
`
`
`
`Secondary Consideration Allegations
`
` No showing of unexpected results over Kappos Phase II study.
` No nexus between commercial performance of Tecfidera and any
`alleged novel aspects of the ᾽514 patent claims.
` No nexus between commercial performance and the ’514 patent
`because of disincentives from Biogen’s existing and potential patent
`rights and extensive marketing for Tecfidera.
` Dr. Jarosz failed to consider favorable marketing and advertising for
`Tecfidera, Biogen’s extensive experience in the MS therapeutic area,
`and Biogen’s significant discounts and allowances for Tecfidera as a
`driver of sales.
` The prior art already satisfied any long-felt need, to the extent any need
`was unmet, others were blocked from competing.
` No nexus between industry praise and the ᾽514 patent claims.
`Petition, Paper 2, 53–61;
`Petitioner’s Reply, Paper 68, 12–14.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`36
`
`
`
`480 mg/day DMF Dose in the
`DEFINE/CONFIRM Trials
`
` Skilled artisans would
`immediately recognize the
`substantial imbalance in baseline
`lesions in the 360 mg/day DMF
`group and would correct for the
`imbalance.
` The results suggest that 480
`mg/day would be as effective as
`720 mg/day.
` Because 720 mg/day was shown
`to be statistically significantly
`effective, it would not be
`surprising that 480 mg/day would
`similarly be statistically
`significantly effective.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`37
`
`Petition, Paper 2, 54–60;
`Petitioner’s Reply, Paper 68, 12–13.
`
`
`
`Confirmation by Drs. Fox and Gold
`
`Ex. 1036, 6.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`38
`
`
`
`Confirmation by Drs. Fox and Gold
`
`Others Corrected for the Imbalance of Mean Baseline Gd+
`Lesions, as Mylan’s Experts Did.
`
`Ex. 1036, 6.
`Petition, Paper 2, 54–60;
`Petitioner’s Reply, Paper 68, 12–13.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`39
`
`
`
`Confirmation by Drs. Phillips and Fox
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`40
`
`Ex. 1066, 5.
`
`
`
`Confirmation by EMA
`
`Ex. 1037, 34.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`41
`
`
`
`Confirmation by Kappos 2008
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Ex. 1048, 8.
`
`42
`
`
`
`Numerical Proximity Is Not Enough
`
`Ex. 1047, 16.
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`43
`
`
`
`Kappos Phase II Study Was Not Solely O’Neill’s Work
`
`LK= Ludwig Kappos
`GNO= Gilmore N. O’Neill
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`44
`
`Ex. 1048, 9.
`
`
`
`Mylan’s Exhibits Are Printed Publications
`
`Biogen’s Press Releases Are Printed Publications
` January 2006 Press Release (Ex. 1005), May 2006 Press Release
`(Ex. 1016), and Biogen 2005 Press Release (Ex. 1026) were
`publicly accessible to a POSA.
` Ms. Rock’s declaration establishes the public availability dates,
`which are confirmed by the copyright dates on press releases.
` Biogen’s SEC filing further corroborates that the January 2006
`Press Release was publicly accessible.
`“In January 2006, we announced that this study had achieved its primary
`
`efficacy endpoint.” Ex. 1078, 12.
`Schimrigk 2004 Poster (Ex. 1012) Is a Printed Publication
` Butler declaration from the Internet Archive is routinely accepted
`without deposition to establish Archive.org availability.
`
`Petitioner’s Reply, Paper 68, 23–25;
`Petitioner’s Opposition to Motion to Exclude, Paper 77, 5–11.
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`45
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
