UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`Neptune Generics, LLC et al.,
`Petitioners,
`v.
`Eli Lilly and Company,
`Patent Owner
`IPR2016-00237, -00240
`
`Sandoz Inc. et al.,
`Petitioners,
`v.
`Eli Lilly and Company,
`Patent Owner
`IPR2016-00318
`Patent Owner’s Demonstratives
`March 16, 2017
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`1
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`Neptune Generics, LLC et al.,
`Petitioners,
`v.
`Eli Lilly and Company,
`Patent Owner
`IPR2016-00237, -00240
`
`Sandoz Inc. et al.,
`Petitioners,
`v.
`Eli Lilly and Company,
`Patent Owner
`IPR2016-00318
`Patent Owner’s Demonstratives
`March 16, 2017
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`1
`
`
`
`Vitamin B12 Pretreatment
`Was Unprecedented
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`2
`
`Ex. 2026 at 111; POR (-318) at 35.
`
`
`
`Vitamin B12 Pretreatment
`Was Unprecedented
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2026 at 273-74; POR (-318) at 35.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`3
`
`
`
`Vitamin B12 Pretreatment
`Was Unprecedented
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2027 at 179-80; POR (-237) at 38, POR (-240) at 40.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`4
`
`
`
`District Court: Vitamin B12
`Pretreatment Was Unprecedented
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1028 (-237), Ex. 1027 (-240), Ex. 1003 (-318) at 16;
`POPR (-237) at 8, POPR (-240) at 8, POPR (-318) at 9-10.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`5
`
`
`
`History of Folic Acid Supplementation
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 69; POR (-237) at 9, POR (-240) at 9, POR (-318) at 9.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`6
`
`
`
`The Same Mechanism Causes
`Pemetrexed’s Efficacy and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 49; POR (-237) at 5-6, POR (-240) at 5-6, POR (-318) at 5.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`7
`
`
`
`The Same Mechanism Causes
`Pemetrexed’s Efficacy and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2118 ¶ 50; POR (-237) at 4-6, POR (-240) at 4-6, POR (-318) at 4-6.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`8
`
`
`
`Folates Compete with Antifolates:
`Methotrexate PDR Entry
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`9
`
`Ex. 2020 at 1398-99; POR (-237) at 19, POR (-240) at 21, POR (-318) at 20.
`
`
`
`Folates Compete With Antifolates:
`Tomudex Label
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`10
`
`Ex. 2021 at 1544; POR (-237) at 19, POR (-240) at 21, POR (-318) at 20.
`
`
`
`Folates Compete With Antifolates:
`Smith and Amyx
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2040 at 6122; POR (-237) at 6, POR (-240) at 6, POR (-318) at 5.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`11
`
`
`
`Folates Compete with Antifolates:
`Quinn
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`12
`
`Ex. 2033 at 2805; POR (-237) at 39, POR (-240) at 41, POR (-318) at 42.
`
`
`
`Folates Compete with Antifolates
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2028 at 325; POR (-237) at 22-23, POR (-240) at 24-25.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`13
`
`
`
`Folates Compete with Antifolates:
`Leucovorin Rescue
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`14
`
`Ex. 2120 ¶ 57; POR (-237) at 28, POR (-240) at 31, POR (-318) at 22.
`
`
`
`Folic Acid is Reduced Quickly To
`Usable Reduced Folates
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2135 at 230; Sur-Reply (-237, -240) at 4.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`15
`
`
`
`Farber: Acceleration Phenomenon
`
`Ex. 2042 (-237, -240), Ex. 1009 (-318) at 1; POR (-237) at 20, POR (-240) at 21-22, POR (-318) at 20.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`16
`
`
`
`Laohavinij: Cause For Concern From
`Folic Acid Pretreatment
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2031 at 333, 335; POR (-237) at 20, 43,
`POR (-240) at 21-22, 28, POR (-318) at 20-21, 33-34.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`17
`
`
`
`Pemetrexed Without Vitamins
`Showed Promising Efficacy
`
`Ex. 2034 (-237, -240), Ex. 1045 (-318) at 107; POR (-237) at 10, POR (-240) at 10, POR (-318) at 9.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`18
`
`
`
`Rusthoven: Toxicities Thought To Be
`Tolerable and Manageable
`
`Ex. 1011 (-237, -240), Ex. 1052 (-318) at 1194, 1198; POR (-237) at 27, POR (-240) at 29, POR (-318) at 21.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`19
`
`
`
`Calvert & Walling: Toxicities Thought
`To Be Tolerable and Manageable
`
`Ex. 1013 (-237, -240), Ex. 1047 (-318) at 39; POR (-237) at 27, POR (-240) at 29, POR (-318) at 21.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`20
`
`
`
`Niyikiza Annals of Oncology Abstract
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1008 (-237, -240), Ex. 1006 (-318).
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`21
`
`
`
`Niyikiza Annals of Oncology Abstract
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 33(d); POR (-237) at 38, POR (-240) at 40, POR (-318) at 38-39.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`22
`
`
`
`Niyikiza Identified Pemetrexed-
`Caused Toxicities
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`23
`
`Ex. 2026 at 116; POR (-318) at 38.
`
`
`
`Rusthoven Does Not Teach Toxicity
`and Homocysteine Relationship
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`Pet. (-240) at 25-26.
`IPR2016-00318
`24
`
`
`
`Hammond ASCO Abstract
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2035 (-237, -240), Ex. 1014 (-318);
`POR (-237) at 10, 46, POR (-240) at 10, 46, POR (-318) at 9, 25.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`25
`
`
`
`Hammond Abstracts
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`26
`
`Ex. 2035 (-237, -240), Ex. 1014 (-318); Ex. 1022 (-237, -240), Ex. 1015 (-318);
`POR (-237) at 46, POR (-240) at 46, POR (-318) at 25.
`
`
`
`Rinaldi Abstract
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2022; POR (-237) at 46, POR (-240) at 46, POR (-318) at 25.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`27
`
`
`
`Hammond Used More Pemetrexed
`Than Rinaldi
`
`Ex. 1022 (-237, -240), Ex. 1015 (-318); Ex. 2022; POR (-237) at 46, POR (-240) at 46, POR (-318) at 25.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`28
`
`
`
`Hammond
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`29
`
`Ex. 2135 at 152-53; Mot. for Obs. (-237, -240) at 9.
`
`
`
`Hammond
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`30
`
`Ex. 2135 at 156; Mot. for Obs. (-237, -240) at 9.
`
`
`
`Hammond: Higher Doses Risk
`Kidney Toxicity
`
`However, Hammond I, in which folic acid
`pretreatment was employed, observed that “7
`of 15 pts with elevated homocysteine,
`cystathionine, or methylmalonic acid levels
`had a significant increase in CrCl [creatinine
`clearance].” . . . In other words, as the dose of
`pemetrexed was increased, toxicity to the
`kidneys increased. Ex. 2120 ¶ 78.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`31
`
`Ex. 1015 (-318); POR (-318) at 28.
`
`
`
`Hammond: Higher Doses Risk
`Kidney Toxicity
`
`A. The sentence that you
`brought to my attention that seven of 15
`patients develop decreased creatinine
`clearance, which is the classic sign of
`renal dysfunction, more than half of the
`patients, seven of 15 patients develop
`renal function. That's a high rate, and
`those are the patients who had an
`elevation of all three vitamins, and I think
`a POSA would then worry -- suspect that
`the predictor is no longer as effective
`because now the drug is causing more
`problems, including the increased toxicity
`just from causing renal dysfunction.
`Ex. 2135 at 131.
`
`Q. All right? And so the patients --
`let me just -- I want to make sure I have this
`correct. The decrease in creatinine clearance
`is an indication of a developing kidney
`problem, you said?
`A. Yes.
`*
`*
`*
`Q. Okay. And so just to orient to
`where we are right now, the person of skill
`would have thought that because of the higher
`doses used in this study, some patients were
`seeing a development of kidney toxicity. So
`far so good?
`A. Yes, so far so good. Ex. 2135
`
`at 133-34.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Mot. for Obs. (-237, -240) at 5-9.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`32
`
`
`
`Hammond: Higher Doses Risk
`Kidney Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`33
`
`Ex. 2120 ¶ 81; POR (-318) at 28-29.
`
`
`
`Hammond: Folic Acid Dose
`
`Ex. 1022 (-237, -240), Ex. 1015 (-318); Ex. 2035 (-237, -240), Ex. 1014 (-318); POR (-237) at 49, POR (-240) at 48, POR (-318) at 50.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`34
`
`
`
`Folic Acid Dose
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2135 at 242-43; Mot. for Obs. (-237, -240) at 11-12.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`35
`
`
`
`Claimed Folic Acid Doses
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`36
`
`
`
`Folic Acid Schedule
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1015 (-318); POR (-318) at 53.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`37
`
`
`
`Folic Acid Schedule
`
`Q. We'll expand it out after -- we have to do this stepwise, Doctor, or we just go
`everywhere. Okay. So Hammond itself, Hammond doesn't give any reason that it would be
`beneficial to lengthen the pretreatment period?
`MS. LYDIGSEN: Objection.
`Q. Right? We can agree on that. Hammond itself doesn't do that?
`MS. LYDIGSEN: Objection. Mischaracterizes.
`THE WITNESS: Hammond does not provide such a reason. That's correct.
`BY MR. PERLMAN:
`Q. And Hammond itself does not identify any problem with the schedule that it was
`using, right?
`A. That's correct, because there's no standard for comparison.
`Q. Right. And would the person of ordinary skill have any reason to believe that if
`you kept the same regimen as Hammond but just started a few days earlier, that you would get
`better results?
`A. No. I think a person of ordinary skill would probably consider that a wash.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2136 at 241-42; Mot. for Obs. (-318) at 6.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`38
`
`
`
`Claimed Schedules
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`39
`
`
`
`Laohavinij: Reduced Efficacy
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2031 at 333; POR (-237) at 43-44, POR (-240) at 10, POR (-318) at 33-34.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`40
`
`
`
`Worzalla: Much More Pemetrexed
`Required To See Same Effect
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`41
`
`Ex. 1013 (-318) at 3238; POR (-318) at 31.
`
`
`
`Worzalla Used an Especially
`Susceptible Tumor
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`42
`
`Ex. 2026 at 210-11; POR (-318) at 30.
`
`
`
`’974 Patent Reports On A
`Single Patient
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1009 (-237), Ex. 2072 (-318) at 8:49-58.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`43
`
`
`
`The POSA Would Not Rely On Results
`From A Single Patient
`
`Q. And would that have been an example to the
`person of ordinary skill of a situation reported in the
`literature where a patient with cancer was reported to
`have their condition worsened when they were given
`cobalamin?
`MS. SPIRES: Objection, incomplete
`hypothetical.
`A. First, only a single patient is cited, and it's the
`very last sentence in the article relegated to the end. As
`I think we know, a single observation in a clinical
`setting -- that means one patient -- is always subject to
`immense skepticism.
`Now I'm going to offer an opinion that may be
`new, and you can strike it from the record or ask me to
`withhold the statement. I frequently say, and I think
`POSAs would agree, or the POSA in this setting,
`beware of the report of one patient.
`I say be careful of the doctor who has a single
`patient example, because often they're just as wrong as
`this one patient might be thought to be right. I don't
`think a POSA would accept that last statement and work
`on it to any significant level of, of evidence or support.
`Q. And is that because it is just an anecdotal
`report of a single patient?
`A. Yes.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2135 at 45-47; Mot. for Obs. (-237) at 2-3.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`44
`
`
`
`’974 Patent Predates Laohavinij
`
`Ex. 1009 (-237), Ex. 2072 (-318) at 2:19-24; POR (-237) at 43-44, POR (-318) at 33-34.
`Neptune Generics, et al. v. Eli Lilly and Company
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`45
`
`
`
`’974 Patent Predates Laohavinij
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2031 at 333; POR (-237) at 43-44, POR (-318) at 33-34.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`46
`
`
`
`Niyikiza Taught No Relationship
`Between Vitamin B12 and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2015 (-237, -240), Ex. 1016 (-318);
`POR (-237) at 30-31, POR (-240) at 33-34, POR (-318) at 40.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`47
`
`
`
`Niyikiza Taught No Relationship
`Between Vitamin B12 and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1028 (-237), Ex. 1027 (-240), Ex. 1003 (-318) at 7; Pet. (-237) at 52.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`48
`
`
`
`Niyikiza Taught No Relationship
`Between Vitamin B12 and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Eli Lilly & Co. v. Teva Parenteral Meds., Inc., et al., No.
`2015-2067, slip op. at 25 (Jan. 12, 2017).
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`49
`
`
`
`Niyikiza Taught No Relationship
`Between Vitamin B12 and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 106; POR (-237) at 30-31, POR (-240) at 33-34, POR (-318) at 40.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`50
`
`
`
`Dr. Schiff’s Rationales Apply Equally
`to Vitamin B12
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1075 (-318) ¶ 34; Reply (-318) at 16.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`51
`
`
`
`Zervos Taught No Relationship
`Between Vitamin B12 and Toxicity
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1016 (-237, -240), Ex. 2064 (-318);
`POR (-237) at 34, POR (-240) at 36, POR (-318) at 40.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`52
`
`
`
`Role of Vitamin B12 in Homocysteine-
`Methionine Reaction
`
`Ex. 1014 (-237, -240), Ex. 1007 (-318) at 9; POR (-237) at 21-22, POR (-240) at 23-24, POR (-318) at 35-36.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`53
`
`
`
`Role of Vitamin B12 in Homocysteine-
`Methionine Reaction
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`54
`
`Ex. 2026 at 86; POR (-318) at 7.
`
`
`
`Role of Vitamin B12 in Homocysteine-
`Methionine Reaction
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`55
`
`Ex. 2134 at 26-27; Mot. for Obs. (-237, -240) at 2.
`
`
`
`Giving Vitamin B12 Would Release
`Unpredictable Amounts of Folate
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`56
`
`Ex. 2118 ¶ 56; POR (-237) at 51, POR (-240) at 50.
`
`
`
`Giving Vitamin B12 Would Release
`Folate In Unpredictable Amounts
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`57
`
`Ex. 2134 at 36; Mot. for Obs. (-237, -240) at 3-4.
`
`
`
`EP 005
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`58
`
`Ex. 1010 (-237, -240), Ex. 1033 (-318) at 2;
`POR (-237) at 41, POR (-240) at 43-44, POR (-318) at 42.
`
`
`
`EP 005
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`59
`
`Ex. 1010 (-237, -240) at 12, 13; POR (-237) at 36-37, POR (-240) at 38-39.
`
`
`
`EP 005
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`60
`
`Ex. 1010 (-237, -240), Ex. 1033 (-318) at 4.
`
`
`
`Niyikiza: Pemetrexed Does Not Cause
`Increased Homocysteine
`
`Ex. 1008 (-237, -240), 1006 (-318); Ex. 2015 (-237, -240), 1016 (-318); POR (-237) at 34, POR (-240) at 35-36, POR (-318) at 38.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`61
`
`
`
`EP 005
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`62
`
`Ex. 2120 ¶ 135; POR (-237) at 41, POR (-240) at 43-44, POR (-318) at 42-43.
`
`
`
`EP 005
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Pet. (-237) at 38, Pet. (-240) at 36; POR (-237) at 50, POR (-240) at 50.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`63
`
`
`
`Vitamin B12 Dose
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Eli Lilly & Co. v. Teva Parenteral Meds., Inc., et al., No.
`2015-2067, slip op. at 27 (Jan. 12, 2017).
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`
`64
`
`
`
`Calvert Addressed Ways to Measure
`Functional Folate Status
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`65
`
`Ex. 1007 (-318) at 8-9 & n.17; POR (-318) at 39.
`
`
`
`Calvert Addressed Ways to Measure
`Functional Folate Status
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`66
`
`Ex. 1007 (-318) at 8-9; POR (-318) at 39.
`
`
`
`Calvert Addressed Measuring
`Functional Folate Status
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 141; POR (-318) at 39.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`67
`
`
`
`Vidal: Vitamin B12
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2032 at 24; POR (-237) at 21, POR (-240) at 23, POR (-318) at 36.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`68
`
`
`
`Arsenyan: Vitamin B12
`Pretreatment Reduces Efficacy
`
`Ex. 2055 (-237, -240), Ex. 1023 (-318) at 1302; POR (-237) at 21, POR (-240) at 22-23, POR (-318) at 36.
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`69
`
`
`
`Sofyina: Administering Vitamin B12
`Stimulates Tumor Growth
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2041 at 3; POR (-237) at 21, POR (-240) at 23, POR (-318) at 36.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`70
`
`
`
`Potential for “Masking” Was Not A
`Motivation to Administer Vitamin B12
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 190; POR (-318) at 44-45.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`71
`
`
`
`Potential for “Masking” Was Not A
`Motivation to Administer Vitamin B12
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`72
`
`Ex. 2118 ¶ 78; POR (-318) at 44-45.
`
`
`
`Potential for “Masking” Was Not A
`Motivation to Administer Vitamin B12
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2120 ¶ 191; POR (-318) at 45.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`73
`
`
`
`Carrasco
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`74
`
`Ex. 2120 ¶¶ 183-84; POR (-237) at 44-45, POR (-318) at 46-47.
`
`
`
`Skepticism: FDA 1998
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`75
`
`Ex. 2100 at 8044; POR (-237) at 56, POR (-240) at 55, POR (-318) at 58.
`
`
`
`Skepticism: FDA 1998
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2132 at 112; Sur-Reply (-318) at 8.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`76
`
`
`
`Skepticism: FDA 1998
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`77
`
`Ex. 2132 at 112-13; Sur-Reply (-318) at 8.
`
`
`
`Skepticism: Chabner
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 2091 at 3; POR (-237) at 55-56, POR (-240) at 55, POR (-318) at 58.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`78
`
`
`
`Sandoz’s POSA
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`Pet. (-318) at 17-18.
`IPR2016-00318
`79
`
`
`
`The Oncologist Article Was Written by
`the Inventor After the Priority Date
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`Ex. 1047 (-237, -240) at 363; Sur-Reply (-237, -240) at 11.
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`IPR2016-00318
`80
`
`
`
`The District Court Expressly Found
`Drs. Chabner and Zeisel Credible
`
`Neptune Generics, et al. v. Eli Lilly and Company
`
`IPR2016-00237, -00240 Sandoz Inc., et al. v. Eli Lilly and Company
`
`IPR2016-00318
`
`81
`
`Ex. 1028 (-237), Ex. 1027 (-240), Ex. 1003 (-318) at 14;
`POR (-237) at 13, POR (-240) at 13, POR (-318) at 12-13.
`
`
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
