Trials@uspto.gov
`571-272-7822
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`Paper No. 67
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`ELI LILLY AND COMPANY,
`Petitioner,
`
`v.
`
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH,
`Patent Owner.
`____________
`
`Case IPR2018-01710 (Patent 8,586,045 B2)
`Case IPR2018-01711 (Patent 9,884,907 B2)
`Case IPR2018-01712 (Patent 9,884,908 B2)
`____________
`
`Record of Oral Hearing
`Held: January 8, 2020
`____________
`
`
`
`
`Before JENNIFER MEYER CHAGNON, JAMES A. WORTH, and
`RICHARD J. SMITH, Administrative Patent Judges.
`
`
`
`
`
`
`
`
`
`571-272-7822
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`
`
`
`Paper No. 67
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`ELI LILLY AND COMPANY,
`Petitioner,
`
`v.
`
`TEVA PHARMACEUTICALS INTERNATIONAL GMBH,
`Patent Owner.
`____________
`
`Case IPR2018-01710 (Patent 8,586,045 B2)
`Case IPR2018-01711 (Patent 9,884,907 B2)
`Case IPR2018-01712 (Patent 9,884,908 B2)
`____________
`
`Record of Oral Hearing
`Held: January 8, 2020
`____________
`
`
`
`
`Before JENNIFER MEYER CHAGNON, JAMES A. WORTH, and
`RICHARD J. SMITH, Administrative Patent Judges.
`
`
`
`
`
`
`
`
`
`
`IPR2018-01710 (Patent 8,586,045 B2)
`IPR2018-01711 (Patent 9,884,907 B2)
`IPR2018-01712 (Patent 9,884,908 B2)
`
`
`
`APPEARANCES:
`
`ON BEHALF OF THE PETITIONER:
`
`
`WILLIAM B. RAICH, ESQ.
`Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
`901 New York Avenue, N.E.
`Washington, D.C. 20001
`
`
`
`ON BEHALF OF THE PATENT OWNER:
`
`
`DEBORAH STERLING, ESQ.
`Sterne, Kessler, Goldstein & Fox, PLLC
`1100 New York Avenue, N.W.
`Suite 600
`Washington, D.C. 20005
`
`
`
`
`
`The above-entitled matter came on for hearing on Wednesday,
`January 8, 2020, commencing at 1:20 p.m., at the U.S. Patent and Trademark
`Office, 600 Dulany Street, Alexandria, Virginia.
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`P R O C E E D I N G S
`- - - - -
`JUDGE WORTH: Good afternoon. This is an oral hearing in cases
`Nos. IPR 2018-01710, 1711 and 1712 between Petitioner Eli Lilly and
`Company and owner of U.S. Patents 8,586,045, 9,884,907 and 9,884,908,
`Teva Pharmaceuticals International GMBH. My name is Judge Worth. To
`my right is Judge Chagnon and participating by teleconference from Texas is
`Judge Smith.
`As you know per our order each party has 60 minutes to present its
`argument. Because Petitioner has the burden to show unpatentability of the
`original claims Petitioner will proceed first followed by Patent Owner.
`Petitioner may reserve rebuttal time but may only use its time to rebut Patent
`Owner's arguments. The Patent Owner may also reserve some final time for
`a surreply.
`At this time we'd like to ask counsel to introduce yourselves and who
`you have brought with you, beginning with the Petitioner please.
`MR. RAICH: Good afternoon, Your Honors. My name is Bill Raich
`from Finnegan on behalf of Petitioner Eli Lilly and Company. With me
`today at counsel's table is Pier DeRoo and also here today from Indianapolis
`are Mark Stewart and Sanjay Jivraj from Eli Lilly.
`JUDGE WORTH: I believe you may have some people in the
`overflow room; is that right?
`MR. RAICH: We do have people in the overflow room, that's correct.
`Would you like me to introduce everybody?
`JUDGE WORTH: If you recall who they are.
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`MR. RAICH: Yes I think Erin Sommers is in the overflow room,
`Yieyie Yang is counsel also who's here and I believe Yoon Jin Lee is in the
`overflow room also.
`JUDGE WORTH: Thank you. For Patent Owner.
`MS. STERLING: Good afternoon. My name is Deborah Sterling.
`I'm with Sterne, Kessler, Goldstein & Fox on behalf of Teva
`Pharmaceuticals. With me at counsel's table is Olga Partington, also from
`Sterne Kessler. Behind me is Jeremiah Frueauf, and then we have Lori
`Wolfe and Sharon Hausdorff from Teva and in the overflow room I believe
`we have David Roadcap and Tyler Liu. Thank you.
`JUDGE WORTH: Petitioner, would you like to reserve time for
`rebuttal?
`MR. RAICH: We would, Your Honor. We'd like to reserve 15
`minutes.
`JUDGE WORTH: And Patent Owner.
`MS. STERLING: We'd like ten please, Your Honor.
`JUDGE WORTH: Okay. I'm setting the clock for 45 minutes to
`begin with. Petitioner, you may begin whenever you're ready.
`MR. RAICH: Okay. Your Honor, we have printed copies of our
`demonstratives if you'd like. May we approach and provide copies?
`JUDGE CHAGNON: That's fine.
`JUDGE WORTH: Yes, please. Thank you. And please recall that
`Judge Smith is participating by teleconference so you may wish to say what
`page number you're on and describe for Judge Smith what you're viewing,
`and that's also for the record.
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`MR. RAICH: I appreciate that. Thank you, Your Honor. Okay, I'd
`like to begin. Your Honors, today we're going to explain why Teva's claims
`are obvious. We're going to focus on actual contemporaneous disclosures,
`not rhetoric or conclusory expert testimony. My intent is to spend 20 to 25
`minutes on the prima facia case of obviousness and then to pivot to
`secondary indicia including Fox Factory.
`Slide 2. So the challenged method patents are broadly directed to
`treating headache including migraine by administering a humanized anti-
`CGRP antagonist antibody and these are incredibly broad claims. There's no
`requirement for the amino acid sequence of the antibody even though the
`sequence of an antibody dictates functional parameters like antibody
`potency, affinity, avidity, specificity, mechanism of action and effector
`functions. So these challenged claims are also very broad in terms of that
`they cover either headache or vasomotor symptom. There are 250 different
`types of headache. There are some dependent claims that are directed to
`migraine where the strong weight of the evidence establishes motivation and
`expectation of success.
`Slide 3. So this shows the combination of references that are asserted
`in these IPRs. There's Olesen 2004. This is a key publication in 2004 that
`opened up the field. It definitively provided proof of concept that
`antagonizing the CGRP pathway effectively treated migraine. After Olesen
`it was obvious to pursue other CGRP antagonists. Tan 1995, Exhibit 1022,
`disclosed one of those CGRP antagonists, specifically Tan used an anti-
`CGRP antibody to antagonize the CGRP pathway in vivo, and Queen,
`Exhibit 1023, disclosed humanized antibodies for therapeutic use and also
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`methods of making therapeutic humanized antibodies and the combination
`achieves the claimed method with a reasonable expectation of success.
`So slide 4. Obviousness is evaluated from the perspective of a person
`of ordinary skill in the art, in this case as of 2005. So what was available at
`that time? Well, first of all Doods, a 2005 publication, Exhibit 1024 and
`Doods states we expect that CGRP antagonists will be effective anti-
`migraine drugs. There's Lassen 2002, Exhibit 1047. CGRP caused
`headache and (indiscernible) to all migraine sufferers whereas placebo did
`not. This finding greatly increases the likelihood that a CGRP antagonist
`may be effective in the treatment of migraine attacks and there's
`Wimalawansa, Exhibit 1096, that discusses the role of CGRP in migraine
`and states that the role of CGRP antagonist and humanized monoclonal
`antibodies should be explored.
`A key publication is Olesen, Exhibit 1025 from 2004. It was a multi-
`center double-blind randomized clinical trial of BIBN and this is shown on
`slide 5. It involved 126 patients with migraine and the drug was
`intravenously administered which means it was systemically administered.
`It went all through the body and it wasn't specific to any one receptor type, it
`inhibited CGRP receptor and it worked. Investigators concluded that proof
`of concept was thus established. The CGRP antagonist BIBN was effective
`in treating acute attacks of migraine and this was a significant event in the
`field. As stated in Arndt 2004, Exhibit 1030, Olesen's data demonstrate the
`validity of the CGRP concept paving a novel way in migraine pain
`treatment. As Dr. Charles explained, Olesen's study encouraged the
`development of additional agents to treat migraine by blocking the CGRP
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`pathway and it's not just Dr. Charles, our expert that says this, it's Teva's
`expert as well.
`Slide 6. Dr. Ferrari stated in 2005 that in view of Olesen CGRP
`antagonists seem promising new anti-migraine drugs without vascular side
`effects. Dr. Ferrari stated in 2007 that Olesen firmly established blockade of
`the CGRP pathway, not just the CGRP receptor, the blockade of the pathway
`as a novel and important new emerging treatment principle for acute
`migraine. Dr. Rapoport, another Teva expert, stated in 2005 Olesen suggests
`that antagonizing the effects of CGRP may provide acute relief of migraine
`headache, preventive drugs might be developed on the same principle.
`JUDGE SMITH: Counsel.
`MR. RAICH: Yes, Your Honor.
`JUDGE SMITH: I have a question. Were there any other studies in
`humans prior to the filing date of actually blocking the CGRP pathway other
`than Olesen?
`MR. RAICH: Yes, so there are. There's Petersen and Iovino, both of
`which were studies in humans that blocked the CGRP pathway. They were
`healthy patients, they did not have migraine. But I'd also point out that the
`triptan studies, triptans had been used for treating migraines for over a
`decade. They were approved by the FDA and triptans inhibit the release of
`CGRP and they were shown to be efficacious. So all of those studies were
`studies in humans that involved inhibiting the CGRP pathway.
`On slide 7 we show advantages for humanized antibodies, why use an
`antibody and there are a number of different reasons for using an antibody
`and a principle one is that antibodies have long half-lives and are therefore
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`useful for treating chronic conditions. Now Teva tries to take this and turn
`this on its head and describe the long half-life as a negative raising concerns
`about safety. We're going to look at the contemporaneous evidence to see
`what people were actually saying about half-life and the effect of half-life
`and how it impacted inhibiting the CGRP pathway.
`Other advantages of antibodies are high affinity and specificity. They
`were described in the prior art as perfect tools for disrupting ligand receptor
`interactions like the interaction between CGRP and its receptor. They were
`described in the prior art as having lower toxicity and fewer side effects as
`compared to small molecules. Teva's argument is that BIBN was a receptor
`antagonist, molecule that was described as potent and safe but that doesn't
`mean that one wouldn't also seek alternative therapies that were also potent
`and safe very high affinity therapies that were perfect tools for disrupting
`these interactions and specifically pursuing therapies that have long half-
`lives.
`
`So why was migraine suitable for drugs with longer half-life? Well as
`Dr. Charles explains, migraine as an episodic disease it comes and it goes so
`you want something that's going to be in your system for longer. A long
`half-life is beneficial for that. Migraine attacks can also last for a long
`period of time between hours and days and so a person would have been
`motivated to look for drugs that persist in the body for longer periods of
`time. Long half-life was also beneficial because it permits less frequent
`administration so full length antibodies are desirable because they have long
`half-lives and therefore would need to be administered less often, and this is
`what Teva's expert said about half-life with respect to available agents for
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`inhibiting the CGRP pathway. Dr. Ferrari said at the time that the short
`plasma half-life of sumatriptan was a main disadvantage. Sumatriptan
`inhibits the CGRP pathway. Dr. Ferrari was indicating that something that
`inhibited the CGRP pathway for a longer period of time would be beneficial.
`Dr. Rapoport advocated daily triptan administration for a full year,
`and again triptans were understood to treat migraine by inhibiting CGRP
`release. Essentially by administering triptans every day this was a attempt to
`compensate for their short half-lives and Dr. Tomlinson described the long
`half-life as antibodies as providing a favorable pharmacokinetic profile.
`There are many other statements. I want to draw your attention to one
`of them not shown in the slide. This is from Araki, a 2005 publication, it's
`Exhibit 2282 and Teva includes a quote on their slide 36 and the authors
`wrote,
`"Since the success of sumatriptan various triptan agents have been
`developed by improving the weak points of sumatriptan, the elimination in
`the half-life in the blood is short."
`So people wanted things with a longer half-life. So what does Teva
`argue? I'm looking now at slide 9. Teva argues that it was unclear whether
`CGRP levels increased during migraine. The background section of Teva's
`patent states that the serum levels of CGRP are elevated in patients during
`migraine headaches so we think they're arguing against their own patent.
`Furthermore, Olesen had been shown to treat migraine patients by inhibiting
`the CGRP pathway. As Dr. Ferrari stated, Olesen firmly established
`blockade of the CGRP pathway as a novel means of treating migraine.
`What else does Teva argue? This is shown on slide 10. Well Teva
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`argues something called the spare receptor theory and Teva's argument is
`that if there's just a little bit of binding between ligand and receptor you can
`see a full biological response so the idea being you would be discouraged
`from inhibiting ligand because you'd have to target so much of it. The
`problem is that this is just purely theoretical and not supported by the prior
`art. The prior art shows that 27 percent of receptors needed to be occupied
`to elicit a half maximal response. That is very different than less than one
`percent of receptors needing to be occupied to elicit a full response which is
`what they argued.
`Furthermore, the clinical evidence undermines the spare receptor
`theory. The clinical evidence indicates that you only need to normalize
`CGRP levels to treat migraine. That's shown in Exhibit 1044 and we have a
`callout on slide 38 if Your Honor's are interested. So this is --
`JUDGE SMITH: Counsel, can I interrupt you?
`MR. RAICH: Yes, Your Honor.
`JUDGE SMITH: Interrupt you for a second here. So, theories about
`this notion of merely normalizing CGRP levels, so are you saying that
`CGRP remains active with respect to both Ajovy and Emgality when it's
`administered but the activity is sort on a spectrum and you're basically just
`trying to essentially if you want to talk about mean arterial pressure and that
`you are sort of dialing that up in this case in the sense of reducing
`vasodilation?
`MR. RAICH: I think --
`JUDGE SMITH: I hope that makes sense.
`MR. RAICH: -- I think --
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`JUDGE SMITH: I just want to understand a little bit about the
`mechanism because I think this is important for purposes of the spare
`receptor theory.
`MR. RAICH: Yes. I think in looking at the prior art, the blood levels
`of CGRP were shown to reduce from something like 60 units -- and I don't
`remember what the units is -- to 40 units following treatment and that was
`with the triptans, and so what the prior art showed is that you only needed to
`reduce the levels of CGRP, you didn't need to drive CGRP levels down to
`nothing in order to see treatment and I think the precise effect of the
`antibodies on CGRP levels may be beyond the record. I think they certainly
`do inhibit CGRP but there's no effect on blood pressure or anything else
`that's associated with that. In fact they are not understood to cause
`vasoconstriction.
`JUDGE SMITH: Well the reason I'm asking is if I'm understanding
`Teva's argument and we'll hear from them of course, but that the spare
`receptor theory would require when you bind the ligands that you have to
`bind all the ligands so it's completely, I mean it's effectively a knockout.
`MR. RAICH: That's right.
`JUDGE SMITH: And on here you're saying that's not true?
`MR. RAICH: Yes. That's just not supported by the evidence. That's
`exactly right.
`JUDGE SMITH: Okay, good. Thank you.
`MR. RAICH: Thank you, Your Honor. So another argument that
`Teva raises just briefly is this idea of cross binding, the idea that you if you
`inhibit CGRP it's disruptive because CGRP also has the capability of
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`binding to other receptors other than the CGRP receptor. But the prior art
`evidence shows that the binding of CGRP to other receptors was poor.
`That's shown in Exhibit 2059, and furthermore I just want to point out that
`neither the spare receptor theory nor cross binding inhibited the development
`of aptamers which were specifically intended to treat migraine and
`specifically bound to ligand. It bound to CGRP, not to CGRP receptors so
`we think this is strong evidence that these are sort of post-hoc litigation
`theories.
`Slide 11. Another Teva argument is the blood brain barrier and Teva
`argues essentially that there was a debate over whether migraine drugs
`function centrally versus peripherally. We think Teva mischaracterizes the
`state of the art in 2005. The body of evidence shows that it was well
`accepted that migraine drugs functioned peripherally and I want to walk
`through this evidence.
`So looking at slide 11, first of all triptans. As Dr. Ferrari published in
`the prior art sumatriptan was understood to have poor penetration of a blood
`brain barrier suggesting a peripheral point of action and again triptans act by
`inhibiting CGRP release. Aptamers, aptamers were reported not to traverse
`the blood brain barrier, they're too large and yet they were being developed
`for treatment of migraine, and then there's BIBN and the great weight of the
`evidence shows that BIBN was acting peripherally and let's walk through
`this.
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`So we have Petersen 2004, which is Exhibit 1090. The present study
`strongly suggests the clinically effective migraine drug BIBN does not cross
`the blood brain barrier. Petersen 2005, this is a study in humans using what
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`Dr. Ferrari admitted was the best available measurement technology and
`BIBN was concluded to prevent or treat headache predominantly in an extra
`cerebral manner. Edvinsson 2005, BIBN does not appear to pass the blood
`brain barrier freely. Ahrami, 2004, BIBN does not seem to penetrate the
`blood brain barrier. Dr. Foord in cross-examination based on the
`pharmacologic properties of BIBN, its size and its charge, testified that it
`would be unlikely that BIBN crosses the blood brain barrier.
`Now Teva introduced two exhibits, Storer and Fischer, but in both
`exhibits peripheral activity was actually shown. BIBN was active
`peripherally. At most those references contemplated whether peripherally
`functioning migraine drugs can also be active centrally, and then against that
`there's Levy which is I think the main reference that Teva relies on. But
`Levy, first of all suffers from various experimental limitations. As explained
`by Dr. Charles, they use an invasive experimental condition in animals. It
`didn't actually evaluate BIBN or any CGRP antagonist and the cyntreate
`(phonetic) that was used was too short and so we think that the great weight
`of the evidence, again, shows that all of these compounds that inhibited the
`CGRP pathway were active peripherally, not centrally. I'll just point out that
`other migraine drugs that act like different mechanisms of action were also
`known to work in the periphery. There's Ergotamine, that's shown in Exhibit
`1334 and Atenolol which is shown in Exhibit 1241.
`I want to talk a little bit about the development of anti-CGRP
`antibodies and there are a number of publications which describe and claim
`anti-CGRP antibodies in the prior art. They include Wong, the Tan thesis,
`the Tan publications, Wimalawansa, Salmon, the 438 patent, and Sveinsson.
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`In addition to that prior to Olesen there's Exhibit 1032, the Frobert paper,
`they discuss the role of CGRP and migraine and tested 30 different anti-
`CGRP monoclonal antibodies. Anti-CGRP antibodies were also for sale
`commercially, you can buy them. They're listed in the SIGMA catalog for a
`number of purposes including neutralization. That's Exhibit 1051. So there
`was obviously a market need for brand anti-CGRP antibodies.
`In 2004 Olesen establishes proof of concept that you could treat
`migraine by antagonizing CGRP. Arulmozhi subsequently publishes that
`inhibition of CGRP or antagonism of CGRP receptors could be a viable
`therapeutic target for the pharmacologic treatment of migraine and within a
`year of Olesen, Teva files its patent application.
`Slide 13. I want to talk briefly about aptamers. So again aptamers are
`described in the prior art as nucleic acid analogs to antibodies. Teva takes
`issue with this characterization but that's what the prior art actually says.
`Aptamers were understood not to cross the blood brain barriers and
`Messlinger, this was a 2005 publication post-Olesen shows that a biostable
`aptamer, and aptamers have long half lives on the order of hours to days --
`that's how they're described in the prior art in the Pendergrast publications
`having long half lives -- and they were shown to be efficacious, they were
`shown to be safe and the authors wrote that the Spiegelmer may open a new
`therapeutic strategy in diseases that are linked to excessive CGRP release
`such as migraine and other primary headaches. Now aptamers are analogs to
`antibodies. All of the arguments that Teva makes; blood brain barrier, safety
`concerns, spare receptor and cross binding, none of that deterred people
`from pursuing aptamers and none of those arguments would have pursued a
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`first (indiscernible) antibodies.
`Briefly on safety, slide 14, and we've discussed this previously. I
`don't want to spend too much time on it but essentially there's numerous
`publications testing CGRP antagonists including aptamers and BIBN and
`CGRP 37, not to mention triptans, and those publications in humans and
`animals showed, as Dr. Charles stated, that it was safe to therapeutically
`target CGRP in animals also.
`Slide 15. Well what about for anti-CGRP antibodies themselves?
`What do we know? Well Tan showed that there was a slight increase in
`blood pressure following antibody administration and recovered within ten
`to fifteen minutes for full length IgG as well as Fab' fragments. This shows
`that the minor increase in blood pressure had no relation to half life and
`would not discourage one from pursuing longer acting agents. What else do
`we know? Wong, Exhibit 1033, administered a monoclonal antibody and
`showed that it had no significant effect on mean arterial pressure and heart
`rate as a anti-CGRP antagonist antibody and Andrew reported that although
`rats had high levels of circulating antibodies to rat CGRP therapy it did not
`show any signs of physical or behavioral abnormality.
`Slide 16. I just want to make the point that Teva again has raised
`these concerns about safety and spare receptor and cross binding and blood
`brain barrier. None of them are addressed in their patent, none of them.
`They're not acknowledged and the data doesn't address them and it's our
`position that if they'd been significant concerns in the prior art they would
`have been addressed in the patent, but they're not and we think that this
`indicates that these are litigation driven hindsight concerns.
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`I want to talk a little bit about Tan. I'm looking at slide 17. So Tan
`reported first of all that full length antibodies blocked the hypotensive effect
`of administered CGRP. They were active in vivo. Second of all, within the
`rat saphenous nerve assay, at two hours there was an effect seen, a modest
`effect not more than 16 percent but it was observed and Tan provided
`guidance, specifically larger doses, longer distribution times, active
`immunization, chronic administration and repeated administration. These
`were things that one could do to use antibodies in vivo such that they would
`eventually distribute into the interstitial space and achieve sufficiently high
`concentrations required for immunoblockade.
`Slide 18. Now Teva argues that well, a person of skill in the art
`would not have understood that antibodies could access the synaptic cleft
`and they enter an argument through their expert Dr. Foord. Dr. Foord's not
`an expert on antibodies. He's not an expert on synapses and he's not an
`expert on the dynamics of an antibody and how they behave in the cleft.
`You can see that testimony on slide 50 of our slides, and we're turning back
`to slide 18.
`Dr. Foord and Teva used the wrong synaptic cleft size. They analyzed
`the wrong antibody type and the wrong antibody size. They ignored the fact
`that antibodies are mobile and three dimensional and can move. Tan
`actually demonstrates that antibodies can access the synaptic cleft and this is
`in vitro, but as paper states that the full length antibody reached equilibrium
`in the synaptic cleft after 45 minutes.
`JUDGE WORTH: Can you explain if your theory is that antibodies
`are acting peripherally why it matters whether they reach the synaptic cleft
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`or what cleft we're talking about?
`MR. RAICH: Yes, that's a good question, Your Honor. So there are
`nerves and neuromuscular junctions that are outside of the blood brain
`barrier, so I think the argument is the blood brain barrier should be thought
`of I think as something separate. It's a separate issue than just whether or
`not antibody can access the synaptic cleft.
`JUDGE WORTH: Are you talking about a receptor on the smooth
`muscle cell?
`MR. RAICH: For the treatment of migraine it's something called the
`trigeminal nucleus and so these are nerves outside of the blood brain barrier
`and so I think Teva's argument, and they can state their argument, you
`wouldn't expect that antibodies could access the synaptic cleft but I think
`that the evidence shows that they could.
`So slide 19. Basically Tan acknowledged in its experiments that it
`took a shorter time for the Fab' fragment to achieve immunoblockade than
`full length antibody and Tan found its observation consistent with the data
`reported in Covell which was a very well known and respected paper in the
`field of antibody pharmacology and as Tan explains in the upper left box
`Covell expressly teaches that Fab' fragments distribute and reach
`equilibrium about 14 times faster than a full length antibody. So given that
`Tan only permitted a two hour distribution time for its full length antibody,
`Tan concluded that with longer distribution times and repeated
`administration a full length antibody should distribute into the interstitial
`space and achieve an improved immunoblockade. As Dr. Balthasar
`explains, Tan's conclusion is consistent with the basic pharmacokinetic
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`principles expressed in Covell.
`Furthermore, slide 20 when you look at Teva's patent Teva used a
`higher dose and a 72 hour incubation instead of the one or two hour
`incubations described in Tan and it's our position that following the express
`teachings of the prior art is simply not inventive.
`Unless there are any other questions I'd like to turn now to secondary
`indicia issues and specifically let me jump to Fox Factory which is on slide
`24. So in Fox Factory, focusing on the second bullet, the court rejected
`Patent Owner's attempt to reduce the coextensiveness requirement to an
`inquiry into whether the patent claims broadly cover the product that is the
`subject of the evidence of secondary considerations. The court rejected
`exactly what Teva seeks to do in this case and I'm going to explain it.
`Further the court stated,
`"When the thing that is commercially successful is not coextensive
`with the patented invention the patentee is not entitled to a presumption of
`nexus."
`Now Teva's counsel was asked questions about this in the previous
`oral hearing for IPRs 2018-1422 to 27. The question was,
`"Question. You're not saying they're coextensive with respect to the
`claims?
`"Answer. Well, Your Honor, I'm not saying they're coextensive."
`All of the same scope and nexus issues apply here given the breadth
`of the functionally defined genus of antibodies in the claimed methods. The
`court in Fox Factory also stated because there are one or more features not
`claimed by the patent that materially impacted the functionality of the
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`IPR2018-01711 (Patent 9,884,907 B2)
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`commercial products, nexus may not be presumed. So let's look at this.
`Slide 25. So in Fox Factory the court rejected changing the
`coextensiveness requirement to an inquiry in whether the patent claims
`broadly cover the product. That is precisely the argument that Teva has
`made here. They argued that Ajovy, which is Teva's antibody and Emgality
`which is Lilly's antibody are covered by the claims. They argued this in
`their Patent Owner response and in their surreply. Dr. Tomlinson, their
`expert who addressed this issue, his analysis solely consisted of determining
`whether the claims cover administration of at least one of Ajovy and
`Emgality, that's Exhibit 2271, paragraph 127.
`The court in Fox Factory stated that there's no presumed nexus when
`the product has one unclaimed feature that materially impacts functionality.
`In that case it was the 80 percent gap filling limitation and here there are
`absolutely multiple limitations that materially impact functionality and I
`want to start with sequence. So the claims of Teva's patents are not
`restricted by sequence. They are incredibly broad, they're entirel
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