DIANE J. BURGESS, PH.D.
`
`Page 1
` UNITED STATES PATENT AND TRADEMARK OFFICE
` _________________
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` _________________
` KVK-TECH, INC.
` Petitioner
` v.
` SHIRE PLC
` Patent Owner(s)
` ______________
` Case IPR2018-00290
` Patent 8,846,100 B2
`
` DEPOSITION OF DIANE J. BURGESS, Ph.D.
`
`DATE: September 24, 2018
`TIME: 9:40 a.m.
`HELD AT: Axinn, Veltrop & Harkrider LLP
` 90 State House Square
` Hartford, Connecticut 06103
`
` By: Sarah J. Miner, RPR, LSR #238
`
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`SHIRE EX. 2071
`KVK v. SHIRE
`IPR2018-00290
`
`
`
`Page 1
` UNITED STATES PATENT AND TRADEMARK OFFICE
` _________________
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` _________________
` KVK-TECH, INC.
` Petitioner
` v.
` SHIRE PLC
` Patent Owner(s)
` ______________
` Case IPR2018-00290
` Patent 8,846,100 B2
`
` DEPOSITION OF DIANE J. BURGESS, Ph.D.
`
`DATE: September 24, 2018
`TIME: 9:40 a.m.
`HELD AT: Axinn, Veltrop & Harkrider LLP
` 90 State House Square
` Hartford, Connecticut 06103
`
` By: Sarah J. Miner, RPR, LSR #238
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`SHIRE EX. 2071
`KVK v. SHIRE
`IPR2018-00290
`
`
`
`DIANE J. BURGESS, PH.D.
`
`Page 2
` UNITED STATES PATENT AND TRADEMARK OFFICE
` _________________
` BEFORE THE PATENT TRIAL AND APPEAL BOARD
` _________________
` KVK-TECH, INC.
` Petitioner
` v.
` SHIRE PLC
` Patent Owner(s)
` ______________
` Case IPR2018-00293
` Patent 9,173,857
`
` DEPOSITION OF DIANE J. BURGESS, Ph.D.
`
`DATE: September 24, 2018
` 9:40 a.m.
`HELD AT: Axinn, Veltrop & Harkrider LLP
` 90 State House Square
` Hartford, Connecticut 06103
`
` By: Sarah J. Miner, RPR, LSR #238
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`DIANE J. BURGESS, PH.D.
`
`Page 3
`
`A P P E A R A N C E S:
`For the Patent Owner Shire PLC:
`Joseph R. Robinson, Esq.
`Troutman Sanders LLP
`875 Third Avenue
`New York, NY 10022
`joseph.robinson@troutman.com
`and
`Tanya Leavey, Ph.D., Patent Agent
`Troutman Sanders LLP
`875 Third Avenue
`New York, NY 10022
`tanya.leavey@troutman.com
`
`For the Petitioner KVK-Tech, Inc.:
`Thomas K. Hedemann, Esq.
`Alexander Alfano, Esq.
`Axinn, Veltrop & Harkrider LLP
`90 State House Square
`Hartford, Connecticut 06103
`thedemann@axinn.com
`aalfano@axinn.com
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`DIANE J. BURGESS, PH.D.
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`Page 4
`
` I N D E X
`WITNESS: Page
`DIANE J. BURGESS, Ph.D.
`Direct Examination by Mr. Robinson 5
` E X H I B I T S
`Deposition
`Exhibits Description Marked
`Exhibit 200 One page typewritten 43
`Exhibit 201 US Patent 6,605,300 80
`Exhibit 202 US Patent Publication 88
` No. US 2004/0059002
`Exhibit 203 PDR label 101
`Exhibit 204 US Patent 6,322,819 112
`Exhibit 205 US Patent 8,313,776 112
`Exhibit 206 Declaration of Dr. Burgess 142
` US Patent 9,173,857
`Exhibit 207 Declaration of Dr. Burgess 142
` US Patent 8,846,100
`Exhibit 208 ADHD Treatment and Outcome 154
` by Dr. Kratochvil
`Exhibit 209 US Patent 9,173,857 171
`Exhibit 210 US Patent 8,846,100 171
`Exhibit 211 Utility Patent 213
` Application Transmittal
` (The exhibits were included with the
`original transcript.)
`
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`DIANE J. BURGESS, PH.D.
`
`Page 5
` DIANE J. BURGESS, Ph.D., 09:38:58
`having first been duly sworn by Sarah J. Miner, LSR, a 09:38:58
`Notary Public in and for the State of Connecticut, was 09:38:58
` 09:38:58
`examined and testified as follows: 09:38:58
` 09:38:58
` DIRECT EXAMINATION 09:38:58
`BY MR. ROBINSON: 09:38:58
` Q. Good morning. 09:39:02
` A. Good morning. 09:39:04
` Q. Thank you for coming today. I will be asking 09:39:05
`you some questions about this inter-party proceeding. 09:39:12
`If you need any clarification or anything like that, 09:39:15
`just feel free to ask. 09:39:18
` A. Okay. 09:39:19
` Q. Could you just give your name, address and 09:39:20
`occupation? 09:39:23
` A. Diane J. Burgess, 626 Browns Road in Storrs 09:39:24
`Mansfield, Connecticut. And I am a distinguished 09:39:29
`professor of pharmaceutics at the University of 09:39:32
`Connecticut. 09:39:36
` Q. What are your duties as a professor? 09:39:38
` A. Teaching, research and service. 09:39:42
` Q. You submitted a declaration. You realize 09:39:44
`that this is -- we are here for two IPRs, right? 09:39:46
` A. Yes, I do. 09:39:50
` Q. And you submitted a declaration in each. 09:39:51
`
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`DIANE J. BURGESS, PH.D.
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`Page 6
`Correct? 09:39:54
` A. Yes. 09:39:55
` Q. You submitted an errata last night? 09:39:55
` MR. HEDEMANN: Do you want me to answer on 09:39:59
`the record? 09:40:00
` MR. ROBINSON: Yes. 09:40:01
` MR. HEDEMANN: We haven't yet submitted an 09:40:01
`errata. We sent you an email asking whether you would 09:40:03
`stipulate to the errors identified as being 09:40:08
`typographical and consent to us submitting an errata. 09:40:13
` MR. ROBINSON: Yes, we will. 09:40:17
` MR. HEDEMANN: Okay. I should say on the 09:40:19
`record that this morning we identified a few more 09:40:21
`typographical issues that we will give to you as well 09:40:25
`and -- you know, a little later today. 09:40:28
` MR. ROBINSON: Is there anything substantive 09:40:32
`or is it just citations like the others? 09:40:34
` MR. HEDEMANN: These are not citations, but 09:40:37
`they are -- as you know, the two declarations are 09:40:39
`pretty much identical. And in the '857 declaration, 09:40:42
`there are a number of references to the '100 patent 09:40:45
`where there should be references to the '857 patent. 09:40:48
`So it's just typographical. 09:40:53
` MR. ROBINSON: So we are talking 09:40:55
`misreferences to which patent we are talking about and 09:40:56
`
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`DIANE J. BURGESS, PH.D.
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`Page 7
`we are talking about citation errors. Correct? 09:41:00
` MR. HEDEMANN: Exactly. 09:41:02
` THE WITNESS: Yes. 09:41:03
` MR. ROBINSON: And citation errors, I assume, 09:41:03
`arose because you were trying to conform the two? 09:41:05
` MR. HEDEMANN: I assume. 09:41:08
` MR. ROBINSON: Not a problem. 09:41:09
`BY MR. ROBINSON: 09:41:10
` Q. Other than the erratas -- the errors that we 09:41:10
`just discussed on the record in front of you, is 09:41:15
`everything else in your declarations correct? 09:41:18
` A. I believe so. 09:41:21
` Q. When is the last time you reviewed your 09:41:23
`declarations? 09:41:25
` A. Last night. 09:41:26
` Q. You didn't find any other errors other than 09:41:26
`what we just discussed. Is that correct? 09:41:30
` A. No, not last night, no. 09:41:32
` Q. Is there a goal of drug delivery? 09:41:38
` A. A goal of drug delivery? 09:41:41
` Q. Yes. 09:41:43
` A. There are many goals to drug delivery. 09:41:44
` Q. What are the goals of drug delivery? 09:41:46
` A. Well, the main goal is to get the patient the 09:41:48
`medication safe and efficacious. That would be the 09:41:51
`
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`DIANE J. BURGESS, PH.D.
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`Page 8
`over-arching goal. 09:41:54
` Q. And other goals? 09:41:57
` A. The other goals would be the -- the -- the 09:41:58
`delivery goals, like sometimes you want immediate 09:42:01
`release. Sometimes you want a controlled release. 09:42:04
`Extended release. Sometimes you would want the 09:42:08
`release to be over a period of weeks, months, years in 09:42:10
`-- in some particular cases. Those would typically be 09:42:17
`injectables. Those mainly for patient compliance 09:42:21
`reasons, we want to have some of these very extended 09:42:26
`release profiles. 09:42:30
` Also because of different disease states, 09:42:31
`sometimes they need -- like you would need maybe a 09:42:36
`bolus of drug at some point, for example, insulin when 09:42:41
`you take a meal and you might need a background level 09:42:46
`of the insulin to be delivered all the time and then a 09:42:49
`bolus at certain times. So there can be many goals 09:42:52
`within that that are to do with the -- the rate of 09:42:56
`drug delivery, and also the place where the drug is 09:43:02
`delivered to. 09:43:05
` For example, for anticancer drug, if the drug 09:43:07
`is released in everyplace in the body, you get many 09:43:12
`deleterious side effects, whereas you can minimize 09:43:17
`these if you are able to specifically target the drug 09:43:20
`to specific cancerous cells, for example. 09:43:23
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` Q. Any other goals of drug delivery? 09:43:26
` A. Oh, gosh. I am sure. There are many things 09:43:29
`I could think about, but mainly it is safe and 09:43:32
`efficacious and then to get the drug in maybe 09:43:35
`controlled release, controlling it, controlling the 09:43:41
`rate, controlling the place that the drug gets to. 09:43:44
` Q. Is -- for an oral drug delivery system or 09:43:48
`formulation, is dissolution of the drug in the GI 09:43:54
`tract a goal? 09:43:57
` A. For oral drug? 09:44:00
` Q. Yes. 09:44:01
` A. That the drug should dissolve in the GI 09:44:02
`tract, I think in most cases that -- that is a goal. 09:44:06
`There are some instances where you might be giving a 09:44:08
`liposome formulation that you want to get taken up 09:44:12
`intact without drug release in the GI tract into the 09:44:16
`lymphatic system, for example. 09:44:20
` Q. Okay. Is drug absorption from the GI tract 09:44:22
`into the blood stream a goal of drug delivery? 09:44:27
` A. Not -- not -- from the GI tract into the 09:44:30
`bloodstream, I would say in most -- in most cases. 09:44:33
`Sometimes you might be treating a disease of the GI 09:44:36
`itself. So it's not necessarily you want the drug to 09:44:40
`be systemically into the bloodstream. 09:44:43
` Q. Is it a simple process to deliver a drug in a 09:44:46
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`DIANE J. BURGESS, PH.D.
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`Page 10
`safe and efficacious manner? 09:44:49
` A. It really depends. It really depends on the 09:44:55
`drug. If you are talking about an anticancer drug, 09:44:57
`obviously, there is a lot of toxicity associated. So, 09:45:01
`you know, may be more challenging. But it really 09:45:04
`depends on the type of drugs. Some drugs are very 09:45:08
`simple to formulate and they have been formulated for 09:45:12
`years and work really well in a very simple 09:45:15
`formulation. 09:45:18
` Q. Is it a simple process to control the rate of 09:45:18
`release of a drug? 09:45:24
` A. There are many processes known to control the 09:45:25
`rate of release. So with -- with the information that 09:45:27
`has been generated over the last hundred years or so, 09:45:33
`couple of hundred years, then there are many, let's 09:45:40
`say, tools that a formulator can pick on to use to 09:45:43
`control the rate of drug release, either whether it is 09:45:47
`in the GI tract or an injectable or -- or into the 09:45:52
`eye. You know, a number of routes of administration 09:45:56
`that we utilize. 09:45:59
` Q. And does the fact that there are many, many 09:46:00
`tools -- you used the word "tools" -- that one can 09:46:12
`pick to make it a simple task to control the rate of 09:46:15
`delivery of drug? 09:46:18
` A. As I said, it really depends on the specific 09:46:21
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`DIANE J. BURGESS, PH.D.
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`Page 11
`drug, on exactly what you are trying to do. But 09:46:25
`because we have a good toolbox to go to, then, you 09:46:29
`know, it -- that does simplify things. 09:46:34
` Q. And what do you mean by simplify things? 09:46:37
` A. Well, if we were starting 300 years ago and 09:46:39
`people had not invented many of the different methods 09:46:43
`of drug delivery that we have now, modifying the rate 09:46:48
`of release, then obviously it would be more difficult. 09:46:51
`But given that, you know, we have made a lot of 09:46:55
`advances, then we -- we have developed different ways 09:46:58
`to control the release of -- of the drug. We have 09:47:02
`developed different polymers that can help with that. 09:47:07
`Then that does simplify things certainly. 09:47:10
` Q. How many ways are there to control the 09:47:13
`release of the drug? 09:47:15
` A. How many ways to control the release of drug? 09:47:16
`There -- there's many ways to control drug release, 09:47:19
`depending on which route of administration you are -- 09:47:22
`you're talking about. 09:47:26
` Q. Let's talk about oral drug release. 09:47:27
` A. Only oral. Okay. So with oral, you can be 09:47:29
`using like a matrix formulation where the drug is 09:47:33
`dispersed in a polymer matrix to slowly release the 09:47:38
`drug. You can use polymer that can again slowly 09:47:43
`release the drug that is coated on top of the drug. 09:47:47
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` You can use a polymer that is coated on top 09:47:51
`of the drug to just maybe delay the drug release for a 09:47:53
`certain period of time and then release it all at 09:47:59
`once. And, for example, that is done with enteric 09:48:02
`coating so that prevents any release of drug until it 09:48:07
`leaves the stomach and goes into the duodenum. So 09:48:10
`then we get bolus release of drug then. 09:48:14
` There are different ways that we can use the 09:48:18
`particle size of the drug itself without using any 09:48:20
`polymers. Some drugs are less soluble than others, 09:48:23
`and they are considered to be poorly soluble. So if 09:48:27
`you use large particle size, then the drug release is 09:48:32
`much slower. If you reduce the particle size then to 09:48:35
`micron and nanoparticles, then you are increasing the 09:48:40
`surface area. And with that increase in surface area, 09:48:44
`there are more drug molecules that are at the surface. 09:48:48
`And drug molecules that are at the surface have 09:48:51
`different activity than drug molecules that are in the 09:48:56
`bulk. Because in the bulk they typically -- 09:49:02
` THE COURT REPORTER: I'm sorry. Then in the 09:49:04
`what? 09:49:04
` THE WITNESS: In the bulk. 09:49:04
` THE COURT REPORTER: Thank you. Sorry. 09:49:04
` THE WITNESS: Say you have a particle of drug 09:49:04
`-- you have a bigger particle, then most of the 09:49:05
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`Page 13
`molecules of that drug are in -- in the middle of the 09:49:08
`center and fewer are on the exterior. And the ones 09:49:12
`that are at the exterior have very different 09:49:17
`properties than the ones that are in the bulk. 09:49:21
`Because the ones that are in the bulk are typically in 09:49:23
`a crystalline matrix and they are surrounded by their 09:49:27
`-- the same molecules. And that really affects their 09:49:31
`activity and their ability to dissolve. 09:49:36
` Whereas, ones that are at the surface have a 09:49:40
`much higher activity because they are only surrounded 09:49:42
`in, you know -- on -- on certain -- like on the planar 09:49:45
`and below with molecules that are the same and then 09:49:51
`they are exposed to different molecules. And that 09:49:55
`really affects their activity and they are not as 09:49:58
`comfortable in that environment and so they are more 09:50:01
`likely to leave the surface and dissolve. 09:50:04
` So in the last, oh, 30 years or so, people 09:50:10
`have been really exploiting this to make nanoparticles 09:50:12
`to enhance the solubility of poorly soluble drugs. So 09:50:18
`that is yet another method. There are many different 09:50:23
`methods. The other one is mucoadhesion. People have 09:50:29
`tried that where they add a polymer which has 09:50:33
`mucoadhesive properties so it can adhere onto the gut 09:50:36
`wall and keep it in a particular part of the gut for a 09:50:42
`period of time and then to release the drug at that 09:50:46
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`part. 09:50:49
` So there are many different options that 09:50:52
`people have envisioned -- 09:50:55
` Q. Can you put a number on the number of 09:50:56
`options? 09:50:58
` A. How many have I said already? 09:50:59
` Q. Four or five. 09:51:02
` A. I think I have said more than that. 09:51:03
` Q. Okay. 09:51:04
` A. I have definitely said more than that. So 09:51:05
`there's a lot. Do you want me to go back through them 09:51:08
`and count them all? 09:51:12
` Q. Are there a hundred? 09:51:13
` A. Well, if you count all the different polymers 09:51:15
`that people have used, there probably could be upwards 09:51:18
`to that because people have used various different 09:51:21
`polymers to delay the release. So if you count each 09:51:25
`one of those, then you can make multiples and increase 09:51:27
`the number. 09:51:31
` Q. Can you increase the number to a thousand? 09:51:32
` A. I don't think so. 09:51:34
` Q. What are the steps that an orally delivered 09:51:36
`drug must go through after it is administered in order 09:51:39
`to have a therapeutic effect? 09:51:43
` A. Well, again, it would depend on where you 09:51:45
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`want the therapeutic effect. If you want the 09:51:47
`therapeutic effect, say, to be in the environment of 09:51:50
`the GI or you want the therapeutic effect to be a 09:51:53
`systemic effect or a specific effect of a specific 09:51:57
`area. 09:52:00
` Q. Let's start with systemic effect. 09:52:00
` A. So for an orally administered drug, it would 09:52:02
`typically be swallowed. If it was a tablet, it would 09:52:06
`need to, first of all, disintegrate. Then the 09:52:09
`disintegrated tablet, so that is that tablet is maybe 09:52:12
`only composed of -- maybe it's composed of many like 09:52:17
`-- many excipients in the tablet so there's not just 09:52:21
`the drugs. There's aspirin, there's also other 09:52:25
`components such as -- what they are called fillers and 09:52:29
`binders. 09:52:32
` And these different excipients, there are 09:52:33
`also some that are disintegrants and they help the 09:52:35
`granules of the tablets to disintegrate. After 09:52:41
`disintegration, then you usually would get 09:52:46
`dissolution. And then after dissolution, you get the 09:52:46
`absorption where the drug is to pass across the GI. 09:52:52
`Then it's -- then it gets into the bloodstream. And 09:52:55
`then from the bloodstream, from the GI, usually the 09:52:58
`drug goes to the liver. 09:53:00
` And then for some drugs, you get hepatic 09:53:01
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`DIANE J. BURGESS, PH.D.
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`Page 16
`first-class metabolism. And then from there, it goes 09:53:04
`all throughout the body. And then some drugs are then 09:53:10
`compartmentalized into specific parts of the body. 09:53:12
`For example, if it is a fat soluble drug, it may get 09:53:17
`-- it may partition into the fatty tissue that may be 09:53:20
`present in the body. And then you have to have -- you 09:53:25
`have an equilibrium between the drug that is 09:53:29
`partitioned into the fatty tissue and the drug that's 09:53:34
`in the blood. Some drugs also absorb onto plasma 09:53:36
`proteins. And then there's an equilibrium between 09:53:39
`that. So -- and so that's for tablets. 09:53:44
` In the case of capsules, for example, you 09:53:46
`don't have to go through this disintegration process 09:53:48
`because usually it could either be a liquid or some 09:53:51
`solid particles that are inside the capsules. So you 09:53:55
`miss the disintegration. And then those -- that 09:54:00
`liquid dose that's inside the capsule might be already 09:54:05
`in solution form so you don't need to have a 09:54:08
`dissolution phase. If it is particles, you might have 09:54:11
`it -- have to have a dissolution phase. 09:54:15
` Sometimes you are taking oral drugs as -- 09:54:17
`completely as liquid, like you take a spoonful of 09:54:21
`cough medicine. And then again, there is no 09:54:24
`dissolution phase. There are some drugs that you take 09:54:27
`that are mucoadhesive in the mouth. In fact, I am 09:54:30
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`DIANE J. BURGESS, PH.D.
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`Page 17
`working on one of those myself right now for -- to 09:54:35
`help with some of the canker sores that you get in the 09:54:39
`mouth with anticancer drugs. 09:54:43
` And those -- those you -- we are formulating 09:54:48
`it in a gel form that is liquid at room temperature. 09:54:50
`And then when we spray it into the mouth, then it 09:54:58
`forms a gel and it would stick onto those ulcerated 09:55:01
`sores in the mouth and release the drug specifically 09:55:06
`at that area to kind of have an anesthetic effect to 09:55:10
`give the patient some alleviation of that problem. 09:55:14
` There are also ones that are designed that 09:55:18
`you put under the tongue and you let them dissolve in 09:55:21
`the mouth and so they don't go all way through the GI. 09:55:26
`In fact, some of the baby aspirins are designed that 09:55:31
`you chew them and kind of keep them in the mouth. And 09:55:33
`so there is a lot of blood supply in the mouth, but 09:55:35
`particularly under the tongue and you can get the drug 09:55:38
`to go from there into the bloodstream and then quickly 09:55:41
`into the -- systemically so you can get a rapid onset 09:55:45
`of action. Just many, many different options. 09:55:50
` Q. With respect to oral drug delivery systems or 09:55:57
`formulations, what does the term "rapid release" mean? 09:56:00
` A. Rapid release would usually mean that the 09:56:04
`drug is dissolved or is released -- say if it is a 09:56:06
`tablet, it might be -- disintegrate very quickly. And 09:56:12
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`DIANE J. BURGESS, PH.D.
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`then the drug is released, meaning that it is 09:56:16
`dissolved very fast from that particular dosage form. 09:56:20
` Q. And what would rapid release mean with 09:56:25
`respect to a capsule of beads? 09:56:28
` THE COURT REPORTER: To a capsule? 09:56:37
`BY MR. ROBINSON: 09:56:37
` Q. Filled with beads. 09:56:37
` A. It would just -- again, it would depend on, 09:56:37
`you know, the specific content, context that you were 09:56:39
`asking me in. It could mean that the release was in 09:56:44
`15 minutes. It might be maybe 30 minutes or maybe an 09:56:47
`hour. Wouldn't expect it to be longer than a hour. 09:56:52
` Q. Is release the same as dissolution? 09:56:58
` A. It is kind of a little bit confusing there 09:57:01
`because you could -- mostly you think of it as the 09:57:05
`same as dissolution. Then if you think of something 09:57:10
`that is already in a liquid form, for example, you 09:57:13
`know, then it is already in a dissolved form, then you 09:57:16
`can get release of those. Or like if in the form of a 09:57:20
`micellar form or -- 09:57:29
` THE COURT REPORTER: I'm sorry. If it's 09:57:30
`what? 09:57:30
` THE WITNESS: In a -- it's formed from 09:57:30
`micelle, those are also considered to be in solution. 09:57:30
` A micelle is when -- when you have some very 09:57:33
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`DIANE J. BURGESS, PH.D.
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`Page 19
`hydrophobic drugs that wouldn't normally dissolve in 09:57:37
`water. You can add surfactant and the surfactant 09:57:42
`creates what is called a micelle. And the micelle is 09:57:46
`made up of the surfactants where you have got 09:57:49
`hydrophilic head group and hydrophobic tail. And the 09:57:53
`hydrophobic tail of the surfactant, although it can 09:57:55
`stay dissolved in the water, if you have a lot of them 09:57:58
`they prefer to aggregate these surfactants. 09:58:02
` These are the same surfactants that you would 09:58:04
`use to wash your hair or wash the dishes. If they are 09:58:06
`higher concentration, they will form into these 09:58:09
`micellar states where the hydrophobic tails is in the 09:58:12
`center. So that creates a hydrophobic environment. 09:58:14
`So you've got these little micelles with these 09:58:18
`hydrophobic head groups that keeps it stabilized in 09:58:18
`water and the hydrophobic tails. 09:58:26
` And then hydrophobic drug can be dissolved 09:58:29
`inside that hydrophobic tail part. And so those are 09:58:29
`considered really being in solution. So again, with 09:58:37
`that example, you don't have to go into solution 09:58:40
`first. So there -- there is some similarities and 09:58:44
`differences. So maybe release is maybe an 09:58:48
`over-arching term and dissolution is maybe more 09:58:52
`specific term. 09:58:52
` Q. Is release -- are release and dissolution the 09:58:54
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`DIANE J. BURGESS, PH.D.
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`Page 20
`same with respect to solid or oral dosage form? 09:58:56
` A. That is usually what you would be meaning, 09:59:00
`yes. 09:59:02
` Q. And what is sustained release with respect to 09:59:03
`a solid oral dosage form? 09:59:05
` A. So that's -- you are doing something to 09:59:08
`sustain or maybe delay the release for some time and 09:59:09
`cause a more extended release of the dosage form. 09:59:14
` Q. What do you mean by "more extended release"? 09:59:18
` A. Well, sustained release is kind of -- can be 09:59:26
`delay and then also sustained. So you can -- so say 09:59:29
`if you have a drug that would normally be immediate 09:59:34
`release or it is maybe a fast dissolving drug and then 09:59:37
`you can put it in a matrix of a polymer or
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