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` UNITED STATES PATENT AND TRADEMARK OFFICE
` THE PATENT TRIAL AND APPEAL BOARD
`------------------------------x
` PAR PHARMACEUTICAL, INC., )
` )
` Petitioner, )
` )
` vs. )
` )
`NOVARTIS AG, )
` )
` Patent Owner. )
`------------------------------x
`
` DEPOSITION OF WILLIAM L. JORGENSEN, PH.D.
` New York, New York
` Tuesday, August 9, 2016
`
`Reported by:
`CORINNE J. BLAIR, CRR, CCR, RPR, CLR
`JOB #: 111153
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` UNITED STATES PATENT AND TRADEMARK OFFICE
` THE PATENT TRIAL AND APPEAL BOARD
`------------------------------x
` PAR PHARMACEUTICAL, INC., )
` )
` Petitioner, )
` )
` vs. )
` )
`NOVARTIS AG, )
` )
` Patent Owner. )
`------------------------------x
`
` DEPOSITION OF WILLIAM L. JORGENSEN, PH.D.
` New York, New York
` Tuesday, August 9, 2016
`
`Reported by:
`CORINNE J. BLAIR, CRR, CCR, RPR, CLR
`JOB #: 111153
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` August 9, 2016
` 9:36 a.m.
`
` Deposition of WILLIAM L. JORGENSEN, Ph.D,
`held at the offices of LATHAM & WATKINS, LLP,
`885 Third Avenue, New York, New York, before
`Corinne J. Blair, a Certified Realtime Reporter,
`Certified Court Reporter, Registered
`Professional Reporter, Certified Livenote
`Reporter, and Notary Public of the State of New
`York.
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`APPEARANCES:
`
` FITZPATRICK, CELLA, HARPER & SCINTO
` Attorneys for Patent Owner, Novartis AG
` 1290 Avenue of the Americas
` New York, New York 10104
` BY: CHRISTINA SCHWARZ, ESQ.
` LISA BUTLER, ESQ.
` WILLIAM SOLANDER, ESQ.
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`APPEARANCES: (continued)
`
` LATHAM & WATKINS
` Attorneys for Petitioner,
` Par Pharmaceutical, Inc.
` 885 Third Avenue
` New York, New York 10022
` BY: DANIEL BROWN, ESQ.
` AND
` 330 North Wabash Avenue
` Chicago, Illinois 60611
` BY: BRENDA DANEK, ESQ.
` AND
` 555 Eleventh Street, NW
` Washington, DC 20004
` BY: JONATHAN STRANG, ESQ.
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` IT IS HEREBY STIPULATED AND AGREED by and
`between the attorneys for the respective parties
`herein, that filing and sealing be and the same
`are hereby waived.
` IT IS FURTHER STIPULATED AND AGREED that
`all objections, except as to the form of the
`question, shall be reserved to the time of the
`trial.
` IT IS FURTHER STIPULATED AND AGREED that
`the within deposition may be sworn to and signed
`before any officer authorized to administer an
`oath, with the same force and effect as if
`signed and sworn to before the Court.
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` William L. Jorgensen, Ph.D
`W-I-L-L-I-A-M L. J-O-R-G-E-N-S-E-N, Ph.D.,
` called as a witness, having been duly sworn
` by a Notary Public, was examined and
` testified as follows:
`EXAMINATION BY
`MS. SCHWARZ:
` Q Good morning, Dr. Jorgensen.
` A Hi.
` Q I'm handing you a copy of document
` Exhibit 1003.
` Can you identify this document for
` me?
` A This is a declaration of myself in
` support of the petition for Inter Parte's
` Review.
` Q Did you draft this declaration
` yourself?
` A I did, with assistance.
` Q Did you carefully review each
` paragraph of the declaration before you signed
` it?
` A Yes.
` Q If there was anything in this
` declaration that was incorrect or inaccurate,
`
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` William L. Jorgensen, Ph.D
`would you have corrected it before you signed
`the declaration?
` A Yes.
` Q Did you carefully review each of the
`exhibits cited before you signed the
`declaration?
` A Yes.
` Q If you could turn to paragraph 18,
`please.
` Do you set forth in paragraph 18 a
` summary of the materials that you relied on
` in forming your opinions?
` A Yes.
` Q So you relied on the 772 patents
`claims disclosure and file history on the
`prior art exhibits to the petition and any
`other materials cited in this declaration?
` A Yes.
` Q Is this a complete list of all of
`the materials that you relied on in forming
`your opinions?
` A Well, it continues: In my own
` experience, expertise, and knowledge of a
` person of ordinary skill in the art.
`
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` William L. Jorgensen, Ph.D
` Q Are there any other specific
`documents that you relied on in forming your
`opinions that are not mentioned in this
`declaration?
` A I would say there are many under the
` heading of my own experience; would include a
` very large range of materials that I've read
` over the years, including on rapamycin.
` Q Are there any particular documents
`that you include in that list?
` A I would say they're all part of my
` expertise and knowledge. There's nothing
` that I would say stands out uniquely.
` Q If there was a document that was
`important to your opinions, would you have
`specifically listed it in this declaration or
`mentioned it in this declaration?
` A I believe that if I felt it was
` specifically highly-relevant to this, I would
` have listed it.
` Q Did you perform your analysis for
`purposes of this IPR from the perspective of a
`person of ordinary skill in the art as of
`October 9th, 1992?
`
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` A Yes.
` Q And you define that person in your
`declaration?
` A Yes.
` Q So for the purpose of today, I'll
`use the definitions set forth in your
`declaration. Okay?
` A Okay.
` Q So if I refer to a person of
`ordinary skill in the art, I'm referring to
`the person that you have defined.
` A Mm-hmm.
` Q And when discussing the
`state-of-the-art, you performed your analysis
`as of the date October 9th, 1992; is that
`correct?
` A Correct.
` Q You did not render your opinions
`from any other date?
` A No.
` Q How would a person of ordinary skill
`in the art in October 1992 have defined ideal
`solubility?
` A Okay. Ideal solubility is a
`
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` William L. Jorgensen, Ph.D
`concept, sort of akin to an ideal gas. It's
`a concept in physical chemistry.
` Neither an ideal gas nor an ideal
`solution exists. These are concepts that are
`used to develop theories that -- where one
`can write analytical expressions such as PV
`equals NRT. Okay. No real gas abase exactly
`the PV equals NRT.
` A person of ordinary skill, as
`defined here, would not be interested in the
`concept of an ideal solution. Okay. It is
`not a concept that medicinal chemists care
`about because it doesn't directly impact
`them.
` They recognize that all solutions
`that they're interested in would be
`non-ideal. And I doubt if 10 percent of
`medicinal chemists would be able to describe
`what an ideal solution is.
` Q Can you define an ideal solution?
` A There are ways of defining it. One
`is that it satisfies Raoult's Law.
` Q What is Raoult's Law?
` A Again, this has no relevance to a
`
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` William L. Jorgensen, Ph.D
` medicinal chemist.
` Raoult's Law has to do with the
` vapor pressure above a solution that has
` multiple components. And that the vapor
` pressure would be equal to the paper
` pressures of the pure substances weighted by
` their composition of a solution.
` Again, of no relevance to a person
` of ordinary skill.
` Q Is another way of defining an ideal
`solution as a solution that exhibits no change
`of internal energy on mixing of solutes in
`solvent and complete uniformity of cohesive
`forces?
` A I've seen it written, seen that as a
` definition.
` Q Is that a fair definition?
` A You can find it in textbooks.
` Q Would a person of ordinary skill
`agree that that's an accepted definition of an
`ideal solution?
` A No. A person of ordinary skill --
` again, a medicinal chemist would have no
` interest in this type of concept, which is
`
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` William L. Jorgensen, Ph.D
` one from sort of very basic physical
` chemistry.
` Q So you're saying a person of
`ordinary skill would not agree with that
`definition?
` A I'm saying a person of ordinary
` skill wouldn't be able to agree with the
` definition without going and looking it up in
` a textbook. If they saw it then in a
` textbook, then he might agree with it.
` Q And I think you agreed with me that
`the definition I read to you is one that
`you've seen in textbooks?
` A Yes.
` Q How would a person of ordinary skill
`in October 1992 have defined water solubility?
` A Water solubility is a concept of
` interest to medicinal chemists and it
` formerly is simply the concentration of a
` solid substance that one can obtain in an
` aqueous solution. This is often done by
` what's called a shake flask method, where you
` shake water and the solid material, say, for
` 24 hours until the aqueous solution is fully
`
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` William L. Jorgensen, Ph.D
` saturated. There still has to be solid
` present in equilibrium with the saturated
` solution. And then the concentration of the
` material that's in water would then be the
` formal definition of the solubility expressed
` in different units, such as micrograms per
` milliliter, or concentration units, such as
` molarity.
` Q You mentioned aqueous solution.
` Is that the same thing as a water
` solution?
` A Yes.
` Q So water solubility is the same
`thing as aqueous solubility?
` A Yes.
` Q Are the terms ideal solubility and
`water solubility synonyms for one another?
` A They're -- I am not familiar with
` people talking of them in the same time.
` Again, the ideal solubility is a --
` an ideal gas-like concept that is not
` relevant to medicinal chemists.
` Water solubility is very relevant to
` medicinal chemists.
`
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` William L. Jorgensen, Ph.D
` Q What's the difference between ideal
`solubility and water solubility?
` A I guess you like to waste time on
` concepts that aren't of relevance to
` medicinal chemists. But given that, so
` aqueous solubility I just defined as obtained
` by having a saturated solution of a compound
` in water.
` Ideal solubility could be something
` where you take even a pure solid of some sort
` and melt it, and then you have an equilibrium
` between the -- on the melt, the liquid, and
` then the solid material. And then the
` concentration of that liquid could be taken
` as a solubility.
` Q If a solute has poor solubility in a
`given solvent, would that solvent be
`considered an ideal solvent for that solute?
` A Those are two independent concepts.
` It doesn't make sense. You can repeat it.
` Q What is the conventional solubility
`range for drug candidates?
` A In reviews I've written, I pointed
` out as being about four micrograms per
`
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` William L. Jorgensen, Ph.D
` milliliter, 4,000 micrograms per milliliter.
` (sic)
` Q Are those reviews written before
`October 1992?
` A No.
` Q How would one of ordinary skill in
`the art in October of 1992 have understood the
`conventional solubility range for drug
`candidates?
` A At that time, I would say a person
` of ordinary skill would have thought it was
` similar to what I said. And certainly people
` knew that when you got down to ranges --
` solubility ranges around ten to the minus six
` molar, you were generally in trouble in
` trying to formulate a compound.
` Q As of October 1992, was rapamycin
`known to be a large molecule with relatively
`few hydrophilic moieties and with large
`hydrophobic regions?
` A Yes. Rapamycin is a large molecule
` that has a mixture of hydrophobic and
` hydrophilic pieces.
` Q In particular, it has a relatively
`
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` William L. Jorgensen, Ph.D
`few hydrophilic moieties?
` A No, I wouldn't say that.
` Q How about you turn to paragraph 139
`of your declaration?
` A You can also look at the structure
` of rapamycin. I can count the number of
` hydrophilic moieties.
` Where do you want me to look?
` Q 139.
` A Yes.
` Q I'm looking at the last sentence.
` A Mm-hmm.
` Q Do you say there that rapamycin has
`relatively few hydrophilic moites?
` A Yes.
` Q Do you agree with that?
` A Compared to the, again, large
` hydrophobic regions. We can go through the
` structure if you'd like.
` Q Sure. Let me ...
` MS. SCHWARZ: I'm going to mark
` Exhibit 2089.
` (Exhibit 2089 Page 7 of Dr.
` Jorgensen's declaration, was marked
`
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` William L. Jorgensen, Ph.D
` for identification at this time.)
`BY MR. BROWN:
` Q So this is just page 7 from your
`declaration.
` Is that the structure of rapamycin
` shown there on this page?
` A Yes.
` Q Can you identify for me on this
`structure the few hydrophilic moieties that
`you reference in paragraph 139?
` A In paragraph 139, I say, "Relatively
` few hydrophilic moieties with large
` hydrophilic regions."
` If we want to do a sort of estimate
` of the two, we can call oxygens and nitrogens
` hydrophilic, and carbons hydrophobic, and
` just count them.
` So there are -- should we count
` them?
` Q Sure. How about I give you a pen,
`and maybe you can circle the large hydrophobic
`regions you've referenced in paragraph 139.
` Can you please do it on the new page
` we've marked there? Perfect. Thank you.
`
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` William L. Jorgensen, Ph.D
` A So the largest hydrophobic region
` would be the one with the triang (ph) unit.
` As I said, we can put every carbon
` as hydrophobic. Some of them, like a methyl
` group, I wouldn't consider to be a large
` hydrophobic region, but it contributes to the
` overall hydrophobicity.
` So if you want to just count again,
` a simpler way is to count on the oxygens and
` nitrogens versus the carbons. But there are,
` you know, substantial regions that I can
` outline with carbons, such as this region,
` include that, but there are other carbons.
` Carbon, carbon, carbon, carbon,
` carbon. This -- the ring here, the typical
` linac ring has carbons. So this ring has
` carbons. So there's a lot of carbon.
` Q Okay.
` A But at the same time, there are
` other functional groups. There are three
` alcohol functional groups. There are
` multiple carbonyl groups.
` Q So you've labeled now on
`Exhibit 2089 the large hydrophobic regions
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` William L. Jorgensen, Ph.D
`referenced in your paragraph 139?
` A Yes.
` Q Okay. Thank you.
` Just going back to the sentence in
` paragraph 139.
` Do you agree with the sentence that
` you've written here that, "Rapamycin is a
` large molecule with relatively few
` hydrophilic moieties and with large
` hydrophilic regions"?
` A Yes.
` Q How would one of ordinary skill in
`the art October -- in October of 1992 define
`"large molecules" as you've used the term
`here?
` A The concept of large molecules
` depends on the type of chemist you're talking
` to.
` Physical chemists might say that a
` large molecule has five atoms.
` Organic chemists might say a large
` molecule has 60 atoms.
` A biochemist might say a large
` molecule has a million atoms.
`
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` William L. Jorgensen, Ph.D
` So it's all very context relevant on
` who you're talking to.
` Q How would the person of ordinary
`skill in the art here in October 1992
`understand the term, "large molecules"?
` A If, again, you'd have to -- the
` person of ordinary skill has familiarity with
` drug-like molecules, he or she would also
` have familiarity with proteins, with DNA, et
` cetera.
` So you'd have to ask the person of
` ordinary skill, you know, what do you think
` is a large molecule when we're talking about
` a drug, you know, typical non-biologic drug,
` or a protein, or a nucleic acid, because a
` person of ordinary skill would have
` experience with all of those.
` Q And what answer would they give if I
`were to ask them that question?
` A For each one?
` You have to specify. Do you want to
` know to a person or a skill what they would
` think is large for a non-biologic drug, a
` RNA, a DNA, a protein, a peptide, because
`
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` William L. Jorgensen, Ph.D
` they will have a different answer depending
` on the type of molecule you're talking about.
` Q Okay. So here in paragraph 139,
`you've used the term, "large molecule."
` A Yes.
` Q How did you use the term, "large
`molecule" in this paragraph?
` A From the standpoint of the drug,
` non-biologic drug.
` Q And what qualifies as a large
`molecule for a non-biologic drug?
` A That's going to vary again depending
` on who you're talking to, but I would say
` everybody would agree that if you had a
` molecular -- it starts getting individual
` above about a molecular weight of 600. So I
` don't think anybody would call something much
` below 600 large. But then other people might
` not call something large until an atom
` molecular weight of a thousand.
` So I'd say for most medicinal
` chemists large drops in somewhere between 600
` and a thousand, and everybody would agree
` that at a thousand you're definitely large.
`
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` William L. Jorgensen, Ph.D
` Rapamycin is large compared to many
` -- what we call -- small-moleculed drugs;
` things like aspirin, for example.
` Q Do you agree that a person of
`ordinary skill would be aware that rapamycin
`is unusually large for a pharmaceutical drug?
` A It is way above average, yes.
` Q Was rapamycin reported to have a
`water solubility of 20 micrograms per mil
`prior to October 1992?
` A Yes.
` Q Would one of ordinary skill in
`October of 1992 characterize rapamycin
`solubility in water as poor?
` A Yes.
` Q Is the solution of rapamycin in
`water an ideal solution?
` A As I said previously, there are no
` ideal gases. There are no ideal solutions.
` The Easter bunny is questionable. And,
` therefore, a person of ordinary skill, if he
` or she knew what an ideal solution was, which
` is highly unlikely, would know that there are
` no ideal solutions.
`
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` William L. Jorgensen, Ph.D
` Q So a solution of rapamycin in water
`would not be an ideal solution?
` A Correct.
` Q I'm handing you a document that's
`been premarked Exhibit 1007. Please identify
`that document.
` A This is a paper by Samuel Yalkowsky
` from Industrial Engineering Chemical
` Fundamentals.
` Yalkowsky is a well-known expert on
` aqueous solubility. Literally wrote the
` book.
` Q Do you rely on this paper in your
`declaration to support your position that the
`addition of flexible side chains at rapamycin
`C40 position would be expected to improve
`rapamycin's water solubility?
` A Yes. This has one item in
` particular that I felt was worth pointing
` with this Figure 2.
` That was the key item that I was
` just trying to illustrate with this
` reference.
` Q Did you reference Figure 2 anywhere
`
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` William L. Jorgensen, Ph.D
`in your declaration?
` A I certainly did, in terms of the
` text that I've included reflects the concepts
` of Figure 2.
` Q But you never specifically mentioned
`Figure 2 anywhere in your declaration?
` A I think we'd have to look to be
` sure.
` Q Sitting here right now, do you
`recall referencing Figure 2 anywhere in your
`declaration?
` A I, again, recall referencing the
` content there, which is to show that when a
` flexible molecule goes from a solid state
` into solution, you have a large increase in
` the number of conformers that are populated.
` Those are geometries of the structure.
` And the solid, very often there's
` only one geometry. When it's released in the
` solution, then there are many geometries.
` And this is an effect that leads to a
` favorable entropy change. It's very
` well-known to undergraduate chemists.
` Q I'm handing you another document
`
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` William L. Jorgensen, Ph.D
`marked Exhibit 1008.
` Please identify that document.
` A This is a -- part of a book by
` Thomas Lemke.
` Q Did you rely on this paper to
`support your position that one of ordinary
`skill would include in the flexible side chain
`at C40 a solubilizing substituent with an
`expectation that it would increase rapamycin's
`water solubility?
` A Yes. The concept here is well-known
` to medicinal chemists. If you would like to
` increase the solubility of a molecule, you
` add flexible side chain that has hydrophilic
` moieties, which basically means nitrogens and
` oxygens.
` Q In your declaration, you've relied
`on both the Yalkowsky 1979 reference and the
`Lemke reference; is that correct?
` A Yes.
` Q Is it your opinion that everolimus
`would be expected to be more water soluble
`than rapamycin based on the combination of the
`Yalkowsky 1979 and Lemke references?
`
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` William L. Jorgensen, Ph.D
` A The -- yes. Everolimus differs from
` rapamycin by the replacement of an OH C40 by
` a hydroxyethoxy group.
` A hydroxyethoxy group has a flexible
` side chain that has two oxygen atoms in it.
` And based on fundamental Medicinal Chemistry
` 101, by adding flexible side chains with
` oxygens and nitrogens, one expects
` improvements in aqueous solubility for
` typical drug-like molecules.
` Q Does your opinion require that the
`Board consider both the Lemke and Yalkowsky
`1979 references to arrive at the conclusion
`that everolimus would be expected to be more
`water soluble than rapamycin?
` A There are other items that are cited
` here that could be -- that support or you
` could interpret in the same way, and
` specifically the Stella patent.
` Q Let's just focus on Lemke and
`Yalkowsky.
` Is one of those references
` sufficient to reach the conclusion that
` everolimus would be expected to be more water
`
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` William L. Jorgensen, Ph.D
`soluble than rapamycin, or do you need the
`combination of the two references?
` A Well, Yalkowsky doesn't address the
`necessity of nitrogen and oxygens in the side
`chain.
` And Lemke isn't really addressing
`the flexibility. You know, it may be
`implicit in some of Lemke's numbers that he
`puts in.
` So I would say, again, Med Chem 101,
`every medicinal chemist understands the
`concept. But in terms of these two
`documents, since Yalkowsky doesn't talk about
`nitrogens and oxygens in the side chain, and
`Yalkowsky isn't directly talking about
`improving drug solubility; he's dealing with
`a more general concept associated with the
`entropy change when you take a long chain
`substance and you go from the crystalline
`state to aqueous solution or ideal solution,
`you know, any liquid state, there's this
`entropy change that is well understood.
` So in terms of your question, one
`would need both references, but there's lots
`
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` William L. Jorgensen, Ph.D
` of other data here, and concepts such as the
` Stella patent that fully support this very
` fundamental notion of flexible side chains
` with Ns and Os is what you try if you want to
` make a compound more soluble.
` Q Let's talk about the Yalkowsky 1979
`reference, Exhibit 1007.
` Did you identify this paper or did
` counsel provide it to you?
` A I identified it.
` Q Were you aware of this paper before
`you became involved in the current IPR?
` A I have Yalkowsky's books, at least
` one book, maybe two books by Yalkowsky. I've
` read them. This is an area I'm very
` interested in.
` It's very possible that at some
` point in the past I came across this paper.
` It's from 1979. I didn't have a hard time
` finding it. So it's very possible that I've
` seen it in the past.
` I'm very familiar with the
` Yalkowsky's work. He has a famous equation
` about solubility.
`
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` William L. Jorgensen, Ph.D
` Q Is that famous equation about
`solubility discussed in Exhibit 1007?
` A I -- I think not. I'm happy to
` write it down for you.
` Q Sure. Let's do that.
` Give you a blank piece of paper.
` We'll mark this exhibit 2090.
` (Exhibit 2090 Page 7 of Dr.
` Jorgensen's declaration, Hand-drawn
` diagram of Yalkowsky's equation by
` Dr. Jorgensen, was marked for
` identification at this time.)
` THE WITNESS: The equation?
` Q Yes, please.
` A What the Yalkowsky equation does is
` it rates solubility S -- and this the terms
` of the logarithm of S. And the key thing is
` that he -- so it's Log S equals a half minus
` a constant, that I think is basically one,
` times Log P-O-W, which is the octanol water
` partition co-efficient, minus the melting
` point of the material minus 25 degrees times
` 0.01.
` Qualitatively, the nice thing about
`
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` William L. Jorgensen, Ph.D
`Yalkowsky's equation is he points out there's
`a very close inverse correlation between
`solubility and octanol water partition
`co-efficient.
` Octanol water partition co-efficient
`is a very fundamental concept in medicinal
`chemistry.
` So this is -- the basic notion here
`is if your solubility goes up, Log P-O-W goes
`down. So that means if you have a substance
`-- and it makes perfect sense -- something
`that is more hydrophilic has a lower Log P,
`and, therefore, it has a higher solubility.
` So this concept, and this equation,
`this is known to medicinal chemists. So they
`-- the way of increasing Log S is to decrease
`Log P. The way you decrease Log P is with
`polar groups, nitrogens and oxygens, and
`they're very consistent with what Lemke is
`saying.
` Lemke, also, I believe, may have
`this equation.
` So actually --
` Q Could you just label Exhibit 2090 as
`
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` William L. Jorgensen, Ph.D
`Yalkowsky's equation for me?
` A (Witness complies.)
` See if Lemke ... he talks about
` Log P. I don't see it immediately in
` Lemke, but I wouldn't be surprised if it's
` somewhere in his book.
` Q Let's go back to Yalkowsky 1979,
`Exhibit 1007.
` You mentioned that you're aware of
` various different publications and books by
` Yalkowsky; is that correct?
` A Yes.
` Q Did you identify this 1979
`reference, Exhibit 1007, as the most relevant
`Yalkowsky reference for the purpose of this
`case?
` A I came, again, to this reference
` because I wanted to make the point that it
` was in Figure 2; that it is, again,
` well-known to chemists, in general.
` As an undergraduate, one of the
` things you learn is that everybody's
` interested in alkanes, because that's what
` things like gasoline are made of. And one is
`
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` William L. Jorgensen, Ph.D
`taught that the crystal structures of alkanes
`are interesting, because the alkane molecules
`are lined up in one conformation; what we
`call all trans. But then when they melt, you
`get many conformations. And that is because
`each bond in an alkane carbon carbon bond --
`and you can have different conformations of
`the two groups attached to that bond that we
`teach in the very beginning of organic
`chemistry. We call them trans and gauche.
`And they're two mirror image gauche forms.
` So you go from the state in the
`solid alkanes, where they're completely
`extended all trans, but then when they melt
`in a pure liquid or if they're in solution,
`you have this huge increase in the number of
`conformations. It's three to the N, or N as
`the number of rotatable bonds.
` So you go from one conformation to
`three to the N possible conformations.
`They're populated to some extent, and they're
`not equally populated, but they all have some
`population.
` And that concept is very well-known.
`
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` William L. Jorgensen, Ph.D
` And that's what Yalkowsky illustrates in
` Figure 2, and that's why I focused on this
` paper of the Yalkowsky, is the one point that
` I wanted to take from it.
` Q So the one point in Yalkowsky that
`you're relying on is Figure 2?
` A I'm relying -- no. I'll rely on
` Yalkowsky in -- you know, he has some very
` good paragraphs or statements; for example,
` page 109.
` His point 4 here is talking about,
` these are things that contribute to the
` entropy of melting, or entropy of fusion.
` And the
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