UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`Page 1
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` ARGENTUM :
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` PHARMACEUTICALS, LLC, :
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`Petitioner,
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`: Patent No. 8,268,299
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` v. :
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` ALCON RESEARCH, LTD., :
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`Patent Owner. :
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`Friday, April 13, 2018
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`Washington, D.C.
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`Deposition of:
`
`SOUMYAJIT MAJUMDAR,
`
`called for oral examination by counsel for the
`
`Petitioner, pursuant to notice, at the law offices
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`of Williams & Connolly, LLP, 725 12th Street,
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`Northwest, Washington, D.C. 20005, before
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`Christina S. Hotsko, RPR, CRR, of Veritext Legal
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`Solutions, a Notary Public in and for the District
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`of Columbia, beginning at 8:42 a.m., when were
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`present on behalf of the respective parties:
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`www.veritext.com
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`Veritext Legal Solutions
`
`Exhibit 1045
`ARGENTUM
`IPR2017-01053
`888-391-3376
`
`000001
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`
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`Page 1
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`- - - - - - - - - - - - -x
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` ARGENTUM :
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` PHARMACEUTICALS, LLC, :
`
`Petitioner,
`
`: Patent No. 8,268,299
`
` v. :
`
` ALCON RESEARCH, LTD., :
`
`Patent Owner. :
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`Friday, April 13, 2018
`
`Washington, D.C.
`
`Deposition of:
`
`SOUMYAJIT MAJUMDAR,
`
`called for oral examination by counsel for the
`
`Petitioner, pursuant to notice, at the law offices
`
`of Williams & Connolly, LLP, 725 12th Street,
`
`Northwest, Washington, D.C. 20005, before
`
`Christina S. Hotsko, RPR, CRR, of Veritext Legal
`
`Solutions, a Notary Public in and for the District
`
`of Columbia, beginning at 8:42 a.m., when were
`
`present on behalf of the respective parties:
`
`www.veritext.com
`
`Veritext Legal Solutions
`
`Exhibit 1045
`ARGENTUM
`IPR2017-01053
`888-391-3376
`
`000001
`
`
`
`Page 2
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` A P P E A R A N C E S
`O n b e h a l f o f P e t i t i o n e r :
` M I C H A E L R . H O U S T O N , E S Q U I R E
` F o l e y & L a r d n e r , L L P
` 3 2 1 N o r t h C l a r k S t r e e t , S u i t e 2 8 0 0
` C h i c a g o , I l l i n o i s 6 0 6 5 4 - 5 3 1 3
` ( 3 1 2 ) 8 3 2 - 4 5 0 0
`
` T Y L E R L I U , J . D .
` A r g e n t u m P h a r m a c e u t i c a l s
` A s s o c i a t e G e n e r a l C o u n s e l
` 1 3 4 S p r i n g S t r e e t
` N e w Y o r k , N e w Y o r k 1 0 0 1 2
` ( 6 4 6 ) 4 0 5 - 6 3 0 0
`
`O n b e h a l f o f P a t e n t O w n e r :
` A L E X A N D E R Z O L A N , E S Q U I R E
` D A V I D M . K R I N S K Y , E S Q U I R E
` W i l l i a m s & C o n n o l l y , L L P
` 7 2 5 1 2 t h S t r e e t , N o r t h w e s t
` W a s h i n g t o n , D . C . 2 0 0 0 5
` ( 2 0 2 ) 4 3 4 - 5 0 0 0
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` C O N T E N T S
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`EXAMINATION BY: PAGE
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` Counsel for Petitioner 04
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`Page 3
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`MAJUMDAR DEPOSITION EXHIBITS: * PAGE
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`Exhibit 1041 USPTO Files 152
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`Exhibit 1042 USPTO Files 152
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`Exhibit 1043 Abstract 152
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`Exhibit 1044 Abstract 152
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` * (Exhibits attached to the transcript.)
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` P R O C E E D I N G S
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`Whereupon,
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` RUSSELL WERMERS,
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`being first duly sworn or affirmed to testify to
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`the truth, the whole truth, and nothing but the
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`truth, was examined and testified as follows:
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` EXAMINATION BY COUNSEL FOR PETITIONER
`
`BY MR. HOUSTON:
`
` Q. Good morning. Would we start by having
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`you state your full name for the record, please.
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` A. Sure. It's Soumyajit Majumdar. I'll
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`spell it out. S-O-U-M-Y-A-J-I-T. Last name is
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`Majumdar, M-A-J-U-M-D-A-R.
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` Q. Good morning, Dr. Majumdar.
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` A. Good morning.
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` Q. My name is Michael Houston. I'm an
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`attorney with Foley & Lardner representing the
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`petitioner Argentum in this proceeding.
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` Do you understand you're here today to
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`sit for a deposition related to a declaration that
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`you've submitted in this proceeding?
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` A. I do.
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` Q. Have you sat for a deposition previously?
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` A. Yes.
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` Q. About how many times would you say you've
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`been deposed?
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` A. I don't recollect offhand, but quite a
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`few.
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` Q. Okay. So multiple times?
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` A. Yes.
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` Q. So you're familiar with sort of the
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`process and how this works?
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` A. Sure.
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` Q. Okay. So in that case I'll kind of skip
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`some of the preliminary descriptions, since you're
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`familiar with it. But if you have any questions
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`or if I ask any questions today that are unclear
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`to you, please speak up and let me know.
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` A. Sure. You might as well go over it just
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`to make sure we were on the same ground.
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` Q. Well, the basic ground rules are that
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`I'll be asking you a series of questions today and
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`you'll be giving me your answers verbally so that
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`the court reporter can take down the things you
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`and I say.
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` And I would ask that unless your counsel
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`instructs you specifically not to answer, perhaps
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`to a privilege issue or something, that you go
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`ahead and answer my questions to the best of your
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`ability, even if your counsel puts an objection on
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`Page 6
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`the record.
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` Do you understand that?
`
` A. I do.
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` Q. One of the things we'll be talking about
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`today, one of the acronyms that I'm sure we'll be
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`using is a POSA, P-O-S-A. You're familiar with
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`that term, correct?
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` A. I am.
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` Q. And at the outset I thought I would just
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`mention that my intention is to use the same
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`definition of a POSA that you provide in your
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`declaration, which is a person of ordinary skill
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`in the art as of the time of the priority date for
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`the patent at issue here, which I believe is
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`September 2006. Okay?
`
` A. Okay.
`
` Q. I'd like to start by talking about some
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`of your own background and experience in this
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`field. In particular, I'd like to know about your
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`personal experience in developing self-preserved
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`aqueous-based ophthalmic solutions.
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` Can you tell me what work you've done in
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`that area in your professional background?
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` A. Could you just repeat that question one
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`more time, the last part?
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` Q. I would just like to know what work
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`you've done in your professional background
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`related to developing self-preserved aqueous-based
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`ophthalmic solutions.
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` A. So when I was working with, first,
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`Sandoz, and then Ciba and Novartis, there were
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`quite a few formulations we were working on which
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`had antibacterial agents. And they were by
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`themselves having enough activity to ward off any
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`microbial growth. So those were some of the
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`formulations that I worked with that were
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`self-preserved.
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` MR. KRINSKY: Can we go off the record a
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`second?
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` (Discussion off the record.)
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` THE WITNESS: And by -- so I'll continue?
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`BY MR. HOUSTON:
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` Q. Yes, please continue.
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` A. Yeah. So by self-preserved, we are
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`meaning which does not have a conventional
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`preservative.
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` Q. Okay. So just to break that down a
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`little bit, I think you said that while working
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`for a number of companies, you worked on
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`self-preserved ophthalmic solutions.
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` A. While -- basically, I've been in Sandoz,
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`which then merged with Ciba and became Novartis.
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`So it's a series of -- the same series
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`of companies.
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` Q. I see what you're saying. Okay.
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` Can you describe for me a little more
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`detail about those self-preserved ophthalmic
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`solutions that you worked on?
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` A. It's been a long time, so I really don't
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`know which agents. I can't remember which. But
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`there were antibacterial agents in combinations
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`with various polymers to enhance their activity.
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`So -- but it's been -- I don't really remember
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`offhand which ones.
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` Q. About when was that work?
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` A. Mostly it was once Sandoz merged with
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`Ciba, so it was somewhere in the -- starting '95
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`to '99, that area.
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` Q. So going back at least to 1995 to '99,
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`the concept of self-preserved ophthalmic solutions
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`was already known and being worked on in the
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`industry?
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` A. Oh, it was -- I mean, that's my personal
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`experience. The self-preserved was -- concept was
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`known, that if you -- there are some formulations
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`which could be unpreserved, and they could be
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`self-preserved because of the components in the
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`formulation.
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` Q. And so the formulations you worked on,
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`they were self -- =you said they had an
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`antimicrobial agent in them. Was it an
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`antimicrobial agent that was not a conventional
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`antimicrobial agent?
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` A. This was -- the drug itself was being
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`used to treat infections, so they are antibiotics,
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`and they are at a high enough concentration to
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`kill off any contamination. So it's not to
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`preserve the formulation. The main purpose of the
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`drug is to treat a disease. And in that process,
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`it preserves the formulation also because of --
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` Q. I see.
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` A. -- its inherent activity.
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` Q. So in that instance, the drug itself was
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`sort of its own preservative against microbial
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`contamination?
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` A. Yes. It by itself retards the growth.
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` Q. I see.
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` Have you worked -- in your professional
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`background, have you worked on any formulations
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`where you had to add a preservative package to a
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`solution -- in other words, where the active
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`ingredient itself was not self-preserving? Have
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`you worked on any situations like that?
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` MR. ZOLAN: Objection to form. Vague.
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` THE WITNESS: So are you talking about
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`ophthalmic formulations or any --
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`BY MR. HOUSTON:
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` Q. Yes, thank you for clarifying. Yes, I am
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`talking about ophthalmic formulations.
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` A. And solutions?
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` Q. Yes.
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` A. There are multiple, I mean, incidences
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`where we are using preservatives. So whenever the
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`components are not self-preserving, we would --
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`and if it's going to be a multi-dose formulation.
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`If it's a single-dose formulation, you don't need
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`a preservative.
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` If it's a multi-dose, I would be using
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`conventional or some preservative. If you mean by
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`preservative package -- are you saying -- could
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`you clarify on that?
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` Q. Yeah. I guess what I'm just thinking
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`of -- the first example you described for me was a
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`situation where the active ingredient itself was
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`active against microbes. And so I think you were
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`explaining that that was sort of the main -- it
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`was self-preserved in that aspect because the
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`active ingredient itself had that property.
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` What I was trying to get at is, have you
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`worked on any other formulations where the active
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`ingredient does not have this self-preservation
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`quality and you had to, therefore, formulate or
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`add in components specifically to achieve
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`preservative efficacy?
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` Do you have experience in that situation?
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` A. There have been -- and again, coming to
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`ophthalmic formulations or in general in
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`parenteral formulations that I worked on, there
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`are numbers of -- a number of cases where we have
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`to include preservatives to maintain
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`the preservative efficacy standards -- the
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`sterility of the formulations so that they pass
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`the preservative efficacy standards.
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` Q. And so do you have any experience in such
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`cases where you were using non-traditional
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`preservatives to achieve that as opposed to a
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`conventional preservative agent?
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` MR. ZOLAN: Objection to form. Vague.
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` THE WITNESS: So in terms of ophthalmic
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`formulations --
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`BY MR. HOUSTON:
`
` Q. Yes.
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` A. -- and solutions? Ophthalmic solutions?
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` Q. Yes.
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` A. I know I've used a lot of the
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`conventional preservatives. But I don't remember
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`if I've used any of the ones which are not
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`conventional.
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` Q. So, for example, you've never worked on
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`an ophthalmic solution formulation that contains
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`zinc as the preservative?
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` A. Personally, I've not made any
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`formulations with zinc as a preservative, as the
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`primary preservative or mainly being used as a
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`preservative in the composition.
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` Q. What about a formulation that uses a
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`Page 13
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`borate-polyol complex as the preservative? Have
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`you had any experience with those?
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` A. By experience with those, in terms of
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`actually making the formulations on my own?
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` Q. Well, working on a project where such a
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`product was being formulated. I -- I would
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`anticipate perhaps as part of a team, typically,
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`but you can tell me if that's incorrect.
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` A. I know about the borate-polyol complexes,
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`but I have not used it in -- as far as I know,
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`remember, sitting here, I don't think I've used
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`any of the borate-polyol complexes as the primary
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`preservative agent.
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` Q. The product that you mentioned earlier
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`that you worked on developing right as Sandoz was
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`merging into Ciba, if it's not confidential, can
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`you tell me what that product was?
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` A. That's what -- I don't really remember
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`what, because there were multiple projects which
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`could get assigned from Austria, and then we would
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`start working with it and then they would change.
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`So -- it's been some time, and I really don't
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`remember which ones.
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` Q. Okay.
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` A. And it was -- again, we used to work as
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`teams. So I was the team leader. And then there
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`would be multiple products under my team members,
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`and I would be leading them. So it's a little bit
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`hazy right now.
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` Q. Was that product ever commercialized?
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` A. One of them was. It was -- actually, one
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`or two of them were commercialized, but they
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`were -- I don't think they were -- I don't know
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`what was the preservative agent in the ones that
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`actually went into the market.
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` One was a lens cleaning tablet. And then
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`another one was a SOLO-CARE solution for, again,
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`cleaning lens. So I don't remember whether they
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`were the ones with a self-care preserve system or
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`they were just containing conventional
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`preservatives.
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` Q. Okay. So I'd like to ask you some
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`questions about what a POSA would do when they're
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`trying to work on developing a commercial
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`ophthalmic solution that's self-preserved.
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` Do you feel like you're qualified to
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`testify about that topic?
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` A. Oh, yes.
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` Q. Okay. When a POSA in 2006 set out to
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`develop an aqueous self-preserved ophthalmic
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`pharmaceutical product, what would their goals
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`have been? Can we start at a high level and then
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`perhaps we can drill down into some more detail?
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` A. So aqueous ophthalmic pharmaceutical for
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`humans?
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` Q. I want to cover the subject matter of the
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`'299 patent here.
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` A. Okay. So you are talking about the broad
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`objective of POSA wanting to develop a
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`self-preserved formulation or trying to develop a
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`formulation with a particular active ingredient in
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`mind?
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` Q. I think we can call it a
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`pharmaceutical -- I mean, the title of the '29
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`[sic] patent says it's a pharmaceutical
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`composition.
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` A. Okay.
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` Q. Does that signify that there's typically
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`going to be an active ingredient there, to call it
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`a pharmaceutical composition?
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` A. I mean, as a POSA, I would need a
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`clarification. Not just a pharmaceutical
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`composition. I could go in all kinds of direction
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`without really knowing where to land.
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` Is it -- what is the active? What is the
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`dose? What is the molecule -- the active that you
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`want to incorporate into the pharmaceutical? Does
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`it have toxic effects? What is the therapeutic
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`index? What is its stability? Is it an ester?
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`Is it a prodrug? Does it have permeability?
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` There are all kinds of things that a POSA
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`would like to know before he can start on a
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`project.
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` Q. Let's assume that it's travoprost. Are
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`you familiar with that drug?
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` A. Yes.
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` Q. Okay.
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` A. So develop a travoprost formulation with
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`the self -- which is a self-preserved.
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` Q. Right. So I would just like to know at a
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`high level what are the high-level concerns or
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`issues or goals that a POSA is going to have to
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`start to think about?
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` A. What's -- so he has -- coming back to
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`this, so the POSA is aware that there is a
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`Travatan formulation already in the market which
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`is optimized?
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` Q. Actually, thank you for asking. So
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`that's why I had mentioned earlier, when we're
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`talking about a POSA, I guess unless we
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`specifically say otherwise, I want it to be just
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`as of the priority date of the '299 patent, so
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`meaning before the '299 patent is filed.
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` So I think what you -- you said -- in
`
`your question, you mentioned Travatan. I don't
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`know for sure if you meant Travatan or Travatan Z.
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`But assuming you meant Travatan, I believe that
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`was on the market as of 2006 and was known.
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` MR. ZOLAN: Is that a question?
`
` MR. HOUSTON: I'm just trying to clarify
`
`the witness' question to me.
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` THE WITNESS: Right. So it's a very -- I
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`mean, the assignment to the POSA is not clear, so
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`if -- in my mind. So the POSA would be looking at
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`this formulation, which is already available in
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`the market. And you are saying that, okay,
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`make -- take the benzalkonium chloride out and
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`replace it with some self-preserved system?
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`BY MR. HOUSTON:
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` Q. You know, I'm not necessarily trying to
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`dictate that. I'm just trying to ask you what you
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`think a POSA would do if they are asked to develop
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`a self-preserved version of a travoprost
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`ophthalmic solution. And I just -- you know,
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`again, we can get into some details, but just at a
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`high level what are the things they're concerned
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`about?
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` A. Well, at a very high level, the main
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`factors that a POSA have to keep in mind is -- any
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`formulation, or any ophthalmic formulation --
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`safety, efficacy, stability.
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` Q. Okay. For efficacy of a given
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`formulation, was a POSA knowledgeable enough and
`
`capable enough to be able to test a given
`
`formulation for efficacy?
`
` A. A POSA is a hypothetical person who has
`
`multiple skills and is not one person. I mean, he
`
`has the skill himself --
`
` Q. Right.
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` A. -- of all kind -- a full team.
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` So he would be able to test. And in this
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`case, since the assignment is for a formulation
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`which is already known, for a pharmaceutical whose
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`activity is already known and established,
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`that's -- you just follow the formulation which
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`has already -- and the dose which has already been
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`established.
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` Q. Is that enough, to just follow the
`
`formulation and dose to establish efficacy, or
`
`would efficacy tests for the new formulation
`
`that's being developed have to be conducted?
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` A. So you have several layers of concepts in
`
`that question, which really we need to understand.
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` You -- if a POSA is given the task of
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`reformulating -- as you said, reformulating a
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`currently available formulation -- to make sure
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`that he or she doesn't fiddle or compromise the
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`efficacy and safety and stability of the
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`formulation, the POSA would make as little a
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`change in the formulation as possible.
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` Q. Okay. Let me try to circle back what I
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`think my original question was and just -- which
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`was just that, would a POSA have been able to
`
`conduct the tests to determine efficacy of their
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`new solutions, whatever they're testing. Are they
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`able to conduct efficacy tests?
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` A. Those would be standard practice if
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`needed. The pharmacologists would be there in
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`their team and they would be able to guide it.
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` Q. Another high-level goal you said a POSA
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`would be concerned with was the safety of the
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`product, right?
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` A. Correct.
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` Q. Okay. What things go into determining
`
`whether or not such a product would be safe?
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` A. And again, ophthalmic formulations --
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` Q. Yes. For this.
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` A. -- and solutions put in the eyedrop --
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`yeah, you do not want to cause -- there's always a
`
`tradeoff between risk and safety, so -- efficacy
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`and safety, actually.
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` So if it has a -- well, you should make
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`sure that it does not contain any agents or it
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`does not cause any reaction on the occular surface
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`like -- which is not acceptable, it doesn't
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`disrupt the corneal membrane or is not toxic to
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`the corneal cells or the conjunctival cells.
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` It doesn't -- basically it should not
`
`cause any harm to the biological tissues.
`
` Q. Would an aspect of product safety be
`
`avoiding particulates or precipitates in the
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`solution or would that fall under some other
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`category? Or would that not be a concern at all
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`of a POSA?
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` A. If it's a solution, it cannot have --
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`there are USP guidelines as to what the number of
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`particles can be. So you don't want particulates
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`in a solution formulation. So there should not
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`be -- if there is precipitation occurring, that
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`means a formulation is unstable. So that's a
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`stability -- it's a physical stability issue, not
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`a safety issue.
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` And of course, why there is a limit on
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`the particle size and -- if it's in suspension is
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`because those particles can cause problems on the
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`occular tissues.
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` But if you are talking about a solution
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`and then there are precipitation issues, then that
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`means that the formulation is physically unstable
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`and, in the long run, you could have efficacy --
`
`loss of activity or decreased efficacy.
`
` Q. Okay. Would a POSA be concerned with
`
`making sure the product stays sterile? And if so,
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`would that fall under the category of a safety
`
`issue or a stability issue? Or something else?
`
` A. Are you talking about a multi-dose
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`formulation ophthalmic solution?
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` Q. Yes.
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` A. They -- both are involved, actually. It
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`depends on which angle you're looking at it from.
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`From a formulator's point of view, microbial
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`stability or -- stability of the preservative is
`
`not being maintained.
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` From an application point of view, if it
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`has got contaminated, then there's a safety issue.
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` So the whole purpose of maintaining
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`sterility is to keep that formulation safe for
`
`use.
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` Q. And a POSA would have been aware that the
`
`types and the amounts of preservative agents
`
`incorporated into the product would affect those
`
`preservation properties; is that right?
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` A. A POSA would be aware how to preserve the
`
`ophthalmic solutions, if that is what you're
`
`meaning.
`
` Q. Well, I wanted to get a little more
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`specific. They'd be aware of how to preserve
`
`it -- at least one way they would be aware of that
`
`is in adjusting the types and amounts of
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`preservative agents in the formula; is that fair?
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` A. Yes. The preservatives which were known
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`at that point of time, the POSA would be able to
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`read the literature and know how to use them and
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`test for preservative efficacy.
`
` Q. In the context of the ophthalmic product
`
`we've just been discussing, what would a POSA have
`
`understood the term "antimicrobial" to mean?
`
` A. Antimicrobial encompasses microorganisms.
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`So antimicrobial means from a preservative which
`
`can act against bacteria or fungi microbes.
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` Q. And I think you said a POSA would know
`
`how to carry out the tests needed to -- the
`
`experiments needed to test for preservation
`
`ability or preservation efficacy; is that right?
`
` A. Yes.
`
` Q. So let's say a POSA is working on a given
`
`formulation and they test for preservative
`
`efficacy and that formulation does not pass the
`
`test. Okay?
`
` Are you with me so far?
`
` A. Which formulation? Any -- self-preserved
`
`or regular conventional preservative?
`
` Q. Yeah. My line of questioning right now
`
`-- I want to focus on what we've been talking
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`about, so trying to develop a self-preserved --
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` A. Okay.
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` Q. -- ophthalmic solution formulation that
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`contains travoprost.
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` A. Okay.
`
` Q. Okay? And let's say they've conducted a
`
`test on a given formulation that doesn't pass the
`
`preservative efficacy test. Okay?
`
` A. Uh-huh.
`
` Q. One of the things a POSA would think to
`
`do in that situation would be to alter the
`
`concentration of whatever their preservative agent
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`is, right?
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` A. I need to understand where the POSA --
`
`what information the POSA is basing his first test
`
`on.
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` Q. Okay. Can you help me understand -- I'm
`
`not sure I understand what you mean.
`
` A. Yeah. A person of ordinary skill is
`
`looking at the literature which is available to
`
`him, and he's trying to use the information to
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`develop a self-preserved formulation. We are not
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`talking about invention, correct? So he is trying
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`to find out what the literature -- how the
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`literature guides him towards a self-preserved
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`formulation.
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` So now, depending on what path he has
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`chosen -- like, there could be multiple guidance
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`out there in the literature at that point of time.
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`So depending on what he has used as his base to
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`start on the first experiment, only -- if I know
`
`that, I can answer that. Otherwise, there would
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`be -- he would have based his first experiment on
`
`some data. So it's too -- that information is
`
`missing.
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` So unless I have that information, then
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`it's difficult to say why it's failing and, based
`
`on that, you would analyze that situation.
`
` Q. So let's say that the formulation that
`
`the POSA is experimenting with to begin with,
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`they're trying to use zinc as their preservative
`
`agent. Okay?
`
` A. Okay.
`
` Q. And they conduct -- are the preservative
`
`efficacy tests standardized? Are there standard
`
`preservative efficacy tests that exist for this
`
`type of issue? For example, the USP27 I think
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`I've seen reference to.
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` A. There are several compendial tests that
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`are there.
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` Q. So let's say a POSA makes up a
`
`formulation, puts zinc in it to try to act as the
`
`preservative, and it fails.
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` Would one of the things a POSA would
`
`consider doing is changing the zinc concentration?
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` A. And again, to bring it back to the
`
`example, so you have this -- you have this
`
`standard formulation. You have taken out
`
`benzalkonium chloride. And zinc -- I'm presuming
`
`in this case you have already got a reference,
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`like Xia, which teaches you how to use zinc in the
`
`formulations. And you have examples which the
`
`POSA would look at the various options available
`
`and choose a formulation which best fits his
`
`situation and he would use that concentration of
`
`zinc.
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` And based on that, even after doing that,
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`there would be a -- I mean, the expectation would
`
`be that if -- like, in this case, if you match the
`
`formulation which -- I think formulation 8 was the
`
`closest to this travoprost formulation, Travatan
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`formulation -- there is high expectation, and it
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`is that it is going to pass.
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` If, counter-expectation, the formulation
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`does not meet the preservative efficacy standards,
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`there could be several approaches that he can
`
`take. And this is all under the hypothesis that
`
`for some reason the POSA has decided to go for
`
`zinc. Because there were other options that he
`
`could have looked at.
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` Q. Okay. So let me back up because,
`
`actually, I don't want to get you hung up on the
`
`idea of it being zinc. And I know that's
`
`obviously a very hot topic in this particular
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`proceeding.
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` So we can even just talk more generally
`
`about the set of tests.
`
` What I'm trying to get at is, for a given
`
`formulation that a POSA is attempting to get to be
`
`self-preserved, if it -- if an initial formulation
`
`doesn't pass preservative efficacy, is at least
`
`one of the options a POSA is going to think about
`
`changing the concentration of the preservative
`
`that's being used?
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` A. Actually, backing up even further and
`
`making it more general, the POSA's goal, like you
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`put it initially, would be to develop a
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`self-preserved formulation, not bother about what
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`is the active. You are trying to develop a
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`self-preserving formulation.
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` So he would look at various options which
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`are out there. And then -- one of the ways is
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`like what Dr. Xia did, build that system. And you
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`try various concentrations of that new system and
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`see which one works. And --
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` Q. So -- yeah, so I think that's what I'm
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`getting at. Why would a POSA try various
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`concentrations? Is it because preservatives are
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`known to have a concentration-dependent
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`antimicrobial behavior?
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` A. It depends, again, what is the molecule
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`that you are looking at. Now, one thing is the
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`POSA is looking at literature, which is all
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`available. There is a distinction between
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`inventing versus looking at the literature.
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` Now, why I said there's a distinction is
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`because there are some chemicals which will just
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`act like boring holes into the microbes as a
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`surfactant system and they kill it. So the
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`microbes do not have any use for them, they do not
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`888-391-3376
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`Veritext Legal Solutions
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`know how to deal with them. They just -- either
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`the concentration is sufficient enough to not
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`kill, and it's not at enough concentration to meet
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`the preservative efficacy, And then, as you go on
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`increasing the concentration, it will meet the
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`preservative efficacy, and then if you go at too
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`high a concentration, then it becomes toxic to the
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`mammalian cells.
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` But there are some -- you have to be
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`cautious about some situations where -- like for
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`zinc, which can actually be u
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