UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`SLAYBACK PHARMA LLC,
`
`Petitioner,
`
`v.
`
`EYE THERAPIES, LLC,
`
`Patent Owner.
`
`__________________
`
`Case IPR2022-00142
`U.S. Patent No. 8,293,742
`__________________
`
`DECLARATION OF ROBERT O. WILLIAMS, III, Ph.D.
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`I.
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`II.
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`III.
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`Case IPR2022-00142
`Declaration of Robert O. Williams, III, Ph.D.
`Table of Contents
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`QUALIFICATIONS AND BACKGROUND ................................................. 1
`Education and Experience ..................................................................... 1
`Documents and Information Considered in Forming Opinions ............ 4
`Scope of Work, Compensation.............................................................. 4
`Testimony as Expert in Last Four Years ............................................... 6
`LEGAL STANDARDS ................................................................................... 6
` Validity .................................................................................................. 6
`1.
`Anticipation ................................................................................. 6
`2.
`Obviousness ................................................................................ 7
`Claim Construction................................................................................ 8
`STATEMENTS OF OPINIONS EXPRESSED AND BASES AND
`REASONS THEREFOR ................................................................................. 8
` U.S. Patent No. 8,293,742 ..................................................................... 8
`A Person of Ordinary Skill in the Art .................................................10
`Claim Construction..............................................................................13
`1.
`“about 0.025%” .........................................................................13
`“about 0.025%” means “0.025% plus or minus 10%,” equating to an
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`upper limit of 0.0275% ................................................................................14
`Specific Responses to Dr. Lasker’s opinions regarding “about 0.025%”
`
`17
`Technical Tutorial: Pharmaceutical Development ..............................19
`Overview of References Cited by Dr. Laskar .....................................21
`1.
`Alphagan® Label 1998 (EX-1008)............................................22
`2.
`Derick 1997 (EX-1027) ............................................................23
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`Declaration of Robert O. Williams, III, Ph.D.
`3.
`Federal Register 1988 (EX-1009) .............................................25
`Pasquali 2013 (EX-1025) ..........................................................27
`4.
`Scruggs 2000 (EX-1023) ..........................................................30
`5.
`U.S. Patent No. 6,294,553 (EX-1004) ......................................30
`6.
`U.S. Patent No. 6,562,873 (EX-1033) ......................................33
`7.
`8. Walters 1991 (EX-1005) ...........................................................35
`Response to Dr. Laskar’s Description of the “Background to the
`’742 Patent” .........................................................................................36
` Dr. Laskar’s Description of the ’742 Patent........................................38
`Response to Dr. Laskar’s Opinion that “A POSA Was Motivated
`to Formulate at a pH between about 5.5 and about 6.5” .....................38
`Response to Dr. Laskar’s Opinion that a “It Was Routine for a
`POSA to Formulate Brimonidine Ocular Drops at Any
`Concentration Between 0.001% and 0.05% and at Any pH
`between about 5.5 and about 6.5” .......................................................45
`Dr. Laskar’s Opinion Regarding “Dose Ranging” ..............................50
` Dr. Laskar’s Opinion Regarding the “Proper Comparison to the
`Prior Art” .............................................................................................51
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`ii
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`I.
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`Case IPR2022-00142
`Declaration of Robert O. Williams, III, Ph.D.
`QUALIFICATIONS AND BACKGROUND
` Education and Experience
`1.
`I, Robert O. Williams, III, Ph.D., submit this declaration at the request
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`of Patent Owner Eye Therapies, LLC (“Eye Therapies” or “the Patent Owner”) as
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`an expert in the design and evaluation of drug products. I understand that this
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`declaration is being submitted in support of the Patent Owner’s Response in
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`connection with IPR2022-00142. My qualifications in these areas, as well as other
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`areas, are established below and by my curriculum vitae, which is attached as
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`Appendix A.
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`2.
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`I am currently the Johnson & Johnson Centennial Chair and Professor
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`in the Division of Molecular Pharmaceutics and Drug Delivery at the University of
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`Texas at Austin College of Pharmacy in Austin, Texas, where I have been teaching
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`and conducting research since 1995. I am also the Division Head of Molecular
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`Pharmaceutics and Drug Delivery.
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`3.
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`I received a B.S. degree in biology from Texas A&M University in
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`1979, a B.S. degree in pharmacy from The University of Texas at Austin in 1981,
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`and a Ph.D. degree in pharmaceutics from The University of Texas at Austin in 1986.
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`I am a licensed pharmacist.
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`4.
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`I have extensive experience and expertise
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`in pharmaceutical
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`formulation and the use of excipients in formulating various types of drug dosage
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`1
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`forms. I am an expert in the field of pharmaceutical development, and I have worked
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`almost exclusively in the field of pharmaceutical development since 1986. While I
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`am not an FDA expert, I work with team members who are FDA experts and have
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`knowledge of relevant FDA regulations governing drug products. Based on my
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`experience, I am also generally familiar with FDA guidance and testing
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`requirements.
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`5.
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`Prior to becoming a professor, I worked in the pharmaceutical industry
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`for several companies including Rhone-Poulenc Rorer Pharmaceuticals, Duramed
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`Pharmaceuticals, and Eli Lilly and Company. Additionally, from 1996 to 2007, I
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`was co-founder and President of PharmaForm, a contract pharmaceutical laboratory,
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`and from 2007 to mid-2010, I was a director of Akela Pharma. I was the Chief
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`Scientist and co-founder of Enavail from 2009 to 2013, a particle engineering
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`contract services company founded based on intellectual property on which I am a
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`co-inventor. I am a scientific consultant to TFF Pharmaceuticals, Inc, a company
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`founded based on intellectual property on which I am a co-inventor. Accordingly, I
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`have relevant industry experience in addition to my academic qualifications.
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`6. My current research focuses on the development, formulation,
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`optimization, and delivery of drugs by a variety of technologies. I have extensive
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`research experience and have authored numerous publications in this area.
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`2
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`Declaration of Robert O. Williams, III, Ph.D.
`I have authored or co-authored over 500 published papers, abstracts,
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`7.
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`books, and book chapters related to my work in the pharmaceutical sciences. A
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`significant number of my papers are directed specifically to pharmaceutical
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`formulation techniques and drug dosage forms. I am a co-inventor on over 40 patents
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`and/or patent applications that deal with drug formulation technology.
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`8.
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`Over the course of my career, I have earned numerous prestigious
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`professional awards and honors, which are described in my curriculum vitae. For
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`example, I was elected as a fellow to the American Association of Pharmaceutical
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`Scientists, the American Institute of Medical and Biological Engineering, and the
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`National Academy of Inventors. I have also received the William J. Sheffield
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`Outstanding Alumnus Award and was a Dean’s Fellow at the University of Texas at
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`Austin College of Pharmacy. I was also awarded the 2017 University of Texas at
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`Austin’s Inventor of the Year Award. I received in 2021 the College of Science
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`Academy of Distinguished Former Students Award at Texas A&M University.
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`9.
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`I am currently the Editor-in-Chief for AAPS PharmSciTech, an official
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`joint publication of the American Association of Pharmaceutical Scientists and
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`Springer Nature Publishing. I was the Editor-in-Chief for Drug Development and
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`Industrial Pharmacy from 2000 to 2014. I am a member of the Editorial Advisory
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`Board for Journal of Drug Delivery Science and Technology and International
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`Journal of Pharmaceutics. I also have served or currently serve as a reviewer for
`
`3
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`Case IPR2022-00142
`Declaration of Robert O. Williams, III, Ph.D.
`many scientific journals, including International Journal of Pharmaceutics,
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`Pharmaceutical Research, Molecular Pharmaceutics, European Journal of
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`Pharmaceutics and Biopharmaceutics, Journal of the Controlled Release Society,
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`Pharmaceutical Development and Technology, AAPS PharmSciTech, Journal of
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`Pharmaceutical Sciences, and Journal of Pharmaceutical and Biomedical Analysis.
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`10.
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`In addition to my research and teaching duties at the University of
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`Texas at Austin, I have consulted for pharmaceutical, chemical, and biotechnology
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`companies. I have consulted for both innovator pharmaceutical companies and
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`generic pharmaceutical companies. Most of these consulting activities have dealt
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`specifically with drug formulation issues.
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` Documents and Information Considered in Forming
`Opinions
`In forming my opinions, I had available the documents cited herein and
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`11.
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`in Appendix B as well as the publications listed in my curriculum vitae at Appendix
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`A. I additionally have based my opinions on my professional and academic
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`experience in the area of pharmaceutical formulation. I reserve the right to testify
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`about these materials and experience.
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`12.
`
`Scope of Work, Compensation
`I have been retained by counsel for Eye Therapies in this matter. I have
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`been asked to consider a POSA’s understanding of the term “about” as it is used in
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`the claims of the ’742 patent and to respond to certain arguments advanced by Dr.
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`Laskar in connection with his opinion regarding the construction of “about 0.025%.”
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`I have also been asked to consider (1) whether a POSA would have been motivated
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`to target a pH between about 5.5 and about 6.5 for a composition with brimonidine
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`at a concentration of about 0.001% to about 0.05% or between about 0.001% and
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`about 0.025%; and (2) whether a POSA could have arrived at the claimed
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`brimonidine composition with a concentration between about 0.001% and about
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`0.025% and a pH between about 5.5 and about 6.5 through routine experimentation.
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`13.
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`I will be compensated for my time preparing for and testifying in this
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`matter at the rate of $650 per hour. No part of my compensation is contingent upon
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`the outcome of this matter or any issue in it.
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`14. To the extent I am provided additional documents or information,
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`including any expert declarations produced by Slayback Pharma LLC (“Petitioner”
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`or “Slayback”) or additional documents produced by the Petitioner, I may offer
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`further opinions. In addition to these materials, I may consider additional documents
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`and information in forming any rebuttal opinions. Additionally, I reserve the right to
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`prepare one or more visual aids or demonstratives to illustrate my opinions,
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`including at trial. I also reserve the right to provide a technical tutorial to provide
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`additional background information on my opinions.
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`5
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` Testimony as Expert in Last Four Years
`15. Appendix C to this Declaration is a list of the cases where I have
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`testified at deposition and/or trial in the last four years.
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`II. LEGAL STANDARDS
`16.
`I have no formal legal training, but I have been informed by Patent
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`Owner’s counsel about the appropriate legal standards as set forth below and I have
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`applied these standards in rendering my opinions. I reserve the right to supplement
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`my report to take into account any modifications to these standards, if I am informed
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`of such.
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` Validity
`17.
`I have been informed that the U.S. patent statute provides that issued
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`patents are presumed valid over the prior art.
`
`1.
`Anticipation
`I have been informed and understand that anticipation requires that
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`18.
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`every claim element of that claim must be found in a single prior art reference
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`arranged as in the claim. I have been informed and understand that if a prior art
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`reference does not expressly disclose every element of a claim, anticipation may be
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`found if the undisclosed claim element is inherent in the prior art’s disclosure. I
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`understand, however, that to find an inherent disclosure, the later-claimed
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`invention’s inherent features must be necessarily and inevitably present in the
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`reference, and not the result of probabilities, possibilities, or possible outcomes.
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`6
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`Declaration of Robert O. Williams, III, Ph.D.
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`2. Obviousness
`I have been informed and understand that to find a patent claim invalid
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`19.
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`for obviousness, the claimed invention, as a whole, when considered against the
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`prior art taken as a whole would have had to have been obvious to a person having
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`ordinary skill in the art at the time the invention was made. I understand that, in
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`making an obviousness determination, it is improper to consider the prior art with a
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`hindsight bias based on the teachings of the patent. One must not use the patent as a
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`template to suggest how the elements of the prior art could have been combined.
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`20.
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`I have also been informed and understand that the claimed invention
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`and the prior art must each be looked at “as a whole.” One must also consider those
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`portions of the prior art that “teach away” from the claimed invention. It is not
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`sufficient to consider an isolated portion of one reference that is similar to what the
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`patent discloses and claims, if either the reference as a whole or another reference or
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`the prior art as a whole teaches or suggests something different from that isolated
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`portion. I also understand that, in resolving whether an invention is obvious based
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`on the teachings of multiple references, one must consider whether the combination
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`yields no more than predictable results or achieves an unexpected result.
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`21.
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`I have also been informed and understand that, in determining whether
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`or not a patented invention would have been obvious, the following factors must be
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`considered: the scope and content of the prior art, the differences between the prior
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`Declaration of Robert O. Williams, III, Ph.D.
`art and the claims at issue, the level of ordinary skill in the art, and whatever
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`objective indicia of non-obviousness may be present.
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` Claim Construction
`22.
`I have been informed and understand that the patent claims, and their
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`terms and phrases, are interpreted according to their ordinary and customary
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`meaning to a person of ordinary skill in the art at the time of filing. I understand that
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`interpreting a term or phrase contained in a patent claim involves reading the
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`language of the claim and considering other materials relevant to the claim,
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`including the patent specification and the prosecution history. I understand that the
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`patent specification and prosecution history may collectively be referred to as the
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`“intrinsic record.” I understand that evidence outside of the patent and its
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`prosecution history may also be consulted, but that such materials should only be
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`considered so long as they are not inconsistent with the claim language, the patent
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`specification, and the prosecution history. I understand that such evidence may be
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`referred to as “extrinsic evidence.”
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`III. STATEMENTS OF OPINIONS EXPRESSED AND BASES AND
`REASONS THEREFOR
` U.S. Patent No. 8,293,742
`23.
`I have reviewed U.S. Patent No. 8,293,742 (“the ’742 patent”) and its
`
`prosecution history. I understand that the ’742 patent claims priority to an
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`application that was filed on August 1, 2008. Specifically, I understand that the ’742
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`patent claims priority to U.S. Provisional Application 61/207,481 filed February 12,
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`2009; U.S. Provisional Application 61/203,120 filed December 18, 2008; U.S.
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`Provisional Application 61/192,777 filed September 22, 2008; and U.S. Provisional
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`Application 61/137,714 filed August 1, 2008. (EX-1001 (’742 patent) at p. 1.)
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`24. Generally speaking, the ’742 patent claims, inter alia, methods for
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`reducing eye redness consisting essentially of administering brimonidine to a patient
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`having an ocular condition, wherein the brimonidine is present at a concentration
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`between about 0.001% w/v and about 0.05% w/v. (EX-1001 (’742 patent) at
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`Abstract, Claims 1-6.) I understand that Dr. Noecker will describe the state of the
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`art, as it relates to redness relieving eye drops and brimonidine, as well as the
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`inventor’s unexpected discovery.
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`25.
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`Independent claim 1 of the ’742 patent is directed, generally speaking,
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`to a method for reducing eye redness consisting essentially of administering
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`brimonidine to a patient having an ocular condition, wherein brimonidine is present
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`at a concentration between about 0.001% weight by volume and about 0.05% weight
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`by volume. (EX-1001 (’742 patent) at 22:17-21.)
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`26. Dependent claim 2 of the ’742 patent is directed, generally speaking, to
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`the method of claim 1, wherein brimonidine is present at a concentration between
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`about 0.001% to about 0.025% weight by volume. (EX-1001 (’742 patent) at 22:22-
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`24.)
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`Independent claim 3 of the ’742 patent is directed, generally speaking,
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`27.
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`to a method for reducing eye redness consisting essentially of topically
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`administering to a patient having an ocular condition a composition consisting
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`essentially of brimonidine into ocular tissue, wherein pH of said composition is
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`between about 5.5 and about 6.5, wherein said brimonidine concentration is between
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`about 0.001% and about 0.025% weight by volume and wherein said composition is
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`formulated as an ocular drop. (EX-1001 (’742 patent) at 22:25-32.)
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`28. Dependent claim 4 of the ’742 patent is directed, generally speaking, to
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`the method of claim 3, wherein said composition is topically administered within
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`about 24 hours after a Lasik surgery on said patient. (EX-1001 (’742 patent) at 22:33-
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`35.)
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`29. Dependent claim 5 of the ’742 patent is directed, generally speaking, to
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`the method of claim 1, wherein said ocular condition is chronic red eye. (EX-1001
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`(’742 patent) at 22:36-37.)
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`30. Dependent claim 6 of the ’742 patent is directed, generally speaking, to
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`the method of claim 3, wherein said ocular condition is chronic red eye. (EX-1001
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`(’742 patent) at 22:38-39.)
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` A Person of Ordinary Skill in the Art
`31.
`I understand that Dr. Noecker will explain that the field to which the
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`’742 patent pertains is interdisciplinary. Thus, I understand that Dr. Noecker will
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`explain that a person of ordinary skill in the relevant art may be represented by a
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`team of individuals with experience and various skills relating to eye care, including,
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`inter alia, the medical and pharmaceutical formulation arts. I further understand that
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`Dr. Noecker will explain that a person of ordinary skill in the relevant art may also
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`have been part of or have access to a team of individuals with experience in
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`chemistry, in designing and evaluating ophthalmic formulations, and/or in
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`administering ophthalmic formulations to treat ocular conditions obtained by some
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`combination of education and work experience.
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`32.
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`I understand that Dr. Noecker will explain that the medical doctor is a
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`specialist in treating diseases of the eye, such as an optometrist or ophthalmologist,
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`with three to four years of experience, who also has experience designing and
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`running clinical
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`trials on ophthalmic formulations. In my opinion,
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`the
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`pharmaceutical formulator had a Bachelor’s degree in pharmaceutics or a related
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`discipline with about three to five years of work experience in this area, or a
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`comparable level of education and training, such as a Ph.D. with one to two years of
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`experience in this area.
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`33.
`
`In light of the above, I understand that Dr. Noecker will explain that the
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`POSA should be defined as follows: The POSA is a composite person engaged in
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`developing pharmaceutical formulations and treatment methods for the eye, and
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`includes a medical doctor and pharmaceutical formulator with the qualifications
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`outlined above. This person may also work in collaboration with other scientists
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`and/or clinicians who have experience with chemistry; developing, designing, and/or
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`evaluating ophthalmic formulations; administering ophthalmic formulations;
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`running clinical trials related to such formulations; and/or treating patients using
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`such formulations.
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`34.
`
`I understand that the Petitioner contends that “[a] POSA was a
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`composite person (or team) that included a medical doctor and a pharmaceutical
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`formulator.” (Petition at § I.C.) I understand that the Petitioner further contends that
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`“[t]he medical doctor was an ophthalmologist with at least three to four years of
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`experience in LASIK surgery, clinical trials and U.S. FDA regulation of eye
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`products, and had experience in the use of topical brimonidine and apraclonidine and
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`topical vasoconstrictors such as naphazoline and tetrahydrozoline” and that “[t]he
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`pharmaceutical formulator had a doctorate in pharmaceutics or a related degree and
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`at least three to five years of experience developing eye drop formulations for
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`clinical trial and regulatory approval.” (Id.) In my opinion, the qualifications that the
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`Petitioner attributes to a POSA go far beyond those of a person of ordinary skill. In
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`any event, my opinions expressed herein would not change regardless of which
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`definition is applied.
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`compositions, and the criticality of the claimed concentration. (See EX-1003 (Laskar
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`Decl.) at ¶¶ 64-71.) I understand that Dr. Noecker will respond to these arguments,
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`which relate to his area of particular expertise. I also understand that Dr. Noecker
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`will explain that a person of ordinary skill in the art would not have understood
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`“about 0.025%” to include “0.03%.”
`
` “about 0.025%” means “0.025% plus or minus 10%,”
`equating to an upper limit of 0.0275%
`39. Dr. Laskar contends that “from the perspective of a pharmaceutical
`
`formulator, ‘about 0.025%’ includes ‘0.03%’ because, as the upper limit of a range,
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`a concentration of ‘about 0.025%’ rounded up to two decimal points is ‘0.03%.’”
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`(EX-1003 (Laskar Decl.) at ¶ 72)). I disagree.
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`40. As an initial matter, in my opinion, a person of ordinary skill in the art
`
`would have understood the word “about” to mean “plus or minus 10%,” which
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`means that “about 0.025%” would have an upper limit of 0.0275%.
`
`41. When considering the construction of the term “about” in the context
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`of a pharmaceutical patent, it is important to note that a POSA formulator—under
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`either Petitioner’s definition or Patent Owner’s definition—has significant
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`experience in the pharmaceutical arts and would have, or would have access to a
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`team member who has, experience with the FDA and knowledge of relevant FDA
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`regulations governing drug products.
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`42. For example, a POSA would have understood that as of the priority
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`date, and today, there is an inherent degree of imprecision in the manufacturing
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`process, which can result in minor variations within and across batches. (See e.g.,
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`EX-2025 (USP 32) at 4.) The FDA recognizes this and thus allows certain tolerance
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`to the amount of an active ingredient in a drug product. (EX-2026 (FDA Guidance
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`Q6A) at 83044-83045 (“When a specification is first proposed, justification should
`
`be presented for each procedure and each acceptance criterion included . . . a
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`reasonable range of expected analytical and manufacturing variability should be
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`considered.”).)
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`43. This tolerance is reflected in the acceptance criteria for the testing
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`required by regulatory authorities. ((EX-2026 (FDA Guidance Q6A) at 83045.)
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`Indeed, a POSA would have understood that FDA requires certain tests for all drug
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`products. (EX-2027 (Remington’s) at 10.) One of those tests is an “assay,” which
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`determines the amount of the active pharmaceutical ingredient present in the drug
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`product. (Id.) The acceptance criteria for the assay is expressed as a percentage of
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`the label claim. (Id. at 11.) Typical acceptance criteria are in the range from 90.0 to
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`110.0 percent of the label claim. (Id.)
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` The tolerance for the amount of an active ingredient is reflected in the acceptance
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`Case IPR2022-00142
`Declaration of Robert O. Williams, III, Ph.D.
`criteria for drug products approved by the FDA for sale in the United States, and
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`would have been known by a POSA.
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`44.
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`In the pharmaceutical formulation context, the term “about” is often
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`used to express quantities for assays and tests. Indeed, the U.S. Pharmacopoeia1
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`explicitly provides a definition for the term “about” in this context. (EX-2025 (USP
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`32) at 8.) Specifically, the USP explains that in stating the appropriate quantities to
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`be taken for assays and tests, the use of the word “‘about’ indicates a quantity within
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`10%” of the specific weight or volume. (Id.) Accordingly, with respect to quantities
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`such as weight percentages of excipients in a formulation, a POSA would understand
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`that the term “about” would include values within 10% of the specified value.
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`45. Based on the above and my experience, in my opinion, a POSA would
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`have understood the word “about” to encompass plus or minus 10%. This is
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`consistent with the definition of “about” in the USP and is consistent with the typical
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`label claim acceptance criteria for FDA-approved drug products. A person of
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`1 The U.S. Pharmacopeia develops and publishes standards for in the United States
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`Pharmacopeia-National Formulary. (EX-2029 (USP - Legal Recognition) at 1.) The
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`USP standards have long been recognized by the FDA and the USP-NF has been
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`deemed an “official compendium.” (Id.)
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`Case IPR2022-00142
`Declaration of Robert O. Williams, III, Ph.D.
`ordinary skill in the art would thus have understood the upper end of “about 0.025%”
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`to be 0.0275%.
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` Specific Responses to Dr. Lasker’s opinions regarding
`“about 0.025%”
`46. As an initial matter, I note that Dr. Laskar’s opinion has no support in
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`the intrinsic record. Indeed, there is nothing in the ’742 patent that suggests that the
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`term “about” should be interpreted based on abstract principles such as rounding or
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`the number of significant figures and, importantly, as described above, that is not
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`how a POSA formulator would understand the term “about” in the context of this
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`pharmaceutical patent. Doing as Dr. Laskar suggests—relying on rounding—relies
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`on a very elementary scientific principle, when there is no support in the intrinsic
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`record for doing so.
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`47. Further, in my opinion, the POSA formulator according to Dr. Laskar’s
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`definition, would not have understood the word “about” to encompass 0.03%, which
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`equates to about 18% higher than the upper end of the recited range, well outside
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`the FDA’s general tolerance for the active ingredient. (EX-2027 (Remington’s) at
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`11.) Tellingly, in Dr. Laskar’s opinion, the POSA formulator “had a doctorate in
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`pharmaceutics or a related degree and at least three to five years of experience
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`developing ocular drop formulations (commonly referred to as eye drops) for clinical
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`trial and regulatory approval.” (EX-1003 (Laskar Decl.) at ¶ 29). But Dr. Laskar’s
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`opinion is inconsistent with the typical acceptance criteria range for FDA-approved
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`drug products.
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`48. Specifically, the acceptance criteria for the amount of the active
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`pharmaceutical ingredient present in the drug product relative to the label claim
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`would inform a person of ordinary skill in the art’s understanding of the range that
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`“about” imparts to “about 0.025%.” As described above, this is reflected in the
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`acceptance criteria for the assay testing, which is typically 90.0 to 110.0 percent of
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`the label claim. (EX-2027 (Remington’s) at 11.) But Dr. Laskar ignores this in favor
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`of rounding. To be clear, I do not dispute that 0.025 would round up to 0.03, if
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`rounding to one significant figure, which Dr. Laskar appears to be suggesting would
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`be done. (EX-1003 (Laskar Decl.) at ¶ 72.) But, in my opinion, based on my
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`experience, a POSA would not look to round 0.025% to one significant figure.
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`49.
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`In the pharmaceutical industry, it is important to be as accurate and
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`precise as possible, but the degree of accuracy and precision that can be attained is
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`often dictated by the equipment. Significant figures represent the degree of precision
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`for a particular measuring tool. The same would be true with respect to the ’742
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`patent, which is clearly a pharmaceutical patent.
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`50. The specification and the claims of the ’742 patent further support my
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`opinion. I understand that Dr. Noecker will explain that the ’742 patent separately
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`discloses concentrations of “about 0.025%” brimonidine and “about 0.03%”
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`Declaration of Robert O. Williams, III, Ph.D.
`brimonidine within the broader concentration range of less than 0.05%. I also
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`understand that Dr. Noecker will explain that the ’742 patent describes distinct
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`compositions with 0.025% brimonidine and 0.03% brimonidine. I further understand
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`that Dr. Noecker will explain that the ’742 patent describes the clinically significant
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`differences between compositions containing 0.025% brimonidine and compositions
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`containing 0.03% brimonidine. A POSA would understand that the ’742 patent
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`recognizes a distinction between these two concentrations and would not arbitrarily
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`round 0.025% up to 0.03%. This is further confirmed by the label for the FDA-
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`approved product, Lumify®, which I understand Dr. Noecker will explain contains
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`brimonidine at a concentration of 0.025%. For at least these reasons, it i