IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`MYLAN PHARMACEUTICALS INC.
`Petitioner,
`v.
`MERCK SHARP & DOHME CORP.
`Patent Owner.
`U.S. Patent No. 7,326,708 to Cypes et al.
`Issue Date: February 5, 2008
`Title: Phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor
`Inter Partes Review No.: IPR2020-00040
`
`Declaration of Dr. Mukund Chorghade, Ph.D.
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`DRL Ex. 1002, p. 001
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`Table of Contents
`INTRODUCTION ........................................................................................... 1
`I.
`II. MY EXPERIENCE AND QUALIFICATIONS ............................................. 3
`III.
`LIST OF MATERIALS CONSIDERED ......................................................10
`IV.
`LEGAL STANDARD ...................................................................................12
`A.
`Anticipation .........................................................................................12
`B.
`Obviousness .........................................................................................13
`BACKGROUND ...........................................................................................16
`V.
`PERSON OF ORDINARY SKILL IN THE ART (“POSA”) .......................17
`VI.
`VII. THE ’708 PATENT .......................................................................................18
`VIII. CLAIM CONSTRUCTION ..........................................................................23
`IX. ANTICIPATION ...........................................................................................25
`A.
`Ground 1: WO 03/004498 anticipates Claims 1-3, 17, 19, and
`21-23 of the ’708 patent ......................................................................25
`1.
`Disclosure of WO ’498 .............................................................26
`2.
`Claim 1 of the ’708 Patent ........................................................36
`3.
`Claim 2 of the ’708 Patent ........................................................39
`4.
`Claim 3 of the ’708 Patent ........................................................39
`5.
`Claim 17 of the ’708 Patent ......................................................40
`a)
`A pharmaceutical composition comprising ....................41
`b)
`a therapeutically effective amount of the salt
`according to claim 2 .......................................................41
`in association with one or more pharmaceutically
`acceptable carriers. .........................................................42
`Claim 19 of the ’708 Patent ......................................................42
`a)
`A method for the treatment of type 2 diabetes
`comprising ......................................................................42
`
`c)
`
`6.
`
`i
`
`DRL Ex. 1002, p. 002
`
`

`

`X.
`
`Declaration of Mukund Chorghade, Ph.D.
`
`b)
`
`d)
`
`B.
`
`administering to a patient in need of such treatment
`a therapeutically effective amount of the salt
`according to claim 2 or a hydrate thereof. ......................42
`Claims 21-22 of the ’708 Patent ...............................................43
`7.
`Claim 23 of the ’708 Patent ......................................................45
`8.
`Ground 2: Claims 1-3, 17, 19, and 22-23 Are Anticipated by the
`’871 Patent ...........................................................................................46
`1.
`Disclosure of the ’871 Patent ....................................................46
`2.
`Claims 1 and 2 ...........................................................................46
`3.
`Claim 3 ......................................................................................47
`4.
`Claims 17 and 19.......................................................................48
`5.
`Claim 21 ....................................................................................50
`6.
`Claim 22 ....................................................................................51
`7.
`Claim 23 ....................................................................................51
`OBVIOUSNESS ............................................................................................51
`A.
`Ground 3: Claims 3, 17, 19, and 21-23 Would Have Been
`Obvious in View of WO ’498 .............................................................52
`1.
`The Level of Ordinary Skill in the Pertinent Art ......................52
`2.
`The Scope and Content of the Prior Art ...................................52
`a) WO ’498 (EX1004) ........................................................52
`b)
`Claim 3 ............................................................................52
`c)
`Claim 17 ..........................................................................54
`“A pharmaceutical composition comprising” ......54
`“A therapeutically effective amount of the
`salt according to claim 2” .....................................54
`“In
`association with one or more
`pharmaceutically acceptable carriers” ..................54
`Claim 19 ..........................................................................55
`“A method for the treatment of type 2
`diabetes comprising” ............................................55
`“administering to a patient in need of such
`treatment a therapeutically effective amount
`
`ii
`
`DRL Ex. 1002, p. 003
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`3.
`
`of the salt according to claim 2 or a hydrate
`thereof” .................................................................55
`Claim 21 ..........................................................................55
`e)
`Claim 22 ..........................................................................56
`f)
`Claim 23 ..........................................................................57
`g)
`Ground 4: Claims 1-3, 17, 19, and 21-23 Would Have Been
`Obvious in View of WO ’498 and Bastin ...........................................57
`1.
`The Level of Ordinary Skill in the Pertinent Art ......................57
`2.
`The Scope and Content of the Prior Art ...................................57
`a) WO ’498 (EX1004) ........................................................57
`b)
`Bastin (EX1006) .............................................................57
`The Differences Between the Claims and Prior Art .................58
`a)
`Claim 1 ............................................................................58
`WO ’498 and Bastin Would Have Rendered
`the Phosphoric Acid Salt Obvious .......................59
`Claims 2 and 3 ................................................................63
`b)
`Claims 17 and 19 ............................................................64
`c)
`Claims 21-23 ...................................................................65
`d)
`Ground 5: Claim 4 Would Have Been Obvious in View of WO
`’498, Bastin, and Brittain ....................................................................66
`1.
`The Level of Ordinary Skill in the Pertinent Art ......................66
`2.
`The Scope and Content of the Prior Art ...................................66
`a) WO ’498 (EX1004) and Bastin (EX1006) .....................66
`b)
`Brittain (EX1005) ...........................................................67
`The Differences Between the Claim and Prior Art ...................68
`a)
`Claim 4 ............................................................................68
`Ground 6: Claim 4 Would Have Been Obvious in View of WO
`’498 and Brittain ..................................................................................69
`1.
`The Level of Ordinary Skill in the Pertinent Art ......................69
`
`3.
`
`iii
`
`B.
`
`C.
`
`D.
`
`DRL Ex. 1002, p. 004
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`2.
`
`The Scope and Content of the Prior Art ...................................69
`a) WO ’498 (EX1004) and Brittain (EX1005) ...................69
`The Differences Between the Claim and Prior Art ...................69
`3.
`SECONDARY CONSIDERATIONS ...........................................................70
`
`XI.
`
`iv
`
`DRL Ex. 1002, p. 005
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`I, Mukund Chorghade, Ph.D., do hereby declare and state as follows:
`
`1.
`
`I have been asked to provide testimony as to what one of ordinary skill
`
`in the art would have understood with respect to the patent at issue and various prior
`
`art discussed herein. I provide this testimony below:
`
`I.
`
`INTRODUCTION
`
`2.
`
`I am over the age of 18 and otherwise competent to make this
`
`Declaration.
`
`3.
`
`I have been retained on behalf of Petitioner Mylan Pharmaceuticals Inc.
`
`for the above-captioned inter partes review (“IPR”). I am being compensated for
`
`my time in connection with this IPR at my standard consulting rate, which is $400
`
`per hour. My compensation does not depend in any way on the outcome of the IPR.
`
`4.
`
`It is my understanding that the Petition for Inter Partes Review in this
`
`matter (the “Petition”) involves U.S. Patent No. 7,326,708 (“the ’708 patent”)
`
`(EX1001).
`
`5.
`
`The ’708 patent names Stephen Howard Cypes, Alex Minhua Chen,
`
`Russell R. Ferlita, Karl Hansen, Ivan Lee, Vicky K. Vydra, and Robert M. Wenslow,
`
`Jr. as the purported inventors.
`
`6.
`
`For the purposes of this declaration, I have been told to assume the
`
`relevant priority date of the ’708 patent is June 24, 2003—the filing date of U.S.
`
`1
`
`DRL Ex. 1002, p. 006
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`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`Provisional Application No. 60/482,161.1 I further understand that the ’708 patent
`
`is assigned to Merck, Sharpe & Dohme Corp. (“Merck,” “Patentee,” or “Patent
`
`Owner”).
`
`7.
`
`As explained below, it is my opinion that Claims 1-4, 17, 19, and 21-23
`
`of the ’708 patent2 are anticipated or would have been obvious to the skilled artisan
`
`as of the time of the priority date of the ’708 patent. Therefore, these claims are
`
`invalid.
`
`1 I have not been asked to analyze whether this is indeed the correct priority
`
`date but rather assume that it is for the purposes of my declaration. I understand that
`
`Patent Owner has recently contended that the priority date is earlier than June 24,
`
`2003. EX1015, 10. I express no opinion at this time as to whether June 24, 2003 is,
`
`in fact, the correct priority date. However, should this become an issue during the
`
`proceeding, I may be called upon to offer my opinion.
`
`2 I have not been asked to express an opinion about any other claim of the
`
`’708 patent, nor do I express such opinion because I have not undertaken such an
`
`analysis.
`
`2
`
`DRL Ex. 1002, p. 007
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`II. MY EXPERIENCE AND QUALIFICATIONS3
`
`8.
`
`I am an expert in the field of medicinal chemistry, and I have been an
`
`expert in this field since well before June 24, 2003. Throughout my career, I have
`
`discovered drugs and provided synthetic chemistry and pharmaceutical drug
`
`development expertise to academic laboratories and pharmaceutical companies. In
`
`formulating my opinions, I have relied upon my training, knowledge, and experience
`
`in the relevant art. A copy of my current curriculum vitae is attached to this
`
`Declaration as EX1003 and it provides a description of my academic and
`
`employment history.4
`
`9.
`
`As an expert in the relevant field since prior to June 24, 2003, I am
`
`qualified to provide an opinion as to what a Person of Ordinary Skill in the Art
`
`(“POSA” or “the skilled artisan”) would have understood, known, or concluded as
`
`of June 24, 2003. Indeed, since 1973, I have accumulated significant training and
`
`experience in the fields of medicinal chemistry, drug development and design, drug
`
`discovery, enzyme interactions (including inhibitor design), enzymatic kinetics, and
`
`3 I reserve the right to explain my background and qualifications during any
`
`deposition or in any subsequent Reply.
`
`4 I reserve the right to supplement my academic and employment history
`
`during any subsequent deposition.
`
`3
`
`DRL Ex. 1002, p. 008
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`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`organic and process chemistry. Moreover, I have a deep understanding and
`
`knowledge of the benefits of incorporating halogens such as fluorine, even at a late
`
`stage into pharmaceutical compounds as part of the drug development, in order to
`
`improve their metabolic stability, biological activity, and/or permeability, including
`
`their methods of preparation.
`
`10.
`
`I have a Ph.D. in Organic Chemistry from Georgetown University and
`
`an M.Sc. and a B.Sc from the University of Poona, India. I have completed
`
`postdoctoral appointments at the University of Virginia and Harvard University. I
`
`am a member of various academic and professional societies, including the
`
`American Chemical Society, the International Union of Pure and Applied
`
`Chemistry, the RSC-Process Chemistry and Technology Committee Group, the
`
`Massachusetts Biotechnology Council, the Committees of Advanced Professional
`
`Thinking Activities and Technology, the International Union of Pure and Applied
`
`Chemistry, and the American Institute of Chemists. In particular, I was an ACS
`
`Section Chair of Brazoria (1990) and of Northeastern Section (2007) and am
`
`currently a Chair of the Princeton Section for 2019 and on its Board of Directors,
`
`while also being the Chair of the RSC Committee on Process Chemistry and
`
`Technology (2018-20). In addition, I am an active participant (as Chair and
`
`Immediate Past-Chair) in ACS’s Career Services / Professional Development /
`
`Entrepreneurship and the Small Chemicals Businesses Division.
`
`4
`
`DRL Ex. 1002, p. 009
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`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`11.
`
`Previously, I was the Secretary of the Division on Chemistry and
`
`Human Health and served on the IUPAC Commissions on Biotechnology, Medicinal
`
`Chemistry, New Technologies and Special Topics and the US National Committee
`
`for IUPAC. I am also a member of the Scientific Advisory Boards of various
`
`corporations and foundations, including Envision Biotech, Civenti Chem, ROW2,
`
`International Brain Research Foundation, CBD Life Sciences and the New Jersey
`
`Stem Cell Research Foundation. I have been honored by election as a Fellow of the
`
`American Chemical Society, American Association for the Advancement of
`
`Science, American Institute of Chemists, and Royal Society of Chemistry, the
`
`Maharashtra, Andhra Pradesh and Telengana Academy of Sciences. I have
`
`published over 100 research publications and edited several books in the field of
`
`medicinal chemistry, drug discovery, and development. In addition, I am the
`
`inventor of 29 U.S. patents. During my career I have given over 200 presentations
`
`and lectures in the field of organic and medicinal chemistry.
`
`12.
`
`I am currently, and have been since June 2006, the President and Chief
`
`Scientific Officer of THINQ Pharma / MVRC Research / Chicago Discovery
`
`Solutions. Before that I was the Principal of THINQ –CRO / Chorghade Enterprises
`
`/ CP Consulting from 1995 to 2003. During this time, I designed, developed, and
`
`directed chemistry for a variety of therapeutic and chemical applications, as well as
`
`consulted with major pharmaceutical and biopharmaceutical companies.
`
`5
`
`DRL Ex. 1002, p. 010
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`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`13.
`
`In particular, I invented the “Chemosynthetic Livers” as powerful
`
`oxidation catalysts for predicting drug metabolites, and valorization of biomass and
`
`environmental remediation. Additional activities included discovering NCEs
`
`through Traditional Medicine using Observational Therapeutics and collaborating
`
`for the in- and out-licensing of pharmaceutically active moieties. I coined the term
`
`“Process Chemistry Driven Medicinal Chemistry.”
`
`14.
`
`From 2003 to 2006, I was Vice President of the Pharmaceutical
`
`Development Sciences and member of the Corporate Steering Committee at
`
`Genzyme Corporation, Inc. In that capacity, I directed chemical process and
`
`formulations research on pre-clinical and clinical candidates and was responsible for
`
`devising and implementing novel strategies for reduction of drug development cycle
`
`times. During my tenure, various “Investigational New Drug Applications” and
`
`marketing approvals were filed with various government agencies.
`
`15.
`
` From 1997 to 1999, I was initially Director, then Senior Director,
`
`Chemical Sciences Research and Development at CytoMed, Inc. My responsibilities
`
`included directing chemical process and formulation research groups. During this
`
`time, I was awarded “Scientist of the Year” for my contributions to drug
`
`development in 1997.
`
`16.
`
`From 1991 to 1995, I was first a Research Investigator (1991-1992) and
`
`was then a Project Manager (1992-1995) at Abbott Laboratories in their
`
`6
`
`DRL Ex. 1002, p. 011
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`Pharmaceutical Research Division. During this time, I designed novel cost-effective
`
`synthetic processes for the preparation of multi-kilo quantities of anti-convulsants,
`
`cholinergic channel activators, and anti-infectives, and reduced the time to market
`
`by 25%. In addition, I launched a new program on the biomimetic synthesis of drug
`
`metabolites via metalloporphyrin-assisted epoxidation and hydroxylation. Due to
`
`my work, elaborate multi-step syntheses were converted to one- or two-step catalytic
`
`reactions, thereby saving 75% of development time and 80% of costs. I was also
`
`awarded the divisional “Scientist of the Year” award for discovery research in June
`
`of 1993.
`
`17.
`
`From 1990 to 1991, I worked as a Research Scientist and then as an
`
`Assistant Director at the College de France, where I researched the phenomena of
`
`designed self-assembly and molecular recognition with Professor Jean-Marie Lehn
`
`(Nobel Laureate), and designed and synthesized diversely substituted pyrimidines,
`
`triazines, and porphyrins.
`
`18.
`
`From 1985 to 1990, I was employed by Dow Chemical first as a Senior
`
`Research Chemist (1985-1989) and then as a Project Leader (1989-1990). During
`
`this time I led a team of researchers to investigate metalloporphyrin-assisted
`
`epoxidation of terminal alkenes, biomedical applications of porphyrins, and
`
`selective functionalization of carbohydrates. I also initiated and successfully
`
`completed projects related to (i) bio rational design of environmentally benign
`
`7
`
`DRL Ex. 1002, p. 012
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`herbicides and (ii) the process development for pharmaceuticals. I received several
`
`performance-based awards during this time.
`
`19.
`
`From 1984 to 1985, I was a Postdoctoral Research Fellow at Harvard
`
`University conducting research under Professor Yoshito Kishi on the synthesis of
`
`complex carbohydrates (potential new drugs and non-calorific sweeteners) and
`
`novel C-C bond-forming reactions.
`
`20.
`
`From 1982 to 1984, I was a Postdoctoral Research Fellow at the
`
`University of Virginia conducting research under Professor Sidney Hecht on routes
`
`for the synthesis of the pyrimidine moiety of Bleomycin (a drug in clinical use for
`
`treatment of carcinomas, melanomas, and Hodgkin’s disease) and 2’ (3’) -0-
`
`acylated pCpA derivatives.
`
`21. At present, I provide consulting services to start-up and academic
`
`laboratories, pharmaceutical, and biopharmaceutical companies on pharmaceutical
`
`projects, as well provide consultations on strategic collaborations with academic,
`
`government, and industrial laboratories. The nature of the projects includes
`
`discovery of drugs by lead identification and optimization, preliminary toxicology
`
`evaluation, and development with IND-enabling studies. I advise on company
`
`entrepreneurial ventures leading to the creation and running of biotech companies,
`
`and how to capitalize on partnerships with entrepreneurs, investors, strategic players,
`
`inventors, and governments as well as various grants and aid programs.
`
`8
`
`DRL Ex. 1002, p. 013
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`22.
`
`The areas in which I consult include active pharmaceutical ingredient
`
`(“API”) route selection, manufacture and qualification, formulation development,
`
`stability assessment, analytical development, manufacturing process development
`
`and transfer, contract laboratory and drug product manufacturer identification and
`
`their management, and preparation of regulatory CMC documents.5
`
`23.
`
`In the course of my employment and during my consulting practice, I
`
`have worked on various projects, including compounds related to diabetes. New
`
`compounds were prepared by initial- and late-stage fluorination, metabolic
`
`parameters were determined, and IND studies were initiated on two compounds.
`
`24.
`
`I was involved in numerous projects involving structure-activity
`
`relationship (“SAR”) studies and the selection and the identification of lead
`
`compounds for further development. Compounds that reached advanced clinical
`
`testing were slagenin, calanolide, Gabitril, ABT-418, LDP-977, and many others.
`
`25.
`
`Throughout my career I have been involved in projects involving
`
`enzymatic inhibition and enzymatic kinetics. These projects involved developing an
`
`understanding of enzymatic metabolites, enzymatic
`
`interactions,
`
`inhibitor
`
`development and assay development. Most of my work has centered around
`
`5 I reserve the right to further explain my background and qualifications in
`
`deposition where needed.
`
`9
`
`DRL Ex. 1002, p. 014
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`Cytochromes P-450 and its inhibition and induction to probe drug metabolites and
`
`drug-drug interactions. I have also played a lead role in the Biorational Design of
`
`Herbicides by Synthesis of Inhibitors of the PFP Enzyme. I have also researched
`
`the role of several enzymes in organic solvents by immobilizing them on
`
`polyethylene glycol supports.
`
`26.
`
`Specifically, I have worked with dipeptidyl peptidase IV, dipeptidyl
`
`peptidase IV (DPP-IV) inhibitors, and their corresponding assays. These assays
`
`were needed for work on several anti-diabetes drugs.
`
`27. Moreover, prior to my involvement with this declaration, through the
`
`literature and my own work, I am familiar with the drugs known as sitagliptin,
`
`saxagliptin, linagliptin, and alogliptin, as well as others spanning the therapeutic
`
`spectrum. I have studied these with a view to alleviating the cardiovascular
`
`problems inherent in anti-diabetes drugs. I have also studied all these compounds in
`
`combination with statins and anti-hypertensive drugs.
`
`III. LIST OF MATERIALS CONSIDERED
`
`28.
`
`In formulating my opinions, I have considered the materials referenced
`
`in this Declaration and the Exhibit List below. I have also reviewed the ’708 patent
`
`(EX1001) and its prosecution history, as well as each of the documents cited herein
`
`in light of the general knowledge in the state of the art as of June 24, 2003.
`
`10
`
`DRL Ex. 1002, p. 015
`
`

`

`Petitioner
`Exhibit #
`1001
`1002
`1003
`1004
`1005
`1006
`
`1007
`1008
`1009
`1010
`
`1011
`1012
`1013
`1014
`1015
`
`1016
`
`Declaration of Mukund Chorghade, Ph.D.
`
`Description
`
`U.S. Patent No. 7,326,708
`
`Declaration of Dr. Mukund Chorghade
`
`CV of Dr. Mukund Chorghade
`
`WO 03/004498 to Edmonson
`
`Brittain, “Polymorphism in Pharmaceutical Solids”
`
`Bastin et al. “Salt Selection and Optimisation [sic] Procedures for
`Pharmaceutical New Chemical Entities”
`
`U.S. Patent No 6,699,871
`
`Orange Book Entry for Janumet®
`
`Orange Book Entry for Januvia®
`
`Complete copy of the prosecution history of the ’708 patent as
`available for download from the USPTO website
`
`U.S. Patent No. 4,572,909
`
`U.S. Provisional Application No. 60/303,475, filed July 6, 2001
`
`Prescribing Information for Janumet®
`
`Prescribing Information for Januvia®
`
`Merck Sharpe & Dohme’s Responses and Objections to
`Defendants’ First Set of Joint Interrogatories (1-10)
`
`Brown et al., Chemistry: The Central Science, 8th Revised Edition
`615-618 (2002)
`
`11
`
`DRL Ex. 1002, p. 016
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`IV. LEGAL STANDARD
`
`29. Although I am not a lawyer, I have been informed by counsel and
`
`provide my general understanding of the law of anticipation and obviousness. I used
`
`these principles in conducting my analysis and drawing any conclusions.
`
`30.
`
`I understand that the first step in determining whether a patent claim
`
`would have been anticipated or obvious is to construe the claims to determine claim
`
`scope and meaning. I understand that in IPR proceedings, the claims must generally
`
`be given “the meaning that the term would have to a person of ordinary skill in the
`
`art in question at the time of the invention.”
`
`A.
`
`31.
`
`Anticipation
`
`I understand that anticipation requires that each and every element of
`
`the claimed invention be disclosed expressly or inherently in a single prior art
`
`reference. I also understand that a reference can anticipate a claim even if it does
`
`not expressly spell out all the limitations arranged or combined as in the claim. For
`
`example, I understand that an element may be inherent in the prior art where the
`
`prior art necessarily functions in accordance with or includes the claimed limitations.
`
`I am also informed that inherency may exist even if a POSA would not appreciate
`
`or recognize the inherent characteristics of the prior art, as the discovery of a
`
`previously unappreciated property does not make an old composition patentable.
`
`12
`
`DRL Ex. 1002, p. 017
`
`

`

`Declaration of Mukund Chorghade, Ph.D.
`
`32. Moreover, a reference anticipates a claim if it discloses the claimed
`
`invention such that a skilled artisan could take its teachings in combination with his
`
`own knowledge of the particular art and be in possession of the invention. In an
`
`anticipation inquiry, it is proper to take into account not only specific teachings of
`
`the reference but also the inferences which one skilled in the art would reasonably
`
`be expected to draw therefrom. It is also my understanding that proof of efficacy is
`
`not required in order for a reference to be enabled for purposes of anticipation, or
`
`for that matter, anticipation does not require actual performance of suggestions in a
`
`disclosure. I also understand that a prior art reference must enable a POSA to make
`
`and use a claimed invention in order to anticipate a patent claim, although I
`
`understand that in an IPR, prior art references are presumed to be enabled.
`
`B.
`
`33.
`
`Obviousness
`
`I understand that a patent claim is invalid if the differences between the
`
`claimed invention and prior art are such that the subject matter as a whole would
`
`have been obvious at the time the invention was made to a POSA.
`
`34.
`
`I have been told the following factors (sometimes referred to as the
`
`Graham factors) are used in making an obviousness determination: a) the scope and
`
`content of the prior art; b) the differences between the prior art and the claimed
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`invention; c) the level of ordinary skill in the pertinent art; and d) any secondary
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`considerations evidencing non-obviousness. The obviousness analysis looks to the
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`Declaration of Mukund Chorghade, Ph.D.
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`state of the art that existed at the time the invention was made. Moreover,
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`obviousness does not require absolute predictability of success; all that is required
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`is a reasonable expectation of success. Moreover, I have been informed that the
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`person of ordinary skill need only have a reasonable expectation of success of
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`developing the claimed invention. Finally, obviousness cannot be avoided simply
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`by a showing of some degree of unpredictability in the art so long as there was a
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`reasonable probability of success.
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`35.
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`I also understand that obviousness can be established by combining or
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`modifying the teachings of the prior art. A claimed invention can be obvious when,
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`for example, there is some teaching, suggestion, or motivation in the prior art that
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`would have led a POSA to modify the prior art reference or to combine prior art
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`reference teachings to arrive at the claimed invention.6
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`36.
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`I also understand that the prior art references themselves do not have to
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`provide an explicit teaching, suggestion, or motivation to combine prior art
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`teachings; rather, the analysis may rely on interrelated teachings, market demands,
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`6 As a general matter, in my view in science and technology a POSA would
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`not view any single disclosure as complete, and thus, look no further. Were that the
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`case, society would have halted progress long ago. Instead, ordinary artisans always
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`seek improvement in their respective fields.
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`Declaration of Mukund Chorghade, Ph.D.
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`the background knowledge possessed by a POSA, and/or common sense. Moreover,
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`the POSA can also take account of the inferences and creative steps that he or she
`
`would employ. Put another way, the motivation to combine or modify prior art
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`references can come from any reason to do so and is not limited to the reasons that
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`may have motivated the patentee.
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`37.
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`I am also informed that a combination of familiar elements according
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`to known methods is likely to be obvious when it does no more than yield predictable
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`results. I also understand that when a POSA would have reached the claimed
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`invention through routine experimentation, the invention may be deemed obvious.
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`38.
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`I understand that various rationales are utilized to determine whether a
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`claim
`
`is obvious,
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`including, among others:
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` (i) simple substitution or
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`interchangeability of one known element for another to obtain predictable results;
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`(ii) use of known techniques to improve similar methods or products in the same
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`way; (iii) applying a known technique to a known method or product ready for
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`improvement to yield predictable results; (iv) “obvious to try”—choosing from a
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`finite number of identified, predictable solutions, with a reasonable expectation of
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`success; and (v) known work in one field of endeavor prompting variations of it for
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`use in either the same field or a different one based on design incentives or other
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`market forces if the variations would have been predictable to one of ordinary skill
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`in the art.
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`Declaration of Mukund Chorghade, Ph.D.
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`39. As stated above, I understand that secondary considerations of
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`non-obviousness are part of the obviousness inquiry. I understand that these
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`secondary considerations may include failure of others, copying, unexpectedly
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`superior results, perception in the industry, commercial success, and long-felt but
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`unmet need. I also understand that for secondary considerations of non-obviousness
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`to be applicable, they must have a nexus to the claimed subject matter. I understand
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`that this nexus (i.e., link) includes a connection between the subject matter of the
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`claim and the alleged secondary considerations.
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`40.
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`I understand that I cannot use hindsight in any obviousness analysis. In
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`connection with my opinions, I did not use hindsight, nor did I use the claims and/or
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`the disclosure of the ’708 patent as a blueprint for piecing together the prior art to
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`arrive at the claimed invention. As part of the obviousness analysis, and to avoid
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`hindsight, I thought back to the time of invention (i.e., the relevant priority date
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`(discussed further below)) and considered the thinking of POSA, guided only by the
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`prior art references and the then-accepted wisdom in the field.
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`V.
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`BACKGROUND
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`41. Medicinal chemistry is a subject that deals with the design, synthesis,
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`evaluation, and development of chemical compounds which exert beneficial effects
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`upon living systems. Medicinal chemists must have a firm understanding of organic
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`Declaration of Mukund Chorghade, Ph.D.
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`and synthetic chemistry as well as knowledge of other disciplines such as biological,
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`medical, and pharmaceutical sciences.
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`42. Medicinal chemists study relationships between the structure of a
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`particular compound or group of compounds and their properties, including their
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`interactions with biological
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`systems.
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` These
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`relationships are called
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`structure-activity relationships (“SAR”). The rationale behind SAR is that the
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`structure of a chemical implicitly determines its physico-chemical and biological
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`properties.
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`43.
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`The goal of the medicinal chemist is to optimize not only the
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`pharmacological properties, such as potency, but also the drug-like properties of the
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`molecules in order to identify a compound suitable for therapeutic use.
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`VI. PERSON OF ORDINAR