UNITED STATES PATENT AND TRADEMARK OFFICE
`________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________
`
`BRECKENRIDGE PHARMACEUTICAL, INC.
`Petitioner
`v.
`
`NOVARTIS PHARMACEUTICALS CORPORATION
`Patent Owner
`________________________
`
`Case IPR2017-015921
`U.S. Patent No. 8,410,131
`________________________
`
`SECOND DECLARATION OF ALLAN J. PANTUCK, M.D.
`IN SUPPORT OF
`INTER PARTES REVIEW OF U.S. PATENT NO. 8,410,131
`
`1
`
`IPR2018-00507 has been joined to this proceeding.
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`TABLE OF CONTENTS
`
`I.
`II.
`
`C.
`
`INTRODUCTION ............................................................................................ 1
`LEGAL PRINCIPLES ...................................................................................... 2
`A.
`Claim Construction ............................................................................... 2
`Priority ................................................................................................... 3
`B.
`C.
`Invalidity by Anticipation ..................................................................... 4
`Invalidity by Obviousness ..................................................................... 4
`D.
`Filing particulars of the '131 Patent ...................................................... 7
`E.
`F.
`Interpreting Claims Before the Patent Office ........................................ 8
`III. POSA ................................................................................................................ 9
`IV. SELECTED ASPECTS OF THE '131 PATENT AND PROSECUTION
`HISTORY ...................................................................................................... 16
`CLAIM CONSTRUCTION ........................................................................... 19
`V.
`VI. ALTERNATIVE NAMES FOR RAPAMYCIN AND ITS DERIVATIVES
` ....................................................................................................................... 27
`VII. State of the Art: Rapamycin and its analogs (temsirolimus and everolimus)
`were known to inhibit growth of solid and liquid tumors ............................. 31
`A.
`Rapamycin was known to inhibit growth of solid and liquid tumors . 31
`B.
`Temsirolimus was known to inhibit growth of solid and liquid tumors
` ............................................................................................................. 39
`Temsirolimus was known to be a prodrug of rapamycin ......... 39
`Temsirolimus In Vitro Activity ................................................ 40
`Temsirolimus In Vivo Activity ................................................. 44
`Disagreement with some of Dr. Burris' Positions ..................... 57
`Everolimus was known to inhibit growth of solid and liquid tumors . 78
`Novartis' statements during the Weckbecker application. ........ 83
`Novartis' statements from the '131 patent. ................................ 86
`mTOR Inhibitors exhibited Class Effects ........................................... 87
`Rapamycin-Sensitive and Rapamycin-Resistant Tumor Models ....... 91
`
`D.
`E.
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`VIII. TREATMENTS FOR RENAL CELL CARCINOMA AND RENAL
`ANGIOMYOLIPOMA .................................................................................. 94
`IX. THE PRIOR ART RELIED UPON ............................................................... 97
`A.
`The Claimed Subject Matter of the '131 Patent is not entitled to the
`filing dates of the '072 and '957 priority applications. ........................ 97
`Schuler ...............................................................................................107
`B.
`Crowe ................................................................................................112
`C.
`Neumayer ..........................................................................................113
`D.
`Alexandre ..........................................................................................117
`E.
`Hidalgo ..............................................................................................120
`F.
`Luan ...................................................................................................128
`G.
`H. Wasik .................................................................................................130
`A POSA would understand that Wasik describes using
`everolimus to inhibit growth of advanced kidney tumors ......142
`Navarro ..............................................................................................145
`I.
`X. MOTIVATIONS TO COMBINE THE PRIOR ART ..................................147
`A. Motivation to Combine Wasik with Navarro ....................................147
`B. Motivation to Combine Wasik, Navarro, Crowe, and Luan .............148
`C. Motivation to Combine Hidalgo, Alexandre, Crowe, Schuler,
`Neumayer, and Navarro ....................................................................151
`D. Motivation to Combine Hidalgo, Alexandre, Crowe, Schuler,
`Neumayer, Navarro, and Luan ..........................................................154
`Dr. Burris' Motivation Rationale .......................................................155
`E.
`XI. GROUNDS OF INVALIDITY ....................................................................160
`A.
`Ground 1: Claims 1-3 and 5-9 of the '131 patent are invalid as
`anticipated by Wasik. ........................................................................161
`The Disclosure of Wasik is Not Limited to Lymphoproliferative
`Disorders or Lymphomas; Wasik Also Relates to Solid
`Excretory System Tumors. ......................................................165
`Dr. Komanduri's Opinion Is Not Relevant Because He Is Not A
`POSA, and He Adds Nothing Beyond Dr. Burris' Analysis. ..176
`Ground 2: Claims 1-3 and 5-9 of the '131 patent are invalid as
`obvious by Wasik alone or in combination with Navarro. ...............186
`
`B.
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`C. 
`
`Ground 3: Claims 1-3 and 5-9 of the '131 patent are invalid as
`obvious by the combination of Wasik, Navarro, Crowe, and Luan ..189 
`D.  Ground 4: Claims 1-3 and 5-9 of the '131 patent are invalid as
`obvious by the combination of Hidalgo, Alexandre, Crowe, Schuler,
`Neumayer, and Navarro ....................................................................192 
`Brief Summary of the State of Art ..........................................193 
` 
`Analysis ...................................................................................198 
` 
`Ground 5: Claims 1-3 and 5-9 of the '131 patent are invalid as
`obvious by the combination of Hidalgo, Alexandre, Crowe, Schuler,
`Neumayer, Navarro, and Luan ..........................................................208 
`XII.  SECONDARY CONSIDERATIONS ..........................................................210 
`
`
`
`
`E. 
`
`
`
`
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`I, Allan J. Pantuck, resident of Los Angeles, California, hereby declare as follows:
`
`I.
`
`INTRODUCTION
`1.
`I am the same Allan J. Pantuck whose declaration (Ex. 1010) and
`
`curriculum vitae (Ex. 1028) were submitted with respect to the petition (IPR2017-
`
`01592) for review of U.S. Patent No. 8,410,131 ("the '131 patent"). My work in this
`
`matter is being billed at my standard rate of $650 per hour, with reimbursement for
`
`necessary and reasonable expenses. My compensation is not in any way contingent
`
`upon the outcome of any Inter Partes Review. I have no financial or personal interest
`
`in the outcome of this proceeding or any related litigation. In the discussion that
`
`follows, I have referred to the Ex. 1010 declaration as "my first declaration" or
`
`simply "Pantuck."
`
`2.
`
`The challenged claims of the '131 patent include claims 1-3 and 5-9 and
`
`relate to methods for inhibiting growth of solid excretory system tumors in a subject,
`
`consisting of administering a therapeutically effective amount of everolimus.
`
`3.
`
`I have reviewed the documents of record in the present IPR proceeding,
`
`including the EXPERT DECLARATION OF DR. HOWARD A. BURRIS, III
`
`("First Burris Declaration" (or "fBD") Ex. 2001) and the CORRECTED EXPERT
`
`DECLARATION OF DR. HOWARD A. BURRIS, III ("Corrected Burris
`
`Declaration" (or "cBD") Ex. 2092) and references cited therein.
`
`
`
`1
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`4.
`
`I understand that Dr. Burris has been working with Novartis on
`
`everolimus since 2003, including serving as an "expert" in three patent proceedings
`
`and receiving research funding from Novartis. (See Burris Tr. (Ex. 1126) 102:3-23;
`
`O'Donnell (Ex. 1122) ("Research Funding...Howard A. Burris, Novartis
`
`Pharmaceutical Corporation");2 PTE Request for Cottens '772 patent (Ex. 1143) pp.
`
`162 of 216 ("New Investigator to Study No. 2101: Dr. Howard A. Burris III, MD");
`
`Dr. Burris' First Everolimus Trial Testimony (Ex. 1129, and associated Trial
`
`Demonstratives (Ex. 1128); and Dr. Burris Second Trial Testimony (Ex. 1130).
`
`II.
`
`LEGAL PRINCIPLES
`A.
`Claim Construction
`5.
`I understand that the current standard in an Inter Partes Review is to
`
`give a claim term the broadest reasonable construction in light of the patent
`
`specification and prosecution history, as understood by a POSA at the time of the
`
`alleged invention. I have applied this broadest reasonable construction standard in
`
`2 During his deposition, Dr. Burris agreed that he did not disclose his research
`
`funding in his C.V., but stated "I did not receive grant support from Novartis for
`
`these trials," but that "[t]he institution received funding from Novartis on a per-
`
`patient – actually, on a per-cycle, per-patient basis for patients that were on the study
`
`to cover research-related activities." (Burris Tr. (Ex. 1126) at 103:5–105:7.
`
`2
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`my analysis. However, I also understand that, during the course of this Inter Partes
`
`Review, the USPTO may decide to start interpreting claim terms in a manner
`
`consistent with the standard used in patent litigation, as set forth in Phillips v. AWH
`
`Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc), in light of a recent Notice of
`
`Proposed Rulemaking issued by the USPTO. Based on that Notice of Proposed
`
`Rulemaking, I understand that the USPTO will look to the patent's claims,
`
`specification (which includes all the figures and discussion) and prosecution history
`
`to see if there is a definition for a given claim term, and if not, will apply the
`
`"ordinary and customary" meaning from the perspective of a POSA at the time in
`
`which the alleged invention was made. The determination of the "ordinary and
`
`customary" meaning of a claim term under the Phillips standard is determined in
`
`view of the claim language, specification, and prosecution history, and where
`
`applicable, relevant other evidence. As such, I have also analyzed the claims below
`
`using a Philips standard for claim construction. It is my opinion (as set forth below)
`
`that the claims would be invalid under either a broadest reasonable interpretation or
`
`Philips claim construction standard.
`
`B.
`6.
`
`Priority
`I understand that a patent must include a written description sufficient
`
`to convey to the person of ordinary skill in the art that the inventor actually invented
`
`and had possession of the claimed subject matter as of the filing date of the patent.
`
`
`
`3
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`I have been informed that for generic claims, there are several factors for evaluating
`
`the adequacy of the disclosure, including the existing knowledge in the particular
`
`field, the extent and content of the prior art, the maturity of the science or technology,
`
`the predictability of the aspect at issue, where the predictability of the particular field
`
`is relevant to deciding how much experimental support is required to adequately
`
`describe the scope of the claimed subject matter.
`
`C.
`7.
`
`Invalidity by Anticipation
`I understand an anticipation analysis involves comparing a claim to the
`
`prior art to determine whether a hypothetical person of ordinary skill ("POSA")
`
`would understand the claimed invention is anticipated in view of the prior art, and
`
`in light of the general knowledge in the art. I understand that to anticipate a claim, a
`
`prior art reference must disclose each and every claim limitation, either expressly or
`
`inherently. I also understand that to explain the meaning of a prior art reference, a
`
`POSA can refer to a secondary reference. For instance, I understand that information
`
`incorporated by reference by the prior art may be considered when understanding
`
`the meaning of that prior art.
`
`D.
`8.
`
`Invalidity by Obviousness
`I understand that obviousness is analyzed from the perspective of a
`
`POSA at the time of the alleged invention. I also understand that a POSA is
`
`
`
`4
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`presumed to have been aware of all pertinent prior art at the time of the alleged
`
`invention.
`
`9.
`
`I understand that Dr. Burris has taken the position, with respect to cases
`
`"involving new methods of treatment involving a known compound," that "the Board
`
`will consider whether a POSA would have selected the claimed compound over
`
`other available prior art compounds." (Corrected Burris Declaration (Ex. 2092) at ¶
`
`36.) It is difficult for me to understand why Dr. Burris has taken this position
`
`considering that the claims of the '131 patent "relate to methods for inhibiting growth
`
`of solid excretory system tumors in a subject, consisting of administering a
`
`therapeutically effective amount of everolimus"—as opposed to methods of
`
`treatment. (See, e.g., id. at ¶ 1.)
`
`10.
`
`I understand that an obviousness analysis involves comparing a claim
`
`to the prior art to determine whether the claimed invention would have been obvious
`
`to a POSA in view of the prior art, and in light of the general knowledge in the art. I
`
`also understand that the invention may be deemed obvious when a POSA would
`
`have reached the claimed invention through routine experimentation.
`
`11.
`
`I understand that obviousness can be established by combining or
`
`modifying the disclosures of the prior art to achieve the claimed invention. It is also
`
`my understanding that where there is a reason to modify or combine the prior art to
`
`achieve the claimed invention, there must also be a reasonable expectation of success
`
`
`
`5
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`in so doing to render the claimed invention obvious. I understand that the reason to
`
`combine prior art references can come from a variety of sources, not just the prior
`
`art itself or the specific problem the patentee was trying to solve. I also understand
`
`that the references themselves need not provide a specific hint or suggestion of the
`
`alteration needed to arrive at the claimed invention; the analysis may include
`
`recourse to logic, judgment, and common sense available to a POSA.
`
`12.
`
`I understand that when a patent claims a genus, that claim is obvious if
`
`a single embodiment falling within the scope of the claims is obvious. I also
`
`understand that a claimed use of a prior art compound may be obvious when the
`
`prior art shows that structurally similar compounds exhibit the same uses claimed
`
`for the prior art compound. I also understand that claims may be considered obvious
`
`if they recite subject matter that would have been obvious to a POSA to try and
`
`develop. I further understand that claims are obvious to try when there is market
`
`pressure to solve a problem and there are only a finite number of identified,
`
`predictable solutions to that problem.
`
`13.
`
`I understand that when there is some recognized reason to solve a
`
`problem, and there are a finite number of identified, predictable solutions, a POSA
`
`has good reason to pursue the known options within his or her technical grasp. If
`
`such an approach leads to the anticipated success, it is likely the product not of
`
`innovation but of ordinary skill and common sense. In such a circumstance, when a
`
`
`
`6
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`patent simply arranges old elements with each performing the same function it had
`
`been known to perform and yields no more than one would expect from such an
`
`arrangement, the combination is obvious.
`
`14.
`
`I understand that when considering the obviousness of an invention,
`
`one should also consider whether there are any objective indicia that support the
`
`non-obviousness of the invention. I further understand that objective indicia of non-
`
`obviousness include failure of others, copying, unexpectedly superior results,
`
`information that "teaches away" from the claimed subject matter, perception in the
`
`industry, commercial success, and long-felt but unmet need. I also understand that
`
`in order for objective indicia of non-obviousness to be applicable, the indicia must
`
`have some sort of nexus to the subject matter in the claim that was not known in the
`
`art. I understand that this nexus includes a factual connection between the patentable
`
`subject matter of the claim and the objective indicia alleged. Finally, I understand
`
`that an independently made invention that is made within a comparatively short
`
`period of time is evidence that the claimed invention was the product of ordinary
`
`skill.
`
`E.
`15.
`
`Filing particulars of the '131 Patent
`I understand that the '131 patent issued on April 2, 2013 from U.S.
`
`Patent Application No. 10/468,520 ("the 520 application" or "the patent application
`
`leading to the '131 patent")), filed as International Patent Application No.
`
`
`
`7
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`PCT/EP02/01714, Ex. 1014) on February 18, 2002. I understand that U.S. Patent
`
`Application No. 13/546,686 (the '686 application"), which issued as U.S. Patent No.
`
`8,778,962 ("the 962 patent"), is reportedly a continuing application of Novartis' 520
`
`application (now the '131 patent). I also understand that the patent application
`
`leading to the '131 patent is based on two earlier-filed Great Britain patent
`
`applications. The first-filed Great Britain patent application (GB 0104072.4, "the
`
`'072 priority application," Ex. 1012) was filed on February 19, 2001, and the second-
`
`filed Great Britain patent application (GB0124957.2, "the '957 priority application,"
`
`Ex. 1013) was filed on October 17, 2001. I have therefore analyzed anticipation and
`
`obviousness as of February 18, 2002 or before, with the understanding that my
`
`conclusions remain the same even if the analysis is performed as of February 18,
`
`2001 or before.
`
`F.
`16.
`
`Interpreting Claims Before the Patent Office
`I understand that the current standard in an Inter Partes Review is to
`
`give a claim term the broadest reasonable construction in light of the patent
`
`specification and prosecution history, as understood by a POSA at the time of the
`
`alleged invention. I have applied this broadest reasonable construction standard in
`
`my analysis. However, I also understand that, during the course of this Inter Partes
`
`Review, the USPTO may decide to start interpreting claim terms in a manner
`
`consistent with the standard used in patent litigation, as set forth in Phillips v. AWH
`
`
`
`8
`
`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
`
`

`

`Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc), in light of a recent Notice of
`
`Proposed Rulemaking issued by the USPTO. Based on that Notice of Proposed
`
`Rulemaking, I understand that the USPTO will look to the patent's claims,
`
`specification (which includes all the figures and discussion) and prosecution history
`
`to see if there is a definition for a given claim term, and if not, will apply the
`
`"ordinary and customary" meaning from the perspective of a POSA at the time in
`
`which the alleged invention was made. The determination of the "ordinary and
`
`customary" of a claim term under the Phillips standard is determined in view of the
`
`claim language, specification, and prosecution history, and where applicable,
`
`relevant other evidence. As such, I have also analyzed the claims below using a
`
`Philips standard for claim construction. It is my opinion (as set forth below) that the
`
`claims would be invalid under either a broadest reasonable interpretation or Philips
`
`claim construction standard.
`
`
`III. POSA
`17. The claims of the '131 patent are directed to a method for inhibiting
`
`growth of solid excretory system tumors in a subject, said method consisting of
`
`administering to said subject a therapeutically effective amount of a compound of
`
`formula I, which is alternatively known as 40-O-(2-hydroxyethyl)-rapamycin (i.e.,
`
`everolimus).
`
`
`
`9
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`

`

`18. The Board adopted Breckenridge′s proposed definition of a POSA in
`
`the Institution Decision, finding that a person of ordinary skill in the art, as of
`
`February 18, 2001 or February, 18, 2002, would possess:
`
`(i)
`
`a medical degree (e.g., MD) with several years of specific experience
`
`in medical or surgical oncology, which may include board certification, as
`
`well as knowledge [of] oncology drug development and clinical
`
`pharmacology; or
`
`(ii) a Ph.D. in cancer biology, molecular biology, medicinal chemistry, or
`
`a related field with several years of experience in oncology drug development
`
`and clinical pharmacology, including evaluating cancer therapeutics in in
`
`vitro and/or in vivo assays, as well as familiarity with the practice of medical
`
`oncology.
`
`(Paper 12 at 7-8.) Further, as I explained at my deposition, it is my view that the
`
`"several years" of practical experience described above would include specific
`
`experience in the treatment of solid excretory system tumors (including advanced
`
`solid excretory system tumors), such as kidney tumors and/or RCC. (Pantuck Tr.
`
`(Ex. 2027) at 14:17-20.) Notably, Novartis adopted this definition of a POSA prior
`
`to the Institution Decision. (Paper 12 at 8.)
`
`19.
`
`It is my opinion that the Board was correct in adopting this definition
`
`of a POSA, and the Board should maintain this definition of a POSA. (Pantuck (Ex.
`
`
`
`10
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`

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`1010) at ¶¶19-20.) This is based on my evaluation of (a) the education level of those
`
`working in the field, (2) the technology at issue, (c) the types of problems
`
`encountered in the art, (d) prior art solutions to the problems encountered in the art,
`
`and (5) the speed at which innovations are made in the art. I also take into account
`
`my knowledge and experience in the field of urologic oncology in determining the
`
`proper definition of a POSA.
`
`20. Novartis and Dr. Burris never propose a definition of a POSA that is
`
`similar to my definition, as acknowledged by Novartis in its Patent Owner Response.
`
`Paper 34 at 3-4; Ex. 2092 at ¶42. The difference in the proposed POSA definitions
`
`is that my definition requires "several years of specific experience in medical or
`
`surgical oncology" if the POSA had a medical degree or "several years of experience
`
`in oncology drug development and clinical pharmacology, including evaluating
`
`cancer therapeutics in in vitro and/or in vivo assays, as well as familiarity with the
`
`practice of medical oncology" if the POSA had a Ph.D. Ex. 1010 at ¶¶19-20. By
`
`contrast, Dr. Burris requires "at least one year of relevant training, experience, or
`
`research in treating patients with solid excretory system tumors, including advanced
`
`RCC." Ex. 2092 at ¶42. Interestingly, Dr. Burris goes into detail about purported
`
`"unusual clinical characteristics" of RCC (a type of solid excretory system tumor)
`
`and alleges that it is difficult to treat RCC (see, e.g., id. at ¶45), but he concludes that
`
`a POSA would only need "one year of relevant training, experience, or research"
`
`
`
`11
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`

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`with RCC. (Id. at ¶42.) I disagree. A POSA would not gain sufficient practical
`
`experience in the treatment of solid excretory system tumors, including RCC, in the
`
`one year of practical experience described in Dr. Burris' definition of a POSA. It
`
`takes several years to become a POSA in that field.
`
`21. Dr. Burris further states that "[t]he POSA would also have collaborated
`
`with others having skills and expertise in areas pertinent to the above subject matter,
`
`including, for example, pharmacologists, formulators and biochemists." (Id. at ¶42.)
`
`I agree with this portion of Dr. Burris' definition.
`
`22. Dr. Burris mischaracterizes my definition of a POSA when he states
`
`that it "does not require that the POSA have any experience with solid excretory
`
`system tumors generally, or kidney tumors, such as advanced RCC, specifically."
`
`(Id. at ¶44.) That is not correct. My definition specifically calls out experience in
`
`"medical or surgical oncology" for an M.D. or "oncology drug development and
`
`clinical pharmacology, including evaluating cancer therapeutics in in vitro and/or in
`
`vivo assays," for a Ph.D. (Pantuck (Ex. 1010), ¶20.) Given that the claims of the
`
`'131 Patent relate to solid excretory system tumors, the oncology experience
`
`referenced in my definition of a POSA clearly would include experience with solid
`
`excretory system tumors, though a POSA would obviously have some understanding
`
`of treatment of liquid tumors (or lymphomas) as well. At my deposition, I stated my
`
`12
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`

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`opinion that a POSA would have specific experience with solid excretory system
`
`tumors:
`
`17
`18
`19
`20
`
`Q. Would a POSA have specific experience in the
`treatment of solid excretory system tumors of the urinary
`system including kidney tumors and RCC?
`A.
`Yes.
`
`(Pantuck Tr. (Ex. 2027) at 14:17-20.) In fact, Dr. Burris acknowledged my
`
`deposition testimony in the same paragraph where he incorrectly states that my
`
`definition of a POSA does not address solid excretory system tumors. (Corrected
`
`Burris Declaration (Ex. 2092) at ¶44.)
`
`23.
`
`Paragraph 45 of Dr. Burris' declaration (Ex. 2092) contains a discussion
`
`about the alleged difficulties in treating RCC as of February 2001. I do not fully
`
`understand why Dr. Burris inserted this Paragraph at this point in his declaration
`
`because the claims of the '131 Patent are not limited to RCC. Instead, they cover
`
`solid excretory system tumors (claim 1), advanced solid excretory system tumors
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`(claim 2) or kidney tumors (claim 3). ('131 patent (Ex. 1001) at 17:43-18:29.) RCC
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`falls within the definitions of these terms, but these terms are not limited to RCC.
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`My definition of a POSA is not restricted to RCC, and Dr. Burris is incorrect to the
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`extent he implicates otherwise. Further, Dr. Burris references the concepts of
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`"disease stabilization" and "tumor regression" in his discussion of a POSA. While I
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`agree that these concepts would have been known by a POSA in February 2001 (or
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`13
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`February 2002), they are not part of the definition of a POSA; thus, they are
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`misplaced in this section. Nonetheless, as explained below in Section VII.B.4.e and
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`in my deposition, it is important to note that tumor stabilization and tumor regression
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`are rare phenomena in patients with certain solid excretory system tumors (such as
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`RCC) and do not change what a POSA would have understood about the art in
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`February 2001 (or February 2002). (See, e.g., Pantuck Tr. (Ex. 2027) at 45:17-49:7.)
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`24. Dr. Burris also alleges that "a POSA would not have been working in
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`the field of mTOR inhibition, and I agree with Dr. Pantuck that a POSA would not
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`have had experience conducting preclinical or clinical research specifically relating
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`to rapamycin or its analogs," citing Paragraph 20 of my original declaration.
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`(Corrected Burris Deposition (Ex. 2092) at ¶46.) I disagree with both points. First,
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`a POSA in February 2001 or February 2002 clearly would have known about mTOR
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`inhibitors and understood their ability to inhibit the growth of solid excretory system
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`tumors. A POSA also would have been aware of other therapies seeking to inhibit
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`growth of solid excretory system tumors (see Pantuck Tr. (Ex. 2027) at 9:23-12:24),
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`but Dr. Burris is incorrect to imply that a POSA would not have been focused on
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`and knowledgeable about mTOR inhibitors as of the date of the alleged invention(s).
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`25. Second, Dr. Burris misrepresents the information in Paragraph 20 of
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`my original declaration, which merely sets out my definition of a POSA. Nowhere
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`does Paragraph 20 of my original declaration state that a POSA would not have
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`
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`14
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`

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`experience with preclinical or clinical research relating to rapamycin or its analogs.
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`In fact, it is my opinion that the experience a POSA would have in "medical or
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`surgical oncology" for an M.D. or "oncology drug development and clinical
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`pharmacology, including evaluating cancer therapeutics in in vitro and/or in vivo
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`assays," for a Ph.D would definitely include knowledge about rapamycin and its
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`analogs given the information taught by the prior art as of February 2001 or February
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`2002.
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`26.
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`In summary, it is my opinion that the proper definition of a POSA is
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`the definition adopted by the Board in the Institution Decision, which was adopted
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`by Novartis at that time. (See Paper 12 at 7-8.) I qualify as POSA under that
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`definition given my education and twenty-five years of practical experience working
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`in the field of urologic oncology. (Pantuck (Ex. 1010) at ¶¶2-8; Ex. 1028.)
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`27. However, even applying Dr. Burris' definition of a POSA, I still qualify
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`as a POSA based on my education and experience, and my opinions would be the
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`same. Specifically, it would remain my opinion that Wasik discloses each and every
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`element of claims 1-3 and 5-9 of the '131 Patent, or, alternatively, that the elements
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`of those claims would have been obvious in light of the prior art.
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`28. Further, my opinion of the definition of a POSA does not depend on
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`whether the challenged claims are entitled to a February 19, 2001 priority date or a
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`February 18, 2002 priority date. The nature and skill of a POSA would have been
`
`
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`15
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`Breckenridge Exhibit 1159
`Breckenridge v. Novartis IPR2017-01592
`Second Pantuck Declaration
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`

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`the same throughout the time between those dates, and thus my opinion on a POSA
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`would have been the same for both dates.
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`
`IV. SELECTED ASPECTS OF THE '131 PATENT AND PROSECUTION
`HISTORY
`29.
`I summarized aspects of the '131 Patent in Sections II and VI of my first
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`declaration. (Pantuck (Ex. 1010) at ¶¶16 and 31-45.)
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`30.
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`In my first declaration, I did not mention that the '131 patent issued on
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`April 2, 2013 and that the '131 patent names three co-inventors: Heidi Lane, Terence
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`O'Reilly, and Jeanette Marjorie Wood.
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`31. As a part of my review of the specification, I stated that "[t]he '131
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`patent describes five different methods associated with the formula I rapamycin
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`derivatives, including: (i) a method for treating solid tumors, (ii) a method for
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`inhibiting growth of solid tumors, (iii) a method for inducing tumor regression, (iv)
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`a method for treating solid tumor invasiveness or symptoms associated with such
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`tumor growth, and (v) a method for preventing metastatic spread of tumors or for
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`preventing or inhibiting growth of micrometastasis." (Pantuck (Ex. 1010) at ¶ 34;
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`citing the '131 patent (Ex. 1001) at 1:65–2:19.)
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`32.
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`I would add that Section 1.1 of the '131 patent is directed to "[a] method
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`for treating solid tumors in a subject in need thereof, comprising ad