`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`BRECKENRIDGE PHARMACEUTICAL, INC.,
`
`
`
`Petitioner,
`
`v.
`
`NOVARTIS PHARMACEUTICALS CORPORATION,
`
`Patent Owner.
`
`
`
`Case IPR2017-01592
`
`Patent No. 8,410,131
`
`
`
`
`
`EXPERT DECLARATION OF DR. HOWARD A. BURRIS, III
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`TABLE OF CONTENTS
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`I.
`
`Introduction ...................................................................................................... 1
`
`II.
`
`Qualifications ................................................................................................... 4
`
`III. Legal Principles ............................................................................................... 7
`
`IV. POSA ............................................................................................................. 10
`
`V.
`
`State Of The Art ............................................................................................. 10
`
`A.
`
`Tumor Background.............................................................................. 10
`
`B.
`
`C.
`
`Lymphoma Background ...................................................................... 12
`
`Kidney Tumor And RCC Background ................................................ 13
`
`D. Advanced Tumors ............................................................................... 13
`
`VI. Summary Of The ’131 Patent ........................................................................ 14
`
`VII. GB ’072 Contains A Written Description Of The Invention ........................ 17
`
`VIII. A POSA Would Have Understood That Wasik Did Not
`Disclose Solid Tumors Or A Method Of Inhibiting Growth Of
`An Advanced Tumor ..................................................................................... 21
`
`A. Wasik Disclosed Only Lymphomas, Not Solid Tumors ..................... 21
`
`B. Wasik Did Not Disclose Inhibiting Growth Of Advanced
`Tumors ................................................................................................. 26
`
`IX. A POSA Would Have Considered Many Approaches To Find
`New Treatments For RCC In 2001 ................................................................ 28
`
`X. A POSA Would Not Have Been Motivated To Combine The
`Everolimus And Rapamycin References In Ground 3 .................................. 35
`
`XI. A POSA Would Not Have Been Motivated To Combine The
`Temsirolimus And Everolimus References In Grounds 4 and 5 ................... 36
`
`A. No References In Grounds 4 Or 5 Established That
`Rapamycin Analogs Were Interchangeable ........................................ 36
`
`i
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`B.
`
`Everolimus, Unlike Temsirolimus, Was Known To Have
`Immunosuppressant Activity, Which Was Associated
`With Increased Rates Of Kidney Cancer ............................................ 38
`
`XII. Conclusion ..................................................................................................... 39
`
`
`
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`ii
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`I.
`
`Introduction
`
`1.
`
`Challenged claims 1-3 and 5-9 of U.S. Patent No. 8,410,131 (“the
`
`’131 Patent”) relate 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 [everolimus].”
`
`2.
`
`At this preliminary stage of the proceedings, I have been asked by
`
`counsel for Novartis Pharmaceuticals Corporation (“Novartis”) to provide my
`
`opinion on six issues: (1) the construction of certain claim terms in the ’131 Patent;
`
`(2) whether application GB 0104072.4 (“the GB ’072 application”) reasonably
`
`conveys to a person of ordinary skill in the art (“POSA”) that the inventors had
`
`possession of the claimed methods directed to “solid excretory system tumors, and
`
`“advanced solid excretory system tumor[s],” and “kidney tumor[s]” as of February
`
`19, 2001 as those terms would be understood in the context of the ’131 Patent; (3)
`
`whether Wasik disclosed, taught or suggested the claim elements “solid excretory
`
`system tumors,” “advanced solid excretory system tumor[s],” “kidney tumor[s],”
`
`and inhibiting growth of “advanced solid excretory system tumor[s]”; (4) whether
`
`a POSA would have been motivated to select everolimus to treat advanced renal
`
`cell carcinoma (“RCC”) in February 2001; (5) whether a POSA would have been
`
`motivated to combine the everolimus and rapamycin references in Ground 3; and
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`1
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`(6) whether a POSA would have been motivated to combine the temsirolimus and
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`everolimus references in Ground 4 or Ground 5.
`
`3.
`
`As to the first issue, in the context of the ’131 Patent, a POSA would
`
`have understood the meaning of the claim terms below as follows:
`
` “solid excretory system tumors” meant “tumors and/or metastases
`
`other than tumors and/or metastases of the blood or lymphatic system,
`
`which arise from the cells of the urinary excretory system”;
`
` “advanced solid excretory system tumors” meant “locally advanced or
`
`metastatic tumors, other than tumors and/or metastases of the blood or
`
`lymphatic system, which arise from the cells of the urinary excretory
`
`system”; and
`
` “kidney tumor” meant “a tumor and/or metastasis, other than a tumor
`
`and/or metastasis of the blood or lymphatic system, which arises from
`
`the cells of the kidney.”
`
`4.
`
`As to the second issue, the GB ’072 application contains a written
`
`description that reasonably conveys to a POSA that the inventors had possession of
`
`the claimed methods directed to “solid excretory system tumors,” “advanced solid
`
`excretory system tumor[s],” and “kidney tumor[s]” as of February 19, 2001 as
`
`those terms would be understood in the context of the ’131 Patent.
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`2
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`5.
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`As to the third issue, Wasik did not disclose, teach, or suggest the
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`claim elements “solid excretory system tumors,” “advanced solid excretory system
`
`tumor[s],” “kidney tumor[s],” or inhibiting growth of “advanced solid excretory
`
`system tumor[s].”
`
`6.
`
`As to the fourth issue, I disagree with Dr. Pantuck that a POSA would
`
`have been motivated to specifically select everolimus for the development of a new
`
`therapy for advanced RCC in February 2001. The reality is that, as of February
`
`2001, it was not known and would not have been reasonably predictable what was
`
`going to be effective to treat RCC so a POSA, like those in the art at that time,
`
`would have considered and pursued many approaches to find new anti-cancer
`
`therapies for RCC including the use of immunotherapy, and efforts to target
`
`growth factors, amongst others.
`
`7.
`
`As to the fifth issue, a POSA would not have been motivated to
`
`combine the everolimus and rapamycin references in Ground 3.
`
`8.
`
`As to the sixth issue, a POSA would not have been motivated to
`
`combine the temsirolimus and everolimus references in Ground 4 or Ground 5.
`
`9.
`
`In forming these opinions, I have considered the materials referenced
`
`in this declaration, including the declaration of Dr. Pantuck (Ex. 1010). My
`
`opinions are based on those materials and my education, knowledge, and
`
`3
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`experience as a practicing physician, including in the field of RCC as of February
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`2001 and up to the present date.
`
`II. Qualifications
`
`10.
`
`I am a board-certified Oncologist at the Sarah Cannon Research
`
`Institute in Nashville, Tennessee. I am currently the President of Clinical
`
`Operations, the Executive Director of Drug Development, and the Chief Medical
`
`Officer at Sarah Cannon Research Institute. I am also an Associate at Tennessee
`
`Oncology, PLLC in Nashville. I began working in both the RCC field and the
`
`breast cancer field in 1988. I have been involved in 27 everolimus clinical trials,
`
`including 9 related to RCC and 9 related to breast cancer.
`
`11.
`
`I obtained my B.S. in chemistry in 1981 at the United States Military
`
`Academy at West Point. I obtained a Doctor of Medicine degree at the University
`
`of South Alabama, College of Medicine in 1985. Between 1985 and 1991, I
`
`completed my Internship, Residency in Internal Medicine, and Fellowship in
`
`Hematology/Medical Oncology at Brooke Army Medical Center at Fort Sam
`
`Houston in San Antonio, Texas.
`
`12. From 1990 to 1991, I was a Clinical Instructor in the Department of
`
`Medicine/Oncology at The University of Texas Health Science Center in San
`
`Antonio, Texas. From 1991 to 1997, I was a staff member in Hematology/
`
`Oncology Service at both the Cancer Therapy and Research Center of South Texas
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`4
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`and the Brooke Army Medical Center. Between 1991 and 1996, I was an Assistant
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`Professor in the Department of Medicine/Oncology at The University of Texas
`
`Health Science Center, and from 1996 to 1997, I was an Associate Professor there.
`
`From 1992 to 1995, I was the Associate Director, and then the Director, of Clinical
`
`Research in the Institute for Drug Development at the Cancer Therapy and
`
`Research Center of South Texas. And, from 1990 through 1997, I was the Director
`
`of the Drug Development Program at the Brooke Army Medical Center.
`
`13.
`
`I am a member of the following Professional Associations: American
`
`Society of Hematology and Southern Association for Oncology (Affiliation of
`
`Southern Medical Association). I am also a Board Member of Gilda’s Club.
`
`14.
`
`I have been involved with the American Society of Clinical Oncology
`
`(ASCO). I have been elected and served as a member of the ASCO Board of
`
`Directors (2006-2009) as well as Chairman of the Nominating Committee (2010-
`
`2012). I currently serve on the Board of the ASCO Conquer Cancer Foundation.
`
`My ASCO Committee Memberships have included Cancer Research, Education,
`
`Scientific Program, Research Community Forum, Audit, and Sponsorship.
`
`15.
`
`I have received numerous professional honors in my field. For
`
`instance, in 2014, I received the Giant of Cancer Care Award from OncLive.
`
`Giants of Cancer Care are chosen by an exclusive advisory board of 29 oncology
`
`educators, clinicians, and researchers. In evaluating criteria for selection to the
`
`5
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`inaugural class of Giants, the Advisory Board considered individuals who have
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`made a significant contribution to patient care, clinical trials, or translational
`
`research. I was one of 16 luminaries nationwide in 2014 selected for my
`
`achievements in research and clinical practice, which includes specific recognition
`
`for my initiation of one of the largest investigational drug development programs
`
`for cancer. In 2006, I was elected by my peers to serve on the American Society of
`
`Clinical Oncology Board of Directors. In 2008, I was elected by my peers to chair
`
`the American Society of Clinical Oncology nominating committee. From 2001 to
`
`2002, I was the President of the Southern Association for Oncology. I am a fellow
`
`of the American College of Physicians.
`
`16.
`
`I have authored more than 360 published manuscripts and book
`
`chapters, and more than 550 abstracts in the oncology field, including publications
`
`concerning a Phase I/II trial in the treatment of advanced RCC with the
`
`combination of bevacizumab/erlotinib/imatinib in 2007, a Phase II trial of
`
`bevacizumab and everolimus in patients with advanced RCC in 2010 (abstract
`
`2008), a Phase II trial of panobinostat in the treatment of patients with refractory
`
`metastatic RCC in 2011, a Phase I/II trial of lenalidomide in combination with
`
`sunitinib in patients with advanced or metastatic RCC in 2014, and a Phase II trial
`
`of atezolizumab in patients with metastatic urothelial carcinoma (a type of urinary
`
`6
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`system cancer) in 2016. I have also co-authored 11 book chapters in the oncology
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`field.
`
`17.
`
`I have treated hundreds of RCC patients since 1988.
`
`18.
`
`I have been involved in more than 1,000 cancer clinical trials,
`
`including Phase I, II, and III trials.
`
`19. My curriculum vitae is attached to this declaration as Exhibit 2002.
`
`III. Legal Principles
`
`20.
`
`I understand that the Patent Trial and Appeal Board (the “Board”)
`
`interprets the terms in patent claims according to their broadest reasonable
`
`construction in light of the specification of the patent. Absent any special
`
`definitions, claim terms are assigned their ordinary and customary meaning, as
`
`would be understood by a POSA at the time of the invention, in the context of the
`
`entire patent disclosure.
`
`21.
`
`I understand that a patentee can rely on the filing date of a priority
`
`application as the invention date of a patent if the priority application contains a
`
`written description of the invention and would have enabled a POSA to practice
`
`the invention as of the date the priority application was filed. I understand that
`
`priority is determined on a claim by claim basis.
`
`22.
`
`I understand that the test for the sufficiency of the written description
`
`is whether the disclosure of the application relied upon reasonably conveys to a
`
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`POSA that the inventors had possession of the claimed subject matter as of the
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`filing date of the application. I further understand that the specification need not
`
`describe what is already known in the art because patent specifications are written
`
`for POSAs, who come to the patent with knowledge of what has come before. In
`
`that context, it is unnecessary to spell out every detail of the invention in the
`
`specification.
`
`23.
`
`I understand that a claim is anticipated only if each and every element
`
`as set forth in the claim is found, either expressly or inherently described, in a
`
`single prior art reference. What a prior art reference discloses or teaches is
`
`determined from the perspective of a POSA.
`
`24.
`
`I understand that the claims of the ’131 Patent are “obvious” only if
`
`their subject matter, as a whole, would have been obvious to a POSA as of the
`
`invention date.
`
`25.
`
`I understand the Board will determine whether an invention is obvious
`
`by assessing: (i) the level of ordinary skill in the art; (ii) the scope and content of
`
`the prior art; (iii) the differences between the prior art and subject matter claimed;
`
`and (iv) the existence of any objective evidence of non-obviousness, such as
`
`unexpected results.
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`26. When considering the differences between the prior art and the subject
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`matter claimed, I understand that the Board will assess whether each element of the
`
`challenged claim is taught or suggested by the prior art.
`
`27.
`
`I further understand that the Board will consider whether the prior art
`
`would have provided a POSA with a motivation to select and combine the
`
`teachings of the references that the Petitioner has relied upon to arrive at the
`
`claimed invention with a reasonable expectation of successfully practicing the
`
`claimed invention. More specifically, in determining obviousness in cases
`
`involving new methods of treatment involving a known compound, I understand
`
`that the Board will consider whether a POSA would have selected the claimed
`
`compound over other available prior art compounds. I understand that a POSA
`
`may select one or more prior art compounds from the available options for further
`
`development in the new method of treatment, and that the claimed compound need
`
`not be the “most desirable” or “preferred” compound, but that a POSA nonetheless
`
`must have a reason to make the selection based on a review of the prior art as a
`
`whole.
`
`28. Finally, I also understand that it is improper in the obviousness
`
`analysis to use hindsight knowledge of the claimed invention itself.
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`IV. POSA
`
`29. For the purposes of this declaration, I have been asked to consider the
`
`state of the art as of February 19, 2001, and to analyze the anticipation and
`
`obviousness issues identified above (in paragraph 2) as of that date. (Ex. 1010,
`
`Pantuck Decl. ¶ 16.) My opinions in this declaration would be the same if I
`
`analyzed the anticipation and obviousness issues as of February 18, 2002, like Dr.
`
`Pantuck does (Ex. 1010, Pantuck Decl. ¶ 16). I have also analyzed the anticipation
`
`and obviousness issues from the perspective of a POSA, and for the purposes of
`
`this declaration, I have adopted the definition of such a person provided by Dr.
`
`Pantuck. (Ex. 1010, Pantuck Decl. ¶ 20.)
`
`V.
`
`State Of The Art
`
`A. Tumor Background
`
`30.
`
`In 2001, tumors were known to be abnormal tissue growths or masses
`
`that served no useful purpose. (Ex. 2004, Altman at 278.) A tumor could have
`
`been benign or malignant. Benign tumors grew in the place where they originated,
`
`whereas malignant tumors spread to other parts of the body. (Ex. 2004, Altman at
`
`278.)
`
`31. Tumors were generally classified into two separate categories based
`
`on the type of cell from which they originated: solid tumors and liquid tumors.
`
`The distinguishing feature between a solid and liquid tumor was not the
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`appearance of the tumor (e.g., a solid mass), but the type of cell from which it
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`originated. The term solid tumor was used to describe any tumor that began as a
`
`distinct mass or lump arising in cells other than the lymphatic system (e.g., lymph
`
`tissue, lymph nodes) and the bone marrow. (Ex. 2003, Laughlin1 at 126.)
`
`Conversely, liquid tumors, which were also known as blood cancers, arose from
`
`cells of the lymphatic system and bone marrow. (Ex. 2003, Laughlin at 126.) Dr.
`
`Pantuck agrees that tumors “can be distinguished as ‘solid’ or ‘liquid’ based on the
`
`type of cells from which they arise…. Liquid tumors … also commonly called
`
`blood cancers, are cancers that arise from cells of the bone marrow, the blood, and
`
`the lymphatic system.” (Ex. 1010, Pantuck Decl. ¶¶ 72, 124; Ex. 1041, Perez-
`
`Atayd at 816.)
`
`32. The term tumor could have applied to both solid and liquid tumors,
`
`depending on the context in which the term appeared. Tumor was “most often
`
`used to indicate a new growth, particularly a solid cancer.” (Ex. 2003, Laughlin at
`
`140.) For example, the term tumor applied to carcinoma, which was a solid tumor
`
`
`
`
` This glossary published a year after the ’131 Patent invention date reflects the
`
` 1
`
`understanding in the art in 2001.
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`originating in the surface tissue of body organs. (Ex. 2004, Altman at 51.) But the
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`term tumor also applied to non-solid, liquid tumors such as myeloma (a cancerous
`
`tumor originating in the plasma cells of the bone marrow) and lymphoma (a
`
`cancerous tumor originating in the lymph system). (Ex. 2004, Altman at 51.)
`
`B.
`
`Lymphoma Background
`
`33. Lymphomas were known to occur in organs throughout the body, but
`
`they arose from lymphatic cells, not organ cells. (Ex. 2003, Laughlin at 188.) A
`
`primary extranodal lymphoma referred to a localized presentation of lymphoma
`
`arising at a site outside the lymph nodes that was deemed to be the site of origin of
`
`the lymphoma. (Ex. 2005, Sutcliffe 1998 at 449.) Extranodal lymphomas had
`
`been observed in virtually every tissue in the body, either as primary or metastatic
`
`lesions, i.e., tumors. (Ex. 2005, Sutcliffe 1998 at 449.) As of 2001, the most
`
`frequent cites for extranodal lymphomas included the stomach, skin, oral cavity
`
`and pharynx, small intestine, and CNS. (Ex. 2006, Pazdur at 584.) However,
`
`extranodal lymphomas had also been identified in less common sites such as the
`
`kidney and bladder (Ex. 2005, Sutcliffe 1998 at 466), breast (Ex. 2006, Pazdur at
`
`591), ovary (Ex. 2007, Sutcliffe 1992 at 209), liver (Ex. 2007, Sutcliffe 1992 at
`
`213), and brain (Ex. 2007, Sutcliffe 1992 at 194, 202).
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`C. Kidney Tumor And RCC Background
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`34. Kidney cancer was a type of cancer that arose from the cells of the
`
`kidney. There were several known types of kidney cancer, including malignant
`
`tumors such as renal cell carcinoma (RCC), transitional cell carcinoma (TCC), also
`
`known as urothelial carcinoma, Wilms’ tumor (nephroblastoma), and renal
`
`sarcoma. (Ex. 2008, Lynch & Cohen at 317-318, 321-22.) There were also benign
`
`kidney tumors (meaning that they did not metastasize to other parts of the body,
`
`although they could still grow and cause problems) including renal adenoma,
`
`oncocytoma, and angiomyolipoma. (Ex. 2009, Ligato at 1.)
`
`35. As of 2001, RCC was the most common type of kidney cancer,
`
`accounting for 90% of kidney cancer. (Ex. 2003, Laughlin at 174.)
`
`36.
`
`In contrast with solid tumors that arose from the cells of the kidney,
`
`renal lymphoma (or kidney lymphoma) was usually a manifestation of a systemic
`
`disease, e.g., non-Hodgkin’s lymphoma. (Ex. 1042, True at 806.)
`
`D. Advanced Tumors
`
`37. The term “advanced” referred to tumors that were locally advanced
`
`(i.e., the tumor had started to spread into surrounding tissues) or metastatic
`
`(meaning the cancer had spread from where it arose to another body organ). (Ex.
`
`2003, Laughlin at 4 (defining “advanced cancer” as “[a] general term describing
`
`the stages of cancer in which the disease has spread from the primary site to other
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`parts of the body. When the cancer has spread only to the surrounding areas, it is
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`called locally advanced. If it has spread further by traveling though the
`
`bloodstream or lymph system, it is called metastatic.”).) Accordingly, in order to
`
`be advanced, a tumor must already have spread beyond its original site. A
`
`metastasis was known to be a type of advanced tumor.
`
`VI. Summary Of The ’131 Patent
`
`38. The ’131 Patent is entitled “Cancer Treatment.” Claim 1 of the ’131
`
`Patent recites “[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 [everolimus].” Claim 2 of the ’131 Patent
`
`recites “[t]he method of claim 1 wherein the solid excretory system tumor is an
`
`advanced solid excretory system tumor.” Claim 3 of the ’131 Patent recites “[t]he
`
`method of claim 1 wherein the solid excretory system tumor is a kidney tumor.”
`
`39. Claim 5 of the ’131 Patent recites “[t]he method of claim 1 wherein
`
`[everolimus] is administered orally.” Claim 6 of the ’131 Patent recites “[t]he
`
`method of claim 5 wherein [everolimus] is administered at a daily dose range of
`
`from about 0.1 to 25 mg, as a single dose or in divided doses.” Claim 7 of the ’131
`
`Patent recites “[t]he method of claim 5 wherein [everolimus] is administered in a
`
`unit dosage form of from about 0.05 to 12.5 mg.” Claim 8 of the ’131 Patent
`
`recites “[t]he method of claim 5 wherein [everolimus] is administered in a unit
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`dosage form of from about 0.25 to 10 mg.” Claim 9 of the ’131 Patent recites
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`“[t]he method of claim 8 wherein [everolimus] is administered in a unit dosage
`
`form of 10 mg.”
`
`40. Consistent with the state of the art in February 2001, the specification
`
`of the ’131 Patent defines solid tumors as “tumors and/or metastasis (wherever
`
`located) other than lymphatic cancer.” (Ex. 1001, ’131 Patent at col. 2, ll. 20-21.)
`
`The ’131 Patent specification defines “lymphatic cancer” as “tumors of the blood
`
`and lymphatic system,” e.g., “Hodgkin’s disease, Non-Hodgkin’s lymphoma . . .
`
`[and] haematopoletic [sic: hematopoietic] and related tissues,” amongst many
`
`others. (Ex. 1001, ’131 Patent at col. 4, ll. 20-30.) Hematopoietic tissue referred
`
`to the bone marrow. (Ex. 1041, Perez-Atayde at 817.)
`
`41. The ’131 Patent specification defines several different classes of solid
`
`tumors by their tissue of origin. “[E]xcretory system tumors” are defined as
`
`tumors arising from the cells of the urinary excretory system, which includes the
`
`“kidney, renal pelvis, ureter, bladder, [sic, and] other unspecified urinary organs.”
`
`(Ex. 1001, ’131 Patent at col. 2, ll. 28-29.) A POSA would have known that other
`
`urinary organs included the urethra. The ’131 Patent specification clearly
`
`distinguishes tumors of the urinary excretory system as separate from other classes
`
`of solid tumors, such as “gastrointestinal tract tumors” (which include the small
`
`intestine and colon), “respiratory tract tumors” (which include the lungs), and “skin
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`tumors.” (Ex. 1001, ’131 Patent at col. 2, ll. 30-32, 43-45, 47-50.) A POSA would
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`have understood that in the context of the ’131 Patent, “excretory system tumors”
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`were limited to tumors of the urinary excretory system.
`
`42. The ’131 Patent specification discloses that a tumor is defined by the
`
`cell type of origin, not the location of the tumor or metastasis. The ’131 Patent
`
`specification states “[w]here hereinbefore and subsequently a tumor, a tumor
`
`disease, a carcinoma or a cancer is mentioned, also metastasis in the original organ
`
`or tissue and/or in any other location are implied alternatively or in addition,
`
`whatever the location of the tumor and/or metastasis is.” (Ex. 1001, ’131 Patent at
`
`col. 2, ll. 58-62.) This means, for example, that if bladder cancer metastasizes to
`
`the lungs (or any other location), the metastasis is made up of abnormal bladder
`
`cells, not of abnormal lung cells. In other words, wherever the location of the
`
`metastasis, it is defined by the cell type of origin.
`
`43. Based on the foregoing disclosures in the specification and the state of
`
`the art, a POSA would have understood “solid excretory system tumor” to mean
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`“tumors and/or metastases, other than tumors and/or metastases of the blood or
`
`lymphatic system, which arise from the cells of the urinary excretory system.”
`
`44.
`
` Based on the foregoing disclosures in the specification and the state
`
`of the art, a POSA would have understood an “advanced solid excretory system
`
`tumor” to mean “locally advanced or metastatic tumors, other than tumors and/or
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`metastases of the blood or lymphatic system, which arise from the cells of the
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`urinary excretory system.”
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`45.
`
` Based on the foregoing disclosures in the specification and the state
`
`of the art, a POSA would have understood a “kidney tumor” to mean “a tumor
`
`and/or metastasis, other than a tumor and/or metastasis of the blood or lymphatic
`
`system, which arises from the cells of the kidney.”
`
`VII. GB ’072 Contains A Written Description Of The Invention
`
`46.
`
`I understand that the ’131 Patent claims priority to the ’GB ’072
`
`application, which was filed on February 19, 2001.
`
`47. Dr. Pantuck alleges that the GB ’072 application does not describe the
`
`full scope of the ’131 Patent claims directed to “solid excretory system tumors,”
`
`“advanced solid excretory system tumor[s],” and “kidney tumor[s].” (Ex. 1010,
`
`Pantuck Decl. ¶¶ 146-147.) I understand that Dr. Pantuck does not allege that GB
`
`’072 would not have enabled a POSA to practice the invention as of February 19,
`
`2001.
`
`48.
`
`In my opinion, as discussed below, the GB ’072 application contains a
`
`written description that reasonably conveys to a POSA that the inventors had
`
`possession of the claimed methods directed to “solid excretory system tumors, and
`
`“advanced solid excretory system tumor[s],” and “kidney tumor[s]” as of February
`
`19, 2001 as those terms would be understood in the context of the ’131 Patent.
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`49. The GB ’072 application discloses the use of compounds of formula I
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`that “have potent antiproliferative properties which make them useful for cancer
`
`chemotherapy, particularly of solid tumors, especially of advanced solid tumors.”
`
`(Ex. 1012 at 2 (emphasis added).) The GB ’072 application discloses everolimus
`
`as a preferred compound. (Ex. 1012 at 1.)
`
`50. The GB ’072 application discloses that “[b]y ‘solid tumors’ are meant
`
`tumors and/or metastasis (whereever located) other than lymphatic cancer, e.g.
`
`pancreatic tumors; melanomas; lung cancer, e.g. small cell lung cancer; breast
`
`cancer; epidermoid carcinomas; renal-cell carcinomas; neuroendocrine tumors;
`
`genitourinary cancer, e.g. cervical, uterine, ovarian, prostate or bladder cancer;
`
`gastrointestinal cancer, e.g. gastric or colon cancer; glioblastomas; head and/or
`
`neck cancer; soft-tissue sarcomas.” (Ex. 1012 at 2 (emphasis added).) As
`
`described above, the term solid tumor was used to describe any tumor arising from
`
`cells other than the lymphatic system and bone marrow cells.
`
`51. The GB ’072 application discloses that a tumor is defined by the cell
`
`type of origin because the GB ’072 application states “[w]here hereinbefore and
`
`subsequently a tumor, a tumor disease, a carcinoma or a cancer is mentioned, also
`
`metastasis in the original organ or tissue and/or in any other location are implied
`
`alternatively or in addition, whatever the location of the tumor and/or metastasis
`
`is.” (Ex. 1012 at 3.) This means, for example, that if bladder cancer metastasizes
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`to the lungs (or any other location), the metastasis is made up of abnormal bladder
`
`cells, not of abnormal lung cells. In other words, wherever the location of the
`
`metastasis, it is defined by the cell type of origin.
`
`52. A POSA would have understood that the “solid tumors” disclosed in
`
`the GB ’072 application can be benign or malignant because the GB ’072
`
`application states that wherever “a tumor” is mentioned “also metastasis in the
`
`original organ or tissue and/or in any other location are implied.” (Ex. 1012 at 3
`
`(emphasis added).) A POSA would have understood that “a tumor” can be benign
`
`or malignant, but a “metastasis” is a malignant growth. Because “a tumor” also
`
`implies a “metastasis,” a POSA would have understood that the tumors referenced
`
`in the GB ’072 application can be benign or malignant. A POSA would also have
`
`understood that “metastasis” as disclosed in the GB ’072 application refers to
`
`advanced tumors.
`
`53. Accordingly, a POSA would have understood that the GB ’072
`
`application describes benign or malignant solid tumors, wherever located, that
`
`arise from cells other than lymphatic system or bone marrow cells.
`
`54.
`
` A POSA would be led by the express disclosures of the GB ’072
`
`application to conclude that the invention includes a method of using everolimus to
`
`treat tumors arising from the cells of the urinary excretory system. As described
`
`above, the GB ’072 application describes “renal-cell carcinomas” and
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`“genitourinary cancer, e.g. cervical, uterine, ovarian, prostate or bladder cancer”
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`as types of solid tumors that everolimus can treat. (Ex. 1012 at 2 (emphasis
`
`added).) A POSA would have understood that other urinary excretory system
`
`tumors apart from RCC and bladder cancer included tumors of the kidney, renal
`
`pelvis, ureter, and urethra. (Ex. 1044, Bahnson at 371-377; Ex. 1043, Jennings at
`
`643.)
`
`55. A POSA would be led by the express disclosures of the GB ’072
`
`application to conclude that the invention includes a method of using everolimus to
`
`treat advanced