`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`__________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`__________________________
`
`DR. REDDY’S LABORATORIES, INC.,
`Petitioner
`v.
`GENENTECH, INC., HOFFMANN-LA ROCHE AG, AND ABBVIE INC.,
`Patent Owner.
`
`__________________________
`
`PTAB Case No. PGR 2022-00023
`
`Patent No. 10,993,942
`__________________________
`
`DECLARATION OF JEFFREY A. GORDON, M.D. IN SUPPORT OF
`PETITION FOR POST GRANT REVIEW OF U.S. PATENT NO. 10,993,942
`__________________________
`
`
`
`DRL EXHIBIT 1020 PAGE 1
`
`

`

`TABLE OF CONTENTS
`
`
`Page
`
`
`I.
`
`II.
`
`INTRODUCTION ....................................................................................... 5
`A.
`Background and Expertise ................................................................ 6
`B.
`Bases for Opinions and Materials Considered ................................ 10
`C.
`Scope of Work ................................................................................. 10
`LEGAL STANDARDS FOR PATENTABILITY .................................... 11
`A.
`Person of Ordinary Skill in the Art ................................................. 12
`B. Written Description ......................................................................... 12
`C.
`Claim Construction.......................................................................... 13
`D.
`Priority Dates ................................................................................... 13
`E.
`Burden of Proof ............................................................................... 14
`PERSON OF ORDINARY SKILL IN THE ART .................................... 14
`III.
`IV. SUMMARY OF OPINIONS ..................................................................... 16
`V. GENERAL BACKGROUND ................................................................... 16
`A. General Background on CD20 ........................................................ 16
`B.
`General Background on Bcl-2 Inhibitors ........................................ 18
`VI. THE ’942 PATENT (EXHIBIT 1001) ...................................................... 19
`A. General Disclosure .......................................................................... 19
`B.
`Prosecution History ......................................................................... 20
`C.
`The ’942 Patent Specification ......................................................... 21
`1.
`Title, Abstract, Technical Field, and Background ................ 21
`2.
`Summary of the Invention .................................................... 23
`3.
`Detailed Description of the Invention ................................... 25
`4.
`Examples ............................................................................... 32
`The ’942 Patent Claims ................................................................... 36
`1.
`Claims 1-3 & 5-6................................................................... 37
`2.
`Claim 14 ................................................................................ 37
`
`D.
`
`DRL EXHIBIT 1020 PAGE 2
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`

`

`Page
`3.
`Claims 26-27 and 30 ............................................................. 38
`Comparison of claims ........................................................... 39
`4.
`VII. THE ’379 PROVISIONAL APPLICATION ............................................ 39
`A.
`The ’379 Provisional Application Specification ............................. 39
`B.
`The ’379 Provisional Application Claims ....................................... 41
`VIII. UNPATENTABILITY OF THE ’942 PATENT ...................................... 42
`A.
`Claims 1-3, 5-6, 14, 25-27, and 30 of the ’942 Patent
`Lack Written Description in the ’942 Patent Specification ............ 42
`1.
`The specification makes clear that the disclosed
`“invention” is a combination therapy. .................................. 42
`GDC-0199 monotherapy is not disclosed. ............................ 45
`The claimed escalating-dose limitations are not
`disclosed. ............................................................................... 47
`Even if the individual elements were disclosed,
`nothing in the specification would disclose their
`combination. .......................................................................... 49
`Claims 1-3, 5-6, 14, 25-27, and 30 of the ’942 Patent
`Lack Written Description in the ’379 Provisional .......................... 52
`IX. CONCLUSION .......................................................................................... 53
`APPENDIX A (CLAIMS OF THE ’942 PATENT) ........................................... 54
`APPENDIX B (CLAIMS OF THE ’379 PROVISIONAL
`APPLICATION) ........................................................................................ 58
`
`2.
`3.
`
`4.
`
`B.
`
`TABLE OF CONTENTS
`(continued)
`
`DRL EXHIBIT 1020 PAGE 3
`
`

`

`
`
`LIST OF APPENDICES
`
`Appendix A
`
`Claims of the ’942 Patent
`
`Appendix B
`
`Claims of the ’379 Provisional Application
`
`DRL EXHIBIT 1020 PAGE 4
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`I, Dr. Jeffrey A. Gordon, declare as follows:
`I. INTRODUCTION
`I, Dr. Jeffrey A. Gordon, am over eighteen years of age and am
`1.
`
`competent to testify as to the matters set forth herein if I am called on to do so.
`
`2.
`
`I have been retained by Dr. Reddy’s Laboratories, Inc. (which I refer
`
`to as “DRL”) as an expert for this post-grant review proceeding.
`
`3.
`
`I understand that this post-grant review (“PGR”) relates to United
`
`States Patent No. 10,993,942 (which I refer to as “the ’942 patent”). The ’942
`
`patent is Exhibit 1001.
`
`4.
`
`I have been asked by counsel for DRL to express my opinions
`
`regarding the validity of certain claims of the ’942 patent. The ’942 patent is titled
`
`“Combination Therapy of a Type II Anti-CD20 Antibody with a Selective Bcl-2
`
`Inhibitor.” The claims of the patent generally concern methods for treating chronic
`
`lymphocytic leukemia (“CLL”) or small lymphocytic lymphoma (“SLL”) in a
`
`patient by administering a chemical compound called GDC-0199 at specific doses.
`
`The patent lists as inventors Deepak Sampath, Christian Klein, Wayne John
`
`Fairbrother, Sari L. Heitner Eschede, Rod A. Humerickhouse, Andrew W. Roberts,
`
`and John F. Seymour, and is assigned to Genentech, Inc.; Hoffman-La Roche Inc.;
`
`and AbbVie Inc. (and I refer to the assignees collectively as “Patent Owner”).
`
`5.
`
`I have only been asked to consider, and have only formed an opinion
`
`DRL EXHIBIT 1020 PAGE 5
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`on, claims 1-3, 5-6, 14, 25-27, and 30 of the ’942 patent.
`
`6.
`
`I submit this Declaration at the request of DRL for consideration by
`
`the Patent Trial and Appeal Board in the above-referenced post-grant review
`
`proceeding.
`
`7.
`
`In forming my opinions, I have relied on my knowledge and
`
`experience in the field of oncology, and on the documents and information
`
`referenced and cited in this Declaration.
`
`A. Background and Expertise
`I am a board-certified diplomat in Medical Oncology and
`8.
`
`Hematology, with over twenty-eight years’ experience in treating patients with
`
`multiple myeloma, eight-and-a-half years serving as the Medical Director of
`
`Hematology-Oncology Services at Day Kimball Hospital, and twelve years serving
`
`as assistant professor at the University of Connecticut School of Medicine and the
`
`University of Massachusetts Medical School.
`
`9.
`
`I received a B.A. from Brandeis University in 1989 and an M.D. from
`
`University of Massachusetts Medical School in 1993. I completed my residency at
`
`the University of Massachusetts Medical Center, Department of Internal Medicine
`
`from 1993 to 1996, and my fellowship training at the University of Massachusetts
`
`Medical Center, Division of Hematology- Oncology from 1996 to 1999.
`
`10. My medical licensures and certifications include the Commonwealth
`
`DRL EXHIBIT 1020 PAGE 6
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`of Massachusetts, State of Connecticut, American Board of Internal Medicine in
`
`Medical Oncology, and American Board of Internal Medicine in Hematology.
`
`11. Post-fellowship, I have been employed by the following hospitals:
`
`Saint Francis Hospital and Medical Center, Hartford, CT (1999-2002); UMass
`
`Memorial Medical Center, Worcester, MA (2002-2011); New London Care
`
`Center, Waterford, CT (2012-2016); Hartford Health Care, Waterford, CT (2016-
`
`2018); Harrington Hospital, Southbridge, MA (2018-2021); and UMassMemorial
`
`Health Harrington, Southbridge, MA (2021-present). Harrington Hospital was
`
`bought by UMassMemorial Health in 2021.
`
`12. Post-fellowship, I have been on the medical staffs of the following
`
`hospitals: Saint Francis Hospital and Medical Center, Hartford, CT (1999-2007);
`
`Bristol Hospital, Bristol, CT (1999-2002); UMass Memorial Medical Center,
`
`Worcester, MA (2002-2013); Day Kimball Hospital, Putnam, CT (2002-2012); W.
`
`Backus Memorial Hospital, Norwich, CT (2012-2018); Harrington Hospital,
`
`Southbridge, MA (2007-2013 and 2018-present); and Lawrence & Memorial
`
`Hospital, New London, CT (2012-present).
`
`13.
`
`I have also been employed as Assistant Professor of Medicine,
`
`University of Connecticut School of Medicine, from 1999 to 2002, and Assistant
`
`Professor of Medicine, University of Massachusetts Medical School, from 2003-
`
`2013.
`
`DRL EXHIBIT 1020 PAGE 7
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`

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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`14.
`
`I have served on a large number of hospital committees from 1999 to
`
`present, including such positions as Medical Executive Committee, elected At-
`
`Large Representative, Lawrence & Memorial Hospital (2013-2016); Quality
`
`Council, Lawrence & Memorial Hospital (2013-2016); Tumor Board, Lawrence &
`
`Memorial Hospital (2012-2018); Medical Director, Hematology-Oncology
`
`Services, Day Kimball Healthcare (2003-2011); Pharmacy and Therapeutics
`
`Committee, Day Kimball Healthcare, Member, Co-Chair, and then Chair (2002-
`
`2011); Medical Care Evaluation Committee, Day Kimball Healthcare (2010-2011);
`
`Pharmacy and Therapeutics Committee, UMass Memorial Medical Center,
`
`Member (2005-2008); Tumor Board, Moderator, Day Kimball Healthcare (2003-
`
`2008; 2010-2011); Hematology-Oncology Fellowship Program, Attending
`
`Physician Supervisor, UMass Memorial Medical Center (2002-2011);
`
`Hematology-Oncology Medical Student Syllabus, Lecturer, University of
`
`Massachusetts Medical School (2003-2010); Enfield Access Center, Medical
`
`Director, Hematology-Oncology Clinic (2000-2002); Hematology-Oncology Drug
`
`Therapeutic Management Subcommittee, Chairman, Saint Francis Hospital (2002);
`
`Hematology-Oncology Medication Safety Committee, Member, Saint Francis
`
`Hospital (2002); and Hematology-Oncology Fellowship Program, Attending
`
`Physician Supervisor, Saint Francis Hospital and University of Connecticut Health
`
`Sciences Center (1999-2002).
`
`DRL EXHIBIT 1020 PAGE 8
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`15.
`
`I have also served the Medical Director of Hematology-Oncology
`
`Services, as a member of the Pharmacy & Therapeutics Committee, and as Tumor
`
`Board Moderator at Harrington Hospital and now the same at UMassMemorial
`
`Health Harrington.
`
`16.
`
`I am or have been a member of the following representative
`
`organizations, for many of which I also held significant leadership roles: American
`
`College of Physicians (1994-2003); American Medical Association (1989-present);
`
`American Society of Clinical Oncology (1989- present); American Society of
`
`Hematology (1997-present); Massachusetts Medical Society (1989-2002);
`
`Connecticut State Medical Society (1999-present); International Association for
`
`the Study of Lung Cancer (2001-2009); New England Cancer Society (2001-2005
`
`(ceased to exist)); Worcester District Medical Society (1989-2002); Hartford
`
`County Medical Association (1999- 2002); and Windham County Medical
`
`Association (2002-present). I am also a member of the American Association of
`
`Blood Banks.
`
`17.
`
`I have been a named author on eleven published papers, including
`
`“Phase I-II trial of daily thalidomide in combination with docetaxel in patients with
`
`relapsed non-small cell lung cancer: A final analysis” (Abstract #17060), published
`
`in 24 Procedures of American Society of Clinical Oncologists in 2004; “A phase
`
`I/II trial of docetaxel and daily thalidomide in patients with preciously treated
`
`DRL EXHIBIT 1020 PAGE 9
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`recurrent non-small cell lung cancer” (Abstract #7281), published in 23 Procedures
`
`of American Society of Clinical Oncologists in 2004. I have been a researcher on
`
`seven clinical trials.
`
`18.
`
`I have been honored by the Rhone-Poulenc Rorer Hematology
`
`Fellows’ Scholarship Program (1998-1999); American Medical Association
`
`Recognition Award for HIV, Pocket Resource Guide (1991); National Heart, Lung,
`
`and Blood Institute Summer Research Fellowship (1989, 1990); and
`
`Undergraduate Research Program, Brandeis University (1988, 1989).
`
`19. Further details of my experience are provided in my curriculum vitae,
`
`which is Exhibit 1021.
`
`B.
`20.
`
`Bases for Opinions and Materials Considered
`In addition to my experience, education, and training, in formulating
`
`and providing these opinions I also considered Exhibits 1001 (the ’942 patent),
`
`1002 (the ’942 patent’s prosecution file history), 1006 (U.S. Patent No. 9,529,251,
`
`or “the ’251 patent”), 1010 (Provisional Application No. 61/698,379), 1013 (U.S.
`
`Patent Publication No. 2017/0281619), and various background journal articles
`
`cited below as Exhibits 1022 to 1030.
`
`C.
`21.
`
`Scope of Work
`I have been retained by DRL as a technical expert in this matter, at my
`
`current standard rate of $600 per hour. No part of my compensation is dependent
`
`DRL EXHIBIT 1020 PAGE 10
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`on my opinions or the outcome of this matter.
`
`22.
`
`I have been asked to opine on various issues related to the ’942 patent,
`
`including whether certain claims have adequate written description support.
`
`23.
`
`I may also testify in response to papers, expert testimony, or other
`
`evidence submitted on behalf of Patent Owner.
`
`24. As noted, the opinions here are based on, among other things, my
`
`personal knowledge, background, education, and experience, as well as materials I
`
`have considered in preparation of this Declaration.
`
`25.
`
`I have reviewed and considered the ’942 patent and related materials
`
`in view of the general knowledge in the relevant field(s) from the perspective of a
`
`person of ordinary skill in the art (or “POSA” for short) relevant to the ’942 patent.
`
`These opinions are made from the point of view of a POSA at the alleged priority
`
`date; that is, the 2012-to-2013 timeframe. My opinions here do not change if the
`
`viewpoint were as of the ’942 patent’s 2020 filing date. To the extent that specific
`
`timing within that timeframe matters to my analysis, I will note it below.
`
`II. LEGAL STANDARDS FOR PATENTABILITY
`I am not a lawyer. In expressing my opinions and considering the
`26.
`
`subject matter of the claims of the ’942 patent, certain legal principles relevant to
`
`this Declaration have been explained to me. My understanding of those principles
`
`is summarized below.
`
`DRL EXHIBIT 1020 PAGE 11
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`

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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`A.
`27.
`
`Person of Ordinary Skill in the Art
`I understand that the written description analysis (which I discuss
`
`next) is to be conducted from the perspective of a person of ordinary skill in the art
`
`(i.e., “POSA”) at the time of the invention.
`
`B. Written Description
`I understand that a patent claim is invalid if the specification (i.e., the
`28.
`
`body of the application) does not contain a written description of that invention.
`
`This is called the “written description requirement” or “written description” for
`
`short. I understand that the test for written description is whether the specification
`
`would have objectively demonstrated to a POSA that the patent applicant actually
`
`invented, or “possessed,” the claimed subject matter when the patent application
`
`was filed.
`
`29.
`
`I understand that the written description requirement does not require
`
`disclosure of examples or an actual reduction to practice of the claimed invention.
`
`I understand that the specification, however, must show possession of the invention
`
`in the document itself, and evidence of reduction to practice outside of that
`
`specification is not sufficient by itself to satisfy the written description
`
`requirement. I understand that to meet the written description requirement, the
`
`patent specification must describe an invention understandable to a POSA and
`
`show that the inventor actually invented and possessed the invention claimed.
`
`DRL EXHIBIT 1020 PAGE 12
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`30.
`
`I understand that the written description requirement is not met if the
`
`invention is not actually described but would nevertheless be obvious from what is
`
`described. I also understand that the written description requirement is not met if
`
`the invention is not actually described even if a POSA would nevertheless be able
`
`to practice the invention.
`
`C. Claim Construction
`31. The claims of a patent define the invention. I understand that in a
`
`post-grant review (or “PGR”), claim terms must be given their ordinary and
`
`customary meaning to a POSA at the relevant time of the invention and in light of
`
`the intrinsic evidence (the specification and the prosecution history).
`
`32. While extrinsic evidence (such as scientific references) may be
`
`considered, I understand that it is less significant than the intrinsic record to
`
`determine the meaning of the claims.
`
`33. To the extent that any specific claim constructions are meaningful to
`
`my analysis, as opposed to the general understanding a POSA would have of claim
`
`terms, I have attempted to address them below.
`
`D.
`34.
`
`Priority Dates
`I understand that a patent may claim priority to the date on which its
`
`patent application was filed. I have also been informed that a patent application is
`
`entitled to the benefit of the filing date of an earlier-filed application, like a
`
`DRL EXHIBIT 1020 PAGE 13
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`

`

`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`provisional application, only if the disclosure of the earlier application provides
`
`support for the claims of the later application. This is called “claiming priority
`
`from” the earlier application.
`
`E.
`35.
`
`Burden of Proof
`I understand that DRL has the burden to prove that the claims of
`
`the’942 patent are invalid by a preponderance of the evidence. I am informed that
`
`this preponderance of the evidence standard means that DRL must show that
`
`unpatentability is more probable than not. I have taken these principles into
`
`account when forming my opinions in this case.
`
`III. PERSON OF ORDINARY SKILL IN THE ART
`36. As noted above, I understand that my analysis is to be conducted from
`
`the perspective of a POSA at the time of the ’942 patent’s effective filing date,
`
`which I will assume for the purposes of this Declaration is either when the
`
`provisional application from which it claims priority was filed (September 7, 2012
`
`for Provisional Application No. 61/698,379) or when the first nonprovisional
`
`application from which it claims priority was filed (September 6, 2013 for
`
`Application No. 14/020,761). If that date was instead when the ’942 patent was
`
`filed on March 23, 2020, or any time in between, my ultimate opinion that the
`
`claims of the ’942 patent are invalid would not change.
`
`37.
`
`I understand that the background and qualifications of a POSA may
`
`DRL EXHIBIT 1020 PAGE 14
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`

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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`be influenced by the following factors: (i) the education level of the inventor; (ii)
`
`the type of problems encountered in the art; (iii) prior art solutions to those
`
`problems; (iv) the rapidity with which innovations are made; and (v) the
`
`sophistication of the technology and education level of active workers in the field.
`
`38. A POSA would have had as of the relevant time above several years
`
`of experience as a medical professional (e.g., an MD with experience in clinical
`
`oncology or pharmacology, a PhD in pharmacology, pharmaceutical chemistry,
`
`cancer biology, or a related discipline, or a PharmD with experience in clinical
`
`oncology), with practical working knowledge of oncology (e.g., direct experience
`
`administering therapeutic agents of the treatment of cancer, as well as familiarity
`
`with the dosing schedules and frequencies of the different therapeutic agents
`
`available for cancer treatment, as well as side effects or adverse events that occur
`
`with these treatments). A POSA would also have had experience with the design
`
`of studies necessary for drug development. This experience may come from the
`
`POSA’s own experience or may come through the guidance of other individual(s)
`
`with experience in the pharmaceutical industry; e.g., as members of a research
`
`team or group. A POSA would also be well versed in the world-wide literature on
`
`cancer that was available as of the priority date. That said, the points in this
`
`Declaration would be unchanged under any reasonable definition of the person of
`
`ordinary skill.
`
`DRL EXHIBIT 1020 PAGE 15
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`

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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
`
`IV. SUMMARY OF OPINIONS
`39. For the reasons set forth below, it is my opinion that claims 1-3, 5-6,
`
`14, 25-27, and 30 of the ’942 patent are invalid because they lack written
`
`description. I have not been asked to form an opinion on the other claims.
`
`V. GENERAL BACKGROUND
`40. This patent involves compounds that target two biologically
`
`significant proteins, CD20 and Bcl-2. See generally Ex. 1001.
`
`A. General Background on CD20
`41. CD20 is a protein found on B-cells, a type of white blood cell. See,
`
`e.g., T. van Meerten et al., CD20-Targeted Therapy: A Breakthrough in the
`
`Treatment of Non-Hodgkin’s Lymphoma, 67(7) NETH. J. MED. 251 (2009)
`
`(Ex. 1022). Its normal function within a healthy individual is to help B-cells
`
`engage in immune responses through its involvement in B-cell activation,
`
`proliferation, and differentiation. See, e.g., Ex. 1022 (van Meerten). But for
`
`patients with certain kinds of B-cell-based lymphomas and leukemias, CD20 is
`
`found in higher-than-normal amounts, and it is involved in the biological
`
`mechanisms that make those cancers harmful. See, e.g., K. Bauer et al., Rituximab,
`
`Ofatumumab and Other Monoclonal Anti-CD20 Antibodies for Chronic
`
`Lymphocytic Leukaemia, 11(11) COCHRANE DATABASE SYST. REVS. (2012)
`
`(Ex. 1023); Ex. 1022 (van Meerten). Accordingly, CD20 has become an important
`
`protein both for diagnosis and for treatment of certain B-cell-based cancers. See,
`
`DRL EXHIBIT 1020 PAGE 16
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`e.g., Ex. 1023 (Bauer); S. Cang et al., Novel CD20 Monoclonal Antibodies for
`
`Lymphoma Therapy, 5 J. HEMATOL. & ONCOL. 64 (2012) (Ex. 1024); Ex. 1025
`
`(van Meerten); E. Oflazoglu et al., Evolution of Anti-CD20 Monoclonal Antibody
`
`Therapeutics in Oncology, 2(1) MABS 14 (2010) (Ex. 1025).
`
`42. Among those therapies are a wide swath of antibodies that target
`
`CD20, which has been used as an anticancer strategy at least since the 1990s. See,
`
`e.g., Ex. 1025 (Oflazoglu); Ex. 1022 (van Meerten). Such antibodies often
`
`function to selectively recognize, bind, and “flag” unwanted cells for removal by
`
`the immune system by means of complement-mediated killing or antibody-
`
`dependent cellular cytotoxicity. See, e.g., Ex. 1022 (van Meerten); Ex. 1025
`
`(Oflazoglu). Others, like antibody-drug conjugates, might selectively bind to
`
`cancer cells and deliver targeted chemotherapy drugs or toxins specifically to those
`
`cells. See, e.g., M. Fanale et al., Phase I/Ib Study of the Novel CD20-Targeted
`
`Immunotoxin MT-3724 in Relapsed/Refractory Non-Hodgkin’s B-Cell Lymphoma,
`
`Proceedings of the 107th Annual Meeting of the American Association for Cancer
`
`Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; 76 (14
`
`Suppl) CANCER RSCH. Abstract No. CT049 (2016) (Ex. 1026); J. Morris et al.,
`
`Antibody-Based Therapy of Leukaemia, 11 EXPERT REVS. MOL. MED. 1 (2009)
`
`(Ex. 1027).
`
`43. Antibodies are structurally and functionally diverse, and are often
`
`DRL EXHIBIT 1020 PAGE 17
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`characterized both by their structure and by the locations on target proteins at
`
`which they bind. See, e.g., A. Beck et al., Strategies and Challenges for the Next
`
`Generation of Therapeutic Antibodies, 10 NAT. REVS. IMMUNOL. 345 (2010)
`
`(Ex. 1028). In the context of this patent, two particular classes of anti-CD20
`
`antibodies (i.e., antibodies that bind selectively to the CD20 protein) are relevant:
`
`type I and type II. Ex. 1001 at 1:61-2:19; see also, e.g., Ex. 1022 (van Meerten).
`
`The two types differ in their modes of CD20 binding and biological activities.
`
`Ex. 1001 at 1:61-2:19; Ex. 1022 (van Meerten). The ’942 patent points this out in
`
`part, suggesting that type I antibodies are “potent in complement mediated
`
`cytotoxicity, whereas type II antibodies . . . effectively initiate target cell death via
`
`caspase-independent apoptosis with concomitant phophatidylserine exposure.”
`
`Ex. 1001 at 1:65-2:3. In effect, type II antibodies directly cause target cell death.
`
`Ex. 1022 (van Meerten).
`
`B. General Background on Bcl-2 Inhibitors
`44. A second set of proteins is the Bcl-2 family. Some proteins in this
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`family promote cell survival, and others drive apoptosis (i.e., programmed cell
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`death). See, e.g., J. Chipuk et al., The BCL-2 Family Reunion, 37 MOL. CELL 299
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`(2010) (Ex. 1029). Selective inhibition of some of them, then, can help control
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`either cell survival or cell death. See, e.g., Ex. 1029 (Chipuk); M. Kang et al., Bcl-
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`2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy,
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`DRL EXHIBIT 1020 PAGE 18
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`15(4) CLIN. CANCER RSCH. 1126 (2009) (Ex. 1030).
`
`45. One selective Bcl-2 inhibitor is GDC-0199, also known by its
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`chemical name 2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-
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`4,4-dimethylcyclohex-1-enyl)methyl)piperazin-1-yl)-N-(3-nitro-4-(((tetrahydro-
`
`2H-pyran-4-yl)methyl)amino)phenylsulfonyl)benzamide. Ex. 1001 at 14:59-67. It
`
`is pictured in the ’942 patent as Formula I:
`
`
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`Ex. 1001 at 15:1-33.
`
`VI. THE ’942 PATENT (EXHIBIT 1001)
`A. General Disclosure
`46. The ’942 patent purports to disclose a “combination therapy”
`
`involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the
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`DRL EXHIBIT 1020 PAGE 19
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`treatment of a patient suffering from cancer, particularly, a CD20-expressing
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`cancer. See, e.g., Ex. 1001 at Abstract.
`
`47. The claims of the ’942 patent, however, are directed to methods for
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`treating chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
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`(SLL) in a patient, the method comprising orally administering GDC-0199 in
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`escalating doses to the patient. See, e.g., Ex. 1001 at claim 1.
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`48. The specification of the ’942 patent does not disclose specific
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`examples or embodiments of escalating-dose GDC-0199 monotherapy. Nor does it
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`disclose any examples or embodiments of treating patients with a GDC-0199
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`monotherapy at all.
`
`B.
`49.
`
`Prosecution History
`I understand that the ’942 patent lists its earliest related application as
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`U.S. provisional application No. 61/698,379, which was filed on September 7,
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`2012. See Ex. 1001 at ¶ (60). I refer to this as “the ’379 provisional application.”
`
`See Ex. 1010 (provisional application).
`
`50.
`
`I also understand that the ’942 lists related two related applications.
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`The first related application listed is No. 15/365,595, which was filed on
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`November 30, 2016. The second related application listed is No. 14/020,761,
`
`which was filed on September 6, 2013. The second application later issued as U.S.
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`Patent No. 9,539,251. See Ex. 1001 at ¶ (63); Ex. 1006.
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`DRL EXHIBIT 1020 PAGE 20
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`51.
`
`I understand that the application leading to the ’942 patent was
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`No. 16/827,650, and that it was filed on March 23, 2020. See Ex. 1001 at ¶¶ (21),
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`(22); see also Ex. 1002 (file history for ’942 patent). The ’942 patent issued on
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`May 4, 2021. See Ex. 1001 at ¶ (45).
`
`C. The ’942 Patent Specification
`In this section, I explain the disclosure of the ’942 patent specification
`52.
`
`from the perspective of a person of ordinary skill in the art (or “POSA”). For
`
`convenience, I will proceed in order through the disclosure.
`
`Title, Abstract, Technical Field, and Background
`1.
`53. The ’942 patent is titled “Combination Therapy of a Type II Anti-
`
`CD20 Antibody with a Selective Bcl-2 Inhibitor.” As a POSA, this says to me that
`
`the application is saying is the invention is only a combination therapy. See
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`Ex. 1001 at 1:1-3.
`
`54. The Abstract of the ’942 patent states that the “present invention is
`
`directed to a combination therapy involving a type II anti-CD20 antibody and a
`
`selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer,
`
`particularly, a CD20-expressing cancer.” See Ex. 1001 at Abstract. As a POSA,
`
`again this tells me that the disclosed invention here is a combination therapy that
`
`uses both the inhibitor and the antibody. It also tells me that the invention is
`
`particularly relevant to cancers that express the CD20 protein, which further
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`DRL EXHIBIT 1020 PAGE 21
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`emphasizes why the anti-CD20 antibody is there.
`
`55. The Technical Field next says that the “present invention” is “directed
`
`to a combination therapy involving a type II anti-CD20 antibody and a selective
`
`Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly a
`
`CD20-expressing cancer.” See Ex. 1001 at 1:20-23. Monotherapy is not
`
`mentioned. As a POSA, this again signals to me that the only disclosure here is of
`
`a combination therapy. This section also mentions that the invention is
`
`“particularly” for a CD20-expressing cancer. This makes sense for a combination
`
`therapy involving an anti-CD20 antibody, but it would not make sense for a
`
`monotherapy, because I see nothing in the patent biologically linking just a Bcl-2
`
`inhibitor (like GDC-0199) to a CD20-expressing cancer.
`
`56. The Background section comes next. See Ex. 1001 at 1:27-3:57. The
`
`first paragraph explains what the CD20 protein is and which kind of cancer cells it
`
`is expressed on. Ex. 1001 at 1:27-43. The Background next discusses specific
`
`structural regions of the CD20 protein. Ex. 1001 at 1:45-60. After that, the
`
`specification differentiates two kinds of anti-CD20 antibodies, type I and type II.
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`Ex. 1001 at 1:61-2:19. The type II antibodies are the ones mentioned in the title
`
`and Technical Field sections above.
`
`57. The next part of the Background section is about the Bcl-2 family of
`
`proteins. Ex. 1001 at 2:20-3:57. This section mentions that the “Bcl-2 family of
`
`DRL EXHIBIT 1020 PAGE 22
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`Declaration of Gordon In Support of Post-Grant Review of U.S. Pat. No. 10,993,942
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`proteins regulates programmed cell death” and that some proteins in this family
`
`promote cell survival whereas others drive apoptosis. Ex. 1001 at 2:20-3:41. It
`
`also points out aspects of the Bcl-2 family that are “poorly understood” or
`
`“uncertain.” E.g., Ex. 1001 at 2:50-52, 3:20-21. This section also mentions that
`
`“various” Bcl-2 inhibitors exist. Ex. 1001 at 3:42. It says that they have the
`
`property of “inhibiting prosurvival members of the Bcl-2 family of proteins and are
`
`therefore promising candidates fo