Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 1 of 50 PageID #: 23718
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`GENENTECH, INC. and CITY OF HOPE,
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`v.
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`AMGEN, INC.,
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`Plaintiffs,
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`Defendant.
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`C.A. No. 18-924-CFC
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`EXPERT DECLARATION OF SUSAN TANNENBAUM M.D. IN SUPPORT OF
`GENENTECH’S EMERGENCY MOTION FOR TEMPORARY RESTRAINING
`ORDER AND PRELIMINARY INJUNCTION
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`PUBLIC VERSION FILED:
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`July 19, 2019
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 2 of 50 PageID #: 23719
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`TABLE OF CONTENTS
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`I. 
`
`II. 
`
`III. 
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`IV. 
`
`V. 
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`INTRODUCTION ...............................................................................................................3 
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`BACKGROUND AND QUALIFICATIONS .....................................................................3 
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`BACKGROUND .................................................................................................................4
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`A. 
`
`B. 
`
`Types of Cancer and Cancer Treatments .................................................................4
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`HER2-Positive Breast Cancer and Herceptin ..........................................................6 
`
`THE DOSING PATENTS .................................................................................................8 
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`INFRINGEMENT ANALYSIS .........................................................................................11
`
`A. 
`
`B. 
`
`C. 
`
`Legal Principles .....................................................................................................11
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`Amgen’s Kanjinti Label .........................................................................................12
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`Infringement of the Dosing Patents .......................................................................13
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`1. 
`
`Physicians Prescribing Kanjinti In Accordance With the Approved Label
`Directly Infringe the Dosing Patents ..........................................................14
`
`a) 
`
`The ’196 Patent, Claim 11 .............................................................14 
`
`i) 
`
`ii) 
`
`iii) 
`
`A method for the treatment of a human patient
`diagnosed with cancer characterized by
`overexpression of ErbB2 receptor, comprising
`administering an effective amount of an anti-ErbB2
`antibody to the human patient, the method
`comprising: ........................................................................14 
`
`administering to the patient an initial dose of at least
`approximately 8 mg/kg of the anti-ErbB2 antibody ..........15 
`
`administering to the patient a plurality of
`subsequent doses of the antibody in an amount that
`is approximately the same or less than the initial
`dose and wherein at least one subsequent dose is
`approximately 6 mg/kg, and ..............................................16 
`
`iv) 
`
`wherein the subsequent doses are separated in time
`from each other by at least three weeks. ............................16 
`
`b) 
`
`The ’379 Patent, Claim 11 .............................................................16 
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 3 of 50 PageID #: 23720
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`i) 
`
`further comprising administering an effective
`amount of a chemotherapeutic agent to the patient ...........17 
`
`c) 
`
`The ’811 Patent, Claim 7 ...............................................................17 
`
`i) 
`
`ii) 
`
`iii) 
`
`iv) 
`
`v) 
`
`A method for the treatment of a human patient
`diagnosed with breast cancer characterized by 2+ or
`3+ overexpression of ErbB2 receptor as determined
`by immunohistochemistry or fluorescence in situ
`hybridization (FISH), the method comprising: ..................17 
`
`administering intravenously to the patient an initial
`dose of 8 mg/kg of anti-ErbB2 huMAb 4D5-8
`antibody..............................................................................19 
`
`and administering intravenously to the patient a
`plurality of subsequent 6 mg/kg doses of the
`antibody, and ......................................................................20 
`
`wherein the initial dose is separated in time from
`the first subsequent dose by three weeks, ..........................20 
`
`wherein the subsequent doses are separated in time
`from each other by at least three weeks. ............................20 
`
`2. 
`
`Amgen Intends for Kanjinti to Be Dosed In Accordance with the
`Approved Label .........................................................................................21 
`
`VI. 
`
`Compensation and Prior Expert Testimony .......................................................................24 
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`VII.  CONCLUSION ..................................................................................................................24 
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 4 of 50 PageID #: 23721
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`I.
`
`INTRODUCTION
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`1.
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`I have been retained as an expert in this case by counsel for Genentech, Inc.
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`(“Genentech”) in connection with this matter.
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`2.
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`I submit this declaration in support of Genentech’s Emergency Motion for
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`Temporary Restraining Order and Preliminary Injunction.
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`3.
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`I have been asked for my opinion concerning infringement of claim 11 of U.S.
`
`Patent No. 6,627,196 (the “’196 patent”); claim 11 of U.S. Patent No. 7,371,379 (the “’379
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`patent”); and claim 7 of U.S. Patent No. 10,160,811 (the “’811 patent”) (collectively, the “dosing
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`patents”). For the reasons set forth in this report and accompanying Appendix A, it is my
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`opinion that Amgen will direct infringement by physicians and intends for them to infringe the
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`asserted claims of the dosing patents through its prescribing information, marketing, and sale of
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`Kanjinti in the United States.
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`II.
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`BACKGROUND AND QUALIFICATIONS
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`4.
`
`I received a B.S. in biology from Cornell University in 1974 and an M.D. from
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`State University of New York at Downstate in 1974. From 1978-1982, I did my Residency and
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`Chief Residency in Internal Medicine at Bronx Municipal Hospital Center/Albert Einstein
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`College of Medicine, after which I was board certified in Internal Medicine. I then trained in
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`Hematology-Oncology at the University of Pennsylvania, from 1982-1986, after which I was
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`board certified in Hematology and Oncology.
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`5.
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`From 1986-1995, I engaged in laboratory research and clinical care of patients at
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`the Clinical Center at the National Institute of Health. During this time, I cared for patients
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`receiving treatments for cancer and blood disorders, including treatment with novel biologics.
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`6.
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`From 1995-1996, I worked as Medical Officer at the Indian Health Service where
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`I helped establish an Oncology Clinic for follow-up of cancer patients.
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 5 of 50 PageID #: 23722
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`7.
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`8.
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`I then joined Wilshire Oncology where I worked from late 1996 through 2003.
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`At Wilshire Oncology, which was part of the UCLA network, 70% of my clinical
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`practice focused on women with breast cancer. While at Wilshire Oncology, I was also part of
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`early clinical trials involving trastuzumab.
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`9.
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`In 2003, I became the primary breast medical oncologist at the University of
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`Connecticut Health Center, now known as UCONN Health. In 2012, I became the Medical
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`Director of the Clinical and Translational Breast Program. In these roles, my practice involved
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`both academic and clinical components.
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`10.
`
`In 2016, I became the Division Chair of Hematology-Oncology and the Clinical
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`Director of the Cancer Center. My clinical responsibilities remain with added responsibilities of
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`managing operations of our Cancer Center as well as developing our mission, recruiting faculty,
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`and setting standards for the Division of Hematology-Oncology. I continue my clinical care and
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`clinical research as well as administrative responsibilities in this setting.
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`11.
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`For the past twenty-four years, I spend 60% of my time focusing on clinical care,
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`with 80% of that time treating breast cancer patients.
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`12. My qualifications and credentials are set forth below and, in my curriculum vitae,
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`attached as Appendix B.
`
`III. BACKGROUND
`A.
`
`Types of Cancer and Cancer Treatments
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`13.
`
`The term “cancer” refers to a collection of related diseases, all of which are
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`characterized by the uncontrolled growth of cells in the body. The “biology” of each cancer, i.e.,
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`how it grows and spreads, is dictated by the genes the cancer cells express and the cells’
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`interactions with the surrounding environment.
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 6 of 50 PageID #: 23723
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`14.
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`Some cancers will stay where they were formed, slowly growing, while others
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`spread as they grow. When a cancer spreads from the part of the body where it started (the
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`primary site) to other parts of the body, it is called “metastatic” cancer.
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`15.
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`Cancer is often categorized as being in one of one of four “stages.” Anatomic
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`Stage I refers to where the cancer is small and localized in a particular area such as, for example,
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`breast tissue, but has not spread to nearby tissues. Stage II and III means that the cancer has
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`grown larger and/or spread into nearby tissues of lymph nodes. Stage IV is the most serious
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`stage of cancer and means that the cancer has metastasized, i.e., spread to other organs or parts of
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`the body. Stage IV cancer is also referred to as “metastatic cancer”.
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`16.
`
` Treatment options depend on the stage of cancer. For example, non-metastatic
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`breast cancer—that is, stage I, II, or III breast cancer—is often treated with “adjuvant” therapy.
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`Adjuvant therapy is treatment, such as chemotherapy, radiation therapy, or biological therapy,
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`given after a primary treatment (e.g., surgery) to lower the risk that the cancer cells should
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`return. Metastatic breast cancer is generally treated with chemotherapy or targeted biologics to
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`control and manage distant disease and to prevent disease progression (i.e., spread of the cancer
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`cells).
`
`17.
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`Chemotherapeutic agents generally act by either killing cells that grow and divide
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`quickly, or by stopping cells from dividing. Chemotherapy is indiscriminate: it attacks cancer
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`cells, but also affects healthy cells. In comparison, a biologic is targeted to the specific type of
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`cancer. A biologic will target the mechanism of how particular cancer cells grow, and “turn off”
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`the signals promoting growth. Some widely used chemotherapy agents include paclitaxel and
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`docetaxel. Anthracyclines derivatives are also a category of agents that are used as
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`chemotherapy agents.
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 7 of 50 PageID #: 23724
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`
`B.
`
`18.
`
`HER2-Positive Breast Cancer and Herceptin
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`Breast cancers were first categorized by the glandular portion of the breast from
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`which they arose (e.g., ducts, lobules, etc.), but are now also categorized by the different
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`receptors that are expressed on the surface of the cancer cells. These receptors affect the biology
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`of the cancer cells and how the cancer cells spread.
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`19.
`
`One cancer receptor is the epidermal growth factor receptor called “ErbB2” or
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`“HER2/neu.” This receptor was discovered in the 1980s and 1990s, and is one of a family of
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`receptors that promotes the growth and spread of cancer cells. Normal breast cells (and other
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`cells in the body) express the HER2 protein at a certain baseline level. About 25-30% of breast
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`cancers, however, overexpress the HER2 protein, meaning that there is an excessive amount of
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`the HER2 protein on the surface of the cell. This is called “HER2-positive” breast cancer, and
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`these cancer cells have enhanced growth compared to other breast cancers. (See, e.g., Ex. 1,
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`’196 patent, at 1:42-47.) This HER2-overexpression also occurs in other types of cancer,
`
`namely, gastric cancer.
`
`20.
`
`HER2-positive breast cancer is known to be more aggressive than other types of
`
`breast cancer. In the 1990s, despite available treatments, HER2-positive breast cancer was
`
`associated with poor prognosis, with cancer progressing and spreading quickly and patients with
`
`advanced disease having a life expectancy of only 18 months. Prior treatments, such as surgery
`
`and chemotherapy, were invasive, potentially disfiguring, and had harsh side effects, but
`
`ultimately added little to patients’ life expectancy.
`
`21.
`
`Beginning in the 1980s, Genentech began developing a novel approach to treat
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`HER2-positive cancer: a monoclonal antibody that targets and neutralizes the cancerous cells of
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`HER2-positive cancers. This monoclonal antibody is known by several different names,
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`including rhuMab HER2, anti-ErbB2 huMAb 4D5-8 antibody, or trastuzumab. The first
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`- 6 -
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 8 of 50 PageID #: 23725
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`commercial trastuzumab product was approved by the FDA in September 1998 with the
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`tradename Herceptin.
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`22.
`
`Herceptin was the first monoclonal antibody approved for treatment of solid
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`tumors. This fundamentally changed the treatment of HER2-positive breast cancer. Following
`
`its FDA approval in 1998, Herceptin was hailed by oncologists as a revolution in the field of
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`cancer treatment—whereas previous treatments did not treat cancerous tumors themselves,
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`Herceptin for the first time was able to treat solid tumors directly with a targeted therapy.
`
`23.
`
`The FDA initially approved Herceptin for treatment of HER2-positive metastatic
`
`breast cancer. Since that initial approval, Genentech conducted additional studies and has
`
`received approval of Herceptin for “adjuvant” treatment of HER2-positive breast cancer, i.e.,
`
`treatment following surgery to help decrease the risk of cancer recurrence, and metastatic gastric
`
`cancer. Patients have substantially benefited from the expansion of Herceptin to treat these
`
`additional indications. For example, whereas Herceptin was able to extend lives when used to
`
`treat advanced, metastatic cancer, once it was approved to treat early breast cancer, it gave
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`patients a significant chance of providing a cure by stopping cancer from recurring again. In the
`
`years since its approval, Herceptin has extended (and in many cases saved) the lives of thousands
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`of patients suffering from HER2-positive breast cancer.
`
`24.
`
`Prior to Herceptin, metastatic HER2-positive breast cancer was one of the worst
`
`cancer prognoses oncologists could give a patient because HER2-positive cancer did not respond
`
`well to existing treatments and patients had an average life expectancy of only 18 months, with
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`50% of those diagnosed dying within two years. With the availability of Herceptin, oncologists
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`can now convey a substantially better prognosis, in fact one of the best prognoses for cancer
`
`patients. Herceptin has vastly improved patient outcomes as well in the adjuvant setting, and 10-
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`- 7 -
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 9 of 50 PageID #: 23726
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`year survival rates for HER2-positive breast cancer patients have increased to over 80% for
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`patients on Herceptin and chemotherapy treatment.
`
`IV.
`
`THE DOSING PATENTS
`
`25.
`
`Herceptin was originally approved for weekly dosing of patients with metastatic
`
`breast cancer. The dosing patents reflect the discovery, found after that initial FDA approval,
`
`that trastuzumab could be administered less frequently without compromising safety or efficacy.
`
`(Ex. 1, ’196 patent, at 6:20-31.) This discovery that Herceptin could be dosed less frequently for
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`adjuvant breast cancer and gastric cancer, while maintaining safety and efficacy, provided great
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`quality of life benefits to patients. Although Herceptin was initially life-changing for HER2-
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`positive patients, treatment is onerous—patients may need to travel great distances to get the care
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`they need (incurring out-of-pocket costs and time away from work and family), and the treatment
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`requires an hour-and-an-half intravenous (“IV”) infusion at a physician’s office. This reduction
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`in the patient’s quality of life takes on added significance where many of these patients are very
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`sick. Extending the interval between doses gave these patients back valuable time and because
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`treatment was less time- and cost- intensive, it made it more likely that patients would continue
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`the proper regimen for their treatment, in other words, ensuring better compliance.
`
`26.
`
`The dosing patents describe how to administer the drug in ways that allow for
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`those longer intervals between doses while still maintaining efficacy, including a method of
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`administering a larger initial dose of 8 mg/kg trastuzumab followed by subsequent doses of 6
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`mg/kg every three weeks.
`
`27.
`
`Each of the claims I address below recite this dosing regimen of administering to
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`HER2-positive patients an initial dose 8 mg/kg trastuzumab followed by subsequent doses of 6
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`mg/kg every three weeks.
`
`28.
`
`For example, Claim 11 of the ’196 patent, written in independent form, recites:
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`- 8 -
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 10 of 50 PageID #: 23727
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`A method for the treatment of a human patient diagnosed with cancer characterized by
`overexpression of ErbB2 receptor, comprising administering an effective amount of an
`anti-ErbB2 antibody to the human patient, the method comprising:
`
`
`administering to the patient an initial dose of at least approximately 8 mg/kg of
`the anti-ErbB2 antibody; and
`
`administering to the patient a plurality of subsequent doses of the antibody in an
`amount that is approximately the same or less than the initial dose and wherein at
`least one subsequent dose is approximately 6 mg/kg, and
`
`wherein the subsequent doses are separated in time from each other by at least
`three weeks.
`
`
`(Ex. 1, ’196 patent, claim 11.)
`
`29.
`
`Claim 11 of the ’397 patent is similar, and recites the additional limitation of
`
`“administering an effective amount of a chemotherapeutic agent to the patient”:
`
` A method for the treatment of a human patient diagnosed with cancer characterized by
`overexpression of ErbB2 receptor, comprising administering an effective amount of an
`anti-ErbB2 antibody to the human patient, the method comprising:
`
`
`administering to the patient an initial dose of at least approximately 8 mg/kg of
`the anti-ErbB2 antibody; and
`
`administering to the patient a plurality of subsequent doses of the antibody in an
`amount that is approximately the same or less than the initial dose and wherein at
`least one subsequent dose is approximately 6 mg/kg; and
`
`wherein the subsequent doses are separated in time from each other by at least
`three weeks, [and]
`
`further comprising administering an effective amount of a chemotherapeutic agent
`to the patient.
`
`(Ex. 2, ’379 patent, claim 11.)
`
`30.
`
`Claim 7 of the ’811 patent is the narrowest of the three patent claims, reciting that
`
`the antibody is anti-ErbB2 huMAb 4D5-8, and that administration is via IV to breast cancer
`
`patients whose HER2-positive status is measured using certain tests, including a technique called
`
`“immunohistochemistry” (or “IHC”), which measures whether a patient’s cells have an excessive
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`- 9 -
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 11 of 50 PageID #: 23728
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`amount of the HER2 protein on the cells’ surface (and scored as 2+ or 3+), or FISH, which
`
`measures the number of copies of HER2 gene in the cell.1 Claim 7 recites:
`
`A method for the treatment of a human patient diagnosed with breast cancer characterized
`by 2+ or 3+ overexpression of ErbB2 receptor as determined by immunohistochemistry or
`fluorescence in situ hybridization (FISH), the method comprising:
`administering intravenously to the patient an initial dose of 8 mg/kg of anti-ErbB2
`huMAb 4D5-8 antibody;
`and administering intravenously to the patient a plurality of subsequent 6 mg/kg
`doses of the antibody,
`wherein the initial dose is separated in time from the first subsequent dose
`by three weeks, and
`the subsequent doses are separated from each other in time by three weeks.
`(Ex. 3, ’811 patent, claim 7.)
`
`31.
`
`The extended, three-week-interval dosing regimen is not only recited in the patent
`
`claims but is reflected in the Herceptin label, which recites the dosing regimen as one of two
`
`options for adjuvant treatment:
`
`(Ex. 7, Herceptin Label, GNE-HER_002466538.)
`
`32.
`
`As between these options for adjuvant treatment, the extended, three-week-
`
`interval dosing regimen is more often prescribed. This is true in my experience,
`
`
`
`1 It is well known to oncologists that HER2-positive, or “overexpressing”, status is determined using
`immunohistochemistry or FISH. For example, the Phase III study used by Genentech to obtain initial FDA approval
`(which is recounted as Study 5 of the Kanjinti label) included only patients with “overexpression of the ErbB2
`(HER2) oncogene (2+ to 3+ as determined by immunohistochemistry or fluorescence in situ hybridization (FISH).”
`(Ex. 3, ’811 patent, at 36:5-7.)
`
`- 10 -
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 12 of 50 PageID #: 23729
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` The extended, three-week-interval
`
`
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`dosing regimen reduces the amount of time a patient must be in the clinic, which benefits both
`
`patients and clinicians. As described above, the extended, three-week-interval dosing regimen
`
`improves patients’ quality of life. Clinicians prefer this dosing regimen because patients are
`
`more satisfied with fewer clinic visits, and clinics have more time to treat additional patients.
`
`33.
`
`Genentech also studied this extended dosing regimen in patients with gastric
`
`cancer, which is described as Study 7 in the Herceptin Label. (Ex. 7, Herceptin Label at GNE-
`
`HER_002466550.) The results of this study led to separate approval of the extended regimen to
`
`treat gastric cancer, which is reflected in the Herceptin label:
`
`
`
`(Id.)
`
`V.
`
`INFRINGEMENT ANALYSIS
`A.
`
`Legal Principles
`
`34.
`
`I have been informed and understand that analyzing whether a method infringes a
`
`patent is a two-step process. First, the patent claims are construed by the Court. Second, the
`
`construed claims are compared to the allegedly infringing method to determine whether the
`
`method falls within the scope of the claims. I have been informed and understand that a patent
`
`claim is “literally” infringed when a method performed by a party includes each and every
`
`element of a patent claim.
`
`35.
`
`I understand that a patent may be infringed indirectly, which may be referred to as
`
`inducement of infringement. I understand that in order for a patent to be infringed indirectly,
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`- 11 -
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 13 of 50 PageID #: 23730
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`
`there must be an underlying direct infringer. I also understand that in order to show that a party
`
`indirectly infringes a patent, the party must intend for the direct infringer to perform the
`
`infringing method and have knowledge that the induced actions constitute infringement. In the
`
`context of method of treatment claims, like those at issue here, I understand that examples of
`
`inducing infringement may include the provision of instructions to medical-care providers to
`
`carry out the elements of recited in the patent claim. This can be in the form of, for example,
`
`clinical guidelines or labelling of a drug.
`
`B.
`
`36.
`
`Amgen’s Kanjinti Label
`
`The FDA approved Kanjinti on June 13, 2019 to treat all the same indications
`
`with all the same dosing regimens as Genentech’s Herceptin. (See Ex. 4, Kanjinti Label at
`
`AMGKAN0298377; see also Ex. 8, June 13, 2019 Amgen press release, at 1 (stating that FDA
`
`“has approved KANJINTI™ (trastuzumab-anns) for all approved indications of the reference
`
`product, Herceptin® (trastuzumab)”).) When it approved Kanjinti, the FDA approved an
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`accompanying document titled “Prescribing Information” that is referred to as the product
`
`“label.” This product label accompanies the drug and instructs physicians on what to prescribe it
`
`for (indications), what dosage regimen to use, and provides clinical study data that explains the
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`efficacy of the drug in trials and forms the basis for safety warnings and potential side effects.
`
`Physicians refer to a drug label to understand more about the safety and efficacy of a drug and
`
`how to use it.
`
`37.
`
`Just like the Herceptin label, Amgen’s approved label for Kanjinti includes
`
`indications for adjuvant treatment of HER2-positive breast cancer, treatment for HER2-positive
`
`metastatic breast cancer, and treatment for HER2-positive gastric cancer. The Kanjinti label
`
`includes the same clinical study data that Genentech provides for Herceptin, including the study
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 14 of 50 PageID #: 23731
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`that led to approval of the once-every-three-weeks dosing regimen. (Ex. 4, at
`
`AMGKAN02982410.)
`
`38.
`
`The Kanjinti label instructs physicians to treat adjuvant breast cancer by either
`
`administering Kanjinti over 52 weeks(1) beginning with 13 doses separated by one week (an
`
`initial dose of 4 mg/kg and then 12 doses of 2 mg/kg) and then additional doses (of 6 mg/kg)
`
`every three weeks thereafter; or (2) beginning with an initial dose of 8 mg/kg followed by
`
`subsequent doses of 6 mg/kg separated by three weeks.
`
`(Id. at section 2.2)
`39.
`The Kanjinti label also instructs physicians to treat metastatic gastric cancer
`
`by administering these patients an initial does of 8 mg/kg, followed by 6 mg/kg every three
`weeks.
`
`
`
`(Id.)
`
`C.
`
`40.
`
`Infringement of the Dosing Patents
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`- 13 -
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`.
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 15 of 50 PageID #: 23732
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` As outlined below, I agree
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`that if Amgen were to launch Kanjinti, it would direct infringement by physicians and intend for
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`them to infringe the claims of the asserted claims of the dosing patents.
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`1.
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`Physicians Prescribing Kanjinti In Accordance With the Approved
`Label Directly Infringe the Dosing Patents
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`41.
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`As described above, a drug product’s label provides instructions to physicians on
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`how to dose and prescribe the drug. Physicians thus will primarily follow the Kanjinti label and
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`prescribe a drug to treat diseases approved for treatment by the FDA at the recited dosing
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`regimens, and will consult with the study data included in the label to confirm the safety and
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`efficacy of that regimen.
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`42.
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`Amgen’s Kanjinti label instructs physicians to administer to HER2-positive
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`patients Kanjinti at an initial dose of 8 mg/kg followed by subsequent doses of 6 mg/kg separated
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`in time by three weeks, just as recited in the asserted claims of the dosing patents. Thus, once
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`Kanjinti is launched, prescribing doctors and clinicians administering Kanjinti according to
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`Amgen’s instructions will directly infringe the asserted claims of the dosing patents. Below, I
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`explain how physicians following the Kanjinti label will meet each limitation of each claim. I
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`also provide this information in chart form as Appendix A.
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`a)
`The ’196 Patent, Claim 11
`The Kanjinti label instructs physicians to practice each limitation of claim 11 of
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`43.
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`the ’196 patent. Each of the limitations of ’196 patent claim 11 is also recited in claim 11 of the
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`’379 patent.
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`i)
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`A method for the treatment of a human patient
`diagnosed with cancer characterized by overexpression
`of ErbB2 receptor, comprising administering an
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 16 of 50 PageID #: 23733
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`effective amount of an anti-ErbB2 antibody to the
`human patient, the method comprising:
`The Kanjinti label instructs physicians to practice this limitation because the label
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`44.
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`recites that Kanjinti is indicated for treating human patients diagnosed with cancer characterized
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`by overexpression of HER2, i.e., cancer that overexpresses the ErbB2 receptor. (See Ex. 4, at
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`AMGKAN02982377 (“KANJINTI is a HER2/neu receptor antagonist indicated for: . . . the
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`treatment of HER2 overexpressing breast cancer. (1.1, 1.2)”).
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`45.
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`The Kanjinti label further explains that Kanjinti contains an anti-ErbB2 antibody.
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`According to the label, Kanjinti contains a humanized IgG1 monoclonal antibody that binds with
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`high affinity to the extracellular domain of human epidermal growth factor receptor 2, i.e., an
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`anti-ErbB2 antibody. (Id. (“Trastuzumab-anns is a humanized IgG1 kappa monoclonal antibody
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`that selectively binds with high affinity to the extracellular domain of the human epidermal
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`growth factor receptor 2 protein, HER2.”).)
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`46.
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`The Kanjinti label instructs physicians to administer Amgen’s trastuzumab
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`product to humans at therapeutically effective doses. Specifically, the label outlines the doses to
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`be administered based on indication. (Id.)
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`ii)
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`administering to the patient an initial dose of at least
`approximately 8 mg/kg of the anti-ErbB2 antibody
`The Kanjinti label instructs physicians to practice this limitation because the label
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`47.
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`recites administering, for treatment of adjuvant treatment of HER2-overexpressing breast cancer,
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`Kanjinti at an “[i]nitial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30–90
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`minutes IV infusion every three weeks for 52 weeks.” (Id.) Similarly, for metastatic HER2-
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`overexpressing gastric cancer, the Kanjinti label instructs physicians to administer Kanjinti at an
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`“[i]nitial dose of 8 mg/kg over 90 minutes IV infusion, followed by 6 mg/kg over 30 to 90
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`minutes IV infusion every 3 weeks.” (Id.)
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 17 of 50 PageID #: 23734
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`iii)
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`administering to the patient a plurality of subsequent
`doses of the antibody in an amount that is
`approximately the same or less than the initial dose and
`wherein at least one subsequent dose is approximately 6
`mg/kg, and
`The Kanjinti label instructs physicians to practice this limitation because the label
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`48.
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`recites administering, for treatment of adjuvant treatment of HER2-overexpressing breast cancer,
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`Kanjinti at an “[i]nitial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30–90
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`minutes IV infusion every three weeks for 52 weeks.” (Id.) Similarly, for metastatic HER2-
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`overexpressing gastric cancer, the Kanjinti label instructs physicians to administer Kanjinti at an
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`“[i]nitial dose of 8 mg/kg over 90 minutes IV infusion, followed by 6 mg/kg over 30 to 90
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`minutes IV infusion every 3 weeks.” (Id.)
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`iv)
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`wherein the subsequent doses are separated in time
`from each other by at least three weeks.
`The Kanjinti label instructs physicians to practice this limitation because the label
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`49.
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`recites administering, for treatment of adjuvant treatment of HER2-overexpressing breast cancer,
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`Kanjinti at an “[i]nitial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30–90
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`minutes IV infusion every three weeks for 52 weeks.” (Id.) Similarly, for metastatic HER2-
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`overexpressing gastric cancer, the Kanjinti label instructs physicians to administer Kanjinti at an
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`“[i]nitial dose of 8 mg/kg over 90 minutes IV infusion, followed by 6 mg/kg over 30 to 90
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`minutes IV infusion every 3 weeks.” (Id.)
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`b)
`The ’379 Patent, Claim 11
`As described above, claim 11 of the ’397 patent includes the same limitations as
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`50.
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`claim 11 of the ’196 patent and Amgen infringes those limitations for the reasons stated in
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`section a). The ’397 patent additionally recites one additional limitation. Physicians following
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`the Kanjinti label will also meet the additional limitation of claim 11 of the ’379 patent.
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`Case 1:18-cv-00924-CFC Document 311 Filed 07/19/19 Page 18 of 50 PageID #: 23735
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`i)
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`further comprising administering an effective amount
`of a chemotherapeutic agent to the patient
`The Kanjinti label instructs physicians to practice this limitation because the
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`51.
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`Kanjinti label instructs that Kanjinti may be administered in adjuvant breast cancer treatment
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`according to the claimed dosing regimen “as a single agent within three weeks following
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`completion of multi-modality, anthracycline-based chemotherapy regimen.” (Id. at 5.)
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`c)
`The ’811 Patent, Claim 7
`The Kanjinti label instructs physicians to practice each limitation of claim 7 of the
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`52.
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`’811 patent.
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`i)
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`A method for