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`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`BRISTOL-MYERS SQUIBB CO. and
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`E. R. SQUIBB & SONS, L.L.C.,
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`Plaintiffs,
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`v.
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`ASTRAZENECA PHARMACEUTICALS LP and )
`ASTRAZENECA UK LTD.,
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`Defendants.
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`COMPLAINT
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`C.A. No. ______________
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` JURY TRIAL DEMANDED
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`Plaintiffs Bristol-Myers Squibb Co. (“BMS”) and E. R. Squibb & Sons, L.L.C.
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`(“Squibb”) for their complaint for patent infringement against Defendants AstraZeneca
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`Pharmaceuticals LP and AstraZeneca UK Ltd. (collectively, “Defendants” or “AstraZeneca”),
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`hereby allege as follows:
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`INTRODUCTION
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`1.
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`According to the United States Centers for Disease Control and Prevention, more
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`than 1.6 million people in the United States are diagnosed with cancer each year
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`(https://www.cdc.gov/chronicdisease/resources/publications/factsheets/cancer.htm). Cancer is a
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`disease that results from the uncontrolled proliferation of cells that were once normal but have
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`transformed into cancerous cells. Although the human immune system sometimes has the
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`potential to eliminate cancerous cells, cancer cells have the ability to “turn off” or evade the
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`immune system, allowing the cancer cells to grow unchecked. Tumor growth and tumor
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`metastasis can lead to devastating disease, and possibly death. Cancer treatments are therefore
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`developed to decrease tumor growth and metastasis.
`1
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 2 of 85 PageID #: 2
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`2.
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`This case relates to groundbreaking treatments for cancer that fall within a field
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`known as “immunotherapy.” The treatment of cancer using immunotherapy represents a
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`scientific breakthrough that is revolutionizing cancer treatment by manipulating a patient’s
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`immune system to eliminate cancer cells.
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`3.
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`The human immune system is formed of organs, specialized cells, and substances
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`that protect individuals from infections and disease. T cells are one class of specialized cells that
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`play an important role in the human immune system. One major function of T cells is to destroy
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`pathogens or malignant cells, and to do that the T cell must distinguish healthy cells from
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`infected or malignant cells through the activation or deactivation of various receptors on the T
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`cell surface. One of the receptors that T cells express on their surface is a protein called
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`programmed death-1 receptor (“PD-1”). PD-1 functions as a checkpoint on the immune system
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`that can downregulate T cell activity to prevent an overactive immune response. To activate its
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`inhibitory function, PD-1 must bind to one of its ligands. Programmed death-ligand 1 (“PD-L1”)
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`is one of these ligands.
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`4.
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`Numerous forms of cancers express PD-L1 on their cell surface, and can therefore
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`exploit PD-1’s ability to downregulate the immune response. When PD-L1 on a cancer cell
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`binds to PD-1 on immune cells, such as a T cell, it can result in the suppression of T cell
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`migration, proliferation, and secretion of cytotoxic mediators. When cancer cells are present,
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`this pathway can prevent the immune system from eliminating those cancer cells. In other
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`words, cancer cells expressing PD-L1 can activate the PD-1 checkpoint to prevent a patient’s
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`immune system from destroying cancer cells.
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`5.
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`Plaintiffs invented methods for treating cancer and methods for enhancing
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`immune responses by administering antibodies that bind to PD-L1 (“anti-PD-L1 antibodies”).
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`2
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 3 of 85 PageID #: 3
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`The inventions also cover using specific types of anti-PD-L1 antibodies to inhibit the interaction
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`between PD-1 and PD-L1. By binding to PD-L1 and blocking its interaction with PD-1, the anti-
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`PD-L1 antibodies act as checkpoint inhibitors that release the brakes on the immune system,
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`freeing the immune cells to recognize, attack and destroy cancer cells. Plaintiffs also invented
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`anti-PD-L1 antibodies with specific properties for use in methods of treatment and methods for
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`enhancing immune responses.
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`6.
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`Plaintiffs also invented antibodies that bind to PD-1 (“anti-PD-1 antibodies”), and
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`put this scientific breakthrough into practice by developing an anti-PD-1 antibody called
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`OPDIVO (nivolumab), the first anti-PD-1 antibody approved anywhere in the world for cancer
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`treatment, and the first anti-PD-1 antibody approved in the United States for the treatment of
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`lung cancer.
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`7.
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`Nivolumab is a monoclonal antibody that recognizes and binds to PD-1. When
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`nivolumab binds to PD-1, it prevents PD-1 from binding to its ligands, e.g., PD-L1. Using
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`nivolumab to block the interaction between PD-1 and its ligands enhances the T cell response
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`generated by the patient’s immune system.
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`8.
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`Clinical testing of nivolumab confirmed the remarkable promise of checkpoint
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`inhibitors as targets for immunotherapy. After rigorous worldwide testing, on July 4, 2014,
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`nivolumab became the first anti-PD-1 antibody approved anywhere in the world for treating
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`cancer, when Japanese regulatory authorities approved nivolumab (OPDIVO) for the treatment
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`of melanoma, a deadly form of skin cancer (https://www.cancerresearch.org/en-
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`us/immunotherapy/timeline-of-progress). On December 22, 2014, the U.S. Food and Drug
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`Administration (“FDA”) approved nivolumab for treatment of advanced melanoma in the United
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`States.
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`3
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 4 of 85 PageID #: 4
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`9.
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`Plaintiffs have continued worldwide development of nivolumab for treatment of a
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`broad range of cancers, including non-small cell lung cancer, urothelial carcinoma, renal cell
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`carcinoma, head and neck cancer, malignant pleural mesothelioma, lymphoma, colorectal cancer,
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`hepatocellular carcinomas, esophageal cancer, and gastric cancers. In Phase III clinical testing
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`for lung cancer, patients with advanced lung cancer who received nivolumab showed superior
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`overall survival (41% reduction in the risk of death) compared to those who received the
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`standard of care chemotherapy agent docetaxol (https://news.bms.com/news/details/2015/FDA-
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`Approves-Opdivo-nivolumab-for-the-Treatment-of-Patients-with-Previously-Treated-Metastatic-
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`Squamous-Non-Small-Cell-Lung-Cancer/default.aspx). Based, at least in part, on these clinical
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`results, on February 27, 2015, the FDA accepted Plaintiffs’ Biologics License Application
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`(“BLA”) for use of nivolumab to treat lung cancer. Just days later, on March 4, 2015, the FDA
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`approved nivolumab for treatment of advanced non-small cell lung cancer in the United States.
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`In Phase III clinical testing for urothelial carcinoma, median disease-free survival was nearly
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`twice as long in patients who received nivolumab as compared to placebo
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`(https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-
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`Opdivo-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-
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`Carcinoma/default.aspx). On August 29, 2021, based at least in part on those clinical results, the
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`FDA approved nivolumab to treat certain types of urothelial carcinoma. The clinical results and
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`the FDA’s approval of nivolumab for the treatment of various additional forms of cancer confirm
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`that the cancer treatments developed by the Plaintiffs can be used to save the lives of patients
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`suffering from cancer.
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`10.
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`AstraZeneca is exploiting Plaintiffs’ inventions and infringing Plaintiffs’
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`intellectual property rights by marketing a later-developed anti-PD-L1 antibody product,
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`4
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 5 of 85 PageID #: 5
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`IMFINZI (durvalumab), which is used in methods for treating cancer and for enhancing the
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`immune response.
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`11.
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`Since Plaintiffs and AstraZeneca are direct competitors in the field of
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`immunotherapy, Plaintiffs have suffered, and continue to suffer, substantial damages, including
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`lost profits, as a result of AstraZeneca’s infringement. Marking pursuant to 35 U.S.C. § 287 was
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`not required because Plaintiffs’ product OPDIVO is an anti-PD-1 antibody and is not a patented
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`article under the asserted patents.
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`PARTIES
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`12.
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`BMS is a corporation organized under the laws of the state of Delaware, with a
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`principal place of business at 345 Park Ave., New York, New York 10154. E. R. Squibb & Sons,
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`L.L.C., is a limited liability company organized and existing under the laws of the state of
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`Delaware, with its principal place of business at Route 206 & Province Line Road, Princeton,
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`New Jersey 08543.
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`13.
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`On information and belief, AstraZeneca Pharmaceuticals LP is a limited
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`partnership organized under the laws of the State of Delaware, with its principal place of
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`business at 1800 Concord Pike, Wilmington, Delaware 19803.
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`14.
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`On information and belief, AstraZeneca UK Limited is a private limited company
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`organized under the laws of England and Wales, with its registered office at 1 Francis Crick
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`Avenue, Cambridge Biomedical Campus, Cambridge, United Kingdom, CB2 0AA.
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`15.
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`AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited are in the business
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`of manufacturing, marketing, distributing, offering for sale, and selling drug products that are
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`distributed and sold throughout the United States, including in Delaware.
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`5
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 6 of 85 PageID #: 6
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`16.
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`AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited are sophisticated
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`pharmaceutical companies. On information and belief, AstraZeneca relies on and actively seeks
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`patent protection for its products. On information and belief, AstraZeneca regularly enforces its
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`patents and other intellectual property rights.
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`JURISDICTION AND VENUE
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`17.
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`This is an action for patent infringement arising under the Patent Laws of the
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`United States, 35 U.S.C. §§ 271 et seq., including an action seeking a declaratory judgment
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`pursuant to 28 U.S.C. §§ 2201-2202.
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`18.
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`This Court has subject matter jurisdiction over this action pursuant to 28 U.S.C.
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`§§ 1331 and 1338(a).
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`19.
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`This Court has personal jurisdiction over AstraZeneca Pharmaceuticals LP
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`because it is a Delaware entity located in Delaware.
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`20.
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`This Court has jurisdiction over AstraZeneca UK Limited, inter alia, because its
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`subsidiary and agent, AstraZeneca Pharmaceuticals LP, is incorporated in Delaware and, upon
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`information and belief, markets and sells IMFINZI in Delaware as AstraZeneca UK Limited’s
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`authorized agent and under AstraZeneca UK Limited’s direction and control.
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`21.
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`On information and belief, AstraZeneca Pharmaceuticals LP and AstraZeneca UK
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`Limited are engaged in a single business activity of biopharmaceuticals and are not separated
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`into multiple operating segments. On information and belief, the biopharmaceuticals business of
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`AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited consists of the discovery and
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`development of products, which are then manufactured, marketed, and sold. On information and
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`belief, all of these functional activities take place (and are managed) globally on a highly
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`6
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 7 of 85 PageID #: 7
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`integrated basis. On information and belief, these individual functional areas are not managed
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`separately.
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`22.
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`On information and belief, AstraZeneca Pharmaceuticals LP and AstraZeneca UK
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`Limited have consented to jurisdiction in Delaware in one or more prior cases arising out of the
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`manufacture, use, offer for sale, sale and/or importation of pharmaceutical products, including
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`cases AstraZeneca initiated as the plaintiff.
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`23.
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`Venue is proper in this district under 28 U.S.C. §§ 1391(c) and 1400(b).
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`THE PATENTS-IN-SUIT
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`24.
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`On February 28, 2017, the USPTO duly and legally issued U.S. Patent No.
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`9,580,505 (“the ’505 patent”) titled “Human Monoclonal Antibodies to Programmed Death
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`Ligand 1 (PD-L1).” A true and correct copy of the ’505 patent is attached hereto as Exhibit 1.
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`The ’505 patent is assigned to E. R. Squibb & Sons, L.L.C.
`
`25.
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`The ’505 patent issued from U.S. Application No. 14/807,522, filed on July 23,
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`2015, which is a divisional of U.S. Application No. 13/746,773, filed January 22, 2013 (now
`
`U.S. Patent No. 9,102,725), which is a divisional application of U.S. Application No.
`
`13/091,936, filed April 21, 2011 (now U.S. Pat. No. 8,383,796), which is a divisional application
`
`of U.S. Application No. 11/917,727, filed June 9, 2008 (now U.S. Pat. No. 7,943,743), which is a
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`national stage entry of PCT Application No. PCT/US2006/026046, filed June 30, 2006, which
`
`claims the benefit of U.S. Provisional Patent Application No. 60/696,426, filed July 1, 2005.
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`26.
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`The claims of the ’505 patent are generally directed to monoclonal antibodies that
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`cross-compete with a specific reference antibody for binding to human PD-L1. By way of
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`example, claim 1 of the ’505 patent is:
`
`
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`7
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 8 of 85 PageID #: 8
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`
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`An anti-PD-L1 monoclonal antibody, or an antigen-binding portion thereof,
`which cross-competes for binding to human PD-L1 with a reference antibody,
`wherein the reference antibody comprises:
`(a) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:1 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:11;
`(b) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:2 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:12;
`(c) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:3 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:13;
`(d) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:4 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:14;
`(e) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:5 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:15;
`(f) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:6 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:16;
`(g) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:7 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:17;
`(h) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:8 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:18;
`(i) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:9 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:19; or
`(j) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:10 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:20; and
`wherein the monoclonal antibody or antigen-binding portion thereof
`comprises a heavy chain variable region and a light chain variable region,
`wherein a framework region of the heavy chain variable region is derived
`from a heavy chain variable germline sequence selected from a (a) human
`VH 1-18 germline sequence; (b) human VH 1-69 germline sequence; (c)
`human VH 1-3 germline sequence; and (d) human VH 3-9 germline
`sequence, or
`a framework region of the light chain variable region is derived from a light
`chain variable germline sequence selected from a (a) human VK L6
`germline sequence, (b) human VK L15 germline sequence, (c) human VK
`A27 germline sequence, and (d) human VK L18 germline sequence.
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`8
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 9 of 85 PageID #: 9
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`27.
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`On February 28, 2017, the USPTO duly and legally issued U.S. Patent No.
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`9,580,507 (“the ’507 patent”) titled “Human Monoclonal Antibodies to Programmed Death
`
`Ligand 1 (PD-L1).” A true and correct copy of the ’507 patent is attached hereto as Exhibit 2.
`
`The ’507 patent is assigned to E. R. Squibb & Sons, L.L.C.
`
`28.
`
`The ’507 patent issued from U.S. Application No. 15/188,860, filed June 21,
`
`2016, which is a divisional of U.S. Application No. 14/807,522, filed July 23, 2015 (now U.S.
`
`Patent No. 9,580,505), which is a divisional of U.S. Application No. 13/746,773, filed January
`
`22, 2013 (now U.S. Pat. No. 9,102,725), which is a divisional application of U.S. Application
`
`No. 13/091,936, filed April 21, 2011 (now U.S. Pat. No. 8,383,796), which is a divisional
`
`application of U.S. Application No. 11/917,727, filed June 9, 2008 (now U.S. Pat. No.
`
`7,943,743), which is a national stage entry of PCT Application No. PCT/US2006/026046, filed
`
`June 30, 2006, which claims the benefit of U.S. Provisional Patent Application No. 60/696,426,
`
`filed July 1, 2005.
`
`29.
`
`The claims of the ’507 patent are generally directed to monoclonal antibodies that
`
`cross-compete with a specific reference antibody for binding to human PD-L1. By way of
`
`example, claim 1 of the ’507 patent is:
`
`A monoclonal anti-PD-L1 antibody, or an antigen-binding portion thereof,
`which cross-competes for binding to human PD-L1 with a reference antibody,
`wherein the reference antibody comprises:
`(a) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:1 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:11;
`(b) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:2 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:12;
`(c) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:3 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:13;
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`9
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 10 of 85 PageID #: 10
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`(d) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:4 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:14;
`(e) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:5 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:15;
`(f) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:6 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:16;
`(g) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:7 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:17;
`(h) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:8 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:18;
`(i) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:9 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:19; or
`(j) a heavy chain variable region comprising amino acids having the sequence
`set forth in SEQ ID NO:10 and a light chain variable region comprising
`amino acids having the sequence set forth in SEQ ID NO:20; and
`wherein the monoclonal anti-PD-L1 antibody or antigen-binding portion
`thereof comprises a heavy chain variable region (VH) and a light chain
`variable region (VL), wherein the VH comprises a framework region
`exhibiting at least 90% sequence identity to a framework region of the
`heavy chain variable region of the reference antibody and/or the VL
`comprises a framework region exhibiting at least 90% sequence identity to
`a framework region of the light chain variable region of the reference
`antibody.
`
`
`30.
`
`On November 27, 2018, the USPTO duly and legally issued U.S. Patent No.
`
`10,138,299 (“the ’299 patent”) titled “Cancer Immunotherapy by Disrupting PD-1/PD-L1
`
`Signaling.” A true and correct copy of the ’299 patent is attached hereto as Exhibit 3. The ’299
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`patent is assigned to Bristol-Myers Squibb Company.
`
`31.
`
`The ’299 patent issued from U.S. Application No. 16/006,473, filed June 12,
`
`2018, a continuation of U.S. Application No. 14/950,748, filed November 24, 2015 (now U.S.
`
`Patent No. 10,072,082), which is a divisional of U.S. Application No. 13/892,671, filed May 13,
`
`2013 (now U.S. Pat. No. 9,212,224), which claims the benefit of U.S. Provisional Patent
`
`
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`10
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`
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 11 of 85 PageID #: 11
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`
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`Application No. 61/790,747, filed on March 15, 2013, and U.S. Provisional Patent Application
`
`No. 61/647,442, filed May 15, 2012.
`
`32.
`
`The claims of the ’299 patent are generally directed to methods of treating a
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`tumor derived from bladder cancer by administering an anti-PD-L1 antibody to the subject. By
`
`way of example, claim 1 of the ’299 patent is:
`
`A method of treating a tumor in a human subject in need thereof, comprising
`administering to the subject about 10 mg/kg of an anti-PD-L1 antibody every 2
`weeks, wherein the anti-PD-L1 antibody is administered intravenously over 60
`minutes infusion;
`wherein the tumor is derived from a bladder cancer;
`and wherein the tumor is refractory to a platinum-based chemotherapy.
`
`33.
`
`On June 4, 2019, the USPTO duly and legally issued U.S. Patent No. 10,308,714
`
`(“the ’714 patent”) titled “Cancer Immunotherapy by Disrupting PD-1/PD-L1 Signaling.” A true
`
`and correct copy of the ’714 patent is attached hereto as Exhibit 4. The ’714 patent is assigned to
`
`Bristol-Myers Squibb Company.
`
`34.
`
`The ’714 patent issued from U.S. Application No. 16/024,340, filed June 29,
`
`2018, which is a continuation of U.S. Application No. 14/950,748, filed November 24, 2015
`
`(now U.S. Patent No. 10,072,082), which is a divisional of U.S. Application No. 13/892,671,
`
`filed May 13, 2013 (now U.S. Patent No. 9,212,224), which claims the benefit of U.S.
`
`Provisional Patent Application No. 61/790,747, filed on March 15, 2013, and U.S. Provisional
`
`Patent Application No. 61/647,442, filed May 15, 2012.
`
`35.
`
`The claims of the ’714 patent are generally directed to methods of treating a
`
`tumor derived from a bladder cancer by administering an anti-PD-L1 antibody to the subject. By
`
`way of example, claim 1 of the ’714 patent is:
`
`A method of treating a tumor in a human subject, comprising administering to
`the subject a therapeutically effective amount of an anti-PD-L1 antibody; wherein
`the anti-PD-L1 antibody is administered intravenously over 60 minutes infusion;
`
`
`
`11
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`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 12 of 85 PageID #: 12
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`
`
`wherein the tumor is derived from a bladder cancer; and wherein the tumor is
`refractory to a platinum based chemotherapy.
`
`36.
`
`On April 23, 2019, the USPTO duly and legally issued U.S. Patent No.
`
`10,266,594 (“the ’594 patent”) titled “Cancer Immunotherapy by Disrupting PD-1/PD-L1
`
`Signaling.” A true and correct copy of the ’594 patent is attached hereto as Exhibit 5. The ’594
`
`patent is assigned to Bristol-Myers Squibb Company.
`
`37.
`
`The ’594 patent issued from U.S. Application No. 16/213,954, filed December 7,
`
`2018, which is a continuation of U.S. Application No. 16/006,365, filed June 12, 2018 (now U.S.
`
`Patent No. 10,316,090), which is a continuation of U.S. Application No. 14/950,748, filed
`
`November 24, 2015 (now U.S. Patent No. 10,072,082), which is a divisional of U.S. Application
`
`No. 13/892,671, filed May 13, 2013 (now U.S. Patent No. 9,212,224), which claims the benefit
`
`of U.S. Provisional Patent Application No. 61/790,747, filed on March 15, 2013, and U.S.
`
`Provisional Patent Application No. 61/647,442, filed May 15, 2012.
`
`38.
`
`The claims of the ’594 patent are generally directed to methods of treating a
`
`tumor derived from a cancer of the renal pelvis by administering an anti-PD-L1 antibody to the
`
`subject. By way of example, claim 1 of the ’594 patent is:
`
`A method of treating a tumor in a human subject in need thereof, comprising
`administering to the subject a therapeutically effective amount of an anti-PD-L1
`antibody; wherein the anti-PD-L1 antibody is administered intravenously over 60
`minutes infusion; wherein the tumor is derived from a cancer of the renal pelvis;
`and wherein the tumor is refractory to a platinum based chemotherapy.
`
`39.
`
`On April 23, 2019, the USPTO duly and legally issued U.S. Patent No.
`
`10,266,595 (“the ’595 patent”) titled “Cancer Immunotherapy by Disrupting PD-1/PD-L1
`
`Signaling.” A true and correct copy of the ’595 patent is attached hereto as Exhibit 6. The ’595
`
`patent is assigned to Bristol-Myers Squibb Company.
`
`
`
`12
`
`
`
`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 13 of 85 PageID #: 13
`
`
`
`40.
`
`The ’595 patent issued from U.S. Application No. 16/213,960, filed December 7,
`
`2018, which is a continuation of U.S. Application No. 16/006,365, filed June 12, 2018 (now U.S.
`
`Patent No. 10,316,090), which is a continuation of U.S. Application No. 14/950,748, filed
`
`November 24, 2015 (now U.S. Patent No. 10,072,082), which is a divisional of U.S. Application
`
`No. 13/892,671, filed May 13, 2013 (now U.S. Patent No. 9,212,224), which claims the benefit
`
`of U.S. Provisional Patent Application No. 61/790,747, filed on March 15, 2013, and U.S.
`
`Provisional Patent Application No. 61/647,442, filed May 15, 2012.
`
`41.
`
`The claims of the ’595 patent are generally directed to methods of treating a
`
`tumor derived from a cancer of the ureter by administering an anti-PD-L1 antibody to the
`
`subject. By way of example, claim 1 of the ’595 patent is:
`
`A method of treating a tumor in a human subject in need thereof, comprising
`administering to the subject a therapeutically effective amount of an anti-PD-L1
`antibody; wherein the anti-PD-L1 antibody is administered intravenously over 60
`minutes infusion; wherein the tumor is derived from a cancer of the ureter; and
`wherein the tumor is refractory to a platinum based chemotherapy.
`
`42.
`
`On April 23, 2019, the USPTO duly and legally issued U.S. Patent No.
`
`10,266,596 (“the ’596 patent”) titled “Cancer Immunotherapy by Disrupting PD-1/PD-L1
`
`Signaling.” A true and correct copy of the ’596 patent is attached hereto as Exhibit 7. The ’596
`
`patent is assigned to Bristol-Myers Squibb Company.
`
`43.
`
`The ’596 patent issued from U.S. Application No. 16/213,965, filed December 7,
`
`2018, which is a continuation of U.S. Application No. 16/006,365, filed June 12, 2018 (now U.S.
`
`Patent No. 10,316,090), which is a continuation of U.S. Application No. 14/950,748, filed
`
`November 24, 2015 (now U.S. Patent No. 10,072,082), which is a divisional of U.S. Application
`
`No. 13/892,671, filed May 13, 2013 (now U.S. Patent No. 9,212,224), which claims the benefit
`
`of U.S. Provisional Patent Application No. 61/790,747, filed on March 15, 2013, and U.S.
`
`Provisional Patent Application No. 61/647,442, filed May 15, 2012.
`13
`
`
`
`
`
`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 14 of 85 PageID #: 14
`
`
`
`44.
`
`The claims of the ’596 patent are generally directed to methods of treating a
`
`tumor derived from a cancer of the urethra by administering an anti-PD-L1 antibody to the
`
`subject. By way of example, claim 1 of the ’596 patent is:
`
`A method of treating a tumor in a human subject in need thereof, comprising
`administering to the subject a therapeutically effective amount of an anti-PD-L1
`antibody; wherein the anti-PD-L1 antibody is administered intravenously over 60
`minutes infusion; wherein the tumor is derived from a cancer of the urethra; and
`wherein the tumor is refractory to a platinum based chemotherapy.
`
`45.
`
`On June 18, 2019, the USPTO duly and legally issued U.S. Patent No. 10,323,092
`
`(“the ’092 patent”) titled “Cancer Immunotherapy by Disrupting PD-1/PD-L1 Signaling.” A true
`
`and correct copy of the ’092 patent is attached hereto as Exhibit 8. The ’092 patent is assigned to
`
`Bristol-Myers Squibb Company.
`
`46.
`
`The ’092 patent issued from U.S. Application No. 16/006,493, filed June 12,
`
`2018, which is a continuation of U.S. Application No. 14/950,748, filed November 24, 2015
`
`(now U.S. Patent No. 10,072,082), which is a divisional of U.S. Application No. 13/892,671,
`
`filed May 13, 2013 (now U.S. Patent No. 9,212,224), which claims the benefit of U.S.
`
`Provisional Patent Application No. 61/790,747, filed on March 15, 2013, and U.S. Provisional
`
`Patent Application No. 61/647,442, filed May 15, 2012.
`
`47.
`
`The claims of the ’092 patent are generally directed to methods of treating a late
`
`stage non-small cell lung cancer tumor by administering an anti-PD-L1 antibody to the subject.
`
`By way of example, claim 1 of the ’092 patent is:
`
`A method of treating a late stage non-small cell lung cancer (NSCLC) tumor
`in a human subject, comprising administering to the subject about 10 mg/kg of an
`anti-PD-L1 antibody every 2 weeks, wherein the anti-PD-L1 antibody is
`administered intravenously over 60 minutes infusion; wherein the subject is
`pretreated for a chemotherapy and a radiotherapy; and wherein at least 1% of
`tumor cells in the tumor exhibit membrane PD-L1 expression.
`
`
`
`14
`
`
`
`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 15 of 85 PageID #: 15
`
`
`
`ASTRAZENECA’S IMFINZI PRODUCT
`
`48.
`
`AstraZeneca UK Limited is the holder of Biologics License Application (“BLA”)
`
`No. 761069 for IMFINZI (durvalumab). According to its prescribing information, IMFINZI
`
`contains a PD-L1 blocking antibody named durvalumab that is indicated for treating patients
`
`with specific types of cancer. The FDA-approved label for IMFINZI indicates that IMFINZI is
`
`manufactured for AstraZeneca Pharmaceuticals LP by AstraZeneca UK Limited. On information
`
`and belief, AstraZeneca Pharmaceuticals LP is marketing, using, distributing, offering for sale,
`
`selling, and importing IMFINZI in the United States as AstraZeneca UK Limited’s authorized
`
`agent.
`
`49.
`
`On May 1, 2017, the FDA approved IMFINZI as a treatment for patients with
`
`locally advanced or metastatic urothelial carcinoma who have disease progression during or
`
`following platinum-containing chemotherapy or have disease progression within 12 months of
`
`neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.1 The prescribing
`
`information that AstraZeneca provided and that the FDA approved in May 2017 instructed that
`
`IMFINZI was to be administered in a 10 mg/kg dose as an intravenous infusion over 60 minutes
`
`every 2 weeks to treat urothelial carcinoma.2
`
`50.
`
`On information and belief AstraZeneca began marketing IMFINZI for the
`
`treatment of urothelial carcinoma according to the prescribing information in the United States
`
`on May 1, 2017.
`
`51.
`
`On February 16, 2018, the FDA approved IMFINZI as a treatment for patients
`
`with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not
`
`
`1 https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761069Orig1s000ltr.pdf.
`2 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761069s000lbl.pdf.
`
`
`
`15
`
`
`
`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 16 of 85 PageID #: 16
`
`
`
`progressed following concurrent platinum-based chemotherapy and radiation therapy.3 The
`
`prescribing information that AstraZeneca provided and the FDA approved for the use of
`
`IMFINZI to treat non-small cell lung cancer indicates that IMFINZI is to be administered in a 10
`
`mg/kg dose as an intravenous infusion over 60 minutes every 2 weeks.4
`
`52.
`
`On information and belief AstraZeneca began marketing IMFINZI for the
`
`treatment of unresectable Stage III non-small cell lung