throbber
Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 1 of 85 PageID #: 1
`
`
`
`UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`
`
`
`
`
`
`
`
`
`)
`
`BRISTOL-MYERS SQUIBB CO. and
`)
`
`E. R. SQUIBB & SONS, L.L.C.,
`
`)
`
`
`
`
`
`
`
`)
`
`
`Plaintiffs,
`
`
`
`)
`
`
`
`
`
`
`
`)
`
`v.
`
`
`
`
`
`)
`
`
`
`
`
`
`
`ASTRAZENECA PHARMACEUTICALS LP and )
`ASTRAZENECA UK LTD.,
`
`
`)
`
`
`
`
`
`
`
`)
`
`Defendants.
`
`
`
`
`)
`
`
`
`
`
`
`
`)
`
`
`
`COMPLAINT
`
`C.A. No. ______________
`
`
`
` JURY TRIAL DEMANDED
`
`
`
`
`Plaintiffs Bristol-Myers Squibb Co. (“BMS”) and E. R. Squibb & Sons, L.L.C.
`
`(“Squibb”) for their complaint for patent infringement against Defendants AstraZeneca
`
`Pharmaceuticals LP and AstraZeneca UK Ltd. (collectively, “Defendants” or “AstraZeneca”),
`
`hereby allege as follows:
`
`INTRODUCTION
`
`1.
`
`According to the United States Centers for Disease Control and Prevention, more
`
`than 1.6 million people in the United States are diagnosed with cancer each year
`
`(https://www.cdc.gov/chronicdisease/resources/publications/factsheets/cancer.htm). Cancer is a
`
`disease that results from the uncontrolled proliferation of cells that were once normal but have
`
`transformed into cancerous cells. Although the human immune system sometimes has the
`
`potential to eliminate cancerous cells, cancer cells have the ability to “turn off” or evade the
`
`immune system, allowing the cancer cells to grow unchecked. Tumor growth and tumor
`
`metastasis can lead to devastating disease, and possibly death. Cancer treatments are therefore
`
`developed to decrease tumor growth and metastasis.
`1
`
`
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 2 of 85 PageID #: 2
`
`
`
`2.
`
`This case relates to groundbreaking treatments for cancer that fall within a field
`
`known as “immunotherapy.” The treatment of cancer using immunotherapy represents a
`
`scientific breakthrough that is revolutionizing cancer treatment by manipulating a patient’s
`
`immune system to eliminate cancer cells.
`
`3.
`
`The human immune system is formed of organs, specialized cells, and substances
`
`that protect individuals from infections and disease. T cells are one class of specialized cells that
`
`play an important role in the human immune system. One major function of T cells is to destroy
`
`pathogens or malignant cells, and to do that the T cell must distinguish healthy cells from
`
`infected or malignant cells through the activation or deactivation of various receptors on the T
`
`cell surface. One of the receptors that T cells express on their surface is a protein called
`
`programmed death-1 receptor (“PD-1”). PD-1 functions as a checkpoint on the immune system
`
`that can downregulate T cell activity to prevent an overactive immune response. To activate its
`
`inhibitory function, PD-1 must bind to one of its ligands. Programmed death-ligand 1 (“PD-L1”)
`
`is one of these ligands.
`
`4.
`
`Numerous forms of cancers express PD-L1 on their cell surface, and can therefore
`
`exploit PD-1’s ability to downregulate the immune response. When PD-L1 on a cancer cell
`
`binds to PD-1 on immune cells, such as a T cell, it can result in the suppression of T cell
`
`migration, proliferation, and secretion of cytotoxic mediators. When cancer cells are present,
`
`this pathway can prevent the immune system from eliminating those cancer cells. In other
`
`words, cancer cells expressing PD-L1 can activate the PD-1 checkpoint to prevent a patient’s
`
`immune system from destroying cancer cells.
`
`5.
`
`Plaintiffs invented methods for treating cancer and methods for enhancing
`
`immune responses by administering antibodies that bind to PD-L1 (“anti-PD-L1 antibodies”).
`
`
`
`2
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 3 of 85 PageID #: 3
`
`
`
`The inventions also cover using specific types of anti-PD-L1 antibodies to inhibit the interaction
`
`between PD-1 and PD-L1. By binding to PD-L1 and blocking its interaction with PD-1, the anti-
`
`PD-L1 antibodies act as checkpoint inhibitors that release the brakes on the immune system,
`
`freeing the immune cells to recognize, attack and destroy cancer cells. Plaintiffs also invented
`
`anti-PD-L1 antibodies with specific properties for use in methods of treatment and methods for
`
`enhancing immune responses.
`
`6.
`
`Plaintiffs also invented antibodies that bind to PD-1 (“anti-PD-1 antibodies”), and
`
`put this scientific breakthrough into practice by developing an anti-PD-1 antibody called
`
`OPDIVO (nivolumab), the first anti-PD-1 antibody approved anywhere in the world for cancer
`
`treatment, and the first anti-PD-1 antibody approved in the United States for the treatment of
`
`lung cancer.
`
`7.
`
`Nivolumab is a monoclonal antibody that recognizes and binds to PD-1. When
`
`nivolumab binds to PD-1, it prevents PD-1 from binding to its ligands, e.g., PD-L1. Using
`
`nivolumab to block the interaction between PD-1 and its ligands enhances the T cell response
`
`generated by the patient’s immune system.
`
`8.
`
`Clinical testing of nivolumab confirmed the remarkable promise of checkpoint
`
`inhibitors as targets for immunotherapy. After rigorous worldwide testing, on July 4, 2014,
`
`nivolumab became the first anti-PD-1 antibody approved anywhere in the world for treating
`
`cancer, when Japanese regulatory authorities approved nivolumab (OPDIVO) for the treatment
`
`of melanoma, a deadly form of skin cancer (https://www.cancerresearch.org/en-
`
`us/immunotherapy/timeline-of-progress). On December 22, 2014, the U.S. Food and Drug
`
`Administration (“FDA”) approved nivolumab for treatment of advanced melanoma in the United
`
`States.
`
`
`
`3
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 4 of 85 PageID #: 4
`
`
`
`9.
`
`Plaintiffs have continued worldwide development of nivolumab for treatment of a
`
`broad range of cancers, including non-small cell lung cancer, urothelial carcinoma, renal cell
`
`carcinoma, head and neck cancer, malignant pleural mesothelioma, lymphoma, colorectal cancer,
`
`hepatocellular carcinomas, esophageal cancer, and gastric cancers. In Phase III clinical testing
`
`for lung cancer, patients with advanced lung cancer who received nivolumab showed superior
`
`overall survival (41% reduction in the risk of death) compared to those who received the
`
`standard of care chemotherapy agent docetaxol (https://news.bms.com/news/details/2015/FDA-
`
`Approves-Opdivo-nivolumab-for-the-Treatment-of-Patients-with-Previously-Treated-Metastatic-
`
`Squamous-Non-Small-Cell-Lung-Cancer/default.aspx). Based, at least in part, on these clinical
`
`results, on February 27, 2015, the FDA accepted Plaintiffs’ Biologics License Application
`
`(“BLA”) for use of nivolumab to treat lung cancer. Just days later, on March 4, 2015, the FDA
`
`approved nivolumab for treatment of advanced non-small cell lung cancer in the United States.
`
`In Phase III clinical testing for urothelial carcinoma, median disease-free survival was nearly
`
`twice as long in patients who received nivolumab as compared to placebo
`
`(https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-
`
`Opdivo-nivolumab-for-the-Adjuvant-Treatment-of-Patients-with-High-Risk-Urothelial-
`
`Carcinoma/default.aspx). On August 29, 2021, based at least in part on those clinical results, the
`
`FDA approved nivolumab to treat certain types of urothelial carcinoma. The clinical results and
`
`the FDA’s approval of nivolumab for the treatment of various additional forms of cancer confirm
`
`that the cancer treatments developed by the Plaintiffs can be used to save the lives of patients
`
`suffering from cancer.
`
`10.
`
`AstraZeneca is exploiting Plaintiffs’ inventions and infringing Plaintiffs’
`
`intellectual property rights by marketing a later-developed anti-PD-L1 antibody product,
`
`
`
`4
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 5 of 85 PageID #: 5
`
`
`
`IMFINZI (durvalumab), which is used in methods for treating cancer and for enhancing the
`
`immune response.
`
`11.
`
`Since Plaintiffs and AstraZeneca are direct competitors in the field of
`
`immunotherapy, Plaintiffs have suffered, and continue to suffer, substantial damages, including
`
`lost profits, as a result of AstraZeneca’s infringement. Marking pursuant to 35 U.S.C. § 287 was
`
`not required because Plaintiffs’ product OPDIVO is an anti-PD-1 antibody and is not a patented
`
`article under the asserted patents.
`
`PARTIES
`
`12.
`
`BMS is a corporation organized under the laws of the state of Delaware, with a
`
`principal place of business at 345 Park Ave., New York, New York 10154. E. R. Squibb & Sons,
`
`L.L.C., is a limited liability company organized and existing under the laws of the state of
`
`Delaware, with its principal place of business at Route 206 & Province Line Road, Princeton,
`
`New Jersey 08543.
`
`13.
`
`On information and belief, AstraZeneca Pharmaceuticals LP is a limited
`
`partnership organized under the laws of the State of Delaware, with its principal place of
`
`business at 1800 Concord Pike, Wilmington, Delaware 19803.
`
`14.
`
`On information and belief, AstraZeneca UK Limited is a private limited company
`
`organized under the laws of England and Wales, with its registered office at 1 Francis Crick
`
`Avenue, Cambridge Biomedical Campus, Cambridge, United Kingdom, CB2 0AA.
`
`15.
`
`AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited are in the business
`
`of manufacturing, marketing, distributing, offering for sale, and selling drug products that are
`
`distributed and sold throughout the United States, including in Delaware.
`
`
`
`5
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 6 of 85 PageID #: 6
`
`
`
`16.
`
`AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited are sophisticated
`
`pharmaceutical companies. On information and belief, AstraZeneca relies on and actively seeks
`
`patent protection for its products. On information and belief, AstraZeneca regularly enforces its
`
`patents and other intellectual property rights.
`
`JURISDICTION AND VENUE
`
`17.
`
`This is an action for patent infringement arising under the Patent Laws of the
`
`United States, 35 U.S.C. §§ 271 et seq., including an action seeking a declaratory judgment
`
`pursuant to 28 U.S.C. §§ 2201-2202.
`
`18.
`
`This Court has subject matter jurisdiction over this action pursuant to 28 U.S.C.
`
`§§ 1331 and 1338(a).
`
`19.
`
`This Court has personal jurisdiction over AstraZeneca Pharmaceuticals LP
`
`because it is a Delaware entity located in Delaware.
`
`20.
`
`This Court has jurisdiction over AstraZeneca UK Limited, inter alia, because its
`
`subsidiary and agent, AstraZeneca Pharmaceuticals LP, is incorporated in Delaware and, upon
`
`information and belief, markets and sells IMFINZI in Delaware as AstraZeneca UK Limited’s
`
`authorized agent and under AstraZeneca UK Limited’s direction and control.
`
`21.
`
`On information and belief, AstraZeneca Pharmaceuticals LP and AstraZeneca UK
`
`Limited are engaged in a single business activity of biopharmaceuticals and are not separated
`
`into multiple operating segments. On information and belief, the biopharmaceuticals business of
`
`AstraZeneca Pharmaceuticals LP and AstraZeneca UK Limited consists of the discovery and
`
`development of products, which are then manufactured, marketed, and sold. On information and
`
`belief, all of these functional activities take place (and are managed) globally on a highly
`
`
`
`6
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 7 of 85 PageID #: 7
`
`
`
`integrated basis. On information and belief, these individual functional areas are not managed
`
`separately.
`
`22.
`
`On information and belief, AstraZeneca Pharmaceuticals LP and AstraZeneca UK
`
`Limited have consented to jurisdiction in Delaware in one or more prior cases arising out of the
`
`manufacture, use, offer for sale, sale and/or importation of pharmaceutical products, including
`
`cases AstraZeneca initiated as the plaintiff.
`
`23.
`
`Venue is proper in this district under 28 U.S.C. §§ 1391(c) and 1400(b).
`
`THE PATENTS-IN-SUIT
`
`24.
`
`On February 28, 2017, the USPTO duly and legally issued U.S. Patent No.
`
`9,580,505 (“the ’505 patent”) titled “Human Monoclonal Antibodies to Programmed Death
`
`Ligand 1 (PD-L1).” A true and correct copy of the ’505 patent is attached hereto as Exhibit 1.
`
`The ’505 patent is assigned to E. R. Squibb & Sons, L.L.C.
`
`25.
`
`The ’505 patent issued from U.S. Application No. 14/807,522, filed on July 23,
`
`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
`
`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.
`
`26.
`
`The claims of the ’505 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 ’505 patent is:
`
`
`
`7
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 8 of 85 PageID #: 8
`
`
`
`
`
`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.
`
`
`
`8
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 9 of 85 PageID #: 9
`
`
`
`27.
`
`On February 28, 2017, the USPTO duly and legally issued U.S. Patent No.
`
`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;
`
`
`
`9
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 10 of 85 PageID #: 10
`
`
`
`(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
`
`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
`
`
`
`10
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 11 of 85 PageID #: 11
`
`
`
`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
`
`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
`
`

`

`Case 1:22-cv-00346-UNA Document 1 Filed 03/17/22 Page 12 of 85 PageID #: 12
`
`
`
`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

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket