Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 1 of 20 PageID #: 1
`
`
`LINDIS BIOTECH, GMBH
`
`
`
`Plaintiff,
`v.
`
`
`
`AMGEN INC.
`
`
`
`Defendant.
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`Case No.
`
`)
`)
`)
`)
`)
`)
`)
`)
`
`COMPLAINT
`
`
`
`Lindis Biotech, GmbH (“Lindis”), by and through its undersigned counsel, for its
`
`complaint against Amgen Inc. (“Amgen”) states as follows:
`
`THE PARTIES
`
`1.
`
`Lindis is a corporate entity organized and existing under the laws of Germany.
`
`Lindis is a biotechnology company that invents, among other things, immunotherapy regimens
`
`for use in treating cancers.
`
`2.
`
`Amgen is a corporate entity organized and existing under the laws of the State of
`
`Delaware. Amgen’s principal place of business is in Thousand Oaks, California. Amgen is a
`
`global pharmaceutical company that develops, manufactures and sells drugs used to treat various
`
`illnesses, including immunotherapy drugs that are used to treat cancers.
`
`NATURE OF THE ACTION, JURISDICTION AND VENUE
`
`3.
`
`4.
`
`This is an action for patent infringement under the laws of the United States.
`
`This Court has subject matter jurisdiction over the patent claims asserted in this
`
`action under 28 U.S.C. §§ 1331 and 1338(a).
`
`5.
`
`Venue is proper under 28 U.S.C. § 1400(b) because defendant is a Delaware
`
`corporation and is deemed to reside in this District.
`
`39488273.1 01/10/2022
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 2 of 20 PageID #: 2
`
`6.
`
`This Court has personal jurisdiction over defendant because it is a Delaware
`
`corporation, has availed itself of rights and benefits conferred by Delaware law, and has
`
`substantial and continuing contacts with Delaware.
`
`FACTUAL BACKGROUND
`
`The Background of the Invention
`
`Lindis is the holder of several patents for the immunotherapy regimen which is
`
`
`
`
`
`7.
`
`the subject of this action. Dr. Horst Lindhofer is a principal at Lindis, and is one of the two
`
`inventors of the relevant patents. The other inventor is Dr. Marcus M. Heiss. Drs. Lindhofer and
`
`Heiss have both worked on the development of immunotherapy regimens for decades.
`
`8.
`
`Two fundamental basic challenges exist in the field of immunotherapy. The first
`
`challenge lies in directing the body’s cell-killing mechanisms (the immune system) to
`
`specifically attack only cancer cells and leave healthy cells largely untouched. The second
`
`challenge is modulating the body’s cell-killing response so that it does not overwhelm the body
`
`and kill other healthy cells and/or cause a dangerous inflammatory response. The patents at issue
`
`here successfully address both challenges.
`
`9.
`
`Immunotherapy is a treatment based on stimulating the body’s own immune
`
`system to fight disease. In case of cancer, immunotherapy enjoys significant advantages over the
`
`use of other cancer treatments, such as chemotherapy or radiation. For one, some cancers do not
`
`respond to radiation or chemotherapy, and such therapies are largely ineffective as to those
`
`cancers, including B-cell precursor acute lymphoblastic leukemia. Chemotherapy and radiation
`
`also have their own unique risks. Both therapies kill healthy cells in addition to cancer cells, and
`
`may damage healthy tissues or organs. Another risk of chemotherapy is that the patient may
`
`later develop leukemia as a result of the chemotherapy regimen. A common side effect of
`
`39488273.1 01/10/2022
`
`-2-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 3 of 20 PageID #: 3
`
`chemotherapy is a significantly impaired immune system, which renders the patient highly
`
`susceptible to infection, a condition known as neutropenia.
`
`10.
`
`The immunotherapy regimen developed by Lindis requires administration of
`
`bispecific antibodies to the patient. As implied by its name, bispecific antibodies have a
`
`specificity for attraction to two target cells: 1) the body’s own cancer killing T-cells and 2)
`
`cancer cells expressing a target antigen.
`
`11.
`
`Bispecific antibodies bind to the target antigen on the surface of cancer cells, and
`
`also bind to T-cells. In this way, these antibodies link the cancer killing T-cells to the specific,
`
`targeted cancer cells and bring them next to each other, triggering an immune response. The
`
`immune response attacks and destroys the cancer cells through the release of cytokines.
`
`Cytokines are regulatory proteins secreted by cells of the body’s immune system, and can have
`
`both cytotoxic and immunoregulatory properties.
`
`12.
`
`Stimulation of an immune response generates the release of cytokines. However,
`
`the presence of cytokines in the body can alone trigger the release of additional cytokines. An
`
`over-secretion of cytokines is known as a “cytokine storm” and is sometimes referred to as
`
`“Cytokine Release Syndrome,” which can result in serious adverse effects from the resulting
`
`cytotoxicity and inflammation. As indicated above, this condition has been an impediment to
`
`immunotherapy.
`
`13.
`
`Glucocorticoids have long been known to be effective at treating inflammation.
`
`For example, glucocorticoids are used together with other immunosuppressive agents to help
`
`prevent the body’s rejection of transplanted organs after transplantation. Skin rashes are another
`
`common ailment frequently treated by glucocorticoids. However, glucocorticoids were typically
`
`given after inflammation had already occurred in a patient, rather than preemptively.
`
`39488273.1 01/10/2022
`
`-3-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 4 of 20 PageID #: 4
`
`14.
`
`The concept of administering glucocorticoids before administering immuno-
`
`stimulating antibodies was a novel idea. Traditional medical opinion taught that administration
`
`of glucocorticoids would interfere with an immunotherapy regimen, and would keep it from
`
`being effective. Before creation of the Lindis immunotherapy regimen and its testing by Drs.
`
`Lindhofer and Heiss, accepted medical treatment involved use of a glucocorticoid as a rescue
`
`medication after administration of antibodies, not before, in order to treat the ill effects of
`
`cytokines.
`
`15.
`
`The inventors of the Lindis immunotherapy regimen proved this traditional
`
`medical opinion wrong. They discovered that administering glucocorticoids and
`
`immunostimulating antibodies surprisingly did not inhibit the effectiveness of the antibodies in
`
`eradicating targeted cancer cells. Rather, they learned that pre-administration of glucocorticoids
`
`reduced the non-specific release of cytokines and the associated inflammation – the so called
`
`“cytokine storm.” The specific, targeted release of cytokines against cancer cells was not
`
`impaired. This discovery, in turn, allowed the dosage of antibodies to be significantly increased
`
`to efficacious levels while retaining a favorable safety profile.
`
`The Invention and the European and U.S. Patents
`
`16.
`
`The immunotherapy regimen at issue in this case is for a treatment regimen which
`
`consists of administration to the patient of at least one recombinant bi-specific
`
`immunostimulatory scFv antibody exhibiting a first specificity against the tumor antigen CD19,
`
`and a second specificity against the T-cell marker CD3. That is, the regimen uses a bi-specific
`
`antibody with a predisposition to attach itself to both to a particular type of cancer cell and also
`
`to a specific type of T-cell.
`
`39488273.1 01/10/2022
`
`-4-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 5 of 20 PageID #: 5
`
`17.
`
`The other key part of the invention is administration of a glucocorticoid as
`
`premedication in order to control and limit the non-specific cytokine release. The specific
`
`glucocorticoid used is dexamethasone, sometimes in combination with another glucocorticoid.
`
`Alternatively, other glucocorticoids, including prednisone, can be used.
`
`18.
`
`A patent application, Application No. 05738161.8, for this Lindis immunotherapy
`
`regimen was filed in the European Patent Office on September 15, 2004, naming Markus M.
`
`Heiss and Horst Lindhofer as inventors. Subsequently, the European patent issued in the name
`
`of Markus M. Heiss and Horst Lindhofer, as EP Patent No. 1 874 821 (the “Lindis European
`
`Patent”).
`
`19.
`
`Amgen challenged the Lindis European Patent and sought its revocation through
`
`its affiliate entity Amgen Research (Munich) GmbH (“Amgen Research”). An entity named
`
`“Strawman Limited” also sought revocation of the Lindis European Patent. Both of these
`
`opposition proceedings in Europe were filed on January 17, 2014. Both opposition proceedings
`
`were in the nature of an appeal of the issued patent, and sought to revoke the Lindis European
`
`Patent. These proceedings have failed to revoke the Lindis European Patent to date.
`
`20.
`
`Amgen’s opposition proceeding challenged the validity of the Lindis European
`
`Patent, which is the European counterpart of the ‘421 Patent. Amgen was therefore aware of the
`
`subject matter and claims of the Lindis European Patent, and the subject matter of the ‘421
`
`Patent, significantly before January 17, 2014.
`
`21.
`
`Lindis filed its first U.S. patent application for this immunotherapy regimen on
`
`April 26, 2005. The first US patent in this series, US 8,709,421, issued on April 29, 2014 (“the
`
`‘421 Patent”). The patent examiner considered 9 US patent documents, 4 foreign patent
`
`39488273.1 01/10/2022
`
`-5-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 6 of 20 PageID #: 6
`
`documents, and 21 other references (publications), in issuing the ‘421 Patent with its 15 method
`
`claims.
`
`22.
`
`Representative claim 1 of the ‘421 Patent recites:
`
`A method for reducing the non-specific release of a cytokine in a subject which is
`
`associated with a treatment of a cancer or tumor with an antibody comprising
`
`
`administering to the subject at least one glucocorticoid immediately before or
`
`immediately after administering at least one trifunctional, bispecific immunostimulating
`antibody directed against a tumor antigen and a CD marker,
`
`which glucocorticoid reduces the non-specific release of the cytokine associated
`
`with the treatment of the cancer or tumor,
`
`wherein the CD marker is selected from the group consisting of CD2, CD3, CD4,
`
`CD5, CD6, CD8, CD28, and CD44.
`
`23.
`
`Lindis filed a continuation patent application in this family, and a second US
`
`patent issued to Lindis in this series, US 10,071,158 (“the ‘158 Patent”), on September 11, 2018.
`
`The ‘158 Patent was the result of extensive prosecution at the US Patent and Trademark Office
`
`(the “PTO”), including consideration of 94 US patent documents, 60 foreign patent documents,
`
`and 126 other references.
`
`24.
`
`Representative claim 1 of the ’158 Patent recites:
`
`A method for reducing the non-specific release of at least one cytokine in a
`subject, which is associated with a treatment of a cancer with at least one bispecific
`immunostimulating antibody, comprising:
`
`administering an effective amount of at least one glucocorticoid to the subject by
`way of premedication on the same day and prior in time relative to the
`administration to the subject of the at least one bispecific immunostimulating
`antibody directed against a tumor antigen and a CD marker such that said
`effective amount of said at least one glucocorticoid reduces cytokine release
`caused by the administration of the least one bispecific immunostimulating
`antibody,
`
`
`wherein
`
`the at least one glucocorticoid comprises dexamethasone,
`
`39488273.1 01/10/2022
`
`-6-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 7 of 20 PageID #: 7
`
`
`the tumor antigen is CD19, and
`
`the CD marker is CD3.
`
`Prior to issue of the ‘158 Patent, Lindis filed another continuation patent
`
`25.
`
`application, and a third US patent issued to Lindis in this series, US 10,576,149 (“the ‘149
`
`Patent”), on March 3, 2020.
`
`26.
`
`Representative claim 1 of the ‘149 patent recites:
`
`A method of using a bispecific antibody for treating lymphoma in a subject,
`
`comprising:
`
`administering dexamethasone to the subject on the same day as and prior in time
`
`to beginning administration of the bispecific antibody,
`
`wherein the bispecific antibody is directed against tumor antigen CD19 and T-cell
`
`marker CD3.
`
`a.
`
`The Infringing Conduct by Amgen
`
`27.
`
`Amgen manufactures and sells an immunotherapy drug named blinatumomab,
`
`which is marketed and sold under the name Blincyto. Blincyto was approved by the U.S. Food
`
`and Drug Administration for use in treating Acute Lymphoblastic Leukemia (“ALL”), a type of
`
`cancer affecting the blood and bone marrow. Blincyto was approved in the US to treat ALL on
`
`December 3, 2014. In a press release for Blincyto, Amgen claimed that it is the “first and only
`
`Bispecific CD 19 Directed CD3 T-Cell Engager (BITE®) Immunotherapy to be Approved by the
`
`FDA.”
`
`28.
`
`Blinatumomab is a bispecific recombinant antibody that links CD19 positive
`
`cells—including malignant cells—to CD3 positive T cells. The Amgen immunotherapy regimen
`
`uses the bispecific antibody blinatumomab to link the same specific cancer antigen (CD19) to the
`
`same type of T-cell (CD3 positive) as does the Lindis regimen.
`
`39488273.1 01/10/2022
`
`-7-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 8 of 20 PageID #: 8
`
`29.
`
`Amgen’s prescribing information for Blincyto gives the instruction to
`
`“[p]remedicate with prednisone or equivalent dexamethasone.” The instruction appears in
`
`multiple places, together with warnings for “CYTOKINE RELEASE SYNDROME” risk from
`
`the administration of Blincyto. Amgen also places a warning on the boxes and product labels for
`
`Blincyto which warn of “Cytokine Release Syndrome (CRS) and Neurological Toxicities.”
`
`30.
`
`According to its prescribing information, Amgen addresses the risk for over
`
`secretion of cytokines from administration of Blincyto through use of a glucocorticoid as a pre-
`
`medication to control the cytokine release in the exact same manner as the method which is
`
`protected by the Lindis patents. Amgen even uses the same glucocorticoids as Lindis,
`
`dexamethasone and prednisone, to control cytokine release.
`
`b.
`
`Infringement of the ‘421 Patent
`
`31.
`
`Using Blincyto as instructed by Amgen satisfies all of the elements recited in
`
`claim 1 of the ‘421 Patent. Using Blincyto according to the method instructed by Amgen
`
`infringes at least claim 1 of the ’421 Patent.
`
`32.
`
`The method for using Blincyto as instructed by Amgen includes reducing the non-
`
`specific release of at least one cytokine in a subject, which is associated with a treatment of a
`
`cancer with at least one bispecific immunostimulating antibody. Amgen’s prescribing
`
`information for Blincyto states, under “Indications and Usage,” that Blincyto “is a bispecific
`
`CD19-directed CD3 T-cell engager indicated for the treatment of … acute lymphoblastic
`
`leukemia (ALL).”
`
`33.
`
`The method for using Blincyto as instructed by Amgen includes administering an
`
`amount of glucocorticoid that reduces cytokine release caused by administration of a bispecific
`
`immunostimulating antibody. Amgen’s prescribing information warns about “Cytokine Release
`
`39488273.1 01/10/2022
`
`-8-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 9 of 20 PageID #: 9
`
`Syndrome,” which may be “life-threatening or fatal” in patients receiving BLINCYTO.
`
`Amgen’s prescribing information further states that “[b]efore you receive BLINCYTO, you will
`
`be given a corticosteroid medicine to help reduce infusion reactions,” and that “Blinatumomab
`
`mediates … production of cytolytic proteins, [and] release of inflammatory cytokines.”
`
`34.
`
`The method for using Blincyto as instructed by Amgen includes premedication
`
`with the glucocorticoid dexamethasone.
`
`35.
`
`The method for using Blincyto, as instructed by Amgen, is for the treatment of
`
`acute lymphoblastic leukemia, a cancer, through use of an immunostimulating, bispecific
`
`antibody with a specificity for the tumor antigen CD19 and the T-cell marker CD3. Amgen’s
`
`prescribing information states that “BLINCYTO is a bispecific CD19-directed CD3 T-cell
`
`engager.”
`
`36.
`
`Amgen has induced and continues to induce infringement in this District and
`
`elsewhere in the United States of the claims of the ‘421 Patent, including at least claim 1, by
`
`actively and successfully encouraging, instructing, enabling, and otherwise causing end users to
`
`use Blincyto in a manner that infringes the ‘421 Patent. As used herein, the term “end users”
`
`includes and refers to physicians who prescribe Blincyto for patients, physicians who administer
`
`Blincyto to patients, and physicians who supervise the administration of Blincyto to patients by
`
`others, such as by oncology nurses.
`
`37.
`
`The ‘421 Patent issued from U.S. Patent Publication No. 2009/0191201 (“the ‘201
`
`Publication”), published July 30, 2009. The disclosure of the ‘421 Patent is the same the
`
`disclosure of the ‘201 Publication. The fact that Lindis was pursuing patent protection in the US
`
`for the subject matter of the ‘421 Patent was therefore public knowledge at least as early as July
`
`30, 2009.
`
`39488273.1 01/10/2022
`
`-9-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 10 of 20 PageID #: 10
`
`38.
`
`By April 29, 2014, the issue date of the ‘421 patent, Amgen had knowledge of the
`
`‘421 Patent, and knew that use of Blincyto as instructed would infringe the ‘421 Patent.
`
`39.
`
`Amgen had knowledge of the subject matter of the ‘421 Patent from its efforts to
`
`oppose and prevent issuance of the European counterpart of the ‘421 Patent. Amgen also had
`
`knowledge of the subject matter of the ‘421 Patent as a result of direct communications between
`
`Amgen (through affiliate Amgen Research) and Lindis. Amgen Research and Lindis entered
`
`into a confidentiality agreement dated November 25, 2013. The parties then exchanged
`
`correspondence until early September 2014 about the possibility of a license from Lindis to
`
`Amgen for bispecific, trifunctional antibody patent rights. Pursuant to those communications,
`
`Amgen obtained information about the subject matter of the ‘421 Patent. The ‘421 Patent issued
`
`on April 29, 2014, during the time period when the parties were corresponding about a possible
`
`license agreement. The ‘421 Patent had already issued by the time Amgen obtained FDA
`
`approval for Blincyto on December 3, 2014.
`
`40.
`
`Amgen would have been aware of the filing of the patent application that
`
`ultimately issued as the ‘421 Patent because this patent issued in the US a few months after
`
`Amgen filed its European opposition. Amgen, by virtue of its detailed analysis of the European
`
`claims in its European opposition, was keenly aware of Lindis’ patent prosecution activity, and
`
`that Blincyto would infringe the claims of the related ‘421 Patent.
`
`41.
`
`Amgen has specifically intended that its end users would use Blincyto in a way
`
`that infringes the ‘421 Patent by, at a minimum, providing prescribing information to its end
`
`users about how to use Blincyto, and Amgen knew its actions would induce, have induced, and
`
`will continue to induce infringement by end users.
`
`39488273.1 01/10/2022
`
`-10-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 11 of 20 PageID #: 11
`
`42.
`
`Amgen has contributed to and continues to contribute to infringement of the ‘421
`
`Patent, including at least claim 1, by offering to sell and selling Blincyto to end users for use in
`
`practicing the patented method covered by the ‘421 Patent. Amgen’s Blincyto constitutes a
`
`material part of the invention, and end users have used Blincyto in a manner that infringes one or
`
`more claims of the ‘421 Patent. At least as early as April 29, 2014, Amgen knew that Blincyto
`
`was specially made and/or adapted for use(s) that would infringe one or more claims of the ‘421
`
`Patent and, therefore, is not a staple article or commodity of commerce suitable for any
`
`substantial non-infringing uses.
`
`43.
`
`Amgen has willfully induced infringement of the ‘421 Patent and willfully
`
`contributed to infringement of one or more claims of the ‘421 Patent.
`
`c.
`
`Infringement of the ‘158 Patent
`
`44.
`
`Using Blincyto as instructed by Amgen satisfies all of the elements recited in
`
`claim 1 of the ‘158 Patent. Using Blincyto according to the method as instructed by Amgen
`
`infringes at least claim 1 of the ‘158 Patent.
`
`45.
`
`The method for using Blincyto as instructed by Amgen includes reducing the non-
`
`specific release of at least one cytokine in a subject, which is associated with a treatment of a
`
`cancer with at least on bispecific immunostimulating antibody. Amgen’s prescribing
`
`information for Blincyto states, under “Indications and Usage,” that Blincyto “is a bispecific
`
`CD19-directed CD3 T-cell engager indicated for the treatment of … acute lymphoblastic
`
`leukemia (ALL).”
`
`46.
`
`The method for using Blincyto as instructed by Amgen includes administering an
`
`effective amount of at least one glucocorticoid to the subject by way of premedication on the
`
`same day and prior in time relative to the administration to the subject of a bispecific
`
`39488273.1 01/10/2022
`
`-11-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 12 of 20 PageID #: 12
`
`immunostimulating antibody directed against a tumor antigen and a CD marker. Amgen’s
`
`prescribing information for Blincyto instructs physicians to “[p]remedicate with prednisone or
`
`equivalent dexamethasone. (2.1).” In addition, the prescribing information states “[p]remedicate
`
`with dexamethasone: For adult patients, premedicate with 20 mg dexamethasone 1 hour prior to
`
`the first dose of BLINCYTO.”
`
`47.
`
`The method for using Blincyto as instructed by Amgen includes administering an
`
`amount of glucocorticoid that reduces cytokine release caused by administration of a bispecific
`
`immunostimulating antibody. Amgen’s prescribing information warns about “Cytokine Release
`
`Syndrome,” which may be “life-threatening or fatal” in patients receiving BLINCYTO.
`
`Amgen’s prescribing information further states that “[b]efore you receive BLINCYTO, you will
`
`be given a corticosteroid medicine to help reduce infusion reactions,” and that “Blinatumomab
`
`mediates … production of cytolytic proteins, [and] release of inflammatory cytokines.”
`
`48.
`
`The method for using Blincyto as instructed by Amgen includes premedication
`
`with the glucocorticoid dexamethasone.
`
`49.
`
`The method for using Blincyto, as instructed by Amgen, is for the treatment of
`
`acute lymphoblastic leukemia, a cancer, through use of an immunostimulating, bispecific
`
`antibody with a specificity for the tumor antigen CD19 and the T-cell marker CD3. Amgen’s
`
`prescribing information states that “BLINCYTO is a bispecific CD19-directed CD3 T-cell
`
`engager.”
`
`50.
`
`Amgen has induced and continues to induce infringement in this district and
`
`elsewhere in the United States of the claims of the ‘158 Patent, including at least claim 1, by
`
`actively and successfully encouraging, instructing, enabling, and otherwise causing end users to
`
`use Blincyto in a manner that infringes the ‘158 Patent. At least as early as September 11, 2018,
`
`39488273.1 01/10/2022
`
`-12-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 13 of 20 PageID #: 13
`
`Amgen had knowledge of the ‘158 Patent, and knew that use of Blincyto as instructed would
`
`infringe the ‘158 Patent.
`
`51.
`
`The ‘158 Patent is part of the patent family that includes the ‘421 Patent, which is
`
`the earliest issued infringed patent. Both the ‘158 Patent and the ‘421 Patent are counterparts of
`
`the Lindis European patent. Amgen had knowledge of the subject matter of the related ‘158
`
`Patent from its efforts to oppose and prevent issuance of the European counterpart of the ‘158
`
`Patent. Amgen also had knowledge of the subject matter of the ‘421 Patent as a result of direct
`
`communications between Amgen Research and Lindis about the possibility of a license from
`
`Lindis for bispecific, trifunctional antibody patent rights, and later during those discussions
`
`Amgen had knowledge of the issuance of the ‘421 Patent on April 29, 2014. Pursuant to these
`
`communications Amgen obtained information about the ‘421 Patent and notice of the ‘158
`
`Patent.
`
`52.
`
`Amgen would have been aware of the filing of the patent application that
`
`ultimately issued as the ‘158 Patent, because this application was filed prior to the issuance of
`
`the ‘421 Patent. Amgen, by virtue of its detailed analysis of the European claims in its European
`
`opposition. was keenly aware of Lindis’ patent prosecution activity, and that Blincyto would
`
`infringe the claims of the related ‘158 Patent.
`
`53.
`
`Amgen has specifically intended that its end users use Blincyto in a way that
`
`infringes the ‘158 Patent by, at a minimum, providing prescribing information to its end users
`
`about how to use Blincyto, and Amgen knew its actions would induce, have induced, and will
`
`continue to induce infringement by end users.
`
`54.
`
`Amgen has contributed to and continues to contribute to infringement of the ‘158
`
`Patent, including at least claim 1, by offering to sell and selling Blincyto to end users for use in
`
`39488273.1 01/10/2022
`
`-13-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 14 of 20 PageID #: 14
`
`practicing the patented method covered by the ‘158 Patent. Amgen’s Blincyto constitutes a
`
`material part of the invention, and end users have used Blincyto in a manner that infringes one of
`
`more claims of the ‘158 Patent. At least as early as September 11, 2018, Amgen knew that
`
`Blincyto was specially made and/or adapted for use(s) that would infringe one or more claims of
`
`the ‘158 Patent and, therefore, is not a staple article or commodity of commerce suitable for any
`
`substantial non-infringing uses.
`
`55.
`
`Amgen has willfully induced infringement of the ‘158 Patent and willfully
`
`contributed to infringement of one or more claims of the ‘158 Patent.
`
`d.
`
`Infringement of the ‘149 Patent
`
`56.
`
`Using Blincyto as instructed by Amgen satisfies all of the elements recited in
`
`claim 1 of the ‘149 patent. Using Blincyto according to the method instructed by Amgen
`
`infringes at least claim 1 of the ‘149 Patent.
`
`57.
`
`The method for using Blincyto as instructed by Amgen includes reducing the non-
`
`specific release of at least one cytokine in a subject, which is associated with a treatment of a
`
`cancer with at least on bispecific immunostimulating antibody. Amgen’s prescribing
`
`information for Blincyto states, under “Indications and Usage,” that Blincyto “is a bispecific
`
`CD19-directed CD3 T-cell engager indicated for the treatment of … acute lymphoblastic
`
`leukemia (ALL).”
`
`58.
`
`The method for using Blincyto as instructed by Amgen includes administering an
`
`amount of glucocorticoid that reduces cytokine release caused by administration of a bispecific
`
`immunostimulating antibody. Amgen’s prescribing information warns about “Cytokine Release
`
`Syndrome,” which may be “life-threatening or fatal” in patients receiving BLINCYTO.
`
`Amgen’s prescribing information further states that “[b]efore you receive BLINCYTO, you will
`
`39488273.1 01/10/2022
`
`-14-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 15 of 20 PageID #: 15
`
`be given a corticosteroid medicine to help reduce infusion reactions,” and that “Blinatumomab
`
`mediates … production of cytolytic proteins, [and] release of inflammatory cytokines.”
`
`59.
`
`The method for using Blincyto as instructed by Amgen includes premedication
`
`with the glucocorticoid dexamethasone.
`
`60.
`
`The method for using Blincyto, as instructed by Amgen, is for the treatment of
`
`acute lymphoblastic leukemia, a cancer, through use of an immunostimulating, bispecific
`
`antibody with a specificity for the tumor antigen CD19 and the T-cell marker CD3. Amgen’s
`
`prescribing information states that “BLINCYTO is a bispecific CD19-directed CD3 T-cell
`
`engager.”
`
`61.
`
`Amgen has induced and continues to induce infringement in this district and
`
`elsewhere in the United States of the claims of the ‘149 Patent, including at least claim 1, by
`
`actively and successfully encouraging, instructing, enabling, and otherwise causing end users to
`
`use Blincyto in a manner that infringes the ‘149 Patent.
`
`62.
`
`The ‘149 Patent is part of the patent family that includes the ‘158 Patent and the
`
`‘421 Patent, the latter of which is the earliest issued infringed patent. The ‘421 Patent, the ‘158
`
`Patent, and the ‘149 Patent are counterparts of the Lindis European Patent. At least as early as
`
`April 29, 2014, the issue date of the ‘421 patent, Amgen had knowledge of the related ‘421
`
`Patent, and knew that use of Blincyto as instructed would infringe the ‘421 Patent.
`
`63.
`
`Amgen had knowledge of the subject matter of the ‘149 Patent from its efforts to
`
`oppose and prevent issuance of the European counterpart of the ‘421 Patent. Amgen also had
`
`knowledge of the subject matter of the ‘421 Patent as a result of direct communications between
`
`Amgen Research and Lindis about the possibility of a license from Lindis for bispecific,
`
`trifunctional antibody patent rights, and later during those discussions Amgen had knowledge of
`
`39488273.1 01/10/2022
`
`-15-
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 16 of 20 PageID #: 16
`
`the issuance of the ‘421 Patent on April 29, 2014. Pursuant to these communications Amgen
`
`obtained information about the ‘421 Patent, and notice of the ‘158 Patent and of the ‘149 Patent.
`
`64.
`
`Amgen would have been aware of the filing of the patent application that
`
`ultimately issued as the ‘149 Patent, because this application was filed and pending in the US
`
`well after Amgen filed its European opposition. Amgen, by virtue of its detailed analysis of the
`
`European claims in its European opposition, was keenly aware of Lindis’ patent prosecution
`
`activity, and that Blincyto would infringe the claims of the related ‘149 Patent.
`
`65.
`
`Amgen has specifically intended that its end users use Blincyto in a way that
`
`infringes the ‘149 Patent by, at a minimum, providing prescribing information to its end users
`
`about how to use Blincyto, and Amgen knew its actions would induce, have induced, and will
`
`continue to induce infringement by end users.
`
`66.
`
`Amgen has contributed to and continues to contribute to infringement of the ‘149
`
`Patent, including at least claim 1, by offering to sell and selling Blincyto to end users for use in
`
`practicing the patented method covered by the ‘149 Patent. Amgen’s Blincyto constitutes a
`
`material part of the invention, and end users have used Blincyto in a manner that infringes one of
`
`more claims of the ‘149 Patent. At least as early as March 3, 2020, Amgen know that Blincyto
`
`was specially made and/or adapted for use(s) that would infringe one or more claims of the ‘149
`
`Patent and, therefore, is not a staple article or commodity of commerce suitable for any
`
`substantial non-infringing uses.
`
`67.
`
`Amgen has willfully induced infringement of the ‘149 Patent and willfully
`
`contributed to infringement of one or more claims of the ‘149 Patent.
`
`
`
`
`
`-16-
`
`39488273.1 01/10/2022
`
`

`

`Case 1:22-cv-00035-UNA Document 1 Filed 01/10/22 Page 17 of 20 PageID #: 17
`
`COUNT I – INFRINGEMENT OF THE ‘421 PATENT
`
`68.
`
`Plaintiff incorporates by reference the allegations of paragraphs 1-67 set forth
`
`above as if fully set forth herein.
`
`69.
`
`Amgen is currently manufacturing, marketing, distributing and selling the
`
`immunotherapy drug Blincyto in the United States, and around the world.
`
`70.
`
`Upon information and belief, Amgen also is manufacturing Blincyto in the United
`
`States for the purpose of selling Blincyto outside of the United States. Upon information and
`
`belief, Amgen ships Blincyto from the US to other countries for distribution, sale and use,
`
`together with the prescribing information for Blincyto. This conduct constitutes acts of
`
`infringement.
`
`71.
`
`Using Blincyto as instructed by Amgen constitutes direct infringement of one or
`
`more claims of the ‘421 Patent.
`
`72.
`
`Amgen’s actions as set forth above constitute contributory and induced
`
`infringement of one or more claims of the ‘421 Patent.
`
`73.
`
`Amgen’s acts of infringement have caused and will continue to cause Lindis to
`
`suffer significan