DCT
1:17-cv-12087
Teva Pharma Intl GmbH v. Eli Lilly Co
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Teva Pharmaceuticals International GmbH (Switzerland) and Teva Pharmaceuticals USA, Inc. (Delaware)
- Defendant: Eli Lilly and Company (Indiana)
- Plaintiff’s Counsel: Goodwin Procter LLP
- Case Identification: 1:17-cv-12087, D. Mass., 01/17/2018
- Venue Allegations: Plaintiff alleges venue is proper because Defendant Eli Lilly resides in the district, maintains a regular and established place of business in Massachusetts, and plans to commit acts of infringement in the district upon receiving FDA approval for its product.
- Core Dispute: Plaintiff alleges that Defendant’s imminent commercial launch of its galcanezumab biologic product will infringe five patents related to methods and compositions for treating migraines using anti-CGRP antagonist antibodies.
- Technical Context: The technology involves humanized monoclonal antibodies designed to target and inhibit the calcitonin gene-related peptide (CGRP), a neuropeptide implicated in the pathology of migraine headaches.
- Key Procedural History: The complaint alleges that Defendant initiated an opposition proceeding against a related European patent in July 2014. This allegation may be used to support claims of pre-suit knowledge of the asserted patent family.
Case Timeline
| Date | Event |
|---|---|
| 2005-11-14 | Earliest Priority Date for all Patents-in-Suit |
| 2013-11-19 | U.S. Patent No. 8,586,045 Issued |
| 2013-12-03 | U.S. Patent No. 8,597,649 Issued |
| 2014-07-16 | Defendant allegedly initiated opposition to related European patent |
| 2016-02-23 | U.S. Patent No. 9,266,951 Issued |
| 2016-05-17 | U.S. Patent No. 9,340,614 Issued |
| 2016-05-24 | U.S. Patent No. 9,346,881 Issued |
| 2017-10-24 | Defendant submitted Biologics License Application (BLA) for Galcanezumab Product |
| 2018-01-17 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,586,045 - "Methods of Using Anti-CGRP Antagonist Antibodies"
- Patent Identification: U.S. Patent No. 8,586,045, "Methods of Using Anti-CGRP Antagonist Antibodies," issued November 19, 2013.
The Invention Explained
- Problem Addressed: The patent’s background section describes the significant public health burden of vasomotor symptoms like migraine headaches and the limitations of existing treatments, which can be ineffective or cause undesirable side effects for many patients ('045 Patent, col. 2:41-3:14).
- The Patented Solution: The invention provides a method for treating or preventing these vasomotor symptoms by administering an "anti-CGRP antagonist antibody." This antibody is designed to bind to the calcitonin gene-related peptide (CGRP), a neuropeptide known to be a potent vasodilator, thereby inhibiting the peptide's biological activity and mitigating migraine symptoms ('045 Patent, col. 3:36-44; Abstract). The detailed description identifies specific antibodies, such as antibody G1, that demonstrate this function ('045 Patent, col. 6:11-13).
- Technical Importance: The invention represented a targeted biological approach to migraine therapy, focusing on a specific mechanism (CGRP antagonism) rather than relying on less-selective small molecule drugs with broad neurological effects. (Compl. ¶3).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶72). Independent claim 1 is representative of the patent’s core method-of-use invention.
- Claim 1 Elements:
- A method for reducing incidence of or treating at least one vasomotor symptom in an individual,
- comprising administering to the individual an effective amount of an anti-CGRP antagonist antibody,
- wherein said anti-CGRP antagonist antibody is a human monoclonal antibody or a humanized monoclonal antibody.
U.S. Patent No. 8,597,649 - "Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide and Methods Using Same"
- Patent Identification: U.S. Patent No. 8,597,649, "Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide and Methods Using Same," issued December 3, 2013.
The Invention Explained
- Problem Addressed: As with the related ’045 Patent, this patent addresses the need for improved treatments for CGRP-associated disorders like migraines ('649 Patent, col. 1:25-2:67).
- The Patented Solution: Rather than claiming a method of treatment, this patent claims the therapeutic agent itself: an isolated human or humanized antibody that binds to CGRP with a specific, high affinity. The claims quantify this high affinity with a specific numerical threshold measured by a particular scientific technique ('649 Patent, col. 3:39-44; Abstract).
- Technical Importance: This patent protects the specific antibody composition, providing a distinct layer of intellectual property protection from the method-of-use claims of the ’045 Patent. (Compl. ¶3).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specification (Compl. ¶78). Independent claim 1 is representative of the patent's core composition-of-matter invention and is cited narratively in the complaint (Compl. ¶46).
- Claim 1 Elements:
- An isolated human or humanized anti-CGRP antagonist antibody
- with a binding affinity (KD) to human α-CGRP of 50 nM or less
- as measured by surface plasmon resonance at 37° C.
U.S. Patent No. 9,266,951
- Patent Identification: U.S. Patent No. 9,266,951, "Antagonist antibodies directed against calcitonin gene-related peptide and methods using same," issued February 23, 2016.
- Technology Synopsis: This patent claims a human or humanized monoclonal anti-CGRP antagonist antibody defined by a specific functional characteristic: its ability to inhibit cyclic adenosine monophosphate (cAMP) activation in cells (Compl. ¶48). This functional limitation distinguishes it from patents defined primarily by binding affinity.
- Asserted Claims: "one or more claims" (Compl. ¶84).
- Accused Features: The Galcanezumab Product is alleged to infringe because it is a humanized monoclonal anti-CGRP antibody that inhibits cAMP activation in cells (Compl. ¶57, ¶63).
U.S. Patent No. 9,340,614
- Patent Identification: U.S. Patent No. 9,340,614, "Antagonist antibodies directed against calcitonin gene-related peptide and methods using same," issued May 17, 2016.
- Technology Synopsis: This patent claims a human or humanized monoclonal anti-CGRP antagonist antibody defined by its preferential binding to human α-CGRP as compared to a related peptide, amylin (Compl. ¶51). This claim language focuses on the antibody's binding selectivity.
- Asserted Claims: "one or more claims" (Compl. ¶90).
- Accused Features: The Galcanezumab Product is alleged to infringe because it is a humanized monoclonal anti-CGRP antibody that preferentially binds to human CGRP as compared to amylin (Compl. ¶57, ¶64).
U.S. Patent No. 9,346,881
- Patent Identification: U.S. Patent No. 9,346,881, "Antagonist antibodies directed against calcitonin gene-related peptide and methods using same," issued May 24, 2016.
- Technology Synopsis: This patent claims a human or humanized monoclonal anti-CGRP antagonist antibody defined by another functional characteristic: its ability to inhibit human α-CGRP from binding to its receptor, as measured by a specific laboratory test (a radioligand binding assay in SK-N-MC cells) (Compl. ¶54).
- Asserted Claims: "one or more claims" (Compl. ¶96).
- Accused Features: The Galcanezumab Product is alleged to infringe because it is a humanized monoclonal anti-CGRP antibody that prevents CGRP from binding to its receptor as measured by the claimed assay (Compl. ¶57, ¶59).
III. The Accused Instrumentality
Product Identification
- Defendant’s Galcanezumab Product, also identified by the laboratory designation LY2951742 (Compl. ¶5).
Functionality and Market Context
- The complaint alleges that the Galcanezumab Product is a humanized monoclonal antibody designed to treat migraines by targeting and inhibiting CGRP (Compl. ¶5, ¶56-57). The complaint cites scientific literature to allege specific technical properties of the Galcanezumab Product, including its ability to bind human α-CGRP, its binding affinity of 31 pM as measured by surface plasmon resonance, its ability to inhibit cAMP activation, and its preferential binding to CGRP over amylin (Compl. ¶58-64).
- The complaint frames the Galcanezumab Product as a direct competitor to Plaintiff's own fremanezumab product (Compl. ¶5). It alleges Defendant has submitted a Biologics License Application (BLA) to the FDA and is actively preparing for a commercial launch immediately upon approval, including building a sales force and developing marketing materials (Compl. ¶15, ¶19, ¶21).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
8,586,045 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for reducing incidence of or treating at least one vasomotor symptom in an individual... | Defendant intends to market the Galcanezumab Product for the prevention of migraine, which the patent identifies as a vasomotor symptom. Defendant will allegedly provide labels and instruct physicians on this use. | ¶55, ¶67, ¶68 | col. 2:32-35 |
| ...comprising administering to the individual an effective amount of an anti-CGRP antagonist antibody... | Defendant's product labeling and physician instructions will allegedly include directions on how to administer an effective dose of the Galcanezumab Product, which is an anti-CGRP antagonist antibody. | ¶56, ¶67, ¶68 | col. 3:41-44 |
| ...wherein said anti-CGRP antagonist antibody is a human monoclonal antibody or a humanized monoclonal antibody. | The Galcanezumab Product is alleged to be a humanized monoclonal antibody. | ¶57 | col. 4:50-52 |
- Identified Points of Contention:
- Scope Questions: A central issue in this declaratory judgment action is one of contingency. The complaint's allegations of infringement are based on Defendant's pre-launch activities and scientific publications. The analysis will depend on whether the final, FDA-approved product and its label for use correspond to the pre-launch information cited in the complaint.
- Technical Questions: What evidence does the complaint provide that Defendant's instructions to physicians will direct the administration of an "effective amount" for "treating" migraines as required by the claim? The complaint alleges the product labeling will provide instructions for administering an "effective dose" for the "prevention" of migraines (Compl. ¶67), raising the question of how the terms "treating" and "prevention" will be construed.
8,597,649 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An isolated human or humanized anti-CGRP antagonist antibody... | The Galcanezumab Product is alleged to be an isolated, humanized monoclonal antibody that functions as an anti-CGRP antagonist. | ¶56, ¶57 | col. 4:50-52 |
| ...with a binding affinity (KD) to human α-CGRP of 50 nM or less... | The Galcanezumab Product is alleged to have a binding affinity to human CGRP of 31 pM, which is substantially less than the 50 nM threshold. | ¶60 | col. 5:35-42 |
| ...as measured by surface plasmon resonance at 37° C. | The complaint alleges that the 31 pM binding affinity was measured by surface plasmon resonance at 37° C. | ¶60 | col. 5:35-39 |
- Identified Points of Contention:
- Scope Questions: What is the proper claim construction for the phrase "as measured by," and does it require that the measurement method used for the accused product be identical to a specific protocol in the patent, or merely that it be a scientifically recognized form of surface plasmon resonance?
- Technical Questions: Does the scientific publication cited for the accused product's binding affinity (Compl. ¶60, citing Benschop, et al.) employ a surface plasmon resonance methodology that is technically and legally consistent with the requirements for measuring affinity as understood from the patent's specification and prosecution history?
V. Key Claim Terms for Construction
The Term: "anti-CGRP antagonist antibody"
- Context and Importance: This term appears in the independent claims of both lead patents and defines the entire class of accused agents. Its construction is critical to determining whether the Galcanezumab Product is within the scope of the claims. Practitioners may focus on this term because its scope could be debated as either a broad functional definition or one limited to specific disclosed embodiments.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition, stating the term includes an antibody that is "able to bind to CGRP and inhibit CGRP biological activity and/or downstream pathway(s) mediated by CGRP signaling" ('045 Patent, col. 13:62-66). This language may support a construction covering any antibody that performs this function, regardless of its specific structure.
- Evidence for a Narrower Interpretation: The specification also provides detailed descriptions and sequences for a specific exemplary antibody, "antibody G1," and its variants ('045 Patent, col. 6:11-13; Fig. 5). A party may argue that the term should be construed more narrowly in light of these specific examples, which represent the invention that was actually made and disclosed.
The Term: "vasomotor symptom"
- Context and Importance: This term in claim 1 of the '045 patent defines the medical conditions for which the claimed treatment method applies. The infringement analysis for this method claim depends on migraine being construed as a "vasomotor symptom."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification explicitly lists "headaches (e.g., migraine, cluster headache, and tension headache)" as a type of CGRP-associated disorder and vasomotor symptom ('045 Patent, col. 1:24-27; col. 3:39-44). This may support a direct and explicit inclusion of migraine within the term's scope.
- Evidence for a Narrower Interpretation: A party could argue that the term should be limited by its technical meaning at the time of the invention, potentially raising scientific questions about whether migraine was universally classified as a "vasomotor symptom" and attempting to distinguish it from other listed examples like "hot flushes" ('045 Patent, col. 1:27).
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement of infringement of the method claims, such as those in the '045 patent (Compl. ¶6, ¶71). The alleged factual basis is that Defendant will market its Galcanezumab Product with labeling and package inserts that will instruct physicians and patients to administer the product for the prevention of migraine, thereby directing others to perform the steps of the claimed methods (Compl. ¶66-68).
- Willful Infringement: The complaint alleges that Defendant's infringement will be knowing and willful (Compl. ¶73, ¶79, ¶85, ¶91, ¶97). The basis for this allegation is Defendant's alleged pre-suit knowledge of the asserted patent family, evidenced by its initiation of an opposition proceeding against a related European patent on July 16, 2014, years before filing its BLA for the accused product (Compl. ¶22-25).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of ripeness and contingency: as a pre-launch declaratory judgment action, the case will first turn on whether Defendant's activities have created an actual and immediate controversy. If so, a key evidentiary question will be whether the final, FDA-approved Galcanezumab Product and its label for use align with the pre-launch technical data and marketing plans alleged in the complaint.
- A central technical question will be one of equivalency of characterization: does the scientific evidence cited by Plaintiff regarding the accused product's binding affinity and functional properties meet the claim limitations when those limitations are construed in light of the specific measurement protocols and definitions provided in the patents-in-suit?
- A key question for damages will be one of pre-suit knowledge and intent: did Defendant's alleged awareness of the asserted patent family since at least 2014, followed by its decision to proceed with developing and seeking approval for a competing product, constitute objective recklessness sufficient to support a finding of willful infringement?