DCT
1:17-cv-00227
Novo Nordisk Inc v. Teva Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Novo Nordisk Inc. and Novo Nordisk A/S (Delaware and Denmark)
- Defendant: Teva Pharmaceuticals USA, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; White & Case LLP
- Case Identification: 1:17-cv-00227, D. Del., 03/03/2017
- Venue Allegations: Venue is alleged to be proper as Defendant is a Delaware corporation that conducts business, is registered, and derives revenue in Delaware.
- Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Victoza® product constitutes an act of infringement of five patents covering the drug's active ingredient, its formulation, and its injection device.
- Technical Context: The technology relates to GLP-1 analog therapeutics, a class of injectable drugs used primarily for the treatment of type 2 diabetes that has significant market presence.
- Key Procedural History: The litigation was initiated under the Hatch-Waxman Act, triggered by Defendant’s submission of an ANDA with a Paragraph IV certification to the FDA. This certification asserts that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 1996-08-30 | ’343 Patent Earliest Priority Date |
| 1999-09-16 | RE ’956 Patent Earliest Priority Date |
| 2001-06-28 | ’618 Patent Earliest Priority Date |
| 2001-07-31 | ’343 Patent Issue Date |
| 2003-11-20 | ’833 Patent Earliest Priority Date |
| 2007-02-05 | ’893 Patent Earliest Priority Date |
| 2010-11-23 | RE ’956 Patent Issue Date |
| 2012-02-14 | ’833 Patent Issue Date |
| 2014-09-30 | ’618 Patent Issue Date |
| 2016-02-23 | ’893 Patent Issue Date |
| 2017-01-20 | Defendant's Paragraph IV Certification Letter to Plaintiff |
| 2017-03-03 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,268,343 - “Derivatives of GLP-1 Analogs” (Issued Jul. 31, 2001)
The Invention Explained
- Problem Addressed: The patent addresses the therapeutic limitation of native human glucagon-like peptide-1 (GLP-1), which, despite its potent insulin-stimulating effects, has a very short biological half-life, making it impractical for treating chronic conditions like diabetes (’343 Patent, col. 2:50-55).
- The Patented Solution: The invention provides modified GLP-1 analogs that have a "protracted profile of action" (’343 Patent, Abstract). This is achieved by attaching a "lipophilic substituent" to the GLP-1 peptide backbone, which prolongs the molecule's activity in the body (’343 Patent, col. 16:55-65). This modification allows the drug to be administered less frequently.
- Technical Importance: The development of long-acting GLP-1 analogs was a significant advance in diabetes treatment, enabling the transition from therapies requiring multiple daily injections to more convenient once-daily regimens.
Key Claims at a Glance
- The complaint asserts independent claim 1 and a number of dependent claims (Compl. ¶21).
- Essential elements of independent claim 1 include:
- A GLP-1 derivative of a specific amino acid sequence (formula I, SEQ ID NO:2).
- The derivative has a lysine (Lys) amino acid at position 26.
- The epsilon-amino group of this lysine is substituted with a lipophilic substituent via a spacer.
- The lipophilic substituent is defined as one of several specified chemical groups, including certain fatty acid acyl groups (e.g., CH3(CH2)nCO-).
- The spacer is defined as one of several chemical groups, including an amino acid residue or an amino diacid.
- The complaint reserves the right to assert additional claims (Compl. ¶21).
U.S. Patent No. 8,114,833 - “Propylene Glycol-Containing Peptide Formulations Which Are Optimal for Production and For Use in Injection Devices” (Issued Feb. 14, 2012)
The Invention Explained
- Problem Addressed: The patent identifies problems associated with using mannitol, a common isotonicity agent in injectable peptide formulations. Mannitol can crystallize during production, leading to deposits on filling equipment, and can also cause clogging of the fine-gauge needles used in injection devices (’833 Patent, col. 1:33-49).
- The Patented Solution: The invention discloses replacing mannitol with propylene glycol as the isotonicity agent in a peptide formulation. This specific substitution is described as reducing deposits on production equipment and reducing the clogging of injection devices, making the formulation "optimal for production and for use" (’833 Patent, Abstract; col. 2:38-49).
- Technical Importance: This technology addresses practical manufacturing and end-user issues, aiming to improve production efficiency and enhance the reliability and safety of the final drug delivery system.
Key Claims at a Glance
- The complaint asserts claims 1-31 (Compl. ¶28).
- Essential elements of independent claim 1 include:
- A pharmaceutical formulation.
- Comprising at least one GLP-1 agonist.
- Comprising a disodium phosphate dihydrate buffer.
- Comprising propylene glycol.
- The propylene glycol is present in a final concentration of from about 1 mg/ml to about 100 mg/ml.
- The formulation has a pH of from about 7.0 to about 10.0.
U.S. Patent No. 8,846,618 - “Stable Formulation of Modified GLP-1” (Issued Sep. 30, 2014)
- Technology Synopsis: This patent addresses the chemical and physical instability of modified GLP-1 compounds in aqueous solutions, which can lead to aggregation and loss of biological activity (’618 Patent, col. 2:20-33). The invention claims a physically stable pharmaceutical formulation comprising a modified GLP-1 compound and a buffer, where the formulation is maintained within a specific pH range of about 7.0 to 10.0, which is asserted to confer long-term stability (’618 Patent, col. 3:12-24).
- Asserted Claims: Claims 1-3 and 5-14 (Compl. ¶34).
- Accused Features: The complaint alleges that Teva’s proposed generic liraglutide product is a formulation that will infringe these claims (Compl. ¶34).
U.S. Patent No. 9,265,893 - “Injection Button” (Issued Feb. 23, 2016)
- Technology Synopsis: This patent relates to the mechanical design of a push-button for an injection pen device. The technical problem is minimizing the friction that occurs when a user pushes a button that must also rotate relative to an internal driving part to administer a dose (’893 Patent, col. 1:40-54). The solution is a specific connection design featuring a pivot bearing and radial bearings that reduce operational force and improve user experience (’893 Patent, Abstract).
- Asserted Claims: Claims 1-6 (Compl. ¶40).
- Accused Features: The complaint alleges that the injection device intended for use with Teva's generic product will infringe these claims (Compl. ¶39-40).
U.S. Patent No. RE41,956 - “Dose Setting Limiter” (Issued Nov. 23, 2010)
- Technology Synopsis: This patent discloses a mechanism for a multi-dose injection pen that prevents a user from setting a dose larger than the amount of medication remaining in the drug cartridge (RE ’956 Patent, Abstract). The solution involves a driver with a track and a track follower coupled to the dose setting member. As doses are administered, the follower moves along the track, and when it reaches the end, it physically blocks the dose setting member from being rotated further (RE ’956 Patent, Abstract).
- Asserted Claims: Claims 1-19 (Compl. ¶46).
- Accused Features: The complaint alleges that the injection device intended for use with Teva's generic product will infringe these claims (Compl. ¶45-46).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is identified as "Teva’s Product," a generic version of Liraglutide Recombinant Solution Injection, 18 mg/3 ml (6 mg/ml), for which Teva has filed ANDA No. 210084 with the FDA (Compl. ¶12). The act of infringement is the filing of this ANDA, which seeks approval to market the product before the expiration of the patents-in-suit (Compl. ¶1, ¶15).
Functionality and Market Context
The complaint alleges that Teva’s ANDA relies upon Novo Nordisk’s approved New Drug Application for Victoza® and contains data demonstrating the bioequivalence of Teva’s Product to Victoza® (Compl. ¶13). As a generic equivalent, Teva's Product is intended to serve the same therapeutic market as Victoza®, a widely used treatment for type 2 diabetes. The infringement allegations also encompass the injection device that would be used to administer Teva's product (Compl. ¶39, ¶45). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a detailed claim chart. The infringement theory is based on 35 U.S.C. § 271(e)(2)(A), where the filing of an ANDA for a generic drug is a statutory act of infringement. The allegations presuppose that because Teva’s Product is a generic version of Victoza®, it will necessarily practice the claims covering the Victoza® active ingredient, formulation, and delivery device.
’343 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A GLP-1 derivative of formula I (SEQ ID NO:2)... | The active ingredient in Teva's Product is alleged to be liraglutide, which the complaint asserts is a GLP-1 derivative covered by the patent. | ¶12, ¶21 | col. 266:55-68 |
| wherein...the c-amino group of a Lys at position 26 is substituted with a lipophilic substituent, optionally via a spacer... | Teva's product is alleged to contain liraglutide, which has a lipophilic substituent attached via a spacer to the lysine at position 26. | ¶12, ¶21 | col. 267:15-20 |
| wherein...the lipophilic substituent is (i) CH3(CH2)nCO-... | The liraglutide molecule in Teva's Product is alleged to contain a hexadecanoyl substituent, which corresponds to the claimed chemical structure. | ¶12, ¶21 | col. 267:21-25 |
’833 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical formulation comprising at least one GLP-1 agonist... | Teva’s Product is alleged to be a pharmaceutical formulation containing liraglutide, a GLP-1 agonist. | ¶12, ¶28 | col. 4:26-34 |
| a disodium phosphate dihydrate buffer... | The formulation of Teva's Product is alleged to contain the claimed buffer system. | ¶12, ¶28 | col. 10:45-59 |
| and propylene glycol...in a final concentration of from about 1 mg/ml to about 100 mg/ml... | The formulation of Teva's Product is alleged to contain propylene glycol as an isotonicity agent within the claimed concentration range. | ¶12, ¶28 | col. 1:56-65; col. 10:17-21 |
| wherein said formulation has a pH of from about 7.0 to about 10.0. | The formulation of Teva's Product is alleged to be maintained within the claimed pH range. | ¶12, ¶28 | col. 1:65-2:2 |
- Identified Points of Contention:
- Evidentiary Questions: The complaint lacks specific factual allegations detailing the composition of Teva’s proposed product or the design of its delivery device. A primary point of contention will be an evidentiary one: what are the precise characteristics of Teva's product and device, and do they meet every limitation of the asserted claims?
- Scope Questions (Formulation): The dispute may raise questions about the scope of formulation terms. For instance, does Teva's use of specific excipients or maintenance of its product within a particular pH range fall within the boundaries defined by terms like "about" as used in the ’833 patent's concentration and pH limitations?
- Scope Questions (Device): For the device patents (’893 and RE ’956), the analysis will question whether the specific mechanical structures in Teva’s chosen injection pen, such as its push-button mechanism or dose-limiting feature, are structurally and functionally equivalent to the claimed inventions.
V. Key Claim Terms for Construction
The complaint does not identify any specific claim terms for construction. However, based on the technology, the following terms may become central to the dispute.
The Term: "GLP-1 agonist" (’833 Patent, Claim 1)
Context and Importance: The definition of this term is fundamental, as it defines the active ingredient covered by the formulation patents. Practitioners may focus on this term if Teva argues its active pharmaceutical ingredient, while bioequivalent, is technically not a "GLP-1 agonist" as defined and understood within the patent.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition: "any peptide which fully or partially activates the human GLP-1 receptor" and binds with a certain affinity (’833 Patent, col. 4:26-31). This functional language may support a broad construction covering any molecule that achieves the specified result.
- Evidence for a Narrower Interpretation: The specification lists numerous specific examples of GLP-1 agonists (’833 Patent, col. 4:40-52; col. 7:4-56). A defendant might argue these examples limit the scope of the term to the structures disclosed or those very similar.
The Term: "about" (e.g., "about 1 mg/ml to about 100 mg/ml") (’833 Patent, Claim 1)
Context and Importance: This term is critical for determining the literal scope of the claimed concentration and pH ranges. The infringement analysis for the formulation patents will depend on whether the precise concentration of propylene glycol and the pH of Teva's product fall within the range encompassed by "about."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not provide an explicit definition for "about," which may suggest it should be given its ordinary meaning in the context of pharmaceutical formulations, allowing for standard manufacturing tolerances.
- Evidence for a Narrower Interpretation: The patent provides specific examples with precise concentrations (e.g., 13.7 mg/ml or 14.0 mg/ml) (’833 Patent, col. 16:11; col. 19:14). A party could argue these precise values inform and limit the reasonable range of the term "about."
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Teva's future commercialization of its product would intentionally induce infringement of at least claim 39 of the ’343 patent (Compl. ¶22). The complaint does not specify the factual basis for inducement, such as instructions on a product label, but alleges it would occur with Teva's knowledge of the patent.
- Willful Infringement: The complaint does not use the term "willful infringement" but requests a finding that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶25, 31, 37, 43, 49). The factual basis for this appears to be pre-suit knowledge, established by Teva's January 20, 2017 letter containing its Paragraph IV certifications (Compl. ¶14).
VII. Analyst’s Conclusion: Key Questions for the Case
This litigation, initiated under the specialized framework of the Hatch-Waxman Act, will likely center on the following key questions for the court:
- A central question of construction and infringement: Do the precise chemical formulation and mechanical design of Teva's proposed generic product and delivery device fall within the scope of the asserted claims? This will involve a detailed, limitation-by-limitation comparison once the specifics of Teva's ANDA are produced in discovery.
- A core issue of patentability: As indicated by Teva's Paragraph IV certification, a determinative aspect of the case will be the validity of Novo Nordisk's patents. The key question will be whether the claimed inventions—covering the liraglutide molecule, its specific formulation, and its delivery pen technology—are valid over the prior art that Teva will present.
- An evidentiary question regarding the device patents: While the infringement of the drug composition and formulation claims is tied to the bioequivalence of the active ingredient, the infringement of the device patents (’893 and RE ’956) presents a separate factual inquiry. A key question will be whether the specific injection pen Teva intends to market incorporates the patented push-button and dose-limiter mechanisms, or if it utilizes a non-infringing alternative design.