DCT
1:17-cv-01631
AbbVie Inc v. Cipla Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AbbVie Inc. (Delaware) and AbbVie Deutschland GmbH & Co. KG (Germany)
- Defendant: Cipla Limited (India) and Cipla USA, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:17-cv-01631, D. Del., 11/10/2017
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Cipla USA, Inc. is incorporated in Delaware.
- Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's Kaletra® (lopinavir/ritonavir) tablets constitutes an act of infringement of nine U.S. patents covering pharmaceutical formulations and methods of use.
- Technical Context: The patents relate to formulations of ritonavir and lopinavir, two HIV protease inhibitors used in combination for the treatment of HIV infection, a significant therapeutic area.
- Key Procedural History: The complaint notes that two of the asserted patents, U.S. Patent Nos. 7,148,359 and 7,364,752, were amended in Inter Partes Reexamination proceedings, which may affect the scope and interpretation of their claims. The litigation was triggered by Defendants' submission of ANDA No. 090-371 with a Paragraph IV certification, asserting that the patents-in-suit are invalid and/or not infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 1998-07-20 | ’359 Patent Priority Date |
| 1999-11-12 | ’752 Patent Priority Date |
| 2003-08-28 | Priority Date for ’899, ’349, ’613, ’952, ’015, ’347, ’878 Patents |
| 2006-12-12 | ’359 Patent Issue Date |
| 2008-04-29 | ’752 Patent Issue Date |
| 2011-09-27 | ’899 Patent Issue Date |
| 2012-09-18 | ’349 Patent Issue Date |
| 2012-11-13 | ’613 Patent Issue Date |
| 2013-02-19 | ’952 Patent Issue Date |
| 2013-03-19 | ’015 Patent Issue Date |
| 2013-06-25 | ’347 Patent Issue Date |
| 2014-04-08 | ’878 Patent Issue Date |
| 2015-01-23 | ’752 Patent Reexamination Certificate Issued |
| 2016-05-23 | ’359 Patent Reexamination Certificate Issued |
| 2017-09-27 | Plaintiff receives Defendant's Paragraph IV Notice Letter |
| 2017-11-10 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,148,359 - "Polymorph of a Pharmaceutical", issued December 12, 2006
The Invention Explained
- Problem Addressed: The patent's background describes the HIV protease inhibitor ritonavir and notes that prior disclosed processes produced a specific crystalline form, termed "Form I" (’359 Patent, col. 2:46-50). The discovery of new polymorphic forms of a drug is a significant challenge, as different crystal structures can affect a drug's physical properties and therapeutic performance (’359 Patent, col. 2:19-21).
- The Patented Solution: The invention is the discovery and characterization of a new crystalline polymorph of ritonavir, designated "Form II," as well as an amorphous form of the drug (’359 Patent, Abstract; col. 2:19-24). The patent discloses methods for preparing these novel solid-state forms, such as by melting Form I ritonavir and rapidly cooling the melt to produce amorphous ritonavir (’359 Patent, col. 14:28-39).
- Technical Importance: Identifying and controlling polymorphism is critical in pharmaceutical development, as different solid forms of the same active ingredient can possess distinct dissolution rates, stability, and bioavailability, impacting both manufacturability and clinical efficacy.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 and dependent claim 8 (Compl. ¶48).
- The essential element of independent claim 1 is:
- Substantially pure amorphous ritonavir.
- The complaint does not explicitly reserve the right to assert other dependent claims but alleges infringement of "one or more claims" (Compl. ¶47).
U.S. Patent No. 7,364,752 - "Solid Dispersion Pharmaceutical Formulations", issued April 29, 2008
The Invention Explained
- Problem Addressed: The patent addresses the poor oral bioavailability of many HIV protease inhibitors, which limits their therapeutic utility (’752 Patent, col. 1:15-21). While liquid oral solutions can provide optimal bioavailability, solid dosage forms like capsules or tablets are generally preferred for patient compliance, but typically exhibit lower bioavailability (’752 Patent, col. 1:35-42).
- The Patented Solution: The invention provides a pharmaceutical composition where the HIV protease inhibitor, such as ritonavir, is formulated as a "solid dispersion" within a water-soluble polymer matrix, such as polyethylene glycol (PEG) (’752 Patent, Abstract; col. 3:1-12). This formulation technique is designed to create a finely dispersed, often amorphous, state of the drug within the carrier, thereby increasing its dissolution rate and subsequent absorption in the body (’752 Patent, col. 4:1-5).
- Technical Importance: Solid dispersion technology is a key strategy for formulating poorly water-soluble drugs, enabling the development of effective oral solid dosage forms for compounds that would otherwise have insufficient bioavailability to be clinically useful.
Key Claims at a Glance
- The complaint asserts at least dependent claims 8 and 38 (Compl. ¶69). These claims depend from other claims, with claim 1 being the base independent composition claim.
- The essential elements of independent claim 1 are:
- A pharmaceutical composition comprising ritonavir.
- Wherein the ritonavir is formulated as a solid dispersion of amorphous ritonavir.
- In a matrix including a water soluble polymer.
- The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶54).
U.S. Patent No. 8,025,899 - "Solid Pharmaceutical Dosage Form", issued September 27, 2011
- Technology Synopsis: This patent describes a solid pharmaceutical dosage form of HIV protease inhibitors (such as lopinavir and ritonavir) formulated as a solid dispersion with a water-soluble polymer and a surfactant. The formulation is intended to provide improved oral bioavailability (’899 Patent, Abstract).
- Asserted Claims: At least independent claim 1 and dependent claim 4 (Compl. ¶78).
- Accused Features: Cipla's Generic Lopinavir/Ritonavir Tablets are alleged to be a "solid pharmaceutical dosage form" containing lopinavir and ritonavir that infringes the patent (Compl. ¶78).
U.S. Patent No. 8,268,349 - "Solid Pharmaceutical Dosage Form", issued September 18, 2012
- Technology Synopsis: This patent is directed to a solid dosage form comprising ritonavir formulated as a solid dispersion. The formulation includes a water-soluble polymer and a surfactant to improve oral bioavailability (’349 Patent, Abstract).
- Asserted Claims: At least independent claim 1 and dependent claim 6 (Compl. ¶87).
- Accused Features: Cipla's Generic Lopinavir/Ritonavir Tablets are alleged to be a "solid pharmaceutical dosage form" containing ritonavir that infringes the patent (Compl. ¶87).
U.S. Patent No. 8,309,613 - "Solid Pharmaceutical Dosage Form", issued November 13, 2012
- Technology Synopsis: This patent claims a method of treating an HIV infection by administering a solid dosage form comprising lopinavir and ritonavir. The formulation is a solid dispersion containing a water-soluble polymer and a surfactant (’613 Patent, Abstract).
- Asserted Claims: At least independent claim 1 and dependent claim 3 (Compl. ¶109).
- Accused Features: Defendants are accused of inducing infringement by seeking FDA approval for their generic tablets for the same indication (treating HIV infection), which will allegedly lead medical practitioners to directly infringe the method claims (Compl. ¶109).
U.S. Patent No. 8,377,952 - "Solid Pharmaceutical Dosage Formulation", issued February 19, 2013
- Technology Synopsis: This patent claims a method of treating HIV by administering a solid dosage form of lopinavir/ritonavir that provides specific pharmacokinetic profiles and can be taken without food or under fasting conditions. The claims are directed at achieving certain bioavailability outcomes with reduced variability (’952 Patent, Abstract; claim 1).
- Asserted Claims: At least independent claim 1 and dependent claim 2 (Compl. ¶132).
- Accused Features: Defendants are accused of inducing infringement, as their product labeling will allegedly instruct medical practitioners and patients to administer the tablets in a manner (e.g., "without food or under a fasting condition") that directly infringes the method claims (Compl. ¶132).
U.S. Patent No. 8,399,015 - "Solid Pharmaceutical Dosage Form", issued March 19, 2013
- Technology Synopsis: This patent describes a solid dosage form comprising a solid dispersion of lopinavir and ritonavir. The formulation includes a water-soluble polymer and a surfactant with a specific hydrophilic-lipophilic balance (HLB) value (’015 Patent, Abstract).
- Asserted Claims: At least independent claim 1 and dependent claim 4 (Compl. ¶141).
- Accused Features: Cipla's Generic Lopinavir/Ritonavir Tablets are alleged to be a "solid pharmaceutical dosage form" containing lopinavir and ritonavir that meets the claim limitations (Compl. ¶141).
U.S. Patent No. 8,470,347 - "Self-Emulsifying Active Substance Formulation and Use of This Formulation", issued June 25, 2013
- Technology Synopsis: This patent is directed to a self-emulsifying formulation containing an active ingredient, a lipid component, and a binder. The formulation is designed to spontaneously form an emulsion in aqueous media, which can improve the bioavailability of poorly soluble active ingredients (’347 Patent, Abstract).
- Asserted Claims: At least independent claim 1 and dependent claim 2 (Compl. ¶150).
- Accused Features: Cipla's tablets are alleged to be a "solid, self-emulsifying formulation" that is "essentially free of lipid and active pharmaceutical ingredient crystals" and contains a lipid component within the claimed weight percentage range (Compl. ¶150).
U.S. Patent No. 8,691,878 - "Solid Pharmaceutical Dosage Form", issued April 8, 2014
- Technology Synopsis: This patent claims a method for treating HIV by administering a solid pharmaceutical dosage form containing ritonavir and a water-soluble polymer. The claims are directed to the method of use for such a formulation (’878 Patent, Abstract).
- Asserted Claims: At least independent claim 1 and dependent claim 2 (Compl. ¶171).
- Accused Features: Defendants are accused of inducing infringement by seeking approval to market their tablets for treating HIV, which will allegedly cause medical practitioners to directly infringe the method claim by administering the product (Compl. ¶171).
III. The Accused Instrumentality
- Product Identification: The accused products are "Cipla's Generic Lopinavir/Ritonavir Tablets" in 100 mg/25 mg and 200 mg/50 mg dosage strengths (Compl. ¶30).
- Functionality and Market Context: The accused product is a proposed generic version of AbbVie's successful Kaletra® tablets, an antiretroviral medication used to treat HIV infection (Compl. ¶29-30). Defendants have filed ANDA No. 090-371 with the FDA seeking approval to market the tablets in the United States (Compl. ¶30). The complaint alleges that Defendants have represented to the FDA that their generic product is bioequivalent, therapeutically equivalent, and pharmaceutically equivalent to AbbVie's Kaletra® tablets (Compl. ¶46).
IV. Analysis of Infringement Allegations
’359 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Substantially pure amorphous ritonavir. | The accused tablets are alleged to comprise "substantially pure amorphous ritonavir." This allegation is based on a review of Defendant's Notice Letter, which allegedly does not contest that the tablets contain amorphous ritonavir or that the amorphous ritonavir is substantially pure. | ¶48 | col. 12:15 |
’752 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising ritonavir, | The accused product is identified as "Cipla's Generic Lopinavir/Ritonavir Tablets." | ¶69 | col. 12:4-6 |
| wherein ritonavir in said composition is formulated as a solid dispersion of amorphous ritonavir | The complaint alleges on information and belief that the ritonavir in the accused tablets is in the form of a solid dispersion of amorphous ritonavir. | ¶69 | col. 12:6-8 |
| in a matrix including a water soluble polymer. | The complaint does not provide sufficient detail for analysis of the specific matrix or water-soluble polymer allegedly used in the accused product. | ¶69 | col. 12:8-9 |
- Identified Points of Contention:
- Scope Questions (’359 Patent): The infringement analysis may turn on the construction of "substantially pure." The reexamination proceeding added new claims that quantify purity levels (e.g., "does not contain more than about 10% of any other compound") (’359 Patent, Reexam Cert., col. 2:20-22). A central question will be whether the term in claim 1 should be interpreted in light of these more specific claims and what level of impurities, if any, are present in the accused product.
- Technical Questions (’752 Patent): The complaint alleges the accused product is a "solid dispersion" but provides no direct technical evidence, such as manufacturing process details or physical characterization data (e.g., X-ray diffraction), to support this structural conclusion (Compl. ¶69). A primary evidentiary question will be whether Defendants' product, alleged to be bioequivalent, actually possesses the specific "solid dispersion" structure in a "water soluble polymer" matrix as required by the claim, or if it achieves bioequivalence through a different, non-infringing formulation.
No probative visual evidence provided in complaint.
V. Key Claim Terms for Construction
The Term: "substantially pure amorphous ritonavir" (’359 Patent, claim 1)
- Context and Importance: This term constitutes the entirety of independent claim 1. Its construction is dispositive for infringement of this patent. The degree of purity required to meet the "substantially pure" limitation will be a central point of dispute. Practitioners may focus on this term because the reexamination certificate introduced new claims with specific percentage limits for impurities, which could influence the interpretation of the original, undefined term.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The original specification uses the term "substantially pure" without providing a quantitative definition, which could support an interpretation based on the ordinary meaning of the term, focusing on the general character rather than a strict numerical threshold (’359 Patent, col. 12:51-60).
- Evidence for a Narrower Interpretation: The reexamination certificate added claims 8, 9, and 10, which depend from claim 1 and specify that the composition "does not contain more than about 10%," "5%," or "3% of any other compound," respectively (’359 Patent, Reexam Cert., col. 2:20-25). A party could argue that these later-added claims suggest a narrower meaning for "substantially pure" or, conversely, that they define distinct inventions, leaving claim 1 with a broader scope.
The Term: "solid dispersion" (’752 Patent, claim 1)
- Context and Importance: This term defines the core technological feature of the claimed formulation. Whether the accused product meets the structural requirements of a "solid dispersion" is critical for infringement. The dispute may focus on whether this term requires a molecular-level dispersion of the drug in the polymer matrix, or if a broader range of physical mixtures could qualify.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a general definition from the literature: "the dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by the melting (or fusion), solvent, or melting-solvent methods" (’752 Patent, col. 1:41-47). This could be read to encompass a variety of physical states.
- Evidence for a Narrower Interpretation: The specification also refers to the formulation as a "solid (molecular) dispersion" and explains that the goal is to have the compound "finely dispersed (molecular dispersion)" to maximize dissolution (’752 Patent, col. 3:1-2; col. 4:1-4). This language may support an argument that the term requires a true molecular solution of the drug within the polymer, not merely a microcrystalline or other less-integrated mixture.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement for U.S. Patent Nos. 7,364,752, 8,309,613, 8,377,952, and 8,691,878. The allegations are based on Defendants' filing of an ANDA with a proposed package insert that allegedly contains directions encouraging and instructing medical practitioners and patients to administer the generic product for the treatment of HIV infection, which would directly infringe the asserted method claims (e.g., Compl. ¶59-60, ¶99-100).
- Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, for each asserted patent, it alleges that Defendants have knowledge of the patent "as evidenced by Cipla's Notice Letter" (e.g., Compl. ¶58, ¶98). These allegations of pre-suit knowledge could form the basis for a later claim of willful infringement.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: How will the term "substantially pure amorphous ritonavir" in the ’359 Patent be construed, particularly in view of the more specific, percentage-based purity limitations added to the patent during a contested reexamination proceeding?
- A key evidentiary question will be one of technical structure: For the multiple formulation patents asserted, what factual evidence can be developed to determine if the accused generic product—alleged in the complaint primarily on the basis of bioequivalence—is in fact a "solid dispersion" in a "water-soluble polymer" matrix, or if it utilizes a different, non-infringing formulation technology?