DCT
1:16-cv-01005
Eli Lilly Co v. Cipla Ltd
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiffs: Eli Lilly and Company (Indiana); Eli Lilly Export S.A. (Switzerland); Acrux DDS Pty Ltd. (Australia)
- Defendants: Cipla Limited (India); Cipla USA, Inc. (Delaware)
- Plaintiff’s Counsel: Finnegan, Henderson, Farabow, Garrett & Dunner, LLP; Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: Eli Lilly and Company, et al. v. Cipla Limited, et al., 1:16-cv-01005, D. Del., 10/28/2016
- Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant Cipla USA, Inc. being a Delaware corporation and both Defendants regularly transacting business in the state.
- Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) for a generic version of the Axiron® transdermal testosterone solution constitutes an act of infringement of three patents directed to methods and compositions for transdermal drug delivery.
- Technical Context: The technology relates to formulations for delivering testosterone through the skin, a method used for hormone replacement therapy in individuals with testosterone deficiency.
- Key Procedural History: The lawsuit was triggered by Defendants' filing of an ANDA with a Paragraph IV certification, a statutory act of infringement under the Hatch-Waxman Act, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product. Plaintiffs state they received a notice letter regarding the ANDA filing on September 16, 2016, and filed this complaint within the statutory 45-day window.
Case Timeline
| Date | Event |
|---|---|
| 2005-06-03 | Priority Date for '944, '520, and '194 Patents |
| 2010-11-23 | FDA Approval of Axiron® New Drug Application |
| 2013-05-07 | U.S. Patent No. 8,435,944 Issues |
| 2015-03-31 | U.S. Patent No. 8,993,520 Issues |
| 2015-11-10 | U.S. Patent No. 9,180,194 Issues |
| 2016-09-16 | Plaintiffs Receive Notice Letter of Defendants' ANDA Filing |
| 2016-10-28 | Complaint for Patent Infringement Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,435,944 - "Method and Composition for Transdermal Drug Delivery," issued May 7, 2013
The Invention Explained
- Problem Addressed: The patent describes challenges with existing transdermal testosterone therapies, including the need to apply compositions over a large area of the body, which increases the risk of accidental transfer to family members (’944 Patent, col. 1:47-54). It also notes that application to specific sites, like the scrotum, can lead to undesirable side effects, and that application to areas prone to perspiration, such as the axilla (underarm), may be hindered by the use of antiperspirants or deodorants (’944 Patent, col. 2:5-30).
- The Patented Solution: The invention is a method and composition for delivering a drug like testosterone through the skin in a way that is rapid, consistent, and confined to a small application area, specifically the axilla (’944 Patent, col. 2:36-39, col. 6:55-58). The composition comprises the active agent (testosterone), a volatile solvent (like a lower alkyl alcohol), a viscosity modulating agent, and a penetration enhancer, formulated to be applied as a non-occlusive lotion or spray that dries quickly (’944 Patent, Abstract; col. 4:39-54). This approach aims to deliver a therapeutic dose while mitigating the risks of accidental transfer and side effects.
- Technical Importance: The claimed method provides a way to achieve systemic testosterone levels comparable to natural production by using the axilla, an application site not conventionally preferred for transdermal delivery due to concerns about perspiration, thereby offering a discrete and convenient alternative to gels or patches applied to the torso or limbs (’944 Patent, col. 1:41-47; col. 19:56-62).
Key Claims at a Glance
- The complaint asserts infringement of at least one claim (Compl. ¶34). Independent claim 1 is representative:
- A method of increasing the testosterone blood level of an adult male subject in need thereof.
- The method comprises applying a non-occlusive transdermal drug delivery composition to at least one axilla of the subject.
- The composition consists of: (a) a pharmaceutically effective amount of testosterone; (b) one or more lower alkyl alcohols (>60% v/v); (c) one or more penetration enhancers from a specific list (e.g., octisalate); (d) one or more viscosity modulating agents; and several optional components including water.
- The application is in an amount effective to achieve a blood level of at least 200 ng/dL.
U.S. Patent No. 8,993,520 - "Method and Composition for Transdermal Drug Delivery," issued March 31, 2015
The Invention Explained
- Problem Addressed: The patent addresses the same technical problems as its parent, the ’944 patent: the risks and inconveniences associated with traditional transdermal testosterone application methods, such as accidental drug transfer and site-specific side effects (’520 Patent, col. 1:44 - col. 2:35).
- The Patented Solution: The '520 patent discloses a similar solution: a method of applying a specific testosterone formulation to the axilla to achieve systemic delivery (’520 Patent, Abstract; col. 2:40-52). The core inventive concept of using the axilla as a primary delivery site with a fast-drying, non-occlusive formulation is maintained from the parent patent (’520 Patent, col. 8:1-14).
- Technical Importance: As with the '944 patent, this invention provides an alternative administration route for testosterone therapy that aims to improve patient convenience and reduce the risk of secondary exposure to the drug (’520 Patent, col. 2:31-39).
Key Claims at a Glance
- The complaint asserts infringement of at least one claim (Compl. ¶51). Independent claim 1 is representative:
- A method of increasing the testosterone blood level of an adult male subject in need thereof.
- The method comprises applying a transdermal drug delivery composition to at least one axilla of the subject, without occlusion by a patch.
- The composition comprises: (a) a pharmaceutically effective amount of testosterone; (b) one or more lower alkyl alcohols (>60% v/v); (c) one or more penetration enhancers from a specified, broad list of chemical classes; and (d) a viscosity modulating agent.
U.S. Patent No. 9,180,194 - "Method and Composition for Transdermal Drug Delivery," issued November 10, 2015
- Technology Synopsis: Continuing the same inventive theme, this patent claims methods for increasing a subject's testosterone blood level by applying a specific transdermal composition to the axilla (’194 Patent, Abstract). The formulation is designed for rapid, non-occlusive delivery from a site not traditionally used for such therapy, aiming to provide a therapeutic effect while minimizing risks associated with other application methods (’194 Patent, col. 1:41-54).
- Asserted Claims: The complaint asserts infringement of at least one claim (Compl. ¶62). Independent claim 1 is representative.
- Accused Features: The accused features are embodied in Defendants' proposed generic transdermal testosterone solution, for which they seek FDA approval via an ANDA (Compl. ¶¶ 29, 61).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is "Cipla's Generic Product," a proposed generic version of Plaintiffs' Axiron® product, which is the subject of ANDA No. 209533 (Compl. ¶29).
- Functionality and Market Context: The complaint describes the accused product as a transdermal "Testosterone solution, metered 30 mg/1.5mL actuation" (Compl. ¶29). It is alleged to contain testosterone as the active ingredient and is intended to be a generic equivalent to Axiron®, which is used to treat conditions associated with testosterone deficiency in males (Compl. ¶¶ 26, 31). The complaint alleges that Defendants' ANDA contains data to establish the bioequivalence of its product to Axiron®, and that Defendants plan to market the product for the same infringing uses upon FDA approval (Compl. ¶¶ 32, 36).
IV. Analysis of Infringement Allegations
The complaint alleges that the filing of the ANDA itself is an act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶33). The infringement theory is that the product for which Defendants seek approval will, upon commercialization, meet the limitations of the asserted method claims. The complaint incorporates the '944 patent as Exhibit A (Compl. ¶27), which includes a graph (Fig. 1) illustrating superior drug uptake in the axilla compared to the inner arm.
'944 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of increasing the testosterone blood level of an adult male subject in need thereof comprising applying to at least one axilla of the subject... a non-occlusive transdermal drug delivery composition... | Defendants are seeking approval to market a generic version of Axiron®, which is indicated for testosterone replacement therapy in males and is applied to the axilla. The proposed product label will allegedly instruct this infringing use. | ¶29, ¶31, ¶36 | col. 11:41-55 |
| ...consisting of: (a) a pharmaceutically effective amount of testosterone; | The accused generic product is alleged to contain testosterone as its active pharmaceutical ingredient. | ¶29, ¶31 | col. 11:13-16 |
| (b) one or more lower alkyl alcohols, wherein the combined volume of the lower alkyl alcohols is more than 60% (v/v) of the composition; | The accused generic product is alleged to be a transdermal solution that, to be bioequivalent to Axiron®, would have a formulation containing a high concentration of a volatile solvent, such as a lower alkyl alcohol. | ¶29, ¶32 | col. 5:9-14 |
| (c) one or more penetration enhancers selected from the group consisting of glycols, oleic acid, isopropyl myristate... octisalate... and combinations thereof; | The accused generic product is alleged to contain one or more penetration enhancers from the claimed list to facilitate transdermal delivery, consistent with the formulation of the reference listed drug, Axiron®. | ¶29, ¶32 | col. 8:46-67 |
| (d) one or more viscosity modulating agents; | The accused generic product is alleged to be a solution whose formulation includes a viscosity modulating agent to achieve the proper consistency for application. | ¶29, ¶32 | col. 3:61 - col. 4:3 |
| wherein the composition is applied in an amount effective to achieve a testosterone blood level in the subject of at least 200 ng/dL. | The accused generic product is allegedly formulated to be bioequivalent to Axiron®, which is dosed to restore testosterone levels to the normal range, alleged to be at least 200 ng/dL. | ¶32, ¶36 | col. 11:48-52 |
'520 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of increasing the testosterone blood level of an adult male subject in need thereof comprising applying to at least one axilla of the subject... | Defendants are seeking approval to market a generic version of Axiron®, which is indicated for testosterone replacement therapy in males and is applied to the axilla. | ¶29, ¶31, ¶36 | col. 11:41-55 |
| ...a transdermal drug delivery composition comprising: (a) a pharmaceutically effective amount of testosterone; | The accused generic product is alleged to contain testosterone as its active pharmaceutical ingredient. | ¶29, ¶31 | col. 11:13-16 |
| (b) one or more lower alkyl alcohols, wherein the combined amount of lower alkyl alcohols is more than 60% v/v of the composition; | The accused generic product is alleged to be a transdermal solution that, to be bioequivalent to Axiron®, would have a formulation containing a high concentration of a volatile solvent, such as a lower alkyl alcohol. | ¶29, ¶32 | col. 5:9-14 |
| (c) one or more penetration enhancers selected from the group consisting of oleic acid, fatty acid esters... sunscreen esters and mixtures thereof; and | The accused generic product is alleged to contain one or more penetration enhancers from the claimed list (which is broader than the list in the '944 patent) to facilitate transdermal delivery. | ¶29, ¶32 | col. 8:46-65 |
| (d) a viscosity modulating agent for increasing the viscosity of the composition. | The accused generic product is alleged to be a solution whose formulation includes a viscosity modulating agent to achieve the proper consistency for application. | ¶29, ¶32 | col. 3:61-64 |
- Identified Points of Contention:
- Scope Questions: Claim 1 of the ’944 patent uses the transitional phrase "consisting of," which is highly restrictive and generally excludes any unrecited ingredients. A primary legal question will be whether Cipla's formulation contains any excipients not explicitly listed in the claim (including the "optional" components), which could be a basis for a non-infringement argument. The ’520 patent uses the more open term "comprising," raising the question of whether the different claim language will lead to a different infringement outcome for the same accused product.
- Technical Questions: The complaint does not disclose the specific formulation of Cipla's generic product. A key factual question for discovery will be whether the accused product's formulation, including the identity and concentration of its excipients, actually falls within the scope of the claimed ingredients and percentages (e.g., >60% lower alkyl alcohol).
V. Key Claim Terms for Construction
The Term: "consisting of" (’944 Patent, Claim 1)
- Context and Importance: This term introduces the list of ingredients in the composition. In claim construction, "consisting of" creates a strong presumption that the claim is "closed" and excludes any elements not recited. Its interpretation is critical because if Cipla's product contains any additional, unrecited excipients (beyond those listed as "optional"), it may avoid literal infringement of this claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim itself lists several "optional" components, such as water and an antiperspirant agent (’944 Patent, col. 23:34-37). A party might argue this demonstrates the patentee did not intend for the term to be absolutely closed, but rather to define a core set of required ingredients while permitting certain specified additions.
- Evidence for a Narrower Interpretation: Standard patent law holds that "consisting of" is a term of exclusion. A party will argue that the explicit listing of optional components reinforces the closed nature of the claim, implying that any other unlisted ingredient is excluded. The specification does not appear to use the term in a way that would rebut this strong presumption.
The Term: "viscosity modulating agent" (’944 Patent, Claim 1; ’520 Patent, Claim 1)
- Context and Importance: This is a required component of the claimed formulation. The definition will determine which substances can satisfy this limitation. Practitioners may focus on this term because its scope (i.e., whether it is limited to specific thickening agents disclosed in the patent or covers any substance that affects viscosity) could be determinative of infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification defines the term functionally as "a component of the composition which alters the viscosity of the overall resulting composition" (’944 Patent, col. 4:4-7). This language could support a broad construction covering any agent that performs this function.
- Evidence for a Narrower Interpretation: The specification repeatedly refers to the agent as a "thickening agent or a gelling agent" and provides specific examples like polyvinyl pyrrolidone (PVP) and hydroxypropylmethylcellulose (’944 Patent, col. 3:63-64; col. 6:7-9). A party could argue the claims should be limited to these disclosed types of agents, rather than anything that might incidentally affect viscosity.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents-in-suit (Compl. ¶¶ 42-48, 53-59, 64-70). The inducement theory is based on allegations that Defendants know and intend for physicians and patients to use the proposed generic product in accordance with its label, which will allegedly instruct the infringing method of application to the axilla (Compl. ¶¶ 34, 44, 55, 66). Contributory infringement is based on the allegation that the product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶¶ 47-48, 58-59, 69-70).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope: can the highly restrictive "consisting of" language in the ’944 patent be overcome, or will the infringement analysis for that patent turn entirely on whether Defendants' confidential formulation contains any unrecited excipients? The different outcomes for the "consisting of" claim versus the "comprising" claims of the other patents will be a central focus.
- A key evidentiary question will be one of compositional identity: will discovery into the confidential ANDA reveal that the formulation of the proposed generic product meets every limitation of the asserted claims? The dispute will likely focus on the precise chemical identity and concentration of the volatile solvent, penetration enhancer, and viscosity modulating agent.
- A final question will concern divided infringement: since the asserted claims are method claims performed by an end-user, and the defendant is the drug manufacturer, can Plaintiffs prove all the elements of indirect infringement, including demonstrating that Defendants possessed the specific intent to encourage the infringing acts by physicians and patients?