DCT
1:20-cv-00123
Amgen Inc v. Centaur Pharma Private Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Amgen Inc. (Delaware) and Les Laboratoires Servier (France)
- Defendant: Centaur Pharmaceuticals Private Ltd. (India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; O'Melveny & Myers LLP
- Case Identification: 1:20-cv-00123, D. Del., 01/24/2020
- Venue Allegations: Venue is alleged to be proper as Defendant is a foreign corporation subject to personal jurisdiction in the district.
- Core Dispute: Plaintiffs allege that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Corlanor® (ivabradine) infringes four patents related to specific crystalline forms of ivabradine hydrochloride.
- Technical Context: The patents concern polymorphs—different crystalline structures—of an active pharmaceutical ingredient, a common strategy for extending patent protection for a drug product by claiming specific, stable, and manufacturable forms.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 214051 and its corresponding Paragraph IV Certification, which asserted that Plaintiffs' patents are invalid, unenforceable, or would not be infringed by the proposed generic product. The patents-in-suit are listed in the FDA's "Orange Book" for Corlanor®. The patents are subject to terminal disclaimers, linking their expiration dates and suggesting they were deemed patentably indistinct during prosecution.
Case Timeline
| Date | Event |
|---|---|
| 2005-02-28 | Earliest Priority Date for ’649, ’650, ’996, and ’842 Patents |
| 2008-04-22 | ’649 Patent Issued |
| 2008-04-22 | ’650 Patent Issued |
| 2011-01-11 | ’996 Patent Issued |
| 2011-02-01 | ’842 Patent Issued |
| 2019-12-12 | Defendant's ANDA Notice Letter Sent to Plaintiffs |
| 2020-01-24 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,361,649 - “β-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It,” issued April 22, 2008
The Invention Explained
- Problem Addressed: The patent addresses the need to produce ivabradine hydrochloride, a drug for treating myocardial ischemia, in a form with "excellent purity" that is "perfectly reproducible, easily formulated and sufficiently stable" for industrial-scale manufacturing and long-term storage. (’649 Patent, col. 2:38-46).
- The Patented Solution: The invention is a specific crystalline polymorph of ivabradine hydrochloride, designated the "β-form." This form is not described in the prior art synthesis patent (EP 0 534 859) and is defined by a unique powder X-ray diffraction (XRPD) pattern, which provides a structural fingerprint for the crystal. (’649 Patent, col. 2:52-65, Abstract). The patent provides a table with 34 characteristic XRPD peaks to identify this specific β-crystalline structure. (’649 Patent, col. 2:1-18).
- Technical Importance: For a pharmaceutical compound, identifying a stable and reproducible crystalline form is critical for ensuring consistent bioavailability, shelf life, and manufacturability of the final drug product. (’649 Patent, col. 2:38-46).
Key Claims at a Glance
- The complaint does not specify which claims are asserted but alleges infringement of "one or more claims" (Compl. ¶34). Independent claim 1 is the primary composition of matter claim.
- Independent Claim 1:
- A β-Crystalline form of ivabradine hydrochloride of formula (I)
- exhibiting essentially the following powder X-ray diffraction data, measured using a PANalytical X’Pert Pro diffractometer...and expressed in terms of ray position (Bragg’s angle 2 theta, expressed in degrees)... [followed by a table of 34 specific XRPD peaks].
U.S. Patent No. 7,361,650 - “γ-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It,” issued April 22, 2008
The Invention Explained
- Problem Addressed: Similar to the ’649 patent, the ’650 patent seeks to address the need for a "well defined" and stable crystalline form of ivabradine hydrochloride suitable for pharmaceutical development and manufacturing. (’650 Patent, col. 2:51-56).
- The Patented Solution: This patent discloses and claims a different crystalline polymorph of ivabradine hydrochloride, designated the "γ-form." Like the β-form, this polymorph is characterized by its own unique powder X-ray diffraction (XRPD) pattern, detailed in a table of 33 characteristic peaks. (’650 Patent, col. 2:57-65, Abstract). The specification provides a method for preparing this specific γ-form using 2-ethoxyethanol as a solvent. (’650 Patent, col. 3:18-28).
- Technical Importance: The existence of multiple polymorphs (like the β- and γ-forms) can present challenges in drug manufacturing; isolating and patenting a single, stable form provides a pathway to a consistent and reliable drug product. (’650 Patent, col. 2:40-50).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" (Compl. ¶43). Independent claim 1 is the primary composition of matter claim.
- Independent Claim 1:
- A γ-Crystalline form of ivabradine hydrochloride of formula (I)
- exhibiting essentially the following powder X-ray diffraction data, measured using a PANalytical X'Pert Pro diffractometer... [followed by a table of 33 specific XRPD peaks].
Multi-Patent Capsule: U.S. Patent No. 7,867,996
- Patent Identification: U.S. Patent No. 7,867,996, “γ-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It,” issued January 11, 2011.
- Technology Synopsis: This patent is a continuation of the application that resulted in the ’650 Patent and also claims the γ-crystalline form of ivabradine hydrochloride. The claims narrow the definition of the γ-form by reciting a smaller subset of the most prominent XRPD peaks, potentially to capture forms that are "essentially" the same but may not exhibit every peak listed in the parent patent. (’996 Patent, col. 3:43-46).
- Asserted Claims: The complaint asserts "one or more claims." Independent claims 1 and 2 are composition of matter claims. (Compl. ¶52).
- Accused Features: The proposed generic product is alleged to contain the claimed γ-crystalline form of ivabradine hydrochloride. (Compl. ¶52).
Multi-Patent Capsule: U.S. Patent No. 7,879,842
- Patent Identification: U.S. Patent No. 7,879,842, “Beta-Crystalline Form of Ivabradine Hydrochloride, a Process for Its Preparation and Pharmaceutical Compositions Containing It,” issued February 1, 2011.
- Technology Synopsis: This patent is related to the ’649 Patent and also claims the β-crystalline form of ivabradine hydrochloride. Similar to the ’996 Patent's strategy, the ’842 Patent's claims define the β-form by a smaller subset of characteristic XRPD peaks compared to the parent patent. (’842 Patent, col. 3:40-44).
- Asserted Claims: The complaint asserts "one or more claims." Independent claims 1 and 2 are composition of matter claims. (Compl. ¶61).
- Accused Features: The proposed generic product is alleged to contain the claimed β-crystalline form of ivabradine hydrochloride. (Compl. ¶61).
III. The Accused Instrumentality
Product Identification
- Defendant's "Proposed ANDA Product," which is a generic version of Corlanor® (ivabradine) in 5 mg and 7.5 mg tablets, for which Defendant seeks FDA approval via ANDA No. 214051. (Compl. ¶1, ¶6).
Functionality and Market Context
- The active pharmaceutical ingredient in the Proposed ANDA Product is ivabradine hydrochloride. (Compl. ¶24). The product is intended to be a bioequivalent generic substitute for Amgen's Corlanor®, a drug used to treat chronic heart failure. (Compl. ¶19, ¶25). The complaint alleges, on information and belief, that the ivabradine hydrochloride in the Defendant's product exists in a patented crystalline form. (Compl. ¶26).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed claim chart or specific evidence of infringement, instead making general allegations. The analysis below is based on the complaint's high-level theory.
’649 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A β-Crystalline form of ivabradine hydrochloride... | The complaint alleges on information and belief that the Proposed ANDA Product contains ivabradine hydrochloride. | ¶24 | col. 4:32-40 |
| exhibiting essentially the following powder X-ray diffraction data... [table of 34 peaks] | The complaint alleges that the ivabradine hydrochloride in the Proposed ANDA Product "exhibits a patented crystalline form" and is "covered by one or more of the claims of the '649 Patent." | ¶26, ¶34 | col. 4:41-59 |
’650 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A γ-Crystalline form of ivabradine hydrochloride... | The complaint alleges on information and belief that the Proposed ANDA Product contains ivabradine hydrochloride. | ¶24 | col. 3:31-37 |
| exhibiting essentially the following powder X-ray diffraction data... [table of 33 peaks] | The complaint alleges that the ivabradine hydrochloride in the Proposed ANDA Product "exhibits a patented crystalline form" and is "covered by one or more of the claims of the '650 Patent." | ¶26, ¶43 | col. 3:38-57 |
- Identified Points of Contention:
- Evidentiary Question: The central dispute will be factual: what is the actual crystalline structure of the ivabradine hydrochloride in Defendant's Proposed ANDA Product? The complaint does not provide any empirical data (e.g., an XRPD analysis of the accused product). This evidence will need to be developed during discovery.
- Scope Questions: The complaint accuses the product of infringing patents covering two distinct polymorphs (β and γ). This raises the question of whether Plaintiffs have a good-faith basis to allege infringement of both sets of patents, or if this is a protective pleading pending discovery. A single product would not typically infringe claims to two different, mutually exclusive crystalline forms.
- Technical Questions: A key technical question will be whether the XRPD pattern of the accused product, once measured, falls within the scope of the claimed peaks. The term "essentially" in the claims suggests that an exact match is not required, creating a potential dispute over how much deviation is permissible.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for a full analysis of claim construction disputes. However, based on the technology, the following term will be critical.
- The Term: "exhibiting essentially the following powder X-ray diffraction data" (appears in claim 1 of both the ’649 and ’650 patents).
- Context and Importance: This term is the linchpin of the infringement analysis. The definition of "essentially" will determine the scope of the claims and how closely the accused product's XRPD pattern must match the patterns recited in the patents. Practitioners may focus on this term because XRPD measurements can have minor variations due to factors like sample preparation, preferred orientation, and instrument calibration; the term "essentially" is intended to account for such minor, non-substantive differences.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification does not explicitly define "essentially." A party arguing for a broader scope may contend that the term should be interpreted to cover any product that is the same crystalline form, even if its measured XRPD pattern shows some shifts in peak position or relative intensity, as long as it is structurally the same polymorph.
- Evidence for a Narrower Interpretation: The patents provide highly specific lists of dozens of peaks, measured to four significant figures. (’649 Patent, col. 2:1-18; ’650 Patent, col. 2:1-17). A party arguing for a narrower scope may argue that "essentially" only covers trivial instrument noise and does not permit meaningful deviation from the long and specific lists of peak data provided, which were presented as the definition of the invention.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant will induce infringement by "instruct[ing] healthcare providers to use the Proposed ANDA Product in accordance with the proposed product labeling." (Compl. ¶36, ¶45, ¶54, ¶63). This is a standard allegation in ANDA litigation, where the use of the drug by patients as directed would constitute direct infringement of method-of-use claims (though only composition of matter claims have been discussed in detail here).
- Willful Infringement: The complaint alleges that Defendant had knowledge of the patents when it submitted its ANDA and filed its Paragraph IV Certification. (Compl. ¶38, ¶47, ¶56, ¶65). This pre-suit knowledge, combined with the act of seeking to market an allegedly infringing product, forms the basis of the willfulness allegation.
VII. Analyst’s Conclusion: Key Questions for the Case
- A Core Evidentiary Question: The primary issue is one of physical characterization: what is the actual crystalline form of the ivabradine hydrochloride in Defendant's proposed generic product? The outcome of the case will likely depend on expert analysis of empirical data, such as XRPD, obtained during discovery.
- A Question of Claim Scope: How broadly will the court construe the term "essentially" as it applies to the extensive XRPD data defining the claimed polymorphs? The resolution of this issue will determine whether minor or moderate deviations in the accused product's crystal structure data are sufficient to avoid a finding of literal infringement.
- A Pleading Strategy Question: Plaintiffs have asserted patents covering two different polymorphs (β and γ) against a single product. This raises the question of which infringement theory, if any, can be substantiated by evidence, and whether the assertion of both is a protective measure pending discovery or an indication of a more complex infringement theory (e.g., the presence of a mixture of forms).