DCT
1:23-cv-00424
Celgene Corp v. Accord Healthcare Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Celgene Corporation (DE), Celgene International Sàrl (Switzerland), and Bristol-Myers Squibb Company (DE)
- Defendant: Accord Healthcare Inc. (NC)
- Plaintiff’s Counsel: Farnan LLP
- Case Identification: 1:23-cv-00424, D. Del., 04/18/2023
- Venue Allegations: Venue is alleged to be proper as Defendant did not dispute venue or personal jurisdiction in a related, pending case before the same Court and is subject to personal jurisdiction for the same reasons.
- Core Dispute: Plaintiffs allege that Defendant’s Abbreviated New Drug Application (ANDA) for a generic version of Plaintiffs' Onureg® drug product constitutes an act of infringement of a patent covering oral formulations of azacitidine.
- Technical Context: The technology concerns oral formulations of azacitidine, a nucleoside metabolic inhibitor used for the continued treatment of acute myeloid leukemia (AML).
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 216741 and a corresponding Paragraph IV certification notice. The certification asserts that the patent-in-suit is invalid for obviousness. This is the second lawsuit related to this ANDA; a prior case involving U.S. Patent No. 8,846,628 remains pending before the same court.
Case Timeline
| Date | Event |
|---|---|
| 2008-05-15 | '436 Patent Priority Date |
| 2021-12-22 | Related case (1:21-cv-01795) filed |
| 2023-02-07 | '436 Patent Issue Date |
| 2023-03-15 | Date of Defendant's ANDA Notice Letter |
| 2023-04-18 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
- Patent Identification: U.S. Patent No. 11,571,436 ("the '436 Patent"), titled "Oral Formulations of Cytidine Analogs and Methods of Use Thereof", issued on February 7, 2023. (Compl. ¶11).
The Invention Explained
- Problem Addressed: The patent addresses the difficulty of creating an oral dosage form for cytidine analogs like 5-azacytidine, which have historically been considered "acid labile and unstable in the acidic gastric environment." ('436 Patent, col. 3:10-16). This instability was believed to make oral delivery challenging, leading to reliance on subcutaneous or intravenous administration.
- The Patented Solution: The invention is a pharmaceutical composition that, contrary to the conventional approach of using protective enteric coatings, is designed to release the 5-azacytidine "substantially in the stomach." ('436 Patent, Abstract). The key features are a specific dosage range of 5-azacytidine in a "non-enteric coated tablet" that is formulated such that a therapeutically effective amount of the drug is not absorbed through the oral mucosa, ensuring it reaches the stomach for release. ('436 Patent, Claim 1).
- Technical Importance: This approach provided a more convenient oral administration route for a cancer therapy, which could improve patient compliance and allow for different, potentially more advantageous, long-term or maintenance dosing regimens compared to injections. ('436 Patent, col. 3:5-10, col. 4:35-40).
Key Claims at a Glance
- The complaint asserts claims 1-22, identifying claim 1 as the sole independent claim. (Compl. ¶¶24, 28).
- The essential elements of independent claim 1 are:
- A pharmaceutical composition for oral administration
- comprising 180 mg to 360 mg of 5-azacytidine
- and at least one pharmaceutically acceptable excipient,
- wherein the composition is a non-enteric coated tablet,
- and wherein a therapeutically effective amount of 5-azacytidine is not absorbed through oral mucosa upon administration to a human subject.
- The complaint reserves the right to assert infringement of all claims 1-22. (Compl. ¶24).
III. The Accused Instrumentality
Product Identification
- The "Accord ANDA Product," identified as 200 mg and 300 mg tablets of azacitidine for which Accord Healthcare Inc. seeks FDA approval via ANDA No. 216741. (Compl. ¶¶2, 30).
Functionality and Market Context
- The complaint alleges the Accord ANDA Product is a generic version of Plaintiffs' Onureg® drug. (Compl. ¶2). As such, it is alleged to have the same active ingredient, dosage form, route of administration, strength, and indications as Onureg®. (Compl. ¶¶19-20).
- The product is described as being "bioequivalent to Onureg®" and, like Onureg®, is a "non-enteric coated tablet" for oral administration that contains at least one pharmaceutically acceptable excipient. (Compl. ¶31). The intended use is for the continued treatment of adult patients with acute myeloid leukemia. (Compl. ¶¶15, 20).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'436 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition for oral administration | The Accord ANDA Product is for oral administration. | ¶31 | col. 6:26-28 |
| comprising 180 mg to 360 mg of 5-azacytidine | Accord’s proposed product consists of 200 mg and 300 mg tablets of azacitidine, which falls within the claimed dosage range. | ¶30 | col. 6:26-28 |
| and at least one pharmaceutically acceptable excipient, | The Accord ANDA Product is alleged to contain at least one pharmaceutically acceptable excipient, based on its bioequivalence to Onureg®, which contains such excipients. | ¶31 | col. 6:26-28 |
| wherein the composition is a non-enteric coated tablet, | The Accord ANDA Product is alleged to be a non-enteric coated tablet, based on its asserted bioequivalence to Onureg®, which is a non-enteric coated tablet. | ¶31 | col. 6:26-28 |
| and wherein a therapeutically effective amount of 5-azacytidine is not absorbed through oral mucosa upon administration to a human subject. | Plaintiffs allege that because the Accord ANDA Product is bioequivalent to Onureg®, it shares the same characteristic of not being absorbed through the oral mucosa. | ¶31 | col. 6:26-28 |
Identified Points of Contention
- Validity vs. Infringement: The complaint alleges that Accord's Notice Letter "has not contested the infringement of any claim of the ’436 patent to the extent that the patent’s claims are valid." (Compl. ¶24). This suggests the primary dispute will center on Accord's § 103 obviousness defense rather than on infringement.
- Scope Questions: Should infringement be contested, a key issue may be whether the legal and factual standard for "bioequivalence" is sufficient to meet every claim limitation. A defendant could question whether bioequivalence, which is based on pharmacokinetic profiles in the blood, necessarily proves the negative limitation that a therapeutically effective amount "is not absorbed through oral mucosa."
V. Key Claim Terms for Construction
The Term: "non-enteric coated tablet"
Context and Importance: This term is central to the patent's purported novelty, as it teaches away from the conventional wisdom of using enteric coatings to protect acid-sensitive drugs in the stomach. The construction of this term will be critical in distinguishing the claimed invention from prior art that may have used other types of coatings or formulations.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification defines a "non-enteric-coated" formulation functionally as one "designed to release the active ingredient(s) substantially in the stomach." ('436 Patent, col. 12:1-4). This may support a construction covering any tablet that lacks a coating intended to delay release beyond the stomach.
- Evidence for a Narrower Interpretation: The specification discloses specific embodiments of non-enteric coatings, such as a "seal coat" comprising hydroxypropyl cellulose. ('436 Patent, col. 66:36-40). A party could argue the term should be limited by these exemplary embodiments, rather than encompassing any tablet that simply lacks a traditional enteric layer.
The Term: "is not absorbed through oral mucosa"
Context and Importance: This negative limitation is crucial for defining how the oral administration is performed. Proving a negative element can present unique evidentiary challenges, and its precise meaning will be central to the infringement analysis. Practitioners may focus on this term because the parties will likely dispute the standard of proof required to demonstrate "non-absorption."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language links this limitation to a "therapeutically effective amount," which suggests that de minimis or therapeutically irrelevant absorption through the oral mucosa might not negate infringement. This could support a construction where only absorption that contributes meaningfully to the drug's efficacy would fall outside the claim.
- Evidence for a Narrower Interpretation: A defendant could argue for a strict interpretation where any detectable absorption through the oral mucosa is sufficient to avoid infringement. The specification does not appear to explicitly define a threshold for what constitutes "not absorbed," which may leave the term open to a narrower reading based on its plain and ordinary meaning.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Accord’s commercialization of its ANDA product would induce infringement by others, presumably through its proposed product label that would instruct patients and physicians on the oral administration of the tablets. (Compl. ¶25).
- Willful Infringement: While the complaint does not use the word "willful," it lays a foundation for such a claim by pleading that Accord had knowledge of the '436 Patent via its listing in the FDA's Orange Book and the subsequent Notice Letter exchange. (Compl. ¶¶16-17). The prayer for relief seeks a finding of an "exceptional case" and an award of attorneys' fees under 35 U.S.C. § 285, which is often associated with findings of willful infringement. (Compl., Prayer for Relief ¶5).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central legal question will be one of validity: as the complaint alleges infringement is not contested, the case will likely turn on whether Accord can prove by clear and convincing evidence that the '436 patent’s claims, which teach a counter-intuitive stomach-release formulation for an acid-labile drug, are invalid as obvious under 35 U.S.C. § 103.
- An underlying evidentiary question will be the sufficiency of pleading based on equivalence: does the allegation that the Accord ANDA Product is "bioequivalent" to Onureg® suffice as a matter of law and fact to establish that it meets every limitation of the asserted claims, including the negative limitation regarding non-absorption through the oral mucosa?