DCT
3:17-cv-05337
Bristol Myers Squibb Co v. Zydus Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bristol-Myers Squibb Company (Delaware)
- Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey)
- Plaintiff’s Counsel: Walsh Pizzi Oreilly Falanga LLP; Wilmer Cutler Pickering Hale and Dorr LLP (Of Counsel)
- Case Identification: 3:17-cv-05337, D.N.J., 07/21/2017
- Venue Allegations: Venue is asserted on the basis that Defendant is a New Jersey corporation with its principal place of business in the district, and therefore resides in the judicial district, and has allegedly committed acts of infringement there.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the HIV drug Reyataz® constitutes an act of infringement of a patent covering the drug's specific bisulfate salt form.
- Technical Context: The technology concerns pharmaceutical salt selection, a critical process for developing a drug compound with sufficient stability, solubility, and oral bioavailability to be effective as an orally administered medicine.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of an ANDA containing a Paragraph IV certification. This certification asserts that the patent-in-suit is invalid, unenforceable, and/or will not be infringed by the proposed generic product. The complaint was filed within the 45-day statutory window after Plaintiff received Defendant's notice letter, triggering a potential 30-month stay of FDA approval for the generic.
Case Timeline
| Date | Event |
|---|---|
| 1998-01-20 | ’383 Patent Priority Date |
| 2000-07-11 | ’383 Patent Issue Date |
| 2017-06-15 | Defendant sent ANDA Notice Letter to Plaintiff |
| 2017-06-16 | Plaintiff received ANDA Notice Letter (no earlier than) |
| 2017-07-21 | Complaint Filing Date |
| 2018-12-21 | ’383 Patent Original Expiration Date |
| 2019-06-21 | ’383 Patent Pediatric Exclusivity Expiration Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,087,383 - "Bisulfate Salt of HIV Protease Inhibitor"
- Issued: July 11, 2000
The Invention Explained
- Problem Addressed: The patent describes a specific azapeptide HIV protease inhibitor (referred to as Compound I) that, in its "free base" form, has an aqueous solubility of less than 1 µg/mL and poor oral bioavailability, making it unsuitable for effective oral drug delivery (’383 Patent, col. 2:39-43).
- The Patented Solution: The invention is a specific crystalline bisulfate salt of Compound I, which is the active ingredient atazanavir (’383 Patent, Abstract; col. 2:5-8). This particular salt form is described as having "unexpectedly superior aqueous solubility" (approximately 4-5 mg/mL) compared to the free base and other common acid addition salts, such as hydrochloride or methanesulfonate, which exhibited lower solubility or an undesirable tendency to convert back to the poorly soluble free base in an aqueous environment (’383 Patent, col. 2:47-62). This enhanced solubility and stability contributes to "significantly improved oral bioavailability" (’383 Patent, col. 1:28-32).
- Technical Importance: The creation of a stable, highly soluble, and orally bioavailable salt form is a critical step in transforming a potent chemical compound into a viable pharmaceutical product for treating diseases like HIV (’383 Patent, col. 2:44-47).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claim 2 (Compl. ¶23).
- Independent Claim 1 recites:
- The bisulfate salt having the formula [shown as formula II, which depicts the atazanavir molecule paired with H₂SO₄].
- Dependent Claim 2 recites a pharmaceutical dosage form comprising the bisulfate salt of claim 1 and a pharmaceutically acceptable carrier.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the "Zydus ANDA Products," comprising 150 mg, 200 mg, and 300 mg capsules of atazanavir sulfate, which are proposed generic versions of Plaintiff's Reyataz® drug product (Compl. ¶2).
Functionality and Market Context
- The Zydus ANDA Products are the subject of ANDA No. 210575, filed with the FDA to obtain approval for marketing a generic drug (Compl. ¶¶1, 15). As part of the ANDA process, Defendant has represented that its products have the same active ingredient, dosage form, and are bioequivalent to the branded Reyataz® product (Compl. ¶17). The complaint alleges that the Zydus ANDA Products "contain atazanavir bisulfate" (Compl. ¶18). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The infringement allegations are based on the submission of the ANDA under 35 U.S.C. § 271(e)(2), which constitutes a technical act of infringement if the product, once approved, would infringe the patent.
’383 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| The bisulfate salt having the formula [II] | The complaint alleges that "the Zydus ANDA Products contain atazanavir bisulfate," which is the chemical entity recited in the claim. | ¶18 | col. 6:30-49 |
- Identified Points of Contention:
- Technical Question: A central issue will be the precise chemical identity and form of the active pharmaceutical ingredient in Defendant's ANDA product. The dispute may turn on whether the product contains the specific "bisulfate salt" as claimed, or a different salt (e.g., a sulfate salt with a different stoichiometric ratio) or a different physical form (e.g., an amorphous versus crystalline structure) that Defendant will argue falls outside the claim scope. The complaint alleges the product contains "atazanavir bisulfate," but Defendant's Paragraph IV certification asserts non-infringement (Compl. ¶¶18, 20).
- Scope Questions: The interpretation of "bisulfate salt" will be critical. A question may arise as to whether this term is limited to the specific crystalline forms exhibiting the "unexpected" properties detailed in the specification, or if it more broadly covers any substance meeting the general chemical formula, including non-crystalline (amorphous) forms.
V. Key Claim Terms for Construction
- The Term: "the bisulfate salt"
- Context and Importance: This term is the lynchpin of the infringement analysis. The patent's specification distinguishes "the bisulfate salt" from the free base, a "sulfate salt," and other acid addition salts based on its superior and "unexpected" solubility and stability properties (’383 Patent, col. 3:37-56). Defendant’s non-infringement defense will likely center on arguing that its product is not "the bisulfate salt" as properly construed in light of the patent's teachings. Practitioners may focus on this term because its construction will determine whether a specific crystalline structure is required for infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain language of claim 1 recites "The bisulfate salt having the formula" without explicitly limiting the claim to a specific crystalline form or polymorph (’383 Patent, col. 6:30-49). This could support a construction that encompasses any form of atazanavir bisulfate, including amorphous material.
- Evidence for a Narrower Interpretation: The specification repeatedly refers to the invention as the "novel crystalline bisulfate salt" (’383 Patent, col. 1:9-10). The abstract and summary of the invention also emphasize the "crystalline" nature of the salt (’383 Patent, Abstract; col. 2:5-8). A party could argue that these statements limit the scope of "the bisulfate salt" to the crystalline forms that were shown to possess the advantageous properties described in the patent.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement and contributory infringement, asserting that upon approval, Defendant's commercial manufacture, use, and sale of the Zydus ANDA Products would induce infringement by others, such as patients and healthcare providers (Compl. ¶¶24, 25).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement or a request for enhanced damages under 35 U.S.C. § 284. It does, however, plead facts that could support post-suit willfulness, noting that Defendant was made aware of the patent via its own Paragraph IV notice letter (Compl. ¶¶15, 20).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of chemical identity: does the active ingredient specified in Defendant's ANDA constitute "the bisulfate salt" of atazanavir as claimed in the '383 patent? The resolution of this question will likely depend on detailed analytical evidence comparing the proposed generic product to the claim language and the patent's description.
- The case will also turn on validity in view of the prior art: as signaled by the Paragraph IV certification, a key defense will likely be that the claimed bisulfate salt was obvious. The patentability of the invention hinges on whether the salt's superior solubility and stability properties were "unexpected," a question the court will have to resolve based on the state of the art at the time of the invention.