DCT
3:24-cv-01972
BeiGene USA Inc v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: BeiGene USA, Inc. (Delaware) and BeiGene Switzerland GmbH (Switzerland)
- Defendant: Sandoz Inc. (Delaware)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP; Williams & Connolly LLP
- Case Identification: 3:24-cv-01972, D.N.J., 03/19/2024
- Venue Allegations: Plaintiff alleges venue is proper because Defendant resides in the district, maintaining a principal place of business in Princeton, New Jersey, where a substantial portion of the events giving rise to the claim allegedly occurred.
- Core Dispute: Plaintiff alleges that Defendant’s proposed generic zanubrutinib product, for which it filed an Abbreviated New Drug Application (ANDA), infringes patents covering specific crystalline forms of the active ingredient and associated methods of use for the branded drug BRUKINSA®.
- Technical Context: The technology relates to pharmaceutical polymorphs, specifically stable crystalline forms of the Bruton's tyrosine kinase (Btk) inhibitor zanubrutinib, which is used to treat certain B-cell cancers.
- Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant’s submission of Paragraph IV certifications asserting non-infringement and/or invalidity of the patents-in-suit. Plaintiff received a first notice letter regarding U.S. Patent Nos. 10,927,117 and 11,591,340 on January 24, 2024, and a second notice letter regarding U.S. Patent No. 11,851,437 on March 7, 2024.
Case Timeline
| Date | Event |
|---|---|
| 2016-08-16 | Earliest Patent Priority Date ('117, '340, '437 Patents) |
| 2021-02-23 | U.S. Patent No. 10,927,117 Issues |
| 2023-02-28 | U.S. Patent No. 11,591,340 Issues |
| 2023-12-26 | U.S. Patent No. 11,851,437 Issues |
| 2024-01-24 | Plaintiff receives Sandoz's First Notice Letter |
| 2024-03-07 | Plaintiff receives Sandoz's Second Notice Letter |
| 2024-03-08 | Original Complaint Filed |
| 2024-03-19 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,927,117 - “Crystalline Form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide, Preparation, and Uses Thereof”
- Issued: February 23, 2021 (Compl. ¶39).
The Invention Explained
- Problem Addressed: The patent’s background section indicates that the previously known form of the active ingredient, zanubrutinib (referred to as "Compound 1"), was amorphous, which can lead to low stability and difficulties in purification and formulation for pharmaceutical use (’117 Patent, col. 2:59-65).
- The Patented Solution: The invention is a specific, stable crystalline form of Compound 1, designated "Crystalline Form A," which possesses a high melting point and improved stability suitable for use in a drug product (’117 Patent, col. 3:7-13). This crystalline form is primarily identified and defined by a characteristic X-ray powder diffraction (XRPD) pattern, illustrated in Figure 1 of the patent (’117 Patent, col. 6:36-50, FIG. 1).
- Technical Importance: The discovery of a stable crystalline polymorph is often a critical step in pharmaceutical development, enabling consistent manufacturing, reliable purity, and predictable shelf-life for a drug product (’117 Patent, col. 2:59-65).
Key Claims at a Glance
- The complaint asserts independent claims 1 (composition of matter) and 6 (pharmaceutical composition) (Compl. ¶¶47, 49).
- Claim 1:
- A crystalline form of Compound 1,
- wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 15.6±0.2°, 16.4±0.2° and 21.4±0.2°.
- Claim 6:
- A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form of claim 1, and
- a pharmaceutically acceptable excipient thereof.
- The complaint alleges infringement of claims 1 through 6 (Compl. ¶52).
U.S. Patent No. 11,591,340 - “Crystalline Form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide, Preparation, and Uses Thereof”
- Issued: February 28, 2023 (Compl. ¶68).
The Invention Explained
- Problem Addressed: This patent addresses the need for methods of treating specific B-cell cancers for which zanubrutinib is effective (’340 Patent, col. 1:29-54).
- The Patented Solution: The patent claims methods of treating specific diseases—including mantle cell lymphoma, Waldenström's macroglobulinemia, and chronic lymphocytic leukemia—by administering the specific crystalline form of Compound 1 disclosed in the parent ’117 Patent (’340 Patent, Abstract; col. 18:7-16). The invention thus connects the stable physical form of the drug to its therapeutic applications.
- Technical Importance: Claiming specific methods of medical treatment provides patent protection directed to the approved commercial uses of the drug, complementing the protection on the compound itself (’340 Patent, col. 18:7-10).
Key Claims at a Glance
- The complaint asserts independent claims 1, 8, 14, and 21, each directed to a method of treating a different B-cell malignancy (Compl. ¶¶76, 78, 80, 82).
- Claim 1:
- A method for treating mantle cell lymphoma in a subject,
- comprising administering to the subject in need thereof a crystalline form of Compound 1,
- wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 15.6±0.2°, 16.4±0.2° and 21.4±0.2°.
- Claims 8, 14, and 21 are structurally parallel to claim 1, claiming methods for treating Waldenström's macroglobulinemia, marginal zone lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, respectively.
- The complaint alleges infringement of claims 1 through 27 (Compl. ¶84).
U.S. Patent No. 11,851,437 - “Crystalline Form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide, Preparation, and Uses Thereof”
- Issued: December 26, 2023 (Compl. ¶100).
The Invention Explained
- This patent claims the same crystalline "Form A" of zanubrutinib but defines it by different characteristics, including its method of preparation (crystallizing from an amorphous form) and its superior stability under specified temperature and humidity conditions (’437 Patent, claims 1, 11). It also claims a composition comprising a mixture of the crystalline Form A and an amorphous form of the compound (’437 Patent, claim 20).
Key Claims at a Glance
- The complaint exemplifies independent claims 1, 11, and 20 (Compl. ¶¶108, 110, 112).
- The complaint alleges on information and belief that Sandoz’s ANDA Product contains the Crystalline Form A of Compound 1, as well as an amorphous form, and is manufactured in a manner that will infringe the patent’s claims (Compl. ¶¶109, 111, 113).
III. The Accused Instrumentality
Product Identification
- "Sandoz's ANDA Product," a proposed generic version of BRUKINSA® (zanubrutinib) capsules, 80 mg (Compl. ¶¶1-2, 30).
Functionality and Market Context
- The accused product is a generic drug containing the active ingredient zanubrutinib, for which Sandoz has filed an Abbreviated New Drug Application (ANDA No. 218957) with the U.S. Food and Drug Administration (Compl. ¶2). Sandoz seeks approval to market its product for the same indications as the branded drug BRUKINSA®, which include the treatment of various B-cell malignancies such as mantle cell lymphoma and chronic lymphocytic leukemia (Compl. ¶¶29, 75). The complaint alleges that upon approval, Sandoz will market its ANDA Product as a generic substitute for BRUKINSA® (Compl. ¶31). The complaint provides a chemical structure diagram of zanubrutinib ("Compound 1") (Compl. ¶47).
IV. Analysis of Infringement Allegations
U.S. Patent No. 10,927,117 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A crystalline form of Compound 1, | Upon information and belief, Sandoz’s ANDA Product contains a crystalline form of zanubrutinib (Compound 1). | ¶48 | col. 2:15-20 |
| wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 15.6±0.2°, 16.4±0.2° and 21.4±0.2°. | Upon information and belief, the crystalline form in Sandoz's ANDA Product exhibits an XRPD pattern with peaks at the recited 2θ angles. | ¶48 | col. 6:36-41 |
- Identified Points of Contention:
- Scope Questions: A potential issue may arise over the interpretation of the term "comprising," which prefaces the list of diffraction peaks. The question for the court may be whether an accused product with additional, unlisted peaks in its diffraction pattern still falls within the scope of the claim.
- Technical Questions: A central evidentiary question will be whether Sandoz's ANDA Product, when tested, actually has a crystalline structure that produces an XRPD pattern matching the four peaks required by the claim, within the specified ±0.2° margin of error. The complaint's allegations are made on "information and belief," making this a key factual dispute to be resolved through discovery (Compl. ¶48).
U.S. Patent No. 11,591,340 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating mantle cell lymphoma in a subject, comprising administering to the subject in need thereof... | Upon information and belief, Sandoz's proposed product labeling will instruct and encourage physicians to administer its ANDA Product to treat mantle cell lymphoma. | ¶77 | col. 18:7-10 |
| a crystalline form of Compound 1, wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 15.6±0.2°, 16.4±0.2° and 21.4±0.2°. | The Sandoz ANDA Product that will be administered is alleged to contain the specifically claimed crystalline form of Compound 1. | ¶77 | col. 18:10-16 |
- Identified Points of Contention:
- Scope Questions: The analysis will likely focus on induced infringement under 35 U.S.C. § 271(b). The question for the court will be whether the instructions in Sandoz's proposed product label are sufficient to demonstrate Sandoz's specific intent to encourage physicians to perform the patented method.
- Technical Questions: Infringement of this method claim is contingent on the outcome of the infringement analysis for the '117 Patent. If Sandoz's product is found not to contain the claimed crystalline form, then administering it cannot infringe this method claim.
V. Key Claim Terms for Construction
The Term: "crystalline form" (’117 Patent, Claim 1)
Context and Importance: The core of the invention is the distinction between the patented crystalline form and the prior art amorphous form. The construction of this term is critical because it defines the physical nature of the claimed substance. Practitioners may focus on this term because the degree of crystallinity in Sandoz's product could become a point of dispute.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification contrasts the invention with the "amorphous form" and highlights the general benefits of crystallinity, such as stability and ease of purification, which could support interpreting the term according to its plain and ordinary meaning in pharmaceutical science (’117 Patent, col. 2:59-65).
- Evidence for a Narrower Interpretation: The specification extensively details the properties of a specific polymorph, "Crystalline Form A," including its XRPD, DSC, and TGA data (’117 Patent, col. 6:15-18; FIGS. 1-3). This detailed description of a single embodiment could be cited to argue that the term "crystalline form" in the claims should be construed as being limited to forms substantially identical to "Crystalline Form A."
The Term: "comprising diffraction peaks having 2θ angle values at..." (’117 Patent, Claim 1)
Context and Importance: This phrase provides the specific, objective criteria used to identify the patented crystalline structure. The interpretation of the transition term "comprising" and the precision of the numerical ranges (±0.2°) will be central to the infringement analysis.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: In patent law, "comprising" is presumptively interpreted as an open-ended term, meaning the claimed structure must have at least the four listed peaks but could also have additional, unlisted peaks. The patent does not use more restrictive language like "consisting of."
- Evidence for a Narrower Interpretation: A defendant may argue that the specification's detailed characterization of "Crystalline Form A" in Table 1, which lists 22 distinct peaks, defines the invention with more specificity than the four peaks recited in the claim (’117 Patent, col. 7-8). This could support an argument that a product exhibiting a significantly different overall pattern, even if it includes the four claimed peaks, is a different polymorph outside the claim's scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Sandoz will induce infringement of the '340 method-of-use patent by providing a product label that instructs and encourages physicians to administer the drug for the claimed therapeutic indications (Compl. ¶89). It also alleges contributory infringement, stating that the accused product is not a staple article of commerce and is especially adapted for infringing uses (Compl. ¶90).
- Willful Infringement: The complaint alleges that Sandoz acted with full knowledge of the patents-in-suit, as evidenced by its Paragraph IV certifications, and proceeded without a reasonable basis for believing it would not be liable for infringement (Compl. ¶¶61, 93, 123).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of structural identity: does the Sandoz ANDA product, once characterized in discovery, actually possess the specific crystalline structure defined by the X-ray powder diffraction peaks recited in the asserted claims, or is it a different, non-infringing polymorph?
- A second core issue will be one of induced infringement: does the language of Sandoz's proposed product label provide sufficient evidence of specific intent to encourage physicians to directly infringe the patented methods of treating specific cancers by administering the generic drug?