DCT
1:24-cv-11770
Radius Health Inc v. Orbicular Pharmaceutical Tech Pvt Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Radius Health, Inc. (Delaware)
- Defendant: Orbicular Pharmaceutical Technologies Private Limited (India); Cipla Limited (India); Cipla USA, Inc. (Delaware)
- Plaintiff’s Counsel: Choate, Hall & Stewart LLP
- Case Identification: 1:24-cv-11770, D. Mass., 07/10/2024
- Venue Allegations: Venue is alleged to be proper as Defendants Orbicular and Cipla Limited are foreign corporations with no state of residence in the United States, and Defendant Cipla USA, Inc. is subject to personal jurisdiction in the district. The complaint notes that Defendants do not contest venue for this action.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) for a generic version of the osteoporosis drug Tymlos® constitutes an act of infringement of a patent covering specific isomers of the active ingredient abaloparatide and pharmaceutical compositions containing them.
- Technical Context: The technology relates to pharmaceutical formulations of abaloparatide, a synthetic peptide analog used as an anabolic (bone-building) agent for treating osteoporosis, a condition characterized by weakened bones and increased fracture risk.
- Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' filing of ANDA No. 217245 with a Paragraph IV certification. The complaint notes a related, pending litigation (No. 22-cv-11546, D. Mass.) involving the same parties and other patents listed in the FDA's Orange Book for Tymlos®. The patent-in-suit is a continuation of patents asserted in that related litigation.
Case Timeline
| Date | Event |
|---|---|
| 2017-04-28 | Earliest Priority Date for '067 Patent |
| 2017-04-28 | FDA first approves Radius's New Drug Application for Tymlos® |
| 2022-08-08 | Orbicular mails First Notice of Paragraph IV Certification (re: other patents) |
| 2022-09-20 | Radius initiates Related Litigation against Orbicular |
| 2024-04-12 | Orbicular mails Second Notice of Paragraph IV Certification (re: other patents) |
| 2024-05-07 | U.S. Patent No. 11,977,067 ('067 Patent) issues |
| 2024-05-16 | '067 Patent is listed in the FDA's Orange Book for Tymlos® |
| 2024-07-10 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,977,067 - "Abaloparatide Formulations and Methods of Testing, Storing, Modifying, and Using Same"
- Patent Identification: U.S. Patent No. 11,977,067, "Abaloparatide Formulations and Methods of Testing, Storing, Modifying, and Using Same," issued May 7, 2024.
The Invention Explained
- Problem Addressed: The patent addresses the discovery of previously unknown degradation products or impurities that can form in abaloparatide formulations ('067 Patent, col. 2:3-7). Specifically, the active peptide can undergo an "intramolecular rearrangement" that results in the formation of isomers, such as beta-Asp10 abaloparatide, which were not identified or quantifiable by prior analytical methods ('067 Patent, col. 10:19-25). The presence of such impurities can affect a drug's stability, efficacy, and safety profile.
- The Patented Solution: The patent claims the specific isomers themselves, such as the beta-Asp10 isomer, as well as pharmaceutical compositions that contain these isomers alongside the primary abaloparatide drug ('067 Patent, Claims 1-4). The invention also provides improved analytical methods (e.g., buffered UPLC) capable of detecting and quantifying these specific isomers, enabling the monitoring of formulation stability and the establishment of purity specifications for the drug product ('067 Patent, col. 2:11-21, 46-57). Figure 1A of the patent visually illustrates the chemical rearrangement of the aspartic acid residue at position 10 that creates the claimed beta-Asp10 isomer ('067 Patent, Fig. 1A).
- Technical Importance: Controlling the purity and degradation profile of peptide-based therapeutics is critical for regulatory approval and ensuring consistent, safe, and effective treatment for patients ('067 Patent, col. 2:51-57).
Key Claims at a Glance
- The complaint focuses on infringement of at least Claim 8, which depends from independent Claim 1 (Compl. ¶64-65).
- Independent Claim 1:
- An isomer of abaloparatide
- comprising beta-Asp10 abaloparatide as set forth in the sequence: Ala-Val-Ser-Glu-His-Gln-Leu-Leu-His-b-Asp-Lys-Gly-Lys-Ser-Ile-Gln-Asp-Leu-Arg-Arg-Arg-Glu-Leu-Leu-Glu-Lys-Leu-Leu-Aib-Lys-Leu-His-Thr-Ala-NH2.
- The complaint notes the dependency chain from Claim 1 through Claims 2, 3, and 4 to arrive at asserted Claim 8, which claims a "formulated drug product" (Compl. ¶65). The plaintiff reserves the right to assert other claims.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the proposed generic abaloparatide injection described in Abbreviated New Drug Application (ANDA) No. 217245, filed by Orbicular (the "ANDA Product") (Compl. ¶¶1, 18).
Functionality and Market Context
- The complaint alleges that the ANDA Product's active ingredient is abaloparatide and that the ANDA filing contains data to demonstrate the product's bioequivalence to the reference listed drug, Tymlos® (Compl. ¶¶47-48). It is further alleged that the ANDA Product's proposed label will recommend the same indications, usage, clinical studies, and dosage as Tymlos®, positioning it as a direct substitute intended to replace Tymlos® sales upon receiving FDA approval (Compl. ¶¶25, 49-51).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
Claim Chart Summary
The complaint’s infringement theory for Claim 8 is based on the premise that by filing an ANDA for a generic version of Tymlos®, Defendants have necessarily represented that their ANDA Product is the "same as" Tymlos® (Compl. ¶66). The complaint alleges that Tymlos® itself contains the claimed beta-Asp10 isomer and is a "formulated drug product," and therefore the ANDA Product, to be the same, must also meet the limitations of Claim 8 (Compl. ¶66).
| Claim Element (from Independent Claim 1 via Dependent Claim 8) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition... | The ANDA Product is alleged to be "a pharmaceutical composition." (Compl. ¶66). | ¶66 | col. 10:40-44 |
| ...comprising an isomer of abaloparatide consisting of beta-Asp10 abaloparatide... | The complaint alleges the ANDA Product will be the same as Tymlos®, which itself contains the beta-Asp10 abaloparatide isomer. The Tymlos® specification is cited as stating it "contains <5% beta-Asp10 abaloparatide." (Compl. ¶66). | ¶66 | col. 10:25-34 |
| ...further comprising abaloparatide... | The ANDA Product's active ingredient is abaloparatide. (Compl. ¶48, 62). | ¶¶48, 62, 66 | col. 10:40-44 |
| ...wherein the pharmaceutical composition is a formulated drug product. | The complaint alleges that the ANDA Product is "a formulated abaloparatide drug product." (Compl. ¶66). | ¶66 | col. 9:56-59 |
Identified Points of Contention
- Scope Questions: A central question is whether a claim to a composition "comprising" an active drug and its known, inherent degradation product is valid and infringed by a product that contains the degradant as an unavoidable impurity. The dispute may focus on whether the term "comprising" requires the isomer to be a substantive component rather than a trace impurity that the patent itself teaches to minimize ('067 Patent, col. 2:4-7, 49-53).
- Technical Questions: What evidence exists within the ANDA filing itself regarding the presence and concentration of the beta-Asp10 isomer? The infringement allegation rests on an inference of sameness between the ANDA Product and Tymlos®. The actual, specified composition of the ANDA Product will be a dispositive factual issue.
V. Key Claim Terms for Construction
The Term: "comprising"
- Context and Importance: This transitional phrase is fundamental to the scope of the composition claims. The infringement theory depends on this term covering the presence of the beta-Asp10 isomer as an impurity. Practitioners may focus on this term because its construction will determine whether the incidental presence of a degradation product brings a formulation within the claim's scope.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "comprising" is well-established in patent law as being open-ended, meaning "including but not limited to." The patent claims compositions that include both the isomer and abaloparatide without specifying purpose or origin, which may support reading the claim on any mixture containing the elements, regardless of how the isomer arose ('067 Patent, Claim 4).
- Evidence for a Narrower Interpretation: The patent repeatedly characterizes the claimed isomer as a "degradant" and "impurity" ('067 Patent, col. 2:5-6). A defendant may argue that in this context, "comprising" should not be construed to cover trace amounts of an undesirable by-product, but rather components that are basic and material to the inventive composition.
The Term: "a formulated drug product"
- Context and Importance: This limitation in asserted Claim 8 distinguishes it from a simple mixture or API. The infringement allegation requires the ANDA Product to be a "formulated drug product" that embodies the claims (Compl. ¶66).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification defines a "formulated abaloparatide drug product" as a formulation where the "API has been formulated in an aqueous vehicle suitable for drug delivery" ('067 Patent, col. 9:56-59), a broad definition that would likely cover the accused ANDA product.
- Evidence for a Narrower Interpretation: A defendant might argue that the term, read in light of the specification, implies a product meeting certain stability and purity profiles taught by the patent. The patent extensively discusses the analysis of formulations after specific storage periods and conditions to ensure impurity levels remain below a threshold (e.g., ≤5% beta-Asp10) ('067 Patent, col. 5:7-21, col. 39:1-15). This could support an argument that a product not meeting these stability characteristics is not the claimed "formulated drug product."
VI. Other Allegations
Indirect Infringement
- The complaint alleges that Defendants will induce infringement by instructing patients and healthcare providers to use the ANDA product in accordance with its label, which is expected to mirror the label for Tymlos® (Compl. ¶¶68, 70). This directed use, if performed, would allegedly constitute direct infringement.
Willful Infringement
- Willfulness is alleged based on Defendants' knowledge of the '067 Patent at least since its listing in the FDA's Orange Book on May 16, 2024 (Compl. ¶46, 71). The complaint alleges that Defendants will proceed without a reasonable basis for believing they are not infringing (Compl. ¶72).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope and patentability: Can a composition claim be validly asserted against a product where the allegedly infringing element is an inherent, unavoidable degradation by-product of the active ingredient, especially when the patent's own disclosure focuses on methods to monitor and minimize that very by-product?
- A key evidentiary question will be one of ANDA product composition: Does the defendants' ANDA submission specify a composition that literally falls within the patent's claims, or does the plaintiff's infringement case rest solely on the inference that the generic must be identical to the brand-name drug's impurity profile? The contents of the confidential ANDA filing will be central to resolving this question.