DCT
1:22-cv-11546
Radius Health Inc v. Orbicular Pharmaceutical Tech Pvt Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Radius Health, Inc. (Delaware) and Ipsen Pharma S.A.S. (France)
- Defendant: Orbicular Pharmaceutical Technologies Private Limited (India)
- Plaintiff’s Counsel: Choate, Hall & Stewart LLP
- Case Identification: 1:22-cv-11546, D. Mass., 04/17/2023
- Venue Allegations: Venue is alleged to be proper because Defendant is a foreign corporation that does not have a state of residence in the United States.
- Core Dispute: Plaintiffs allege that Defendant’s Abbreviated New Drug Application (ANDA) for a generic version of the osteoporosis drug Tymlos® infringes four U.S. patents related to the drug's active ingredient (abaloparatide), its formulation, and methods of use.
- Technical Context: The technology concerns abaloparatide, a synthetic analog of a human parathyroid hormone-related peptide, which functions as a bone-building (anabolic) agent for treating postmenopausal women with osteoporosis.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 217245 to the FDA, which included a Paragraph IV Certification challenging the asserted patents. Defendant sent a formal notice letter to Plaintiffs on August 8, 2022. Notably, U.S. Patent No. RE49,444 is a reissue of U.S. Patent No. 7,803,770, which was the patent originally challenged in Defendant's ANDA certification.
Case Timeline
| Date | Event |
|---|---|
| 2006-10-03 | Priority Date for ’444, ’333, and ’382 Patents |
| 2012-04-03 | U.S. Patent No. 8,148,333 Issues |
| 2014-06-10 | U.S. Patent No. 8,748,382 Issues |
| 2017-04-28 | FDA Approves Tymlos® (abaloparatide) |
| 2017-04-28 | Priority Date for ’208 Patent |
| 2021-05-04 | U.S. Patent No. 10,996,208 Issues |
| 2022-08-08 | Defendant Mails Notice of Paragraph IV Certification |
| 2023-03-07 | U.S. Patent No. RE49,444 Issues |
| 2023-04-17 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Reissue Patent No. RE49,444 - “Method of Treating Osteoporosis Comprising Administration of PTHRP Analog”
The Invention Explained
- Problem Addressed: The complaint notes that at the time of the invention, there was a need for new anabolic (bone-building) agents to treat osteoporosis, as existing therapies were primarily anti-resorptive (slowing bone loss) (Compl. ¶5).
- The Patented Solution: The invention is a specific method of treatment for osteoporosis using the PTHrP analogue abaloparatide. The patent claims a method that comprises administering a specific daily subcutaneous dose—80 µg—of the abaloparatide peptide to a human patient (Compl. ¶26, ¶63).
- Technical Importance: The complaint alleges that upon its approval, Tymlos® (abaloparatide) was the first new anabolic agent for postmenopausal women with osteoporosis in the United States in nearly fifteen years (Compl. ¶5).
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 (Compl. ¶63).
- Essential elements of independent claim 1:
- A method of treating osteoporosis
- comprising daily subcutaneous administration
- of a composition comprising 80 µg of [Glu22,25, Leu23,28,31, Aib29, Lys26,30]hPTHrP(1-34)NH2
- to a human in need thereof.
U.S. Patent No. 8,148,333 - “Stable Composition Comprising a PTHRP Analogue”
The Invention Explained
- Problem Addressed: The complaint explains that the patent is directed to stable pharmaceutical compositions (Compl. ¶27). Peptide-based drugs like abaloparatide can be susceptible to degradation in aqueous solutions, making it difficult to create liquid formulations with a long shelf life suitable for multi-dose pens.
- The Patented Solution: The patent claims a storage-stable liquid composition of abaloparatide that includes an effective amount of a pH buffer to maintain the solution’s pH within a specific narrow range of about 4.5 to 5.6 (Compl. ¶27, ¶85). This controlled pH environment is described as enhancing the stability of the peptide in the formulation (’333 Patent, col. 1:36-43).
- Technical Importance: This technology facilitates a ready-to-use, multi-dose liquid formulation, which may improve patient convenience compared to products requiring lyophilization and reconstitution before use (’333 Patent, col. 1:40-43).
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 (Compl. ¶85).
- Essential elements of independent claim 1:
- A storage-stable composition suitable for administration to a subject comprising:
- a) a PTHrP analogue having the sequence [Glu22,25, Leu23,28,31, Aib29, Lys26,30] hPTHrP(1-34)NH2 (SEQ ID NO.2); and
- b) an effective amount of a pH buffer to maintain the pH in a range of about 4.5 to about 5.6.
U.S. Patent No. 8,748,382 - “Method of Drug Delivery for Bone Anabolic Protein”
- Technology Synopsis: This patent claims methods of stimulating bone growth in a subject by administering the storage-stable abaloparatide compositions that are buffered to maintain a pH between approximately 4.5 and 5.6, as claimed in the ’333 Patent (Compl. ¶28, ¶106).
- Asserted Claims: The complaint asserts at least independent Claim 1 (Compl. ¶106).
- Accused Features: The administration of Defendant's ANDA product to patients is alleged to infringe, as the product is asserted to be a storage-stable, buffered abaloparatide composition and its label will instruct its use for stimulating bone growth (Compl. ¶106, ¶107).
U.S. Patent No. 10,996,208 - “Abaloparatide Formulations and Methods of Testing, Storing, Modifying, and Using Same”
- Technology Synopsis: This patent relates to quality control and product purity, claiming formulated abaloparatide drug products that comprise a specific low level (≤5% w/w) of an impurity known as beta-Asp10. It also claims methods for establishing the suitability of a product for administration by detecting and quantifying the presence of this impurity (Compl. ¶29, ¶128).
- Asserted Claims: The complaint asserts at least independent Claim 14 (Compl. ¶128).
- Accused Features: Defendant's ANDA product is alleged to be a formulated drug product that meets the specific concentration, pH, and purity limitations recited in the claims, including the limit on beta-Asp10 content (Compl. ¶129).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendant Orbicular’s generic abaloparatide injection, 3120 MCG / 1.56 ML (2000 MCG/ML), which is the subject of ANDA No. 217245 filed with the FDA (Compl. ¶1, ¶13). The technical act of infringement alleged is the submission of the ANDA itself to seek approval for commercial manufacture and sale prior to the expiration of the patents-in-suit (Compl. ¶1).
Functionality and Market Context
The ANDA Product is an injection solution for subcutaneous use with abaloparatide as its active ingredient (Compl. ¶41, ¶63). The complaint alleges, upon information and belief, that the product's label will recommend the same indication, dosage (80 µg per day), and administration as the branded drug Tymlos® for the treatment of postmenopausal women with osteoporosis (Compl. ¶42, ¶44, ¶45). The product is intended to serve as a generic substitute for Tymlos® and is expected to compete directly with and replace sales of the branded product upon approval (Compl. ¶19). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
RE49,444 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating osteoporosis | Defendant's ANDA Product label will allegedly recommend the same "Indication and Usage" as Tymlos®, which is for the treatment of osteoporosis in postmenopausal women at high risk for fracture. | ¶42, ¶45 | col. 13:2-15 |
| comprising daily subcutaneous administration | The product is described as an "injection solution for subcutaneous use" and its proposed label will allegedly recommend the same "Dosage and Administration" as Tymlos®, which is administered subcutaneously once daily. | ¶30, ¶44, ¶63 | col. 13:3-4 |
| of a composition comprising 80 µg of [Glu22,25, Leu23,28,31, Aib29, Lys26,30]hPTHrP(1-34)NH2 | The active ingredient in the ANDA Product is identified as abaloparatide, the claimed peptide. The proposed dosage will be 80 µg per day, and the product will deliver 80 µg. | ¶41, ¶63 | col. 13:4-7 |
| to a human in need thereof. | The intended patient population is postmenopausal women with osteoporosis at high risk for fracture. | ¶45 | col. 13:7 |
- Identified Points of Contention:
- Technical Questions: The infringement theory for this method patent depends on the specific instructions that will appear on the final, FDA-approved label for Defendant's product (Compl. ¶64). A primary question for the court will be whether the ANDA, as filed and as will be approved, contains a proposed label that instructs users to perform each step of the claimed method, thereby inducing infringement.
8,148,333 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A storage-stable composition suitable for administration to a subject | The complaint alleges that Defendant has represented to the FDA that its ANDA Product will be the same as Tymlos®, which embodies the claimed storage-stable composition. | ¶86 | col. 1:36-37 |
| comprising: a) a PTHrP analogue having the sequence [Glu22,25...] hPTHrP(1-34)NH2 (SEQ ID NO.2); | The active ingredient in the ANDA Product is identified as abaloparatide, which has the claimed amino acid sequence. | ¶85 | col. 1:50-54 |
| and b) an effective amount of a pH buffer to maintain the pH in a range of about 4.5 to about 5.6. | The complaint alleges, on information and belief, that the ANDA Product contains this element because it is represented as being the same as Tymlos®, which contains a buffer to maintain the specified pH range. | ¶86 | col. 1:55-57 |
- Identified Points of Contention:
- Technical Questions: The complaint's allegation regarding the presence of a specific buffering system is made "on information and belief" based on the ANDA's asserted bioequivalence to Tymlos® (Compl. ¶86). A key evidentiary question will be whether Orbicular's product formulation actually contains a buffer that performs the claimed function of maintaining the pH within the claimed range, or if it achieves stability or its target pH through alternative means not covered by the claim.
V. Key Claim Terms for Construction
The Term: “storage-stable” (’333 Patent, Claim 1)
Context and Importance: This term is a preamble limitation that is central to the claimed composition in the ’333 patent. The definition will be critical in determining whether Defendant’s product, which will have its own demonstrated stability profile, meets this limitation. Practitioners may focus on this term because the parties may dispute the specific duration and conditions (e.g., room temperature vs. refrigeration) required to satisfy the “storage-stable” requirement.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states the invention provides a composition that “may be stored at room temperature for at least several weeks,” suggesting stability is not strictly limited to long-term refrigeration (’333 Patent, col. 1:40-42).
- Evidence for a Narrower Interpretation: The patent's figures depict stability data measured over a 24-month period under specific temperature conditions (5°C and 25°C) (’333 Patent, FIG. 1). A defendant could argue these examples define the scope of stability required by the claims.
The Term: “an effective amount of a pH buffer to maintain the pH” (’333 Patent, Claim 1)
Context and Importance: This is a functional limitation that defines a key component of the claimed formulation. The dispute will likely center on what constitutes an “effective amount” and whether the agent must actively “maintain” the pH, as opposed to the formulation merely having an incidental pH within the claimed range.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification lists several types of buffers, including acetate, tartrate, phosphate, and citrate, suggesting the claim is not limited to a single chemical entity (’333 Patent, col. 2:62-64). This supports a functional interpretation based on the result of maintaining pH.
- Evidence for a Narrower Interpretation: The detailed description provides a specific example of a suitable buffer concentration of “about 6 mM” (’333 Patent, col. 3:9-10). A defendant might argue that this example limits the scope of what constitutes an “effective amount.”
VI. Other Allegations
Indirect Infringement
The complaint alleges that Defendant will induce infringement of the method claims of the ’444 and ’382 patents. This allegation is based on the assertion that Defendant's proposed product labeling will instruct patients, prescribers, and physicians to administer the ANDA product in a manner that directly infringes those claims (Compl. ¶64, ¶66, ¶107).
Willful Infringement
The complaint alleges that Defendant had knowledge of the patents-in-suit at least since the date it filed its ANDA with a Paragraph IV certification (Compl. ¶69, ¶90, ¶112, ¶134). Plaintiffs further allege that Defendant's assertions of non-infringement or invalidity are “devoid of any objective good-faith basis,” which forms the foundation for a claim of willful infringement (Compl. ¶70, ¶91, ¶113, ¶135).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of compositional fact: does Orbicular’s ANDA product actually contain the specific formulation claimed in the ’333 patent—namely, an “effective amount of a pH buffer to maintain the pH” in the claimed range—and does it meet the purity requirements of the ’208 patent? The complaint's allegations rely on an assumption of sameness with the branded drug, which will be subject to factual discovery.
- A key legal question will be one of induced infringement: assuming the method claims of the ’444 and ’382 patents are valid, will the final, FDA-approved label for Orbicular’s product contain instructions that are specific enough to lead a court to conclude that Orbicular intended for physicians and patients to perform the patented methods?
- The case may also turn on a question of definitional scope: how broadly will the court construe the term “storage-stable”? The interpretation of this term will be critical for determining whether Orbicular's formulation, with its own unique stability data, falls within the scope of the ’333 patent claims.