DCT
1:23-cv-10861
Ossifi MAB LLC v. Amgen Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Ossifi-Mab LLC (Kansas)
- Defendant: Amgen Inc. (Delaware)
- Plaintiff’s Counsel: Goodwin Procter LLP
- Case Identification: 1:23-cv-10861, D. Mass., 01/04/2024
- Venue Allegations: Venue is based on Defendant's "regular and established place of business" in Cambridge, Massachusetts, which includes a large research and development facility operated since 2001.
- Core Dispute: Plaintiff alleges that Defendant’s osteoporosis drug, Evenity®, infringes four patents related to methods of increasing bone density through the administration of a sclerostin antagonist in combination with an antiresorptive drug.
- Technical Context: The technology lies in the field of antibody-based therapeutics, specifically targeting the sclerostin protein (Sost) pathway to stimulate bone growth for the treatment of diseases like osteoporosis.
- Key Procedural History: The complaint alleges that the prior owner of the patents-in-suit, OsteoGeneX, engaged in licensing discussions with Defendant in 2012-2013 regarding the ’099 Patent and related applications. These discussions allegedly included an offer from Defendant for an exclusive license in August 2012, though no agreement was reached. The complaint also notes that Defendant cited the ’099 Patent during the prosecution of one of its own patents. These allegations may be significant for establishing pre-suit knowledge in the context of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2006-12-29 | Earliest Priority Date for all Patents-in-Suit |
| 2012-05-15 | U.S. Patent No. 8,178,099 Issues |
| 2012-08-01 | Defendant allegedly makes offer to license '099 Patent family |
| 2014-11-04 | U.S. Patent No. 8,877,196 Issues |
| 2016-05-31 | Defendant's patent, which cited the '099 Patent, issues |
| 2019-04-09 | Accused Product (Evenity®) Approved by FDA |
| 2023-03-21 | U.S. Patent No. 11,608,373 Issues |
| 2023-11-07 | U.S. Patent No. 11,807,681 Issues |
| 2024-01-04 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,178,099 - Methods of Altering Bone Growth by Administration of SOST or WISE Antagonist or Agonist, Issued May 15, 2012
The Invention Explained
- Problem Addressed: At the time of the invention, there was a "serious and unmet need...for new bone-building therapeutics" to treat conditions like osteoporosis, which are characterized by decreased bone mineral density and increased fracture risk (Compl. ¶17, ¶36).
- The Patented Solution: The invention proposes a method for increasing bone density by administering a Sclerostin (Sost) antagonist, such as an antibody, which blocks the Sost protein from binding to its LRP receptor (Compl. ¶42; ’373 Patent, col. 1:21-28). Sclerostin is a negative regulator of bone formation; by inhibiting it, the patented method aims to promote bone growth. The method combines this Sost antagonist with an antiresorptive drug to achieve a therapeutic effect (’099 Patent, Abstract at Compl. ¶41).
- Technical Importance: The invention represented a novel therapeutic approach focused on actively building bone mass (anabolic), as opposed to solely preventing bone loss (antiresorptive), addressing a key need in osteoporosis treatment (Compl. ¶36).
Key Claims at a Glance
- The complaint asserts Claim 12 as exemplary (Compl. ¶42).
- Essential elements of independent claim 12 include:
- A method of systemically increasing bone density.
- Administering a therapeutic to a mammalian patient.
- The therapeutic comprises a Sclerostin antagonist together with an antiresorptive drug.
- The Sclerostin antagonist is an antibody or FAB fragment that specifically binds to a peptide from a defined group of sequences (SEQ ID NOs: 2-13, 22 and 23).
- The antibody interferes with Sclerostin's ability to bind to LRP.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 8,877,196 - Methods of Altering Bone Growth by Administration of SOST or WISE Antagonist or Agonist, Issued November 4, 2014
The Invention Explained
- Problem Addressed: The ’196 Patent addresses the same technical problem as the ’099 Patent: the need for effective bone-building therapeutics for conditions like osteoporosis (Compl. ¶17, ¶36).
- The Patented Solution: The solution is nearly identical to that of the ’099 Patent, involving the administration of a Sclerostin antagonist antibody that interferes with Sclerostin-LRP binding to increase bone density (’196 Patent, Abstract at Compl. ¶47). The key distinction in the asserted claim is the timing of administration relative to the antiresorptive drug (’196 Patent, claim 1 at Compl. ¶48).
- Technical Importance: This patent, as part of the same family, contributes to the novel therapeutic strategy of promoting bone growth by inhibiting Sclerostin (Compl. ¶48).
Key Claims at a Glance
- The complaint asserts Claim 1 as exemplary (Compl. ¶48).
- Essential elements of independent claim 1 include:
- A method of increasing bone density in a mammalian patient.
- Systemically administering a therapeutic.
- The therapeutic comprises a Sclerostin antagonist administered sequentially with an antiresorptive drug.
- The Sclerostin antagonist is an antibody or FAB fragment that specifically binds to a peptide from a defined group of sequences (SEQ ID NOS:2-13, 22 and 23).
- The antibody interferes with Sclerostin's ability to bind to LRP.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 11,608,373 - Methods of Altering Bone Growth by Administration of SOST or WISE Antagonist or Agonist, Issued March 21, 2023
- Patent Identification: U.S. Patent No. 11,608,373 (Compl. ¶49).
- Technology Synopsis: The ’373 Patent is directed to methods of increasing bone density by administering a Sost antagonist together with an antiresorptive drug (Compl. ¶53). The asserted claims focus on methods for promoting bone growth in a human subject already being treated with a sclerostin-recognizing antibody by further administering an antiresorptive drug (Compl. ¶54).
- Asserted Claims: Claims 1 and 15 are identified as exemplary (Compl. ¶54).
- Accused Features: The accused features are the instructions on the Evenity® product label that encourage physicians to administer an antiresorptive drug to patients being treated with Evenity®, a sclerostin-recognizing antibody (Compl. ¶104).
U.S. Patent No. 11,807,681 - Methods of Altering Bone Growth by Administration of SOST or WISE Antagonist or Agonist, Issued November 7, 2023
- Patent Identification: U.S. Patent No. 11,807,681 (Compl. ¶55).
- Technology Synopsis: The ’681 Patent is directed to methods of increasing bone density and formation by administering a Sost antagonist with an antiresorptive drug (Compl. ¶59). Asserted claims cover methods where a human subject being treated with a sclerostin-recognizing antibody is administered an antiresorptive drug, with specific claims directed to the use of alendronate and Vitamin D (Compl. ¶60).
- Asserted Claims: Claims 1 and 27 are identified as exemplary (Compl. ¶60).
- Accused Features: The accused features are the instructions on the Evenity® product label encouraging physicians to administer an antiresorptive drug (such as alendronate or Vitamin D) to patients receiving treatment with Evenity® (Compl. ¶116).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant's drug Evenity® (romosozumab-aqqg) and the method of its use as instructed by its product label (Compl. ¶1, ¶62, ¶64).
Functionality and Market Context
- Evenity®'s active ingredient, romosozumab-aqqg, is a humanized monoclonal antibody (IgG2) that works by binding to and inhibiting sclerostin (Compl. ¶67). This inhibition of sclerostin, a regulatory factor in bone metabolism, increases bone formation (Compl. ¶65, ¶67). The complaint alleges that Evenity® interferes with sclerostin's ability to bind to LRP (Compl. ¶68).
- The drug is indicated for the treatment of osteoporosis in postmenopausal women at high risk of fracture (Compl. ¶66). The complaint alleges that global sales of Evenity® exceeded $780 million in 2022, highlighting its commercial significance (Compl. ¶62).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’099 Patent Infringement Allegations
| Claim Element (from Independent Claim 12) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| [a] method of systemically increasing bone density, comprising the steps of administering, to a mammalian patient in need thereof, a therapeutic | The use of Evenity® is for treating osteoporosis, a condition of low bone density, in human patients. | ¶66 | col. 1:40-44 |
| comprising an effective amount of a Sclerostin antagonist together with an antiresorptive drug | The Evenity® label instructs that patients be supplemented with calcium and Vitamin D during treatment. The complaint alleges Vitamin D is an antiresorptive drug, administered at the same time as Evenity®. | ¶69 | col. 10:5-12 |
| wherein said Sclerostin antagonist comprises an antibody or FAB fragment specifically binding a peptide comprising 10 contiguous amino acids of a sequence selected from the group consisting of SEQ ID NOs: 2-13, 22 and 23 | Evenity®'s active ingredient is romosozumab-aqqg, a humanized monoclonal antibody that inhibits sclerostin. The complaint alleges this satisfies the binding limitation. | ¶67, ¶81 | col. 9:1-4 |
| and wherein the antibody interferes with Sclerostin's ability to bind to LRP, thereby systemically increasing bone density. | The complaint alleges that Evenity® interferes with sclerostin's ability to bind to LRP, and its purpose is to increase bone formation and density. | ¶68, ¶81 | col. 1:26-28 |
- Identified Points of Contention:
- Scope Questions: A central question may be whether Vitamin D supplementation, as instructed on the Evenity® label, constitutes administration of an "antiresorptive drug" within the meaning of the claim. While the patent specification lists "Vitamin D or analog" as an example of an antiresorptive, a defendant may argue that its routine use as a supplement differs from its classification as a "drug" in this therapeutic context.
- Technical Questions: The complaint alleges that Evenity® binds to a peptide sequence required by the claim, but does not provide specific data mapping the antibody's binding site to one of the recited SEQ ID NOs. This raises the evidentiary question of whether the accused antibody actually meets this specific structural limitation.
’196 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| [a] method of increasing bone density in a mammalian patient in need thereof, comprising the steps of: systemically administering to a said mammalian patient a therapeutic | The use of Evenity® is for treating osteoporosis, a condition of low bone density, in human patients. | ¶66 | col. 1:40-44 |
| comprising an effective amount of a Sclerostin antagonist sequentially with an antiresorptive drug | The Evenity® label instructs that after 12 months of therapy, "continued therapy with an anti-resorptive agent should be considered." Clinical trial data cited on the label describes patients transitioning from Evenity® to antiresorptive drugs like denosumab or alendronate. | ¶69, ¶70, ¶71 | col. 10:5-6 |
| said Sclerostin antagonist comprising an antibody or FAB fragment specifically binding a peptide selected from the group consisting of SEQ ID NOS:2-13, 22 and 23 | Evenity®'s active ingredient is romosozumab-aqqg, a humanized monoclonal antibody that inhibits sclerostin. The complaint alleges this satisfies the binding limitation. | ¶67, ¶93 | col. 9:1-4 |
| wherein the antibody interferes with Sclerostin's ability to bind to LRP, thereby systemically increasing bone density. | The complaint alleges that Evenity® interferes with sclerostin's ability to bind to LRP, and its purpose is to increase bone formation and density. | ¶68, ¶93 | col. 1:26-28 |
- Identified Points of Contention:
- Scope Questions: The analysis may focus on whether the label’s instruction to "consider" a subsequent therapy constitutes the claimed step of "administering" a Sclerostin antagonist "sequentially with" an antiresorptive drug. This raises a potential divided infringement issue, as Defendant sells Evenity® while third-party physicians and patients would administer the subsequent antiresorptive.
- Technical Questions: As with the ’099 Patent, the complaint does not provide specific evidence that Evenity® binds to one of the particular peptide sequences recited in the claim, which may become a key point of factual dispute.
V. Key Claim Terms for Construction
The Term: "together with" (from ’099 Patent, Claim 12)
- Context and Importance: The construction of this term is critical for the infringement theory of the ’099 Patent, which relies on the co-administration of Vitamin D and Evenity®. Practitioners may focus on this term because its definition will determine whether simultaneous but separate supplementation during a course of therapy meets the claim limitation.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification, shared across the asserted patents, discloses that the Sost antagonist may be "coadministered or serially administered with an antiresorptive drug," suggesting the patent contemplates different modes of combination therapy, not just a single formulation (’373 Patent, col. 10:5-6).
- Evidence for a Narrower Interpretation: A defendant may argue that in the context of the claim, "together with" implies a more direct combination, such as in a single formulation or a prescribed, concurrent injection schedule, rather than general dietary supplementation.
The Term: "antiresorptive drug" (from ’099 Patent, Claim 12 and ’196 Patent, Claim 1)
- Context and Importance: This term's scope is central to the infringement allegation against the ’099 Patent. The plaintiff's theory depends on Vitamin D, taken as a supplement, being classified as an "antiresorptive drug."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification explicitly lists examples of antiresorptive drugs, including "Vitamin D or analog," providing strong intrinsic support for the plaintiff's proposed construction (’373 Patent, col. 10:7-12).
- Evidence for a Narrower Interpretation: A defendant may argue that the primary examples listed in the specification (bisphosphonates, SERMs, calcitonin) define the core meaning of the term as potent, prescription pharmaceuticals, and that Vitamin D should be read as a less-preferred embodiment or one that requires administration in a particular, drug-like manner.
VI. Other Allegations
Indirect Infringement
- The complaint alleges both induced infringement under 35 U.S.C. § 271(b) and contributory infringement under § 271(c) for all asserted patents (Compl. ¶¶ 82, 84, 94, 96, 106, 108, 118, 120). The inducement theory is based on allegations that Defendant’s Evenity® label "instructs and encourages" physicians and patients to perform the claimed methods, such as by recommending Vitamin D supplementation concurrently with Evenity® treatment or by suggesting follow-on therapy with another antiresorptive agent (Compl. ¶80, ¶92).
Willful Infringement
- The complaint alleges that Defendant’s infringement was "knowing and willful" (Compl. ¶86, ¶98, ¶110, ¶122). The basis for this allegation is alleged pre-suit knowledge of the patents. Specifically, the complaint alleges that Defendant cited the ’099 Patent during the prosecution of its own patent and, further, that Defendant engaged in licensing negotiations for the ’099 patent family with the previous owner in 2012-2013, which included a license offer from Defendant (Compl. ¶73-74).
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this dispute may turn on the following central questions:
- A core issue will be one of definitional scope: Will the term "antiresorptive drug" be construed to encompass routine Vitamin D supplementation as instructed on the Evenity® label, and does such supplementation satisfy the "together with" administration requirement of the ’099 Patent?
- A key legal question will be one of indirect infringement: Can the plaintiff establish that Defendant induced infringement of the "sequentially with" limitation of the ’196 Patent, where the accused conduct is a product label's suggestion to "consider" a separate, subsequent therapy administered by third-party healthcare providers?
- A central evidentiary question will be one of technical proof: What factual evidence will be required to demonstrate that the accused antibody "specifically bind[s]" to one of the precise amino acid sequences recited in the asserted claims, a technical limitation for which the complaint provides only conclusory allegations?