DCT
1:17-cv-00914
Bioverativ Inc v. CSL Behring LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bioverativ Inc., Bioverativ Therapeutics Inc., and Bioverativ U.S. LLC (Delaware)
- Defendant: CSL Behring LLC (Delaware), CSL Behring GmbH (Germany), and CSL Behring Recombinant Facility AG (Switzerland)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Foley Hoag LLP
- Case Identification: 1:17-cv-00914, D. Del., 07/07/2017
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant CSL Behring LLC is a Delaware corporation that resides in the district, and the other foreign defendants are alleged to have sufficient contacts with the forum.
- Core Dispute: Plaintiff alleges that Defendant’s hemophilia B therapy, Idelvion®, infringes three patents related to long-acting recombinant Factor IX polypeptides and methods of their use.
- Technical Context: The technology concerns recombinant protein therapies for hemophilia B, a genetic disorder impairing blood clotting, with a focus on extending the therapeutic protein's half-life to reduce the frequency of intravenous infusions.
- Key Procedural History: The complaint notes that Plaintiff’s product, Alprolix®, received FDA approval in March 2014, approximately two years before the March 2016 FDA approval of Defendant’s accused product, Idelvion®, establishing a timeline of market competition. No prior litigation or post-grant proceedings are mentioned in the complaint.
Case Timeline
| Date | Event |
|---|---|
| 2010-07-09 | Priority Date for ’475, ’091, and ’903 Patents |
| 2014-03-28 | Plaintiff's Alprolix® receives FDA Approval |
| 2016-03-XX | Defendant's Idelvion® receives FDA Approval |
| 2017-04-18 | U.S. Patent No. 9,623,091 Issues |
| 2017-04-25 | U.S. Patent No. 9,629,903 Issues |
| 2017-06-06 | U.S. Patent No. 9,670,475 Issues |
| 2017-07-07 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,670,475 - “Factor IX Polypeptides and Methods of Use Thereof” (Issued June 6, 2017)
The Invention Explained
- Problem Addressed: The patent background describes that conventional treatments for hemophilia B, a Factor IX deficiency, require frequent intravenous infusions (e.g., 2-3 times per week) due to the short half-life of recombinant or plasma-derived Factor IX protein, creating a significant treatment burden for patients (’091 Patent, col. 2:10-21).
- The Patented Solution: The invention is a chimeric polypeptide created by fusing a Factor IX protein to an "FcRn binding partner," such as an Fc fragment of an antibody or albumin. This fusion leverages the body’s natural neonatal Fc receptor (FcRn) recycling pathway, which prevents the fused protein from being broken down as quickly, thereby extending its circulation time and allowing for less frequent dosing intervals (’091 Patent, col. 2:34-54).
- Technical Importance: This technological approach enabled the development of prophylactic hemophilia B therapies with significantly longer dosing intervals (e.g., weekly or longer), which was a key advancement for improving patient quality of life and treatment compliance (Compl. ¶20, ¶23).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶37).
- Essential elements of claim 1 include:
- A method of controlling a bleeding episode in a human subject in need thereof,
- comprising administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric Factor IX polypeptide comprising FIX and an FcRn binder partner,
- at a dosing interval of about 7 days between two doses,
- wherein the FcRn binder partner comprises Fc or albumin, and
- wherein the subject exhibits the plasma FIX activity above 1 IU/dL during the dosing interval.
- The complaint reserves the right to assert dependent claims 2, 4-19, 24-25, 29, and 34 (Compl. ¶35).
U.S. Patent No. 9,623,091 - “Factor IX Polypeptides and Methods of Use Thereof” (Issued April 18, 2017)
The Invention Explained
- The technology of the ’091 Patent is the same as that described for the ’475 Patent, involving a chimeric Factor IX polypeptide with an extended half-life.
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶49).
- Essential elements of claim 1 include:
- A method of treating hemophilia B in a human subject in need thereof,
- comprising intravenously administering multiple doses of about 50 IU/kg to about 100 IU/kg of a chimeric Factor IX polypeptide comprising FIX and an FcRn binding partner,
- at a dosing interval of about 10 days to about 14 days between two doses,
- wherein the FcRn BP comprises Fc or albumin,
- wherein the administration maintains the plasma FIX activity of the subject above 1 IU/dL between the dosing interval, and
- wherein the administration treats the human subject by reducing the frequency of spontaneous bleeding.
- The complaint reserves the right to assert dependent claims 2-7, 11-16, 18, 19, 21, and 23-27 (Compl. ¶47).
Multi-Patent Capsule: U.S. Patent No. 9,629,903 - “Factor IX Polypeptides and Methods of Use Thereof” (Issued April 25, 2017)
Technology Synopsis
- The ’903 Patent covers the same core technology as the ’475 and ’091 patents: a method of treating hemophilia B using a Factor IX protein fused to an FcRn binding partner (Fc or albumin) to extend its therapeutic half-life. This patent claims a specific method of treatment characterized by a particular dosing regimen and resulting in a minimum trough level of Factor IX activity after a set period.
Asserted Claims
- The complaint asserts independent claim 1 and dependent claims 2-10, 13-15, and 17-28 (Compl. ¶59, ¶61).
Accused Features
- The accused features are the manufacture, importation, sale, and administration of Idelvion® in accordance with its label, which is alleged to constitute a method of treating hemophilia B that meets the dosage, interval, and resulting plasma FIX activity levels recited in the claims (Compl. ¶62-66).
III. The Accused Instrumentality
Product Identification
- Idelvion® [Coagulation Factor IX (Recombinant), Albumin Fusion Protein] (Compl. ¶28).
Functionality and Market Context
- Idelvion® is a biological molecule described as a recombinant Factor IX molecule fused to albumin (Compl. ¶29). The complaint alleges this fusion extends the half-life of the Factor IX protein by utilizing the same FcRn recycling pathway as Plaintiff's Alprolix® product (Compl. ¶29). Idelvion® is approved for intravenous administration in adults and children with hemophilia B for purposes including routine prophylaxis to reduce the frequency of bleeding episodes (Compl. ¶28, ¶52, ¶64). The complaint alleges that Idelvion® was approved by the FDA in March 2016, two years after Plaintiff's competing product, positioning it as a direct competitor in the market for long-acting hemophilia B therapies (Compl. ¶28).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
U.S. Patent No. 9,670,475 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of controlling a bleeding episode in a human subject in need thereof, | Idelvion® is indicated for controlling bleeding episodes in humans. | ¶39 | col. 1:41-42 |
| comprising administering to the subject multiple doses of about 25 IU/kg to about 50 IU/kg of a chimeric Factor IX (“FIX”) polypeptide comprising FIX and an FcRn binder partner (“FcRn BP”) | Idelvion® is a chimeric FIX polypeptide comprising FIX and albumin (as the FcRn BP), with labeled dosages that include a 25-55 IU/kg range. | ¶38, ¶40-41 | col. 2:34-45 |
| at a dosing interval of about 7 days between two doses, | The Idelvion® label recommends a dosing interval of every seven days. | ¶40-41 | col. 2:54-55 |
| wherein the FcRn BP comprises Fc or albumin | The FcRn BP in Idelvion® is albumin. | ¶38 | col. 10:60-62 |
| and wherein the subject exhibits the plasma FIX activity above 1 IU/dL during the dosing interval. | On information and belief, patients receiving the specified doses of Idelvion® exhibit plasma Factor IX activity above 1 IU/dL during the dosing interval. | ¶42 | col. 2:55-65 |
U.S. Patent No. 9,623,091 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating hemophilia B in a human subject in need thereof | Idelvion® is indicated for treating humans with hemophilia B. | ¶51 | col. 1:41-42 |
| comprising intravenously administering to the subject multiple doses of about 50 IU/kg to about 100 IU/kg of a chimeric factor IX (“FIX”) polypeptide comprising FIX and an FcRn binding partner (“FcRn BP”) | Idelvion® is a chimeric FIX-albumin polypeptide administered intravenously, with a labeled dosage of 50-75 IU/kg for certain patients. | ¶50, ¶52-53 | col. 2:34-45 |
| at a dosing interval of about 10 days to about 14 days between two doses, | The Idelvion® label recommends a dosing interval of 14 days for the 50-75 IU/kg dose. | ¶53 | col. 4:26-31 |
| wherein the FcRn BP comprises Fc or albumin, | The FcRn BP in Idelvion® is albumin. | ¶50 | col. 10:60-62 |
| wherein the administration maintains the plasma FIX activity of the subject above 1 IU/dL between the dosing interval, | On information and belief, administering multiple doses of Idelvion® as specified maintains plasma Factor IX activity above 1 IU/dL between doses. | ¶54 | col. 2:55-65 |
| and wherein the administration treats the human subject by reducing the frequency of spontaneous bleeding. | Idelvion® is indicated for reducing the frequency of spontaneous bleeding. | ¶51 | col. 2:25-30 |
Identified Points of Contention
- Scope Questions: The asserted claims recite dosage and timing limitations using the term "about" (e.g., "about 7 days," "about 50 IU/kg"). The infringement allegations rely on specific dosage ranges and fixed intervals from the Idelvion® label (e.g., "25-40 IU/kg," "every seven days"). A potential point of contention may be whether the specific, approved uses of Idelvion® fall within the scope of the claim term "about."
- Evidentiary Questions: The allegations that administering Idelvion® results in specific clinical outcomes—namely, maintaining plasma FIX activity "above 1 IU/dL" (’475 and ’091 Patents) or achieving a "trough level ... of at least 3 IU/dL after six days" (’903 Patent)—are made "on information and belief" (Compl. ¶42, ¶54, ¶66). This raises the evidentiary question of what proof Plaintiff will offer to demonstrate that the accused method necessarily results in these claimed pharmacokinetic effects, which will likely require clinical data and expert testimony.
V. Key Claim Terms for Construction
The Term: "FcRn binder partner"
Context and Importance
- This term defines the molecule fused to Factor IX to extend its half-life. Its construction is critical because the accused product, Idelvion®, uses albumin, whereas Plaintiff's own product, Alprolix®, uses an Fc fragment. The infringement case hinges on this term being construed to plainly cover albumin as used in the accused product.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The claims of all three patents explicitly state, "wherein the FcRn BP comprises Fc or albumin" (’475 Patent, claim 1; ’091 Patent, claim 1; ’903 Patent, claim 1). The specification further states that "FcRn BP also include albumin and fragments thereof that bind to the FcRn" (’091 Patent, col. 10:60-62). This language provides strong support for a construction that includes albumin.
- Evidence for a Narrower Interpretation: The specification extensively uses "FIXFc" as the exemplary embodiment and provides numerous figures and examples related to the Factor IX-Fc fusion (’091 Patent, Fig. 1, Example 1). A defendant might argue that the invention's true scope and enablement are centered on Fc fusions and that the mention of albumin is ancillary, potentially raising questions under written description or enablement for the albumin embodiment.
The Term: "trough level of the plasma FIX activity after each administration is at least 3 IU/dL after six days" (’903 Patent, claim 1)
Context and Importance
- This limitation defines the invention not just by the administered drug but by a specific, measurable clinical result. Infringement requires proof that the accused method achieves this precise pharmacokinetic outcome. Practitioners may focus on this term because proving this element will likely require clinical data from patients using Idelvion®, which Plaintiff may not have possessed at the time of filing, as suggested by its "information and belief" pleading.
Intrinsic Evidence for Interpretation
- The patent specification provides clinical trial data for its own FIX-Fc product that allegedly demonstrates this outcome, which a plaintiff would argue provides context for the claimed level (’091 Patent, Example 1, Tables 5-13). A defendant could argue that this clinical data is specific to the tested FIX-Fc molecule and cannot be used to interpret what would happen with a different molecule like the accused FIX-albumin fusion protein, making this a factual question of infringement rather than one of claim construction.
VI. Other Allegations
Indirect Infringement
- The complaint alleges both induced and contributory infringement for all three patents. Inducement is based on the allegation that Defendants’ Idelvion® label and other communications instruct and encourage physicians and patients to perform the patented methods with knowledge of the patents (Compl. ¶35, ¶47, ¶59). Contributory infringement is based on the sale of Idelvion®, which is alleged to be a material component of the invention, not suitable for substantial non-infringing use, and especially adapted for infringement (Compl. ¶36, ¶48, ¶60).
Willful Infringement
- Willfulness is alleged for all three patents. The complaint asserts that Defendants had knowledge of the patents at least by the date of service of the complaint and that their continued infringement is therefore willful (Compl. ¶45, ¶57, ¶69).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of evidentiary proof: can Plaintiff, through discovery and expert testimony, demonstrate that the administration of Idelvion® according to its label necessarily results in the specific, quantitative clinical outcomes required by the claims, such as maintaining plasma Factor IX activity above 1 IU/dL or achieving a trough level of at least 3 IU/dL? The complaint’s pleading of these elements on "information and belief" signals this as a central factual battleground.
- A key legal and factual question will be one of technical equivalence and enablement: While the patents explicitly name "albumin" as a potential "FcRn binder partner," the case will likely examine whether the patent's disclosure, which is heavily reliant on data from a Factor IX-Fc fusion, provides sufficient written description and enablement for the distinct Factor IX-albumin fusion of the accused product to achieve the claimed pharmacokinetic results.