DCT
3:18-cv-14895
Par Pharmaceutical Inc v. Sandoz Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Par Pharmaceutical, Inc. (New York); Par Sterile Products, LLC (Delaware); Endo Par Innovation Company, LLC (Delaware)
- Defendant: Sandoz Inc. (Colorado)
- Plaintiff’s Counsel: Dechert LLP
- Case Identification: 3:18-cv-14895, D.N.J., 10/11/2018
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey as Defendant Sandoz has its principal place of business in the state and maintains laboratories and facilities there, establishing residency in the district.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiffs' VASOSTRICT® product constitutes an act of infringement of six patents directed to vasopressin formulations and methods for treating hypotension.
- Technical Context: The technology relates to stable, injectable formulations of vasopressin, a hormone used to increase blood pressure in critical care patients experiencing vasodilatory shock, a life-threatening condition.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 212069 and issuance of a Paragraph IV Notice to Plaintiffs. The complaint notes that one or more of the patents-in-suit are the subject of other pending litigation against different pharmaceutical companies in the District of New Jersey, the District of Delaware, and the Western District of New York.
Case Timeline
| Date | Event |
|---|---|
| 2012-09-25 | JHP Pharmaceuticals submits NDA for VASOSTRICT® |
| 2014-04-17 | FDA approves original VASOSTRICT® NDA No. 204485 |
| 2015-01-30 | Earliest Priority Date for all Patents-in-Suit |
| 2016-03-18 | FDA approves supplemental NDA for 20 units/mL formulation of VASOSTRICT® |
| 2016-06-28 | U.S. Patent No. 9,375,478 issues |
| 2016-12-17 | FDA approves supplemental NDA for 200 units/10mL formulation of VASOSTRICT® |
| 2017-06-27 | U.S. Patent No. 9,687,526 issues |
| 2017-08-29 | U.S. Patent No. 9,744,209 issues |
| 2017-08-29 | U.S. Patent No. 9,744,239 issues |
| 2017-09-05 | U.S. Patent No. 9,750,785 issues |
| 2018-04-10 | U.S. Patent No. 9,937,223 issues |
| 2018-08-31 | Sandoz submits ANDA No. 212069 for generic vasopressin product (on or before this date) |
| 2018-08-31 | Sandoz sends Paragraph IV Notice to Plaintiffs (on or about this date) |
| 2018-10-11 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,744,239 - "Vasopressin Formulations for Use in Treatment of Hypotension"
- Issued: August 29, 2017
The Invention Explained
- Problem Addressed: The patent background describes that prior vasopressin formulations had poor long-term stability, requiring either refrigeration or the reconstitution of lyophilized powders before use in a clinical setting (U.S. Patent No. 9,375,478, col. 1:21-24).
- The Patented Solution: The invention claims a method for increasing blood pressure by administering a specific, stable aqueous formulation of vasopressin. The formulation is defined by a narrow set of components—vasopressin, optional chlorobutanol, acetic acid/acetate, limited degradation products, and water—at a specific concentration and pH range, which is then diluted and administered intravenously at a specified rate (Compl. ¶34; U.S. Patent No. 9,744,239, Claim 1). This combination of parameters is described as providing a stable, ready-to-use liquid formulation (’478 Patent, col. 1:21-24, col. 5:50-54).
- Technical Importance: The claimed method provides clinicians with a standardized protocol for using a specific, shelf-stable vasopressin formulation, potentially improving safety and efficiency in critical care environments where rapid administration is necessary (Compl. ¶21).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶34).
- The essential elements of Claim 1 are:
- A method of increasing blood pressure in a human in need thereof, comprising:
- a) providing a pharmaceutical composition for intravenous administration consisting of, in a unit dosage form: i) vasopressin at a concentration from about 0.01 mg/mL to 0.07 mg/mL, ii) optionally chlorobutanol, iii) acetic acid/acetate, iv) 0-2% vasopressin degradation products, and v) water;
- b) diluting the unit dosage form to provide a vasopressin concentration of about 0.1 units/mL to 1 unit/mL; and
- c) administering the diluted form intravenously to a hypotensive human;
- wherein the unit dosage form has a pH of 3.5 to 4.1, and the administration provides vasopressin at a rate of 0.01 to 0.1 units per minute.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 9,937,223 - "Vasopressin Formulations for Use in Treatment of Hypotension"
- Issued: April 10, 2018
The Invention Explained
- Problem Addressed: As with the related patents, the invention addresses the poor long-term stability of prior vasopressin formulations ('478 Patent, col. 1:21-24). This patent specifically addresses challenges related to multi-dose vials, where a formulation must remain stable after its sterile seal is first punctured.
- The Patented Solution: The invention claims a method of using a specific vasopressin formulation provided in a container, wherein a portion is drawn by puncturing a dispensing region, administered, and then a second portion is drawn and administered "at least 48 hours after the first time that the dispensing region of the container is punctured" (Compl. ¶42; U.S. Patent No. 9,937,223, Claim 1). This method relies on the formulation's stability in a multi-dose context, even after initial use ('478 Patent, col. 22:34-36).
- Technical Importance: This method enables the use of multi-dose vials for vasopressin, which can reduce waste and improve workflow efficiency in a hospital setting, by claiming a usage protocol that leverages the formulation's extended post-puncture stability.
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶42).
- The essential elements of Claim 1 are:
- A method of increasing blood pressure in a hypotensive human, comprising:
- a) providing a pharmaceutical composition in a container, comprising vasopressin, acetate buffer, and water, at a pH from about 3.7 to 3.8;
- b) puncturing a dispensing region of the container a first time and drawing a portion;
- c) intravenously administering that portion;
- d) puncturing the dispensing region a second time and drawing a second portion, wherein the second puncture occurs at least 48 hours after the first; and
- e) intravenously administering the second portion at a specified rate.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
Multi-Patent Capsule: U.S. Patent No. 9,375,478
- Patent Identification: U.S. Patent No. 9,375,478 (“’478 Patent”), “Vasopressin Formulations for Use in Treatment of Hypotension,” issued June 28, 2016 (Compl. ¶14).
- Technology Synopsis: The patent claims a method of increasing blood pressure using a unit dosage form that "consists essentially of" vasopressin, a 10 mM acetate buffer, and water, with a specific pH of 3.8 (Compl. ¶50). This "consists essentially of" language is generally less restrictive than "consisting of," allowing for the presence of other components that do not materially affect the basic and novel properties of the invention.
- Asserted Claims: Independent claim 1 (Compl. ¶50).
- Accused Features: The composition of Sandoz’s proposed generic product and its intended method of administration are alleged to infringe (Compl. ¶¶48, 51).
Multi-Patent Capsule: U.S. Patent No. 9,687,526
- Patent Identification: U.S. Patent No. 9,687,526 (“’526 Patent”), “Vasopressin Formulations for Use in Treatment of Hypotension,” issued June 27, 2017 (Compl. ¶15).
- Technology Synopsis: The patent claims a method that adds a specific manufacturing or storage step to the administration protocol. It requires "storing the pharmaceutical composition at 2-8° C. for at least 4 weeks" and claims that the composition exhibits "less than about 5% degradation" after that period (Compl. ¶58).
- Asserted Claims: Independent claim 1 (Compl. ¶58).
- Accused Features: The allegation is that Sandoz’s product is manufactured and/or stored in a way that meets the claimed stability and storage requirements before it is administered as intended (Compl. ¶¶56, 59).
Multi-Patent Capsule: U.S. Patent No. 9,750,785
- Patent Identification: U.S. Patent No. 9,750,785 (“’785 Patent”), “Vasopressin Formulations for Use in Treatment of Hypotension,” issued September 5, 2017 (Compl. ¶18).
- Technology Synopsis: This patent claims a pharmaceutical composition, rather than a method. The claim is directed to a unit dosage form of vasopressin further defined by a specific impurity profile (impurities present in an amount of 0.9% to 1.7% that have a certain sequence homology to vasopressin) and a specific pH range of 3.7-3.9 (Compl. ¶66).
- Asserted Claims: Independent claim 1 (Compl. ¶66).
- Accused Features: The formulation of Sandoz's proposed generic product itself is alleged to meet the claimed compositional and impurity profile limitations (Compl. ¶¶64, 67).
Multi-Patent Capsule: U.S. Patent No. 9,744,209
- Patent Identification: U.S. Patent No. 9,744,209 (“’209 Patent”), “Vasopressin Formulations for Use in Treatment of Hypotension,” issued August 29, 2017 (Compl. ¶16).
- Technology Synopsis: This patent claims a method of increasing blood pressure by administering a unit dosage form that is defined by the same impurity profile and pH range as the composition claimed in the ’785 Patent (Compl. ¶74).
- Asserted Claims: Independent claim 1 (Compl. ¶74).
- Accused Features: The composition of Sandoz’s proposed generic product and its intended method of administration are alleged to infringe (Compl. ¶¶72, 75).
III. The Accused Instrumentality
Product Identification
- Sandoz's proposed generic Vasopressin Injection USP, 200 units/10mL (20 units/mL), which was the subject of ANDA No. 212069 (Compl. ¶28).
Functionality and Market Context
- The accused product is identified as a "multiple dose injection solution" that references Par's VASOSTRICT® products as the reference listed drug (Compl. ¶28). VASOSTRICT® is an FDA-approved drug indicated to increase blood pressure in adults with vasodilatory shock (e.g., post-cardiotomy or sepsis) (Compl. ¶27). The complaint alleges that VASOSTRICT® has enjoyed "tremendous commercial success," with annual sales of $400 million in 2017 (Compl. ¶27). Sandoz's product is intended to be a generic equivalent for this market. No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’239 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of increasing blood pressure in a human in need thereof, the method comprising: | Sandoz’s submission of its ANDA for a product indicated for increasing blood pressure, which allegedly induces infringement of the claimed method. | ¶32, ¶35 | col. 3:41-43 |
| a) providing a pharmaceutical composition for intravenous administration consisting of, in a unit dosage form: i) from about 0.01mg/mL to about 0.07 mg/mL of vasopressin... ii) optionally chlorobutanol; iii) acetic acid, acetate, or a combination thereof; ...and v) water; | The complaint alleges that Sandoz’s proposed ANDA product is a composition that, when administered as intended, will meet these specific compositional requirements. | ¶34, ¶35 | col. 8:1-9 |
| b) diluting the unit dosage form in a diluent to provide a concentration from about 0.1 units/mL to about 1 unit/mL of vasopressin...; and | It is alleged that Sandoz's proposed product label will instruct medical personnel to perform the claimed dilution step. | ¶35 | col. 22:47-50 |
| c) administering the diluted unit dosage form to the human by intravenous administration; wherein: the unit dosage form has a pH of 3.5 to 4.1; the administration provides...from about 0.01 units...to about 0.1 units...per minute; and the human is hypotensive. | It is alleged that Sandoz’s proposed product label will instruct medical personnel to administer the product intravenously to hypotensive patients at a rate and pH meeting the claim limitations. | ¶35 | col. 22:53-67 |
- Identified Points of Contention:
- Scope Questions: A central question will be whether the Sandoz product formulation meets the "consisting of" limitation. This is a closed term, meaning infringement requires that the accused composition has only the listed ingredients (and unavoidable impurities). If the Sandoz product includes any other excipients, such as alternative buffering agents or stabilizers, it may fall outside the claim's scope.
- Technical Questions: The complaint does not specify the exact composition, concentration, or pH of the Sandoz product. A key factual dispute will be whether discovery confirms that the Sandoz product's parameters (vasopressin concentration, pH, degradation products) align with the ranges recited in Claim 1.
’223 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of increasing blood pressure in a human in need thereof, the method comprising: a) providing a pharmaceutical composition for intravenous administration comprising: i) from about 0.01 mg/mL to about 0.07 mg/mL of vasopressin... ii) acetate buffer; and iii) water; wherein the pharmaceutical composition has a pH from about 3.7 to about 3.8; wherein the pharmaceutical composition is provided in a container; | Sandoz’s proposed ANDA product is alleged to be a multi-dose vial containing a vasopressin formulation that meets these compositional and pH requirements. | ¶28, ¶42 | col. 10:49-54 |
| b) puncturing a dispensing region of the container a first time and drawing from the container a portion of the pharmaceutical composition; | Sandoz’s proposed product label is alleged to instruct medical personnel to puncture the vial and draw a dose. | ¶43 | col. 22:34-36 |
| d) puncturing the dispensing region of the container a second time and drawing from the container a second portion of the pharmaceutical composition; wherein: the second time that the dispensing region of the container is punctured occurs at least 48 hours after the first time that the dispensing region of the container is punctured; | It is alleged that Sandoz's product is a "multiple dose injection solution" and that its label will instruct or encourage a second use at least 48 hours after the first, consistent with the product's stability profile. | ¶28, ¶43 | col. 22:34-36 |
| e) intravenously administering the second portion of the pharmaceutical composition to the human... | Sandoz's proposed product label is alleged to instruct intravenous administration of the second drawn portion. | ¶43 | col. 22:53-67 |
- Identified Points of Contention:
- Scope Questions: The core issue for this method claim will likely be inducement. The question for the court will be whether Sandoz’s proposed product label instructs, encourages, or promotes the specific act of puncturing the vial a second time at least 48 hours after the first. Sandoz may argue its label merely permits multiple uses from the vial without specifying or requiring this infringing timing.
- Technical Questions: Does the stability data in Sandoz's ANDA support or suggest a 48-hour post-puncture use window? The complaint relies on the fact that the accused product is a "multiple dose" solution (Compl. ¶28) to support the allegation that its label will induce the claimed multi-day use pattern.
V. Key Claim Terms for Construction
The Term: “consisting of” (’239 Patent, Claim 1)
Context and Importance: This transitional phrase is legally distinct from "comprising" and is highly restrictive. Its construction will be critical because if Sandoz’s formulation contains any unlisted active or inactive ingredients that are not impurities, it would likely not infringe this claim. Practitioners may focus on this term because it presents a straightforward, non-infringement defense if additional excipients are present in the accused product.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that the term allows for manufacturing impurities or other components present in amounts that do not materially alter the basic and novel characteristics of the claimed composition. The claim itself allows for "0-2% vasopressin degradation products," suggesting some tolerance for substances beyond the core listed ingredients (Compl. ¶34).
- Evidence for a Narrower Interpretation: The plain meaning of "consisting of" creates a strong presumption that the claim is closed to any other elements. The patent specification's exemplary formulations often list only the claimed components, which may be used to argue that the inventors intended to exclude other substances ('478 Patent, col. 21:10-18, TABLE 5).
The Term: “puncturing the dispensing region of the container a second time ... occurs at least 48 hours after the first time” (’223 Patent, Claim 1)
Context and Importance: This term defines the central, novel feature of the claimed method: a multi-day use protocol from a single vial. The infringement analysis will turn on whether Sandoz’s product label induces users to perform this specific sequence with this timing.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A defendant may argue that for inducement, the label must require or recommend this specific timing, not merely make it possible.
- Evidence for a Narrower Interpretation: The patentee may point to specification language indicating the formulation's stability, such as the product information stating vials "are to be discarded 48 hours after first puncture" ('478 Patent, col. 22:34-36), as evidence that the 48-hour window is a key feature of the invention intended for clinical use and that a label for a multi-dose vial would inherently teach or encourage use throughout this period.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Sandoz will actively and intentionally induce infringement of all asserted method claims (Compl. ¶¶ 35, 43, 51, 59, 67, 75). The basis for these allegations is Sandoz's proposed product label and other conduct, which allegedly will instruct doctors and other medical personnel to perform the claimed steps of treatment.
- Willful Infringement: The complaint alleges willful infringement of all six patents (Compl. ¶¶ 38, 46, 54, 62, 70, 78). The basis for this allegation is that Sandoz was aware of the patents-in-suit, as evidenced by its service of a Paragraph IV Notice, and is aware that its commercial activity will lead to infringement (Compl. ¶¶ 37, 45, 53, 61, 69, 77).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: For claims with the restrictive "consisting of" language, will discovery show that Sandoz’s generic formulation is strictly limited to the recited components, or will the presence of additional excipients provide a clear path to non-infringement?
- A second central question will be one of induced infringement: For the asserted method patents, particularly the ’223 Patent, does the language of Sandoz's proposed product label meet the legal standard for encouraging or instructing the specific multi-step, timed administration protocol, or does it merely describe a product whose administration could be performed in an infringing manner?
- A key evidentiary question will be one of biochemical equivalence: For patents defined by a specific impurity profile (e.g., ’785 and ’209 Patents), will the chemical analysis of Sandoz's product reveal an impurity profile that falls within the claimed ranges, or will it differ in a way that avoids infringement?