DCT
1:23-cv-00401
Novartis Pharma Corp v. Nanjing Noratech Pharmaceutical Co Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Novartis Pharmaceuticals Corporation (Delaware)
- Defendant: Nanjing Noratech Pharmaceutical Co., Limited (China)
- Plaintiff’s Counsel: McCarter & English, LLP; Venable LLP
- Case Identification: 1:23-cv-00401, D. Del., 04/10/2023
- Venue Allegations: Venue is alleged to be proper because Defendant is a foreign entity. The complaint also notes that Defendant has agreed not to challenge venue in the District of Delaware for patent actions concerning its Abbreviated New Drug Application (ANDA).
- Core Dispute: Plaintiff alleges that Defendant’s submission of an ANDA to the FDA seeking approval to market generic versions of Plaintiff's Entresto® (sacubitril/valsartan) tablets constitutes an act of patent infringement.
- Technical Context: The technology concerns pharmaceutical compositions and dosing regimens combining an angiotensin receptor blocker (valsartan) with a neprilysin inhibitor (sacubitril) for the treatment of heart failure.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of notice that Defendant had filed ANDA No. 213671 with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic product. The complaint references a prior court order in a related multidistrict litigation (MDL) proceeding.
Case Timeline
| Date | Event |
|---|---|
| 2002-01-17 | ’659 Patent Priority Date |
| 2012-01-24 | ’659 Patent Issue Date |
| 2015-05-11 | ’667 Patent Priority Date |
| 2021-07-13 | ’667 Patent Issue Date |
| 2022-06-10 | Date of Noratech's Notice Letter to Novartis |
| 2023-04-10 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,101,659 - "Methods of Treatment and Pharmaceutical Composition", issued January 24, 2012
The Invention Explained
- Problem Addressed: The patent describes the complex hormonal pathways, including the renin-angiotensin system (RAAS), that contribute to hypertension and heart failure. It notes that while existing therapies like ACE inhibitors are useful, they have limitations, and there is a need for more efficacious treatments. (’659 Patent, col. 2:3-10).
- The Patented Solution: The invention is a combination therapy that dually targets cardiovascular disease pathways. It combines an angiotensin receptor (AT1) antagonist, valsartan, with a neutral endopeptidase (NEP) inhibitor, sacubitril. This approach is designed to simultaneously block the harmful vasoconstrictive effects of angiotensin II while preventing the breakdown of beneficial, naturally occurring vasodilator peptides (natriuretic peptides), creating a synergistic therapeutic effect. (’659 Patent, col. 5:41-49; Abstract).
- Technical Importance: This combination represented a novel therapeutic mechanism that went beyond single-pathway agents, offering the potential for improved outcomes in treating complex cardiovascular conditions like heart failure. (’659 Patent, col. 5:41-54).
Key Claims at a Glance
- The complaint does not specify asserted claims, but its allegations track the elements of Independent Claim 1.
- Independent Claim 1 requires:
- A pharmaceutical composition comprising:
- (i) the AT1-antagonist valsartan or a pharmaceutically acceptable salt thereof;
- (ii) the NEP inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic acid ethyl ester (sacubitril prodrug) or its active metabolite, or a pharmaceutically acceptable salt thereof; and
- (iii) a pharmaceutically acceptable carrier;
- wherein (i) and (ii) are administered in combination in about a 1:1 ratio.
- The complaint reserves the right to assert additional claims. (Compl. ¶30).
U.S. Patent No. 11,058,667 - "Sacubitril-Valsartan Dosage Regimen for Treating Heart Failure", issued July 13, 2021
The Invention Explained
- Problem Addressed: The patent explains that while the clinical efficacy of sacubitril/valsartan was established, the pivotal clinical trial provided "limited information on how the physician should initiate the... therapy in clinical practice," particularly for patients who were either new to such treatments or were previously on low doses of other RAAS inhibitors. (’667 Patent, col. 2:26-34).
- The Patented Solution: The invention provides specific, structured dosage and up-titration regimens for initiating sacubitril/valsartan therapy. As illustrated in the patent's Figure 1, the regimen involves starting patients at a low dose (e.g., 50 mg twice daily), followed by a stepwise increase to an intermediate dose (100 mg twice daily) and then a target dose (200 mg twice daily) over a defined period of several weeks. The patent particularly distinguishes regimens for patients naive to prior treatments or on low doses of such treatments. (’667 Patent, col. 3:15-32; FIG. 1).
- Technical Importance: The invention provided clinicians with data-driven protocols to safely and effectively start patients on this novel combination therapy, which was found to improve treatment success rates and tolerability, especially in more sensitive patient populations. (’667 Patent, col. 3:55-65).
Key Claims at a Glance
- The complaint alleges infringement of one or more claims, noting that Defendant’s notice letter does not dispute infringement of claims 1 and 7. (Compl. ¶39).
- Independent Claim 1 requires:
- A regimen for treating chronic heart failure with reduced ejection fraction, comprising administering a twice-daily target dose of 200 mg of sacubitril and valsartan (in a 1:1 molar ratio).
- The target dose is reached via a specific titration schedule: a starting dose of 50 mg for 3-4 weeks, then a dose of 100 mg for 3-4 weeks, then the target dose of 200 mg.
- The starting dose of 50 mg is specified for use in a patient who is either (i) not currently taking an ACE inhibitor or ARB, or (ii) is taking a "low dose" of an ACE inhibitor or ARB, defined as equivalent to less than 10 mg of enalapril per day.
- The complaint reserves the right to assert additional claims. (Compl. ¶36).
III. The Accused Instrumentality
- Product Identification: Defendant’s proposed sacubitril/valsartan tablets, for which it seeks FDA approval via ANDA No. 213671 ("Noratech ANDA Products"). (Compl. ¶1, ¶5).
- Functionality and Market Context: The accused products are generic versions of Novartis’s Entresto® tablets, intended to be marketed in 24 mg/26 mg, 49 mg/51 mg, and 97 mg/103 mg dosages. (Compl. ¶1, ¶5). The complaint alleges these products, if approved, will be labeled for the treatment of heart failure and will compete directly with Entresto®. (Compl. ¶23, ¶38). The complaint further alleges that, pursuant to a prior court order, Defendant has represented that its products "will be pharmaceutical compositions comprising physically separate valsartan... and physically separate sacubitril." (Compl. ¶33).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’659 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising: (i) the AT1-antagonist valsartan or a pharmaceutically acceptable salt thereof; | The Noratech ANDA Products will be pharmaceutical compositions that contain valsartan or a pharmaceutically acceptable salt thereof. | ¶31 | col. 4:30-32 |
| (ii) the NEP inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic acid ethyl ester... or a pharmaceutically acceptable salt thereof; | The Noratech ANDA Products will be pharmaceutical compositions that contain sacubitril or a pharmaceutically acceptable salt thereof. | ¶31 | col. 4:50-54 |
| (iii) a pharmaceutically acceptable carrier; | The Noratech ANDA Products will contain a pharmaceutically acceptable carrier. | ¶31 | col. 4:55-58 |
| wherein said (i)... and said (ii)... are administered in combination in about a 1:1 ratio. | The valsartan and sacubitril components in the Noratech ANDA Products are administered in combination in about a 1:1 ratio. | ¶31, ¶32 | col. 1:49-51 |
- Identified Points of Contention:
- Scope Questions: A central dispute may concern the scope of "pharmaceutical composition comprising" and "administered in combination." The complaint notes Defendant’s representation that its product will contain "physically separate" valsartan and sacubitril (Compl. ¶33). This raises the question of whether a co-formulation of separate active ingredients meets the claim limitations, or if the claims, when read in light of the specification, require a more integrated structure, such as a single supramolecular complex.
’667 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A regimen for treating chronic heart failure... comprising administering to a human patient... a twice-daily target dose of 200 mg of (i) sacubitril... with (ii) valsartan... provided in a 1:1 molar ratio | The labeling for the Noratech ANDA Products, if approved, will instruct the use of the product in a regimen for treating chronic heart failure that includes a twice-daily target dose of 200 mg (total sacubitril/valsartan) in a 1:1 molar ratio. | ¶37, ¶38 | col. 5:56-63 |
| wherein the twice daily target dose of 200 mg is reached after a titration with a twice daily starting dose of 50 mg... followed by a twice daily dose of 100 mg... | The product labeling will allegedly instruct users to reach the 200 mg target dose by first administering a 50 mg starting dose, followed by a 100 mg dose, before reaching the target dose. | ¶37, ¶38 | col. 6:1-7 |
| wherein the human patient is not taking an ACE inhibitor or an ARB or is taking a low dose of an ACE inhibitor or an ARB before initiating treatment with (i) and (ii) | The product labeling will allegedly direct this titration regimen for patients who are either not on prior ACE inhibitor/ARB therapy or are on a low dose of such therapy before starting treatment with the accused product. | ¶37, ¶38 | col. 6:30-44 |
- Identified Points of Contention:
- Technical Questions: A key evidentiary question will be whether Defendant’s proposed product label will, in fact, instruct, direct, or encourage administration according to the specific multi-step titration regimen required by Claim 1. The dispute will center on the content of the final, FDA-approved instructions for use.
V. Key Claim Terms for Construction
Term: "administered in combination" (’659 Patent, Claim 1)
- Context and Importance: This term is critical because Defendant has allegedly represented its product will contain "physically separate" active ingredients. (Compl. ¶33). The construction of "in combination" will determine whether such a formulation falls within the scope of the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent repeatedly refers to administering the two components "together" in "one combined unit dose form" or "separately." (’659 Patent, col. 10:28-32). This language suggests that co-formulation or co-administration, not necessarily a specific chemical complex, is what is contemplated.
- Evidence for a Narrower Interpretation: Plaintiff may argue that the specification’s focus on the benefits of the dual-acting therapy implies a formulation that ensures simultaneous delivery and action, potentially using specific embodiments to argue for a narrower meaning than simple co-packaging.
Term: "low dose of an angiotensin-converting enzyme (ACE) inhibitor or... an angiotensin II receptor blocker (ARB)" (’667 Patent, Claim 1)
- Context and Importance: The applicability of Claim 1 is expressly tied to a patient's prior treatment status. The definition of "low dose" is therefore central to identifying the patient population covered by the claim and, consequently, to the analysis of induced infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim itself provides a definition: "wherein the low dose of the ACE inhibitor or the low dose of the ARB is equivalent to a dose of <10 mg of enalapril per day." (’667 Patent, col. 21:13-16). This provides a specific, quantitative benchmark that appears to limit interpretive flexibility.
- Evidence for a Narrower Interpretation: The patent also provides this definition in the specification. (’667 Patent, col. 5:40-44). Given this explicit definition within the patent, the primary dispute is less likely to be one of claim construction and more a factual question of whether Defendant's proposed label will instruct use in this specifically defined patient population.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Defendant will induce infringement of the ’667 Patent because its product, if approved, must be labeled with instructions for use that will direct physicians and patients to practice the patented dosing regimen. (Compl. ¶37, ¶39). It is also alleged that the Noratech ANDA Products are especially made or adapted for this infringing use and have no substantial non-infringing use, supporting a claim of contributory infringement. (Compl. ¶38).
- Willful Infringement: The complaint does not use the term "willful infringement," but it alleges that Defendant was "aware of the '659 and '667 patents" at the time it filed its ANDA and that this filing constituted an act of infringement. (Compl. ¶29). Plaintiff also seeks a declaration that the case is "exceptional" under 35 U.S.C. § 285, which could entitle it to attorney's fees. (Compl. ¶50).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim scope: For the ’659 patent, can the term "pharmaceutical composition... administered in combination" be construed to read on a formulation containing physically separate active ingredients, as Defendant has allegedly represented its product to be?
- A key evidentiary question for the ’667 patent will be one of inducement: Will the final, FDA-approved label for Defendant's generic product contain instructions that direct or encourage physicians and patients to follow the specific, multi-step dose-titration regimen recited in the asserted method claims for the defined patient populations?