DCT

1:21-cv-00712

KAI Pharma Inc v. MSN Life Sciences Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-00712, D. Del., 05/19/2021
  • Venue Allegations: Venue is alleged to be proper as to the foreign defendants (MSN Labs, MSN Life) because they may be sued in any judicial district, and as to the domestic defendant (MSN Pharma) because it is a Delaware corporation and therefore resides in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s proposed generic version of the drug Parsabiv® (etelcalcetide) infringes six patents covering the active pharmaceutical ingredient, related peptide compounds, and stable liquid formulations of the drug.
  • Technical Context: The technology relates to calcimimetic agents, specifically synthetic peptides designed to treat secondary hyperparathyroidism in patients with chronic kidney disease by modulating calcium-sensing receptors to decrease parathyroid hormone levels.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA. The asserted patents are listed in the FDA’s "Orange Book" for Parsabiv®, putting Defendant on notice of the patents. Defendant’s ANDA included a "Paragraph IV Certification," asserting that the patents are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2009-07-29 U.S. Patent No. 8,999,932 Priority Date
2009-10-28 U.S. Patent No. 8,377,880 Priority Date
2010-03-12 U.S. Patent No. 9,278,995 Priority Date
2010-03-12 U.S. Patent No. 9,701,712 Priority Date
2013-02-19 U.S. Patent No. 8,377,880 Issued
2013-06-28 U.S. Patent No. 9,820,938 Priority Date
2013-06-28 U.S. Patent No. 10,344,765 Priority Date
2015-04-07 U.S. Patent No. 8,999,932 Issued
2016-03-08 U.S. Patent No. 9,278,995 Issued
2017-02-07 FDA grants approval to market Parsabiv® (etelcalcetide)
2017-07-11 U.S. Patent No. 9,701,712 Issued
2017-11-21 U.S. Patent No. 9,820,938 Issued
2019-07-09 U.S. Patent No. 10,344,765 Issued
2021-04-08 Plaintiff receives Defendant's ANDA Notice Letter
2021-05-19 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,377,880 - "Therapeutic Agents for Reducing Parathyroid Hormone Levels"

The Invention Explained

  • Problem Addressed: The patent addresses the need for compounds that can treat diseases associated with excess parathyroid hormone (PTH), such as secondary hyperparathyroidism, which is common in patients with chronic kidney disease ('880 Patent, col. 2:50-57). Existing treatments may have limitations or side effects.
  • The Patented Solution: The invention provides specific synthetic peptide compounds that act on the calcium-sensing receptor (CaSR) on parathyroid cells. Activation of this receptor signals the cells to decrease PTH secretion ('880 Patent, col. 2:58-64). The patent claims a specific peptide conjugate, identified as Ac-c(C)arrrar-NH₂ (SEQ ID NO:3), which has a defined amino acid sequence and structure designed for this therapeutic purpose ('880 Patent, col. 26:1-26).
  • Technical Importance: The invention provided a novel peptide-based calcimimetic agent for lowering PTH levels, offering a potential therapeutic alternative for managing mineral and bone disorders in patients on dialysis (Compl. ¶22).

Key Claims at a Glance

  • Asserted Independent Claim: Claim 1
  • Claim 1 Elements:
    • A compound comprising Ac-c(C)arrrar-NH₂ (SEQ ID NO:3).

U.S. Patent No. 8,999,932 - "Therapeutic Agents for Reducing Parathyroid Hormone Levels"

The Invention Explained

  • Problem Addressed: Similar to the '880 Patent, this patent addresses the need for compounds that modulate PTH levels to treat conditions like hyperparathyroidism ('932 Patent, col. 2:50-57).
  • The Patented Solution: This patent claims the therapeutic agents more broadly as a "conjugate" structure. The solution involves a peptide linked to a "conjugating group" via a disulfide bond, where the peptide has a specific amino acid sequence ('932 Patent, col. 204:63-67). This structure is designed to provide therapeutic activity against the CaSR. Claim 11 specifically claims a method of using this conjugate to treat secondary hyperparathyroidism ('932 Patent, col. 206:17-25).
  • Technical Importance: By defining the active agent as a specific type of peptide conjugate, the patent provided a structural framework for a class of compounds with PTH-lowering activity (Compl. ¶22).

Key Claims at a Glance

  • Asserted Independent Claims: 1, 11
  • Claim 1 Elements:
    • A conjugate, comprising a peptide and a conjugating group,
    • wherein the peptide comprises the amino acid sequence carrrar (SEQ ID NO:2), and
    • wherein the peptide is linked to the conjugating group by a disulfide bond.
  • Claim 11 Elements:
    • A method of treating secondary hyperparathyroidism (SHPT) in a subject,
    • comprising administering to the subject a therapeutically effective amount of a conjugate,
    • wherein the conjugate comprises a peptide and a conjugating group,
    • wherein the peptide comprises the amino acid sequence carrrar (SEQ ID NO:2), and
    • wherein the peptide is linked to the conjugating group by a disulfide bond.

Multi-Patent Capsules

U.S. Patent No. 9,278,995 - "Therapeutic Agents for Reducing Parathyroid Hormone Levels"

  • Technology Synopsis: This patent claims a compound defined by a specific chemical formula (X₁-X₂-X₃-X₄-X₅-X₆-X₇) representing a peptide sequence with defined amino acid types at each position, linked to a conjugating group via a disulfide bond ('995 Patent, Abstract; Compl. ¶82). The invention provides specific peptide structures with PTH-lowering activity.
  • Asserted Claims: Claim 1 is asserted (Compl. ¶83).
  • Accused Features: The complaint alleges that etelcalcetide, the active ingredient in MSN's product, comprises a peptide that has the amino acid sequence defined by the claimed formula (Compl. ¶83).

U.S. Patent No. 9,701,712 - "Therapeutic Agents for Reducing Parathyroid Hormone Levels"

  • Technology Synopsis: This patent claims a "pharmaceutically acceptable salt" of the peptide Ac-c(C)arrrar-NH₂ (etelcalcetide) ('712 Patent, Abstract; Compl. ¶96). It also claims a method of treating secondary hyperparathyroidism by administering this salt. The invention protects salt forms of the active ingredient, which are often used in pharmaceutical formulations.
  • Asserted Claims: Claims 8 and 15 are asserted (Compl. ¶¶96-98).
  • Accused Features: The complaint alleges that MSN's product contains etelcalcetide hydrochloride, which is a pharmaceutically acceptable salt of etelcalcetide, and will be used in a method of treating secondary hyperparathyroidism (Compl. ¶98).

U.S. Patent No. 9,820,938 - "Stable Liquid Formulation of AMG 416 (Etelcalcetide)"

  • Technology Synopsis: This patent addresses the technical challenge of peptide instability in aqueous solutions ('938 Patent, col. 1:53-57). The invention is a stable liquid pharmaceutical formulation containing etelcalcetide (also referred to as AMG 416) in an aqueous solution with a specific pH range of 2.0 to 5.0, which is claimed to provide improved stability ('938 Patent, Abstract; Compl. ¶112).
  • Asserted Claims: Claim 1 is asserted (Compl. ¶113).
  • Accused Features: The complaint alleges that MSN's product is a pharmaceutical formulation comprising etelcalcetide in an aqueous solution with a pH between 2.0 and 5.0 (Compl. ¶¶48, 113).

U.S. Patent No. 10,344,765 - "Stable Liquid Formulation of AMG 416 (Etelcalcetide)"

  • Technology Synopsis: This patent is directed to a stable liquid formulation of etelcalcetide hydrochloride in an aqueous solution ('765 Patent, Abstract). Similar to the '938 patent, this invention solves the problem of peptide instability by claiming a specific formulation, here specifying the hydrochloride salt form of the peptide within a pH range of 2.0 to 5.0 ('765 Patent, col. 28:1-3; Compl. ¶126).
  • Asserted Claims: Claim 1 is asserted (Compl. ¶127).
  • Accused Features: The complaint alleges that MSN's product is a pharmaceutical formulation containing etelcalcetide hydrochloride in an aqueous solution with a pH between 2.0 and 5.0 (Compl. ¶¶126-127).

III. The Accused Instrumentality

  • Product Identification: Defendant MSN’s Proposed Abbreviated New Drug Application (ANDA) Product, a generic version of Parsabiv® (etelcalcetide) for intravenous injection (Compl. ¶1).
  • Functionality and Market Context:
    • The accused product is a pharmaceutical formulation containing etelcalcetide as the active ingredient (Compl. ¶48). Etelcalcetide is a synthetic peptide that acts as a calcium-sensing receptor agonist, which decreases parathyroid hormone secretion (Compl. ¶22).
    • The proposed product is an aqueous solution formulated at a pH between 2.0 and 5.0 (Compl. ¶48). It is intended for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis, the same indication as Parsabiv® (Compl. ¶1).
    • The complaint alleges that MSN's ANDA relies on the FDA's prior finding of safety and effectiveness for Parsabiv® and seeks to demonstrate bioequivalence (Compl. ¶49).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'880 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound comprising Ac-c(C)arrrar-NH₂ (SEQ ID NO:3) MSN's Proposed ANDA Product contains etelcalcetide, which is the compound Ac-c(C)arrrar-NH₂ (SEQ ID NO:3). ¶52, ¶53 col. 202:44-46

'932 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A conjugate, comprising a peptide and a conjugating group, MSN's product contains etelcalcetide, which is alleged to be a conjugate comprising a peptide and a conjugating group. ¶66, ¶68 col. 204:63-64
wherein the peptide comprises the amino acid sequence carrrar (SEQ ID NO:2), The peptide component of etelcalcetide allegedly comprises the specified amino acid sequence. ¶66, ¶68 col. 204:64-65
and wherein the peptide is linked to the conjugating group by a disulfide bond. The peptide in etelcalcetide is allegedly linked to the conjugating group by a disulfide bond. ¶66, ¶68 col. 204:66-67
  • Identified Points of Contention:
    • Scope Questions: In this ANDA context, where the accused product is designed to be a generic copy, infringement is often a direct consequence of the product's chemical identity and formulation. The primary disputes may therefore lie in validity rather than infringement. However, based on the pleadings, a question for the court could be whether minor variations in the defendant's manufacturing process result in a final product that falls outside the literal scope of the asserted claims.
    • Technical Questions: The complaint's allegations for infringement of the compound patents ('880, '932, '995, '712) appear to rest on the assertion that MSN's active ingredient is etelcalcetide or a salt thereof (Compl. ¶¶53, 68, 83, 98). The central technical question will be the chemical and structural identity of the active pharmaceutical ingredient in MSN's Proposed ANDA Product. For the formulation patents ('938, '765), the key technical question is whether MSN's formulation has a pH within the claimed 2.0 to 5.0 range (Compl. ¶¶113, 127).

V. Key Claim Terms for Construction

  • For the '880 Patent:

    • The Term: "a compound comprising Ac-c(C)arrrar-NH₂"
    • Context and Importance: This term defines the entire scope of the independent claim. The dispute will hinge on whether MSN's active ingredient is correctly identified as this specific chemical structure. Practitioners may focus on whether "comprising" allows for the presence of other components or impurities without defeating the claim, a standard question in chemical patent litigation.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the open-ended term "comprising" is standard patent language that typically means the claimed subject matter must include the recited elements but may also include other, unrecited elements.
      • Evidence for a Narrower Interpretation: The specification repeatedly and specifically identifies the compound of SEQ ID NO:3 as the invention, which could suggest that the claim is directed to that precise molecule, potentially limiting the scope of "comprising" in the context of the overall disclosure ('880 Patent, col. 26:25-26).

  • For the '932 Patent:

    • The Term: "conjugate"
    • Context and Importance: The definition of "conjugate" is critical to establishing the claimed structure. The infringement theory depends on etelcalcetide being understood as a "conjugate" composed of a "peptide" and a "conjugating group" linked by a disulfide bond.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent does not appear to provide an explicit, limiting definition of "conjugate," which may support giving the term its plain and ordinary meaning as understood by a person of ordinary skill in the art—a compound formed by the joining of two or more molecules.
      • Evidence for a Narrower Interpretation: The specification describes the structure as a first contiguous sequence of amino acids (the peptide) linked to a second contiguous sequence (the conjugating group), where the second sequence may facilitate transport across a cell membrane ('932 Patent, col. 4:58-63). A defendant might argue that "conjugate" requires two functionally distinct moieties, and that etelcalcetide should be viewed as a single, integrated peptide molecule rather than a "conjugate" of separate parts.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for the method claims. Inducement is alleged based on the grounds that MSN's proposed product labeling will instruct healthcare providers to administer the product in an infringing manner (Compl. ¶77). Contributory infringement is alleged on the basis that MSN's product is especially made for use in an infringing manner and is not suitable for substantial non-infringing use (Compl. ¶78).
  • Willful Infringement: While the complaint does not contain an explicit count for "willful infringement," it lays the groundwork for such a claim. It alleges that MSN had knowledge of the asserted patents at least because they are listed in the FDA’s Orange Book for Parsabiv® (Compl. ¶¶61, 76, 91, 106, 121, 135). The complaint further alleges that MSN has "no reasonable basis" to believe its product would not infringe (Compl. ¶¶57, 72, 87, 102, 117, 131). These allegations of pre-suit knowledge and a lack of a reasonable non-infringement basis could be used to support a future claim for willfulness.

VII. Analyst’s Conclusion: Key Questions for the Case

This ANDA litigation will likely center on the validity of the asserted patents, but based on the infringement allegations in the complaint, the following key questions are presented for the court:

  • A primary issue will be one of chemical identity: does the active pharmaceutical ingredient in MSN's proposed generic product meet the specific structural limitations of the asserted compound claims, including the exact amino acid sequence and conjugate structure?
  • A second issue will be one of formulation parameters: does MSN's proposed product, as described in its ANDA, constitute a liquid formulation with a pH that falls within the specific ranges recited in the later-issued formulation patents?
  • A third evidentiary question will be one of intent for indirect infringement: does MSN's proposed product label provide sufficient instruction and encouragement to healthcare providers to perform the patented methods of treatment, thereby establishing the specific intent required for induced infringement?