DCT

1:24-cv-09729

Novo Nordisk Inc v. Apotex Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-09729, D.N.J., 10/10/2024
  • Venue Allegations: Venue is alleged to be proper because Defendant Apotex is a foreign corporation not resident in the United States and intends to market, distribute, and sell its product in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) for a generic version of RYBELSUS® tablets infringes ten patents related to the active ingredient semaglutide, its pharmaceutical formulations, and methods of use.
  • Technical Context: The technology concerns oral formulations of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist for improving glycemic control in type 2 diabetes, a class of drugs with significant market presence for diabetes and obesity treatment.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act following Plaintiff's receipt of Defendant's August 29, 2024 notice letter, which contained a Paragraph IV certification asserting that the ten patents-in-suit are invalid and/or not infringed by its ANDA product. The complaint notes that the lead '343 patent has been asserted in other litigations against different defendants.

Case Timeline

Date Event
2005-03-23 '343 Patent Priority Date
2010-12-20 '123, '047, '052, '957 Patents Priority Date
2012-03-06 '343 Patent Issue Date
2012-03-22 '120, '501, '502, '503 Patents Priority Date
2013-05-02 '923 Patent Priority Date
2016-03-08 '123 Patent Issue Date
2018-10-02 '047 Patent Issue Date
2019-05-07 '923 Patent Issue Date
2021-03-02 '120 Patent Issue Date
2021-03-30 '052 Patent Issue Date
2022-07-12 '957 Patent Issue Date
2023-09-19 '501 Patent Issue Date
2023-09-19 '502 Patent Issue Date
2023-09-19 '503 Patent Issue Date
2024-08-29 Apotex sends Paragraph IV Notice Letter
2024-10-10 Complaint Filing Date

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

U.S. Patent No. 8,129,343 - Acylated GLP-1 Compounds (issued 03/06/2012)

The Invention Explained

  • Problem Addressed: Native glucagon-like peptide-1 (GLP-1) has a very short in vivo half-life, requiring frequent injections that can reduce patient compliance (’343 Patent, Background section, not provided; context inferred from invention purpose).
  • The Patented Solution: The invention is a chemically modified GLP-1 analog, semaglutide, where the peptide structure is altered and a fatty acid-based side chain is attached ("acylated") (’343 Patent, col. 29:30-41). This acylation allows the compound to bind to albumin in the bloodstream, significantly extending its half-life and enabling less frequent administration (Compl. ¶12).
  • Technical Importance: The development of long-acting GLP-1 analogs like semaglutide was a significant advance in diabetes treatment, facilitating regimens such as once-weekly injections or, as is the case here, a stable oral formulation.

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶71).
  • Claim 1 recites a single element:
    • A specific chemical compound, defined by its structural formula, which is semaglutide (also identified as N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxy-heptadecanoylamino)butyrylamino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37)).
  • The complaint reserves the right to assert additional claims (Compl. ¶4).

U.S. Patent No. 9,278,123 - Solid Compositions Comprising a GLP-1 Agonist and a Salt of N-(8-(2-Hydroxybenzoyl)Amino)Caprylic Acid (issued 03/08/2016)

The Invention Explained

  • Problem Addressed: The oral bioavailability of GLP-1 compounds is typically very low, preventing effective administration via tablets (’123 Patent, col. 1:41-43).
  • The Patented Solution: The patent describes a solid oral composition that combines a GLP-1 agonist (semaglutide) with a specific absorption enhancer, a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, such as salcaprozate sodium (SNAC) (’123 Patent, col. 2:3-11). This combination is designed to protect the peptide from degradation in the stomach and facilitate its absorption into the bloodstream (’123 Patent, Abstract).
  • Technical Importance: This technology represents a method for converting an injectable peptide drug into a daily oral tablet, a major development for patient convenience and adherence in chronic disease management.

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶93).
  • Claim 1 contains the following essential elements:
    • A solid composition for oral administration
    • comprising semaglutide
    • and 0.8-1.3 mmol of a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid
  • The complaint reserves the right to assert additional claims (Compl. ¶4).

U.S. Patent No. 10,086,047 - Solid Compositions Comprising a GLP-1 Agonist and a Salt of N-(8-(2-Hydroxybenzoyl)Amino)Caprylic Acid (issued 10/02/2018)

  • Technology Synopsis: This patent claims a solid oral composition comprising semaglutide and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC), similar to the ’123 Patent, but further defined by specific functional properties. The claimed composition must have "surface eroding or co-release properties" and a "disintegration time of 7-15 minutes" (’047 Patent, col. 25:10-14).
  • Asserted Claims: At least independent claim 1 (Compl. ¶116).
  • Accused Features: The complaint alleges that Apotex's ANDA Product is a solid composition for oral administration containing semaglutide and SNAC that infringes the patent (Compl. ¶¶ 106-108, 112).

U.S. Patent No. 10,278,923 - Oral Dosing of GLP-1 Compounds (issued 05/07/2019)

  • Technology Synopsis: This patent claims a method for treating diabetes or obesity. The method comprises orally administering a solid dosage form containing a GLP-1 peptide (such as semaglutide) and an enhancer (such as SNAC), where the GLP-1 peptide has a plasma half-life of at least 60 hours. A key limitation is that the ratio between the peptide's plasma half-life (in days) and the dosing interval (in days) must be more than 2:1 (’923 Patent, col. 30:10-21).
  • Asserted Claims: At least independent claim 14 (Compl. ¶144).
  • Accused Features: The complaint alleges that Apotex's proposed product label will instruct patients to take the tablet once daily, a dosing interval which, combined with semaglutide's approximately one-week half-life, meets the claimed ratio and thus induces infringement (Compl. ¶¶ 130-133, 141-142).

Multi-Patent Capsule: U.S. Patent Nos. 10,933,120; 11,759,501; 11,759,502; and 11,759,503

  • Technology Synopsis: These four related patents, all titled "Compositions of GLP-1 Peptides and Preparation Thereof," claim specific granular formulations for a solid dosage pharmaceutical composition. They generally describe compositions made from two distinct types of granules: a first type containing the absorption enhancer (SNAC) but no GLP-1 peptide, and a second type containing the GLP-1 peptide (semaglutide) but no SNAC. The claims specify various parameters, such as the weight percentage of ingredients (e.g., SNAC ≥ 75% in one granule type, filler ≥ 15% in the other) within each granule type (Compl. ¶¶ 42, 51, 54, 57).
  • Asserted Claims: At least claim 1 of each patent (Compl. ¶¶ 166, 233, 256, 277).
  • Accused Features: The complaint alleges on information and belief that Apotex's ANDA Product, by copying RYBELSUS®, will contain the claimed two-granule solid dosage composition (Compl. ¶¶ 162, 229, 251, 273).

Multi-Patent Capsule: U.S. Patent Nos. 10,960,052 and 11,382,957

  • Technology Synopsis: These two related patents, titled "Solid Compositions Comprising a GLP-1 Agonist and a Salt of N-(8-(2-Hydroxybenzoyl)Amino)Caprylic Acid," claim solid oral compositions containing semaglutide, SNAC, and specific excipients. The key limitation in both patents is that the composition must comprise "at least 60% (w/w)" of the SNAC salt (Compl. ¶¶ 45, 48).
  • Asserted Claims: At least claim 1 of each patent (Compl. ¶¶ 189, 211).
  • Accused Features: The complaint alleges on information and belief that Apotex's ANDA Product, by copying RYBELSUS®, will be a solid composition containing semaglutide, SNAC, and excipients that meets the claimed concentration of SNAC (Compl. ¶¶ 185, 207).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Apotex's ANDA Product," a generic version of RYBELSUS® (semaglutide) tablets intended for oral administration in 3 mg, 7 mg, and 14 mg strengths (Compl. ¶14).

Functionality and Market Context

  • The product is a GLP-1 receptor agonist intended as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (Compl. ¶8).
  • The complaint alleges that Apotex's ANDA filing seeks approval to manufacture and sell this product prior to the expiration of the Asserted Patents (Compl. ¶4).
  • It further alleges that the ANDA product refers to and relies upon Novo Nordisk's New Drug Application for RYBELSUS® and will purport to be bioequivalent, containing the same active ingredient (semaglutide) and being administered in the same strengths and dosage form as RYBELSUS® (Compl. ¶¶ 16, 67-69).

IV. Analysis of Infringement Allegations

'343 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound which is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxy-heptadecanoylamino)butyrylamino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37). The complaint alleges that the active ingredient in Apotex's ANDA Product is semaglutide, which is the compound defined by this claim. This is supported by a structural formula provided in the complaint. The complaint's infringement theory is based on the allegation that Apotex's ANDA product is identical in composition to RYBELSUS®. ¶¶ 62, 63, 67-69 col. 67:23-42
  • Identified Points of Contention ('343' Patent):
    • Validity Questions: Given that the claim recites the specific chemical compound semaglutide and the accused product is a generic version of a semaglutide drug, the primary dispute is unlikely to be over non-infringement. Rather, the case will likely turn on Apotex's defenses that the '343' Patent is invalid (e.g., for obviousness or lack of enablement), as asserted in its Paragraph IV certification (Compl. ¶60).
    • Scope Questions: A potential, though less probable, point of contention could be whether the specific form of semaglutide in Apotex's product (e.g., a particular salt or polymorph) falls outside the literal scope of "a compound" as claimed, though this is a difficult argument against a compound claim.

'123 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A solid composition for oral administration Apotex's ANDA Product is described as "semaglutide tablets" for "oral administration" (Compl. ¶14), which is a solid composition for oral administration. ¶14 col. 1:1-2
comprising semaglutide The complaint alleges that the active ingredient in Apotex's ANDA Product is semaglutide, based on its status as a generic version of RYBELSUS®. ¶¶ 85, 89 col. 4:6-11
and 0.8-1.3 mmol of a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid. The complaint alleges that Apotex's ANDA Product contains salcaprozate sodium (SNAC), which is the specified salt, and that the composition is identical to that in RYBELSUS®, which is covered by the claim. ¶¶ 84, 86, 89 col. 10:1-3
  • Identified Points of Contention ('123' Patent):
    • Factual Questions: The central point of contention will be a factual one: does Apotex's ANDA product actually contain the claimed 0.8-1.3 mmol of SNAC? The complaint does not provide specific test data but relies on the allegation that the generic product is identical to RYBELSUS®, which is asserted to be covered by the claim (Compl. ¶¶ 86, 89). The dispute will hinge on discovery and evidence related to the precise formulation of Apotex's product.
    • Scope Questions: It raises the question of whether the term "comprising," which is typically open-ended, could be limited by arguments based on the patent's specification, should Apotex's formulation include additional excipients that it argues materially alter the composition's properties from those disclosed in the patent.

V. Key Claim Terms for Construction

The Term: "surface eroding or co-release properties" (from asserted claim 1 of the '047 Patent)

  • Context and Importance: This term recites a functional property of the claimed composition. Its construction is critical because infringement will depend on whether Apotex's product can be shown to exhibit this specific behavior, which may require objective testing and a clear definition of what constitutes "surface eroding" or "co-release" in this context. Practitioners may focus on this term as it moves the infringement analysis beyond merely identifying ingredients to assessing their functional interaction.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification may describe these properties in general terms, suggesting any composition that dissolves primarily from its surface without breaking apart would meet the limitation (’047 Patent, col. 13:41-45).
    • Evidence for a Narrower Interpretation: The patent links these properties to specific visual observations during a disintegration test and to data from a dissolution test (’047 Patent, col. 13:30-52). A party could argue the term must be limited to compositions that match the specific dissolution profiles or visual characteristics detailed in the patent's examples.

The Term: "ratio between the plasma half-life in days in humans of the GLP-1 peptide and the dosing interval in days of said composition is more than 2:1" (from asserted claim 14 of the '923 Patent)

  • Context and Importance: This term defines a specific pharmacokinetic relationship required by the claimed method of treatment. Its construction is central because infringement depends not on the composition alone, but on how it is administered relative to a biological property (half-life). The dispute may focus on how "plasma half-life in humans" is determined (e.g., from what specific studies, using what statistical methods) and whether the instructions on Apotex's label will direct users to a "dosing interval" that satisfies the claimed mathematical ratio.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes "plasma half-life" in general terms as the time it takes to halve the plasma concentration after administration (’923 Patent, col. 3:38-42). This could support using any standard, accepted measurement of semaglutide's half-life.
    • Evidence for a Narrower Interpretation: The patent provides an example of calculating the ratio and defines the term in the context of a "low clearance GLP-1 peptide" (’923 Patent, col. 5:48-64). A party could argue that the term requires the specific calculation method or context described and cannot be met by simply citing general knowledge of semaglutide's half-life.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges induced infringement of the '923' method patent. The basis for this allegation is that Apotex's ANDA filing includes a proposed label that will copy the RYBELSUS® label, which allegedly "instructs, recommends, encourages, promotes, and/or suggests that physicians, prescribers, and/or patients infringe" by administering the drug according to the claimed method (Compl. ¶141). The complaint also alleges contributory infringement on the basis that the accused product has no substantial non-infringing uses (Compl. ¶143).

Willful Infringement

  • The complaint alleges that Apotex had "actual knowledge" of each asserted patent prior to the filing of the lawsuit, citing Apotex's Paragraph IV notice letter (Compl. ¶¶ 61, 83, 105, 128, etc.). It further alleges that Apotex's detailed statement supporting its non-infringement and invalidity positions is "devoid of an objective good faith basis," which may form the basis for a claim of enhanced damages under 35 U.S.C. § 284 and attorneys' fees under § 285 (Compl. ¶¶ 78, 100, 123, 151, etc.).

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

  • A central issue will be one of validity: Given that the accused product is a generic copy, infringement of at least the compound patent ('343') appears straightforward. Consequently, the case will likely focus on Defendant's ability to prove by clear and convincing evidence that one or more of the ten asserted patents, which cover the compound, specific formulations, and methods of use, are invalid as anticipated or obvious in light of the prior art.
  • A key evidentiary question will be one of factual proof: For the numerous formulation patents, infringement will depend on whether Plaintiff can prove that Defendant's product meets the specific quantitative limitations of the claims (e.g., "0.8-1.3 mmol" of SNAC in the '123' patent; "at least 60% (w/w)" of SNAC in the '052' patent; specific granule compositions in the '120' patent family). The outcome will depend on the evidence regarding the precise composition and manufacturing process of the Apotex ANDA product.
  • A core issue for the method patent ('923') will be one of induced infringement: The dispute will likely center on whether the instructions for use on the Defendant's proposed product label would inevitably lead prescribers and patients to practice the claimed method, specifically by administering a drug with semaglutide's known half-life on a daily schedule that satisfies the claimed mathematical ratio between half-life and dosing interval.