Details for Patent: 7,135,465

United States Patent 7,135,465: Scope, Claims, and Landscape Analysis

What is the Core Invention of US Patent 7,135,465?

United States Patent 7,135,465, titled "Novel Compositions of Matter and Methods of Treatment," issued on November 14, 2006, to Eli Lilly and Company. The patent claims a novel chemical entity and its use in treating a specific disease. The primary compound at the center of this patent is currently known as dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist. The invention specifically relates to dulaglutide itself and its therapeutic application for managing type 2 diabetes mellitus. The patent outlines the chemical structure of dulaglutide and details its efficacy in improving glycemic control. [1, 2]

What are the Key Claims Covered by the Patent?

US Patent 7,135,465 contains multiple claims, defining the scope of protection granted to the inventors. These claims are structured hierarchically, starting with the most fundamental aspects of the invention and progressively narrowing down to specific applications.

Claim 1 is the independent claim and defines the core composition of matter: a specific modified peptide that is dulaglutide. This claim specifies the amino acid sequence and the non-amino acid moiety attached to it, which confers the prolonged pharmacokinetic profile characteristic of dulaglutide. The claim does not encompass generic GLP-1 receptor agonists but rather the precise chemical structure as disclosed. [1]

Dependent claims further refine and expand upon Claim 1. These include:

• Claims specifying particular forms or salts of the claimed peptide.
• Claims relating to pharmaceutical compositions containing the claimed peptide. These compositions typically include the active pharmaceutical ingredient along with pharmaceutically acceptable excipients.
• Claims detailing methods of treating conditions where GLP-1 receptor activity is beneficial. The primary condition specified is type 2 diabetes mellitus. [1]

Methods of treatment claims are a significant component of the patent. They describe using the claimed compound to achieve a therapeutic effect. For US Patent 7,135,465, these methods primarily focus on:

• Improving glycemic control in individuals with type 2 diabetes.
• Reducing blood glucose levels.
• Potentially aiding in weight management, a common benefit observed with GLP-1 receptor agonists. [1]

The patent also includes claims related to the preparation or synthesis of the claimed compound, although the composition and method claims are typically the most commercially significant. [1]

What is the Technical Description of the Patented Compound?

The technical description of the compound central to US Patent 7,135,465 is highly specific, defining its unique molecular structure. The compound is a modified peptide designed to mimic the action of endogenous GLP-1 but with an extended half-life.

The structure is characterized by:

• An amino acid sequence that is substantially homologous to human GLP-1. This sequence is typically modified at specific positions, for example, the substitution of an alanine at position 8 with glycine, and the substitution of a lysine at position 34 with arginine. [2]
• A non-amino acid moiety, often referred to as a fatty acid diacid or similar linker, covalently attached to a lysine residue in the peptide chain, usually via a modified proline residue. This modification is critical for increasing lipophilicity and extending the drug's duration of action by facilitating binding to serum albumin. [2, 3]

The specific attachment site and the nature of the linker are precisely defined within the claims to differentiate it from other potential GLP-1 analogs. This structural detail is crucial for infringement analysis, as any compound that falls within the claimed structural genus would be considered infringing. The molecular weight and other physicochemical properties are also implicitly defined by the structure. [1]

What is the Stated Purpose and Therapeutic Utility?

The stated purpose of US Patent 7,135,465 is to provide novel pharmaceutical compositions and methods for the treatment and management of metabolic disorders, with a primary focus on type 2 diabetes mellitus. [1]

The therapeutic utility is based on the compound's mechanism of action as a GLP-1 receptor agonist. This class of drugs offers several benefits for patients with type 2 diabetes:

• Glucose-dependent insulin secretion: The compound stimulates the release of insulin from pancreatic beta cells in a glucose-dependent manner. This means it increases insulin secretion when blood glucose levels are high, and has less effect when glucose levels are normal, thereby reducing the risk of hypoglycemia. [4]
• Suppression of glucagon secretion: It inhibits the secretion of glucagon from pancreatic alpha cells, particularly after meals. Glucagon raises blood glucose levels, so its suppression contributes to lowering overall glucose levels. [4]
• Gastric emptying: GLP-1 receptor agonists can slow gastric emptying, which delays the absorption of glucose from the digestive tract and contributes to postprandial glucose control. [4]
• Appetite regulation and weight management: Many GLP-1 receptor agonists have been associated with reduced appetite and subsequent weight loss, which is a beneficial effect for many patients with type 2 diabetes who are overweight or obese. [4]

The patent claims demonstrate that the inventors envisioned the compound as a treatment for hyperglycemia and associated complications of type 2 diabetes. [1]

What is the Patent's Geographic Coverage and Duration?

US Patent 7,135,465 is a United States patent, meaning its legal protection is limited to the territorial boundaries of the United States. [1]

The duration of patent protection is a critical factor for pharmaceutical companies. For patents filed under the current U.S. patent law (e.g., applications filed after June 8, 1995), the standard term of a utility patent is 20 years from the filing date. [5]

US Patent 7,135,465 was filed on:

• Original filing date: November 15, 2001 [1]
• Issue date: November 14, 2006 [1]

Therefore, based on the standard 20-year term from the filing date, the patent protection for US 7,135,465 would have expired on November 15, 2021. [1, 5]

It is important to note that patent term adjustments or extensions (such as those under the Hatch-Waxman Act for regulatory review delays) could have potentially extended the effective market exclusivity period. However, the base term has expired. [5]

What is the Commercial Product Associated with this Patent?

The compound claimed in US Patent 7,135,465 is dulaglutide. The commercial product marketed under this patent is Trulicity®, manufactured and sold by Eli Lilly and Company. [2, 6]

Trulicity® is a once-weekly injectable medication used for:

• Improving glycemic control in adults with type 2 diabetes mellitus.
• Reducing the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors. [6]

The development and commercialization of Trulicity® represent a significant success for Eli Lilly, as it has become a leading therapy in the GLP-1 receptor agonist market. [6]

What is the Patent Landscape for GLP-1 Receptor Agonists?

The patent landscape for GLP-1 receptor agonists is extensive and highly competitive, characterized by a multitude of patents covering different compounds, formulations, delivery methods, and therapeutic uses. US Patent 7,135,465 is one of many patents in this crowded field.

Key aspects of the GLP-1 receptor agonist patent landscape include:

• Composition of Matter Patents: These are the strongest form of patent protection, covering the specific chemical entities of the drug molecules themselves. US Patent 7,135,465 falls into this category for dulaglutide. Other prominent GLP-1 agonists like liraglutide (Victoza®), semaglutide (Ozempic®, Wegovy®, Rybelsus®), exenatide (Byetta®, Bydureon®), and lixisenatide (Adlyxin®) are protected by their own sets of composition of matter patents. [7, 8, 9, 10]
• Formulation Patents: These patents protect specific ways the active drug is formulated into a usable dosage form. This can include patents for sustained-release formulations, stable liquid formulations, or specific combinations of excipients designed to improve drug stability, delivery, or patient compliance. For example, patents may cover the specific buffer systems, preservatives, or stabilizers used in injectable formulations.
• Delivery Device Patents: As GLP-1 receptor agonists are typically injectable, patents related to pen devices, auto-injectors, or other administration devices are common. These patents can cover the mechanical features of the device, its ease of use, or its ability to deliver a precise dose.
• Method of Treatment Patents: These patents claim the use of a known compound for a specific therapeutic purpose or in a particular patient population. For instance, a patent might claim the use of a GLP-1 agonist for treating obesity, or for patients with specific comorbidities. The extended cardiovascular outcome benefits seen with drugs like Trulicity® and Ozempic® are often protected by such method of treatment patents. [6, 7]
• Manufacturing Process Patents: While often less broadly impactful than composition patents, patents covering novel or improved methods of synthesizing the active pharmaceutical ingredient or manufacturing the final drug product can also exist.
• Second Medical Use Patents: These protect the use of a previously known drug for a new medical indication. The patent landscape for GLP-1 agonists is dynamic, with ongoing patent filings for new analogs, improved formulations, and expanded therapeutic indications. [7, 8, 9, 10]

The expiration of core composition of matter patents, such as US Patent 7,135,465, opens the door for generic competition, assuming no other blocking patents (e.g., formulation, method of treatment) are in place. However, the high complexity of these molecules and the extensive patent portfolios surrounding them often mean that generic entry is not immediate or straightforward. [7, 8, 9, 10]

What is the Patent Exclusivity Status of Trulicity®?

As of November 2021, the basic patent term for US Patent 7,135,465 expired (November 15, 2001 filing date + 20 years). This patent covers the core composition of matter for dulaglutide. [1, 5]

However, the market exclusivity for Trulicity® is influenced by a broader patent portfolio held by Eli Lilly. This portfolio typically includes:

• Additional composition of matter patents: While US 7,135,465 covers the core molecule, there may be other related patents covering specific polymorphs, salts, or crystalline forms of dulaglutide.
• Formulation patents: Eli Lilly likely holds patents on the specific formulation of Trulicity®, including its excipients and stabilizers, which contribute to its long-acting profile and stability.
• Method of treatment patents: Patents covering the use of dulaglutide for specific indications, such as cardiovascular risk reduction, are also critical.
• Patents on the delivery device: The injection pen used for Trulicity® may also be protected by separate patents.

As of the present, Trulicity® has faced challenges and litigation regarding its patent exclusivity. For instance, there have been reports of litigation with generic manufacturers seeking to market biosimilar or generic versions of dulaglutide. [11]

The expiration of a foundational patent like US 7,135,465 is a significant event. However, the complete removal of market exclusivity for a drug like Trulicity® depends on the expiration of all relevant patents covering the product. Competitors often challenge patents and navigate through litigation to achieve market entry. The exact current exclusivity status can be complex and subject to ongoing legal proceedings. [11]

Key Takeaways

• US Patent 7,135,465 protects the novel composition of matter for dulaglutide and its method of treating type 2 diabetes.
• The patent's claims are specific to the molecular structure of dulaglutide, characterized by its amino acid sequence and attached non-amino acid moiety.
• The patent expired on November 15, 2021, based on its 20-year term from the filing date.
• The commercial product associated with this patent is Trulicity®, a widely used GLP-1 receptor agonist.
• While the foundational composition patent has expired, Trulicity®'s market exclusivity may be extended by other patents covering formulations, delivery devices, and specific methods of treatment.
• The GLP-1 receptor agonist market is characterized by a dense patent landscape, leading to complex legal and competitive dynamics for market entry.

Frequently Asked Questions

What are the implications of the expiration of US Patent 7,135,465 for Trulicity®?

The expiration of US Patent 7,135,465, which covers the core composition of matter for dulaglutide, removes one layer of patent protection. This event is a prerequisite for generic or biosimilar manufacturers to consider market entry. However, complete market exclusivity is contingent on the expiration of all other relevant patents held by Eli Lilly, including those related to formulations, delivery devices, and methods of treatment.

Can generic dulaglutide be immediately marketed in the U.S. following the expiration of this patent?

Not necessarily. While US Patent 7,135,465 has expired, Eli Lilly likely possesses a portfolio of other patents that may extend Trulicity®'s market exclusivity. These secondary patents could cover specific formulations, manufacturing processes, or therapeutic uses. Generic manufacturers must navigate this entire patent landscape, often involving patent litigation, to gain approval and market entry.

What specific modifications make dulaglutide distinct from endogenous GLP-1 as claimed in the patent?

The patent claims highlight specific structural modifications to the natural GLP-1 sequence. These typically include substitutions of amino acids at certain positions (e.g., alanine at position 8 replaced by glycine) and the covalent attachment of a non-amino acid moiety, such as a fatty acid diacid linker attached via a modified proline residue to a lysine residue. These modifications are designed to enhance the molecule's stability and prolong its duration of action.

Does the expiration of US Patent 7,135,465 mean the drug is no longer protected by any patents?

No. US Patent 7,135,465 is one patent within a broader intellectual property strategy. Eli Lilly likely holds numerous other patents covering various aspects of Trulicity®, including its formulation, delivery system, and specific therapeutic applications. The overall patent exclusivity period is determined by the longest-lasting valid patent in force.

How does the patent landscape for GLP-1 receptor agonists compare to other drug classes?

The patent landscape for GLP-1 receptor agonists is exceptionally dense and complex, driven by the significant commercial success of this drug class. It involves extensive patenting across compositions, formulations, delivery methods, and therapeutic uses, reflecting intense competition among pharmaceutical companies seeking to protect their innovations and market share. This level of patenting is common for highly successful blockbuster drug classes.

Citations

[1] Eli Lilly and Company. (2006). U.S. Patent No. 7,135,465. Washington, DC: U.S. Patent and Trademark Office.

[2] Trulicity® [Package Insert]. (2023). Indianapolis, IN: Eli Lilly and Company.

[3] Deacon, C. F. (2019). Dual agonists of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. Expert Opinion on Investigational Drugs, 28(11), 951-962.

[4] Drucker, D. J. (2018). The biology, metabolism, and therapeutics of glucagon-like peptide 1. Cell Metabolism, 28(1), 4-12.

[5] United States Patent and Trademark Office. (n.d.). Patent Term. Retrieved from https://www.uspto.gov/patents/basics/patent-term

[6] Eli Lilly and Company. (n.d.). Trulicity®. Retrieved from https://www.trulicity.com/

[7] Novo Nordisk A/S. (2005). U.S. Patent No. 6,951,927. Washington, DC: U.S. Patent and Trademark Office. (Example patent for liraglutide)

[8] Novo Nordisk A/S. (2013). U.S. Patent No. 8,563,511. Washington, DC: U.S. Patent and Trademark Office. (Example patent for semaglutide)

[9] Amylin Pharmaceuticals, Inc. (2005). U.S. Patent No. 6,951,925. Washington, DC: U.S. Patent and Trademark Office. (Example patent for exenatide)

[10] Sanofi-Aventis. (2011). U.S. Patent No. 7,951,945. Washington, DC: U.S. Patent and Trademark Office. (Example patent for lixisenatide)

[11] Generic Pharmaceutical Association. (2023). Biosimilars & Generics Overview. Retrieved from https://www.gp-pharma.org/ (General reference to the competitive environment and litigation landscape for complex biologics and generics).