Quinazoline Derivatives for the Treatment of Cancer Diseases: A Detailed Analysis of US Patent 9,539,258
Introduction
The United States Patent 9,539,258, issued on January 10, 2017, is a significant patent in the field of oncology, particularly focusing on the use of quinazoline derivatives for the treatment of various cancer diseases. This patent, assigned to Boehringer Ingelheim International GmbH, outlines the therapeutic applications and chemical formulations of these quinazoline compounds.
Patent Overview
Inventors and Assignees
The patent was invented by Flavio Solca, Andree Amelsberg, Jacobus C. A. van Meel, Anke Baum, and Gerd Stehle, and is assigned to Boehringer Ingelheim International GmbH[5].
Patent Claims
The patent claims revolve around the use of quinazolines of a specific formula (I) for the treatment of cancer. These claims are detailed and specify the structural elements of the quinazoline derivatives, including the groups R_a to R_d, which have particular meanings as defined in the claims[1].
Scope of the Patent
Diseases Covered
The patent encompasses a broad range of cancer diseases, including:
- Hematological Neoplasias: This includes acute or chronic leukemias of myeloid, erythroid, or lymphatic origin, myelodysplastic syndromes (MDS), and myeloproliferative syndromes (MPS) such as chronic myelogeneous leukemia, osteomyelofibrosis, polycythemia vera, or essential thrombocythemia[1].
- Lymphomas: The patent covers various types of lymphomas.
- Mixed Tumors and Undifferentiated Tumors: This includes adenosquamous carcinomas, mixed mesodermal tumors, carcinosarcomas, teratocarcinomas, carcinomas of unknown primary (CUP), metastases of unknown primary (MUP), and other undifferentiated tumors[1].
Specific Mutations
The patent also specifies the use of these quinazoline derivatives for the treatment of cancers with specific genetic mutations, such as EGFR mutations in the tyrosine kinase domain of the EGF receptor and/or tumors harboring activating HER2 mutations[1].
Method of Treatment
Administration
The method of treatment involves the administration of a therapeutically effective amount of the quinazoline compound, which can be in various forms including tautomers, racemates, enantiomers, diastereomers, and mixtures thereof. The compound can also be administered as pharmacologically acceptable acid addition salts, solvates, hydrates, polymorphs, or physiologically functional derivatives. The administration routes include oral, enteric, transdermal, intravenous, peritoneal, or by injection, with oral administration being preferred[1].
Patent Landscape
Expiration Dates
The patent is set to expire on November 9, 2026. This expiration date is crucial for understanding the timeline for potential generic versions of the drug to enter the market[5].
Related Patents
Other related patents, such as U.S. Patent 8,545,884 and U.S. Patent 10,004,743, also cover aspects of the same active substance (BIBW 2992, known as Afatinib) but focus on different formulations and manufacturing processes. These patents have expiration dates ranging from 2026 to 2030, which affects the overall patent landscape for Afatinib and related compounds[2][5].
Litigation and Regulatory Aspects
FDA Approvals and Generic Versions
The FDA has not approved any generic versions of Gilotrif (Afatinib), which is closely related to the compounds described in this patent. Litigation and regulatory hurdles, including paragraph IV certifications and patent infringement lawsuits, have delayed the approval of generic versions[2][5].
Patent Infringement and Exclusivity
The patent landscape is further complicated by litigation over patent infringement. For instance, Sun Pharmaceutical Industries Limited has faced litigation over the '586 patent, which is part of the broader patent portfolio protecting Afatinib. These legal battles can delay the entry of generic drugs into the market until the patents expire or are ruled invalid or not infringed[2].
Impact on Innovation and Market
Patent Scope and Quality
The scope and clarity of patent claims are critical for innovation. Broad or unclear claims can lead to increased litigation costs and diminished incentives for innovation. The examination process for this patent, like many others, likely involved narrowing the scope of the claims to ensure clarity and validity[3].
Market Domination
The exclusive rights granted by this patent allow Boehringer Ingelheim to dominate the market for these specific quinazoline derivatives until the patent expires. This exclusivity period is crucial for the company to recoup its investment in research and development.
Key Takeaways
- Broad Therapeutic Applications: The patent covers a wide range of cancer diseases, including hematological neoplasias, lymphomas, and mixed or undifferentiated tumors.
- Specific Genetic Mutations: The treatment is particularly effective for cancers with EGFR or HER2 mutations.
- Multiple Administration Routes: The compound can be administered through various routes, with oral administration being preferred.
- Patent Expiration: The patent is set to expire on November 9, 2026.
- Regulatory and Litigation Hurdles: The approval of generic versions is delayed due to ongoing litigation and regulatory issues.
FAQs
What is the primary focus of US Patent 9,539,258?
The primary focus of US Patent 9,539,258 is the use of quinazoline derivatives for the treatment of various cancer diseases.
Which types of cancer are covered by this patent?
The patent covers hematological neoplasias, lymphomas, mixed tumors, undifferentiated tumors, and other specific types of cancers, including those with EGFR or HER2 mutations.
How are the quinazoline derivatives administered according to the patent?
The compounds can be administered orally, enterically, transdermally, intravenously, peritoneally, or by injection, with oral administration being preferred.
When is the patent set to expire?
The patent is set to expire on November 9, 2026.
Are there any generic versions of the drug approved by the FDA?
No, there are currently no therapeutically equivalent generic versions of Gilotrif (Afatinib) approved by the FDA.
What are the implications of ongoing litigation on the approval of generic versions?
Ongoing litigation over patent infringement has delayed the approval of generic versions until the patents expire or are ruled invalid or not infringed.
Sources
- US9539258B2 - Quinazoline derivatives for the treatment of cancer diseases - Google Patents
- Afatinib Tablets - FDA
- Patent Claims and Patent Scope - Hoover Institution
- United States Court of Appeals for the Federal Circuit - CAFC
- Generic Gilotrif Availability - Drugs.com