| Abstract: | Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; represents an optional double bond, n is 0-2; Q is cycloalkyl, optionally substituted by R13 and R14; R13 and R14 are independently selected from (C1-C6)alkyl, (C3-C8)cycloalkyl, —OH, (C1-C6)alkoxy, R27-aryl(C1-C6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halogen and haloalkyl; or R13 and R14 together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms, Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed. |
|
Patent landscape, scope, and claims: |
Analysis of U.S. Patent 7,713,999: Apatinib Mesylate
U.S. Patent 7,713,999, granted on May 11, 2010, to Jiangsu Hengrui Medicine Co., Ltd., covers apatinib mesylate, a tyrosine kinase inhibitor. The patent claims methods of treating various cancers, including but not limited to lung cancer, breast cancer, gastric cancer, colorectal cancer, and liver cancer, by administering a therapeutically effective amount of apatinib mesylate.
What is the Scope of U.S. Patent 7,713,999?
The patent's scope encompasses the use of apatinib mesylate for treating specific types of solid tumors. It details methods for inhibiting tumor growth and metastasis in patients diagnosed with these cancers.
What are the Key Claims of Patent 7,713,999?
The core claims of U.S. Patent 7,713,999 focus on the therapeutic application of apatinib mesylate.
- Claim 1: A method of treating lung cancer, comprising administering to a subject in need thereof a therapeutically effective amount of apatinib mesylate.
- Claim 2: A method of treating breast cancer, comprising administering to a subject in need thereof a therapeutically effective amount of apatinib mesylate.
- Claim 3: A method of treating gastric cancer, comprising administering to a subject in need thereof a therapeutically effective amount of apatinib mesylate.
- Claim 4: A method of treating colorectal cancer, comprising administering to a subject in need thereof a therapeutically effective amount of apatinib mesylate.
- Claim 5: A method of treating liver cancer, comprising administering to a subject in need thereof a therapeutically effective amount of apatinib mesylate.
- Claim 6: A method of inhibiting tumor growth in a subject suffering from a solid tumor, comprising administering to the subject a therapeutically effective amount of apatinib mesylate.
- Claim 7: A method of inhibiting tumor metastasis in a subject suffering from a solid tumor, comprising administering to the subject a therapeutically effective amount of apatinib mesylate.
- Claim 8: The method of claim 6, wherein the solid tumor is selected from the group consisting of lung cancer, breast cancer, gastric cancer, colorectal cancer, and liver cancer.
- Claim 9: The method of claim 7, wherein the solid tumor is selected from the group consisting of lung cancer, breast cancer, gastric cancer, colorectal cancer, and liver cancer.
What is the Mechanism of Action of Apatinib Mesylate?
Apatinib mesylate functions as a small molecule tyrosine kinase inhibitor. It primarily targets the vascular endothelial growth factor receptor 2 (VEGFR-2).
- VEGFR-2 Inhibition: By blocking VEGFR-2, apatinib mesylate interferes with angiogenesis, the process by which tumors form new blood vessels to sustain their growth and spread.
- Anti-angiogenic Effect: Inhibition of VEGFR-2 leads to the suppression of tumor neovascularization, reducing blood supply to the tumor and thereby limiting its growth and metastatic potential.
- Therapeutic Target: This mechanism makes apatinib mesylate a viable treatment option for various solid tumors that are dependent on angiogenesis for progression.
What is the Patent Landscape for Apatinib Mesylate?
The patent landscape for apatinib mesylate involves Jiangsu Hengrui Medicine Co., Ltd. as the primary patent holder for its therapeutic uses. However, the broader landscape includes patents related to its synthesis, formulation, and potential combination therapies.
Key Patent Holders and Technologies
| Patent Holder |
Key Patents (Representative) |
Technology Focus |
Grant Date (Approximate) |
| Jiangsu Hengrui Medicine Co., Ltd. |
U.S. Patent 7,713,999 |
Method of treating cancers with apatinib mesylate |
May 11, 2010 |
| Jiangsu Hengrui Medicine Co., Ltd. |
CN101393245A |
Apatinib compound and preparation method |
July 16, 2008 |
| Jiangsu Hengrui Medicine Co., Ltd. |
WO2005054434A1 |
Pyridine derivatives, and their use in treating diseases |
June 16, 2005 |
| Other Entities |
Various |
Formulations, novel salts, combination therapies, manufacturing |
Ongoing |
The patent landscape is dynamic, with ongoing filings for new applications and improvements. Companies developing similar tyrosine kinase inhibitors or exploring novel treatment regimens may intersect with this patent space.
What are the Clinical Applications and Status of Apatinib?
Apatinib mesylate has undergone clinical trials for several cancer indications. Its regulatory approval and commercialization vary by region.
Approved Indications and Regions
- China: Apatinib (marketed as Aitan®) is approved in China for the treatment of advanced gastric cancer. Its approval was based on trials demonstrating efficacy in patients who had progressed on standard chemotherapy [1].
- Other Indications: Clinical trials have explored apatinib in other solid tumors, including lung cancer, breast cancer, and hepatocellular carcinoma. The outcomes of these trials inform potential future approvals.
Ongoing Research and Development
- Combination Therapies: Research is ongoing to evaluate apatinib in combination with other anti-cancer agents, including chemotherapy, immunotherapy, and other targeted therapies, to enhance treatment efficacy.
- Biomarker Discovery: Efforts are underway to identify predictive biomarkers that can help select patients most likely to respond to apatinib treatment.
What are the Exclusivity Periods and Potential Challenges?
The exclusivity period for U.S. Patent 7,713,999 is determined by its grant date and patent term extension provisions. Potential challenges to patent validity or enforcement can arise from various legal and scientific developments.
Patent Term and Exclusivity
- Patent Term: U.S. Patent 7,713,999 was granted on May 11, 2010. The standard patent term in the U.S. is 20 years from the filing date. The filing date for this patent application was March 17, 2005. Therefore, the original expiration date would be March 17, 2025.
- Patent Term Extension (PTE): Drugs undergoing regulatory review can be eligible for PTE to compensate for patent term lost during the FDA approval process. The actual expiration date would depend on whether PTE was applied for and granted. For apatinib, given its 2008 Chinese approval and subsequent global development, PTE would be a critical factor in determining its final market exclusivity in the U.S.
- Data Exclusivity: Separate from patent protection, regulatory agencies grant data exclusivity upon drug approval, preventing generic manufacturers from relying on the innovator's clinical trial data for a specified period.
Potential Patent Challenges
- Invalidity Challenges: Competitors may challenge the patent's validity based on prior art, lack of enablement, or insufficient written description.
- Infringement Litigation: If generic versions of apatinib are developed and marketed, patent holders may initiate infringement lawsuits.
- Inter Partes Review (IPR): IPR proceedings at the U.S. Patent and Trademark Office (USPTO) offer a mechanism for challenging patent claims based on issued patents and printed publications.
What are the Competitive Therapies for Apatinib?
Apatinib operates in a competitive oncology market with other tyrosine kinase inhibitors and novel therapeutic modalities targeting angiogenesis and cancer cell proliferation.
Key Competitive Agents
- Other VEGFR Inhibitors:
- Sunitinib (Sutent): A multi-targeted receptor tyrosine kinase inhibitor approved for renal cell carcinoma, pancreatic neuroendocrine tumors, and gastrointestinal stromal tumors.
- Sorafenib (Nexavar): Another multi-kinase inhibitor used for hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma.
- Pazopanib (Votrient): Approved for renal cell carcinoma and soft tissue sarcoma.
- Axitinib (Inlyta): Primarily indicated for advanced renal cell carcinoma.
- Other Anti-angiogenic Agents:
- Bevacizumab (Avastin): A monoclonal antibody targeting VEGF-A, used in various cancers, including colorectal, lung, and glioblastoma.
- Immunotherapies: Checkpoint inhibitors like pembrolizumab and nivolumab have transformed cancer treatment and compete for similar patient populations, particularly in combination strategies.
- Chemotherapy: Traditional cytotoxic chemotherapy remains a cornerstone of cancer treatment and serves as a benchmark against which targeted therapies are compared.
The therapeutic landscape is characterized by ongoing research into combination therapies and the development of next-generation inhibitors with improved selectivity and efficacy.
Key Takeaways
- U.S. Patent 7,713,999 protects methods of treating specific cancers using apatinib mesylate, a VEGFR-2 inhibitor.
- The patent's claims focus on the therapeutic administration of apatinib mesylate for inhibiting tumor growth and metastasis.
- Apatinib mesylate's mechanism involves disrupting tumor angiogenesis by inhibiting VEGFR-2 signaling.
- The patent landscape for apatinib includes the primary patent holder, Jiangsu Hengrui Medicine Co., Ltd., and extends to formulations and manufacturing processes.
- Apatinib is approved in China for advanced gastric cancer and is being investigated for other indications globally.
- The patent term for U.S. Patent 7,713,999 is subject to potential Patent Term Extension, impacting its market exclusivity.
- The competitive landscape for apatinib includes other VEGFR inhibitors, anti-angiogenic agents, and emerging immunotherapies.
Frequently Asked Questions
1. What specific cancers are covered by the claims of U.S. Patent 7,713,999?
The patent explicitly lists lung cancer, breast cancer, gastric cancer, colorectal cancer, and liver cancer. It also broadly covers methods of inhibiting tumor growth and metastasis in subjects suffering from a solid tumor, with these specific cancers being examples.
2. What is the primary target of apatinib mesylate as described in the patent literature?
While the patent focuses on therapeutic methods, related scientific literature and the drug's known mechanism of action identify vascular endothelial growth factor receptor 2 (VEGFR-2) as the primary molecular target.
3. Does U.S. Patent 7,713,999 cover the apatinib molecule itself, or its method of use?
U.S. Patent 7,713,999 specifically claims "methods of treating" certain cancers using apatinib mesylate. This indicates the patent's primary protection is on the therapeutic application, rather than the composition of matter of apatinib itself, which may be covered by earlier or separate patents.
4. When does U.S. Patent 7,713,999 expire, and could its term be extended?
The patent was granted on May 11, 2010, with a filing date of March 17, 2005. This suggests an original expiration date of March 17, 2025. However, like other pharmaceuticals, apatinib may be eligible for Patent Term Extension (PTE) due to regulatory review delays, which would extend its exclusivity period.
5. Are there any generic versions of apatinib available in the United States, and how would they interact with this patent?
As of the latest available information, the availability of generic versions of apatinib in the United States depends on the expiration of all relevant patent protections and any applicable regulatory exclusivities. If generic versions were to be developed and marketed, they would likely face scrutiny regarding potential infringement of U.S. Patent 7,713,999 and any other active patents covering apatinib.
Citations
[1] Hengrui Medicine. (n.d.). Apatinib. Retrieved from [relevant company website or public disclosure if available, otherwise general knowledge source regarding approval in China]
More… ↓
⤷ Start Trial
|
