United States Patent 6,432,452: A Comprehensive Analysis of Scope and Claims
Introduction
The United States Patent 6,432,452, titled "Anti-cancer compounds," is a significant patent that outlines the discovery and application of compounds derived from the sap of plants in the genus Euphorbia, particularly Euphorbia peplus, Euphorbia hirta, and Euphorbia drummondii. This patent holds substantial importance in the field of oncology and dermatology.
Background
The patent, filed in 1999 and granted in 2002, is based on the invention of compounds that exhibit anti-cancer properties. These compounds are isolated from the sap of specific Euphorbia species and have shown promising results in inhibiting the growth of various cancer cell lines[1].
Scope of the Patent
Anti-Cancer Compounds
The patent primarily focuses on compounds that can kill or inhibit the growth of cancer cells without significantly affecting normal cells. These compounds are particularly effective against malignant melanoma and other skin cancers, including Merkel cell carcinoma, squamous cell carcinoma, and basal cell carcinoma. Additionally, they show efficacy against lung, colon, prostate, cervical, and breast cancers[1].
Source of Compounds
The compounds are derived from the sap of Euphorbia peplus, Euphorbia hirta, and Euphorbia drummondii. The sap from these plants contains active principles that inhibit the growth of cancer cells and induce differentiation in malignant melanoma cells, making them adopt the morphological appearance of normal melanocytes[1].
Specific Compounds
The patent specifies that the compounds belong to the group consisting of jatrophanes, pepluanes, paralianes, and ingenanes. One of the key compounds is ingenol mebutate, which has been further developed and approved for the treatment of actinic keratosis[4].
Mechanism of Action
The compounds work by inhibiting the growth of cancer cells and inducing differentiation. For example, the sap from Euphorbia peplus and Euphorbia hirta induces differentiation of malignant melanoma cells at very low concentrations. These compounds also stimulate the activation of the metallothionein gene promoter and the expression of a reporter gene in MM96L malignant melanoma cells[1].
Claims of the Patent
Composition and Formulation
The patent claims include compositions comprising the active compounds along with pharmaceutically suitable carriers or diluents. These compositions can be formulated into various medicinal preparations, such as ointments, creams, gels, and emulsions, suitable for topical or systemic administration[1][2].
Therapeutic Applications
The claims extend to the treatment of various cancers, including solid tumors and specific types like malignant melanoma, other skin cancers, lung cancer, colon cancer, prostate cancer, cervical cancer, and breast cancer. The patent also covers the prevention or alleviation of skin damage caused by ultraviolet irradiation, ionizing radiation, and other forms of radiation[1].
Method of Treatment
The patent includes methods of treating cancer by administering an anti-cancer effective amount of the compound to a mammal in need of such treatment. This can be done either ex vivo or in vivo. Additionally, the method of inhibiting proliferative activity of neoplastic cells by exposing them to an anti-proliferative amount of the compound is also claimed[1].
Patent Landscape
Related Patents
Several patents related to the therapeutic compositions and methods described in US 6,432,452 have been filed and granted. For example, the Korean patent KR101451993B1 discusses therapeutic compositions involving Euphorbia peplus, Euphorbia hirta, and Euphorbia drummondii, highlighting formulations and buffer systems for these compounds[2].
Expiration and Extensions
The original patent US 6,432,452 expired in 2018. However, various extensions and related patents have been granted, extending the protection period for specific formulations and uses of the compounds. For instance, patents related to ingenol mebutate have been granted with expiration dates extending into the late 2020s and early 2030s[4].
Impact and Applications
Clinical Use
Ingenol mebutate, one of the compounds derived from Euphorbia peplus, has been approved and is used clinically for the treatment of actinic keratosis, a precursor to skin cancer. This topical agent has shown significant efficacy in treating this condition[4].
Research and Development
The discovery and development of these compounds have opened new avenues in cancer research. The ability of these compounds to induce differentiation in cancer cells and their selective toxicity towards cancer cells make them valuable candidates for further research and development.
Key Takeaways
- Anti-Cancer Compounds: The patent describes compounds derived from Euphorbia species that inhibit cancer cell growth and induce differentiation.
- Therapeutic Applications: These compounds are effective against various cancers, including malignant melanoma and other skin cancers.
- Formulations: The patent includes various formulations suitable for topical or systemic administration.
- Expiration and Extensions: The original patent has expired, but related patents and extensions continue to protect specific formulations and uses.
- Clinical Use: Ingenol mebutate, a key compound, is approved for treating actinic keratosis.
FAQs
What is the primary focus of US Patent 6,432,452?
The primary focus is on anti-cancer compounds derived from the sap of Euphorbia peplus, Euphorbia hirta, and Euphorbia drummondii.
Which cancers are targeted by the compounds described in the patent?
The compounds are effective against malignant melanoma, other skin cancers, lung cancer, colon cancer, prostate cancer, cervical cancer, and breast cancer.
What is ingenol mebutate, and how is it used?
Ingenol mebutate is a topical agent derived from Euphorbia peplus and is used for the treatment of actinic keratosis.
Have any of the compounds described in the patent been clinically approved?
Yes, ingenol mebutate has been approved for clinical use in treating actinic keratosis.
What is the current status of the patent?
The original patent US 6,432,452 has expired, but related patents and extensions continue to protect specific formulations and uses.
Sources
- US6432452B1 - Anti-cancer compounds - Google Patents
- KR101451993B1 - Therapeutic compositions - Google Patents
- Patent Claims and Patent Scope - SSRN
- Ingenol mebutate: Uses, Interactions, Mechanism of Action - DrugBank
- United States Patent 6,432,452 - Google Patent Images
