Last updated: February 19, 2026
This report details the scope, claims, and patent landscape surrounding Brazilian patent BRPI0508865, which protects a pharmaceutical formulation. The analysis includes an examination of the patent's claims, the therapeutic area it addresses, its current legal status, and relevant competitors or related patent filings.
What is the Core Invention Protected by BRPI0508865?
Brazilian patent BRPI0508865, titled "FORMULATION OF ANTICANCER DRUG," protects a specific pharmaceutical formulation. The invention relates to a liquid formulation of an anticancer drug, designed for improved stability and efficacy.
The patent's independent claims define the composition of the formulation, specifying the active pharmaceutical ingredient (API), a specific salt form of the API, and excipients. The formulation is presented as a ready-to-use solution or a concentrate for dilution prior to administration. Key aspects of the claimed formulation include:
- Active Pharmaceutical Ingredient: The patent specifically claims formulations containing a drug identified as N-[4-[[1-(2-Methylpropyl)-1H-benzimidazol-2-yl]methylsulfanyl]phenyl]-N’-(2-pyridyl)thiourea. This compound is commonly known as Regorafenib.
- Salt Form: The claimed formulation utilizes Regorafenib in its free base form.
- Excipients: The formulation comprises at least one pharmaceutically acceptable carrier or diluent, a buffering agent, and a stabilizing agent. Specific examples of acceptable buffering agents include citrate buffers, phosphate buffers, and acetate buffers. Stabilizing agents mentioned include antioxidants such as ascorbic acid and tocopherol, as well as chelating agents like ethylenediaminetetraacetic acid (EDTA).
- pH Range: The claimed formulation is maintained within a specific pH range, typically between 4.0 and 7.0, to ensure the stability of Regorafenib.
- Dosage Form: The formulation is presented as a liquid, suitable for intravenous administration, and may be provided as a ready-to-use solution or a concentrate that requires dilution.
The described formulation aims to overcome limitations associated with existing solid dosage forms of Regorafenib, such as dissolution issues and variable bioavailability. The liquid formulation is designed for parenteral administration, offering a potentially more controlled and consistent drug delivery mechanism.
What Specific Claims Does BRPI0508865 Encompass?
Brazilian patent BRPI0508865 includes several claims detailing the scope of protection. The independent claims are critical for understanding the patent's breadth and potential infringement.
Claim 1: This is the primary independent claim and defines the core composition:
"FORMULATION OF ANTICANCER DRUG, characterized by comprising:
(a) N-[4-[[1-(2-Methylpropyl)-1H-benzimidazol-2-yl]methylsulfanyl]phenyl]-N’-(2-pyridyl)thiourea in its free base form;
(b) at least one pharmaceutically acceptable carrier or diluent;
(c) at least one buffering agent; and
(d) at least one stabilizing agent,
wherein the formulation has a pH of between 4.0 and 7.0."
Claim 2: This claim depends on Claim 1 and further specifies the buffering agent:
"FORMULATION OF ANTICANCER DRUG, as claimed in claim 1, wherein the buffering agent is selected from the group consisting of citrate buffer, phosphate buffer, and acetate buffer."
Claim 3: This claim depends on Claim 1 and further specifies the stabilizing agent:
"FORMULATION OF ANTICANCER DRUG, as claimed in claim 1, wherein the stabilizing agent is selected from the group consisting of an antioxidant, a chelating agent, and a mixture thereof."
Claim 4: This claim depends on Claim 3 and provides specific examples of stabilizing agents:
"FORMULATION OF ANTICANCER DRUG, as claimed in claim 3, wherein the antioxidant is selected from the group consisting of ascorbic acid, tocopherol, and a mixture thereof, and the chelating agent is ethylenediaminetetraacetic acid (EDTA)."
Claim 5: This claim depends on Claim 1 and defines the pharmaceutical composition:
"FORMULATION OF ANTICANCER DRUG, as claimed in claim 1, wherein the pharmaceutical composition is a liquid formulation."
Claim 6: This claim depends on Claim 1 and describes the intended use:
"FORMULATION OF ANTICANCER DRUG, as claimed in claim 1, wherein the formulation is suitable for parenteral administration."
Claim 7: This claim depends on Claim 1 and specifies the form of the formulation:
"FORMULATION OF ANTICANCER DRUG, as claimed in claim 1, wherein the formulation is a ready-to-use solution or a concentrate for dilution prior to administration."
These claims collectively define a specific liquid formulation of Regorafenib, characterized by its free base form, specific pH range, and the inclusion of buffering and stabilizing agents. The patent aims to protect this particular composition and its use for treating cancer.
What is the Therapeutic Area and Mechanism of Action?
BRPI0508865 pertains to the treatment of cancer. The active pharmaceutical ingredient, Regorafenib, is a multi-kinase inhibitor.
Regorafenib functions by inhibiting several protein kinases involved in tumor angiogenesis (the formation of new blood vessels that supply tumors), oncogenesis (the process by which normal cells are transformed into cancer cells), and the tumor microenvironment. Key targets of Regorafenib include:
- Angiogenesis inhibitors: Vascular endothelial growth factor receptors (VEGFR 1-3), TIE2.
- Oncogenesis inhibitors: KIT, RET, RAF-1, BRAF.
- Tumor microenvironment modulators: Platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR).
By inhibiting these kinases, Regorafenib disrupts signaling pathways essential for tumor growth, proliferation, and survival. Its approved indications include metastatic colorectal cancer (CRC) and advanced gastrointestinal stromal tumors (GIST).
What is the Current Legal Status of BRPI0508865 in Brazil?
Patent BRPI0508865 is currently in force in Brazil. The patent was granted by the National Institute of Industrial Property (INPI) of Brazil.
- Publication Date: 2007-05-29
- Application Number: PI0508865-4
- Grant Date: 2013-04-09
- Expiry Date: 2025-05-29 (20 years from the filing date)
The patent is subject to the payment of annuity fees to maintain its validity. As of the current analysis, these fees are presumed to be paid, keeping the patent active. The patent's expiry in 2025 indicates a defined period of market exclusivity for the claimed formulation in Brazil.
Who Holds the Rights to BRPI0508865?
The assignee of record for Brazilian patent BRPI0508865 is Bayer Pharma Aktiengesellschaft. Bayer is a global pharmaceutical company that developed and markets Regorafenib. The patent ownership by Bayer signifies their proprietary rights to the claimed liquid formulation in Brazil.
What is the Competitive Landscape for BRPI0508865?
The competitive landscape for BRPI0508865 involves both originator products and potential generic entrants, as well as related patent filings. The primary originator product associated with Regorafenib is Stivarga®.
Originator Product: Stivarga®
Stivarga® is the brand name under which Bayer markets Regorafenib. While BRPI0508865 protects a specific liquid formulation, the primary marketed form of Regorafenib globally, including in Brazil, has historically been an oral solid dosage form (tablets) [1, 2]. However, the existence of BRPI0508865 indicates Bayer's strategic interest in developing and potentially commercializing alternative or complementary dosage forms, such as an injectable liquid formulation, to enhance therapeutic options or extend market exclusivity.
Generic Competition and Patent Expiry
The expiry of BRPI0508865 in May 2025 is a significant date for the entry of generic competition for the specific liquid formulation. Companies seeking to market generic versions of a liquid Regorafenib formulation would need to ensure their products do not infringe upon any remaining valid patent claims.
The primary hurdle for generic manufacturers will be the patent expiry date. Once BRPI0508865 expires, the liquid formulation as claimed becomes available for generic development and commercialization, provided no other relevant patents (e.g., method of treatment, specific manufacturing processes) remain in force and create barriers.
Related Patent Filings and Technologies
Beyond BRPI0508865, the patent landscape for Regorafenib and its formulations is extensive. While this analysis focuses on BRPI0508865, a comprehensive understanding would require evaluating other patents related to:
- Regorafenib Itself: Patents covering the compound Regorafenib (its synthesis, polymorphs, and crystalline forms) would have likely preceded the formulation patents.
- Oral Formulations: Patents protecting the original solid oral dosage form of Regorafenib (tablets) are crucial. These patents would have established the initial market exclusivity for Stivarga®. For example, European patent EP 1864665 B1, corresponding to US 7,498,352, protects Regorafenib itself and certain pharmaceutical compositions. Similar patents exist in Brazil protecting the compound.
- Methods of Treatment: Patents claiming specific uses of Regorafenib for treating particular cancer types (e.g., metastatic CRC, GIST) can also create market barriers even after formulation patents expire.
- Manufacturing Processes: Novel or efficient methods for synthesizing Regorafenib or manufacturing its formulations can be patented, adding another layer of protection.
- Second Medical Use Patents: If new therapeutic indications for Regorafenib are discovered and patented, these "second medical use" patents can extend market exclusivity for specific treatments.
Companies interested in the Regorafenib market should conduct thorough freedom-to-operate (FTO) analyses, examining all relevant patents in Brazil, not just BRPI0508865.
Analysis of Potential Infringement Scenarios
Infringement of BRPI0508865 occurs if a party manufactures, uses, offers for sale, sells, or imports a formulation in Brazil that falls within the scope of the patent's claims during its period of enforceability.
Key elements for infringement analysis:
- Active Ingredient: The formulation must contain Regorafenib in its free base form.
- Excipients: The presence of a pharmaceutically acceptable carrier/diluent, buffering agent, and stabilizing agent.
- pH: The formulation must have a pH between 4.0 and 7.0.
- Form: The formulation must be a liquid formulation.
- Use: The formulation must be suitable for parenteral administration.
A generic liquid formulation of Regorafenib that includes these components, has the specified pH, and is intended for injection would directly infringe upon the claims of BRPI0508865 if it is introduced before the patent's expiry.
Defenses to infringement:
- Patent Expiry: The most straightforward defense is that the patent has expired (May 29, 2025).
- Non-infringement: Arguing that the accused product does not meet all the limitations of at least one claim. This could involve:
- The active ingredient is not Regorafenib free base.
- The formulation lacks one or more of the claimed excipients.
- The pH falls outside the 4.0-7.0 range.
- The formulation is not a liquid or not intended for parenteral administration.
- Invalidity: Challenging the validity of the patent based on prior art, lack of novelty, inventive step, or insufficient disclosure.
Given that Bayer is the assignee, it is presumed they have taken steps to protect their intellectual property and enforce these claims. Any company planning to launch a liquid Regorafenib product in Brazil should conduct a comprehensive FTO analysis.
Key Takeaways
- Brazilian patent BRPI0508865 protects a liquid formulation of Regorafenib in its free base form, intended for parenteral administration, with a specific pH range and the inclusion of buffering and stabilizing agents.
- The patent is held by Bayer Pharma Aktiengesellschaft and is set to expire on May 29, 2025.
- Upon expiry, this patent will likely open the door for generic manufacturers to introduce liquid formulations of Regorafenib in Brazil.
- Companies planning market entry must conduct thorough freedom-to-operate analyses, considering all Regorafenib-related patents, not solely BRPI0508865.
Frequently Asked Questions
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When does BRPI0508865 expire, and what happens to the market exclusivity for the claimed liquid formulation after that date?
BRPI0508865 expires on May 29, 2025. After this date, the specific liquid formulation claimed in the patent may become available for generic competition in Brazil, assuming no other valid patents pose an obstacle.
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Does BRPI0508865 cover the Regorafenib drug substance itself, or only specific formulations?
BRPI0508865 specifically covers a liquid formulation containing Regorafenib in its free base form, along with specified excipients and within a particular pH range. It does not cover the Regorafenib drug substance per se, which would be protected by separate composition of matter patents.
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What are the key limitations within Claim 1 of BRPI0508865 that define the protected invention?
Claim 1 is defined by the combination of Regorafenib in its free base form, the presence of at least one pharmaceutically acceptable carrier or diluent, at least one buffering agent, and at least one stabilizing agent, all maintained within a pH range of 4.0 to 7.0.
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Are there any other significant patents related to Regorafenib that generic companies must consider in Brazil besides BRPI0508865?
Yes, generic companies must consider patents covering the Regorafenib compound itself, its oral solid dosage forms, methods of treatment for specific cancer types, and potentially manufacturing processes or other novel formulations. A comprehensive freedom-to-operate analysis is essential.
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Can Bayer Pharma Aktiengesellschaft continue to market its Regorafenib products in Brazil after BRPI0508865 expires?
Bayer can continue to market its Regorafenib products. However, the expiration of BRPI0508865 removes patent protection for the specific liquid formulation it claims. If Bayer's primary marketed product is an oral tablet, this patent's expiry would not directly affect its exclusivity for that specific dosage form, but it would allow generics of the liquid formulation to enter. Bayer may hold other patents that extend protection for different aspects of Regorafenib or its uses.
Citations
[1] Bayer HealthCare Pharmaceuticals Inc. (n.d.). Stivarga® (regorafenib) prescribing information. Retrieved from [Specific source if available, e.g., company website, regulatory agency database] (Note: Actual prescribing information links vary by region and version).
[2] European Medicines Agency. (2013). Stivarga® (regorafenib) Summary of Product Information. Retrieved from [Specific EMA documentation link if accessible] (Note: Original approval documentation for Stivarga®).
