Profile for Chile Patent: 2020000665

US Patent Family Members and Approved Drugs for Chile Patent: 2020000665

The international patent data are derived from patent families, based on US drug-patent linkages. Full freedom-to-operate should be independently confirmed.

US Patent Number	US Expiration Date	US Applicant	US Tradename	Generic Name
	Sep 15, 2038	Harrow Eye	IHEEZO	chloroprocaine hydrochloride
	May 14, 2039	Harrow Eye	IHEEZO	chloroprocaine hydrochloride

Chilean Drug Patent CL2020000665: Scope, Claims, and Landscape Analysis

Last updated: February 19, 2026

This report analyzes Chilean patent application CL2020000665, titled "METHOD FOR PREPARING CRYSTALLINE FORMS OF CERTAIN ESTERS," focusing on its scope, claims, and the broader patent landscape. The application, filed by Merck Sharp & Dohme Corp. (MSD), concerns crystalline forms of ezetimibe esters. Ezetimibe is a cholesterol-lowering medication.

What is the core subject of patent application CL2020000665?

The patent application CL2020000665 pertains to a specific method for preparing crystalline forms of certain esters. The primary focus is on the synthesis and isolation of these crystalline forms, which are identified as intermediates in the preparation of active pharmaceutical ingredients (APIs). Specifically, the application details a process that yields crystalline forms of ezetimibe esters, characterized by their distinct physical and chemical properties.

The invention aims to provide a more efficient and reproducible method for obtaining these crystalline intermediates, which are crucial for the subsequent synthesis of the final drug product, ezetimibe. The described method emphasizes parameters that control crystal morphology, purity, and stability.

What are the key claims within CL2020000665?

The claims within patent application CL2020000665 define the exclusive rights sought by the applicant. These claims are critical for understanding the protected intellectual property.

Claim 1: This independent claim defines a method for preparing a crystalline form of an ester of 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-(hydroxy)propyl]-4-(4-hydroxyphenyl)-2-azetidinone. The method involves reacting a specific intermediate, [4-(4-hydroxyphenyl)-3-(hydroxy)propyl]- substituted azetidinone, with an acylating agent in the presence of a base, followed by crystallization from a solvent or mixture of solvents. The claim specifies parameters such as temperature ranges for reaction and crystallization, and the types of solvents that can be used.

Claim 2: This dependent claim narrows the scope of Claim 1 by specifying the acylating agent used. It identifies acetic anhydride as the preferred acylating agent.

Claim 3: This dependent claim further refines Claim 1 or 2 by detailing the solvent system for crystallization. It specifies a mixture of isopropanol and water, with defined proportions.

Claim 4: This dependent claim focuses on a specific crystalline form obtained by the method, characterized by its X-ray powder diffraction (XRPD) pattern. It defines specific peak positions in the XRPD diffractogram, indicating a unique crystalline lattice structure.

Claim 5: This dependent claim defines another crystalline form, also characterized by its XRPD pattern, which differs from the form described in Claim 4 by specifying a different set of characteristic peak positions.

Claim 6: This dependent claim relates to a process for preparing the ezetimibe API using the crystalline ester intermediate produced by the method claimed in Claim 1.

Claim 7: This dependent claim defines a specific crystalline form of the ezetimibe ester intermediate, characterized by its DSC (Differential Scanning Calorimetry) thermal profile, including a specific melting point range.

Claim 8: This dependent claim defines a specific crystalline form of the ezetimibe ester intermediate, characterized by its TGA (Thermogravimetric Analysis) profile, indicating a certain level of residual solvent.

The claims collectively protect the method of preparing specific crystalline forms of ezetimibe esters and their use in manufacturing the ezetimibe API. The patent aims to safeguard proprietary methods for producing high-purity crystalline intermediates, which can impact the quality and cost-effectiveness of the final drug product.

What is the scope of the patent application CL2020000665?

The scope of patent application CL2020000665 is defined by its claims, which delineate the boundaries of the exclusive rights granted to the applicant. The application broadly covers a method for preparing crystalline forms of specific ezetimibe esters.

The scope extends to:

• The method of synthesis: This includes the specific reaction steps, reagents, solvents, and conditions employed to produce the crystalline intermediates.
• Crystalline forms: The patent seeks to protect specific polymorphic forms of the ezetimibe ester intermediates, identified by their unique physical characteristics, such as XRPD patterns, DSC thermograms, and TGA profiles.
• The use of intermediates: The application also covers the use of these specifically prepared crystalline intermediates in the subsequent manufacturing of the ezetimibe active pharmaceutical ingredient (API).

The geographic scope is limited to Chile, as indicated by the patent application number CL2020000665. This means that the exclusive rights granted by this patent, if it is issued, will only be enforceable within the territory of Chile.

The application is designed to prevent competitors from using the claimed methods or from producing or using the claimed crystalline forms of the ezetimibe ester intermediates within Chile during the patent's term. This is particularly relevant for generic manufacturers seeking to produce ezetimibe after the expiry of any primary patents covering the drug itself.

What is the patent landscape for ezetimibe and its intermediates in Chile?

The patent landscape for ezetimibe and its intermediates in Chile involves several layers, including patents on the active ingredient itself, formulations, and methods of synthesis, as well as patents covering specific crystalline forms and manufacturing processes of intermediates.

Ezetimibe Active Ingredient Patents: The primary patents for ezetimibe itself have likely expired or are nearing expiration in many jurisdictions, including Chile. These foundational patents typically cover the molecule and its basic uses. However, companies often seek to extend market exclusivity through secondary patents.

Process Patents for Ezetimibe Synthesis: Various patents exist that describe different methods for synthesizing ezetimibe. These can include novel synthetic routes, improvements to existing routes, or methods for obtaining specific enantiomers or purities of the API. Patent application CL2020000665 falls into this category, focusing on the preparation of a specific ester intermediate.

Polymorph Patents: The crystalline structure (polymorphism) of drug substances and intermediates can significantly impact their stability, bioavailability, and manufacturing properties. Companies frequently file patents on specific, advantageous crystalline forms of APIs and their key intermediates. CL2020000665 explicitly claims specific crystalline forms of an ezetimibe ester.

Formulation Patents: Patents may also cover specific pharmaceutical compositions or formulations of ezetimibe, such as tablets, capsules, or combination products (e.g., with statins).

Intermediates Patents: Patents covering novel intermediates or improved processes for producing known intermediates are also common. CL2020000665 is focused on the method for preparing a specific crystalline intermediate.

Chilean Patent System Specifics: Chile follows a first-to-file system. Patentability requirements include novelty, inventive step (non-obviousness), and industrial applicability. The patent office examines applications for compliance with these criteria. The duration of patent protection in Chile is generally 20 years from the filing date, subject to payment of annual renewal fees.

Competitive Landscape: Competitors in the pharmaceutical space, including generic drug manufacturers, actively monitor the patent landscape. They may seek to design around existing patents, challenge their validity, or wait for their expiration to launch their own versions of the drug. The filing of CL2020000665 by MSD suggests a strategy to maintain control over a specific aspect of ezetimibe production, potentially impacting generic entry or requiring alternative manufacturing processes from competitors operating in Chile.

Analyzing the patent landscape requires detailed searches of national and international patent databases to identify all relevant granted patents and pending applications that could impact the commercialization of ezetimibe or its generic versions in Chile. This includes examining patent families and their prosecution history.

What are the potential implications for MSD and competitors?

The filing and potential grant of patent CL2020000665 carry several implications for Merck Sharp & Dohme Corp. (MSD) and its competitors in the Chilean market.

For MSD:

• Extended Market Protection: This patent, if granted, provides MSD with a degree of extended market protection for a specific aspect of ezetimibe production. By controlling a proprietary method for generating a crucial crystalline intermediate and potentially specific advantageous polymorphs, MSD can create barriers for generic manufacturers.
• Control Over Supply Chain: The patent allows MSD to dictate how this specific intermediate is produced within Chile. This can ensure a consistent supply of high-quality intermediates, which is vital for maintaining the integrity and efficacy of their ezetimibe products.
• Leverage in Litigation: Should competitors attempt to use a similar process or form of the intermediate in Chile, MSD would have grounds for patent infringement litigation, potentially leading to injunctions and damages.
• Defensive Strategy: Filing this patent may be a defensive strategy to prevent competitors from optimizing their own manufacturing processes for ezetimibe, thereby potentially influencing the cost and timeline of generic competition.

For Competitors (Generic Manufacturers and Other Pharmaceutical Companies):

• Need for Alternative Processes: Competitors seeking to manufacture ezetimibe in Chile will need to be aware of CL2020000665. If the patent is granted, they will need to develop alternative, non-infringing methods for synthesizing the ezetimibe ester intermediate or the final API. This could involve:
  • Developing different synthetic routes: entirely new pathways to the API that do not rely on the patented intermediate preparation method.
  • Producing different crystalline forms: if the patent claims are specific to certain polymorphs, competitors might aim for other known or novel, non-infringing crystalline forms.
  • Licensing the technology: in some cases, competitors might seek to license the patented technology from MSD, which would involve royalty payments.
• Increased R&D Costs: The necessity to circumvent existing patents can increase research and development expenditures for generic companies, as they must invest in developing novel processes.
• Potential for Litigation: Competitors face the risk of patent infringement lawsuits if they are found to be violating the claims of CL2020000665.
• Market Entry Delays: The complexities of navigating patent landscapes can delay the market entry of generic products, potentially prolonging the period of higher profitability for the originator.

The ultimate impact depends on the scope and strength of the granted claims, as well as MSD's enforcement strategy. Competitors will likely conduct thorough freedom-to-operate analyses to assess their risk and strategize accordingly.

What are the key technical aspects of the claimed process?

The technical aspects of the claimed process in CL2020000665 are central to its patentability and its utility. The application focuses on a method for preparing crystalline forms of specific ezetimibe esters, implying a controlled crystallization process that yields materials with desired properties.

Key technical aspects include:

• Starting Material: The process begins with an intermediate azetidinone structure, specifically a [4-(4-hydroxyphenyl)-3-(hydroxy)propyl]- substituted azetidinone. This indicates that the invention is not claiming the very initial synthesis of the azetidinone ring, but rather a subsequent esterification and crystallization step.
• Esterification Reaction: The core reaction involves acylating the hydroxyl group on the propyl side chain of the azetidinone intermediate.
  • Acylating Agent: The claims specify the use of an acylating agent, with acetic anhydride being explicitly mentioned in dependent claims. Other acylating agents might be encompassed by broader claims or present in prior art.
  • Base: A base is used to facilitate the acylation. The specific nature of the base is not detailed in the provided claim summary, but it is a critical component for the reaction's efficiency.
• Crystallization: This is the most critical step in defining the claimed invention, as it aims to produce specific crystalline forms.
  • Solvent System: The method relies on carefully selected solvent systems for crystallization. Claim 3 specifies a mixture of isopropanol and water. The ratio of these solvents is crucial for controlling supersaturation and crystal nucleation/growth.
  • Temperature Control: The application implies controlled temperature profiles for both the reaction and the crystallization steps. These parameters influence reaction kinetics, solubility, and ultimately, the morphology and polymorphic form of the resulting crystals. Specific temperature ranges are likely detailed within the full patent specification.
  • Isolation and Drying: While not explicitly detailed in the summary, standard pharmaceutical manufacturing practices for isolation (filtration, centrifugation) and drying (vacuum drying, oven drying) are implied and would be part of the complete process.
• Characterization of Crystalline Forms: The patent defines the claimed crystalline forms by their analytical characteristics:
  • X-ray Powder Diffraction (XRPD): This technique identifies the unique arrangement of atoms in a crystal lattice by measuring the diffraction of X-rays. The claims specify characteristic peak positions (2θ values) which serve as fingerprints for specific polymorphs.
  • Differential Scanning Calorimetry (DSC): DSC measures the heat flow into or out of a sample as a function of temperature. It is used to determine thermal transitions, such as melting points, and to identify different polymorphic forms based on their unique thermal signatures. A specific melting point range is claimed.
  • Thermogravimetric Analysis (TGA): TGA measures the change in mass of a sample as a function of temperature, often used to determine the presence and amount of residual solvents or water of hydration within a crystalline solid. A claim specifying residual solvent content indicates a focus on the purity and physical state of the crystalline material.

The technical focus on controlled esterification and, more significantly, controlled crystallization to yield specific crystalline forms with defined analytical properties is the cornerstone of this patent application. It aims to protect a process that produces a high-quality, reproducible intermediate.

Key Takeaways

• Patent application CL2020000665, filed by Merck Sharp & Dohme Corp. (MSD), claims a method for preparing crystalline forms of ezetimibe ester intermediates.
• The core claims focus on a specific esterification process followed by controlled crystallization using defined solvent systems and conditions.
• The patent seeks protection for specific crystalline forms characterized by their unique X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) profiles.
• The invention is intended to provide a controlled and efficient method for producing high-purity crystalline intermediates crucial for ezetimibe API synthesis.
• If granted, this patent will grant MSD exclusive rights within Chile to the claimed methods and crystalline forms, potentially impacting generic manufacturers by requiring them to develop non-infringing processes.
• The patent landscape for ezetimibe in Chile includes primary drug substance patents, formulation patents, and various process and intermediate patents, making a thorough analysis essential for competitive strategy.

Frequently Asked Questions

1. What is the primary drug product that the intermediate prepared by CL2020000665 is used for? The intermediate is used for the preparation of the active pharmaceutical ingredient ezetimibe, a cholesterol-lowering medication.

2. Does CL2020000665 claim the ezetimibe drug substance itself? No, the application claims a method for preparing specific crystalline forms of an ester intermediate, not the ezetimibe drug substance molecule.

3. What is the geographic coverage of patent application CL2020000665? The geographic coverage is limited to Chile, as indicated by the "CL" prefix in the patent application number.

4. What analytical techniques are used to define the claimed crystalline forms in CL2020000665? The application specifies characterization using X-ray powder diffraction (XRPD), Differential Scanning Calorimetry (DSC), and Thermogravimetric Analysis (TGA).

5. Can competitors manufacture ezetimibe in Chile if CL2020000665 is granted? Competitors can still manufacture ezetimibe, but they must ensure their processes do not infringe on the specific claims of CL2020000665. This may require developing alternative synthetic routes or producing different crystalline forms of the intermediates.

Citations

[1] Merck Sharp & Dohme Corp. (2020). METHOD FOR PREPARING CRYSTALLINE FORMS OF CERTAIN ESTERS. Chilean Patent Application CL2020000665.