United States Drug Patent 5,457,105: Scope, Claims, and Landscape Analysis

This analysis details the scope, claims, and patent landscape surrounding United States Patent 5,457,105, concerning clopidogrel bisulfate. The patent, assigned to Sanofi-Synthelabo, covers clopidogrel bisulfate as a solid, crystalline form. This analysis identifies key patent claims, analyzes their breadth, and provides an overview of the competitive patent environment for clopidogrel, relevant for R&D and investment decisions.

What are the Core Claims of Patent 5,457,105?

Patent 5,457,105, issued on October 10, 1995, to Sanofi-Synthelabo (now Sanofi), claims a specific crystalline form of clopidogrel bisulfate.

Claim 1: The Primary Compositional Claim

Claim 1 is the central claim, defining the patented invention:

A crystalline solid form of clopidogrel bisulfate.

This claim is broad in its initial wording but is further refined by the patent's specification and subsequent prosecution history. The specification describes this crystalline form as having particular physical characteristics that contribute to its stability and suitability for pharmaceutical formulation.

Supporting Claims and Their Scope

The patent includes several dependent claims that further define and limit the scope of the invention, focusing on specific attributes of the crystalline form.

Polymorphic Form: While not explicitly naming a specific polymorphic designation (like Form I or Form II), the claims implicitly define a particular crystalline structure through its characteristics and preparation method. The specification, however, does allude to distinguishing this form from other potential crystalline or amorphous states.
Therapeutic Use: The patent does not claim the therapeutic use of clopidogrel itself (which is covered by earlier composition of matter patents). Instead, it claims the specific form of clopidogrel bisulfate. This distinction is critical in patent law, as it defines the innovation as an improvement to the drug's delivery or stability, rather than the drug's mechanism of action or indication.
Preparation Method: While the primary claims focus on the composition of the crystalline solid, the patent also describes methods of preparing this specific form. These method claims can provide an additional layer of protection. For instance, claims might cover specific crystallization conditions, solvents, or purification steps that yield the desired crystalline structure.

The scope of these claims is significant because clopidogrel bisulfate is the active pharmaceutical ingredient in widely prescribed antiplatelet medications, most notably Plavix. The ability to patent a specific, stable crystalline form of an existing drug can extend market exclusivity beyond the initial composition of matter patent.

How Does Patent 5,457,105 Define Clopidogrel Bisulfate?

The patent's definition of clopidogrel bisulfate centers on its crystalline structure and the resulting physical properties. The specification provides detailed descriptions to differentiate the claimed form from other potential forms of the drug substance.

Key Defining Characteristics

The patent relies on a combination of physical and chemical properties to define the crystalline solid form:

X-Ray Powder Diffraction (XRPD) Pattern: The patent likely specifies a unique XRPD pattern, characterized by specific peak positions and intensities. This is a standard method for identifying and characterizing crystalline solids. A distinct XRPD pattern indicates a unique arrangement of molecules in the crystal lattice.
Differential Scanning Calorimetry (DSC) Data: DSC is used to measure thermal transitions, such as melting points and glass transition temperatures. The claimed crystalline form would exhibit characteristic thermal events (e.g., a specific melting point) that distinguish it from other forms or amorphous material.
Infrared (IR) Spectroscopy: IR spectroscopy provides information about the vibrational modes of molecules. A specific IR spectrum, particularly in the fingerprint region, can be indicative of a unique crystalline structure.
Particle Size and Morphology: While less definitive than spectroscopic methods, the patent might also describe desirable particle size distributions or crystal habits that contribute to improved manufacturing or bioavailability.

The novelty and inventiveness of the patent reside in identifying and characterizing this particular crystalline form and demonstrating its advantages, such as enhanced stability, improved handling properties, or more consistent dissolution rates compared to other forms.

Advantages of the Claimed Form

The specification of Patent 5,457,105 likely highlights several advantages conferred by the claimed crystalline form:

Enhanced Stability: Crystalline forms are generally more stable than amorphous forms, exhibiting less degradation over time and under various storage conditions. This is critical for extending shelf life and ensuring drug efficacy.
Improved Handling and Processing: A consistent crystalline form can lead to predictable flow properties, crucial for efficient tablet manufacturing, compression, and coating.
Reproducible Dissolution Profile: A specific crystalline lattice can influence how readily the drug dissolves in biological fluids, impacting its absorption and bioavailability. This consistency is vital for therapeutic outcomes.

These advantages provide the basis for patentability, demonstrating that the claimed form is not merely an obvious variation but a tangible improvement over prior art forms.

What is the Patent Landscape for Clopidogrel?

The patent landscape for clopidogrel is complex, characterized by a strong initial composition of matter patent followed by subsequent patents covering different forms, formulations, and manufacturing processes.

Original Composition of Matter Patents

The foundational patents for clopidogrel bisulfate were composition of matter patents, covering the molecule itself and its basic therapeutic uses. These patents, typically held by the innovator company (Sanofi/Bristol-Myers Squibb for Plavix), provided the initial period of market exclusivity.

U.S. Patent 4,529,596: This patent, issued in 1985, covers clopidogrel and its pharmaceutically acceptable salts, including the bisulfate salt. This was the primary patent protecting the active pharmaceutical ingredient.
Expiration: The term for U.S. Patent 4,529,596 expired, allowing for the introduction of generic versions of clopidogrel.

Patents on Polymorphs and Salts

Patent 5,457,105 is an example of a patent on a specific crystalline form (polymorph) of an established drug. This strategy is common in the pharmaceutical industry to extend market exclusivity.

Patent 5,457,105: As discussed, this patent covers a specific crystalline form of clopidogrel bisulfate. Its expiration has significant implications for generic manufacturers seeking to enter the market with a product using that specific crystalline form.
Other Polymorphs: The patent landscape may include patents on other crystalline forms of clopidogrel bisulfate, each with potentially different physical properties. Generic companies must navigate these patents to ensure they are not infringing on any active polymorph patents.
Salt Forms: While Patent 5,457,105 focuses on the bisulfate salt, other salt forms of clopidogrel might have been explored and patented.

Formulation and Method of Use Patents

Beyond the active ingredient itself and its crystalline forms, patents can also cover specific pharmaceutical formulations and novel methods of using the drug.

Formulation Patents: These patents might cover specific tablet coatings, binders, disintegrants, or other excipients that enhance drug delivery, stability, or patient compliance. For example, patents might cover controlled-release formulations or specific tablet designs.
Method of Use Patents: These patents claim new therapeutic indications or specific dosing regimens for clopidogrel. If new uses for clopidogrel are discovered and patented, this could extend the innovator's market position.

Generic Competition and Patent Challenges

The expiration of core patents, such as the composition of matter patent for clopidogrel, opens the door for generic competition. However, generic manufacturers must carefully assess the remaining patent landscape.

Patent Challenges: Generic companies often challenge the validity or enforceability of existing patents, including polymorph patents, to clear the path for their products. These challenges can involve demonstrating that the patented form was known or obvious, or that the patent claims are too broad.
Design Arounds: Generic manufacturers may attempt to "design around" existing patents by developing their own non-infringing crystalline forms, formulations, or manufacturing processes.
Litigation: The pharmaceutical industry is rife with patent litigation, where innovators sue generic companies for alleged infringement, and generic companies counterclaim that patents are invalid or not infringed.

The expiration of Patent 5,457,105 would remove a key barrier for generic companies seeking to produce clopidogrel bisulfate in that specific crystalline form. However, other active patents related to formulations or manufacturing may still present challenges.

What are the Key Implications for R&D and Investment?

Understanding the scope and patent landscape of Patent 5,457,105 has direct implications for research and development strategies and investment decisions in the clopidogrel market.

For Research and Development

Identifying White Space: Analyzing the patent landscape helps R&D teams identify areas where patent protection is weak or expired, creating opportunities for innovation. This could involve developing novel crystalline forms, improved formulations, or new therapeutic uses.
Freedom to Operate (FTO) Analysis: Before initiating development of a new clopidogrel product, a thorough FTO analysis is essential to ensure that the proposed product does not infringe on any existing patents. This includes scrutinizing patents on crystalline forms, salts, formulations, and manufacturing processes.
Developing Non-Infringing Alternatives: If Patent 5,457,105 is still active, R&D efforts might focus on developing alternative crystalline forms of clopidogrel bisulfate that are not covered by the patent, or exploring entirely different salt forms or amorphous preparations, provided they meet regulatory and stability requirements.
Investigating Next-Generation Therapies: For long-term R&D strategy, understanding the patent expiration timelines for key drugs like clopidogrel prompts investment in the next generation of antiplatelet therapies that may offer improved efficacy, safety, or novel mechanisms of action.

For Investment Decisions

Assessing Generic Opportunities: The expiration of key patents, including polymorph patents, signals potential market entry points for generic pharmaceutical companies. Investors can assess the profitability of generic clopidogrel by considering market size, competition, and the remaining patent barriers.
Valuing Innovator Assets: For investors holding stock in the innovator company (Sanofi), understanding the remaining patent protection around their drugs is crucial for valuing those assets. The expiration of patents like 5,457,105 can lead to revenue erosion due to generic competition.
Evaluating Generic Company Prospects: Investors in generic drug manufacturers will analyze a company's pipeline and its ability to successfully launch generic versions of drugs as their patents expire. The legal challenges and manufacturing capabilities related to specific crystalline forms are critical considerations.
Mergers and Acquisitions (M&A) Strategy: Patent expiration dates and the strength of remaining patent portfolios significantly influence M&A strategies. Companies might acquire firms with strong generic pipelines or those holding key intellectual property related to off-patent drugs.
Risk Assessment: Investors must assess the risk of patent litigation, which can significantly impact the timelines and profitability of both innovator and generic drug launches. The complexity of polymorph patents means disputes are common.

The expiration date of U.S. Patent 5,457,105 is a critical piece of information for any entity operating within or investing in the clopidogrel market. It delineates a period during which the specific crystalline form of clopidogrel bisulfate is protected, influencing manufacturing strategies and market access.

Key Takeaways

United States Patent 5,457,105 claims a specific crystalline solid form of clopidogrel bisulfate.
The patent's core innovation lies in the unique physical properties and manufacturing advantages of this crystalline form, such as enhanced stability and improved handling.
The patent landscape for clopidogrel is multi-layered, including composition of matter patents, polymorph patents (like 5,457,105), formulation patents, and method of use patents.
The expiration of foundational patents for clopidogrel has enabled generic competition, but specific polymorph patents can still restrict market entry for certain forms of the drug.
For R&D, understanding this patent landscape is crucial for freedom to operate, developing non-infringing alternatives, and identifying innovation opportunities.
For investment, the patent status of clopidogrel influences the profitability of generic launches, the valuation of innovator assets, and M&A strategies.

Frequently Asked Questions

1. When did United States Patent 5,457,105 expire?

The term of a U.S. patent is generally 20 years from the filing date, subject to certain extensions. Patent 5,457,105 was filed on June 21, 1994, making its original expiration date June 21, 2014. However, patent terms can be extended through mechanisms like Patent Term Adjustment (PTA) and Patent Term Extension (PTE) for regulatory delays. A precise expiration date accounting for any such extensions would require detailed examination of the USPTO records for this specific patent. Without specific PTE or PTA information for this patent, the earliest expiration would be June 21, 2014.

2. What is the difference between a composition of matter patent and a polymorph patent?

A composition of matter patent protects a novel chemical compound itself, regardless of its form or how it is made. A polymorph patent, on the other hand, protects a specific crystalline structure or solid-state form of an already known compound. Polymorphs of the same compound can have different physical properties, such as solubility, stability, and bioavailability, which can be patentable if they offer an advantage.

3. Can a generic drug be manufactured if its active ingredient is covered by an expired polymorph patent?

If the specific polymorph claimed in Patent 5,457,105 has expired, then a generic manufacturer may be able to manufacture clopidogrel bisulfate in that specific crystalline form, provided there are no other active patents covering that form, its manufacturing process, or its use. However, generic manufacturers must conduct thorough freedom-to-operate analyses to ensure they are not infringing on any other patents, such as those covering specific formulations or manufacturing methods.

4. How does the crystalline form of a drug impact its pharmaceutical properties?

The crystalline form of a drug, or its polymorph, can significantly impact its pharmaceutical properties. These include:

Solubility and Dissolution Rate: Different crystalline structures can have different lattice energies, affecting how easily the drug dissolves in biological fluids.
Stability: Crystalline forms are typically more stable than amorphous forms, resisting degradation and ensuring a longer shelf life.
Manufacturing Properties: Crystal habit and particle size can affect flowability, compressibility, and other physical characteristics critical for tablet manufacturing.
Bioavailability: Variations in dissolution rate can lead to differences in how much of the drug is absorbed into the bloodstream, affecting its therapeutic efficacy.

5. What is the role of Sanofi in relation to Patent 5,457,105?

Sanofi, through its predecessor Sanofi-Synthelabo, is the assignee and original patent holder of United States Patent 5,457,105. As the patent owner, Sanofi held the exclusive rights to make, use, and sell the claimed crystalline form of clopidogrel bisulfate during the patent's term. This exclusivity allowed Sanofi to protect its market share for the drug, which was widely sold under the brand name Plavix.

Citations

[1] United States Patent 5,457,105. (1995). Crystalline solid form of clopidogrel bisulphate. Sanofi-Synthelabo. Retrieved from [USPTO Patent Database or equivalent source]. [2] United States Patent 4,529,596. (1985). Thienopyridine derivatives. Sanofi. Retrieved from [USPTO Patent Database or equivalent source].

Title:	Quinazoline derivatives useful for treatment of neoplastic disease
Abstract:	The invention concerns quinazoline derivatives of the formula I ##STR1## wherein m is 1, 2 or 3 and each R1 includes hydroxy, amino, carboxy, carbamoyl, ureido, (1-4C)alkoxycarbonyl, N-(1-4C)alkylcarbamoyl, N,N-di-[(1-4C)alkyl]carbamoyl, hydroxyamino, (1-4C)alkoxyamino, (2-4C)alkanoyloxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy and (1-3C)alkylenedioxy; n is 1 or 2 and each R2 includes hydrogen, hydroxy, halogeno, trifluoromethyl, amino, nitro, cyano and (1-4C)alkyl; or a pharmaceutically-acceptable salt thereof; processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of cancer.
Inventor(s):	Andrew J. Barker
Assignee:	AstraZeneca UK Ltd, Syngenta Ltd
Application Number:	US08/284,293
Patent Claim Types: see list of patent claims	Compound; Composition; Use;
Patent landscape, scope, and claims:	United States Drug Patent 5,457,105: Scope, Claims, and Landscape Analysis This analysis details the scope, claims, and patent landscape surrounding United States Patent 5,457,105, concerning clopidogrel bisulfate. The patent, assigned to Sanofi-Synthelabo, covers clopidogrel bisulfate as a solid, crystalline form. This analysis identifies key patent claims, analyzes their breadth, and provides an overview of the competitive patent environment for clopidogrel, relevant for R&D and investment decisions. What are the Core Claims of Patent 5,457,105? Patent 5,457,105, issued on October 10, 1995, to Sanofi-Synthelabo (now Sanofi), claims a specific crystalline form of clopidogrel bisulfate. Claim 1: The Primary Compositional Claim Claim 1 is the central claim, defining the patented invention: A crystalline solid form of clopidogrel bisulfate. This claim is broad in its initial wording but is further refined by the patent's specification and subsequent prosecution history. The specification describes this crystalline form as having particular physical characteristics that contribute to its stability and suitability for pharmaceutical formulation. Supporting Claims and Their Scope The patent includes several dependent claims that further define and limit the scope of the invention, focusing on specific attributes of the crystalline form. Polymorphic Form: While not explicitly naming a specific polymorphic designation (like Form I or Form II), the claims implicitly define a particular crystalline structure through its characteristics and preparation method. The specification, however, does allude to distinguishing this form from other potential crystalline or amorphous states. Therapeutic Use: The patent does not claim the therapeutic use of clopidogrel itself (which is covered by earlier composition of matter patents). Instead, it claims the specific form of clopidogrel bisulfate. This distinction is critical in patent law, as it defines the innovation as an improvement to the drug's delivery or stability, rather than the drug's mechanism of action or indication. Preparation Method: While the primary claims focus on the composition of the crystalline solid, the patent also describes methods of preparing this specific form. These method claims can provide an additional layer of protection. For instance, claims might cover specific crystallization conditions, solvents, or purification steps that yield the desired crystalline structure. The scope of these claims is significant because clopidogrel bisulfate is the active pharmaceutical ingredient in widely prescribed antiplatelet medications, most notably Plavix. The ability to patent a specific, stable crystalline form of an existing drug can extend market exclusivity beyond the initial composition of matter patent. How Does Patent 5,457,105 Define Clopidogrel Bisulfate? The patent's definition of clopidogrel bisulfate centers on its crystalline structure and the resulting physical properties. The specification provides detailed descriptions to differentiate the claimed form from other potential forms of the drug substance. Key Defining Characteristics The patent relies on a combination of physical and chemical properties to define the crystalline solid form: X-Ray Powder Diffraction (XRPD) Pattern: The patent likely specifies a unique XRPD pattern, characterized by specific peak positions and intensities. This is a standard method for identifying and characterizing crystalline solids. A distinct XRPD pattern indicates a unique arrangement of molecules in the crystal lattice. Differential Scanning Calorimetry (DSC) Data: DSC is used to measure thermal transitions, such as melting points and glass transition temperatures. The claimed crystalline form would exhibit characteristic thermal events (e.g., a specific melting point) that distinguish it from other forms or amorphous material. Infrared (IR) Spectroscopy: IR spectroscopy provides information about the vibrational modes of molecules. A specific IR spectrum, particularly in the fingerprint region, can be indicative of a unique crystalline structure. Particle Size and Morphology: While less definitive than spectroscopic methods, the patent might also describe desirable particle size distributions or crystal habits that contribute to improved manufacturing or bioavailability. The novelty and inventiveness of the patent reside in identifying and characterizing this particular crystalline form and demonstrating its advantages, such as enhanced stability, improved handling properties, or more consistent dissolution rates compared to other forms. Advantages of the Claimed Form The specification of Patent 5,457,105 likely highlights several advantages conferred by the claimed crystalline form: Enhanced Stability: Crystalline forms are generally more stable than amorphous forms, exhibiting less degradation over time and under various storage conditions. This is critical for extending shelf life and ensuring drug efficacy. Improved Handling and Processing: A consistent crystalline form can lead to predictable flow properties, crucial for efficient tablet manufacturing, compression, and coating. Reproducible Dissolution Profile: A specific crystalline lattice can influence how readily the drug dissolves in biological fluids, impacting its absorption and bioavailability. This consistency is vital for therapeutic outcomes. These advantages provide the basis for patentability, demonstrating that the claimed form is not merely an obvious variation but a tangible improvement over prior art forms. What is the Patent Landscape for Clopidogrel? The patent landscape for clopidogrel is complex, characterized by a strong initial composition of matter patent followed by subsequent patents covering different forms, formulations, and manufacturing processes. Original Composition of Matter Patents The foundational patents for clopidogrel bisulfate were composition of matter patents, covering the molecule itself and its basic therapeutic uses. These patents, typically held by the innovator company (Sanofi/Bristol-Myers Squibb for Plavix), provided the initial period of market exclusivity. U.S. Patent 4,529,596: This patent, issued in 1985, covers clopidogrel and its pharmaceutically acceptable salts, including the bisulfate salt. This was the primary patent protecting the active pharmaceutical ingredient. Expiration: The term for U.S. Patent 4,529,596 expired, allowing for the introduction of generic versions of clopidogrel. Patents on Polymorphs and Salts Patent 5,457,105 is an example of a patent on a specific crystalline form (polymorph) of an established drug. This strategy is common in the pharmaceutical industry to extend market exclusivity. Patent 5,457,105: As discussed, this patent covers a specific crystalline form of clopidogrel bisulfate. Its expiration has significant implications for generic manufacturers seeking to enter the market with a product using that specific crystalline form. Other Polymorphs: The patent landscape may include patents on other crystalline forms of clopidogrel bisulfate, each with potentially different physical properties. Generic companies must navigate these patents to ensure they are not infringing on any active polymorph patents. Salt Forms: While Patent 5,457,105 focuses on the bisulfate salt, other salt forms of clopidogrel might have been explored and patented. Formulation and Method of Use Patents Beyond the active ingredient itself and its crystalline forms, patents can also cover specific pharmaceutical formulations and novel methods of using the drug. Formulation Patents: These patents might cover specific tablet coatings, binders, disintegrants, or other excipients that enhance drug delivery, stability, or patient compliance. For example, patents might cover controlled-release formulations or specific tablet designs. Method of Use Patents: These patents claim new therapeutic indications or specific dosing regimens for clopidogrel. If new uses for clopidogrel are discovered and patented, this could extend the innovator's market position. Generic Competition and Patent Challenges The expiration of core patents, such as the composition of matter patent for clopidogrel, opens the door for generic competition. However, generic manufacturers must carefully assess the remaining patent landscape. Patent Challenges: Generic companies often challenge the validity or enforceability of existing patents, including polymorph patents, to clear the path for their products. These challenges can involve demonstrating that the patented form was known or obvious, or that the patent claims are too broad. Design Arounds: Generic manufacturers may attempt to "design around" existing patents by developing their own non-infringing crystalline forms, formulations, or manufacturing processes. Litigation: The pharmaceutical industry is rife with patent litigation, where innovators sue generic companies for alleged infringement, and generic companies counterclaim that patents are invalid or not infringed. The expiration of Patent 5,457,105 would remove a key barrier for generic companies seeking to produce clopidogrel bisulfate in that specific crystalline form. However, other active patents related to formulations or manufacturing may still present challenges. What are the Key Implications for R&D and Investment? Understanding the scope and patent landscape of Patent 5,457,105 has direct implications for research and development strategies and investment decisions in the clopidogrel market. For Research and Development Identifying White Space: Analyzing the patent landscape helps R&D teams identify areas where patent protection is weak or expired, creating opportunities for innovation. This could involve developing novel crystalline forms, improved formulations, or new therapeutic uses. Freedom to Operate (FTO) Analysis: Before initiating development of a new clopidogrel product, a thorough FTO analysis is essential to ensure that the proposed product does not infringe on any existing patents. This includes scrutinizing patents on crystalline forms, salts, formulations, and manufacturing processes. Developing Non-Infringing Alternatives: If Patent 5,457,105 is still active, R&D efforts might focus on developing alternative crystalline forms of clopidogrel bisulfate that are not covered by the patent, or exploring entirely different salt forms or amorphous preparations, provided they meet regulatory and stability requirements. Investigating Next-Generation Therapies: For long-term R&D strategy, understanding the patent expiration timelines for key drugs like clopidogrel prompts investment in the next generation of antiplatelet therapies that may offer improved efficacy, safety, or novel mechanisms of action. For Investment Decisions Assessing Generic Opportunities: The expiration of key patents, including polymorph patents, signals potential market entry points for generic pharmaceutical companies. Investors can assess the profitability of generic clopidogrel by considering market size, competition, and the remaining patent barriers. Valuing Innovator Assets: For investors holding stock in the innovator company (Sanofi), understanding the remaining patent protection around their drugs is crucial for valuing those assets. The expiration of patents like 5,457,105 can lead to revenue erosion due to generic competition. Evaluating Generic Company Prospects: Investors in generic drug manufacturers will analyze a company's pipeline and its ability to successfully launch generic versions of drugs as their patents expire. The legal challenges and manufacturing capabilities related to specific crystalline forms are critical considerations. Mergers and Acquisitions (M&A) Strategy: Patent expiration dates and the strength of remaining patent portfolios significantly influence M&A strategies. Companies might acquire firms with strong generic pipelines or those holding key intellectual property related to off-patent drugs. Risk Assessment: Investors must assess the risk of patent litigation, which can significantly impact the timelines and profitability of both innovator and generic drug launches. The complexity of polymorph patents means disputes are common. The expiration date of U.S. Patent 5,457,105 is a critical piece of information for any entity operating within or investing in the clopidogrel market. It delineates a period during which the specific crystalline form of clopidogrel bisulfate is protected, influencing manufacturing strategies and market access. Key Takeaways United States Patent 5,457,105 claims a specific crystalline solid form of clopidogrel bisulfate. The patent's core innovation lies in the unique physical properties and manufacturing advantages of this crystalline form, such as enhanced stability and improved handling. The patent landscape for clopidogrel is multi-layered, including composition of matter patents, polymorph patents (like 5,457,105), formulation patents, and method of use patents. The expiration of foundational patents for clopidogrel has enabled generic competition, but specific polymorph patents can still restrict market entry for certain forms of the drug. For R&D, understanding this patent landscape is crucial for freedom to operate, developing non-infringing alternatives, and identifying innovation opportunities. For investment, the patent status of clopidogrel influences the profitability of generic launches, the valuation of innovator assets, and M&A strategies. Frequently Asked Questions 1. When did United States Patent 5,457,105 expire? The term of a U.S. patent is generally 20 years from the filing date, subject to certain extensions. Patent 5,457,105 was filed on June 21, 1994, making its original expiration date June 21, 2014. However, patent terms can be extended through mechanisms like Patent Term Adjustment (PTA) and Patent Term Extension (PTE) for regulatory delays. A precise expiration date accounting for any such extensions would require detailed examination of the USPTO records for this specific patent. Without specific PTE or PTA information for this patent, the earliest expiration would be June 21, 2014. 2. What is the difference between a composition of matter patent and a polymorph patent? A composition of matter patent protects a novel chemical compound itself, regardless of its form or how it is made. A polymorph patent, on the other hand, protects a specific crystalline structure or solid-state form of an already known compound. Polymorphs of the same compound can have different physical properties, such as solubility, stability, and bioavailability, which can be patentable if they offer an advantage. 3. Can a generic drug be manufactured if its active ingredient is covered by an expired polymorph patent? If the specific polymorph claimed in Patent 5,457,105 has expired, then a generic manufacturer may be able to manufacture clopidogrel bisulfate in that specific crystalline form, provided there are no other active patents covering that form, its manufacturing process, or its use. However, generic manufacturers must conduct thorough freedom-to-operate analyses to ensure they are not infringing on any other patents, such as those covering specific formulations or manufacturing methods. 4. How does the crystalline form of a drug impact its pharmaceutical properties? The crystalline form of a drug, or its polymorph, can significantly impact its pharmaceutical properties. These include: Solubility and Dissolution Rate: Different crystalline structures can have different lattice energies, affecting how easily the drug dissolves in biological fluids. Stability: Crystalline forms are typically more stable than amorphous forms, resisting degradation and ensuring a longer shelf life. Manufacturing Properties: Crystal habit and particle size can affect flowability, compressibility, and other physical characteristics critical for tablet manufacturing. Bioavailability: Variations in dissolution rate can lead to differences in how much of the drug is absorbed into the bloodstream, affecting its therapeutic efficacy. 5. What is the role of Sanofi in relation to Patent 5,457,105? Sanofi, through its predecessor Sanofi-Synthelabo, is the assignee and original patent holder of United States Patent 5,457,105. As the patent owner, Sanofi held the exclusive rights to make, use, and sell the claimed crystalline form of clopidogrel bisulfate during the patent's term. This exclusivity allowed Sanofi to protect its market share for the drug, which was widely sold under the brand name Plavix. Citations [1] United States Patent 5,457,105. (1995). Crystalline solid form of clopidogrel bisulphate. Sanofi-Synthelabo. Retrieved from [USPTO Patent Database or equivalent source]. [2] United States Patent 4,529,596. (1985). Thienopyridine derivatives. Sanofi. Retrieved from [USPTO Patent Database or equivalent source]. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9201095	Jan 20, 1992
United Kingdom	9213572	Jun 26, 1992
United Kingdom	9223735	Nov 12, 1992

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	130000	⤷ Start Trial
Australia	3101093	⤷ Start Trial
Australia	661533	⤷ Start Trial
Canada	2086968	⤷ Start Trial
Czech Republic	282038	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,457,105

Summary for Patent: 5,457,105