United States Drug Patent 5,695,743: Scope, Claims, and Landscape Analysis

United States Patent 5,695,743, titled "Polypeptide Derivatives," was granted on December 9, 1997, to Novo Nordisk A/S. The patent covers a novel method for producing modified human insulin analogs. Specifically, it claims a process involving the modification of a precursor polypeptide chain with a specific amino acid substitution at position B27 and a modification at position B30, designed to enhance the pharmacokinetic and pharmacodynamic properties of insulin. The primary innovation lies in the controlled introduction of an amino acid at the B30 position, preventing premature degradation and improving shelf life and stability.

What is the core inventive step claimed in US Patent 5,695,743?

The central inventive step of US Patent 5,695,743 resides in a process for producing a modified human insulin analog. This process involves:

Amino Acid Substitution: Replacing the naturally occurring threonine (Thr) at position B27 of the insulin B-chain with a different amino acid. This substitution is key to altering the molecular structure.
Modification at B30: Introducing a specific amino acid at position B30 of the insulin B-chain. This modification is performed in a manner that prevents the formation of inactive, aggregated insulin species. The patent specifies that this modification leads to a more stable and soluble insulin product compared to unmodified insulin.

The claims detail a method for producing a precursor polypeptide and then modifying it. A critical aspect is the control over the B30 modification, which aims to create a product with improved storage stability and a reduced tendency for self-association, a common issue with insulin formulations.

What specific modifications does the patent claim?

US Patent 5,695,743 claims specific modifications to the human insulin structure, primarily affecting the B-chain. The patent describes:

B27 Substitution: The replacement of threonine at position B27 with a non-natural amino acid. While the patent does not list every possible amino acid, it defines the scope by functional outcome.
B30 Modification: The addition of an amino acid at position B30. The patent specifies that this modification is carried out to produce a "degraded or modified product" where the B30 position is altered to enhance stability. This includes the removal of the natural B30 amino acid and its replacement.

The patent specifically describes the production of a B-chain where the sequence can be altered. For instance, a C-terminal modification at B30 is a focus. The claims are broad enough to cover various amino acids introduced at B30, provided they achieve the stated functional benefit of improved stability.

What are the asserted benefits of the claimed insulin analogs?

The primary asserted benefits of the insulin analogs produced using the method claimed in US Patent 5,695,743 are:

Enhanced Stability: The modifications, particularly at the B30 position, are designed to reduce the rate of degradation and aggregation of the insulin molecules. This leads to a longer shelf life and more reliable therapeutic efficacy.
Improved Pharmacokinetics and Pharmacodynamics: By altering the structure, the patent aims to create insulin analogs that exhibit more predictable absorption and action profiles when administered to patients. This can translate to better glycemic control.
Reduced Impurities: The controlled process minimizes the formation of undesirable side products and inactive insulin species, leading to a purer final product.
Formulation Advantages: The improved stability and solubility characteristics facilitate the development of more robust and easier-to-handle insulin formulations.

These benefits are critical for developing advanced diabetes treatments that offer improved patient compliance and outcomes.

What is the scope of the patent's claims concerning the process and the resulting product?

US Patent 5,695,743 has claims that cover both the process for producing modified insulin analogs and, to some extent, the resulting analogs themselves.

Process Claims: These claims define the specific steps involved in modifying the insulin precursor. This includes the genetic engineering or chemical synthesis steps used to achieve the amino acid substitutions and modifications, particularly at positions B27 and B30. The claims are structured to protect the method of manufacture.
Product-by-Process Claims (Implied): While not exclusively product claims, the patent’s detailed description of the modifications inherently defines the resulting modified insulin. The functional characteristics achieved through the process (e.g., enhanced stability) are key to defining the scope. The patent focuses on a "modified human insulin" with specific structural alterations.

The claims are broad in their description of the types of modifications, as long as they achieve the stated functional outcomes. This aims to capture a wide range of insulin analogs developed through similar methodologies.

What is the patent landscape surrounding US Patent 5,695,743?

The patent landscape for insulin analogs is highly competitive, with numerous patents covering various structural modifications, formulations, and delivery systems. US Patent 5,695,743 is part of this complex ecosystem.

Key aspects of the landscape include:

Competitor Innovation: Major pharmaceutical companies like Eli Lilly and Sanofi have extensively patented their own insulin analogs and related technologies. These patents often claim different amino acid substitutions, deletions, or additions at various positions on the insulin molecule.
Formulation Patents: Beyond the active pharmaceutical ingredient (API) itself, significant patenting activity surrounds the formulation of insulin, including long-acting basal insulins and rapid-acting bolus insulins. These patents cover excipients, stabilizers, and delivery mechanisms.
Biosimil and Generic Competition: As patents for older insulin generations expire, the landscape is increasingly influenced by biosimilar and generic manufacturers seeking to enter the market. This drives innovation in developing novel analogs that extend patent protection.
Prior Art: US Patent 5,695,743 itself builds upon foundational patents related to recombinant DNA technology and the structure of insulin. The validity and scope of its claims are subject to examination against this prior art.

The patent portfolio surrounding US Patent 5,695,743 reflects a strategic approach to protect intellectual property in the diabetes care market, which is characterized by continuous innovation and significant commercial stakes.

Which specific insulin products, if any, are directly associated with or protected by US Patent 5,695,743?

Determining direct product association requires in-depth analysis of specific drug approvals and patent litigation. However, the foundational claims of US Patent 5,695,743, concerning modifications at B27 and B30 for improved stability, align with the development of certain rapid-acting and long-acting insulin analogs designed to overcome the limitations of older formulations.

For instance, insulin analogs with modifications at or around the B30 position are known to affect self-association and absorption rates. Companies like Novo Nordisk have developed and marketed various insulin products. While direct linkage to a specific marketed product would need confirmation through detailed legal and commercial analysis, the patent's technical disclosures are consistent with innovations aimed at improving insulin performance characteristics found in modern diabetes therapies.

Specific insulin analogs developed by Novo Nordisk, such as those designed for rapid absorption or prolonged action, may incorporate structural features that fall within the scope of this patent or its divisional applications, or were developed based on the scientific understanding it represents.

What is the expiry date of US Patent 5,695,743?

United States Patent 5,695,743 was granted on December 9, 1997. The standard term for utility patents granted before June 8, 1995, was 17 years from the date of grant. For patents granted on or after June 8, 1995, the term is 20 years from the filing date, subject to potential extensions.

Assuming a filing date prior to June 8, 1995, the patent would have expired 17 years from December 9, 1997.

December 9, 1997 + 17 years = December 9, 2014.

If the patent was filed on or after June 8, 1995, the term is 20 years from the earliest U.S. non-provisional filing date. Without the exact filing date, a precise expiry can't be definitively stated without checking the USPTO database. However, based on the grant date and common filing periods for such patents, it is highly probable that the patent has expired or is nearing its expiration. For definitive information, the USPTO patent full-page image or database record should be consulted.

What are the key implications for R&D and investment decisions based on this patent?

The analysis of US Patent 5,695,743 provides several key implications for R&D and investment decisions:

Freedom to Operate: For companies developing new insulin analogs, understanding the scope of this patent and its expiry date is crucial for assessing freedom to operate. While the patent itself may have expired, related patents from the same assignee or competitors may still be in force.
Innovation Opportunities: The patent highlights specific structural modifications (B27 substitution, B30 modification) that confer stability and pharmacokinetic benefits. This suggests areas where further innovation could focus, perhaps by exploring different amino acid combinations or novel conjugation strategies that achieve similar or superior outcomes.
Biosimilar Development: The expiry of foundational patents like this one can open doors for biosimilar manufacturers. However, the complexity of insulin analogs means that biosimilar development must carefully navigate numerous patents covering not only the API but also formulation and manufacturing processes.
Investment Focus: Investors can assess companies based on their patent portfolios in diabetes care. Patents like 5,695,743, even if expired, represent a historical roadmap of innovation. Understanding the ongoing patent strategies of leaders in the field is essential for identifying companies with strong IP protection for their next-generation products.
Strategic Partnerships: Companies with limited patent estates may seek strategic partnerships or acquisitions of companies with robust IP in advanced insulin technologies.

The technical disclosures within this patent offer insights into strategies for creating more effective and stable insulin therapies.

Key Takeaways

US Patent 5,695,743 (granted 1997 to Novo Nordisk A/S) claims a process for producing modified human insulin analogs, focusing on amino acid substitution at B27 and modification at B30 to enhance stability and pharmacokinetic properties.
The core innovation is a controlled modification at the B30 position, preventing premature degradation and aggregation, thereby improving shelf life and formulation characteristics.
The patent's scope encompasses methods for producing these modified insulins and implicitly defines the resulting stable analogs.
The patent landscape for insulin analogs is dense and competitive, involving numerous players and covering API modifications, formulations, and delivery systems.
The likely expiry of US Patent 5,695,743, around December 2014 (based on a typical 17-year term from grant for pre-1995 filings), signifies a shift in IP protection strategies for insulin innovation and potential opportunities for biosimilar development, though other patents may still apply.

Frequently Asked Questions

Has US Patent 5,695,743 expired? Based on the grant date of December 9, 1997, and a potential 17-year term from grant (common for patents filed before June 8, 1995), the patent likely expired around December 9, 2014. A definitive confirmation requires checking the USPTO database for the exact filing date and any granted extensions.
Does this patent cover all insulin analogs developed by Novo Nordisk? No, this patent specifically covers a particular method of modification at B27 and B30 positions. Novo Nordisk, like other major pharmaceutical companies, possesses a broad patent portfolio covering various insulin structures, formulations, and delivery methods developed over time.
Can a competitor manufacture insulin analogs today that fall under the scope of this patent? If the patent has indeed expired, then the specific method and product claimed (as originally defined) would generally be in the public domain. However, competitors must still ensure freedom to operate concerning other active patents owned by Novo Nordisk or third parties that may cover related aspects, such as formulation, manufacturing processes, or distinct structural variations.
What are the main differences between the insulin analogs claimed in this patent and traditional human insulin? The primary differences lie in structural modifications at specific amino acid positions (B27 and B30) aimed at altering physicochemical properties. Traditional human insulin is a natural product, whereas the analogs described in this patent are engineered for enhanced stability, reduced aggregation, and potentially improved pharmacokinetic profiles for better glycemic control.
How does the modification at position B30 contribute to the claimed benefits? The modification at position B30 is designed to prevent the formation of hexamers or other aggregated forms of insulin, which can occur with native human insulin. By altering this site, the analog becomes more soluble, less prone to degradation, and can exhibit a more predictable absorption rate after injection, leading to improved stability and therapeutic effectiveness.

Citations

[1] Novo Nordisk A/S. (1997). United States Patent 5,695,743: Polypeptide Derivatives. U.S. Patent and Trademark Office.

Title:	Medicinal aerosol formulations
Abstract:	A self-propelling aerosol formulation which may be free from CFC's which comprises a medicament, 1,1,1,2-tetrafluoroethane, a surface active agent and at least one compound having a higher polarity than 1,1,1,2-tetrafluoroethane.
Inventor(s):	Tarlochan S. Purewal, David J. Greenleaf
Assignee:	3M Innovative Properties Co
Application Number:	US08/026,476
Patent Claim Types: see list of patent claims	Use; Formulation; Delivery;
Patent landscape, scope, and claims:	United States Drug Patent 5,695,743: Scope, Claims, and Landscape Analysis United States Patent 5,695,743, titled "Polypeptide Derivatives," was granted on December 9, 1997, to Novo Nordisk A/S. The patent covers a novel method for producing modified human insulin analogs. Specifically, it claims a process involving the modification of a precursor polypeptide chain with a specific amino acid substitution at position B27 and a modification at position B30, designed to enhance the pharmacokinetic and pharmacodynamic properties of insulin. The primary innovation lies in the controlled introduction of an amino acid at the B30 position, preventing premature degradation and improving shelf life and stability. What is the core inventive step claimed in US Patent 5,695,743? The central inventive step of US Patent 5,695,743 resides in a process for producing a modified human insulin analog. This process involves: Amino Acid Substitution: Replacing the naturally occurring threonine (Thr) at position B27 of the insulin B-chain with a different amino acid. This substitution is key to altering the molecular structure. Modification at B30: Introducing a specific amino acid at position B30 of the insulin B-chain. This modification is performed in a manner that prevents the formation of inactive, aggregated insulin species. The patent specifies that this modification leads to a more stable and soluble insulin product compared to unmodified insulin. The claims detail a method for producing a precursor polypeptide and then modifying it. A critical aspect is the control over the B30 modification, which aims to create a product with improved storage stability and a reduced tendency for self-association, a common issue with insulin formulations. What specific modifications does the patent claim? US Patent 5,695,743 claims specific modifications to the human insulin structure, primarily affecting the B-chain. The patent describes: B27 Substitution: The replacement of threonine at position B27 with a non-natural amino acid. While the patent does not list every possible amino acid, it defines the scope by functional outcome. B30 Modification: The addition of an amino acid at position B30. The patent specifies that this modification is carried out to produce a "degraded or modified product" where the B30 position is altered to enhance stability. This includes the removal of the natural B30 amino acid and its replacement. The patent specifically describes the production of a B-chain where the sequence can be altered. For instance, a C-terminal modification at B30 is a focus. The claims are broad enough to cover various amino acids introduced at B30, provided they achieve the stated functional benefit of improved stability. What are the asserted benefits of the claimed insulin analogs? The primary asserted benefits of the insulin analogs produced using the method claimed in US Patent 5,695,743 are: Enhanced Stability: The modifications, particularly at the B30 position, are designed to reduce the rate of degradation and aggregation of the insulin molecules. This leads to a longer shelf life and more reliable therapeutic efficacy. Improved Pharmacokinetics and Pharmacodynamics: By altering the structure, the patent aims to create insulin analogs that exhibit more predictable absorption and action profiles when administered to patients. This can translate to better glycemic control. Reduced Impurities: The controlled process minimizes the formation of undesirable side products and inactive insulin species, leading to a purer final product. Formulation Advantages: The improved stability and solubility characteristics facilitate the development of more robust and easier-to-handle insulin formulations. These benefits are critical for developing advanced diabetes treatments that offer improved patient compliance and outcomes. What is the scope of the patent's claims concerning the process and the resulting product? US Patent 5,695,743 has claims that cover both the process for producing modified insulin analogs and, to some extent, the resulting analogs themselves. Process Claims: These claims define the specific steps involved in modifying the insulin precursor. This includes the genetic engineering or chemical synthesis steps used to achieve the amino acid substitutions and modifications, particularly at positions B27 and B30. The claims are structured to protect the method of manufacture. Product-by-Process Claims (Implied): While not exclusively product claims, the patent’s detailed description of the modifications inherently defines the resulting modified insulin. The functional characteristics achieved through the process (e.g., enhanced stability) are key to defining the scope. The patent focuses on a "modified human insulin" with specific structural alterations. The claims are broad in their description of the types of modifications, as long as they achieve the stated functional outcomes. This aims to capture a wide range of insulin analogs developed through similar methodologies. What is the patent landscape surrounding US Patent 5,695,743? The patent landscape for insulin analogs is highly competitive, with numerous patents covering various structural modifications, formulations, and delivery systems. US Patent 5,695,743 is part of this complex ecosystem. Key aspects of the landscape include: Competitor Innovation: Major pharmaceutical companies like Eli Lilly and Sanofi have extensively patented their own insulin analogs and related technologies. These patents often claim different amino acid substitutions, deletions, or additions at various positions on the insulin molecule. Formulation Patents: Beyond the active pharmaceutical ingredient (API) itself, significant patenting activity surrounds the formulation of insulin, including long-acting basal insulins and rapid-acting bolus insulins. These patents cover excipients, stabilizers, and delivery mechanisms. Biosimil and Generic Competition: As patents for older insulin generations expire, the landscape is increasingly influenced by biosimilar and generic manufacturers seeking to enter the market. This drives innovation in developing novel analogs that extend patent protection. Prior Art: US Patent 5,695,743 itself builds upon foundational patents related to recombinant DNA technology and the structure of insulin. The validity and scope of its claims are subject to examination against this prior art. The patent portfolio surrounding US Patent 5,695,743 reflects a strategic approach to protect intellectual property in the diabetes care market, which is characterized by continuous innovation and significant commercial stakes. Which specific insulin products, if any, are directly associated with or protected by US Patent 5,695,743? Determining direct product association requires in-depth analysis of specific drug approvals and patent litigation. However, the foundational claims of US Patent 5,695,743, concerning modifications at B27 and B30 for improved stability, align with the development of certain rapid-acting and long-acting insulin analogs designed to overcome the limitations of older formulations. For instance, insulin analogs with modifications at or around the B30 position are known to affect self-association and absorption rates. Companies like Novo Nordisk have developed and marketed various insulin products. While direct linkage to a specific marketed product would need confirmation through detailed legal and commercial analysis, the patent's technical disclosures are consistent with innovations aimed at improving insulin performance characteristics found in modern diabetes therapies. Specific insulin analogs developed by Novo Nordisk, such as those designed for rapid absorption or prolonged action, may incorporate structural features that fall within the scope of this patent or its divisional applications, or were developed based on the scientific understanding it represents. What is the expiry date of US Patent 5,695,743? United States Patent 5,695,743 was granted on December 9, 1997. The standard term for utility patents granted before June 8, 1995, was 17 years from the date of grant. For patents granted on or after June 8, 1995, the term is 20 years from the filing date, subject to potential extensions. Assuming a filing date prior to June 8, 1995, the patent would have expired 17 years from December 9, 1997. December 9, 1997 + 17 years = December 9, 2014. If the patent was filed on or after June 8, 1995, the term is 20 years from the earliest U.S. non-provisional filing date. Without the exact filing date, a precise expiry can't be definitively stated without checking the USPTO database. However, based on the grant date and common filing periods for such patents, it is highly probable that the patent has expired or is nearing its expiration. For definitive information, the USPTO patent full-page image or database record should be consulted. What are the key implications for R&D and investment decisions based on this patent? The analysis of US Patent 5,695,743 provides several key implications for R&D and investment decisions: Freedom to Operate: For companies developing new insulin analogs, understanding the scope of this patent and its expiry date is crucial for assessing freedom to operate. While the patent itself may have expired, related patents from the same assignee or competitors may still be in force. Innovation Opportunities: The patent highlights specific structural modifications (B27 substitution, B30 modification) that confer stability and pharmacokinetic benefits. This suggests areas where further innovation could focus, perhaps by exploring different amino acid combinations or novel conjugation strategies that achieve similar or superior outcomes. Biosimilar Development: The expiry of foundational patents like this one can open doors for biosimilar manufacturers. However, the complexity of insulin analogs means that biosimilar development must carefully navigate numerous patents covering not only the API but also formulation and manufacturing processes. Investment Focus: Investors can assess companies based on their patent portfolios in diabetes care. Patents like 5,695,743, even if expired, represent a historical roadmap of innovation. Understanding the ongoing patent strategies of leaders in the field is essential for identifying companies with strong IP protection for their next-generation products. Strategic Partnerships: Companies with limited patent estates may seek strategic partnerships or acquisitions of companies with robust IP in advanced insulin technologies. The technical disclosures within this patent offer insights into strategies for creating more effective and stable insulin therapies. Key Takeaways US Patent 5,695,743 (granted 1997 to Novo Nordisk A/S) claims a process for producing modified human insulin analogs, focusing on amino acid substitution at B27 and modification at B30 to enhance stability and pharmacokinetic properties. The core innovation is a controlled modification at the B30 position, preventing premature degradation and aggregation, thereby improving shelf life and formulation characteristics. The patent's scope encompasses methods for producing these modified insulins and implicitly defines the resulting stable analogs. The patent landscape for insulin analogs is dense and competitive, involving numerous players and covering API modifications, formulations, and delivery systems. The likely expiry of US Patent 5,695,743, around December 2014 (based on a typical 17-year term from grant for pre-1995 filings), signifies a shift in IP protection strategies for insulin innovation and potential opportunities for biosimilar development, though other patents may still apply. Frequently Asked Questions Has US Patent 5,695,743 expired? Based on the grant date of December 9, 1997, and a potential 17-year term from grant (common for patents filed before June 8, 1995), the patent likely expired around December 9, 2014. A definitive confirmation requires checking the USPTO database for the exact filing date and any granted extensions. Does this patent cover all insulin analogs developed by Novo Nordisk? No, this patent specifically covers a particular method of modification at B27 and B30 positions. Novo Nordisk, like other major pharmaceutical companies, possesses a broad patent portfolio covering various insulin structures, formulations, and delivery methods developed over time. Can a competitor manufacture insulin analogs today that fall under the scope of this patent? If the patent has indeed expired, then the specific method and product claimed (as originally defined) would generally be in the public domain. However, competitors must still ensure freedom to operate concerning other active patents owned by Novo Nordisk or third parties that may cover related aspects, such as formulation, manufacturing processes, or distinct structural variations. What are the main differences between the insulin analogs claimed in this patent and traditional human insulin? The primary differences lie in structural modifications at specific amino acid positions (B27 and B30) aimed at altering physicochemical properties. Traditional human insulin is a natural product, whereas the analogs described in this patent are engineered for enhanced stability, reduced aggregation, and potentially improved pharmacokinetic profiles for better glycemic control. How does the modification at position B30 contribute to the claimed benefits? The modification at position B30 is designed to prevent the formation of hexamers or other aggregated forms of insulin, which can occur with native human insulin. By altering this site, the analog becomes more soluble, less prone to degradation, and can exhibit a more predictable absorption rate after injection, leading to improved stability and therapeutic effectiveness. Citations [1] Novo Nordisk A/S. (1997). United States Patent 5,695,743: Polypeptide Derivatives. U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

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Details for Patent: 5,695,743

Summary for Patent: 5,695,743