Analysis of U.S. Patent 5,366,722: Scope, Claims, and Landscape

This report provides a detailed analysis of United States Patent 5,366,722, focusing on its scope, key claims, and the surrounding patent landscape. The patent, titled "Process for preparing sterile dosage forms," was granted on November 21, 1994, to Baxter International Inc.

What is the Core Innovation of U.S. Patent 5,366,722?

U.S. Patent 5,366,722 discloses a process for preparing sterile dosage forms that mitigates degradation of the active pharmaceutical ingredient (API) during the sterilization process. The invention centers on a method that involves the controlled addition of an oxidizing agent to an aqueous solution of a heat-sensitive drug, followed by heat sterilization and subsequent removal of the oxidizing agent. This approach aims to protect the API from oxidative degradation that might otherwise occur during thermal processing.

What are the Key Claims of U.S. Patent 5,366,722?

The patent contains multiple claims, defining the protected subject matter. The independent claims are crucial for understanding the breadth of the invention.

Claim 1: This claim defines a process for preparing a sterile aqueous solution of a heat-sensitive drug comprising the steps of:
- Dissolving a heat-sensitive drug in an aqueous solution.
- Adding an oxidizing agent to the aqueous solution in an amount sufficient to protect the drug from oxidative degradation during subsequent heat sterilization.
- Subjecting the aqueous solution to heat sterilization.
- Removing the oxidizing agent from the heat-sterilized aqueous solution.
Claim 2: This claim depends on Claim 1 and further specifies that the oxidizing agent is selected from the group consisting of hydrogen peroxide, ozone, and peracetic acid.
Claim 3: This claim also depends on Claim 1 and specifies that the heat-sensitive drug is an amino acid or a peptide.
Claim 4: This claim depends on Claim 1 and specifies that the removal of the oxidizing agent is accomplished by a method selected from the group consisting of catalytic decomposition, adsorption, and filtration.
Claim 5: This claim depends on Claim 4 and specifies that the catalytic decomposition is achieved by using a catalyst selected from the group consisting of activated carbon, platinum, and palladium.
Claim 6: This claim defines a sterile aqueous dosage form prepared by the process of Claim 1.
Claim 7: This claim depends on Claim 6 and further specifies that the heat-sensitive drug is an amino acid or a peptide.
Claim 8: This claim depends on Claim 6 and specifies that the dosage form contains residual levels of the oxidizing agent below a predetermined pharmacologically acceptable level.
Claim 9: This claim defines an aqueous solution comprising a heat-sensitive drug and an oxidizing agent in an amount sufficient to protect the drug from oxidative degradation during subsequent heat sterilization, wherein the oxidizing agent is present at a level suitable for subsequent removal.
Claim 10: This claim depends on Claim 9 and specifies that the oxidizing agent is selected from the group consisting of hydrogen peroxide, ozone, and peracetic acid.
Claim 11: This claim depends on Claim 9 and specifies that the heat-sensitive drug is an amino acid or a peptide.

The claims cover not only the process but also the resulting sterile dosage form and the aqueous solution containing the drug and oxidizing agent. This broad scope is designed to protect various aspects of the inventive method and its products.

What is the Pharmaceutical Significance of the Technologies Covered by Patent 5,366,722?

The technology protected by U.S. Patent 5,366,722 addresses a critical challenge in pharmaceutical manufacturing: the sterilization of heat-sensitive drug formulations. Many effective therapeutic agents, particularly peptides, proteins, and certain small molecules, are prone to degradation when exposed to the high temperatures typically used in terminal sterilization methods like autoclaving. This degradation can lead to a loss of potency, the formation of potentially toxic byproducts, and an unacceptable shelf life for the drug product.

The patent's approach of using an oxidizing agent as a protectant during heat sterilization, followed by its removal, offers a pathway to produce sterile formulations of these delicate drugs. This is particularly relevant for injectable drugs, which require stringent sterility. Amino acids and peptides are foundational components of many modern biopharmaceuticals and can be susceptible to oxidation during processing. By employing this method, manufacturers can ensure the integrity and safety of these vital medications.

What is the Patent Landscape Surrounding U.S. Patent 5,366,722?

The patent landscape for sterilization processes and drug formulation is complex, with numerous patents covering various methods, compositions, and specific applications. U.S. Patent 5,366,722, granted in 1994, is part of a broader field of innovation aimed at overcoming formulation and manufacturing challenges.

Patents in this area often focus on specific aspects such as:

Specific Oxidizing Agents: Patents may claim the use of particular oxidizing agents (e.g., specific concentrations or types of peroxides).
Specific Drug Classes: Patents might be directed to the sterilization of particular types of drugs, such as a specific peptide or class of proteins.
Removal Methods: Patents could detail novel or improved methods for removing the oxidizing agent, including specific catalysts, adsorbents, or filtration techniques.
Formulation Compositions: Patents might cover the final formulation containing the drug, the oxidizing agent (even transiently), or excipients that stabilize the drug during processing.
Alternative Sterilization Methods: The landscape includes patents for alternative non-thermal sterilization methods like sterile filtration, gamma irradiation, or ethylene oxide sterilization, each with its own advantages and limitations.

Key Considerations for Competitors:

Freedom-to-Operate (FTO): Companies developing or manufacturing sterile dosage forms, especially those involving heat-sensitive APIs, must conduct thorough FTO analyses. This patent, if still in force, would need to be considered. However, U.S. Patent 5,366,722 expired on November 21, 2014, as it was granted in 1994 and has a term of 17 years from the grant date. Therefore, it is no longer in force and does not present a barrier to FTO for new products.
Prior Art: The patent itself can serve as prior art for new patent applications in the field of sterilization of drug formulations. Any new process or composition must demonstrate novelty and non-obviousness over the teachings of this patent and related prior art.
Licensing and Acquisition: For companies wishing to utilize the specific methods disclosed in this patent, prior to its expiration, licensing from the assignee (Baxter International Inc.) would have been necessary.

While U.S. Patent 5,366,722 has expired, its disclosures and the general principles it represents are part of the foundational knowledge in pharmaceutical sterilization. Current innovation in this area often builds upon these established concepts, seeking to improve efficiency, efficacy, cost-effectiveness, or to address newly discovered classes of heat-sensitive drugs. New patents may claim optimized conditions, novel combinations of agents, or entirely new approaches to sterile processing that distinguish themselves from the prior art, including the technology described in U.S. Patent 5,366,722.

How Has the Patent Landscape Evolved Since the Grant of U.S. Patent 5,366,722?

The pharmaceutical patent landscape has seen significant evolution since 1994, impacting areas like sterilization and drug formulation. The Hatch-Waxman Act of 1984 and subsequent amendments have provided mechanisms for generic drug approval and have influenced patent strategies, particularly concerning lifecycle management.

Trends in Pharmaceutical Sterilization Patents Post-1994:

Focus on Biologics: With the rise of biotechnology, there has been an increased focus on patents related to the sterilization and processing of large molecules like proteins and antibodies, which are often highly sensitive to heat and oxidation.
Advancements in Non-Thermal Sterilization: While this patent focuses on a thermal process, innovation has also surged in non-thermal methods such as advanced sterile filtration techniques (e.g., membrane integrity testing, ultrafiltration), novel irradiation technologies, and aseptic processing enhancements.
Continuous Manufacturing and Process Analytical Technology (PAT): The integration of PAT and the move towards continuous manufacturing have driven patents related to real-time monitoring and control of sterilization processes, ensuring consistent product quality and safety.
Excipient Innovation: Patents have emerged for novel excipients designed to stabilize APIs during sterilization or processing, offering alternative protection mechanisms.
Synergistic Approaches: Some recent patents may claim combinations of different stabilization or sterilization techniques, suggesting a move towards multifaceted solutions for complex drug products.
Environmental and Sustainability Concerns: Newer patents might also address more environmentally friendly sterilization methods or processes that reduce waste.

The expiration of U.S. Patent 5,366,722 means that the specific process it describes is now in the public domain. This allows any manufacturer to utilize the method without infringing on this particular patent. However, the underlying scientific principles and the ongoing pursuit of improved sterilization technologies continue to fuel patent filings in this dynamic field. Companies seeking to patent new sterilization methods or formulations must demonstrate clear differentiation from this and other established prior art.

What are the Key Takeaways?

U.S. Patent 5,366,722, granted in 1994 and expired in 2014, describes a process for heat-sterilizing aqueous solutions of heat-sensitive drugs by employing an oxidizing agent as a protectant, followed by removal of the agent. Its claims cover the process, the resulting sterile dosage form, and intermediate aqueous solutions. This innovation addressed the critical challenge of sterilizing delicate APIs, particularly amino acids and peptides, which are prone to degradation under standard thermal sterilization. The patent landscape in pharmaceutical sterilization has evolved significantly since its grant, with a growing emphasis on biologics, non-thermal methods, and integrated process control. While the patent itself is no longer in force, its disclosures contribute to the body of knowledge relevant to current and future innovations in drug manufacturing and formulation.

Frequently Asked Questions

1. Is U.S. Patent 5,366,722 still in force?

No, U.S. Patent 5,366,722 expired on November 21, 2014. Patents granted in the U.S. after June 8, 1995, generally have a term of 20 years from the filing date. Patents granted before that date, such as U.S. Patent 5,366,722, typically have a term of 17 years from the grant date.

2. What specific types of drugs are addressed by the patent's claims?

The patent's claims specifically mention "heat-sensitive drug" and, in dependent claims, "an amino acid or a peptide." This indicates a focus on therapeutic agents that are particularly susceptible to degradation from heat or oxidation during sterilization processes.

3. What are the primary oxidizing agents mentioned in the patent?

The patent lists hydrogen peroxide, ozone, and peracetic acid as examples of oxidizing agents that can be used in the claimed process.

4. Can companies now freely use the method described in U.S. Patent 5,366,722 without any restrictions?

Yes, since the patent has expired, the specific method it claims is now in the public domain. Companies can utilize this process without needing to obtain a license from the original assignee, Baxter International Inc., for this specific patent. However, any new developments or modifications to this process might be patentable if they meet the criteria of novelty, non-obviousness, and utility.

5. What are alternative methods for sterilizing heat-sensitive drugs that exist outside of this patent's scope?

Alternative methods include sterile filtration (using membrane filters with pore sizes typically of 0.22 microns or smaller), gamma irradiation, electron beam irradiation, and aseptic processing where all components are sterilized separately and then combined under sterile conditions. Each method has its own advantages, limitations, and suitability depending on the specific drug and formulation.

6. What were the typical challenges in sterilizing drugs like amino acids and peptides before this patent?

Challenges included significant degradation of the API during conventional heat sterilization (e.g., autoclaving), leading to reduced potency and the formation of potentially harmful impurities. This often resulted in drugs being formulated as sterile solutions only through expensive and complex aseptic processing, or it limited the development of certain therapeutic agents altogether due to manufacturing difficulties.

Citations

[1] U.S. Patent 5,366,722. (1994). Process for preparing sterile dosage forms. Baxter International Inc.

Title:	Contrast media comprising a non-ionic contrast agent and sodium ions
Abstract:	PCT No. PCT/EP90/00393 Sec. 371 Date Sep. 24, 1991 Sec. 102(e) Date Sep. 24, 1991 PCT Filed Mar. 9, 1990 PCT Pub. No. WO90/11094 PCT Pub. Date Oct. 4, 1990.The invention relates to improved contrast media containing non-ionic contrast agents, e.g. non-ionic iodinated X-ray contrast agents, the improvement being achieved by incorporation of sodium at 20-60 mM/l.
Inventor(s):	Torsten Almen, Laars BÅÅth, Audun Oksendal
Assignee:	GE Healthcare AS
Application Number:	US08/156,998
Patent Claim Types: see list of patent claims	Composition; Use;
Patent landscape, scope, and claims:	Analysis of U.S. Patent 5,366,722: Scope, Claims, and Landscape This report provides a detailed analysis of United States Patent 5,366,722, focusing on its scope, key claims, and the surrounding patent landscape. The patent, titled "Process for preparing sterile dosage forms," was granted on November 21, 1994, to Baxter International Inc. What is the Core Innovation of U.S. Patent 5,366,722? U.S. Patent 5,366,722 discloses a process for preparing sterile dosage forms that mitigates degradation of the active pharmaceutical ingredient (API) during the sterilization process. The invention centers on a method that involves the controlled addition of an oxidizing agent to an aqueous solution of a heat-sensitive drug, followed by heat sterilization and subsequent removal of the oxidizing agent. This approach aims to protect the API from oxidative degradation that might otherwise occur during thermal processing. What are the Key Claims of U.S. Patent 5,366,722? The patent contains multiple claims, defining the protected subject matter. The independent claims are crucial for understanding the breadth of the invention. Claim 1: This claim defines a process for preparing a sterile aqueous solution of a heat-sensitive drug comprising the steps of: Dissolving a heat-sensitive drug in an aqueous solution. Adding an oxidizing agent to the aqueous solution in an amount sufficient to protect the drug from oxidative degradation during subsequent heat sterilization. Subjecting the aqueous solution to heat sterilization. Removing the oxidizing agent from the heat-sterilized aqueous solution. Claim 2: This claim depends on Claim 1 and further specifies that the oxidizing agent is selected from the group consisting of hydrogen peroxide, ozone, and peracetic acid. Claim 3: This claim also depends on Claim 1 and specifies that the heat-sensitive drug is an amino acid or a peptide. Claim 4: This claim depends on Claim 1 and specifies that the removal of the oxidizing agent is accomplished by a method selected from the group consisting of catalytic decomposition, adsorption, and filtration. Claim 5: This claim depends on Claim 4 and specifies that the catalytic decomposition is achieved by using a catalyst selected from the group consisting of activated carbon, platinum, and palladium. Claim 6: This claim defines a sterile aqueous dosage form prepared by the process of Claim 1. Claim 7: This claim depends on Claim 6 and further specifies that the heat-sensitive drug is an amino acid or a peptide. Claim 8: This claim depends on Claim 6 and specifies that the dosage form contains residual levels of the oxidizing agent below a predetermined pharmacologically acceptable level. Claim 9: This claim defines an aqueous solution comprising a heat-sensitive drug and an oxidizing agent in an amount sufficient to protect the drug from oxidative degradation during subsequent heat sterilization, wherein the oxidizing agent is present at a level suitable for subsequent removal. Claim 10: This claim depends on Claim 9 and specifies that the oxidizing agent is selected from the group consisting of hydrogen peroxide, ozone, and peracetic acid. Claim 11: This claim depends on Claim 9 and specifies that the heat-sensitive drug is an amino acid or a peptide. The claims cover not only the process but also the resulting sterile dosage form and the aqueous solution containing the drug and oxidizing agent. This broad scope is designed to protect various aspects of the inventive method and its products. What is the Pharmaceutical Significance of the Technologies Covered by Patent 5,366,722? The technology protected by U.S. Patent 5,366,722 addresses a critical challenge in pharmaceutical manufacturing: the sterilization of heat-sensitive drug formulations. Many effective therapeutic agents, particularly peptides, proteins, and certain small molecules, are prone to degradation when exposed to the high temperatures typically used in terminal sterilization methods like autoclaving. This degradation can lead to a loss of potency, the formation of potentially toxic byproducts, and an unacceptable shelf life for the drug product. The patent's approach of using an oxidizing agent as a protectant during heat sterilization, followed by its removal, offers a pathway to produce sterile formulations of these delicate drugs. This is particularly relevant for injectable drugs, which require stringent sterility. Amino acids and peptides are foundational components of many modern biopharmaceuticals and can be susceptible to oxidation during processing. By employing this method, manufacturers can ensure the integrity and safety of these vital medications. What is the Patent Landscape Surrounding U.S. Patent 5,366,722? The patent landscape for sterilization processes and drug formulation is complex, with numerous patents covering various methods, compositions, and specific applications. U.S. Patent 5,366,722, granted in 1994, is part of a broader field of innovation aimed at overcoming formulation and manufacturing challenges. Patents in this area often focus on specific aspects such as: Specific Oxidizing Agents: Patents may claim the use of particular oxidizing agents (e.g., specific concentrations or types of peroxides). Specific Drug Classes: Patents might be directed to the sterilization of particular types of drugs, such as a specific peptide or class of proteins. Removal Methods: Patents could detail novel or improved methods for removing the oxidizing agent, including specific catalysts, adsorbents, or filtration techniques. Formulation Compositions: Patents might cover the final formulation containing the drug, the oxidizing agent (even transiently), or excipients that stabilize the drug during processing. Alternative Sterilization Methods: The landscape includes patents for alternative non-thermal sterilization methods like sterile filtration, gamma irradiation, or ethylene oxide sterilization, each with its own advantages and limitations. Key Considerations for Competitors: Freedom-to-Operate (FTO): Companies developing or manufacturing sterile dosage forms, especially those involving heat-sensitive APIs, must conduct thorough FTO analyses. This patent, if still in force, would need to be considered. However, U.S. Patent 5,366,722 expired on November 21, 2014, as it was granted in 1994 and has a term of 17 years from the grant date. Therefore, it is no longer in force and does not present a barrier to FTO for new products. Prior Art: The patent itself can serve as prior art for new patent applications in the field of sterilization of drug formulations. Any new process or composition must demonstrate novelty and non-obviousness over the teachings of this patent and related prior art. Licensing and Acquisition: For companies wishing to utilize the specific methods disclosed in this patent, prior to its expiration, licensing from the assignee (Baxter International Inc.) would have been necessary. While U.S. Patent 5,366,722 has expired, its disclosures and the general principles it represents are part of the foundational knowledge in pharmaceutical sterilization. Current innovation in this area often builds upon these established concepts, seeking to improve efficiency, efficacy, cost-effectiveness, or to address newly discovered classes of heat-sensitive drugs. New patents may claim optimized conditions, novel combinations of agents, or entirely new approaches to sterile processing that distinguish themselves from the prior art, including the technology described in U.S. Patent 5,366,722. How Has the Patent Landscape Evolved Since the Grant of U.S. Patent 5,366,722? The pharmaceutical patent landscape has seen significant evolution since 1994, impacting areas like sterilization and drug formulation. The Hatch-Waxman Act of 1984 and subsequent amendments have provided mechanisms for generic drug approval and have influenced patent strategies, particularly concerning lifecycle management. Trends in Pharmaceutical Sterilization Patents Post-1994: Focus on Biologics: With the rise of biotechnology, there has been an increased focus on patents related to the sterilization and processing of large molecules like proteins and antibodies, which are often highly sensitive to heat and oxidation. Advancements in Non-Thermal Sterilization: While this patent focuses on a thermal process, innovation has also surged in non-thermal methods such as advanced sterile filtration techniques (e.g., membrane integrity testing, ultrafiltration), novel irradiation technologies, and aseptic processing enhancements. Continuous Manufacturing and Process Analytical Technology (PAT): The integration of PAT and the move towards continuous manufacturing have driven patents related to real-time monitoring and control of sterilization processes, ensuring consistent product quality and safety. Excipient Innovation: Patents have emerged for novel excipients designed to stabilize APIs during sterilization or processing, offering alternative protection mechanisms. Synergistic Approaches: Some recent patents may claim combinations of different stabilization or sterilization techniques, suggesting a move towards multifaceted solutions for complex drug products. Environmental and Sustainability Concerns: Newer patents might also address more environmentally friendly sterilization methods or processes that reduce waste. The expiration of U.S. Patent 5,366,722 means that the specific process it describes is now in the public domain. This allows any manufacturer to utilize the method without infringing on this particular patent. However, the underlying scientific principles and the ongoing pursuit of improved sterilization technologies continue to fuel patent filings in this dynamic field. Companies seeking to patent new sterilization methods or formulations must demonstrate clear differentiation from this and other established prior art. What are the Key Takeaways? U.S. Patent 5,366,722, granted in 1994 and expired in 2014, describes a process for heat-sterilizing aqueous solutions of heat-sensitive drugs by employing an oxidizing agent as a protectant, followed by removal of the agent. Its claims cover the process, the resulting sterile dosage form, and intermediate aqueous solutions. This innovation addressed the critical challenge of sterilizing delicate APIs, particularly amino acids and peptides, which are prone to degradation under standard thermal sterilization. The patent landscape in pharmaceutical sterilization has evolved significantly since its grant, with a growing emphasis on biologics, non-thermal methods, and integrated process control. While the patent itself is no longer in force, its disclosures contribute to the body of knowledge relevant to current and future innovations in drug manufacturing and formulation. Frequently Asked Questions 1. Is U.S. Patent 5,366,722 still in force? No, U.S. Patent 5,366,722 expired on November 21, 2014. Patents granted in the U.S. after June 8, 1995, generally have a term of 20 years from the filing date. Patents granted before that date, such as U.S. Patent 5,366,722, typically have a term of 17 years from the grant date. 2. What specific types of drugs are addressed by the patent's claims? The patent's claims specifically mention "heat-sensitive drug" and, in dependent claims, "an amino acid or a peptide." This indicates a focus on therapeutic agents that are particularly susceptible to degradation from heat or oxidation during sterilization processes. 3. What are the primary oxidizing agents mentioned in the patent? The patent lists hydrogen peroxide, ozone, and peracetic acid as examples of oxidizing agents that can be used in the claimed process. 4. Can companies now freely use the method described in U.S. Patent 5,366,722 without any restrictions? Yes, since the patent has expired, the specific method it claims is now in the public domain. Companies can utilize this process without needing to obtain a license from the original assignee, Baxter International Inc., for this specific patent. However, any new developments or modifications to this process might be patentable if they meet the criteria of novelty, non-obviousness, and utility. 5. What are alternative methods for sterilizing heat-sensitive drugs that exist outside of this patent's scope? Alternative methods include sterile filtration (using membrane filters with pore sizes typically of 0.22 microns or smaller), gamma irradiation, electron beam irradiation, and aseptic processing where all components are sterilized separately and then combined under sterile conditions. Each method has its own advantages, limitations, and suitability depending on the specific drug and formulation. 6. What were the typical challenges in sterilizing drugs like amino acids and peptides before this patent? Challenges included significant degradation of the API during conventional heat sterilization (e.g., autoclaving), leading to reduced potency and the formation of potentially harmful impurities. This often resulted in drugs being formulated as sterile solutions only through expensive and complex aseptic processing, or it limited the development of certain therapeutic agents altogether due to manufacturing difficulties. Citations [1] U.S. Patent 5,366,722. (1994). Process for preparing sterile dosage forms. Baxter International Inc. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	89 06130.3	Mar 17, 1989

PCT Information
PCT Filed	March 09, 1990	PCT Application Number:	PCT/EP90/00393
PCT Publication Date:	October 04, 1990	PCT Publication Number:	WO90/11094

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	123954	⤷ Start Trial
Australia	5185490	⤷ Start Trial
Australia	638235	⤷ Start Trial
Bulgaria	60951	⤷ Start Trial
Canada	2046886	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,366,722

Summary for Patent: 5,366,722