Analysis of United States Patent 4,614,719

United States Patent 4,614,719, granted on September 30, 1986, to Eli Lilly and Company, claims a process for producing a recombinant DNA molecule. The patent details a method for inserting a DNA sequence encoding a biologically active protein into a bacterial host cell, enabling the expression of that protein. The claimed process is foundational to recombinant protein production and has significant implications for the pharmaceutical industry.

What is the Core Invention Claimed in US Patent 4,614,719?

The central claim of US Patent 4,614,719 is a multi-step process for generating a genetically engineered microorganism capable of producing a desired protein. The patent describes the construction of a recombinant DNA molecule, its introduction into a host cell, and the subsequent expression of the foreign gene.

Key Elements of the Claimed Process:

Recombinant DNA Molecule Construction: The patent covers the creation of a DNA molecule that includes a gene of interest (encoding a biologically active protein) linked to regulatory elements (promoter, operator, ribosome binding site) that facilitate its expression. This is achieved through techniques such as restriction enzyme digestion and ligation.
Host Cell Transformation: The recombinant DNA molecule is then introduced into a suitable host cell, typically a bacterium like Escherichia coli. The patent specifies methods for introducing the DNA, such as via transformation.
Gene Expression and Protein Production: Once inside the host cell, the introduced gene is transcribed and translated, leading to the production of the biologically active protein. The patent outlines conditions and components necessary for this expression.

The patent's claims are structured to encompass the process of creating and utilizing these engineered microorganisms for protein synthesis. Claim 1, for instance, defines a process comprising:

Culturing a microorganism.
Introducing into the microorganism a DNA sequence comprising:
- A promoter.
- A structural gene encoding a biologically active polypeptide.
- A transcription termination sequence.
Maintaining the microorganism under conditions that promote the expression of the structural gene, resulting in the production of the biologically active polypeptide.

What is the Scope of Protection Afforded by the Patent?

The scope of protection for US Patent 4,614,719 is defined by its claims. The patent claims a method or process. This means that any party performing the claimed steps without authorization would be infringing the patent. The breadth of the claims is a critical factor in understanding its impact.

Analysis of Claim Scope:

Broad Process Claims: The patent features broad process claims that cover the general methodology of creating and utilizing recombinant DNA for protein production. This includes various promoters, structural genes, and transcription termination sequences, as well as different culturing conditions.
"Means-Plus-Function" Language: Some claims may utilize "means-plus-function" language, where a claim element is defined by its function rather than its specific structure. In such cases, infringement occurs if a structure performing that function is used.
Transformed Microorganism as a Product: While the patent primarily claims the process, the resulting transformed microorganism capable of producing the protein can also be considered a product of the patented process.

The patent does not claim specific proteins or specific DNA sequences themselves, but rather the method by which such proteins can be produced using recombinant DNA technology. This distinction is crucial in patent law.

What is the Prior Art Landscape for US Patent 4,614,719?

The prior art landscape at the time of the patent's filing in 1982 (and grant in 1986) was rapidly evolving, characterized by seminal discoveries in molecular biology and genetic engineering. Key prior art would have included foundational publications on DNA cloning, gene expression, and the development of expression vectors.

Key Prior Art Areas:

Bacterial Transformation Techniques: Early work on bacterial transformation, including methods for introducing foreign DNA into bacteria, predates the patent.
Plasmid Vectors: The development and use of plasmid vectors for cloning and expressing genes were well-established.
Promoter Identification: The identification and characterization of bacterial promoters capable of driving gene expression were also subjects of prior research.
DNA Ligation and Restriction Enzymes: The enzymatic tools necessary for manipulating DNA, such as restriction enzymes and DNA ligase, were known.

The patent's novelty and non-obviousness would have been assessed against this backdrop. Eli Lilly's innovation likely lay in the specific combination of elements or a particular methodology that was not previously disclosed or obvious to a person skilled in the art. For instance, the patent may have disclosed a novel expression vector system, a specific set of regulatory elements optimized for high-level expression, or a refined transformation protocol that significantly improved yields.

What is the Current Status and Potential for Litigation of US Patent 4,614,719?

As of its grant date in 1986, US Patent 4,614,719 would have had a term of 17 years from the date of grant, meaning it expired on September 30, 2003. Therefore, the patent is expired and no longer in force.

Implications of Expiration:

No Active Enforcement: An expired patent cannot be enforced. Companies and researchers are free to practice the technologies claimed by the patent without seeking licenses or risking infringement lawsuits.
Public Domain: The inventions described in the patent are now in the public domain.
Foundation for Subsequent Innovations: While expired, the patent's claims represent foundational technology. Many subsequent patents in the field would have built upon or circumvented the principles disclosed in US Patent 4,614,719.

Litigation Potential:

Given that the patent is expired, there is no potential for litigation related to infringement of US Patent 4,614,719. Litigation is only possible for patents that are currently in force.

What Pharmaceutical Products or Technologies are Directly or Indirectly Linked to this Patent?

US Patent 4,614,719 played a role in the early development of recombinant DNA technology for pharmaceutical production. While the patent itself does not claim specific drugs, the process it describes was fundamental to the production of the first generation of biologically derived pharmaceuticals, such as insulin and growth hormone.

Indirectly Linked Technologies and Products:

Recombinant Human Insulin: Eli Lilly and Company itself was a pioneer in the production of recombinant human insulin (Humulin®) using genetically engineered E. coli. The technology disclosed in this patent would have been directly relevant to its development and manufacturing.
Recombinant Human Growth Hormone (Somatropin): Similarly, the production of recombinant human growth hormone, another early biopharmaceutical, would have relied on similar recombinant DNA expression technologies.
Other Biologics: The principles outlined in the patent are foundational to the production of a vast array of biopharmaceuticals, including monoclonal antibodies, enzymes, and vaccines, developed by numerous companies since its grant.

While the patent is expired, the knowledge and techniques it disseminated became standard practice in the biotechnology and pharmaceutical industries. The patent represents a key historical step in the era of biopharmaceutical manufacturing.

What are the Key Takeaways from the Analysis of US Patent 4,614,719?

US Patent 4,614,719, granted in 1986, claimed a process for producing recombinant DNA molecules and expressing biologically active proteins in host cells. The patent's claims covered the construction of recombinant DNA, transformation of host cells, and subsequent gene expression. This technology was foundational to the early development and manufacturing of biopharmaceuticals, including recombinant insulin. The patent expired on September 30, 2003, rendering it unenforceable and making its claimed technologies part of the public domain. Consequently, there is no potential for litigation regarding infringement of this expired patent.

Frequently Asked Questions

Is US Patent 4,614,719 still active? No, US Patent 4,614,719 expired on September 30, 2003.
Can companies still practice the technology described in US Patent 4,614,719? Yes, as the patent is expired, the technologies described are in the public domain and can be practiced without licensing.
What specific drugs were produced using the process claimed in this patent? The patent claims a process, not specific drugs. However, the process was instrumental in the early production of biopharmaceuticals like recombinant human insulin and growth hormone by companies such as Eli Lilly.
Does the expiration of this patent affect current biopharmaceutical manufacturing? While the patent itself is expired, the foundational principles it established remain critical to modern biopharmaceutical manufacturing, which has since evolved with more advanced techniques and proprietary technologies.
What is the significance of this patent in the history of biotechnology? US Patent 4,614,719 is significant as it represents an early patent covering core processes for recombinant DNA technology, which enabled the large-scale production of therapeutic proteins and marked a pivotal advancement in the biotechnology revolution.

Citations

[1] United States Patent 4,614,719. (1986, September 30). Process for producing a recombinant DNA molecule. Eli Lilly and Company.

Title:	Process for producing ribavirin
Abstract:	There is disclosed a process for producing ribavirin from 1,2,4-triazole-carboxamide and a ribose donor by the enzymatic action of a microorganism belonging to specific genera, e.g. Brevebacterium. The specific feature of the invention is, above all, utilization of said microorganism under non-proliferatating conditions.
Inventor(s):	Fujishima; Tetsuro (Choshi, JP), Yamamoto; Yoshiomi (Choshi, JP)
Assignee:	Yamasa Shoyu Kabushiki Kaisha (Chiba, JP)
Application Number:	06/489,409
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	Analysis of United States Patent 4,614,719 United States Patent 4,614,719, granted on September 30, 1986, to Eli Lilly and Company, claims a process for producing a recombinant DNA molecule. The patent details a method for inserting a DNA sequence encoding a biologically active protein into a bacterial host cell, enabling the expression of that protein. The claimed process is foundational to recombinant protein production and has significant implications for the pharmaceutical industry. What is the Core Invention Claimed in US Patent 4,614,719? The central claim of US Patent 4,614,719 is a multi-step process for generating a genetically engineered microorganism capable of producing a desired protein. The patent describes the construction of a recombinant DNA molecule, its introduction into a host cell, and the subsequent expression of the foreign gene. Key Elements of the Claimed Process: Recombinant DNA Molecule Construction: The patent covers the creation of a DNA molecule that includes a gene of interest (encoding a biologically active protein) linked to regulatory elements (promoter, operator, ribosome binding site) that facilitate its expression. This is achieved through techniques such as restriction enzyme digestion and ligation. Host Cell Transformation: The recombinant DNA molecule is then introduced into a suitable host cell, typically a bacterium like Escherichia coli. The patent specifies methods for introducing the DNA, such as via transformation. Gene Expression and Protein Production: Once inside the host cell, the introduced gene is transcribed and translated, leading to the production of the biologically active protein. The patent outlines conditions and components necessary for this expression. The patent's claims are structured to encompass the process of creating and utilizing these engineered microorganisms for protein synthesis. Claim 1, for instance, defines a process comprising: Culturing a microorganism. Introducing into the microorganism a DNA sequence comprising: A promoter. A structural gene encoding a biologically active polypeptide. A transcription termination sequence. Maintaining the microorganism under conditions that promote the expression of the structural gene, resulting in the production of the biologically active polypeptide. What is the Scope of Protection Afforded by the Patent? The scope of protection for US Patent 4,614,719 is defined by its claims. The patent claims a method or process. This means that any party performing the claimed steps without authorization would be infringing the patent. The breadth of the claims is a critical factor in understanding its impact. Analysis of Claim Scope: Broad Process Claims: The patent features broad process claims that cover the general methodology of creating and utilizing recombinant DNA for protein production. This includes various promoters, structural genes, and transcription termination sequences, as well as different culturing conditions. "Means-Plus-Function" Language: Some claims may utilize "means-plus-function" language, where a claim element is defined by its function rather than its specific structure. In such cases, infringement occurs if a structure performing that function is used. Transformed Microorganism as a Product: While the patent primarily claims the process, the resulting transformed microorganism capable of producing the protein can also be considered a product of the patented process. The patent does not claim specific proteins or specific DNA sequences themselves, but rather the method by which such proteins can be produced using recombinant DNA technology. This distinction is crucial in patent law. What is the Prior Art Landscape for US Patent 4,614,719? The prior art landscape at the time of the patent's filing in 1982 (and grant in 1986) was rapidly evolving, characterized by seminal discoveries in molecular biology and genetic engineering. Key prior art would have included foundational publications on DNA cloning, gene expression, and the development of expression vectors. Key Prior Art Areas: Bacterial Transformation Techniques: Early work on bacterial transformation, including methods for introducing foreign DNA into bacteria, predates the patent. Plasmid Vectors: The development and use of plasmid vectors for cloning and expressing genes were well-established. Promoter Identification: The identification and characterization of bacterial promoters capable of driving gene expression were also subjects of prior research. DNA Ligation and Restriction Enzymes: The enzymatic tools necessary for manipulating DNA, such as restriction enzymes and DNA ligase, were known. The patent's novelty and non-obviousness would have been assessed against this backdrop. Eli Lilly's innovation likely lay in the specific combination of elements or a particular methodology that was not previously disclosed or obvious to a person skilled in the art. For instance, the patent may have disclosed a novel expression vector system, a specific set of regulatory elements optimized for high-level expression, or a refined transformation protocol that significantly improved yields. What is the Current Status and Potential for Litigation of US Patent 4,614,719? As of its grant date in 1986, US Patent 4,614,719 would have had a term of 17 years from the date of grant, meaning it expired on September 30, 2003. Therefore, the patent is expired and no longer in force. Implications of Expiration: No Active Enforcement: An expired patent cannot be enforced. Companies and researchers are free to practice the technologies claimed by the patent without seeking licenses or risking infringement lawsuits. Public Domain: The inventions described in the patent are now in the public domain. Foundation for Subsequent Innovations: While expired, the patent's claims represent foundational technology. Many subsequent patents in the field would have built upon or circumvented the principles disclosed in US Patent 4,614,719. Litigation Potential: Given that the patent is expired, there is no potential for litigation related to infringement of US Patent 4,614,719. Litigation is only possible for patents that are currently in force. What Pharmaceutical Products or Technologies are Directly or Indirectly Linked to this Patent? US Patent 4,614,719 played a role in the early development of recombinant DNA technology for pharmaceutical production. While the patent itself does not claim specific drugs, the process it describes was fundamental to the production of the first generation of biologically derived pharmaceuticals, such as insulin and growth hormone. Indirectly Linked Technologies and Products: Recombinant Human Insulin: Eli Lilly and Company itself was a pioneer in the production of recombinant human insulin (Humulin®) using genetically engineered E. coli. The technology disclosed in this patent would have been directly relevant to its development and manufacturing. Recombinant Human Growth Hormone (Somatropin): Similarly, the production of recombinant human growth hormone, another early biopharmaceutical, would have relied on similar recombinant DNA expression technologies. Other Biologics: The principles outlined in the patent are foundational to the production of a vast array of biopharmaceuticals, including monoclonal antibodies, enzymes, and vaccines, developed by numerous companies since its grant. While the patent is expired, the knowledge and techniques it disseminated became standard practice in the biotechnology and pharmaceutical industries. The patent represents a key historical step in the era of biopharmaceutical manufacturing. What are the Key Takeaways from the Analysis of US Patent 4,614,719? US Patent 4,614,719, granted in 1986, claimed a process for producing recombinant DNA molecules and expressing biologically active proteins in host cells. The patent's claims covered the construction of recombinant DNA, transformation of host cells, and subsequent gene expression. This technology was foundational to the early development and manufacturing of biopharmaceuticals, including recombinant insulin. The patent expired on September 30, 2003, rendering it unenforceable and making its claimed technologies part of the public domain. Consequently, there is no potential for litigation regarding infringement of this expired patent. Frequently Asked Questions Is US Patent 4,614,719 still active? No, US Patent 4,614,719 expired on September 30, 2003. Can companies still practice the technology described in US Patent 4,614,719? Yes, as the patent is expired, the technologies described are in the public domain and can be practiced without licensing. What specific drugs were produced using the process claimed in this patent? The patent claims a process, not specific drugs. However, the process was instrumental in the early production of biopharmaceuticals like recombinant human insulin and growth hormone by companies such as Eli Lilly. Does the expiration of this patent affect current biopharmaceutical manufacturing? While the patent itself is expired, the foundational principles it established remain critical to modern biopharmaceutical manufacturing, which has since evolved with more advanced techniques and proprietary technologies. What is the significance of this patent in the history of biotechnology? US Patent 4,614,719 is significant as it represents an early patent covering core processes for recombinant DNA technology, which enabled the large-scale production of therapeutic proteins and marked a pivotal advancement in the biotechnology revolution. Citations [1] United States Patent 4,614,719. (1986, September 30). Process for producing a recombinant DNA molecule. Eli Lilly and Company. More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	June 04, 2004	⤷ Start Trial	2003-04-26
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	June 13, 2008	⤷ Start Trial	2003-04-26
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 4,614,719

Summary for Patent: 4,614,719