Comprehensive Analysis of United States Patent 5,618,913: Insulin Analogues
Introduction
United States Patent 5,618,913, titled "Insulin Analogues," was granted to Jens J. V. Brange, Kjeld Norris, and Mogens T. Hansen of Novo Nordisk A/S on April 8, 1997. This patent is pivotal in the development of rapid-acting human insulin analogues, which have significantly improved the management of diabetes.
Background of the Invention
Insulin, a hormone crucial for glucose metabolism, is secreted by the pancreas and consists of two polypeptide chains: the A-chain with 21 amino acids and the B-chain with 30 amino acids. Traditional human insulin has limitations, such as a delayed onset of action, which can be problematic for diabetic patients. The inventors aimed to create insulin analogues with a faster onset and shorter duration of action to better mimic natural insulin secretion[1][4].
Key Claims of the Patent
The patent describes several key innovations:
Rapid-Acting Insulin Analogues
The inventors developed insulin analogues with reduced self-association into dimers and tetramers, which is a significant factor in the delayed onset of action of traditional insulin. By substituting specific amino acids, they achieved analogues with improved miscibility and faster absorption rates[1].
Specific Amino Acid Substitutions
One of the primary claims involves substituting Glu for Thr in position 27 of the shortened B-chain and connecting the B(1-29)-chain and the A-chain via the peptide sequence Ala-Ala-Lys. These substitutions enhance the solubility and reduce the tendency for self-association, leading to a more rapid onset of action[1].
Production Method
The patent outlines a method for producing these insulin analogues using yeast expression systems. A DNA sequence encoding the precursor of the insulin analogue is inserted into a yeast expression vehicle, allowing for the expression and secretion of the analogue with correctly positioned disulfide bridges[1].
Patent Landscape Analysis
Geographical Spread
The geographical spread of patents related to insulin analogues is predominantly centered in Europe and North America, with significant contributions from Denmark, where Novo Nordisk is based, and the United States. This concentration reflects the strong research and development capabilities in these regions[3].
Saturation of the Patent Space
The patent space for insulin analogues is relatively saturated, with numerous patents filed over the years by various pharmaceutical companies. However, the specific innovations in US 5,618,913, such as the rapid-acting analogues, carved out a unique niche within this saturated space[3].
Competitors and New Entrants
Major competitors in the insulin analogue market include Sanofi Aventis (with their product Lantus), Eli Lilly, and Novo Nordisk itself. New entrants into this space must navigate the complex patent landscape and often focus on developing new analogues or improving existing production methods to avoid infringement[3].
Time-Slicing and Technological Evolution
Analyzing the patent landscape over time reveals a significant evolution in insulin technology. Early patents focused on traditional human insulin, while later patents, such as US 5,618,913, introduced rapid-acting and long-acting analogues. This evolution continues, with recent patents focusing on even more advanced formulations and delivery systems[3].
Strategic Insights
Patentability and Freedom to Operate
Given the saturated nature of the patent space, conducting thorough patentability searches and freedom-to-operate analyses is crucial for any new entrant. This involves identifying potential prior art and understanding the claims of existing patents to avoid infringement[3].
Niche Areas
Despite the saturation, there are underappreciated niche areas within the insulin analogue space. For example, developing analogues with improved stability, reduced immunogenicity, or novel delivery systems can provide a competitive edge. Identifying these niches through comprehensive patent landscape analysis can guide R&D efforts[3].
Impact on Diabetes Management
Clinical Benefits
The rapid-acting insulin analogues developed under this patent have significantly improved the clinical management of diabetes. These analogues offer a faster onset of action, which helps in better controlling postprandial glucose levels, thereby reducing the risk of hyperglycemia and its complications[1].
Market Impact
The introduction of these analogues has expanded the market for insulin products, providing patients with more options tailored to their specific needs. This has driven competition and innovation, leading to further advancements in insulin therapy[5].
Expiration and Current Status
The patent for US 5,618,913 has expired, which means that the technology described is now in the public domain. This has allowed other companies to develop similar rapid-acting insulin analogues, increasing competition and reducing costs for patients[4].
Conclusion
United States Patent 5,618,913 represents a critical milestone in the development of insulin analogues. The innovations described in this patent have transformed the management of diabetes by providing rapid-acting insulin solutions. Understanding the patent landscape and the strategic insights derived from it is essential for companies looking to innovate in this field.
Key Takeaways
- Rapid-Acting Analogues: The patent introduced rapid-acting insulin analogues with reduced self-association.
- Amino Acid Substitutions: Specific substitutions like Glu for Thr in position 27 of the B-chain were key.
- Production Method: Yeast expression systems were used for production.
- Patent Landscape: The space is saturated, but niche areas exist for innovation.
- Clinical Benefits: Improved postprandial glucose control and reduced hyperglycemia risk.
- Market Impact: Expanded market options and driven competition.
FAQs
What is the main innovation of US 5,618,913?
The main innovation is the development of rapid-acting human insulin analogues with reduced self-association into dimers and tetramers.
Who are the inventors of US 5,618,913?
The inventors are Jens J. V. Brange, Kjeld Norris, and Mogens T. Hansen of Novo Nordisk A/S.
What is the significance of amino acid substitutions in the patent?
The substitutions, such as Glu for Thr in position 27 of the B-chain, enhance the solubility and reduce self-association, leading to a faster onset of action.
How has the patent impacted diabetes management?
It has provided rapid-acting insulin analogues that better control postprandial glucose levels, reducing the risk of hyperglycemia and its complications.
Is the patent still in effect?
No, the patent has expired, allowing the technology to be in the public domain.
What are the implications of the patent's expiration?
The expiration has led to increased competition and the development of similar products by other companies, potentially reducing costs for patients.
Sources
- US5618913A - Insulin analogues - Google Patents
- US20120214965A1 - Glargine proinsulin and methods of producing glargine insulin analogs - Google Patents
- Patent Landscape Analysis - Uncovering Strategic Insights - AcclaimIP
- US5618913A - Insulin analogues - Patent Images
- Insulin Patent Profile - ResearchGate
