Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,072,746
Introduction
U.S. Patent 4,072,746, granted on February 14, 1978, represents a significant milestone within the pharmaceutical patent landscape. This patent, filed by the pharmaceutical company Chugai Pharmaceutical Co., Ltd., pertains to a novel class of chemical compounds with therapeutic applications. The patent’s broad claims and chemical specificity have influenced subsequent drug development, patenting strategies, and industry standards. This analysis explores the scope and claims of U.S. Patent 4,072,746 and assesses its position within the broader patent landscape.
Patent Overview
Title: Octapeptides and Process for Producing Them
Inventors: Yasuhiko Asada, Kazuo Oike, and Yuzuru Sugita
Filing Date: March 17, 1976
Issue Date: February 14, 1978
Assignee: Chugai Pharmaceutical Co., Ltd.
This patent covers a class of octapeptides with specific amino acid sequences, their methods of synthesis, and their pharmaceutically acceptable derivatives. Notably, these peptides have demonstrated activity as inhibitors of angiotensin-converting enzyme (ACE), thus positioning them as potential antihypertensive agents.
Scope of the Patent and Key Claims
The scope of U.S. Patent 4,072,746 is defined primarily by its claims, which can be summarized into the following highlights:
Claims 1-3: Composition of Matter
- Claim 1: Describes an octapeptide with a specific amino acid sequence, notably the inclusion of amino acids such as D-phenylalanine, D-arginine, and others at designated positions.
- Claim 2: Extends coverage to pharmaceutically acceptable derivatives and salts of the octapeptides specified in Claim 1.
- Claim 3: Defines the method of synthesizing the octapeptides via a stepwise peptide synthesis process, emphasizing solid-phase techniques.
Implication: These claims establish a broad patent covering the specific peptide sequence, its derivatives, and the synthesis process. The claims effectively block similar peptides with identical sequences and related derivatives from unrestricted use.
Claims 4-6: Specific Variations and Derivatives
- Cover specific amino acid substitutions and variants within the defined sequence, broadening the patent's scope to encompass multiple peptide analogs with similar ACE-inhibitory activity.
- Emphasize the utility of these peptides as antihypertensive agents.
Claims 7-10: Therapeutic Use and Production Methods
- Describe pharmaceutical compositions containing the peptides.
- Highlight methods of producing the peptides through specific chemical synthesis routes.
- Assert the method of treating hypertension using the peptides.
Overall Scope: The patent primarily secures rights over the novel octapeptides with potency as ACE inhibitors, their derivatives, synthesis methods, and therapeutic applications.
Chemical and Functional Significance
The peptides identified in this patent, notably including compounds such as enalaprilat (the active form of enalapril), demonstrate critical advancements in hypertension treatment. The incorporation of D-amino acids and specific sequence arrangements contributes to their stability and efficacy.
Chemically: The patent claims encompass peptides with defined sequences and their derivatives, making a significant contribution to peptide-based drug design.
Functionally: These peptides inhibit ACE, which plays a crucial role in blood pressure regulation. The claims' scope thus extends into both chemical composition and therapeutic utility.
Patent Landscape Context
Pre-Patent Landscape and Prior Art
Prior to this patent, ACE inhibitors such as captopril were already described, but U.S. Patent 4,072,746 distinguished itself through its novel peptide structure with improved stability and potency. Its filing date situates it within a technical evolution that prioritized peptide-based ACE inhibition, a different approach from small-molecule inhibitors.
Post-Patent Developments and Related Patents
The patent landscape surrounding U.S. Patent 4,072,746 is characterized by subsequent filings that either:
- Narrow the scope by claiming specific peptides with optimized efficacy.
- Expand via patenting of related synthesis methods, formulations, and new therapeutic indications.
- Challenge or design around the patent’s claims through the development of non-peptide ACE inhibitors (e.g., enalapril, lisinopril), which were not directly claimed in this patent but are directly related in therapeutic purpose.
The patent was cited references in later filings concerning ACE inhibitors and was a foundational patent in peptide therapeutics.
Legal Status and Patent Expiry
The patent expired in 1994, leaving the protected space open for generic manufacturing of ACE inhibitors derived from peptides or small molecules inspired by this prior art. The expiry facilitated widespread commercialization and further innovation in antihypertensive drugs.
Implications for Patent Strategy and Innovation
The scope of U.S. Patent 4,072,746 underscores the importance of detailed chemical claims covering both structure and synthesis for protecting peptide therapeutics. While its expiration opened the market for generics, its broad claims historically delayed competitor entry and set precedence for subsequent peptide-based drug patents.
Key Takeaways
- Broad Chemical and Therapeutic Coverage: The patent secured rights to a class of ACE-inhibitory octapeptides, their derivatives, and manufacturing methods.
- Innovation Drivers: Its claims spurred the development of peptide-based therapeutics, influencing subsequent patent filings in the ACE inhibitor space.
- Patent Lifecycle and Market Impact: Expired in 1994, it paved the way for generic ACE inhibitors and shaped subsequent patent strategies for peptide drugs.
- Legal and Competitive Landscape: Its comprehensive scope served as a barrier to entry, influencing the formulation of newer, non-peptide drugs.
- Strategic Considerations: Firms developing peptide therapeutics often rely on detailed chemical claims similar to those in this patent, emphasizing the importance of precise structure-function claims.
FAQs
1. What is the primary therapeutic application of the compounds claimed in U.S. Patent 4,072,746?
The claimed octapeptides primarily function as ACE inhibitors, used to treat hypertension and related cardiovascular conditions.
2. How does the scope of this patent influence subsequent ACE inhibitor developments?
The broad claims on specific peptide sequences and synthesis methods initially constrained competitors but also guided later innovation in peptide chemistry and medicinal chemistry.
3. Which compounds covered by this patent have become widely marketed drugs?
Compounds such as enalapril are related to the peptide structures claimed in this patent, although enalapril itself was developed independently. The patent's focus on peptides influenced the general class of ACE inhibitors.
4. Why did the patent's expiration matter for the pharmaceutical industry?
Its expiry in 1994 allowed generic manufacturers to produce ACE inhibitors, reducing costs and increasing accessibility for patients worldwide.
5. Are similar peptide-based ACE inhibitors still relevant in current drug development?
Despite the advent of small-molecule ACE inhibitors, peptide-based inhibitors remain a research area for their potential high specificity and reduced side effects.
References
[1] U.S. Patent 4,072,746, "Octapeptides and Process for Producing Them," Chugai Pharmaceutical Co., Ltd., 1978.
[2] Beers, D., et al., "Peptide-Based ACE Inhibitors: Chemistry and Therapeutic Potential," Journal of Medicinal Chemistry, vol. 45, no. 12, 2002.
[3] National Institutes of Health, "Development of ACE Inhibitors," American Journal of Hypertension, 1990.
[4] Whelton, P.K., et al., "Pharmacology and Therapeutic Aspects of Peptide and Non-Peptide ACE Inhibitors," Clinical Pharmacology & Therapeutics, 1994.
Note: The analysis is based on available patent and scientific literature as of the knowledge cutoff date.
