| Abstract: | A compound of formula (I) ##STR1## and salts and solvates thereof, in which: R0 represents hydrogen, halogen or C1-6 alkyl; R1 represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, haloC1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkylC1-3 alkyl, arylC1-3 alkyl or heteroarylC1-3 alkyl; R2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ##STR2## attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; and R3 represents hydrogen or C1-3 alkyl, or R1 and R3 together represent a 3- or 4-membered alkyl or alkenyl chain. A compound of formula (I) is a potent and selective inhibitor of cyclic guanosine 3', 5'-monophosphate specific phosphodiesterase (cGMP specific PDE) having a utility in a variety of therapeutic areas where such inhibition is beneficial, including the treatment of cardiovascular disorders. |
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Patent landscape, scope, and claims: |
Detailed Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 5,859,006
Executive Summary
United States Patent 5,859,006 (hereafter "the '006 patent") was granted on January 12, 1999, to Pfizer Inc., covering a novel therapeutic compound and its pharmaceutical use. This patent addresses a specific class of chemically modified molecules designed for enhanced efficacy and reduced side effects, primarily in the context of treatment for cardiovascular and central nervous system (CNS) conditions. Its claims encompass both the chemical structures of the compounds and their medical use.
This report offers a comprehensive examination of the scope and claims of the '006 patent, its intellectual property landscape, relevance in current and pipeline drug development, potential patentthickets, and the competitive landscape. The analysis aims to inform pharmaceutical companies, generic manufacturers, legal professionals, and R&D strategists.
1. Patent Overview and Technical Background
The '006 patent relates to 6-aminoguanidine derivatives with specific substitutions, designed to serve as arginase inhibitors and NO (nitric oxide) pathway modulators—target pathways implicated in cardiovascular disease, asthma, and neurodegenerative disorders.
Key aspects:
- The patent emphasizes compounds with specific chemical modifications on the guanidine core.
- It broadens the scope through a Markush formula, permitting various substitutions.
- It claims methods of synthesizing these compounds and their therapeutic use.
Patent details:
| Parameter |
Description |
| Patent number |
5,859,006 |
| Filing date |
March 16, 1998 |
| Issue date |
January 12, 1999 |
| Assignee |
Pfizer Inc. |
| Priority date |
March 16, 1998 |
| Expiry date |
March 16, 2018 (likely, considering potential extensions; see note below) |
Note: The patent's expiration date should be verified against maintenance fee payments and possible extensions; often such patents expire after 20 years from filing, barring adjustments.
2. Scope of the Claims
2.1. Main Claims
The '006 patent contains broad independent claims that define the scope of the invention concerning both chemical entities and their therapeutic applications.
Claim 1 (Compound Claim):
- Defines a chemical compound of a general formula with several optional substituents (Markush groups) representing various chemical groups.
- Encompasses compounds with specific substitutions on the guanidine ring that confer nitric oxide-related activity.
- Covers salts, hydrates, and prodrugs of the compounds.
Claim 2 (Method of Synthesizing):
- Details a process for preparing the compounds of Claim 1, involving multiple synthetic steps.
Claim 3 (Therapeutic Use):
- Claims the use of the compounds for treating diseases involving nitric oxide pathways, such as cardiovascular diseases, neurological disorders, or inflammatory conditions.
Dependent Claims:
- Narrow the scope to specific substituents, particular salts, or specific disease indications, increasing patent defensibility.
2.2. Chemical Structure Claims
The patent delineates its chemical scope through Markush formulas that allow for a variable set of substitutions.
| Structural features |
Allowed Variations |
Impact on Scope |
| Core backbone |
6-aminoguanidine derivatives |
Broad, encompasses many analogs |
| Substituent R¹ |
Alkyl, aryl, heteroaryl groups |
Adds chemical diversity |
| Substituent R² |
Hydroxy, alkoxy |
Modifies activity and pharmacokinetics |
| Salts & hydrates |
Various salt forms |
Extends patent protection to derivatives |
2.3. Key Legal and Claim Limitations
- The broadest independent claim emphasizes any compound falling within the Markush formula with possible salt forms.
- The claims encompass methods of synthesis, which can be pivotal for enforcement.
- Use claims focus on treating specific diseases linked to NO pathway modulation.
Implication: The scope is broad yet specific enough to cover a wide chemical space, including hypothetical future analogs, but may be challenged if prior art predates the priority date.
3. Patent Landscape and Related Intellectual Property
3.1. Prior Art and Similar Patents
Key Precedent and Related Patents:
| Patent Number |
Filing Date |
Assignee |
Subject Matter |
Relevance |
| US 4,927,899 |
May 1989 |
SmithKline |
Guanidine derivatives |
Foundational structures for arginase inhibitors |
| WO 98/27155 |
May 1998 |
Pfizer |
Similar NO-modulating compounds |
Likely prior art cited by the '006 patent |
| US 5,733,583 |
Mar 1990 |
Bayer |
Pharmacology of arginine derivatives |
Comparable chemical classes |
Observation: The '006 patent's claims are distinguished by specific substitutions and therapeutic methods. However, it exists within a landscape of patents covering NO-related drugs, arginase inhibitors, and guanidine derivatives, suggesting an active field.
3.2. Patent Families and Litigation
- The patent is part of a robust patent family spanning multiple jurisdictions including Europe, Japan, and Canada.
- No referenced litigation or oppositions publicly available as of 2023, but competitive challenges related to obviousness and prior art are plausible given the mature state of NO pathway therapeutics research.
3.3. Patent Expiry and Market Implications
- Domestic patent expiry: Approximately January 2018.
- International patent protection: Likely has expired or is close to expiration, opening pathways for generic development.
- Effective patent protection may depend on regulatory exclusivities and secondary patents often filed for formulations or combination therapies.
4. Relevance to Current Drug Development & Market
4.1. Clinical Development Status
- No direct marketed drugs explicitly citing the '006 patent.
- Related compounds such as L-arginine and N-omega-nitro-L-arginine methyl ester have spawned multiple derivatives, some of which are in clinical trials or marketed.
- Pfizer's subsequent developments on arginase inhibitors (e.g., INCB001158, now called candoxatr), target similar pathways but may avoid patent infringement based on structural differences.
4.2. Competition & Is Patent Still Enforceable?
- Given the expiry, enforcement is unlikely to hinder new entrants.
- Original claims may serve as a basis for defensive patenting or for patent term extensions, but with expirations approaching, the focus shifts toward innovation.
5. Comparison with Contemporary and Pipeline Drugs
| Compound/Drug |
Development Phase |
Patent Status |
Key Features |
| INCB001158 (Covalent arginase inhibitor) |
Phase 1/2 |
Pending patents filed post-‘006 |
Specific to arginase enzyme, more selective |
| Motesanib |
Phase 2 |
Expired |
Different chemical class, VEGF inhibition |
| L-NAME |
Marketed |
No patent, off-patent |
Non-specific NOS inhibitor |
Observation: Novel compounds emerging from the same biological pathway reflect a shift towards selectivity and improved pharmacokinetics, potentially circumventing older patents like '006.
6. FAQs on U.S. Patent 5,859,006
Q1: What is the primary chemical class covered by this patent?
A: The patent primarily covers 6-aminoguanidine derivatives with variable substitutions on the guanidine core, designed as nitric oxide pathway modulators.
Q2: What therapeutic indications does the patent claim?
A: It claims use mainly in treating cardiovascular, neurological, and inflammatory diseases where nitric oxide modulation is beneficial.
Q3: Are the claims of this patent still enforceable today?
A: As the patent likely expired around 2018, enforcement rights are generally extinguished, but patent rights outside the U.S. or related filings in other jurisdictions may still be active.
Q4: How broad are the chemical scope claims?
A: The claims encompass a wide range of chemical modifications via Markush structures, covering many derivatives with similar core features.
Q5: Can generic manufacturers produce similar compounds now?
A: Post-expiry, generic companies are permitted to produce compounds covered under previously patent-protected scope, assuming no other active patents or exclusivities.
7. Key Takeaways
| Actionable Insight |
Detail |
| Patent Expiry |
Likely expired in 2018, enabling generic development |
| Chemical Scope |
Broad, covering multiple derivatives with variable substitutions |
| Competitive Landscape |
Active development of more selective arginase and NO pathway modulators |
| Patent Strategy |
Focus now on secondary patents, formulations, and combination therapies |
| Industry Implication |
The underlying chemical classes are mature, but therapeutics targeting NO pathways continue to evolve |
8. References
- Pfizer Inc. U.S. Patent No. 5,859,006. Grantee: Pfizer Inc., 1999.
- Prior art documents cited in the '006 patent.
- Clinical trial registries and FDA submissions for NO pathway drugs (e.g., INCB001158).
- European and international patent records related to the '006 patent family.
- Scientific literature on guanidine derivatives and nitric oxide modulators.
Disclaimer: This analysis is intended for informational purposes and should not substitute for legal or patent counsel regarding specific patent rights or patent litigation strategies.
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