US Patent 5,723,606: Scope, Claims, Expiration and Vasopressin-Antagonist Patent Landscape
US Patent 5,723,606 covers a broad Markush class of nitrogen-containing, five-membered-ring-condensed benzazepine derivatives, their salts, pharmaceutical compositions, and use as arginine vasopressin antagonists. The claims narrow through substituted heterocyclic ring structures and substituted benzanilide groups, then identify four specific compounds in claims 10-13. The patent issued March 3, 1998, and its ordinary 20-year term has expired. The patent therefore has no current blocking effect in the United States, subject to any recorded term adjustment or other patent-specific event in the USPTO file.
What does US Patent 5,723,606 protect?
The patent protects chemical compounds built around three structural elements:
- A benzazepine core.
- A nitrogen-containing aromatic five-membered ring fused to that core.
- A benzene ring connected through an amide-containing linker and bearing an aryl or heteroaryl substituent.
The independent chemical claim is claim 1. It covers the following general structure:
- A fused benzazepine derivative.
- Ring B as a nitrogen-containing aromatic five-membered ring.
- Ring B optionally containing oxygen or sulfur.
- Substituents R1 and R2 consisting of hydrogen, halogen, lower alkyl, substituted amino, or lower alkoxy.
- Linker A consisting of a single bond or a diamide-containing alkylene bridge.
- Ring C consisting of a benzene ring substituted with an aryl or heteroaryl group.
- Pharmaceutically acceptable salts of the compounds.
The claim is a composition-of-matter claim. It does not depend on a particular indication, dosage, formulation, manufacturing process, or commercial product.
What chemical scaffold is claimed?
The central scaffold is a fused tetrahydrobenzazepine-imidazole system. Claims 2 through 7 progressively narrow the permitted ring-B and ring-C substitutions.
The core structural concept is:
Substituted imidazo-fused benzazepine
|
carbonyl
|
Substituted benzanilide or related aryl amide
The claim language uses broad functional definitions rather than one named molecule. "Lower alkyl" and related terms encompass multiple carbon-chain alternatives, subject to the patent specification's definitions and applicable claim-construction principles.
How do claims 1 through 7 narrow the patent scope?
Claims 2 through 7 form a nested chemical claim set.
| Claim |
Principal limitation |
Commercial relevance |
| 1 |
Broad fused benzazepine derivative with substituted aryl or heteroaryl ring C |
Broad genus claim |
| 2 |
Defines ring B and limits ring C to specific phenyl or heteroaryl substituents |
Major narrowing of heterocyclic scope |
| 3 |
Requires one ring-B atom to be imine nitrogen and defines X2 as carbon |
Excludes several ring-B alternatives |
| 4 |
Narrows ring B to the specific fused-ring arrangement shown in the patent |
Captures the preferred scaffold |
| 5 |
Limits R6 and ring-C substitution patterns |
Focuses on preferred pharmacophores |
| 6 |
Limits ring C to unsubstituted or lower-alkyl-substituted phenyl |
Targets the principal benzanilide series |
| 7 |
Narrows R6 to hydrogen, selected alkyl groups, cyclopropyl, amino-derived groups, guanidino, or amidino substituents |
Encompasses named lead compounds |
Claim 1 has substantial genus breadth, but its enforceability would depend on written-description and enablement support across the full range of claimed heterocycles, linker structures, and substituents. Claims 4 through 7 are materially narrower and would generally present a stronger validity position because they track the preferred chemical series more closely.
Which compounds are specifically claimed?
Claims 10 through 13 recite four named compounds or their salts:
| Claim |
Named compound |
| 10 |
4'-(2-Methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl-2-phenylbenzanilide |
| 11 |
4'-(2-Ethyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl-2-phenylbenzanilide |
| 12 |
4'-(2-Cyclopropyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl-2-phenylbenzanilide |
| 13 |
4'-(2-Propyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)carbonyl-2-phenylbenzanilide |
These claims are narrower than claim 1 and focus on the 2-substituted tetrahydroimidazo-benzazepine series attached to a 2-phenylbenzanilide group.
The specific compounds are likely the patent's principal pharmaceutical candidates rather than incidental examples. Their claim position is stronger than the broader genus because infringement analysis can be conducted directly against a defined molecular structure.
What pharmaceutical and method-of-use rights are claimed?
Pharmaceutical composition claim
Claim 8 covers a pharmaceutical composition containing:
- A therapeutically effective amount of a claim 1 compound or salt; and
- A pharmaceutically acceptable carrier or diluent.
This is a conventional composition claim. It is broad as to dosage form and excipient selection. It can encompass oral, parenteral, liquid, solid, and other dosage forms if supported by the specification.
The claim does not require:
- A specific strength.
- A specific release profile.
- A particular excipient.
- A specific route of administration.
- A particular disease.
Method-of-treatment claim
Claim 9 covers treating diseases impacted by arginine vasopressin by administering a claim 1 compound or salt as an arginine vasopressin antagonist.
The claim is functionally broad. It may cover treatment of disorders involving excessive vasopressin activity, including water-retention and cardiovascular indications described in the patent disclosure. The claim does not identify a single receptor subtype. It therefore potentially reaches V1a, V1b, V2, or mixed vasopressin-antagonist activity, depending on the compound and the patent's disclosure.
The claim requires administration to a patient and a therapeutic purpose. It does not independently cover the compound as a composition of matter where claim 1 is unavailable.
What is the patent's priority, filing and expiration timeline?
| Event |
Date or status |
| Earliest Japanese priority |
Mid-1990s Japanese priority filings associated with the invention |
| US application |
Filed in the 1990s |
| US patent |
US 5,723,606 |
| Issue date |
March 3, 1998 |
| Patent term basis |
20 years from the applicable US nonprovisional filing date |
| Ordinary US expiration |
Approximately late 2016 |
| Current status |
Expired by ordinary patent term |
The patent was prosecuted under the modern 20-year patent-term regime. The issue date does not determine expiration. A patent issued in 1998 can expire in 2016 or earlier or later depending on the effective filing date, patent-term adjustment, terminal disclaimer, and any continuation history.
The patent should be treated as expired for current US freedom-to-operate analysis unless the USPTO record shows an unusual term adjustment or a related unexpired continuation with overlapping claims. The original patent itself cannot support a new US infringement action after expiration. Expiration also eliminates the ability to obtain an injunction based solely on this patent.
What is the Orange Book status of US Patent 5,723,606?
US Patent 5,723,606 has no apparent current Orange Book significance.
The patent covers an older vasopressin-antagonist chemical series, but the patent does not correspond to a currently marketed FDA-approved product identified by the patent number in the FDA Orange Book. The likely associated compounds were investigated as vasopressin antagonists, but the patent's named compounds are not the active ingredient in a currently approved US product protected by this patent.
The Orange Book lists patents submitted by sponsors for approved drugs. A patent that is not listed for an approved reference product does not create an ANDA Paragraph IV certification pathway by itself.
Are there Paragraph IV challenges to this patent?
No current Paragraph IV challenge should be expected against US Patent 5,723,606.
Paragraph IV litigation requires an ANDA applicant to challenge a patent listed for an FDA-approved reference product. Because this patent is expired and is not the operative Orange Book patent for an approved product, it is not a current Paragraph IV barrier.
A generic applicant could still face other patent issues if a related compound, formulation, polymorph, or process patent remained unexpired. Those rights would need to be assessed separately. They would not revive the expired claims of US 5,723,606.
Does the patent create biosimilar risk?
No. Biosimilar provisions do not apply to this patent.
The claimed subject matter consists of small-molecule chemical compounds and salts. The relevant regulatory pathway would be an abbreviated new drug application, a 505(b)(2) application, or a full new drug application, not a biologics license application and biosimilar application.
The commercial risk is therefore generic or hybrid-drug competition rather than biosimilar competition.
What formulations are protected by the patent?
Claim 8 covers pharmaceutical compositions generally, but it does not contain detailed formulation limitations. The patent does not appear to claim:
- A specific tablet architecture.
- A controlled-release matrix.
- A transdermal system.
- A liposomal formulation.
- A defined particle-size distribution.
- A particular crystalline polymorph.
- A specific amorphous solid dispersion.
The formulation protection is therefore subordinate to the composition-of-matter claims. During the patent term, a formulation containing a covered compound could have infringed claim 8 even if the formulation itself was conventional. After expiration, claim 8 no longer blocks commercial formulation of the claimed compounds.
What manufacturing and intellectual-property barriers did the patent create?
The patent's principal barrier was chemical synthesis and compound coverage, not manufacturing technology.
Potential manufacturing issues include:
- Formation of the fused tetrahydroimidazo-benzazepine ring.
- Construction of the benzazepine intermediate.
- Amide coupling to the substituted benzanilide.
- Control of regioisomers and ring-substitution patterns.
- Isolation and characterization of pharmaceutically acceptable salts.
- Reproducible production of the named compounds at pharmaceutical scale.
The patent's claims do not appear to be directed primarily to a specific synthetic route. A competitor could therefore have pursued a noninfringing process after the composition claims expired, provided that no separate process patent remained in force.
How strong is the patent estate?
Strengths
- Claim 1 uses a broad chemical genus.
- Claims 10 through 13 identify specific compounds directly.
- The claims cover compounds, salts, compositions, and therapeutic use.
- The patent targets a defined pharmacological class, arginine vasopressin antagonists.
- The preferred claims narrow toward a coherent chemical series rather than unrelated structures.
Weaknesses
- The broad genus includes many heterocyclic and substitution alternatives.
- Broad Markush language can create written-description and enablement challenges.
- Claim 9 is a functional method claim with broad disease language.
- No remaining term exists in the original US patent.
- There is no current Orange Book leverage associated with the patent.
- Any commercial product would require separate review of later patents covering formulations, salts, polymorphs, indications, or manufacturing processes.
The patent was commercially meaningful during its term, but its current value is primarily historical, technical, and landscape-related.
How does this patent compare with later vasopressin-antagonist patents?
US 5,723,606 should be separated from later patents covering approved vasopressin antagonists.
| Category |
US 5,723,606 |
Later vasopressin-antagonist patents |
| Technology |
Fused benzazepine-imidazole derivatives |
Separate chemical series depending on product |
| Claimed subject matter |
Compounds, salts, compositions, treatment |
Often compounds plus formulation and indication layers |
| US regulatory status |
Not a current Orange Book barrier |
May support approved-product exclusivity |
| Regulatory pathway |
Small molecule |
Small molecule |
| Current term |
Expired |
Depends on later filing and patent dates |
| Main risk |
Historical prior art and structural overlap |
Active freedom-to-operate and launch barriers |
A structural comparison is necessary before concluding that a later vasopressin antagonist falls within claim 1. Similar pharmacology does not establish chemical infringement. The relevant question is whether the accused molecule contains the claimed benzazepine-fused five-membered nitrogen heterocycle, linker, and ring-C substitution pattern.
What generic launch scenarios existed during the patent term?
During the patent's effective term, the main launch scenarios were:
- A direct generic or alternative sponsor product using one of the claimed compounds, which would have faced composition-of-matter claims.
- A noninfringing analog outside the Markush scope, subject to validity and doctrine-of-equivalents analysis.
- A product using a different vasopressin-antagonist scaffold.
- A later formulation or process product that avoided the claims but potentially faced separate patents.
- A 505(b)(2) product relying on published clinical or safety data, if an approved reference product and suitable regulatory basis existed.
After expiration, the composition and treatment claims no longer present a US patent launch barrier. Remaining risks would come from separate patents, regulatory exclusivity, controlled-substance rules if applicable, trade secrets, know-how, or manufacturing capability.
What is the current commercial exposure?
The direct revenue exposure attributable to US 5,723,606 is effectively zero because the patent has expired and its claimed compounds are not the active ingredient in a major current US Orange Book product protected by this patent.
The historical exposure was greater because a composition-of-matter patent can block both the active ingredient and products containing it. The patent's expiry converted the issue from exclusivity protection to freedom-to-operate and competitive feasibility.
The patent may still matter for:
- Prior-art analysis.
- Patentability of later vasopressin antagonists.
- Invalidity attacks against related patents.
- Chemical-family mapping.
- Historical ownership and licensing analysis.
- Identification of disclosed synthetic intermediates and lead compounds.
Key Takeaways
- US Patent 5,723,606 claims fused benzazepine-imidazole vasopressin antagonists and related salts.
- Claims 1 through 7 define a broad-to-narrow chemical Markush structure.
- Claims 10 through 13 specifically cover methyl, ethyl, cyclopropyl, and propyl analogs.
- Claim 8 covers pharmaceutical compositions; claim 9 covers treatment of vasopressin-related diseases.
- The patent issued March 3, 1998, and its ordinary US term expired around late 2016.
- It is not a current Orange Book or Paragraph IV barrier.
- Biosimilar risk is irrelevant because the patent covers small molecules.
- Current commercial risk must be assessed against later compound, formulation, polymorph, method-of-use, and process patents.
- The patent remains relevant as chemical prior art and as a map of the fused benzazepine vasopressin-antagonist series.
FAQs
What drug is associated with US Patent 5,723,606?
The patent is associated with a research and development series of fused benzazepine vasopressin antagonists, including the specifically claimed methyl, ethyl, cyclopropyl, and propyl analogs. The patent should not be equated automatically with conivaptan or tolvaptan without a structure-level comparison.
Can a company commercialize a claim 10 compound in the United States?
The expired patent itself does not prevent commercialization. A company would still need to evaluate other active patents, regulatory requirements, manufacturing rights, data exclusivity, and any unexpired foreign rights.
Does patent expiration eliminate all regulatory barriers?
No. Patent expiration removes the patent barrier but does not eliminate FDA approval requirements, clinical data obligations, manufacturing controls, or other exclusivity rights.
Are salts covered separately from the active compounds?
Yes. Claims 1 through 7 and claims 10 through 13 expressly extend to salts. The salt language broadens coverage beyond the neutral parent compound during the patent term.
Does a different vasopressin receptor selectivity profile avoid infringement?
Not necessarily. The claims are primarily structural. A compound with V1a, V1b, V2, or mixed activity could still infringe if its structure falls within the claimed genus or specific compound claims.
References
-
United States Patent No. 5,723,606. (1998, March 3). Nitrogen-containing aromatic 5-membered ring-condensed benzazepine derivatives. United States Patent and Trademark Office.
-
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/
-
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
-
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application regulations and Paragraph IV certifications. https://www.fda.gov/drugs
-
World Intellectual Property Organization. (n.d.). PATENTSCOPE international patent and priority-document records. https://patentscope.wipo.int/
