United States Drug Patent 4,636,499: Claim Scope, Patent Landscape, and Exclusivity Analysis
U.S. Patent No. 4,636,499 covers a broad class of substituted pyrido-benzimidazole thiadiazinium salts, their pharmaceutically acceptable salts, preparation processes, pharmaceutical compositions, and gastrointestinal treatment uses. The patent was granted on January 13, 1987, and, as a pre-URAA U.S. patent, its ordinary term expired on January 13, 2004, absent an unusual terminal-disclaimer or restoration issue. The patent is therefore not a current U.S. barrier to commercial activity. [1, 2]
What compounds does U.S. Patent 4,636,499 protect?
The principal composition-of-matter claim is claim 1. It protects compounds identified as formula IIIa, a fused heterocyclic pyridinium/thiadiazino/benzimidazole system bearing variable substituents and a pharmaceutically acceptable counterion.
The claim has four core structural elements:
- A benzimidazole-derived fused aromatic or partially fused ring system.
- A pyridinium-containing heterocycle with variable substitution at positions represented by R5a through R8a.
- A sulfur- and nitrogen-containing thiadiazino bridge.
- A positively charged compound paired with a pharmaceutically acceptable anion, X-.
The Markush definition allows extensive variation at nearly every substitutable position.
Substitution permitted on the benzimidazole ring
R1a, R2a, R3a, and R4a may independently be:
- Hydrogen
- Alkyl or alkoxy groups
- Fluorinated or chlorinated alkyl or alkoxy groups
- Halogen
- Cyano
- Trifluoromethyl
- Nitro
- Acyl or ester groups
- Aryl, aryloxy, or arylalkoxy groups
The claim also covers fused ring alternatives in which adjacent substituents form 5-, 6-, or 7-membered monocyclic rings, or 9-, 10-, or 11-membered bicyclic rings. Those rings may contain nitrogen or oxygen and may be saturated or unsaturated.
This creates a broad chemical genus rather than protection limited to one named molecule.
Substitution permitted on the pyridinium ring
R5a and R6a may be hydrogen or alkyl, or may form an alkylene bridge. R7a may be hydrogen, alkyl, alkoxy, alkenyloxy, or alkynyloxy. R8a may be hydrogen or alkyl.
The claim also encompasses additional fused or bridged ring systems involving R6a/R7a or R7a/R8a. The expressly identified bridges include:
- Conjugated diene structures
- Oxa- and thia-alkylene bridges
- Nitrogen-containing bridges
- Partially unsaturated oxygen-containing rings
These alternatives materially expand the claim beyond the simple dimethyl-methoxy examples recited in dependent claims 4 through 6.
How many patent claims are directed to compounds, processes, formulations, and methods?
The 18 claims divide into four functional groups.
| Claim group |
Claims |
Subject matter |
| Composition of matter |
1-8 |
Formula IIIa compounds, anions, specific substitution patterns, mixtures, and solid forms |
| Manufacturing process |
9-11 |
Acid-catalyzed conversion of formula Ia compounds into formula IIIa salts |
| Pharmaceutical preparations |
12-14 |
Compositions for gastrointestinal inflammation, acid suppression, and cytoprotection |
| Therapeutic methods |
15-18 |
Administration for gastrointestinal inflammation, gastric acid suppression, and cytoprotection |
Claims 1, 4, 5, and 6 carry the primary value from a drug-discovery perspective because they define the chemical entities. Claims 12 through 18 are downstream use claims and would have depended on an approved or commercially developed compound within the composition-of-matter genus.
What specific compounds are protected by claims 4, 5, and 6?
Claim 4: BF4- compounds
Claim 4 narrows the structure to:
- R1a, R4a, R5a, and R8a: hydrogen
- R2a and R3a: methyl
- R7a: methoxy
- R6a: hydrogen or methyl
- X-: tetrafluoroborate, BF4-
This claim targets a highly specific dimethyl/methoxy substitution pattern with a tetrafluoroborate counterion.
Claim 5: PF6- and AuCl4- compounds
Claim 5 narrows the structure to:
- R1a, R3a, R4a, and R5a: hydrogen
- R6a and R8a: methyl
- R7a: methoxy
- R2a: hydrogen or methoxy
- X-: hexafluorophosphate, PF6-, or tetrachloroaurate, AuCl4-
The claim therefore covers a different positional isomeric pattern from claim 4 and expressly protects alternative counterions.
Claim 6: Isomeric tetrafluoroborate mixture
Claim 6 specifically protects an isomeric mixture of:
- 2,4-dimethyl-3,9-dimethoxy-5H-pyrido-[1',2':4,5][1,2,4]-thiadiazino[2,3-a]benzimidazol-13-ium tetrafluoroborate
- 2,4-dimethyl-3,10-dimethoxy-5H-pyrido[1',2':4,5][1,2,4]-thiadiazino[2,3-a]benzimidazol-13-ium tetrafluoroborate
This is the narrowest chemically identifiable subject matter in the supplied claims. It is directed to a defined regioisomeric mixture rather than an individual purified isomer.
What formulation patents are covered by U.S. Patent 4,636,499?
Claims 12 through 14 cover pharmaceutical preparations containing a claim 1 compound and a pharmaceutically acceptable carrier. The claimed therapeutic objectives are:
- Treatment of inflammatory diseases of the gastrointestinal tract
- Inhibition of gastric acid secretion
- Cytoprotection of the gastrointestinal tract
The formulation claims do not identify a specific dosage form, excipient, release profile, particle size, polymorph, coating, capsule, tablet, suspension, or manufacturing parameter. Their scope is therefore functional and composition-based.
Claim 8 adds protection for a compound of formula IIIa in solid form. It does not, on its face, require a particular crystalline polymorph, hydrate, solvate, particle-size distribution, or solid-state purity threshold. The claim could face substantial validity and infringement disputes if the specification does not adequately support the full range of solid forms.
What method-of-use patents are covered?
Claims 15 through 18 are method claims covering administration of a claim 1 compound for:
- Gastrointestinal inflammatory disease
- Gastric acid suppression
- Cytoprotection
Claim 18 requires formulation with a pharmaceutically acceptable carrier before administration. The claims do not specify:
- A particular disease diagnosis
- A dosing amount
- A dosing frequency
- A treatment duration
- A patient subgroup
- A route of administration
- A biomarker or treatment-response threshold
The breadth of these claims increases potential coverage but also creates vulnerability under written-description, enablement, indefiniteness, and utility doctrines if the patent disclosure does not support the full claimed therapeutic range.
What process claims does the patent contain?
Claim 9 covers preparation of formula IIIa compounds by reacting a formula Ia compound under transformation conditions with an acid catalyst to form the corresponding salt, followed by isolation.
Claim 10 identifies three acid catalysts:
- Hexafluorophosphoric acid, HPF6
- Tetrafluoroboric acid, HBF4
- Tetrachloroauric acid, HAuCl4
The process claim is broader than the catalyst list in claim 10. Claim 9 does not limit the acid catalyst to those three acids, while claim 10 creates a narrower dependent position.
From an infringement perspective, a process that forms the same claimed salt through a materially different route would not necessarily infringe claim 9. The analysis would turn on whether the route satisfies the claim's acid-catalyzed transformation and isolation limitations.
When did U.S. Patent 4,636,499 lose exclusivity?
| Event |
Date |
| U.S. patent grant |
January 13, 1987 |
| Ordinary pre-URAA expiration |
January 13, 2004 |
| Current status |
Expired |
U.S. Patent 4,636,499 was granted before the June 8, 1995 transition to the modern patent-term regime. Under the law applicable to such patents, the ordinary term was 17 years from grant. [1, 2]
Patent-term adjustment is not generally relevant to this patent because the modern PTA framework applies to applications filed on or after May 29, 2000. Patent-term extension under 35 U.S.C. § 156 would require an eligible approved product and regulatory review period. No such extension is established by the patent claims or supplied record. [2]
What is the Orange Book status of U.S. Patent 4,636,499?
U.S. Patent 4,636,499 is not, by itself, evidence of an Orange Book-listed drug product or an FDA-approved reference listed drug. The patent claims an investigational chemical class and therapeutic uses, but the claims do not establish FDA approval, approval of a named active ingredient, or submission of the patent for an approved product.
The Orange Book lists patents submitted by sponsors in connection with approved drug products, including patents covering active ingredients, formulations, and methods of use. A historical chemical patent may therefore have no Orange Book relevance if no corresponding product obtained approval. [3]
The practical regulatory conclusion is that U.S. Patent 4,636,499 does not create a current Orange Book-based paragraph IV barrier.
Are paragraph IV challenges or generic entry risks relevant?
Paragraph IV status
A paragraph IV certification is relevant only to an ANDA referencing an FDA-approved drug and a patent listed for that reference product. Because the patent expired in 2004 and no approved reference product is established here, there is no current paragraph IV exclusivity issue associated with U.S. Patent 4,636,499. [3, 4]
Generic launch risk
The patent itself presents no current generic launch barrier. The commercial risk is different: the claimed compounds may not have an approved reference product against which an ANDA could be filed.
Potential development pathways would depend on the status of the active ingredient:
- If an identical active ingredient had an approved reference product, an ANDA or 505(b)(2) pathway could be considered.
- If no reference product existed, a new drug application or other development route would be required.
- If the product were reformulated or chemically modified, separate patents could become relevant even though the 1987 patent is expired.
Does the patent raise biosimilar risk?
No. U.S. Patent 4,636,499 covers small-molecule heterocyclic compounds, not a biologic, therapeutic protein, antibody, vaccine, cell therapy, or other biological product.
Biosimilar pathways under the Biologics Price Competition and Innovation Act are therefore not relevant. Any follow-on risk would be a small-molecule generic, hybrid, or new-drug-development issue rather than biosimilar substitution. [5]
How strong is the patent estate?
The patent had strong theoretical breadth at issuance but has no remaining U.S. exclusionary value.
| Dimension |
Assessment |
| Chemical genus |
Broad |
| Specific exemplified compounds |
Narrower and more commercially actionable |
| Counterion coverage |
Broad in claim 1; specific in claims 2, 4, and 5 |
| Solid-form coverage |
Broad but potentially vulnerable without detailed solid-state support |
| Process coverage |
Moderate; requires acid-catalyzed transformation and isolation |
| Formulation coverage |
Broad functional composition claims |
| Method-of-use coverage |
Broad gastrointestinal indications and effects |
| Current enforceability |
None after expiration |
| Biosimilar relevance |
None |
| Orange Book relevance |
Not established |
| Present generic barrier |
None from this patent |
The key distinction is between historical claim scope and current freedom to operate. The claim set was drafted to capture a chemical platform and downstream applications. That platform strategy matters for historical portfolio analysis, but expiration eliminates the patent's ability to block current U.S. manufacture, use, sale, or importation.
Which companies are challenging U.S. Patent 4,636,499?
No current litigation, paragraph IV dispute, or settlement agreement is established in the supplied record. Because the patent expired in 2004, a new U.S. validity challenge would generally have limited commercial purpose unless tied to historical damages, ownership, licensing, or a collateral proceeding.
The patent's assignee, prosecution history, cited references, foreign counterparts, and any historical litigation should be verified through USPTO Patent Center and the federal court docket systems before relying on the patent for ownership, licensing, or litigation conclusions. [6]
What geographic coverage did the patent provide?
U.S. Patent 4,636,499 provided territorial rights only in the United States. Any foreign protection would have depended on separate national or regional applications.
Potential family jurisdictions for a European-origin pharmaceutical invention could have included:
- Germany
- United Kingdom
- France
- Switzerland
- The Netherlands
- European Patent Office member states
- Japan
- Canada
- Australia
Foreign counterparts would have had separate filing dates, claim amendments, prosecution histories, and expiration dates. The U.S. patent cannot establish foreign scope or current foreign enforceability.
What manufacturing and intellectual-property barriers remain?
The expired patent does not block manufacture of the claimed compounds in the United States. Residual barriers could arise from other sources:
- Later patents covering a specific salt, polymorph, solvate, formulation, or process
- Trade secrets concerning synthesis, purification, or scale-up
- Regulatory exclusivity tied to a later-approved product
- Foreign patents still in force
- Contractual licensing restrictions
- Controlled access to clinical, toxicology, or manufacturing data
- Unresolved ownership or inventorship disputes
The original process claims do not create a continuing manufacturing barrier after expiration. Any current process risk must be assessed against later-issued patents, not against U.S. Patent 4,636,499 alone.
Key Takeaways
- U.S. Patent 4,636,499 claims a broad Markush genus of pyrido-benzimidazole thiadiazinium salts.
- Claims 4 through 6 identify narrower methyl/methoxy compounds and specific counterions.
- Claims 9 through 11 cover acid-catalyzed preparation processes.
- Claims 12 through 18 cover gastrointestinal formulations and treatment methods involving acid suppression and cytoprotection.
- The patent was granted January 13, 1987, and ordinarily expired January 13, 2004.
- It presents no current U.S. patent barrier to generic manufacture, development, or commercialization.
- It is a small-molecule patent, so biosimilar analysis is irrelevant.
- No current Orange Book listing, paragraph IV proceeding, litigation, or settlement is established for this patent.
- Later patents, foreign counterparts, regulatory exclusivity, and trade secrets remain separate issues.
FAQs About U.S. Patent 4,636,499
Is U.S. Patent 4,636,499 still active?
No. Its ordinary U.S. patent term expired on January 13, 2004.
Does U.S. Patent 4,636,499 cover omeprazole or another marketed proton-pump inhibitor?
The supplied claims do not identify omeprazole, lansoprazole, pantoprazole, rabeprazole, or another marketed proton-pump inhibitor. They cover a different heterocyclic salt genus.
Can a company manufacture a claim 6 compound in the United States?
The expired patent does not prevent manufacture. Separate later patents, trade secrets, regulatory requirements, or foreign-market restrictions could still affect the project.
Does claim 8 protect a particular polymorph?
No specific polymorph is identified in the supplied claim. Claim 8 broadly refers to the compound in solid form.
Is a new patent infringement suit possible based solely on U.S. Patent 4,636,499?
No practical current infringement claim can be based solely on an expired patent. Historical issues such as damages, ownership, or licensing could require separate legal analysis.
References
-
U.S. Patent No. 4,636,499. (1987). Pyrido-[1',2':4,5][1,2,4]-thiadiazino[2,3-a]benzimidazole derivatives. United States Patent and Trademark Office.
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35 U.S.C. §§ 154, 156 (2024).
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U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations. FDA.
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U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions: Refuse-to-receive standards. FDA.
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Biologics Price Competition and Innovation Act of 2009, 42 U.S.C. § 262.
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United States Patent and Trademark Office. (2025). Patent Center. USPTO.
