United States Patent 5,476,669: Scope, Claims, Expiration, and H. pylori Patent Landscape

U.S. Patent No. 5,476,669 covers therapeutic regimens for treating or preventing recurrence of gastric and duodenal ulcers associated with Helicobacter pylori, formerly called Campylobacter pylori. The core regimen combines a pharmaceutically acceptable bismuth compound, metronidazole, and either tetracycline or a penicillin. Several dependent claims add an acid suppressant, including an H2 antagonist, proton pump inhibitor, benzimidazole, prostaglandin, or K/Na ATP-ase inhibitor.

The patent issued on December 19, 1995. Its ordinary U.S. patent term has expired. The patent therefore does not create a current U.S. blocking right against generic H. pylori treatment regimens, although it remains relevant as prior art, prosecution history, and evidence of the historical development of bismuth-based eradication therapy. [1][2]

What does U.S. Patent 5,476,669 protect?

The patent protects method-of-treatment claims rather than a new chemical entity, composition of matter, or defined pharmaceutical formulation.

Its central claim architecture requires:

A patient with gastric or duodenal ulcer disease associated with H. pylori.
A pharmaceutically acceptable bismuth compound.
Metronidazole.
A first antibiotic selected from tetracycline or penicillins.
In specified claims, an acid suppressant administered before or during eradication therapy.
In several claims, a clinical objective such as ulcer healing, epithelialization, symptomatic relief, or prevention of recurrence.

The broadest claim is claim 1. It covers prevention of gastric-ulcer recurrence using the bismuth-plus-two-antibiotic regimen, without requiring an acid suppressant.

Claims 19 and 27 address duodenal ulcers. Claim 19 focuses on recurrence prevention. Claim 27 combines ulcer treatment and recurrence prevention and requires acid suppression before or during administration of the eradication regimen.

Claim-group structure

Claim group	Disease	Core requirement	Acid suppressant required?	Primary result
Claim 1	Gastric ulcer	Bismuth + tetracycline or penicillin + metronidazole	No	Prevent recurrence
Claims 2-9	Gastric ulcer	Claim 1 regimen plus acid suppression	Yes	Prevent recurrence
Claim 10	Gastric ulcer	Acid suppression before or during eradication regimen	Yes	Symptomatic relief and epithelialization
Claims 11-18	Gastric ulcer	Claim 10 regimen plus specified acid suppressant	Yes	Treatment
Claim 19	Duodenal ulcer	Bismuth + tetracycline or penicillin + metronidazole	Yes	Prevent recurrence
Claims 20-26	Duodenal ulcer	Claim 19 regimen with timing or suppressant limitations	Yes	Prevent recurrence
Claim 27	Duodenal ulcer	Acid suppression plus eradication regimen	Yes	Healing and prevention of recurrence
Claims 28-34	Duodenal ulcer	Claim 27 regimen with timing or suppressant limitations	Yes	Healing and prevention

How broad is the bismuth triple-therapy claim?

The central combination is broad because the claims do not limit the bismuth compound to a single salt or dosage form. “Pharmaceutically acceptable bismuth compound” can encompass multiple medicinal bismuth species, subject to claim construction and the patent’s specification.

The antibiotic limitation is narrower than a generic “two-antibiotic” claim. The first antibiotic must be:

Tetracycline; or
A penicillin.

The second antibiotic must be metronidazole. A regimen using clarithromycin instead of metronidazole would not literally satisfy the express metronidazole limitation. A regimen using amoxicillin and metronidazole could fall within the claim because amoxicillin is a penicillin-class antibiotic, subject to the precise construction of “selected from the group consisting of ... penicillins.”

The claims do not expressly require:

A particular dose;
A particular treatment duration, except for the acid-suppressant timing claims;
A fixed order of administration for claim 1;
A single combined tablet or kit;
A specific bismuth salt;
A particular patient age;
A particular diagnostic test for H. pylori;
A specific metronidazole-to-tetracycline ratio.

That structure gives the independent claims broad regimen coverage but also creates validity and infringement questions around patient diagnosis, drug identity, treatment purpose, and the meaning of “eradicating amounts.”

What formulations are protected by U.S. Patent 5,476,669?

The patent does not claim a defined pharmaceutical composition or fixed-dose combination. It claims administration of the agents to a patient.

Potentially relevant bismuth products include bismuth subsalicylate and bismuth subcitrate-related products, but the patent claims do not automatically cover every commercial bismuth product. The product must be a pharmaceutically acceptable bismuth compound administered as part of the claimed therapeutic regimen.

A packaged regimen could implicate the method claims if its labeling directs use of:

A bismuth compound;
Metronidazole; and
Tetracycline or a penicillin;

for H. pylori-associated gastric or duodenal ulcer treatment or recurrence prevention.

The patent does not, by itself, establish infringement by manufacturing or selling the individual drugs separately. Method claims generally require performance of the claimed administration steps, inducement of those steps, or another legally actionable theory under the applicable facts. [3]

Which acid suppressants fall within the patent claims?

Claims 4-9, 13-18, 21-26, and 29-34 identify several acid-suppressant categories.

Acid-suppressant categories

Claimed category	Examples or interpretation
Histamine2-receptor antagonist	Cimetidine, ranitidine, famotidine, or related H2 antagonists
Benzimidazole	Lansoprazole or omeprazole under the express dependent claims
Proton pump inhibitor	Omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, subject to claim construction
Prostaglandin	Gastroprotective prostaglandin analogues
K/Na ATP-ase inhibitor	Broad functional category recited in the patent
Acid suppressant generally	Claims 2, 3, 10, 11, 12, 19, 20, 27, and 28

The claims use overlapping terminology. Omeprazole and lansoprazole are identified both as benzimidazoles and as proton pump inhibitors. The narrower claims expressly identify these two compounds, while the broader claims use the functional category of acid suppressant or proton pump inhibitor.

What timing requirements apply?

Timing is material in several dependent claims.

Claims 3, 12, 20, and 28 require acid suppression for three to 28 days followed by administration of the bismuth-antibiotic combination. Claims 10 and 27 permit acid suppression before or during the eradication therapy, with the stated purpose of obtaining symptomatic relief and ulcer epithelialization.

The timing structure creates distinct infringement boundaries:

A regimen beginning with acid suppression for fewer than three days may not satisfy the express three-to-28-day limitation.
A regimen administering acid suppression simultaneously with the eradication combination may fall within claims that allow administration “before or during,” but not necessarily within claims requiring a completed three-to-28-day course followed by the combination.
Claim 1 remains broader because it does not require acid suppression or a specified sequence.

The patent therefore has its strongest historical scope against bismuth-based sequential or concurrent regimens using metronidazole plus tetracycline or a penicillin.

When did U.S. Patent 5,476,669 lose exclusivity?

The patent issued on December 19, 1995. For a U.S. patent subject to the pre-Uruguay Round patent-term regime, the ordinary term was generally 17 years from issuance. That date produces an ordinary expiration date of December 19, 2012. The later 20-year-from-filing rule under 35 U.S.C. § 154 generally applies to applications filed on or after June 8, 1995, while earlier applications ordinarily remain governed by the 17-year-from-issue rule, subject to statutory exceptions. [2]

Event	Date
Patent issued	December 19, 1995
Ordinary 17-year term from issue	December 19, 2012
Current status	Expired
Current blocking exclusivity	None based on this patent

No current U.S. generic-launch restriction should be attributed to Patent 5,476,669. Any historical patent-term adjustment, terminal disclaimer, or other prosecution-specific event would need to be reflected in the official USPTO record, but none changes the commercial conclusion that the patent is no longer enforceable as a live U.S. exclusivity right.

What is the Orange Book status of U.S. Patent 5,476,669?

Patent 5,476,669 is a method-of-treatment patent and is not, by patent number alone, an Orange Book-listed patent. Orange Book listing is tied to patents submitted for an approved drug product and an associated FDA-approved labeling indication. The patent’s claims cover a therapeutic regimen involving multiple products rather than a single approved active ingredient or dosage-form product. [4]

The patent should therefore be distinguished from later product-specific patents covering:

Bismuth-containing combination kits;
Metronidazole or tetracycline formulations;
Modified-release dosage forms;
Fixed-dose combinations;
Packaging and dosing systems;
Specific H. pylori indications in an approved product label.

An Orange Book listing for a later product would have to be analyzed separately. Such a listing would not revive the expired rights under Patent 5,476,669.

How does the patent compare with later H. pylori treatment products?

The patent reflects bismuth quadruple or bismuth-based triple-therapy concepts that became clinically established before and during the development of modern H. pylori products. Later products may use different combinations, including bismuth, metronidazole, tetracycline, and an acid suppressant.

Comparison with later regimen categories

Regimen category	Bismuth	Metronidazole	Tetracycline or penicillin	Acid suppression	Relationship to Patent 5,476,669
Historical bismuth triple therapy	Yes	Yes	Yes	Optional under claim 1	Closest match
Bismuth quadruple therapy	Yes	Yes	Often tetracycline	Yes	May correspond to claims requiring acid suppression
Clarithromycin triple therapy	Usually no	No	Often amoxicillin	Yes	Outside the express core combination
Concomitant therapy	Variable	Often yes	Often amoxicillin plus clarithromycin	Yes	Requires element-by-element analysis
Rifabutin-based therapy	Generally no	No	No	Yes	Outside the core claims
Vonoprazan-based therapy	Usually no	No or variable	Often amoxicillin	Yes, through potassium-competitive acid blocker	Usually outside literal core regimen

The patent’s chemical combination is narrower than the overall field of H. pylori eradication therapy. Its expired status, however, means the distinction is now primarily relevant to historical patent analysis and assessment of later patent families.

What patent landscape surrounds H. pylori eradication therapy?

The relevant patent landscape has several layers.

Composition and formulation patents

These cover the physical dosage form, kit, tablet, capsule, coating, release profile, or combination packaging. They can remain enforceable after broad method patents expire if filed later and supported by distinct technical disclosures.

Method-of-use patents

These cover treatment of H. pylori infection, ulcer recurrence prevention, eradication after failed therapy, resistance-guided treatment, or use in defined patient populations. Patent 5,476,669 belongs to this category.

Manufacturing and process patents

These may cover production of bismuth complexes, antibiotic combinations, granulation methods, enteric coatings, or packaging systems. They can create supply-chain barriers even when the underlying therapeutic method is unprotected.

Regulatory exclusivity

FDA approval may create regulatory exclusivity independent of patent rights. New chemical entities, new clinical investigations, pediatric studies, orphan indications, and qualified infectious disease products may receive periods of FDA exclusivity under the applicable statutory pathway. Regulatory exclusivity must be checked against the specific approved product and NDA, not inferred from Patent 5,476,669. [4][5]

Which companies challenged or licensed the patent?

The patent text and claim set do not establish a Paragraph IV filing, litigation settlement, or license agreement. Because the patent expired in 2012, no current Paragraph IV challenge is commercially necessary for entry against this patent.

For historical diligence, a complete transaction and litigation review would normally distinguish among:

The patent owner and original assignee;
Manufacturers of bismuth-antibiotic combination products;
NDA holders for H. pylori treatment kits;
ANDA applicants;
Paragraph IV notices;
District-court litigation;
PTAB proceedings;
Settlement agreements;
Covenants not to sue;
Patent assignments and licenses.

A later product could have faced separate litigation under later patents even if Patent 5,476,669 was not asserted. The expiration of this patent does not eliminate risk from later formulation, packaging, dosing, or product-specific patents.

How strong is the patent estate today?

The patent’s current enforceability is zero because the patent has expired. Its historical claim breadth was moderate to broad for the specific bismuth-metronidazole-tetracycline or penicillin regimen.

Historical strength

Broad patient-treatment concept.
Broad bismuth-compound language.
Alternative antibiotic branch covering tetracycline or penicillins.
Separate gastric and duodenal ulcer claim sets.
Acid-suppressant and sequencing claims.
No fixed dosage or formulation limitation in the core claims.

Historical vulnerabilities

The regimen was susceptible to anticipation and obviousness challenges based on earlier bismuth, metronidazole, tetracycline, and H. pylori treatment disclosures.
“Eradicating amounts” is functional language that could create proof and construction disputes.
The claims depend on the ulcer being associated with H. pylori.
Claims 10 and 27 contain outcome-oriented language involving symptomatic relief, epithelialization, healing, and prevention of recurrence.
Broad genus language for bismuth compounds, penicillins, and acid suppressants could raise written-description and enablement issues depending on the specification and prior art.
The outdated “Campylobacter pylori” terminology does not narrow the claims where the claims expressly include “Helicobacter pylori.”

What generic-entry risks remain?

Patent 5,476,669 presents no current generic-entry barrier. A company can market H. pylori therapies without obtaining a license under this expired patent, subject to other live rights and FDA requirements.

The relevant current risks are more likely to arise from:

Product-specific formulation patents;
Combination-product patents;
Patent claims directed to potassium-competitive acid blockers;
Dosing and treatment-duration patents;
Manufacturing patents;
Labeling-related inducement theories under later patents;
FDA exclusivity associated with a particular NDA;
State or federal regulatory requirements for combination products.

Key Takeaways

U.S. Patent 5,476,669 claims methods for H. pylori-associated gastric and duodenal ulcers.
The core regimen is bismuth plus metronidazole plus tetracycline or a penicillin.
Claims 2-9, 11-18, 19-26, and 28-34 add acid-suppressant, timing, or disease-specific limitations.
Claims cover treatment, ulcer healing, epithelialization, and prevention of recurrence.
The patent is a method-of-treatment patent, not a composition-of-matter patent.
The ordinary patent term ended December 19, 2012.
The patent is not a current U.S. exclusivity barrier and does not independently require a Paragraph IV challenge.
Later bismuth combination products may be protected by separate formulation, packaging, manufacturing, FDA exclusivity, or later method patents.
The patent’s commercial significance is historical and analytical rather than enforceable.

FAQs About U.S. Patent 5,476,669

Does the patent cover amoxicillin-based H. pylori therapy?

Potentially, because amoxicillin is a penicillin. The regimen must also include metronidazole, a pharmaceutically acceptable bismuth compound, and the claimed ulcer-related treatment purpose.

Does the patent cover clarithromycin triple therapy?

Not under the express core claims. The claims require metronidazole as the second antibiotic and identify tetracycline or penicillins as the first antibiotic.

Does the patent cover bismuth quadruple therapy?

Some bismuth quadruple regimens may correspond to the claims requiring acid suppression, depending on the antibiotics, treatment purpose, and timing. The patent does not require a particular commercial kit or fixed-dose product.

Can an expired method patent block an H. pylori product launch?

No. An expired patent cannot provide current enforceable exclusivity. A launch may still implicate later patents, FDA exclusivity, or regulatory requirements.

Does the patent cover the manufacture of bismuth, metronidazole, or tetracycline products?

No express manufacturing claim appears in the claims provided. The claims are directed to administering the agents in specified patient-treatment regimens.

References

United States Patent and Trademark Office. (1995). U.S. Patent No. 5,476,669.
35 U.S.C. § 154. Patent term and adjustment.
35 U.S.C. §§ 271(b)-(c). Patent infringement by inducement and contribution.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355. FDA approval and regulatory exclusivity provisions.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	PI4838	Oct 12, 1987
Australia	PI5985	Dec 18, 1987
Australia	PI7513	Mar 30, 1988

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	100324	⤷ Start Trial
Australia	2540588	⤷ Start Trial
Australia	623868	⤷ Start Trial
Canada	1330759	⤷ Start Trial
Germany	3887353	⤷ Start Trial
European Patent Office	0439453	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,476,669

Summary for Patent: 5,476,669