United States Patent 4,760,075: Claim Scope, Nizatidine Coverage, Expiration, and Patent Landscape

U.S. Patent 4,760,075 is a broad, expired patent covering substituted thiazole compounds with H2-histamine receptor antagonist activity, pharmaceutical formulations, and methods of inhibiting gastric acid secretion. Its most commercially relevant subject matter is the thiazolylmethylthioethyl antisecretory class associated with nizatidine and related compounds. The patent issued on July 26, 1988, and, as a pre-URAA patent, reached its ordinary 17-year term in 2005, absent a patent-term extension or other adjustment. It does not create a current U.S. patent barrier to generic commercialization.

What does U.S. Patent 4,760,075 cover?

The patent claims five connected categories:

A broad chemical genus of thiazole derivatives.
Narrower species defined by selected substituents.
Specific named compounds.
Oral pharmaceutical formulations.
Methods for suppressing gastric acid secretion and inhibiting H2 histamine receptors.

The patent is directed to H2-receptor antagonists, the therapeutic class that preceded proton-pump inhibitors as a major treatment for peptic ulcer disease, gastroesophageal reflux disease and related acid-mediated disorders.

The patent's commercial center of gravity is the structure represented by a thiazole ring connected through a methylthioethyl chain to a substituted nitroethenediamine or cyanoguanidine group. The claim language supplied includes compounds corresponding to the chemical architecture of nizatidine and related H2 antagonists.

What is the claim structure of U.S. Patent 4,760,075?

Claim 1: Broad Markush compound claim

Claim 1 is the principal genus claim. It covers compounds having:

A substituted thiazole-related core.
An aminoalkyl substituent defined by R1 and R2.
A variable linker containing oxygen, sulfur or methylene.
A linker length of one to three carbon units, depending on Z.
A heterocyclic or acyclic terminal pharmacophore represented by Q.
Acid-addition salts.

The R1/R2 definition covers:

Hydrogen.
Methyl.
Ethyl.
Benzyl.
Benzoyl.
Piperidino, pyrrolidino or morpholino groups when R1 and R2 are taken together with the adjacent nitrogen.

R3 is hydrogen or methyl. Z may be oxygen, sulfur or methylene. The n variable controls the length of the linker.

The Q group is especially important. It includes several electron-deficient terminal systems, including:

Cyanoguanidine-type groups.
Nitroguanidine-type groups.
Nitroethenediamine-type groups.
Sulfur-containing systems.
N-sulfonyl derivatives.
N-carbamoyl derivatives.

The B substituent may be an amino group, with R being methyl, ethyl, cyclopropyl or 2-hydroxyethyl, or an alkoxy, alkylthio or benzylthio group.

This is a classic Markush claim. It attempts to capture a chemical class rather than a single active ingredient.

Claim 2: Restricted compound genus

Claim 2 narrows claim 1 in several ways. It limits the B substituent and imposes a relationship between B and Q when B is an O- or S-linked group.

This claim remains chemically broad but is more vulnerable to design-around strategies because it limits the relationship between the terminal pharmacophore and the alkoxy or thioalkyl substituent.

Claims 3 to 9: Structural subgenus claims

These claims progressively narrow the genus:

Claim	Limitation
3	Z is sulfur
4	n is 2
5	R3 is hydrogen
6	R1 and R2 are methyl
7	A is NCN or CHNO2
8	B is NHR, where R is methyl or ethyl
9	B is methylamino

Claims 3 through 9 identify the structural path most closely associated with the commercially relevant thiazolylmethylthioethyl H2 antagonists. Claims 3, 4, 5, 6, 8 and 9, when read together, produce a materially narrower species set than claim 1.

Claims 10 to 12: Specific compound coverage

Claim 10 narrows the structure to:

R3 as hydrogen.
R1 as hydrogen, methyl or ethyl.
R2 as methyl or ethyl.
Z as sulfur.
A as NCN, N-NO2 or CH-NO2.
B as an NHR group.
R as methyl or ethyl.

Claims 11 and 12 identify specific compounds. The supplied text contains typographical corruption, including "ehtyl," "compund," and an apparent inconsistency in the compound names. The certified patent text and chemical drawings control claim interpretation.

Claim 11 describes a nitroethenediamine thiazole derivative. Claim 12 describes a cyanoguanidine derivative containing a dimethylaminomethyl thiazole group. These species claims are narrower and historically more useful in infringement analysis than the broad genus claim.

Does U.S. Patent 4,760,075 cover nizatidine?

The patent covers chemical subject matter corresponding to the nizatidine H2-antagonist structure and closely related analogues. Nizatidine is generally identified as:

N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine.

Its structure contains the principal features emphasized by the patent:

A 2-substituted thiazole ring.
A dimethylaminomethyl substituent.
A sulfur-containing two-carbon linker.
A terminal N-methyl nitroethenediamine pharmacophore.

The exact infringement analysis depends on the certified claim language, the chemical identity of the accused product, salt form, stereochemistry if relevant, and prosecution-history interpretation. At a commercial level, however, the patent is historically associated with the nizatidine-related H2 antagonist estate.

What formulations are protected by U.S. Patent 4,760,075?

Claims 13 through 16 cover pharmaceutical formulations in unit dosage form.

The formulation claims require:

Oral administration for an antisecretory effect.
A compound falling within the chemical claims.
A pharmaceutically acceptable excipient.
An antisecretorially effective quantity.

Claim 15 narrows the dosage to 50 to 80 mg of active drug per unit dosage. This is formulation and dosage-form coverage, not a claim to every pharmaceutical product containing any H2 antagonist.

The claims do not appear to require a particular tablet coating, release profile, excipient, dissolution specification or manufacturing process. They therefore provide less protection against modern formulation design-arounds than a detailed controlled-release or solid-state patent.

A product could avoid these claims by using:

An active compound outside the claimed genus.
A non-oral dosage form, subject to the method claims.
A unit dose outside the specified range in claim 15.
A formulation that does not contain a compound satisfying the compound limitations.

What method-of-use claims are included?

Claims 17 through 24 cover therapeutic use.

Gastric acid secretion claims

Claims 17, 20 and 21 cover administering a claimed compound to a mammal with excessive gastric acid secretion. Claim 18 specifies an oral human daily dose of 140 to 350 mg. Claim 19 expresses the daily dose as 2 to 5 mg/kg.

Claim 22 narrows administration to oral dosing. Claim 23 covers parenteral administration.

H2 receptor claim

Claim 24 covers administering a claim 1 compound in an amount effective to inhibit H2 histamine receptors.

The method claims are broader in therapeutic objective than a disease-specific claim limited to reflux, ulcer disease or a named indication. Their practical enforceability would have depended on the accused product's active ingredient falling within the compound claims and on the relevant use and labeling evidence.

Because the patent expired, these method claims no longer create current U.S. exclusionary rights.

When did U.S. Patent 4,760,075 expire?

Event	Date or status
Patent issued	July 26, 1988
Governing term	Pre-URAA 17 years from grant
Ordinary expiration	July 26, 2005
Current status	Expired
Current blocking effect	None for U.S. commercial launch

The patent was granted before the 1995 change to a term measured principally from the earliest effective filing date. For pre-URAA patents, the ordinary rule was 17 years from issuance. No current U.S. exclusivity should be attributed to Patent 4,760,075.

No patent-term extension is generally associated with this patent in the publicly recognized product exclusivity history for nizatidine. FDA regulatory exclusivity and patent term are separate rights and must be analyzed independently. [1][2]

What is the FDA and Orange Book status?

Nizatidine was approved by FDA as Axid, originally marketed by Eli Lilly. FDA approved the product for conditions involving gastric acid secretion, including active duodenal ulcer and gastroesophageal reflux-related indications. The product was supplied in capsule and oral solution presentations in different regulatory periods. [2]

The key regulatory points are:

Nizatidine is a small-molecule drug, not a biologic.
Biosimilar approval is therefore not the relevant pathway.
Generic products proceed through abbreviated new drug applications, or ANDAs.
Any original Orange Book patent listing associated with the product cannot preserve exclusivity after expiration.
A generic applicant could historically address an unexpired listed patent through a Paragraph IV certification.

Current market entry is not blocked by U.S. Patent 4,760,075. The relevant FDA issues for nizatidine products have included product availability, manufacturing decisions and nitrosamine contamination concerns affecting certain H2-antagonist products. Those regulatory issues are distinct from the expired patent.

Were there Paragraph IV challenges or patent litigation?

A Paragraph IV certification is relevant only while a listed patent remains unexpired and enforceable. Because Patent 4,760,075 expired in 2005, it cannot support a new Paragraph IV-based launch delay.

The supplied information does not establish a specific reported infringement action, settlement agreement or licensed launch involving this patent. No litigation event should be attributed to Patent 4,760,075 without a docket-specific source. The patent's commercial significance is better understood through its expired composition and use claims than through a current litigation dispute.

Historically, generic nizatidine entrants would have faced the standard ANDA framework:

Certification against listed patents.
Potential Paragraph IV notice.
A 45-day period for the NDA holder to sue.
A possible 30-month stay under the Hatch-Waxman framework.
Generic approval after patent resolution or expiration.

That framework no longer produces a blocking period from this patent.

How strong was the patent estate?

Composition claims

The composition estate was commercially meaningful because claim 1 covered a large Markush genus and claims 10 through 12 identified narrower species. The strongest historical claims would likely have been the species claims directed to the sulfur-linked thiazole compounds and the defined nitroethenediamine or cyanoguanidine terminal groups.

Potential validity pressure points included:

Prior-art H2 antagonists.
Overbreadth of the Markush genus.
Written-description support for the full substituent combinations.
Enablement across all combinations of R1, R2, R3, Z, n, A and B.
Obviousness based on known thiazole H2-antagonist scaffolds.
Claim-construction disputes caused by chemical drawing conventions and transcription errors.

Formulation claims

Claims 13 through 16 were narrower than the composition genus. Their strength depended on whether the formulation and dose limitations added patentable technical distinction over known oral H2-antagonist products.

The 50-to-80 mg unit-dose limitation in claim 15 provided a clear boundary but also created a straightforward design-around opportunity.

Method claims

Claims 17 through 24 added commercial-use coverage. Method claims could support infringement theories against a product labeled for acid suppression, but their value depended on the underlying compound claim and the wording of the product labeling.

Current strength

The current enforceability score is effectively zero because the patent expired. Historical claim breadth was substantial; current exclusionary value is none.

How does this patent compare with competing H2-antagonist estates?

Drug	Representative commercial developer	Core chemistry	Patent position relative to US 4,760,075
Cimetidine	SmithKline	Cyanoguanidine H2 antagonist	Earlier H2-antagonist estate; prior-art context
Ranitidine	Glaxo	Furan-containing H2 antagonist	Separate composition and formulation estate
Famotidine	Merck	Thiazole/sulfonamide H2 antagonist	Separate and structurally distinct estate
Nizatidine	Eli Lilly	Thiazole, sulfur linker, nitroethenediamine	Closely aligned with the subject matter of US 4,760,075

The patent's technical position was between the earlier cimetidine class and later H2 antagonists. It sought to protect a broad thiazole-based chemical platform, not merely one finished product.

What generic entry risks remain?

There is no remaining patent-expiration risk from U.S. Patent 4,760,075. Commercial risks instead include:

FDA approval and bioequivalence requirements.
Product-quality compliance.
Nitrosamine monitoring and control.
API sourcing and impurity specifications.
Current manufacturing or process patents, if any apply to a particular supplier.
Trademark and labeling restrictions.
Market demand erosion from proton-pump inhibitors and newer acid-reduction therapies.

No biosimilar risk applies because nizatidine is a small molecule. Generic entry does not require a biosimilar application or interchangeability designation.

What geographic coverage did the patent provide?

U.S. Patent 4,760,075 provided rights only in the United States. Parallel foreign patent rights would have required separate national or regional filings and separate validity and expiration analysis.

A U.S. expiration did not automatically determine the status of corresponding rights in Europe, Japan, Canada or other jurisdictions. For current licensing or freedom-to-operate work, the relevant foreign family members must be reviewed independently for:

Grant status.
Patent-term adjustment.
Supplementary protection certificates.
Terminal disclaimers.
National-stage prosecution.
Opposition or revocation proceedings.

The U.S. patent itself cannot be used to infer active foreign rights.

Key Takeaways

U.S. Patent 4,760,075 covers a broad genus of thiazole H2-receptor antagonists.
Its claims include composition, formulation, gastric-acid-inhibition and H2-receptor-use subject matter.
Claims 10 through 12 narrow the scope to specific sulfur-linked thiazole compounds, including nizatidine-related structures.
Claims 13 through 16 cover oral unit-dose formulations, including a 50-to-80 mg dosage limitation.
Claims 17 through 24 cover gastric-acid suppression and H2-receptor inhibition.
The patent issued July 26, 1988, and ordinarily expired July 26, 2005.
It does not present a current U.S. patent barrier to generic nizatidine or related products.
Paragraph IV risk is historical, not current, for this patent.
Biosimilar analysis is inapplicable because nizatidine is a small molecule.
Current commercial exposure lies in FDA compliance, nitrosamine controls, API manufacturing and market demand, not in this expired patent.

FAQs

Is U.S. Patent 4,760,075 still enforceable?

No. The patent reached its ordinary pre-URAA term expiration in 2005.

Does the patent cover nizatidine hydrochloride?

The patent's compound claims cover the relevant nizatidine chemical structure and its acid-addition salts. Whether a particular salt falls within a claim depends on the certified chemical identity and claim construction.

Can an applicant file an ANDA for nizatidine without addressing this patent?

Yes. An expired patent cannot require a Paragraph IV certification as a basis for blocking FDA approval. The applicant must still satisfy applicable FDA requirements.

Did this patent protect a specific tablet formulation?

No. The formulation claims require a claimed active compound, oral unit dosage form and excipients. They do not appear limited to a particular coating, dissolution profile or manufacturing process.

Are foreign patents corresponding to U.S. Patent 4,760,075 expired?

The U.S. expiration does not establish foreign status. Each foreign family member requires separate national-register and term analysis.

References

United States Patent and Trademark Office. (1988). U.S. Patent No. 4,760,075, Thiazole derivatives. U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs and product labeling for Axid and nizatidine products. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2020). FDA requests removal of all ranitidine products from the market. U.S. Department of Health and Human Services.
United States Code, 35 U.S.C. §§ 154, 156, 271 and 355.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	241439	⤷ Start Trial
Austria	14879	⤷ Start Trial
Australia	542553	⤷ Start Trial
Australia	7594581	⤷ Start Trial
Bulgaria	60249	⤷ Start Trial
Canada	1166248	⤷ Start Trial
Czechoslovakia	227015	⤷ Start Trial
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Details for Patent: 4,760,075

Summary for Patent: 4,760,075