United States Patent 3,935,267: Nadolol Claims, Scope, Expiration, and Patent Landscape

U.S. Patent No. 3,935,267 covers substituted tetrahydronaphthalene compounds, including the beta-blocker nadolol and related stereoisomers, salts, and analogues. The patent issued on January 27, 1976, and, under the pre-1995 patent-term rule, expired approximately 17 years later on January 27, 1993. The patent no longer creates a U.S. market-entry barrier for nadolol or its generic equivalents.[1]

The most commercially important claim is claim 5, which specifically covers the tert-butylamino compound known as nadolol in a cis configuration. Claim 3 covers the corresponding isopropylamino analogue. Claims 1, 2, 4, 6, and 7 extend protection to broader chemical families, stereoisomers, salts, and related substitution patterns.

What drug does U.S. Patent 3,935,267 cover?

The patent covers nadolol, a nonselective beta-adrenergic receptor blocker formerly marketed as Corgard. Nadolol is chemically a substituted tetrahydronaphthalene derivative with a beta-hydroxyamino-propoxy side chain.

The compound identified in claim 5 is:

2,3-cis-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(tert-butylamino)propoxy]-2,3-naphthalenediol

That compound corresponds to nadolol, subject to the stereochemical convention used in the patent and later regulatory nomenclature.

Nadolol was approved by the FDA for hypertension and angina. The original product was Corgard, associated with Bristol-Myers Squibb and its predecessor entities. The patent itself appears to have been assigned to E. R. Squibb & Sons, Inc., the corporate predecessor associated with the original Corgard business.[1][2]

What are the key claims in U.S. Patent 3,935,267?

The claims fall into two categories: broad genus claims and narrower compound claims.

Claim	Scope	Commercial relevance
1	Broad Markush genus covering substituted tetrahydronaphthalene compounds, stereoisomers, and salts	Captures a broad chemical platform
2	A narrower cis-diol subgroup with a lower-alkyl amino substituent	Encompasses specific beta-blocker analogues
3	Specific isopropylamino compound	Related analogue; not the marketed nadolol structure
4	Separate structural genus covering compounds, stereoisomers, and salts	Potentially overlaps with additional analogues
5	Specific tert-butylamino compound in the cis configuration	Core nadolol claim
6	Structural genus with lower alkyl substitution	Additional compound family
7	Structural genus with lower alkyl substitution	Additional compound family

The supplied patent text does not display the chemical drawings associated with the ##SPC## placeholders. As a result, the exact atom-by-atom boundaries of claims 1, 2, 4, 6, and 7 cannot be reconstructed from the text alone. Their legal scope must be read against the drawings and the patent specification. The specific chemical identities in claims 3 and 5 are identifiable from the quoted claim language.

How broad is claim 1 of U.S. Patent 3,935,267?

Claim 1 is a Markush composition claim. It covers compounds having the patent-defined tetrahydronaphthalene framework, together with:

A lower-alkyl group at R1.
Hydrogen or lower alkyl at R3 through R7.
Hydrogen, lower alkyl, lower alkoxy, or cycloalkyl at R8 through R10.
Stereoisomers of the claimed compounds.
Salts of the claimed compounds.

This structure gives claim 1 potentially broad coverage across a family of substituted beta-blocker-like molecules. The claim is not limited to nadolol. It reaches compounds differing in ring substitution, amino-substituent substitution, and stereochemistry, provided that the claimed core structure and substituent definitions are met.

The principal legal limitations are:

The compound must conform to the specific chemical scaffold shown in the missing structural formula.
R1 must be lower alkyl.
Each listed substituent must fall within the enumerated substituent classes.
The compound must be a stereoisomer or salt of the claimed structure.

A generic manufacturer would need to determine whether its active ingredient falls within the exact Markush formula, not merely whether it has similar beta-blocking activity.

What does claim 2 cover?

Claim 2 narrows the invention to compounds containing the claimed tetrahydronaphthalene diol system in which the two adjacent hydroxy groups are cis.

The cis limitation is material. A compound with the same connectivity but a trans relationship between the two adjacent hydroxyl groups would not literally satisfy claim 2. It could still raise an infringement issue under another claim or under the doctrine of equivalents, but that would require a separate analysis.

Claim 2 also retains the lower-alkyl requirement for R1 and covers stereoisomers and salts. Claim 3 then identifies one specific member of this subgroup.

What compound is covered by claim 3?

Claim 3 covers:

2,3-cis-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(isopropylamino)propoxy]-2,3-naphthalenediol

This compound differs from nadolol principally in the amino substituent:

Claim 3: isopropylamino group.
Claim 5: tert-butylamino group.

The claim 3 compound is therefore a close chemical analogue of nadolol but is not the compound identified in claim 5. The claim does not depend on commercial use. A claim to a specific chemical compound generally covers the compound regardless of whether it is sold as a drug, used as an intermediate, or investigated for another therapeutic indication.

What compound is covered by claim 5?

Claim 5 covers the cis tert-butylamino compound identified above as nadolol.

This is the most commercially important claim in the patent because it directly identifies the active ingredient used in Corgard and later generic nadolol products. It is narrower than claim 1 but provides a direct composition claim to the marketed compound.

The claim also depends on claim 4. That means claim 5 incorporates the structural requirements of claim 4 and adds the specific compound name and configuration. A product containing nadolol in the claimed configuration would have been exposed to claim 5 during the patent term, subject to the usual questions concerning claim construction, stereochemical identity, salt form, and infringement.

How do the composition claims differ from method-of-use claims?

U.S. Patent 3,935,267, based on the supplied claims, is primarily a composition patent. The quoted claims cover:

Chemical compounds.
Stereoisomers.
Salts.
Defined structural genera.
Specific compounds.

The supplied claims do not recite a therapeutic method, dosage regimen, patient population, or disease indication. They therefore do not operate as method-of-use claims.

This distinction mattered during generic approval. A generic applicant seeking approval for nadolol could face a listed composition patent even if it proposed a different labeling strategy. Conversely, an unexpired method-of-use patent could remain relevant after a composition patent expired. The quoted claims do not provide that type of indication-specific protection.

What formulations are protected by U.S. Patent 3,935,267?

The supplied claims do not claim a tablet, capsule, solution, extended-release formulation, excipient system, particle size, coating, or manufacturing process.

The patent covers salts of the claimed compounds, but that does not make it a conventional formulation patent. A salt claim is a chemical composition claim. It may reach a pharmaceutical salt of the active compound, while leaving formulation features outside the claim unless the formulation necessarily contains the claimed compound or salt.

For nadolol, the major commercial dosage forms have been immediate-release tablets. The supplied claims do not identify a particular tablet strength, excipient, dissolution profile, or release mechanism.

When did U.S. Patent 3,935,267 expire?

The patent issued on January 27, 1976. Because it was filed and issued before the 1995 transition to the modern patent-term regime, its ordinary term was generally 17 years from issuance. On that basis, the expiration date was approximately:

Event	Date
U.S. application filing	1970s, based on the patent record
Patent issuance	January 27, 1976
Ordinary 17-year term	January 27, 1993
Current status	Expired

The patent predates the Hatch-Waxman Act and the modern patent-term-adjustment system. It therefore did not receive the type of patent-term extension commonly associated with later pharmaceutical patents. Any definitive historical term calculation would also account for terminal disclaimers or other recorded events, but the patent is long expired in any event.[1][3]

What was the FDA exclusivity status for nadolol?

Nadolol’s regulatory exclusivity has also expired. FDA small-molecule exclusivity periods do not preserve market exclusivity decades after approval.

The relevant framework was:

Five-year new chemical entity exclusivity, if applicable.
Three-year exclusivity for certain new clinical investigations, where applicable.
Patent protection under the Orange Book system.
ANDA approval and Paragraph IV procedures for generic applicants.

Those periods expired long before the current market. Nadolol is now available through abbreviated new drug applications from multiple manufacturers. The product is not a biologic, so biosimilar exclusivity rules do not apply.[2][4]

What is the Orange Book status of nadolol?

The Orange Book identifies approved drug products and, where applicable, patents and exclusivity information submitted by NDA holders. The original composition patent is not a live Orange Book barrier because U.S. Patent 3,935,267 expired in 1993.

Current Orange Book relevance for nadolol is primarily administrative and commercial:

Identification of the reference listed drug.
Identification of approved generic products.
Dosage-form and strength comparisons.
Any later-listed patents, if present.
Therapeutic-equivalence evaluations.

An expired patent can remain visible in historical patent records, but it cannot support a current Paragraph IV enforcement action. The Orange Book listing of a patent does not extend its statutory term.[3][4]

Were there Paragraph IV challenges to nadolol?

Generic nadolol entry would historically have involved ANDA certifications under the Hatch-Waxman framework. A Paragraph IV certification would assert that a listed patent was invalid, unenforceable, or not infringed.

Because U.S. Patent 3,935,267 expired in 1993, any current nadolol ANDA applicant does not need to overcome this patent through a present-day Paragraph IV dispute. The patent’s expiration independently removes the composition patent as a basis for blocking approval or launch.

Historical Paragraph IV filings and litigation may have occurred during the transition to generic nadolol, but they do not affect present freedom to market products covered by the expired patent. A complete historical litigation chronology requires review of PACER, district-court dockets, FDA Paragraph IV notifications, and contemporaneous ANDA records.

What patent litigation affects nadolol today?

No active enforcement right remains under U.S. Patent 3,935,267. The patent cannot support:

A new infringement action against a nadolol manufacturer.
A preliminary injunction based on the patent.
A patent-based launch prohibition.
A new 30-month stay under Hatch-Waxman.
A patent settlement controlling current U.S. entry.

Any current litigation involving nadolol would need to rely on a different patent, a non-patent theory, regulatory conduct, product liability, trademark rights, or another legal basis.

Are there formulation patents or manufacturing barriers for nadolol?

The expired patent does not claim a specific formulation or manufacturing process in the quoted claims. Potential barriers therefore shift from core active-ingredient exclusivity to ordinary pharmaceutical execution:

Sourcing nadolol or a permitted intermediate.
Controlling stereochemical purity.
Controlling impurity profiles.
Demonstrating dissolution and bioequivalence.
Establishing validated commercial-scale manufacturing.
Meeting FDA current good manufacturing practice requirements.
Maintaining supply-chain economics.

These are regulatory and operational barriers, not surviving exclusivity rights under Patent 3,935,267.

How strong was the patent estate for nadolol?

The patent was strong during its term because it combined:

A broad structural genus.
Claims to stereoisomers.
Claims to salts.
A cis-configuration limitation.
A direct claim to the commercially important tert-butyl compound.

The direct nadolol claim reduced dependence on the broader Markush language. Even if a court narrowed a genus claim, claim 5 could have provided a focused composition claim if valid and infringed.

The estate is weak as a current commercial barrier because all rights under the patent have expired. Its present value is historical, technical, and freedom-to-operate related rather than exclusionary.

How does nadolol compare with competing beta-blockers?

Drug	Core class	Major historical patent issue	Current U.S. patent barrier
Nadolol	Nonselective beta blocker	U.S. Patent 3,935,267 and related historical rights	None from Patent 3,935,267
Propranolol	Nonselective beta blocker	Early composition and formulation patents	Core patents expired
Atenolol	Relatively beta-1 selective blocker	Later composition and regulatory protections	Core patents expired
Metoprolol	Beta-1 selective blocker	Separate immediate- and extended-release estates	Core patents expired; formulation history more important
Carvedilol	Nonselective beta and alpha blocker	Later patents and formulation claims	Depends on specific product and formulation
Bisoprolol	Beta-1 selective blocker	Separate later patent estate	Core generic availability established

Nadolol’s patent profile is unusual mainly because the principal compound patent is very old and the active ingredient is a small molecule with no biosimilar pathway.

What generic launch risks exist for nadolol?

The risk of a patent-blocked generic launch is effectively zero for U.S. Patent 3,935,267 because the patent expired three decades ago.

Remaining launch risks are commercial and regulatory:

Failure to demonstrate bioequivalence.
Product-quality deficiencies.
Manufacturing interruptions.
Inability to compete with established generic suppliers.
State substitution and formulary dynamics.
Market contraction caused by low reimbursement.
Product-specific labeling or supply obligations.

A company developing a nadolol generic would normally focus on FDA ANDA requirements, reference-product selection, dissolution, stability, and commercial supply rather than patent litigation.

Does nadolol have biosimilar risk?

No. Nadolol is a chemically synthesized small-molecule drug. It is regulated through the generic-drug pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not through the biosimilar pathway under section 351(k) of the Public Health Service Act.

The relevant competitive threat is generic substitution, not biosimilar competition.

Are licensing deals or settlements associated with this patent commercially relevant?

The original patent was connected to the Squibb nadolol development program. Any historical licensing, assignment, or settlement agreement would have commercial relevance only for the period before expiration.

No license can revive an expired patent right. A private agreement could govern royalties, know-how, trademarks, supply, or confidential manufacturing information, but it cannot impose patent exclusivity against unrelated generic manufacturers after January 27, 1993.

Key Takeaways

U.S. Patent 3,935,267 covers a family of substituted tetrahydronaphthalene compounds.
Claim 5 specifically covers nadolol in the claimed cis configuration.
Claim 3 covers an isopropylamino analogue rather than nadolol.
Claims 1, 2, 4, 6, and 7 provide broader or separate genus protection, subject to the structural drawings not reproduced in the supplied text.
The patent issued January 27, 1976, and expired approximately January 27, 1993.
The patent contains composition claims, not the quoted formulation or method-of-use claims.
Nadolol is a small molecule and has no biosimilar pathway.
The patent cannot support a current Paragraph IV challenge, 30-month stay, injunction, or launch block.
Current nadolol competition is governed by FDA approval, bioequivalence, manufacturing, reimbursement, and supply economics.

FAQs

What is the chemical name of nadolol in U.S. Patent 3,935,267?

The patent identifies nadolol as 2,3-cis-1,2,3,4-tetrahydro-5-[2-hydroxy-3-(tert-butylamino)propoxy]-2,3-naphthalenediol.

Does claim 5 cover all nadolol stereoisomers?

No. Claim 5 is tied to the configuration stated in the dependent claim structure, including the cis relationship of the adjacent hydroxyl groups. Other stereoisomers may fall outside claim 5, although they could be addressed by broader claims or other patent rights.

Can an expired composition patent still block an FDA approval?

No. An expired patent cannot create a current statutory patent stay or prevent FDA approval. Historical patent information may remain in public databases, but expiration removes enforceable patent exclusivity.

Is a nadolol salt covered by the patent?

The broader claims expressly include salts. Whether a particular salt falls within a claim depends on the exact structure, the salt-form language, and the limitations incorporated through any dependent claim.

Is U.S. Patent 3,935,267 relevant to current nadolol licensing negotiations?

It may be relevant as historical background or as evidence of the original compound development program. It has no current exclusionary value because the patent expired in 1993.

References

U.S. Patent No. 3,935,267. (1976). Substituted tetrahydronaphthalene derivatives. United States Patent and Trademark Office. https://patents.google.com/patent/US3935267
U.S. Food and Drug Administration. (n.d.). Corgard (nadolol) prescribing information. Drugs@FDA. https://www.accessdata.fda.gov/scripts/cder/daf/
U.S. Patent and Trademark Office. (n.d.). Patent term calculator and patent term guidance. https://www.uspto.gov/patents/laws/patent-term-calculator
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	198638	⤷ Start Trial
Argentina	198639	⤷ Start Trial
Belgium	849191	⤷ Start Trial
Canada	979912	⤷ Start Trial
Canada	979926	⤷ Start Trial
Switzerland	548978	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 3,935,267

Summary for Patent: 3,935,267