U.S. Patent 4,258,062: Claim Scope, Expiration, Orange Book Relevance, and Patent Landscape

U.S. Patent 4,258,062 covers a broad genus of phenoxy-amino-propanol beta-adrenergic antagonists, their physiologically acceptable acid-addition salts, pharmaceutical compositions, therapeutic use, and one specifically identified compound. The patent issued March 24, 1981. Under the pre-URAA patent term applicable to this patent, its ordinary U.S. term ended March 24, 1998, absent an unusual terminal-disclaimer or other historical adjustment. It is therefore expired and does not create current U.S. exclusivity for generic or competing development [1, 2].

What does U.S. Patent 4,258,062 claim?

The patent has three substantive protection layers:

A Markush genus of phenoxy-amino-propanol compounds.
Pharmaceutical compositions and therapeutic methods using those compounds.
A specifically named chemical species in claim 9.

The central structure is a substituted phenoxypropanol bearing a secondary amino group:

A phenoxypropanol core.
A para-substituted alkoxyalkyl group attached through a methylene linker.
An amino substituent at the terminal side chain.
A broad range of N-substituents.
Physiologically acceptable acid-addition salts.

The claimed compounds are beta-adrenergic antagonists described functionally by their ability to produce isoprenaline antagonism affecting heart rate or blood pressure.

What is the independent chemical claim?

Claim 1 covers compounds of the following general type:

The phenoxy ring contains a para-alkoxyalkyl substituent.
R1 is p-alkoxyalkyl with 2 to 6 carbon atoms.
R2 is an alkyl, hydroxyalkyl, cycloalkyl, aralkyl, or substituted aralkyl group within specified carbon-count and substitution limits.
Physiologically acceptable acid-addition salts are included.

The claim is a composition-of-matter claim. A compound falling within the defined structural boundaries would be within claim 1, regardless of whether it is specifically named in the specification, provided the claim is interpreted as enabled and valid for that compound.

The R1 and R2 limitations operate independently. A compound must satisfy both:

The para-substituent definition for R1.
The amino-substituent definition for R2.

The carbon-count language is material. It limits the permitted alkoxyalkyl and aralkyl groups and prevents the claim from covering all possible alkoxy or aryl-containing substituents.

How broad is the Markush scope?

The chemical genus is materially broader than claim 9. It covers multiple combinations of para-alkoxyalkyl groups and amino substituents.

R1 scope

Claim 1 defines R1 as p-alkoxyalkyl with 2 to 6 carbon atoms. Claim 2 narrows that category to 2-alkoxyethyl groups having 3 to 5 carbon atoms.

Examples within the claim 2 category include:

2-methoxyethyl
2-ethoxyethyl
2-propoxyethyl

The named compound in claim 9 uses a 2-isopropoxyethoxy group. That substituent contains five carbon atoms in the alkoxyethyl segment and falls within the narrower claim 2 definition.

R2 scope

Claim 1 covers several classes of amino substituent:

R2 category	Scope under claim 1
Alkyl	1-6 carbon atoms
Hydroxyalkyl	1-6 carbon atoms
Cycloalkyl	3-8 carbon atoms
Aralkyl	7-15 total carbon atoms
Substituted aralkyl	Aryl substituted by alkyl, alkoxy, hydroxyl, fluorine, chlorine, or combinations

Claim 3 narrows R2 to alkyl groups with 1 to 6 carbon atoms. Claim 4 narrows it further to tert-butyl. Claim 5 identifies selected substituents, including isopropyl, tert-butyl, 2-phenylethyl, 1,1-dimethyl-2-phenylethyl, and 2-(3,4-dimethoxyphenyl)ethyl.

Claim 6 covers:

Alkyl with 1 to 6 carbon atoms.
Phenylalkyl with 7 to 10 carbon atoms.
Methoxy-substituted phenylalkyl groups with 9 to 13 total carbon atoms.

The dependent claims do not replace claim 1. They create narrower fallback positions that inherit all limitations of claim 1.

What compound is specifically protected by claim 9?

Claim 9 specifically covers:

1-(p-2-isopropoxyethoxymethyl-phenoxy)-3-isopropylamino-propan-2-ol

This compound has:

A phenoxypropanol core.
A para-[(2-isopropoxyethoxy)methyl] substituent.
An isopropylamino group.
A secondary alcohol at the 2-position of the propanol chain.

The compound falls within the broader genus of claim 1 and the narrower categories in claims 2, 3, and 5.

Claim 9 provides a direct species claim. If a product had been marketed as this exact compound, claim 9 would have been the most straightforward product claim for enforcement. Because the patent expired in 1998, the claim has no current blocking effect in the United States [1, 2].

What do the pharmaceutical composition and method claims cover?

Claim 7: pharmaceutical compositions

Claim 7 covers a pharmaceutical composition comprising:

An amount of a claim 1 compound effective to achieve isoprenaline antagonism on heart rate or blood pressure.
A pharmaceutically acceptable adjuvant.

This is a composition claim, but it is not limited to a specific tablet, capsule, injectable formulation, excipient, release profile, dosage strength, or route of administration. The adjuvant language is broad and would ordinarily encompass conventional pharmaceutical excipients.

The claim does not expressly require:

A particular salt.
A specific dosage form.
A specific therapeutic indication.
A particular concentration.
A particular release mechanism.
A named active ingredient other than a compound falling within claim 1.

Claim 8: therapeutic method

Claim 8 covers administering a claim 1 compound to a mammal in an amount effective to achieve isoprenaline antagonism on heart rate or blood pressure.

The method claim is narrower than a general beta-blocker use claim because it is tied to:

A compound within claim 1.
Administration to a mammal.
The stated pharmacological result.

The claim is not expressly limited to humans. It includes mammalian treatment generally. Its functional language would be assessed through the administered compound, dose, observed pharmacology, and intended therapeutic use.

What is the scope of the dependent claims?

Claim	Subject matter	Practical significance
1	Broad compound genus and salts	Principal chemical claim
2	R1 is 2-alkoxyethyl with 3-5 carbon atoms	Narrows the para side chain
3	R2 is C1-C6 alkyl	Excludes non-alkyl R2 groups
4	R2 is tert-butyl	Specific beta-blocker subclass
5	Selected R2 groups	Identifies commercially relevant or experimentally preferred species
6	Alkyl and selected phenylalkyl groups	Alternative narrowed genus
7	Pharmaceutical composition	Product-use formulation claim
8	Mammalian treatment method	Therapeutic use claim
9	Named isopropyl species	Specific compound claim

The principal infringement risk during the patent term would have arisen from a compound whose structure literally satisfied claim 1. A product could infringe claim 1 even if it did not match claim 9, provided its R1 and R2 groups met the claim definitions.

When did U.S. Patent 4,258,062 lose exclusivity?

The patent issued on March 24, 1981. Patents subject to the pre-June 8, 1995 term rule generally ran for 17 years from issuance. On that basis, the ordinary expiration date was March 24, 1998 [1, 3].

Event	Date or status
U.S. patent issued	March 24, 1981
Governing term framework	Pre-URAA, generally 17 years from issue
Ordinary expiration	March 24, 1998
Current status	Expired
Current U.S. blocking rights	None from this patent

The patent is too old to support a current Paragraph IV strategy or a present-day patent-infringement exclusion. Any historical exclusivity analysis would need to examine the patent’s prosecution record, maintenance history, terminal disclaimers, and possible patent-term adjustments. Those considerations do not ordinarily revive an expired 1981 patent.

What is the Orange Book status of U.S. Patent 4,258,062?

The patent number alone does not establish an Orange Book listing. Orange Book listings are tied to an approved drug application and a specific approved product, active ingredient, dosage form, strength, and approved use [4].

A patent of this age could have been listed historically only if:

The claimed compound was the subject of an approved NDA.
The NDA holder submitted the patent for listing.
The patent met the statutory listing requirements.
The listed patent had not been removed or expired.

Because U.S. Patent 4,258,062 expired in 1998, it cannot presently provide an unexpired Orange Book patent barrier. Any current generic applicant would not face a live patent certification obligation based solely on this patent. A historical Orange Book entry, if one existed, would not create current exclusivity after expiration.

Are Paragraph IV challenges relevant?

Paragraph IV litigation is relevant only to an unexpired patent listed in the Orange Book for an approved drug product [5].

For U.S. Patent 4,258,062:

The patent is expired.
A new Paragraph IV challenge would have no practical commercial purpose against this patent.
The patent cannot support the 30-month stay mechanism associated with a qualifying listed patent.
Historical Paragraph IV activity, if any, would relate to the patent’s pre-1998 life and a specific NDA.

The patent claims chemical subject matter rather than a modern, drug-specific formulation or method-of-use listing. That distinction matters because Orange Book litigation normally focuses on the relationship between the approved product and the listed patent claims.

Does the patent create biosimilar risk?

No. Biosimilar regulation applies to biological products, not conventional small-molecule phenoxy-amino-propanols [6].

The relevant competitive pathways would have been:

Abbreviated New Drug Application approval for a small-molecule generic.
A full NDA for a different product or clinical strategy.
Competing development of another beta-adrenergic antagonist.
Historical off-patent manufacture of the claimed compound.

A biosimilar applicant would not be the relevant competitor for this patent family.

What formulation patents are protected by the patent?

Claim 7 is a broad pharmaceutical composition claim, but it is not a detailed formulation patent. It does not expressly claim:

Sustained release.
Controlled release.
A particular polymer.
A specific particle size.
A transdermal system.
Ophthalmic delivery.
A fixed-dose combination.
A defined impurity profile.
A manufacturing process.
A specific salt form beyond the general acid-addition-salt language in claim 1.

The formulation protection is therefore ancillary to the chemical genus. A later formulation patent could have created separate protection if it claimed a particular dosage form, excipient combination, salt, polymorph, release profile, or manufacturing process. Such later rights cannot be inferred from U.S. Patent 4,258,062 itself.

What manufacturing and process barriers does the patent create?

The supplied claims do not include a manufacturing method. They do not claim:

A specific synthetic route.
A reaction intermediate.
A catalyst.
A purification process.
A crystallization condition.
A polymorph.
A manufacturing specification.

During the patent term, manufacturing the claimed active compound could have infringed the composition claim even if the manufacturer used a different synthetic route. After expiration, the patent no longer creates a U.S. manufacturing barrier.

Trade secrets, regulatory controls, process patents, and impurity specifications could still affect commercial manufacture, but those rights are separate from the claims provided and cannot be attributed to this patent.

How strong was the patent estate?

The patent had meaningful historical breadth at the core chemical level but limited claim diversification.

Estate characteristic	Assessment
Core composition claim	Broad Markush genus
Species protection	Strong for the named compound in claim 9
Salt coverage	Included through acid-addition-salt language
Composition protection	Broad but functionally defined
Method-of-use protection	Broad mammalian isoprenaline-antagonism claim
Formulation specificity	Low
Process protection	None apparent in the supplied claims
Biologic relevance	None
Current enforceability	None, due to expiration

The strongest historical feature was the combination of a broad genus claim and a specifically identified species claim. The weakest feature from a lifecycle perspective was the absence, in the supplied claims, of differentiated formulation, process, polymorph, or dosage-regimen claims that could have supported later exclusivity.

How does this patent compare with modern pharmaceutical patent estates?

Modern small-molecule estates commonly divide protection across:

Composition of matter.
Specific salts and polymorphs.
Solid-state forms.
Formulations.
Dosage regimens.
Combination therapies.
Pediatric formulations.
Manufacturing processes.
Method-of-use claims.
Device or delivery technology.

U.S. Patent 4,258,062 is concentrated on the active chemical class and its broad pharmacological use. It resembles an early medicinal-chemistry patent rather than a modern layered lifecycle estate.

That structure had two consequences:

It could block direct synthesis and commercialization of covered molecules during the term.
Once the composition and method claims expired, the patent offered little residual protection against reformulation, process redesign, or alternative therapeutic positioning.

What generic launch scenarios existed?

During the patent term, the principal launch scenarios would have been:

Direct generic of the claimed species

A company seeking to market the exact claim 9 compound would have faced the composition claim and potentially the composition and method claims.

Different compound within the genus

A structurally different compound could still infringe claim 1 if its R1 and R2 groups satisfied the Markush definitions. A non-infringing alternative would need to fall outside at least one material limitation, such as:

An R1 group outside the specified carbon range.
An alkoxyalkyl arrangement outside the claimed structure.
An R2 group outside the listed classes or carbon ranges.
A non-covered core structure.

Post-expiration entry

After March 24, 1998, the patent no longer prevented manufacture or sale in the United States. The remaining barriers would have been regulatory approval, market demand, manufacturing economics, clinical differentiation, and any separate unexpired patent rights.

What geographic coverage does the patent provide?

U.S. Patent 4,258,062 provides only U.S. patent rights. It does not establish protection in:

Europe.
Japan.
Canada.
China.
Australia.
Latin America.
Any other jurisdiction.

International coverage would require corresponding national or regional applications. Patent families often include foreign counterparts, but a U.S. patent number alone does not establish their existence, scope, prosecution outcome, or expiration dates [2, 7].

The U.S. patent’s expiration does not determine the status of foreign counterparts. Each jurisdiction applies its own filing-date, term, maintenance, supplementary-protection, and lapse rules.

What litigation and settlement issues affect the patent?

The claims provided do not identify litigation, settlement, licensing, or a commercial product. Patent litigation cannot be inferred solely from the claim language.

Any historical enforcement analysis would require review of:

Federal district court dockets.
Court of Appeals decisions.
Patent reexamination records.
Paragraph IV notices.
ANDA litigation records.
License and settlement agreements.
Orange Book history.
Foreign opposition or revocation proceedings.

The absence of a current blocking right means that historical litigation would have limited relevance to present U.S. launch planning unless it established claim construction, invalidity, ownership, or estoppel principles affecting a related patent family.

Key Takeaways

U.S. Patent 4,258,062 claims a broad genus of phenoxy-amino-propanol beta blockers.
Claim 1 is the principal composition-of-matter claim.
Claims 2 through 6 narrow the R1 and R2 substituent classes.
Claim 7 covers pharmaceutical compositions.
Claim 8 covers mammalian treatment using the claimed compounds.
Claim 9 specifically claims 1-(p-2-isopropoxyethoxymethyl-phenoxy)-3-isopropylamino-propan-2-ol.
The patent issued March 24, 1981 and ordinarily expired March 24, 1998.
It does not create current U.S. generic, biosimilar, Orange Book, manufacturing, or licensing barriers.
The patent does not itself claim a specific formulation technology, manufacturing process, polymorph, or delivery system.
Foreign protection cannot be determined from the U.S. patent number alone.
Any current freedom-to-operate analysis must focus on later patents, regulatory exclusivity, trademarks, and other members of the relevant patent family.

FAQs

Is U.S. Patent 4,258,062 still enforceable?

No. Its ordinary U.S. patent term ended in 1998.

Does claim 9 protect a specific active pharmaceutical ingredient?

Yes. Claim 9 is directed to a specifically named phenoxy-amino-propanol compound rather than only a broad chemical genus.

Can a generic company rely on the patent’s expiration?

For this patent, yes. After expiration, the patent no longer blocks U.S. manufacture, sale, or use of a product covered solely by its claims.

Does the patent cover beta blockers generally?

No. It covers a defined structural genus of phenoxy-amino-propanols and related salts. Other beta blockers outside those structural limits are not covered by the claims provided.

Does the patent include a patent on a specific salt?

It includes physiologically acceptable acid-addition salts of the claimed compounds. It does not identify one particular salt, crystal form, polymorph, or salt manufacturing process.

References

United States Patent No. 4,258,062, Phenoxy-amino-propanols. U.S. Patent and Trademark Office. (1981). https://patents.google.com/patent/US4258062
United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/
Leahy-Smith America Invents Act, Pub. L. No. 112-29, § 3, 125 Stat. 284 (2011).
U.S. Food and Drug Administration. (2024). 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
Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).
Biologics Price Competition and Innovation Act of 2009, 42 U.S.C. § 262.
World Intellectual Property Organization. (n.d.). PATENTSCOPE. https://patentscope.wipo.int/

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	2645710	Oct 09, 1976

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	357143	⤷ Start Trial
Austria	A717377	⤷ Start Trial
Australia	2946477	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,258,062

Summary for Patent: 4,258,062