United States Patent 4,092,315: Scope, Claims, Expiration, and Prazosin Patent Landscape

US Patent 4,092,315 protects a specific crystalline polymorph of prazosin hydrochloride, known in the patent as the crystalline alpha form. It does not broadly protect prazosin, prazosin hydrochloride, or all solid forms of the active ingredient. The patent also protects a narrowly defined manufacturing process using a C5-C7 alkanol or cycloalkanol, with dependent claims focused on isoamyl alcohol and a temperature of about 132°C. Issued May 30, 1978, the patent expired under the pre-URAA 17-year term on May 30, 1995.[1]

Because the patent is expired, it presents no current US exclusivity barrier to generic prazosin, no enforceable patent basis for a new Paragraph IV action, and no current Orange Book protection.

What drug and active ingredient does US Patent 4,092,315 cover?

US 4,092,315 covers the crystalline alpha form of prazosin hydrochloride.

The chemical name recited in the claims is:

2-[4-(2-furoyl)piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride

This compound is prazosin hydrochloride, the hydrochloride salt of prazosin. Prazosin is an alpha-1 adrenergic receptor antagonist used primarily for hypertension and, in some markets and clinical settings, for other conditions including trauma-related nightmares.

The patent is a solid-state and manufacturing patent. Its legal focus is the physical form of the hydrochloride salt, not the pharmacological mechanism or the underlying quinazoline compound class.

Attribute	Patent position
Active ingredient	Prazosin
Protected salt	Prazosin hydrochloride
Protected solid form	Crystalline alpha form
Patent type	Polymorph and process patent
US patent	4,092,315
Issue date	May 30, 1978
Original patent term	17 years from issue
Expiration date	May 30, 1995
Current enforceability	Expired
Biologic relevance	None
Current generic barrier	None from this patent

What does claim 1 of US 4,092,315 protect?

Claim 1 is a product claim to the crystalline alpha form of prazosin hydrochloride, defined by a specified infrared spectrum in potassium bromide.

The claim has two principal limitations:

The product must be prazosin hydrochloride.
It must be the crystalline alpha form identified by the listed infrared absorption bands.

The infrared spectrum is not merely descriptive background. It is the principal claim limitation distinguishing the alpha form from other physical forms, including hydrates, solvates, amorphous material, and potentially other prazosin hydrochloride polymorphs.

Why the infrared limitation matters

Crystalline polymorph claims commonly use an analytical signature to define the claimed form. In this patent, the signature is an IR spectrum measured in potassium bromide and expressed in microns.

The listed absorption bands include the following values:

Group	IR bands in microns
Low and mid range	2.95, 3.10, 3.25, 3.50, 6.12, 6.26, 6.39, 6.54, 6.75, 6.81
Mid range	7.02, 7.22, 7.30, 7.81, 8.08, 8.28, 8.40, 8.70, 9.02
Higher range	9.25, 9.60, 9.85, 10.02, 10.67, 11.05, 11.30, 11.66, 11.90, 12.60, 13.10, 13.31, 13.87, 13.95, 14.82

The claim does not expressly state a tolerance for peak position, intensity, sample preparation, instrument resolution, or permitted missing or additional peaks. Those issues would have been relevant in a historical infringement dispute involving a marginally different analytical result.

A product would generally need to satisfy both the chemical identity and the claimed alpha-form fingerprint. Prazosin hydrochloride in a different polymorphic form would not automatically fall within claim 1.

How broad is claim 1 compared with claims 2 through 4?

Claim 1 is the broadest claim because it covers the alpha-form product regardless of how it was manufactured. Claims 2 through 4 are process claims and narrow the scope to specified preparation conditions.

Claim	Claim category	Core limitation	Relative scope
1	Product	Crystalline alpha-form prazosin hydrochloride identified by IR spectrum	Broadest
2	Process	Heating prazosin hydrochloride, hydrate, or methanolate in a C5-C7 alkanol or cycloalkanol at about 125-160°C until alpha-form precipitation is substantially complete	Narrower
3	Process	Claim 2 process using isoamyl alcohol	Narrower than claim 2
4	Process	Claim 3 process with isoamyl alcohol at about 132°C	Narrowest

Claim 2 appears to depend on claim 1 even though it is drafted as a process claim. The wording links the process to preparation of the product of claim 1. The typographical error in "whrein" does not materially affect the technical subject matter.

What process is protected by claim 2?

Claim 2 requires all of the following:

A starting material consisting of prazosin hydrochloride, a hydrate, or a methanolate.
An alcoholic solvent.
The solvent must be an alkanol or cycloalkanol containing about five to seven carbon atoms.
Heating at about 125°C to 160°C.
Continuing until formation of the crystalline alpha form is substantially complete.
Precipitation of the alpha form.

The solvent limitation is important. The claim does not cover every solvent system capable of producing the alpha form. It identifies a limited class of alcohol solvents by carbon number and chemical type.

Examples potentially within the literal solvent class include:

1-pentanol
2-pentanol
3-pentanol
isoamyl alcohol
other amyl alcohol isomers
hexanol isomers
heptanol isomers
selected C5-C7 cycloalkanols

The phrase "about 5 to 7 carbon atoms" introduces a claim-construction issue concerning the permissible range. Solvents materially outside the C5-C7 range would present a stronger noninfringement position, subject to any doctrine-of-equivalents analysis applicable at the time of the patent.

What do claims 3 and 4 add to the patent?

Claim 3 limits claim 2 to isoamyl alcohol. Isoamyl alcohol is a branched C5 alcohol and is also known as 3-methyl-1-butanol or isopentyl alcohol.

Claim 4 further limits the process to heating the isoamyl alcohol system at approximately 132°C. It is narrower than claim 3 because it adds a specific operating temperature.

The dependent claims create clear process design-around options:

Process variable	Within the express language of claims 3 and 4?
Isoamyl alcohol at about 132°C	Yes
Isoamyl alcohol at 125-160°C but not about 132°C	Claim 3 potentially, claim 4 not necessarily
1-pentanol at 132°C	Claim 2 potentially, claims 3 and 4 no
Ethanol or methanol	Outside the express C5-C7 solvent limitation
Water-only crystallization	Outside the express alcoholic-solvent limitation
Nonthermal precipitation	Outside the express heating limitation
Alpha form made by a different process	Potentially within claim 1, but not claims 2-4
Amorphous prazosin hydrochloride	Outside claim 1 if not the claimed crystalline alpha form
Another polymorph	Outside claim 1 if its IR spectrum does not meet the claim

The process claims therefore have substantially narrower practical scope than the product claim.

When did US Patent 4,092,315 lose exclusivity?

US Patent 4,092,315 expired on May 30, 1995.

The patent issued in 1978, when US patent terms for this type of application were generally calculated as 17 years from issuance. The application predates the Uruguay Round Agreements Act transition that changed the standard US term to 20 years from the earliest effective nonprovisional filing date.[1]

Event	Date
Patent issued	May 30, 1978
Statutory term	17 years from issue
Expiration	May 30, 1995
Current status	Expired

No patent term extension or patent term adjustment can restore an expired patent to enforceability. The original patent also predates the modern Hatch-Waxman framework governing many Orange Book-listed drug patents.

What patents protect prazosin beyond US 4,092,315?

The broader historical prazosin patent estate would have included several potential categories:

Compound patents covering the quinazoline chemical class or prazosin itself.
Salt and solid-state patents covering prazosin hydrochloride forms.
Formulation patents covering capsules, excipients, dissolution, or dosage delivery.
Method-of-use patents covering treatment of hypertension or other indications.
Manufacturing patents covering intermediates, coupling reactions, purification, or crystallization.

US 4,092,315 is distinct from a basic compound patent. It does not claim all prazosin derivatives, all prazosin salts, or all therapeutic uses of prazosin. Its contribution is the alpha crystalline form and a process for producing that form.

The supplied record does not establish a complete worldwide patent family or identify every historical US patent covering prazosin. The reliable conclusion from US 4,092,315 itself is that the patent is a later-stage solid-state patent layered over the underlying active ingredient.

What is the Orange Book status of US Patent 4,092,315?

US 4,092,315 cannot currently provide Orange Book patent exclusivity because it expired in 1995.

Prazosin hydrochloride products have been marketed as prescription capsules, including the historical Minipress product and generic equivalents. A generic applicant seeking approval today would not face a live patent claim from US 4,092,315.

The Orange Book generally identifies patents submitted by approved applicants that claim the drug substance, drug product, or approved method of use. Even where an expired patent remains visible in historical regulatory records, expiration eliminates its ability to block approval or commercial launch.[2]

Orange Book issue	Assessment
Current patent term	None
Current patent-based delay to approval	None
Current 30-month stay potential	None based on this patent
Current Paragraph IV exposure	None based on this patent
Current formulation exclusivity	None established by this patent
Current method-of-use exclusivity	None established by this patent

Which companies challenged or relied on this patent?

A complete litigation and Paragraph IV history cannot be inferred from the patent claims alone. The patent issued before the modern Hatch-Waxman litigation regime and expired before current generic prazosin competition became the primary regulatory framework.

The practical legal position is clear:

A new Paragraph IV certification against US 4,092,315 would have no commercial purpose because the patent has expired.
A complaint based solely on this patent would face the threshold issue that the patent no longer confers enforceable exclusionary rights.
Any historical dispute would have concerned whether a product was the claimed alpha form or whether a manufacturing process met the C5-C7 solvent and temperature limitations.
Settlement agreements involving this patent would have no current launch-blocking effect after expiration.

No current patent litigation can extend the term of US 4,092,315.

How strong is the patent estate for prazosin?

The patent estate is commercially weak today because the relevant patents are historic and the active ingredient is generic. During the patent term, US 4,092,315 had meaningful value as a solid-state barrier if the marketed product used the alpha form. Its strength depended on the ability to establish the polymorph through IR testing and to prove that a competing product was the claimed form.

Strength factor	Assessment
Product claim	Stronger than the process claims because it is not limited by manufacturing route
Analytical definition	Potentially enforceable but dependent on test methodology and spectrum interpretation
Process claims	Narrow due to solvent and temperature limitations
Design-around potential	Material
Duration	Expired
Current blocking value	None
Historical lifecycle value	Potentially significant
Biosimilar relevance	None

The product claim would have been more difficult to design around than claims 2 through 4. A competitor could avoid the process claims by using a different solvent or crystallization method, but it would need to avoid producing the claimed alpha form to avoid claim 1.

What generic entry risks exist for prazosin?

Current generic entry risk is not a patent risk arising from US 4,092,315. The relevant issues are regulatory, manufacturing, quality, and commercial.

A generic prazosin applicant would generally need to address:

Abbreviated New Drug Application requirements.
Bioequivalence to the reference listed drug.
Capsule strength and dissolution specifications.
Stability of prazosin hydrochloride.
Control of polymorphic form, if the approved reference product has a specified form.
Manufacturing reproducibility.
Supply economics in a mature generic market.

The expired patent may still have technical relevance. A manufacturer producing the same crystalline form may use the patent disclosure as historical process knowledge, but it cannot be sued for practicing the expired claims.

Does prazosin face biosimilar risk?

No. Prazosin is a chemically synthesized small molecule, not a biologic. The relevant competitors are generic drug manufacturers, not biosimilar applicants.

The FDA pathway is therefore the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act, rather than the biosimilar pathway under section 351(k) of the Public Health Service Act.[3]

What manufacturing and geographic barriers remain?

US 4,092,315 provides no current geographic barrier in the United States. Its US rights expired in 1995.

Foreign equivalents, if any, would have required separate national filings and would have had separate expiration dates. A US patent cannot block manufacture, importation, sale, or use outside the United States. Nor can a foreign patent create a current US restriction after the US patent has expired.

Any remaining manufacturing barrier is operational rather than patent-based. It may include:

Control of crystal form.
Reproducible particle size.
Prevention of hydrate or solvate conversion.
Batch-to-batch dissolution consistency.
Qualified suppliers for prazosin intermediates.
Regulatory documentation for the drug substance and finished capsule.

What is the commercial impact of US Patent 4,092,315?

The patent has no current direct revenue exposure for the originator because it cannot prevent generic sales. Its historical commercial role was to protect a selected crystalline form of prazosin hydrochloride after the underlying compound technology had been developed.

For an investor or licensing party, the patent should be valued as:

Expired prior art.
Historical manufacturing disclosure.
Evidence of early polymorph control strategy.
A potential source of technical information for solid-form development.
Not an asset capable of supporting current royalty income, exclusivity, or launch delay.

No current revenue forecast should attribute protected sales to this patent.

Key Takeaways

US Patent 4,092,315 covers the crystalline alpha form of prazosin hydrochloride.
Claim 1 is a product claim defined by a specific potassium-bromide IR spectrum.
Claim 2 covers a crystallization process using a C5-C7 alkanol or cycloalkanol at about 125-160°C.
Claim 3 is limited to isoamyl alcohol.
Claim 4 is limited to isoamyl alcohol at about 132°C.
The patent issued May 30, 1978, and expired May 30, 1995.
It does not currently block generic prazosin approval or launch.
It does not create current Orange Book exclusivity or Paragraph IV risk.
Prazosin has generic, not biosimilar, competition.
The patent has historical solid-state and manufacturing value but no current enforceable commercial value.

FAQs

Is prazosin hydrochloride the same as the alpha form in US Patent 4,092,315?

No. Prazosin hydrochloride identifies the chemical salt. The patent covers one specific crystalline form of that salt, identified as the alpha form by its IR spectrum.

Could a different prazosin polymorph avoid claim 1?

Potentially. A different polymorph that does not meet the claim's chemical and IR-spectrum limitations would have a strong noninfringement position against claim 1, subject to claim construction and equivalents analysis.

Does US Patent 4,092,315 cover prazosin capsules?

Not expressly. The claims cover the crystalline active pharmaceutical ingredient and a process for producing it. They do not recite a capsule, excipient system, dosage strength, or finished pharmaceutical composition.

Can a company use the isoamyl-alcohol process disclosed in the patent?

Yes, because the patent expired in 1995. The process disclosure may still be technically useful, but the expired claims cannot be enforced.

Does the patent support a current royalty or licensing program?

No. An expired US patent generally cannot support ongoing patent exclusivity or a new royalty claim based solely on practicing the claimed invention.

References

United States Patent No. 4,092,315. (1978). Crystalline alpha-form of 2-[4-(2-furoyl)piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and generic drugs. Center for Drug Evaluation and Research.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	210937	⤷ Start Trial
Australia	2244377	⤷ Start Trial
Australia	506937	⤷ Start Trial
Belgium	851878	⤷ Start Trial
Bulgaria	29724	⤷ Start Trial
Canada	1068269	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,092,315

Summary for Patent: 4,092,315