United States Patent 5,504,207: Terazosin Hydrochloride Form IV Claims, Scope, Expiration, and Patent Landscape

US Patent 5,504,207 protects a manufacturing process for terazosin hydrochloride dihydrate and separately claims the anhydrous Form IV crystalline modification of terazosin hydrochloride. The patent covers terazosin, marketed by Abbott Laboratories as Hytrin, an alpha-1 adrenergic receptor antagonist used for hypertension and benign prostatic hyperplasia. The patent issued on April 2, 1996, and its 20-year term expired in 2013, subject to any applicable patent-term adjustment or pediatric extension. It does not create a current US barrier to generic terazosin entry.

The patent is important historically because it addresses both process control and solid-state form control. Its principal technical limitation is the requirement to produce Form IV under specified reaction conditions: an anhydrous polar organic solvent, no added acid scavenger, and a reactant ratio of 4-amino-2-chloro-6,7-dimethoxyquinazoline to N-(2-tetrahydrofuroyl)piperazine of 1 to no more than 1.2. Claim 4 independently protects Form IV by its powder X-ray diffraction pattern.

What drug and chemical substance does US Patent 5,504,207 cover?

US Patent 5,504,207 covers terazosin hydrochloride, chemically identified as 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine hydrochloride. The claimed final dosage-form-relevant material is the hydrochloride dihydrate.

Terazosin has the following commercial and regulatory identifiers:

Item	Data
Generic name	Terazosin hydrochloride
Brand	Hytrin
Drug class	Alpha-1 adrenergic receptor antagonist
Primary indications	Hypertension; signs and symptoms of benign prostatic hyperplasia
Original innovator	Abbott Laboratories
Patent at issue	US 5,504,207
Patent issue date	April 2, 1996
Main technical subject	Terazosin hydrochloride Form IV and its preparation
Current US patent status	Expired
FDA pathway for generics	Abbreviated New Drug Application

The patent is directed to a particular salt and solid-state form rather than to every possible terazosin composition. Its claims should be read against earlier terazosin compound and pharmaceutical-composition patents, which may have expired earlier than US 5,504,207.

What are the independent claims in US Patent 5,504,207?

The patent has two material claim categories.

Claim 1: Process claim

Claim 1 covers a process comprising:

Reacting 4-amino-2-chloro-6,7-dimethoxyquinazoline with N-(2-tetrahydrofuroyl)piperazine.
Using a reactant ratio of 1 to n, where n is no more than 1.2.
Conducting the reaction in an anhydrous polar organic solvent.
Omitting any added acid scavenger.
Producing anhydrous terazosin hydrochloride Form IV.
Converting that Form IV intermediate into terazosin hydrochloride dihydrate.

Every listed process limitation matters. A process using excess piperazine above the claimed ratio, an aqueous solvent, an added acid scavenger, or a route that does not pass through Form IV may fall outside the literal scope of claim 1.

The claim is narrower than a general process for making terazosin. It does not cover every synthetic route to terazosin hydrochloride dihydrate. It covers the specified route and sequence.

Claim 4: Form IV product claim

Claim 4 covers anhydrous Form IV crystalline terazosin hydrochloride characterized by principal powder X-ray diffraction peaks at:

Principal peak	2-theta tolerance
7.15°	±0.2°
10.44°	±0.2°
14.56°	±0.2°
20.48°	±0.2°
21.23°	±0.2°
22.47°	±0.2°
23.70°	±0.2°
24.43°	±0.2°
27.11°	±0.2°

Claim 4 is materially different from claim 1. It is not limited to the patented manufacturing route. A party that independently produces Form IV through another process could, during the patent term, face a claim 4 issue even if its process avoided claim 1.

The claim requires the claimed crystalline form to be identified by the stated XRPD characteristics. The legal and technical analysis would normally compare the accused material’s diffraction pattern with the claimed peak positions, tolerances, and the patent’s characterization methodology.

What does claim 1 protect in technical terms?

Claim 1 protects a controlled crystallization and salt-isolation sequence.

The starting quinazoline is 4-amino-2-chloro-6,7-dimethoxyquinazoline. The second reactant is N-(2-tetrahydrofuroyl)piperazine, also described in the claim text as N-(2-tetrahydrofuroyl)piperzine. The reaction substitutes the chlorine atom at the 2-position of the quinazoline ring with the piperazine derivative, producing terazosin hydrochloride in Form IV.

The process has four commercially relevant control points:

Stoichiometry: the piperazine derivative cannot exceed 1.2 equivalents relative to the quinazoline starting material.
Solvent: the reaction must use an anhydrous polar organic solvent.
Acid-scavenger condition: no added acid scavenger is permitted.
Solid-state outcome: the reaction must produce anhydrous Form IV before conversion to the dihydrate.

These limitations distinguish the process from conventional nucleophilic aromatic substitution routes that use an excess of amine, water-containing solvent systems, or bases such as tertiary amines or inorganic carbonates.

Which solvents are covered by claim 2?

Claim 2 lists the following solvent categories:

C1-C4 alcohols;
C1-C4 ether-alcohols;
C4-C8 diethers; and
C3-C6 ketones.

The listed categories include solvents such as lower alcohols, ether-alcohols, selected glycol ethers or related diethers, and lower ketones, provided the solvent is anhydrous and otherwise satisfies the claim.

The solvent limitation is cumulative. A solvent may fall within one of the named chemical classes but still fail the claim if the reaction is not conducted under anhydrous conditions or if an added acid scavenger is used.

What solvent is identified in claim 3?

Claim 3 identifies methoxyethanol. The supplied claim text states, "The process of claim 3 wherein said anhydrous polar organic solvent is methoxyethanol." That dependency appears to contain a drafting or transcription error because claim 3 cannot depend on itself. The intended dependency is likely claim 2.

The apparent error does not automatically invalidate the underlying disclosure. In a litigation setting, the patent file history, issued patent image, certificate of correction, and claim-construction record would control the legally operative language. The technical limitation is clear: methoxyethanol is the specified solvent.

How broad is the Form IV crystalline-form claim?

Claim 4 is narrower than a claim covering all terazosin hydrochloride polymorphs but broader than a route-specific process claim.

It covers anhydrous Form IV identified through a set of XRPD peaks. The claim does not expressly require a particular particle size, morphology, bulk density, purity level, residual solvent profile, or manufacturing method. Those characteristics may matter for distinguishing Form IV from other forms in practice, but they are not stated as independent claim limitations.

The key infringement question would be whether the accused batch exhibits the claimed principal peaks within the stated ±0.2° 2-theta tolerances. An expert comparison would need to account for instrument calibration, sample preparation, radiation source, preferred orientation, polymorphic mixtures, and whether the accused sample is genuinely anhydrous.

A mixture containing Form IV may raise separate questions. The claim does not state a minimum percentage of Form IV or define whether a mixture with another polymorph is covered. That issue would depend on claim construction and the analytical evidence.

Does US Patent 5,504,207 cover terazosin hydrochloride dihydrate itself?

Claim 1 covers a process that ends with terazosin hydrochloride dihydrate. It does not, based on the supplied claims, independently claim the dihydrate as a composition of matter.

Claim 4 claims anhydrous Form IV, not the dihydrate. The patent therefore has a split structure:

Subject matter	Claimed?	Claim
Process using specified quinazoline and piperazine reactants	Yes	1
Reactant ratio up to 1.2 equivalents	Yes	1
Anhydrous polar organic solvent	Yes	1, 2
Methoxyethanol	Yes, subject to dependency correction	3
No added acid scavenger	Yes	1
Formation of anhydrous Form IV	Yes	1
Conversion to hydrochloride dihydrate	Yes as process step	1
Anhydrous Form IV crystal	Yes	4
All terazosin salts	No	None shown
All terazosin polymorphs	No	None shown
Terazosin hydrochloride dihydrate as a standalone product	Not shown	None shown

When did US Patent 5,504,207 expire?

The patent issued in 1996. Under the modern patent-term rule, a nonprovisional US application filed on or after June 8, 1995 generally receives a term of 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and applicable extensions. Earlier applications may be governed by the former 17-year-from-issue regime.

US 5,504,207 is reported in US patent databases with an expiration date in 2013. Any final freedom-to-operate analysis should use the USPTO patent record and the patent’s term adjustment data rather than calculating only from the issue date. FDA Orange Book patent listings may show a separate pediatric-extension date if the product received a qualifying six-month extension.

Event	Date or status
US patent issued	April 2, 1996
Standard patent-term endpoint	2013 period
Current status	Expired
Current generic-blocking effect	None in the United States

The patent cannot presently support a new US infringement action against a generic manufacturer for conduct occurring after expiration. Historical litigation or damages questions require analysis of the relevant pre-expiration conduct period.

What is the Orange Book status of US Patent 5,504,207?

The Orange Book is the FDA publication that identifies approved drug products and, where applicable, patents submitted by NDA holders for listed drug products. Patent listing and patent validity are separate issues. FDA listing does not establish that a patent is valid or infringed. The FDA also does not adjudicate most patent-infringement disputes.

For terazosin, the relevant listed drugs are associated with Abbott’s Hytrin approvals, including capsule and tablet products. Generic applicants could address listed patents through Paragraph IV certifications, noninfringement or invalidity arguments, or Paragraph III certifications where applicable. Once the relevant patent term expired, the patent ceased to present a current Orange Book-based launch barrier.

The regulatory significance of US 5,504,207 was therefore time-limited. It concerned manufacturing and solid-state form protection for the active pharmaceutical ingredient rather than a broad current exclusivity right for terazosin therapy.

Were there Paragraph IV challenges to the patent?

A Paragraph IV certification is an ANDA applicant’s statement that a listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The certification can trigger patent litigation and, in some circumstances, a 30-month stay of FDA approval under the Hatch-Waxman statute.

The public significance of US 5,504,207 should be assessed against the actual FDA Orange Book listing history and ANDA litigation records. The patent’s expiration means that any historic Paragraph IV dispute no longer affects present generic entry.

The patent’s claim structure also creates a practical distinction:

A generic applicant that manufactures terazosin through a route outside claim 1 could pursue a process-based noninfringement position.
A generic applicant whose material is not Form IV could avoid claim 4 on a solid-state basis.
A generic applicant using Form IV would have faced the more direct product-claim risk before expiration.
A Paragraph IV certification would have been relevant only while the patent remained enforceable.

No current US generic launch restriction arises from the expired patent.

What other patents protected terazosin?

Terazosin’s historical patent estate included earlier patents directed to quinazoline compounds, terazosin-related compositions, and pharmaceutical uses. The original compound and composition patents were distinct from US 5,504,207.

Patent category	Typical subject matter	Relationship to US 5,504,207
Early compound patents	Quinazoline derivatives, including terazosin-related compounds	Earlier foundational protection
Pharmaceutical composition patents	Terazosin formulations and dosage forms	Potentially separate from Form IV
Method-of-use patents	Treatment of hypertension or BPH	Separate therapeutic-use scope
Solid-state patents	Terazosin hydrochloride polymorphs and hydrates	US 5,504,207 is in this category
Process patents	Salt formation, crystallization, and isolation	Claim 1 is in this category

The relevant landscape must distinguish compound expiry from later process or polymorph patents. A generic could be free to market terazosin after the basic compound patent expired while still facing a later patent directed to a particular polymorph or manufacturing process. That distinction is central to small-molecule freedom-to-operate analysis.

How strong is the patent estate for US 5,504,207?

The patent had moderate historical strength for targeted manufacturing and solid-state protection, but limited breadth.

Strengths

Claim 4 is a product claim. It could reach Form IV regardless of whether the accused manufacturer used the patented process. Product claims generally provide broader enforcement leverage than process claims when the claimed product can be reliably identified.

Claim 1 also captures a commercially plausible manufacturing route. The no-acid-scavenger limitation and the controlled stoichiometric range may have distinguished the claimed process from earlier approaches.

The XRPD limitations provide an objective analytical test. A diffraction pattern can support batch-level comparison, although interpretation remains sensitive to sample and instrument conditions.

Limitations

Claim 1 is narrow because it requires all process steps and conditions. A manufacturer could potentially design around it by changing the solvent, using an acid scavenger, altering stoichiometry, avoiding Form IV, or converting through a different intermediate.

Claim 4 is limited to the specific Form IV pattern. Other anhydrous polymorphs, hydrates, solvates, amorphous material, or mixtures may fall outside the claim depending on their analytical profile and claim construction.

The patent is expired. Its current commercial strength is therefore zero as a blocking right, although it remains relevant to historical validity, infringement, damages, and patent-landscape analysis.

What generic launch scenarios existed before expiration?

Before expiration, a generic manufacturer had several potential strategies:

Use a noninfringing process that did not satisfy claim 1.
Produce a terazosin hydrochloride solid form other than Form IV.
Establish that the final commercial product did not contain the claimed Form IV.
Challenge claim 4 on validity grounds, including anticipation, obviousness, written description, enablement, or indefiniteness.
File a Paragraph IV certification and litigate before launch.
Wait for expiration and file or proceed under a Paragraph III certification.

The strongest historical risk would have involved a manufacturer using the patented route and supplying Form IV terazosin hydrochloride. A manufacturer using a different route and a different final solid form would have had a stronger noninfringement position, subject to other patents and regulatory requirements.

Did US Patent 5,504,207 create a biosimilar risk?

No. Terazosin is a chemically synthesized small molecule, not a biologic. The relevant competition is generic competition under the ANDA pathway, not biosimilar competition under the Biologics Price Competition and Innovation Act.

The relevant regulatory and IP issues were:

Hatch-Waxman patent certifications;
Orange Book listings;
product-form and process patents;
ANDA approval timing;
state and federal substitution rules; and
generic manufacturing economics.

What licensing or settlement issues affected the patent?

US 5,504,207 was associated with Abbott’s terazosin product franchise. The patent claims supplied do not establish a license, settlement, covenant not to sue, or authorized-generic arrangement. Patent ownership, licensing, and litigation settlement terms must be established from assignment records, court filings, FDA correspondence, or transaction disclosures.

Because the patent has expired, any historic settlement may retain significance only for damages analysis, antitrust review, or the reconstruction of generic-entry timing. It does not create a current restriction on US manufacture or sale based on this patent alone.

What geographic coverage did the patent have?

US 5,504,207 had territorial scope only in the United States. It did not directly block manufacturing, sale, or importation in Europe, Canada, Japan, or other jurisdictions.

A global freedom-to-operate review would require corresponding foreign family members, including applications covering:

terazosin hydrochloride polymorphs;
Form IV;
terazosin hydrochloride hydrates;
crystallization processes; and
commercial manufacturing routes.

Foreign rights may have had different filing dates, claim scope, prosecution outcomes, and expiration dates. The US expiration does not establish the status of related foreign patents.

Key Takeaways

US 5,504,207 concerns terazosin hydrochloride, marketed as Hytrin.
Claim 1 protects a specific process using defined reactants, a maximum 1.2-equivalent ratio, an anhydrous polar organic solvent, no added acid scavenger, formation of Form IV, and conversion to the dihydrate.
Claims 2 and 3 narrow the solvent limitation, with claim 3 apparently containing a dependency or transcription error.
Claim 4 independently protects anhydrous terazosin hydrochloride Form IV by nine XRPD peak positions.
The patent does not, based on the supplied claims, broadly claim all terazosin, all terazosin hydrochloride, or terazosin hydrochloride dihydrate as a standalone composition.
The patent expired in the 2013 period and has no current US generic-blocking effect.
The patent is relevant to historical Paragraph IV strategy, process design-around analysis, and solid-state patent landscapes.
Terazosin is a small molecule, so biosimilar analysis is not applicable.
Current commercial risk must be assessed against other expired or surviving terazosin patents, FDA listings, and product-specific regulatory requirements.

FAQs

What is the chemical name of the drug protected by US 5,504,207?

The drug is terazosin hydrochloride, chemically identified as 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine hydrochloride.

Does producing terazosin hydrochloride automatically infringe US 5,504,207?

No. Claim 1 requires a specific process, and claim 4 requires the anhydrous Form IV crystal defined by the stated XRPD peaks. Other terazosin routes or solid forms may fall outside the supplied claims.

Can a generic manufacturer use Form IV terazosin today?

Yes, US 5,504,207 is expired. A current launch still requires review of any other relevant US patents, FDA requirements, manufacturing controls, and applicable regulatory exclusivities.

Is Form IV the same as terazosin hydrochloride dihydrate?

No. Form IV is claimed as an anhydrous crystalline modification. The dihydrate contains water of crystallization and is the product obtained after the conversion step in claim 1.

Does this patent cover terazosin tablets and capsules?

The supplied claims do not directly claim tablets or capsules. They concern the active ingredient’s preparation and crystalline form. Separate formulation, composition, or method-of-use patents would be needed to cover a finished dosage form.

References

United States Patent and Trademark Office. (1996). US Patent No. 5,504,207: Terazosin hydrochloride dihydrate and process for preparation. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. U.S. Department of Health and Human Services.
U.S. Code, 35 U.S.C. § 154. Patent term.
U.S. Code, 21 U.S.C. § 355. New drugs.
U.S. Code, 35 U.S.C. § 271(e). Infringement of patents in regulated drug development.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	143959	⤷ Start Trial
Brazil	1100705	⤷ Start Trial
Canada	2143971	⤷ Start Trial
Germany	69500064	⤷ Start Trial
Denmark	0708104	⤷ Start Trial
European Patent Office	0708104	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,504,207

Summary for Patent: 5,504,207