United States Patent 4,822,807: Torsemide Polymorph Scope, Expiration, and Patent Landscape

U.S. Patent No. 4,822,807 protects pharmaceutical compositions containing rapidly dissolving crystalline torsemide, also known as torasemide, in pure or substantially pure Modification I. The patent does not claim torsemide generally. Its central limitations are the specific crystal form, exclusion of Modification II, and defined dissolution performance.

The patent issued on April 18, 1989. Under the pre-Uruguay Round patent-term rule, its basic term was 17 years from issuance, producing an expected expiration date of April 18, 2006, absent a term extension or other adjustment.[1] The claims supplied are therefore expired and do not create a current U.S. barrier to generic torsemide products.

What does U.S. Patent 4,822,807 protect?

The patent protects compositions that combine four required elements:

An effective amount of crystalline torsemide Modification I.
The defined monoclinic crystal structure with space group P21/c.
Substantial absence of crystalline torsemide Modification II.
Dissolution performance of at least 60% in water after 15 minutes and at least 80% after 30 minutes.
A pharmacologically acceptable carrier.

The principal inventive feature is the use of a specific torsemide polymorph with faster dissolution characteristics than Modification II.

Claim limitation	Scope
Active ingredient	Torsemide, also called torasemide
Crystal form	Modification I
Crystal system	Monoclinic
Space group	P21/c
Melting point	Approximately 169°C
Excluded form	Modification II, monoclinic P2/n
Modification II melting point	Approximately 162°C
Dissolution threshold	At least 60% at 15 minutes and at least 80% at 30 minutes
Dosage form	Pharmaceutical composition
Carrier	Pharmacologically acceptable carrier
Therapeutic purpose	Diuretic pharmaceutical composition

The claim is composition-based. It does not, on the supplied claim language, claim torsemide Modification I as an isolated chemical substance, a manufacturing process, a method of treating edema or hypertension, or a specific tablet unless the tablet satisfies the composition limitations.

How broad is independent claim 1?

Claim 1 is narrower than a conventional active-ingredient claim and broader than the two formulation claims that follow it.

A product would likely need to satisfy the following technical questions to fall within claim 1:

Does the product contain torsemide in Modification I?
Is the material substantially free of Modification II?
Does the material exhibit the specified crystallographic characteristics?
Does the composition meet both dissolution thresholds?
Is the material incorporated into a pharmaceutical composition with an acceptable carrier?

The claim uses both structural and functional limitations. The structural limitations identify Modification I by crystallographic form, space group, and melting point. The dissolution limitations add performance requirements.

A torsemide product containing Modification I but failing the 60% and 80% dissolution thresholds would present a noninfringement argument based on the express claim limitations. The same analysis would apply to a formulation containing a mixture of Modifications I and II if the mixture were not "substantially free" of Modification II.

The phrase "substantially free" is material to claim scope. It does not establish a numerical impurity threshold in the supplied claim text. Its interpretation would depend on the specification, prosecution history, analytical method, and potentially expert evidence. A product with trace quantities of Modification II may still fall within the claim, while a substantial mixture of the two polymorphs would present a stronger noninfringement position.

What do claims 2 and 3 protect?

Claims 2 and 3 are dependent formulation claims. Each incorporates every limitation of claim 1 and adds a specified excipient composition.

Claim 2 formulation

Claim 2 covers a composition comprising approximately:

Component	Parts by weight
Torsemide Modification I	100
Lactose monohydrate	20
Maize starch	77
Silicon dioxide	2
Magnesium stearate	1

The stated total is approximately 200 parts. On a normalized basis, the formulation contains about 50% torsemide, 10% lactose monohydrate, 38.5% maize starch, 1% silicon dioxide, and 0.5% magnesium stearate.

Claim 3 formulation

Claim 3 covers a lower-strength composition comprising approximately:

Component	Parts by weight
Torsemide Modification I	25
Lactose monohydrate	605
Maize starch	160
Silicon dioxide	6
Magnesium stearate	4

The stated total is approximately 800 parts. On a normalized basis, the formulation contains about 3.125% torsemide, 75.625% lactose monohydrate, 20% maize starch, 0.75% silicon dioxide, and 0.5% magnesium stearate.

Because claims 2 and 3 depend on claim 1, a formulation must satisfy the polymorph, purity, dissolution, and carrier requirements of claim 1 before the excipient ratios become relevant.

What is the difference between Modification I and Modification II?

Modification I and Modification II are polymorphs of torsemide. They have the same molecular composition but different crystal packing arrangements.

Property	Modification I	Modification II
Crystal system	Monoclinic	Monoclinic
Space group	P21/c	P2/n
Melting point	Approximately 169°C	Approximately 162°C
Role in patent	Claimed form	Form substantially excluded by claim 1
Claimed performance	Rapid dissolution	Not the claimed rapid-dissolution form

Polymorph differences can affect dissolution rate, manufacturing behavior, stability, compressibility, and bioavailability. The patent’s claim strategy links the crystal form to a measurable dissolution profile rather than relying only on crystallographic identification.

In a patent dispute, the parties would likely examine powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy, microscopy, and dissolution testing. The melting point alone would usually be insufficient to establish the complete identity of the claimed polymorph.

Does the patent claim torsemide itself?

No. Based on the supplied claims, U.S. Patent 4,822,807 does not claim torsemide in every form.

A product containing amorphous torsemide, Modification II, or another polymorph would not satisfy the express Modification I limitation. A product containing Modification I could still avoid infringement if it failed another limitation, such as the dissolution thresholds or the requirement that the composition be substantially free of Modification II.

The patent also does not claim:

The torsemide molecule as a chemical entity.
Every pharmaceutical composition containing torsemide.
A method of administering torsemide.
A particular tablet manufacturing process.
A specific dosage strength independent of formulation.
A sustained-release or injectable formulation, unless those products otherwise satisfy the composition claim.

When did U.S. Patent 4,822,807 lose exclusivity?

The expected expiration date was April 18, 2006, 17 years after issuance.[1] The patent issued before the 1995 change that generally shifted U.S. patent terms to 20 years from the earliest effective nonprovisional filing date. Pre-URAA patents generally retained the longer of the applicable 17-year-from-issue term or 20-year-from-filing term, subject to statutory exceptions.[2]

No current enforceable exclusivity should be attributed to this patent without evidence of a patent-term extension under 35 U.S.C. § 156. A diuretic small-molecule product such as torsemide would not present a biosimilar issue. Any historical regulatory exclusivity or patent listing would be separate from the expired patent term.

What is the Orange Book status of U.S. Patent 4,822,807?

The Orange Book is relevant only if the patent was submitted for listing against an approved drug application and accepted by the FDA under its listing rules.[3] The supplied claim text does not establish whether Patent 4,822,807 was listed against a specific torsemide NDA, nor does it establish the patent’s historical listing code.

Even if the patent was listed, an expired listing would not block approval or launch of a therapeutically equivalent torsemide product. A historical Orange Book listing could have been relevant to Paragraph IV certifications before expiration, but it would not create present-day market exclusivity.

For small-molecule torsemide products, the relevant FDA pathway is an abbreviated new drug application, or ANDA. The relevant regulatory questions are therapeutic equivalence, bioequivalence, labeling, manufacturing, and product quality. The patent’s expiration removes the principal composition-patent obstacle described by the supplied claims.

Were Paragraph IV challenges or settlements relevant?

A Paragraph IV certification would have been relevant if an ANDA applicant sought approval before patent expiration and asserted that the listed patent was invalid, unenforceable, or not infringed.[4]

The supplied information does not establish a specific Paragraph IV filing, first-filer status, litigation docket, or settlement agreement involving U.S. Patent 4,822,807. The patent’s April 2006 expiration means that any historical Paragraph IV dispute would now have no continuing blocking effect from this patent.

There is no basis in the supplied claims to identify a particular generic company, settlement date, launch restriction, or authorized-generic arrangement.

What patent litigation affects torsemide products?

The patent could have supported an infringement action against a product containing Modification I in a formulation meeting the dissolution and carrier limitations. The most important litigation issues would have been:

Whether the accused torsemide was Modification I.
Whether Modification II was present in more than a negligible amount.
Whether the product met the dissolution thresholds.
Whether the accused formulation used a pharmacologically acceptable carrier.
Whether claims 2 or 3 applied based on the excipient ratios.

A product containing a different polymorph would have had a substantial noninfringement position. A product containing Modification I but using a materially different formulation would still need to address claim 1, because claim 1 is not limited to the specific excipient ratios in claims 2 and 3.

The patent’s expiration eliminates current infringement exposure under the supplied claims. It does not eliminate potential historical issues involving damages, prior settlements, or past sales, which would depend on the applicable limitation periods and litigation record.

How strong is the patent estate for torsemide?

The supplied patent has a focused historical estate rather than a broad current estate.

Risk category	Assessment
Active-ingredient patent	Not established by the supplied claims
Polymorph protection	Strongly defined for Modification I
Formulation protection	Narrow, dependent on claim 1
Method-of-use protection	Not present in the supplied claims
Manufacturing protection	Not present in the supplied claims
Biosimilar risk	Not applicable to torsemide
Current patent barrier	None from this expired patent
Historical design-around potential	Available through different polymorphs, mixtures, or dissolution profiles
Current generic launch risk	Low from Patent 4,822,807 itself

The historical patent strategy was technically meaningful because it targeted a pharmaceutical solid form with improved dissolution. Its commercial value depended on maintaining control over Modification I and preventing competitors from using the same form in rapidly dissolving compositions.

Its present value is limited by expiration. Any remaining torsemide patent risk would have to arise from later patents covering a different polymorph, formulation, dosage form, combination, manufacturing process, or method of treatment.

How does the patent compare with competing diuretics?

Torsemide competes primarily with loop diuretics such as furosemide and bumetanide. Patent landscapes for those products are separate from the torsemide polymorph estate.

Product	Active ingredient	Patent issue represented by U.S. 4,822,807
Torsemide	Torsemide	Modification I composition claims
Furosemide	Furosemide	Not covered
Bumetanide	Bumetanide	Not covered
Hydrochlorothiazide	Hydrochlorothiazide	Not covered

The patent does not create exclusivity over the loop-diuretic market. It addressed a particular solid form and formulation of torsemide.

What generic entry risks exist for torsemide?

For a current generic applicant, U.S. Patent 4,822,807 presents no live patent-term barrier because the expected term ended in 2006. Generic entry risk is more likely to arise from:

FDA bioequivalence requirements.
Variability in polymorph control.
Batch-to-batch dissolution performance.
Stability of the selected solid form.
Manufacturing reproducibility.
Other later-expiring patents not identified in the supplied record.
State or federal regulatory issues unrelated to this patent.

A manufacturer using Modification I should still control polymorph identity and dissolution because those characteristics can affect product quality even though the patent has expired.

Key Takeaways

U.S. Patent 4,822,807 is directed to rapidly dissolving crystalline torsemide Modification I.
Claim 1 requires Modification I, substantial absence of Modification II, both dissolution thresholds, and a pharmaceutical carrier.
Claims 2 and 3 add narrow approximate excipient formulations.
The supplied claims do not cover torsemide generally, methods of treatment, or manufacturing processes.
The patent issued April 18, 1989, and its expected 17-year term ended April 18, 2006.
The patent is not a current barrier to generic torsemide entry.
Torsemide is a small-molecule drug, so biosimilar analysis does not apply.
Any current competitive or patent risk must arise from later patents or FDA requirements outside the supplied claims.

FAQs

Can a generic torsemide product use Modification II?

Yes, the supplied claims do not claim Modification II. Claim 1 expressly requires Modification I and substantial freedom from Modification II. The product would remain subject to FDA quality and bioequivalence requirements.

Does a tablet infringe if it contains only a small amount of Modification I?

Not necessarily. The claim requires an effective amount of Modification I and the stated dissolution performance. A minor incidental amount may not satisfy the claim, depending on the evidence and claim construction.

Are claims 2 and 3 limited to exact excipient quantities?

No. The claims use "approximately," which creates tolerance around the stated parts by weight. The permissible range would depend on the specification, prosecution history, and ordinary meaning in the field.

Could an amorphous torsemide formulation infringe this patent?

An amorphous formulation would have a strong noninfringement position against the supplied claims because those claims require crystalline Modification I. Other patent claims, if any, would require separate analysis.

Does expiration of the patent eliminate all torsemide patent risk?

No. It eliminates the blocking effect of U.S. Patent 4,822,807. Later patents covering other polymorphs, formulations, combinations, manufacturing processes, or methods of use would require separate review.

References

United States Patent and Trademark Office. (1989). U.S. Patent No. 4,822,807.
35 U.S.C. § 154. Patent term provisions.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
21 U.S.C. § 355(j)(2)(A)(vii)(IV). Paragraph IV patent certification provisions.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3529529	Aug 17, 1985

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	49196	⤷ Start Trial
Australia	573454	⤷ Start Trial
Australia	6105586	⤷ Start Trial
Canada	1307277	⤷ Start Trial
Czechoslovakia	259891	⤷ Start Trial
Czechoslovakia	8605945	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,822,807

Summary for Patent: 4,822,807