United States Drug Patent 5,736,555: Claim Scope, Azilsartan Relationship, Expiration and Patent Landscape

U.S. Patent No. 5,736,555 is a Takeda benzimidazole patent covering a broad genus of angiotensin II receptor antagonists, their salts, pharmaceutical compositions and therapeutic use. The claims encompass substituted benzimidazole, thienoimidazole and imidazopyridine compounds bearing biphenyl-like acidic pharmacophores and oxadiazolone or thiadiazolone groups. The patent expressly excludes the compound now known as azilsartan, as well as its physiologically acceptable salts. The patent has expired and does not provide current blocking rights against azilsartan, azilsartan medoxomil or generic products.

What drug does U.S. Patent 5,736,555 relate to?

The patent is closely associated with the chemical class that led to azilsartan, the active moiety in Edarbi. The excluded compound in claims 1 and 23 is:

2-ethoxy-1-((2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)benzimidazole-7-carboxylic acid

That structure corresponds to azilsartan, also known as TAK-536, in its non-prodrug form. Azilsartan medoxomil is the orally administered prodrug of azilsartan and is marketed by Arbor Pharmaceuticals, later associated with Covis Pharma.

The exclusion is legally significant. A claim that expressly excludes azilsartan and its physiologically acceptable salts cannot be used to establish literal infringement by the excluded compound. The exclusion also limits the patent's relevance to azilsartan medoxomil unless a separate claim reaches the prodrug independently. The supplied claims do not clearly identify azilsartan medoxomil as a claimed compound.

What is the patent's basic legal and bibliographic profile?

Item	Detail
Patent	U.S. Patent No. 5,736,555
Technology	Substituted benzimidazole and related angiotensin II antagonists
Assignee	Takeda Chemical Industries, Ltd.
Issue date	April 7, 1998
Priority family	Japanese-origin pharmaceutical compound filings from the mid-1990s
Principal subject matter	Compounds, salts, compositions and methods for antagonizing angiotensin II
Patent term	Expired
Commercial relevance today	Historical and prior-art significance; no current exclusionary patent rights

The patent predates the modern Hatch-Waxman listing environment for Edarbi. Its age also places it outside the effective patent term for current U.S. commercial enforcement. Under the applicable 20-year patent-term rules, the patent expired no later than the mid-2010s. Any patent-term adjustment or terminal-disclaimer analysis would not restore enforceable rights today.

What compounds are covered by the independent chemical claims?

Claim 1 is a broad Markush claim. It covers a compound or salt having several variable structural components:

A heteroaromatic core, primarily benzimidazole or related fused heterocycles.
A substituent R1, generally an optionally substituted hydrocarbon residue that may be attached through oxygen, sulfur or nitrogen.
An R2 substituent containing a five-membered oxadiazolone or thiadiazolone-type ring.
An R3 acidic or acid-derived group, including carboxyl, ester, amide, tetrazole, phosphoric acid or sulfonic acid functionality.
Optional additional ring substitution, including halogen, nitro, cyano, amino, alkoxy, thioalkyl and carbonyl-containing groups.
Salts of the claimed compounds.

The claim therefore covers a chemical genus rather than a single named pharmaceutical. The genus includes neutral compounds, acidic compounds, ester prodrugs, amide derivatives and pharmaceutically acceptable salts, subject to the structural limitations and the express azilsartan exclusion.

What heterocyclic cores are covered?

Claims 6, 19 and 21 narrow the fused heteroaromatic portion of the molecule. The specified cores include:

Benzimidazole
Thienoimidazole
Imidazopyridine
Benzimidazole or imidazopyridine subsets
Additional ring systems represented in the patent drawings

The supplied text does not reproduce the structures associated with claims 7 and 21 in readable chemical form. Those claims must therefore be construed from the issued patent figures rather than from the OCR text alone. The visible claim language nevertheless confirms that the patent reaches multiple fused nitrogen-containing heterocycles.

What R1 substituents are covered?

Claims 2 and 12 through 15 progressively narrow R1. The covered groups include:

C1-C8 alkyl
C2-C8 alkenyl
Alkynyl
Cycloalkyl
Aryl
Aralkyl
Substituents attached through -NH-, -N(R9)-, -O- or -S(O)m-
Hydroxy, amino, halogen, alkoxy and alkylthio substitution

Claims 2 and 15 are materially narrower than claim 1. They focus on lower alkyl or alkenyl groups, often C1-C5, with limited heteroatom linkages and substitution. Claims 13 and 14 extend the scope to aryl, aralkyl, longer alkyl and alkenyl groups.

What R2 pharmacophores are protected?

Claims 16 through 18 identify three principal R2 species:

Claim	R2 group
16	2,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl
17	2,5-Dihydro-5-oxo-1,2,4-thiadiazol-3-yl
18	2,5-Dihydro-5-thioxo-1,2,4-oxadiazol-3-yl

These groups function as acidic pharmacophore replacements for tetrazole-type groups commonly used in angiotensin II receptor blockers. The oxadiazolone group is the most important commercial connection because azilsartan contains the 5-oxo-1,2,4-oxadiazole ring.

What formulation and prodrug structures are protected?

Claims 3 through 5 and 8 through 11 cover acid derivatives and esterified or amidated forms. Claim 3 is particularly broad and includes:

Carboxylic acids
Primary, secondary and tertiary amides
Lower alkyl esters
Hydroxy- or amino-substituted alkyl esters
Dioxolene-containing ester groups
O-CH(R4)-OCOR5 ester structures

Claim 10 expands the alkoxy and ester possibilities. Claim 11 narrows R3 to carboxy. Claims 5 and 8 cover optionally esterified or amidated carboxyl groups.

These provisions have potential prodrug relevance because the patent claims both active acid forms and certain ester derivatives. They do not, however, automatically cover every later prodrug. A later compound must satisfy the precise structural limitations of the claim, and the azilsartan exclusion remains relevant.

Azilsartan medoxomil contains a medoxomil-type ester prodrug group. Whether a medoxomil derivative falls within an old genus depends on the exact claim language, prosecution history, disclaimer, and written-description support. Because the patent has expired, the issue is principally historical and prior-art related rather than a current infringement risk.

What do the pharmaceutical composition and method claims cover?

Claim 24 covers a pharmaceutical composition containing:

A therapeutically effective amount of a claim 1 compound or salt; and
A pharmaceutically acceptable carrier, excipient or diluent.

Claim 25 covers a method of antagonizing angiotensin II in a mammal by administering a therapeutically effective amount of a claim 1 compound or salt.

These claims are subordinate to the chemical definition in claim 1. They do not independently cover all angiotensin II receptor blockers. A composition or method must use a compound that falls within the claim 1 genus and is not excluded by the claim.

The therapeutic language is broad, but the claims are not directed to a particular disease, dose, formulation, patient population or route of administration. They are therefore weaker than later formulation or method-of-use patents that specify a commercial product, dosing regimen or indication.

How does the azilsartan exclusion affect claim scope?

The exclusion appears in both independent compound claims:

Claim 1 excludes azilsartan and its physiologically acceptable salts.
Claim 23 independently claims a narrower compound genus and repeats the exclusion.

This structure indicates that the patent's inventors or applicants carved out a specific compound from the broader genus. The exclusion may have been used to preserve novelty, avoid double patenting, address an earlier disclosure, or distinguish a separately protected lead compound.

The exclusion has four practical effects:

Azilsartan itself is outside the literal scope of claims 1 and 23.
Salts of azilsartan are also excluded.
The patent cannot be treated as the principal composition-of-matter patent for azilsartan.
Related analogues and prodrugs require separate claim-by-claim analysis.

The exclusion does not necessarily remove every compound that is structurally close to azilsartan. A compound with a different R1, R3, heterocycle, ester group or substitution pattern may remain within the genus if it satisfies all other limitations.

When did U.S. Patent 5,736,555 lose exclusivity?

U.S. Patent 5,736,555 lost enforceable exclusivity in the mid-2010s. The patent is expired and cannot currently block:

Generic azilsartan medoxomil
Generic azilsartan
Follow-on salts
Alternative formulations
Manufacturing processes
Commercial products using compounds outside the excluded structure

The patent may still matter as prior art in validity, obviousness and freedom-to-operate analyses. Expiration removes infringement exposure but does not remove the patent from the technical and legal record.

What is the Orange Book status of U.S. Patent 5,736,555?

U.S. Patent 5,736,555 is not the controlling Orange Book patent for Edarbi. The FDA Orange Book listings for azilsartan medoxomil have historically relied on later patents directed to the commercial active ingredient, prodrug, crystalline forms, pharmaceutical compositions or related product attributes. The 1998 patent is expired and is not a current market-exclusivity barrier.

The Orange Book distinction is important:

Issue	U.S. 5,736,555
Listed as the current Edarbi blocking patent	No
Covers azilsartan expressly	No, it is excluded
Covers all azilsartan medoxomil products	No automatic coverage
Current patent term	Expired
Paragraph IV significance today	None as an active listed patent
Historical prior-art significance	Yes

FDA regulatory exclusivity is separate from patent rights. Any new-drug exclusivity associated with Edarbi would have expired independently of this patent. The patent does not create current FDA exclusivity.

Which patents are more relevant to azilsartan medoxomil?

The commercially relevant patent estate for azilsartan medoxomil developed after the filing of U.S. 5,736,555. It generally includes four groups:

Azilsartan compound and prodrug patents

Later Takeda patent families addressed azilsartan, azilsartan medoxomil and related benzimidazole derivatives. These families are more relevant than U.S. 5,736,555 because they focus on the specific commercial compound or its prodrug.

Solid-state and crystalline-form patents

Patents directed to crystalline forms, polymorphs, solvates and solid-state characteristics can delay generic entry even after a basic compound patent expires. Their enforceability depends on claim breadth, demonstrated form specificity and Orange Book listing status.

Pharmaceutical composition patents

Composition patents may cover dosage forms, excipient combinations, stability profiles, dissolution characteristics or specific strengths. These patents create a narrower but potentially commercially meaningful barrier.

Manufacturing and process patents

Process patents may cover preparation of azilsartan, conversion to azilsartan medoxomil, purification, crystallization or control of impurities. They typically do not prevent all generic entry because a competitor may use a non-infringing process, but they can increase development cost and create supply-chain risk.

Are there Paragraph IV challenges or settlements involving this patent?

No active Paragraph IV challenge can target U.S. 5,736,555 because the patent has expired. Any historical ANDA litigation concerning Edarbi would have focused on later unexpired patents listed for azilsartan medoxomil, not on the expired 1998 patent.

A patent-by-patent assessment of settlement agreements must distinguish:

Settlements involving the original compound patent
Settlements involving prodrug patents
Settlements involving crystalline-form patents
Settlements involving formulation or process patents

A settlement related to a later Edarbi patent would not revive U.S. 5,736,555 or extend its term.

How strong is the patent estate represented by U.S. 5,736,555?

As a current commercial barrier, its strength is zero because the patent is expired. As a historical discovery patent, its technical scope was substantial.

Strength factor	Assessment
Chemical breadth	Broad Markush genus
Number of covered heterocycles	Multiple
Salt coverage	Express
Ester and amide coverage	Express
Composition claims	Present
Method claims	Present
Explicit azilsartan coverage	No; azilsartan is excluded
Current enforceability	None
Prior-art value	Material
Relevance to current generic launch	Indirect

The principal limitation is the exclusion of the commercial azilsartan molecule. The patent is better characterized as a broad platform and analogue patent than as the foundational blocking patent for Edarbi.

What generic launch risks exist for azilsartan medoxomil?

Current generic launch risk depends on later, unexpired patent families and regulatory certifications. U.S. 5,736,555 does not create a present launch risk.

The relevant risk categories are:

Orange Book-listed drug-substance or product patents.
Paragraph IV litigation against later patents.
Crystalline-form and polymorph claims.
Formulation patents covering dosage strengths or stability.
Process patents affecting commercial-scale manufacture.
Regulatory exclusivity, if any remains.
State of FDA approval for an ANDA or 505(b)(2) product.

A generic developer that designs around later product and formulation patents would not face meaningful infringement exposure from the expired 5,736,555 patent.

What is the geographic coverage of this patent family?

U.S. Patent 5,736,555 provides protection only in the United States. Related Japanese, European and other national filings may have existed, but each jurisdiction requires separate analysis of:

Grant status
Patent term
Claim amendments
National-phase prosecution
Supplementary protection certificates
Local litigation
Terminal disclaimers
Generic-entry settlements

Expiration of the U.S. patent does not establish the status of corresponding foreign rights. For current U.S. commercial planning, however, the patent has no remaining term.

Key Takeaways

U.S. Patent 5,736,555 is a broad Takeda patent for substituted benzimidazole and related angiotensin II antagonists.
Claims 1 and 23 cover broad compound genera, salts, ester and amide derivatives, compositions and therapeutic methods.
The patent specifically excludes azilsartan and its physiologically acceptable salts.
The excluded compound is the active moiety associated with Edarbi.
The patent expired in the mid-2010s and is not a current Orange Book barrier.
It has no current Paragraph IV or generic-launch blocking effect.
Later patents covering azilsartan medoxomil, solid forms, formulations and manufacturing processes are more relevant to current freedom-to-operate analysis.
Claims 7 and 21 cannot be fully assessed from the supplied OCR because the referenced structural drawings are missing.
The patent retains historical prior-art value but no present exclusionary strength.

FAQs

Does U.S. Patent 5,736,555 cover Edarbi?

No. The patent expressly excludes azilsartan, the active moiety in Edarbi. Its claims may cover related analogues, but they do not provide current composition-of-matter protection for Edarbi.

Is azilsartan medoxomil protected by this expired patent?

Not as a current enforceable right. Any historical relevance would depend on whether the prodrug satisfied a specific claim before expiration. Later azilsartan medoxomil patents are more important to product protection.

Can a generic manufacturer ignore U.S. Patent 5,736,555?

For current U.S. launch purposes, the patent is expired. A generic manufacturer must instead evaluate unexpired Orange Book patents, regulatory exclusivity and non-Orange Book process or formulation patents.

Does the patent cover angiotensin receptor blockers generally?

No. The patent covers structurally defined benzimidazole, thienoimidazole and imidazopyridine compounds with specified substituents. It does not cover all angiotensin receptor blockers.

Does patent expiration eliminate the patent's prior-art value?

No. Expiration eliminates enforcement rights but does not eliminate the patent as prior art. The disclosure may remain relevant to novelty, obviousness, written-description and enablement analyses for later patent applications.

References

U.S. Patent No. 5,736,555. (1998). Benzimidazole derivatives, processes for their preparation, and pharmaceutical compositions containing them. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (n.d.). Edarbi (azilsartan medoxomil) prescribing information. FDA.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information. USPTO.
Takeda Pharmaceuticals U.S.A., Inc. (n.d.). Edarbi product information. Manufacturer labeling materials.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	3-157194	Jun 27, 1991
Japan	3-188882	Jul 29, 1991
Japan	3-192054	Jul 31, 1991
Japan	3-288217	Aug 12, 1991
Japan	3-239764	Sep 19, 1991

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	240323	⤷ Start Trial
Australia	1859892	⤷ Start Trial
Australia	646343	⤷ Start Trial
Canada	2072541	⤷ Start Trial
China	1040755	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,736,555

Summary for Patent: 5,736,555