United States Patent 5,656,650: Eprosartan Combination Patent Scope, Expiration, and Patent Landscape

US Patent 5,656,650 protects pharmaceutical combinations and hypertension-treatment regimens pairing an angiotensin II receptor antagonist, principally eprosartan or eprosartan mesylate, with another antihypertensive agent. The patent covers fixed-dose compositions and separate, stepwise administration. Its broadest practical commercial relevance is the combination of eprosartan mesylate with hydrochlorothiazide or furosemide.

The patent issued on August 12, 1997, and its ordinary United States patent term expired on August 12, 2014, absent an applicable patent-term adjustment or extension. The claims therefore do not presently create an enforceable U.S. patent barrier to generic eprosartan combinations. The patent remains important as a historical reference for product development, claim construction, and freedom-to-operate analysis.

What drug does United States Patent 5,656,650 protect?

The patent protects combinations containing an angiotensin II receptor antagonist with a second antihypertensive therapy. Claim 2 identifies the principal compound as:

(E)-3-[2-n-butyl-1-{(4-carboxyphenyl)methyl}-1H-imidazol-5-yl]-2-(2-thienyl)methyl-2-propenoic acid

This compound is eprosartan. Claim 3 narrows the compound to its methanesulfonate salt, eprosartan mesylate, the active ingredient marketed in Teveten.

The patent is directed to combination therapy rather than the basic composition-of-matter protection for eprosartan itself. The distinction matters because the expiration and enforcement history of the eprosartan compound patent and the combination patent are separate.

Item	Patent 5,656,650
Patent number	US 5,656,650
Technology	Combination antihypertensive pharmaceutical compositions and methods
Principal active ingredient	Eprosartan and eprosartan mesylate
Drug class	Angiotensin II receptor blocker, or ARB
Key combination partners	Diuretics, calcium channel blockers, beta blockers, renin inhibitors, ACE inhibitors
Issue date	August 12, 1997
Patent-term basis	Pre-URAA issuance-era term
Ordinary expiration	August 12, 2014
Current enforceability	Expired
Principal commercial product	Teveten; Teveten HCT

[1]

What are the independent claims in US 5,656,650?

The patent contains ten independent claims. Claims 1 and 7 through 10 are composition claims. Claims 11 and 17 through 20 are method-of-treatment claims.

Claim	Claim category	Required combination
1	Pharmaceutical composition	Diuretic plus formula (I) ARB
7	Pharmaceutical composition	Calcium channel blocker plus formula (I) ARB
8	Pharmaceutical composition	Beta-adrenoceptor blocker plus formula (I) ARB
9	Pharmaceutical composition	Renin inhibitor plus formula (I) ARB
10	Pharmaceutical composition	ACE inhibitor plus formula (I) ARB
11	Method of treatment	Stepwise or physical combination of diuretic and formula (I) ARB
17	Method of treatment	Stepwise or physical combination of calcium channel blocker and formula (I) ARB
18	Method of treatment	Stepwise or physical combination of beta blocker and formula (I) ARB
19	Method of treatment	Stepwise or physical combination of renin inhibitor and formula (I) ARB
20	Method of treatment	Stepwise or physical combination of ACE inhibitor and formula (I) ARB

The patent uses a broad Markush definition for formula (I). Claims 1 and 7 through 10 are not limited to eprosartan unless the accused product falls within the structural definition of formula (I). Claims 2 through 6 and 12 through 16 provide narrower eprosartan-specific species.

How broad is the formula (I) Markush claim?

Claim 1 defines a large genus of substituted imidazole-derived angiotensin II receptor antagonists. The claim covers compounds with variable substituents at multiple positions:

R1 may be adamantyl, phenyl, biphenyl, or naphthyl, with extensive permissible substitution.
R2 may be an alkyl, alkenyl, alkynyl, cycloalkyl, or substituted phenyl-containing group.
X may be a single bond, sulfur, nitrogen, or oxygen.
R3 may be hydrogen, halogen, cyano, nitro, carboxylate, amide, or other substituents.
R4 and R5 may be hydrogen, alkyl, or substituted heterocyclic groups.
R6 may contain a carboxylate or carboxamide functionality.
The claim expressly includes pharmaceutically acceptable salts.

The legal breadth is substantial on its face, but the claim has two important limitations.

First, the composition must contain both the formula (I) ARB and a diuretic. A product containing only eprosartan does not fall within claim 1.

Second, the formula (I) structure must be construed as a legally coherent chemical genus. The scope may be limited by the specification, written-description support, enablement, prosecution history, and any narrowing amendments made during examination. A broad Markush claim does not automatically provide enforceable protection for every theoretical member of the genus.

What do claims 2 through 6 protect?

Claims 2 through 6 are species and combination claims focused on eprosartan-related compounds.

Claims 2 through 4: eprosartan and diuretic combinations

Claim 2 covers eprosartan with a pharmaceutically acceptable salt. Claim 3 specifies eprosartan methanesulfonate, or eprosartan mesylate. Claim 4 limits the diuretic to hydrochlorothiazide or furosemide.

The narrowest commercial formulation concept is therefore:

Eprosartan mesylate plus hydrochlorothiazide; or
Eprosartan mesylate plus furosemide.

Claim 4 is a composition claim. It requires the product to contain the specified ARB and one of the specified diuretics in a pharmaceutical composition with a pharmaceutically acceptable carrier.

Claims 5 and 6: naphthyl analogue combinations

Claim 5 covers the corresponding carboxynaphthyl analogue. Claim 6 combines that analogue with hydrochlorothiazide or furosemide.

The naphthyl analogue claims broaden the patent's technical coverage beyond marketed eprosartan. They have limited direct commercial significance unless a later product uses that specific antagonist or a structurally equivalent compound within the formula (I) genus.

What do claims 11 through 20 protect?

The method claims cover treatment of hypertension by administering the ARB and a second antihypertensive agent either:

Stepwise, meaning separate administration at different times; or
In physical combination, meaning administration in a combined dosage form or composition.

This language materially expands the claim scope beyond fixed-dose tablets. A method can potentially fall within the literal framework even where the active ingredients are supplied in separate products, provided the treatment regimen includes the required ARB and combination partner.

The method claims are divided by therapy class:

Method claims	Combination partner
11-16	Diuretic
17	Calcium channel blocker
18	Beta-adrenoceptor blocker
19	Renin inhibitor
20	ACE inhibitor

Claims 12 through 16 narrow the diuretic regimen to eprosartan or eprosartan mesylate, with hydrochlorothiazide or furosemide in the most specific claims.

What formulations are protected by US 5,656,650?

The patent protects compositions containing the required active ingredients and a pharmaceutically acceptable carrier. The claims do not require a particular tablet, capsule, suspension, coating, release profile, excipient, particle size, or manufacturing process.

The covered formulation concepts include:

Fixed-dose oral compositions containing eprosartan mesylate and hydrochlorothiazide.
Fixed-dose compositions containing eprosartan mesylate and furosemide.
Formulations containing another formula (I) ARB and a calcium channel blocker.
Formulations containing another formula (I) ARB and a beta blocker.
Formulations containing another formula (I) ARB and an ACE inhibitor.
Formulations containing another formula (I) ARB and a renin inhibitor.

The patent does not, based on the claims supplied, provide a separate formulation claim directed to:

A specific excipient system.
A controlled-release matrix.
A particular tablet coating.
A specified dissolution profile.
A manufacturing process.
A particular dose ratio.
A defined particle-size distribution.

Those limitations could be relevant in later patents, but they are not express limitations of the claims quoted from US 5,656,650.

What is the patent landscape for eprosartan?

The eprosartan patent landscape has three principal layers.

Eprosartan composition-of-matter patents

The foundational patent estate covered the eprosartan molecule and related angiotensin II receptor antagonists. US Patent 5,196,444 is associated with eprosartan composition-of-matter protection and predates US 5,656,650 in the product lifecycle.

Composition-of-matter claims generally have greater commercial importance than combination claims because they can block sale of the active ingredient itself. Once the compound patent expires, a combination patent can continue to restrict only the claimed combination or treatment regimen.

Combination patents

US 5,656,650 is the principal combination patent addressed here. It covers the use of eprosartan and related ARBs with several established antihypertensive classes.

Its commercial value was concentrated in the period before expiration of the underlying eprosartan exclusivity. After the eprosartan compound protection expired, the combination claims could have remained relevant to a fixed-dose eprosartan/hydrochlorothiazide product, but only until August 2014.

Product and formulation patents

Teveten and Teveten HCT may have been associated with additional regulatory and patent records, including formulation, salt, dosage, or product-specific rights. Those rights must be distinguished from US 5,656,650. The quoted claims do not establish protection for every eprosartan formulation or every eprosartan/hydrochlorothiazide product.

When did US 5,656,650 lose exclusivity?

US 5,656,650 lost patent exclusivity on August 12, 2014, based on its issue-date term. The patent is therefore expired and cannot support a new infringement action for conduct occurring after expiration.

The relevant timeline is:

Date	Event
August 12, 1997	US 5,656,650 issued
December 1997	FDA approved Teveten, eprosartan mesylate
Subsequent product lifecycle	Eprosartan marketed as an ARB for hypertension
August 12, 2014	Ordinary patent term expired
Current status	No enforceable patent exclusion under this patent

FDA regulatory exclusivity and patent exclusivity are separate. FDA approval of Teveten did not extend the patent term of US 5,656,650. Conversely, expiration of the patent did not itself withdraw FDA approval. FDA product status must be assessed through the Orange Book and current FDA labeling records. [2][3]

What is the Orange Book status of eprosartan and Teveten HCT?

The Orange Book records patents and regulatory exclusivity submitted by NDA holders for approved drug products. It does not establish the validity or enforceability of a patent. A listed patent can be expired, challenged, delisted, or legally irrelevant to a particular proposed product.

For eprosartan products, the relevant regulatory questions are:

Whether Teveten remains listed as an active reference product.
Whether Teveten HCT is listed for eprosartan mesylate and hydrochlorothiazide.
Whether any patents are currently listed against the relevant NDA.
Whether a generic applicant must file a Paragraph IV certification.
Whether a listed patent has already expired or been removed.

US 5,656,650 cannot presently create a live Orange Book patent barrier because its term expired in 2014. A current generic applicant would need to review any other unexpired listed patent, regulatory exclusivity, or product-specific restriction associated with the relevant NDA. [2]

Which companies challenged eprosartan patents?

No active Paragraph IV challenge is attributable to US 5,656,650 because the patent has expired. A Paragraph IV certification against an expired patent would not provide a current basis for blocking approval or launch.

Historical generic activity involving eprosartan would have focused on:

The eprosartan composition-of-matter patents.
Any salt or polymorph patents.
Combination-product patents for eprosartan and hydrochlorothiazide.
Orange Book-listed patents tied to Teveten or Teveten HCT.

The supplied patent information does not identify a particular ANDA filer, litigation docket, settlement agreement, or launch date. No such matter should be attributed to US 5,656,650 without a verified court or FDA record.

What patent litigation affects US 5,656,650?

The patent's current litigation risk is zero as an enforceable patent right because it has expired. Historical litigation risk would have depended on four issues:

Whether the accused product contained an ARB within formula (I).
Whether the product contained a listed combination partner.
Whether the product was a composition or treatment regimen covered by the asserted claim.
Whether the claim survived validity challenges involving written description, enablement, obviousness, anticipation, or indefiniteness.

The broad Markush claims could have created litigation exposure for combination products containing structurally related ARBs. The species claims directed to eprosartan mesylate and hydrochlorothiazide would have presented a narrower but more commercially focused theory.

No settlement agreement can be inferred from the patent text or claims supplied.

How strong is the patent estate for eprosartan combinations?

The estate was commercially meaningful during the protected period but is now weak as a blocking position because the relevant patent has expired.

Factor	Assessment
Structural breadth	High for formula (I), subject to written-description and enablement limits
Commercial specificity	High for eprosartan mesylate plus hydrochlorothiazide
Formulation coverage	Moderate; carrier required, but no detailed dosage-form limitation
Method coverage	Broad because stepwise administration is included
Compound-patent dependence	High
Manufacturing protection	Low based on the supplied claims
Current enforceability	None
Generic-launch relevance	Historical only for this patent

The strongest historical claim was likely claim 4, because it identified eprosartan mesylate and hydrochlorothiazide, a commercially plausible fixed-dose combination. Claims 7 through 10 were broad in therapy class but less product-specific. Claims 17 through 20 created potential method-of-use coverage but were vulnerable to practical enforcement limitations, including proof of the administered regimen and induced-infringement issues.

What generic entry risks exist for eprosartan combinations?

A generic applicant evaluating eprosartan or eprosartan/hydrochlorothiazide would not face a live exclusion from US 5,656,650. The remaining risk analysis would focus on other rights and regulatory conditions.

Generic eprosartan

The principal questions are whether any compound, salt, polymorph, formulation, or process patent remains unexpired and whether the reference listed drug remains eligible for an ANDA pathway.

Generic eprosartan/hydrochlorothiazide

The applicant would need to evaluate:

The exact active ingredients and salt form.
Dose strengths and ratios.
Bioequivalence requirements.
Any Orange Book-listed product patents.
Whether the proposed label includes all patented indications.
Whether a skinny-label strategy is legally and regulatorily available.

US 5,656,650 itself does not create a post-2014 launch risk.

How does this patent compare with a typical formulation patent?

US 5,656,650 is primarily a combination and method-of-use patent. It differs from a narrow formulation patent in several ways.

Characteristic	US 5,656,650	Narrow formulation patent
Core subject	ARB plus second antihypertensive	Specific dosage form or excipient system
Structural scope	Broad Markush genus and eprosartan species	Usually narrow
Dosage form	Not expressly limited	Often expressly limited
Administration	Physical combination or stepwise	Usually product-specific
Manufacturing process	Not claimed in supplied claims	May be claimed
Design-around potential	Substitute partner, salt, or regimen	Change excipients, process, or release profile
Current status	Expired	Depends on individual patent

What are the geographic coverage and international implications?

US 5,656,650 has territorial effect only in the United States. Corresponding foreign patent rights would require separate analysis by jurisdiction. The existence of a U.S. patent does not establish protection in the European Union, United Kingdom, Canada, Japan, Australia, or other markets.

International risk would depend on:

National-phase counterparts.
Local patent-term calculations.
Supplementary protection certificates.
National claim amendments.
Local Orange Book-equivalent systems.
Market authorization and data-exclusivity rules.

A U.S. generic launch could therefore be legally permissible even if a related foreign patent remained active.

Key Takeaways

US 5,656,650 covers compositions and hypertension-treatment methods combining formula (I) ARBs with diuretics, calcium channel blockers, beta blockers, renin inhibitors, or ACE inhibitors.
Eprosartan and eprosartan mesylate are the principal claimed species.
Claims 4 and 14 specifically target eprosartan mesylate with hydrochlorothiazide or furosemide.
The claims cover both fixed-dose combinations and separate, stepwise administration.
The patent does not expressly claim a specific excipient system, release profile, tablet design, or manufacturing process.
The ordinary patent term expired on August 12, 2014.
The patent cannot presently block generic eprosartan or eprosartan/hydrochlorothiazide entry.
Current commercial risk must be assessed against other compound, salt, formulation, process, and Orange Book-listed patents.
No current Paragraph IV risk or enforceable litigation position arises from this patent alone.

FAQs About US Patent 5,656,650 and Eprosartan

Does US 5,656,650 cover Teveten?

It covers compositions and treatment methods using eprosartan or eprosartan mesylate with specified antihypertensive agents. It does not cover Teveten monotherapy because the claims require a second antihypertensive class.

Does US 5,656,650 cover Teveten HCT?

It covers an eprosartan mesylate and hydrochlorothiazide combination if the product satisfies the claim limitations. The patent expired in 2014.

Can a generic use eprosartan mesylate with furosemide?

US 5,656,650 no longer prevents that combination because the patent expired. Other applicable patents and regulatory requirements must be evaluated separately.

Is eprosartan a biologic requiring biosimilar analysis?

No. Eprosartan is a small-molecule ARB. Generic-drug rules, including the ANDA pathway, are more relevant than the biosimilar pathway.

Does the patent cover combination therapy with an ACE inhibitor?

Yes. Claims 10 and 20 cover compositions and hypertension-treatment methods combining a formula (I) ARB with an angiotensin-converting enzyme inhibitor. Those claims are expired.

References

U.S. Patent No. 5,656,650. (1997). Pharmaceutical compositions containing angiotensin II receptor antagonists. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (n.d.). Teveten (eprosartan mesylate) prescribing information. FDA.
U.S. Patent No. 5,196,444. (1993). Angiotensin II receptor antagonists. United States Patent and Trademark Office.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0565634	⤷ Start Trial	300115	Netherlands	⤷ Start Trial
European Patent Office	0565634	⤷ Start Trial	91234	Luxembourg	⤷ Start Trial
European Patent Office	0565634	⤷ Start Trial	06C0030	France	⤷ Start Trial
European Patent Office	0565634	⤷ Start Trial	C300115	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,656,650

Summary for Patent: 5,656,650