US Patent 6,455,574: Claim Scope, Expiration, FDA Status, and Patent Landscape for the Amlodipine-Atorvastatin Combination

US Patent 6,455,574 protected prescribed treatment of hypertension and hyperlipidemia using amlodipine and atorvastatin in a single pharmaceutical composition. The patent covered the therapeutic method used by Pfizer’s Caduet product, including amlodipine besylate and atorvastatin calcium. Its nominal United States patent term ended in 2018, subject to any applicable patent-term adjustment or extension. The patent no longer creates a current United States patent barrier to generic amlodipine-atorvastatin products.

The claims are method claims rather than composition claims. They require the administration of both active ingredients together in one pharmaceutical composition. They do not require a particular dose, tablet strength, release profile, excipient, manufacturing process, or clinical outcome.

What does US Patent 6,455,574 protect?

The patent protects a fixed-dose combination treatment method for patients with hypertension and hyperlipidemia.

Feature	Claim requirement
First active ingredient	Amlodipine or a pharmaceutically acceptable acid addition salt
Preferred first ingredient	Amlodipine besylate
Second active ingredient	Atorvastatin or a pharmaceutically acceptable salt
Preferred second ingredient	Atorvastatin hemicalcium, commonly called atorvastatin calcium
Disease condition	Combined hypertension and hyperlipidemia, or the relevant risk or diagnosis in claims 5 through 12
Administration	Both ingredients administered together
Dosage form requirement	A single pharmaceutical composition
Carrier	Pharmaceutically acceptable carrier or diluent
Claim type	Therapeutic method claims
Express dose limitation	None
Express ratio limitation	None
Express tablet limitation	None
Express mechanism or outcome limitation	None

The core commercial embodiment is a tablet containing amlodipine besylate and atorvastatin calcium, corresponding to Caduet. The claims are broader than a specific Caduet strength because they do not recite a particular milligram combination.

How are the 12 claims structured?

The claims contain three overlapping claim groups.

Claims 1 through 4: broad combination-treatment claims

Claim 1 is the principal broad claim. It requires:

A mammal suffering from combined hypertension and hyperlipidemia.
Administration of amlodipine or an acceptable acid addition salt.
Administration of atorvastatin or an acceptable salt.
Administration of both ingredients together in a single pharmaceutical composition.

Claims 2 through 4 narrow the chemical forms:

Claim 2 specifies amlodipine besylate.
Claim 3 specifies both amlodipine besylate and atorvastatin hemicalcium.
Claim 4 specifies atorvastatin hemicalcium but leaves the amlodipine form broader than claim 3.

Claims 5 through 8: diagnosed or prescribed patients

Claims 5 through 8 add clinical and prescribing facts. The patient must have been diagnosed with hypertension and hyperlipidemia, or the risk of those conditions, and combined administration must have been prescribed.

This group may be narrower in litigation because it includes requirements concerning diagnosis, therapeutic benefit, and prescription. Claims 6 through 8 repeat the salt limitations found in claims 2 through 4.

Claims 9 through 12: medical examination and diagnosis

Claims 9 through 12 require that the mammal:

Was examined for both hypertension and hyperlipidemia by a medical practitioner.
Was diagnosed as needing therapy for both conditions.
Received joint administration of the two active ingredients in one composition.

This is the most fact-specific group. It places greater emphasis on the physician’s examination and diagnosis before administration.

What are the key claim limitations in US 6,455,574?

The single-composition limitation is the principal technical limitation.

A regimen using separate amlodipine and atorvastatin tablets would not literally satisfy the requirement that both active ingredients be administered together in a single pharmaceutical composition. A patient taking one amlodipine tablet and one atorvastatin tablet at the same time would therefore present a materially different infringement analysis from a patient taking a fixed-dose combination tablet.

The claims also require the two ingredients to be administered together. The patent does not expressly define whether “together” requires simultaneous ingestion, administration within a specified time interval, or simply joint inclusion in one product. For the commercial fixed-dose product, that issue is largely immaterial because both ingredients are contained in the same dosage unit.

The following limitations are absent:

No specified dose of amlodipine.
No specified dose of atorvastatin.
No requirement for immediate release or extended release.
No required pharmaceutical excipient.
No required particle size or crystal form.
No required manufacturing route.
No requirement that atorvastatin be a particular polymorph.
No requirement for a particular hypertension threshold or lipid threshold.
No requirement to demonstrate a synergistic effect.

Does the patent cover Caduet?

Yes. Caduet combines amlodipine besylate and atorvastatin calcium in a single oral tablet. That product falls within the central technical formulation described by claims 1 through 4 and, when prescribed following examination and diagnosis, can also fall within claims 5 through 12. The FDA-approved Caduet label identifies the product as a combination of amlodipine besylate and atorvastatin calcium for patients requiring treatment of hypertension and dyslipidemia or additional blood-pressure and lipid lowering [2].

The patent does not depend on the Caduet trademark. It covers the active-ingredient combination and method of use, regardless of brand name.

When did US Patent 6,455,574 expire?

The patent issued on September 24, 2002. Public patent records identify an earliest relevant United States filing date in 1998, with an earlier provisional priority claim. The nominal 20-year patent term therefore ran to approximately June 5, 2018, subject to patent-term adjustment or any applicable extension recorded by the USPTO [1].

Event	Date
Earliest provisional priority	June 6, 1997
United States nonprovisional filing	June 5, 1998
Patent issued	September 24, 2002
Nominal 20-year expiration	Approximately June 5, 2018
Current status	Expired; no current exclusionary term

A provisional application does not ordinarily begin the 20-year patent term. The operative term calculation is generally tied to the qualifying nonprovisional or international application filing date, not the provisional priority date.

What was the Orange Book status of US 6,455,574?

US 6,455,574 was listed in connection with Caduet, an FDA-approved fixed-dose combination product marketed by Pfizer. The patent listing supported regulatory exclusivity against ANDA applicants that sought approval for an equivalent amlodipine-atorvastatin product during the patent term [3].

The listing did not convert the patent into a composition patent. The patent remained a method patent, and the regulatory consequences depended on the product’s proposed labeling, certification, and the scope of the listed method of use.

After expiration, the patent ceased to block FDA approval or commercial launch on patent-term grounds. The Orange Book’s current status should be distinguished from historical listing status. An expired patent may remain visible in historical regulatory records even though it no longer provides enforceable exclusivity.

Were Paragraph IV challenges relevant to this patent?

Yes. Generic applicants seeking approval for fixed-dose amlodipine-atorvastatin products could challenge the patent through an ANDA Paragraph IV certification. The principal arguments available to an ANDA applicant would have included:

Noninfringement based on separate administration or labeling that does not direct the claimed method.
Invalidity based on obviousness over the known use of amlodipine for hypertension and atorvastatin for hyperlipidemia.
Invalidity based on written description or enablement, although the claims are chemically and therapeutically straightforward.
Lack of infringement of the diagnosis-specific claims where the generic label does not require the claimed examination or diagnosis.
A regulatory carve-out for a method of use, where legally available.

A fixed-dose generic tablet containing amlodipine and atorvastatin would have faced the greatest exposure under claim 1 because the product itself satisfies the single-composition feature and the generic label would ordinarily describe treatment of hypertension and dyslipidemia.

The diagnosis and prescription wording in claims 5 through 12 could create narrower infringement questions. A manufacturer generally does not administer the product to the patient. Liability would therefore depend on the conduct of prescribers, dispensers, patients, and the content of the product labeling under the applicable direct and induced-infringement standards.

What patent landscape surrounded amlodipine, atorvastatin, and Caduet?

The combination patent was only one component of the historical exclusivity structure.

Patent or protection category	Subject matter	Commercial relevance
Amlodipine compound patents	Amlodipine and related medicinal chemistry	Expired before the Caduet combination patent
Atorvastatin compound patents	Atorvastatin and cholesterol-lowering use	Expired before or around the early generic period
Atorvastatin calcium patents	Salt, crystal, or formulation-related protection	Could affect atorvastatin products separately from the combination method
US 6,455,574	Amlodipine plus atorvastatin in one composition	Primary Caduet combination-method patent
FDA exclusivity	New-drug and regulatory exclusivity associated with Caduet	Time-limited and distinct from patent rights
Manufacturing patents	Processes, polymorphs, intermediates, or tablet production	Potentially relevant to specific suppliers, not necessarily to the finished-product method

The underlying active ingredients were already established drugs. The commercial value of US 6,455,574 came from combining them into one product and linking the combination to patients requiring treatment of both cardiovascular risk factors.

A separate patent covering atorvastatin calcium crystal form, manufacturing, or formulation would not automatically extend the term of US 6,455,574. Each patent must be analyzed claim by claim and jurisdiction by jurisdiction.

How strong was the patent estate for Caduet?

The patent estate was commercially effective during its term but technically concentrated.

Strengths

The claims covered the central fixed-dose product configuration.
No specific dose or strength was required.
The claims covered both generic active moieties and the commercially preferred salts.
The single-composition limitation aligned with the product’s principal market differentiation.
Claims 5 through 12 provided alternative fact patterns based on prescription, diagnosis, and medical examination.

Weaknesses

The patent did not claim the composition itself as a standalone product claim.
Separate-tablet regimens were outside the literal single-composition limitation.
The combination of two well-known cardiovascular medicines could present obviousness issues.
Claims 5 through 12 depend on clinical facts that may not be fully controlled by the manufacturer.
The patent did not claim a new chemical entity, novel dosage range, novel release technology, or manufacturing process.
Once the patent expired, the method claims provided no continuing United States exclusivity.

Overall, the patent was stronger as a product-linked method patent than as a broad platform patent. Its practical value depended on fixed-dose combination products and labeling that encouraged the claimed treatment.

What generic launch risks existed after expiration?

After the patent’s expiration, the principal barriers shifted from patent enforcement to FDA approval, formulation development, manufacturing scale, bioequivalence, and commercial pricing.

Generic product risks

A generic manufacturer still had to address:

Bioequivalence to the relevant reference product.
Salt and dosage-form selection.
Stability of the two-active-ingredient tablet.
Content uniformity and dissolution.
Compatibility between amlodipine and atorvastatin.
Labeling and substitution requirements.
Supply of qualified active pharmaceutical ingredients.
Market share erosion from multiple generic entrants.

The patent did not prevent a generic company from developing separate amlodipine and atorvastatin products. Its historical importance was directed to the single-tablet combination.

Biosimilar risk

There is no biosimilar pathway relevant to this patent. Amlodipine and atorvastatin are small-molecule drugs regulated through the ANDA pathway, not biologic products regulated under the Public Health Service Act. The competitive threat is generic substitution, not biosimilar interchangeability.

How does Caduet compare with separate amlodipine and atorvastatin products?

Issue	Caduet-type fixed-dose tablet	Separate products
Dosage form	One pharmaceutical composition	Two compositions
Historical claim exposure	High under US 6,455,574	Lower on the single-composition limitation
Dose flexibility	More limited by fixed strengths	Greater independent titration
Adherence	One prescription product	Two products
Patent relevance	Central target of the combination patent	Primarily ingredient, formulation, and use patents
FDA pathway	ANDA for equivalent combination product	Separate ANDAs
Current patent barrier from 6,455,574	None after expiration	None after expiration

What litigation and settlement issues affected the patent?

A complete litigation history requires review of the USPTO patent file, PACER docket records, FDA Orange Book history, and any publicly filed settlement agreements. The supplied claim text establishes the patent’s scope but does not establish the parties, dates, or terms of any particular Paragraph IV litigation or settlement.

The legally material settlement provisions would include:

Generic entry date.
Authorized-generic commitments.
Restrictions on launch or supply.
Patent challenge concessions.
License scope.
Acceleration clauses.
Payment or value-transfer provisions.
Treatment of subsequent ANDA applicants.

No settlement can be inferred solely from the issued claims.

What geographic coverage did US 6,455,574 provide?

The patent provided rights only in the United States. It did not automatically protect Caduet or an equivalent combination in Canada, Europe, Japan, or other markets.

Foreign protection would require corresponding national or regional patent rights. The existence, term, claim scope, and enforceability of foreign family members had to be assessed separately. Patent expiration in the United States did not necessarily establish simultaneous expiration elsewhere.

Key Takeaways

US 6,455,574 is a method patent covering combined treatment with amlodipine and atorvastatin in one pharmaceutical composition.
The commercial embodiment is a Caduet-type fixed-dose tablet containing amlodipine besylate and atorvastatin calcium.
Claims 1 through 4 are the broadest and most commercially important claims.
Claims 5 through 12 add diagnosis, prescription, examination, and medical-need limitations.
The patent does not claim a specific dose, ratio, release profile, excipient, crystal form, or manufacturing process.
Separate administration of two tablets does not literally satisfy the single-composition limitation.
The nominal United States patent term ended approximately June 5, 2018.
The patent is expired and does not present a current United States exclusionary barrier.
Generic competition is governed primarily by ANDA approval, bioequivalence, manufacturing capability, and pricing.
Biosimilar analysis is not applicable because both active ingredients are small molecules.

FAQs About US Patent 6,455,574

Does US 6,455,574 cover atorvastatin alone?

No. The claims require both amlodipine and atorvastatin in the claimed treatment method.

Does the patent cover two separate tablets taken together?

The claims expressly require administration in a single pharmaceutical composition. Two separate tablets generally do not satisfy that limitation literally.

What salts are covered by the patent?

The claims cover amlodipine and pharmaceutically acceptable acid addition salts, including amlodipine besylate. They also cover atorvastatin and pharmaceutically acceptable salts, including atorvastatin hemicalcium.

Is Caduet still protected by this patent?

No. US 6,455,574 is expired. Current commercial protection, if any, must be evaluated under other patents, regulatory exclusivities, trademarks, or market-specific rights.

Can a company launch a generic amlodipine-atorvastatin tablet after patent expiration?

Yes, provided the product receives FDA approval and satisfies applicable requirements for bioequivalence, labeling, manufacturing, quality, and market authorization.

References

United States Patent and Trademark Office. (2002). U.S. Patent No. 6,455,574, pharmaceutical composition comprising atorvastatin and amlodipine.
Pfizer Laboratories. (2023). Caduet: Amlodipine besylate and atorvastatin calcium prescribing information. U.S. Food and Drug Administration.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
United States Patent and Trademark Office. (2024). Patent term calculator and patent term adjustment records.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1003503	⤷ Start Trial	SZ 30/2006	Austria	⤷ Start Trial
European Patent Office	1003503	⤷ Start Trial	91253	Luxembourg	⤷ Start Trial
European Patent Office	1003503	⤷ Start Trial	05C0048	France	⤷ Start Trial
European Patent Office	1003503	⤷ Start Trial	C01003503/01	Switzerland	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,455,574

Summary for Patent: 6,455,574