United States Patent 6,828,339: Amlodipine Besylate Monohydrate Patent Scope, Claims, Expiration, and Generic Risk

U.S. Patent No. 6,828,339 protects a specific crystalline solid form of amlodipine besylate: crystalline amlodipine besylate monohydrate. Its claims also cover selected analytical characteristics, particle-size ranges, and immediate-release tablet compositions containing the crystalline material with microcrystalline cellulose, sodium starch glycolate, and magnesium stearate.

The patent is a solid-state and formulation patent, not a basic active-ingredient patent. Its commercial relevance depended on whether a generic manufacturer used the claimed monohydrate form or the claimed excipient combination. Based on the patent’s filing and issue chronology, the 20-year patent term has expired. The patent therefore does not currently block U.S. manufacture, approval, or sale of amlodipine products, subject to other patents, regulatory exclusivities, and applicable legal issues.

What does U.S. Patent 6,828,339 protect?

The patent protects five connected subject-matter groups:

A crystalline amlodipine besylate monohydrate.
The monohydrate identified by DSC, purity, IR, and powder X-ray diffraction characteristics.
The monohydrate in defined particle-size ranges.
Pharmaceutical compositions containing 1 to 20 mg of the monohydrate with three named excipients.
Tablets consisting essentially of that active form and excipient system.

The independent claims are claims 1 and 9. Claim 1 is a product claim. Claim 9 is a composition claim.

Claim group	Claims	Protected subject matter
Crystalline drug substance	1	Crystalline amlodipine besylate monohydrate
Thermal property	2	DSC melting range of 92°C to 104°C
Purity	3	At least 99% purity
Infrared identity	4	IR spectrum corresponding to Figure 6
XRPD identity	5	X-ray powder diffraction pattern corresponding to Figure 9C
Particle size	6-8	Average particle size of 100 microns or less, 50 microns or less, or 10 microns or less
Pharmaceutical composition	9	1 to 20 mg active ingredient plus three specified excipients
Tablet form	10-11	Tablet, including a composition that consists essentially of the listed ingredients
Analytical and particle limitations	12-15	IR, XRPD, and particle-size limitations incorporated into the composition claims

How broad is claim 1 for crystalline amlodipine besylate monohydrate?

Claim 1 is formally broad within the category of crystalline amlodipine besylate monohydrate. It does not expressly require the DSC range, 99% purity, Figure 6 IR spectrum, Figure 9C XRPD pattern, or any particle-size limitation. Those limitations appear in dependent claims 2 through 8.

The central infringement question would be whether an accused material is:

amlodipine besylate;
crystalline;
a monohydrate; and
within the meaning of the claim’s product definition.

A competitor could attempt to avoid claim 1 by using a different solid form, such as an anhydrous form, another hydrate or solvate, an amorphous form, or a different salt. The practical strength of the claim would therefore depend on the scope of “crystalline” and “monohydrate,” as well as the patent’s specification and prosecution history.

Claims 2 through 5 provide narrower identity markers. They are useful for proving that a sample is the patented material, but they also create narrower claim elements that an accused product must satisfy.

What do the DSC, IR, and XRPD claims cover?

DSC limitation in claim 2

Claim 2 requires a DSC melting point within 92°C to 104°C. DSC is a thermal characterization technique. The limitation may be affected by:

heating rate;
sample preparation;
instrument calibration;
water loss before melting;
polymorphic conversion during heating; and
interpretation of endothermic events.

A product that has the claimed monohydrate but produces a DSC result outside the stated range may create an evidentiary dispute. The range is not necessarily a complete structural definition of the material.

IR limitation in claim 4

Claim 4 requires an IR spectrum corresponding to Figure 6. The claim contains an apparent typographical error in the supplied text, which refers to “IR spetra” and later “JR spectra.” The intended limitation is infrared spectroscopy.

“Corresponding to” generally requires comparison with the figure and the specification’s characterization method. The analysis would focus on peak positions, intensity, tolerances, sample preparation, and whether the figure is intended as a qualitative fingerprint or a precise numerical limitation.

XRPD limitation in claim 5

Claim 5 requires an X-ray powder diffraction pattern corresponding to Figure 9C. XRPD is usually the most important identity test for a crystalline pharmaceutical form. Relevant variables include:

characteristic peak positions;
relative intensities;
instrument configuration;
sample orientation;
crystallinity;
hydration state; and
acceptable measurement error.

A materially different XRPD pattern could support a non-infringement position, even if the product has similar chemical composition and therapeutic performance.

What particle sizes are covered by claims 6 through 8?

The particle-size claims are nested:

Claim	Average particle-size limitation
6	100 microns or less
7	50 microns or less
8	10 microns or less

Claim 8 is the narrowest particle-size claim. A product averaging 10 microns or less also falls within the broader 50-micron and 100-micron limitations, assuming the other claim elements are met.

The measurement method matters. “Average particle size” can produce different results depending on whether the parties use laser diffraction, microscopy, sieve analysis, or another technique. The patent’s specification and prosecution history would determine the proper measurement approach.

What formulation does claim 9 protect?

Claim 9 covers a pharmaceutical composition containing:

1 to 20 mg crystalline amlodipine besylate monohydrate;
microcrystalline cellulose;
sodium starch glycolate; and
magnesium stearate.

The claim does not expressly require a tablet. Claim 10 adds the tablet limitation, while claim 11 narrows the composition to one that “consists essentially of” the listed components.

The “consisting essentially of” language in claim 11 is commercially significant. It generally permits components that do not materially affect the basic and novel characteristics of the composition, while potentially excluding additional ingredients that materially change those characteristics. The precise scope would depend on the specification and claim construction.

Claims 12 through 15 add the analytical and particle-size limitations to the formulation:

claim 12: Figure 6 IR spectrum;
claim 13: Figure 9C XRPD pattern;
claim 14: average particle size of 50 microns or less;
claim 15: average particle size of 10 microns or less.

A tablet containing the same active form but different excipients could avoid claims 9 through 15 while still raising issues under claim 1.

How does the patent compare with basic amlodipine and salt patents?

U.S. Patent 6,828,339 sits downstream from the foundational amlodipine patents.

Patent category	Typical protected subject matter	Relevance to U.S. 6,828,339
Basic compound patent	Amlodipine molecule and pharmaceutically acceptable salts	Earlier, broader chemical protection
Besylate-salt patent	Amlodipine besylate salt	Covers salt selection or preparation
Solid-state patent	Crystalline monohydrate or polymorph	Directly aligned with U.S. 6,828,339
Formulation patent	Tablet composition and excipient system	Overlaps claims 9-15
Method-of-use patent	Treatment of hypertension or related conditions	Potentially separate from the solid form
Process patent	Manufacture, crystallization, drying, or milling	Could create separate manufacturing barriers

The patent does not claim the amlodipine molecule generally. It does not claim every amlodipine besylate product. Its scope is concentrated on the specified crystalline monohydrate and formulations using it.

When did U.S. Patent 6,828,339 expire?

The patent was issued on December 7, 2004. U.S. utility patents filed after June 8, 1995 generally expire 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and applicable priority rules (35 U.S.C. § 154).

The relevant patent-term analysis is:

Event	Date or status
Patent	U.S. 6,828,339
Issue date	December 7, 2004
Statutory term	20 years from the applicable earliest nonprovisional filing date
Current status	Expired by statutory term
Patent-term extension relevance	No FDA patent-term extension is identified for this solid-state patent
Current blocking effect	None from this patent alone

The exact expiration date should be taken from the USPTO patent-term record for the patent family, including any patent-term adjustment or terminal disclaimer. The patent’s current commercial significance is therefore historical rather than exclusionary.

What was the FDA and Orange Book status?

Amlodipine besylate is the active ingredient in Norvasc, Pfizer’s branded amlodipine product. FDA-approved products include tablets in strengths such as 2.5 mg, 5 mg, and 10 mg, while the patent claims a composition containing 1 to 20 mg of crystalline amlodipine besylate monohydrate.

U.S. Patent 6,828,339 should be distinguished from patents listed in the FDA Orange Book for an approved reference product. An Orange Book listing depends on FDA submission and certification requirements, not merely on the existence of a patent covering a pharmaceutical composition. Solid-state patents may be listed if they meet the applicable listing standards, but the patent number alone does not establish that it was listed for Norvasc.

The controlling regulatory sources are:

the FDA Orange Book;
the approved product labeling;
the patent and exclusivity information submitted by the NDA holder; and
any applicable Paragraph IV certification record.

What Paragraph IV challenges and generic-entry risks existed?

A generic applicant seeking approval before expiration of a listed patent may file a Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed under the Hatch-Waxman Act (21 U.S.C. § 355(j)(2)(A)(vii)(IV)).

For this patent, potential generic strategies included:

Use a non-monohydrate solid form.
Use an amorphous or anhydrous form.
Use a different salt or formulation.
Use the monohydrate but challenge the validity of the claims.
Use different excipients to avoid claims 9 through 15.
Challenge the interpretation of the IR or XRPD limitations.
Argue that the claimed monohydrate was anticipated or obvious from earlier amlodipine besylate disclosures.

Because the patent has expired, a new Paragraph IV challenge directed solely to this patent would generally have no commercial purpose. Generic applicants may still need to address other unexpired patents, listed patents, regulatory exclusivities, or litigation obligations associated with the reference product.

How strong was the patent estate?

The patent estate was technically focused rather than broad.

Strength factor	Assessment
Chemical breadth	Limited; it does not claim all amlodipine
Solid-form specificity	High; the monohydrate is the central limitation
Analytical definition	Strong for product identification, but dependent on test conditions
Formulation coverage	Moderate; limited to specified excipients and dose range
Manufacturing protection	Limited from the supplied claims; no express process claim appears
Design-around potential	Meaningful through alternative solid forms, excipients, or particle sizes
Current enforceability	None after expiration
Historical generic risk	Concentrated on products using the claimed monohydrate

The absence of process claims is important. A competitor could potentially manufacture the same claimed monohydrate by a different process and still face product-claim exposure, but a process different from the patent’s disclosure would not itself avoid a product claim if the resulting material met the claim limitations.

What manufacturing and intellectual-property barriers remain?

The expired patent does not eliminate technical barriers. Amlodipine besylate development still requires control of:

hydration state;
polymorphic form;
crystallization conditions;
drying temperature and humidity;
milling conditions;
particle-size distribution;
content uniformity;
dissolution;
tablet compression;
stability; and
analytical release methods.

Other potential barriers include active pharmaceutical ingredient supplier controls, confidential manufacturing know-how, regulatory chemistry, manufacturing and controls requirements, and separate patents covering processes or formulations.

Patent expiration also does not remove regulatory requirements. A generic product must still satisfy FDA requirements for abbreviated new drug application approval, bioequivalence, manufacturing quality, labeling, and current good manufacturing practice compliance.

What is the commercial impact and revenue exposure?

Norvasc was a major cardiovascular product, but its principal composition and product exclusivity periods ended years before the present date. Amlodipine is now a mature generic antihypertensive market with multiple manufacturers and substantial price competition.

The expired patent’s revenue exposure was tied to the extent to which a manufacturer used the specific crystalline monohydrate and the claimed tablet excipient system. It did not provide continuing exclusivity over:

all amlodipine products;
all amlodipine besylate products;
all calcium-channel-blocker products;
every tablet formulation; or
every manufacturing process.

Current commercial risk should be assessed against active patents and regulatory barriers, not U.S. 6,828,339.

Key Takeaways

U.S. Patent 6,828,339 claims crystalline amlodipine besylate monohydrate.
The dependent claims define DSC, IR, XRPD, purity, particle-size, and formulation limitations.
Claims 9 through 15 are directed to a narrow tablet composition using microcrystalline cellulose, sodium starch glycolate, and magnesium stearate.
The patent is a solid-state and formulation patent, not a basic amlodipine compound patent.
Its 20-year U.S. patent term has expired.
The patent no longer creates a standalone barrier to generic entry.
Historical design-around options included alternative hydrates, polymorphs, amorphous material, excipients, and particle-size profiles.
Current amlodipine market risk depends on other active patents, FDA requirements, manufacturing know-how, and product-specific regulatory records.

FAQs

Does U.S. Patent 6,828,339 cover all amlodipine besylate tablets?

No. It covers tablets using the claimed crystalline amlodipine besylate monohydrate and, for the formulation claims, the specified excipient combination and related limitations.

Can a generic use amlodipine besylate without infringing this patent?

Yes, potentially. A product using a different solid form or a formulation outside the asserted claim limitations may avoid infringement. The expired status of the patent also removes its current exclusionary effect.

Is the 10-micron particle-size limitation required for every claim?

No. It appears only in claims 8 and 15. Claim 1 has no express particle-size limitation, and claim 6 uses the broader 100-micron threshold.

Does the patent claim the method of treating hypertension?

No method-of-use claim appears in the supplied claims. The claims are directed to a crystalline drug substance and pharmaceutical compositions.

Are amlodipine biosimilars relevant to this patent?

No. Amlodipine is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is generic-drug approval, not biosimilar approval under the Public Health Service Act.

References

U.S. Patent No. 6,828,339. (2004). Crystalline amlodipine besylate monohydrate and pharmaceutical compositions. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Code, 21 U.S.C. § 355. (2024). New drugs.
U.S. Code, 35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension records. USPTO.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	037565	⤷ Start Trial
Australia	2002343257	⤷ Start Trial
European Patent Office	1448197	⤷ Start Trial
Norway	20042539	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,828,339

Summary for Patent: 6,828,339