US Patent 6,365,180: Claim Scope, Expiration, Litigation Risk and Pharmaceutical Patent Landscape

US Patent 6,365,180 protects a broad formulation platform for improving the dissolution, absorption rate, therapeutic onset and gastrointestinal tolerability of acidic or acid-generating pharmaceutical agents. The claims combine an active agent with a dispersing agent, solubilizer and, in selected claims, a surfactant or plasticizer. The patent also covers alkaline processing methods, capsule filling and optional enteric coating.

The patent is no longer a live U.S. exclusivity barrier. Because US 6,365,180 issued in 2002 from an application filed well before the current date, its 20-year patent term has ended under 35 U.S.C. §154, absent an unusual patent-term adjustment or extension. No current U.S. blocking right should be attributed to this patent.

What technology does US Patent 6,365,180 protect?

The patent covers liquid, semi-liquid or solubilized pharmaceutical compositions intended to improve delivery of poorly soluble or acid-functional drugs.

Its central formulation architecture is:

Required or optional element	Claim requirement
Active agent	Acid-containing drug or agent that forms an acid in situ or in vivo
Acid solubility	Soluble in acid at an acid-to-solute ratio of approximately 3:1 to 10,000:1
Dispersing agent	Polymer-based or carbohydrate-based dispersing agent
Polymer dispersant ratio	Active agent to dispersant from approximately 3:1 to 1:50 by weight
Carbohydrate dispersant ratio	Active agent to dispersant from approximately 3:1 to 1:20 by weight
Solubilizer	Required by claim 1
Surfactant	Optional in composition claims; required for claims 21 and 22
Plasticizer	Optional
Dosage form	Capsule, including soft or hard gelatin capsules
Manufacturing condition	For acid-labile agents, pH of at least 9.0 during preparation

The patent is therefore directed to a formulation system rather than to a single active pharmaceutical ingredient.

How broad is claim 1 of US 6,365,180?

Claim 1 is the principal composition claim and is drafted in open-ended “comprising” language. This means an accused formulation could include additional excipients, coatings, stabilizers or active ingredients and still fall within the claim if every required limitation is present.

The claim has five principal limitations:

At least one qualifying pharmaceutical active agent.
A polymer-based or carbohydrate-based dispersing agent.
The specified active-agent-to-dispersant ratio.
At least one solubilizing agent.
Optional surfactant and plasticizing agent components.

Active-agent limitation

The active-agent definition is unusually expansive. It includes:

Molecules containing at least one acid moiety.
Molecules containing an ester or other chemically active group that is hydrolyzed or removed in vivo or in situ to produce an acid moiety.
Pharmaceutically acceptable salts of qualifying agents.

The claim language potentially reaches both direct acid drugs and prodrugs that generate acidic metabolites. The active-agent limitation is functional and chemically broad, but it is narrowed by the acid-solubility requirement.

Acid-solubility limitation

Claim 1 requires the active agent to be soluble in acid at an acid-to-solute ratio of approximately 3:1 to 10,000:1. This limitation creates an important infringement issue because the claim does not specify:

The acid identity.
Acid concentration.
Temperature.
Mixing time.
Particle size.
Analytical method.
Whether the ratio is based on volume, mass or another measurement convention.

The absence of a defined testing protocol could create claim-construction and indefiniteness disputes under 35 U.S.C. §112(b). A challenger would likely argue that the solubility boundary is not objectively measurable without identifying the relevant acid and test conditions.

Dispersing-agent limitation

The claim covers two excipient classes:

Polymer-based dispersants, including polyvinylpyrrolidone.
Carbohydrate-based dispersants, including hydroxypropylcellulose, hydroxypropylmethylcellulose and cyclodextrin.

The required ratio is material. A formulation using the same excipients but falling outside the stated weight ranges would have a noninfringement position against claim 1, subject to doctrine-of-equivalents analysis.

What dependent claims protect specific formulations?

Claims 2 through 20 narrow the composition claims by identifying specific dispersants, solubilizers, concentration ranges and excipients.

Claims	Subject matter
2-3	Polyvinylpyrrolidone, including PVP K29-32
4	Hydroxypropylcellulose, hydroxypropylmethylcellulose or cyclodextrin
5-9	Water or polyethylene glycol as solubilizer, including PEG molecular weight of about 200 to 8,000
8	PEG concentration of approximately 20% to 99% by weight
10-14	Specified active agents, including NSAIDs, statins, quinapril, fexofenadine, omeprazole, antibiotics and other acidic drugs
15-18	Plasticizer concentrations up to approximately 75% by weight
16 and 18	Glycerin, propylene glycol or sorbitol
19-20	Surfactant concentrations up to approximately 10% by weight

Claims 2, 3, 8, 16 and 18 are commercially more concrete than claim 1 because they identify common excipients and narrower compositional parameters. They would have been easier to evaluate in a product comparison, but they also would have faced a more direct prior-art comparison against conventional PVP, PEG and softgel formulations.

The claim text contains drafting errors, including “propylene, glycol,” “tometin,” “liothryonine,” “atorvastin,” “cervistatin” and repeated or inconsistent claim dependencies. Those errors do not automatically invalidate the claims. Their effect would depend on whether a skilled person could determine the intended meaning from the specification and prosecution history.

Which active pharmaceutical ingredients fall within the claimed Markush group?

Claim 10 identifies a broad group of active agents. The listed compounds include:

NSAIDs.
Quinapril.
Fluvastatin.
Lovastatin.
Pravastatin.
Cerivastatin.
Atorvastatin.
Simvastatin.
Fexofenadine.
Cromolyn.
Omeprazole.
Gemfibrozil.
Ciprofibrate.
Ciprofloxacin.
Lomefloxacin.
Ofloxacin.
Carbidopa and levodopa.
Retinoic acid.
Carboprost.
Penicillins and beta-lactams.
Cephalosporins.
Liothyronine.
Probenecid.

Claims 11 through 14 narrow the NSAID and antibiotic categories. The specifically named NSAIDs include diclofenac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, naproxen, sulindac, etodolac, tolmetin, diflunisal, mefenamic acid, meclofenamic acid and flufenamic acid.

The inclusion of omeprazole is significant because claims 42 through 51 separately target proton-pump-inhibitor processing and capsule products.

What method-of-use claims are covered?

Claims 21 through 34 cover therapeutic and pharmacokinetic uses.

Absorption and therapeutic-onset claims

Claims 21 and 22 cover administering the composition to improve:

The rate of absorption.
The onset of therapeutic benefit.

Both claims require the composition to include the optional surfactant. This is a critical distinction. A composition otherwise meeting claim 1 but lacking a surfactant would have a stronger noninfringement position against claims 21 and 22.

These claims are method claims requiring administration to a mammal. They would not directly cover manufacture, sale or possession of a formulation unless the relevant conduct also involved the claimed method.

Gastrointestinal-protection claim

Claim 23 covers administering a composition containing an NSAID to inhibit gastroirritation. Unlike claims 21 and 22, the claim does not expressly require the optional surfactant.

This claim has several potential weaknesses:

“Inhibiting gastroirritation” may require proof of a clinical or pharmacological effect.
The claim does not define the comparator or baseline level of irritation.
The composition must still satisfy claim 1.
The NSAID must be administered in an “effective amount.”

A generic or follow-on product would face a more substantial risk only if its formulation met the compositional limitations and its labeling or use supported the claimed gastroirritation-reduction method.

Specific treatment claims

Claims 27 through 34 narrow the treatment methods to:

NSAID analgesic and anti-inflammatory treatment.
Diclofenac, indomethacin or sulindac.
Optional metoclopramide as a motility agent.
Fexofenadine for antihistamine treatment.
Omeprazole for inhibition of gastric acid secretion.
Capsule administration, including optional enteric coating.

Claim 53 separately identifies metoclopramide as the optional motility agent.

What manufacturing process does US 6,365,180 protect?

Claims 35 through 45 and 48 through 51 cover preparation processes for acid-labile active agents.

The process requires:

Forming a solution containing a dispersing agent and solubilizer.
Optionally adding a C1-C4 lower alkanol.
Adding sufficient base to establish a pH of at least 9.0.
Adding the active agent while maintaining the pH at least 9.0.
Optionally adding surfactant or plasticizer.
Filling a hard or soft gelatin capsule.
Optionally applying a non-toxic coating, including an enteric coating.

The pH requirement is the principal process limitation. A manufacturing process that dissolves or disperses omeprazole without maintaining the mixture at pH 9.0 or higher would have a potential noninfringement position against claim 35, although the composition claims could still be implicated if the resulting product met their limitations.

Claims 46 and 47 are product-by-process claims. They cover a pharmaceutical composition “when prepared by” the claimed process, with claim 47 specifying omeprazole. Product-by-process claims generally turn on the identity and characteristics of the resulting product, not merely the fact that a particular process was used. The practical value of these claims would depend on whether the process imparts detectable product properties.

How does the patent compare with omeprazole formulation patents?

US 6,365,180 is broader than a conventional omeprazole patent because it is not limited to omeprazole. Its platform extends to NSAIDs, statins, fluoroquinolones, beta-lactams, antihistamines and other acidic or acid-generating drugs.

Omeprazole-specific patent estates historically focused on different technical features, including:

Enteric-coated dosage forms.
Alkaline stabilizers.
Multiple-unit pellets.
Delayed-release capsules and tablets.
Specific salt or polymorph forms.
Manufacturing processes.
Combination products.

By contrast, US 6,365,180 focuses on a liquid or solubilized composition containing dispersant and solubilizer components, with alkaline processing for acid-labile drugs.

Issue	US 6,365,180	Typical omeprazole product patent
Technical focus	Solubilized or dispersed formulation platform	Delayed release, coating, salt, pellet or dosage form
Active ingredient	Broad Markush group	Usually omeprazole or a specific PPI
Key excipients	PVP, cellulose derivatives, cyclodextrin, PEG, water	Alkaline stabilizers, coating polymers, pellet excipients
Process requirement	pH at least 9.0 during addition of acid-labile drug	Product-specific coating or granulation process
Regulatory relevance	Usually formulation or platform patent	Potential Orange Book-listed product patent
Current term	Expired	Depends on the individual patent

What is the Orange Book status of US 6,365,180?

US 6,365,180 should not be treated as an Orange Book barrier merely because it mentions omeprazole or other approved drugs.

The FDA Orange Book lists patents submitted by an NDA holder for an approved drug product under the applicable FDA patent-listing rules. A broad formulation patent is relevant to Orange Book analysis only if:

It claims the approved drug substance, drug product or approved method of use within the statutory listing framework.
The NDA holder submitted it.
FDA accepted the listing.

The supplied claim set does not establish an Orange Book listing. The patent’s broad platform claims and expired status also make it unlikely to create a current Hatch-Waxman stay or Paragraph IV settlement issue.

When did US 6,365,180 lose exclusivity?

The patent term ended under the 20-year term framework in 35 U.S.C. §154. The relevant calculation is based on the earliest effective U.S. nonprovisional filing date, subject to patent-term adjustment and any applicable extension.

Event	Date or status
Patent issued	April 2, 2002
Statutory term framework	20 years from earliest effective nonprovisional filing date
Current enforceability	No current enforceable term
Orange Book exclusivity	Not established by the supplied record
Generic stay risk	None based solely on this expired patent
Patent-term extension	No extension is established in the supplied record

The patent’s expiration does not eliminate any separate, later-issued continuation, divisional, improvement, formulation, salt, polymorph or process patent. Those later rights must be analyzed independently.

Which companies are challenging US 6,365,180?

No active Paragraph IV challenge, federal patent litigation, settlement agreement or biosimilar dispute can be attributed to US 6,365,180 on the basis of the claim text alone.

The patent is directed to small-molecule pharmaceuticals, not a biologic. Biosimilar litigation under the Biologics Price Competition and Innovation Act is therefore not relevant. Any historical generic dispute would more likely have involved:

A product-specific omeprazole patent.
An enteric-release patent.
A formulation or pellet patent.
A method-of-use patent.
A patent listed for an approved NDA product.

A current generic entrant would not need to clear this expired patent, although it would still need to evaluate later patents covering the same active ingredient, dosage form, release profile or manufacturing process.

How strong was the patent estate?

The patent had broad nominal scope but a mixed enforcement profile.

Strengths

Open “comprising” composition language.
Broad active-agent Markush group.
Coverage of both composition and manufacturing process.
Specific claims directed to omeprazole.
Capsule, softgel and enteric-coating coverage.
Multiple excipient classes and concentration ranges.

Weaknesses

Broad functional definition of acid solubility.
Ambiguous acid-to-solute testing ratio.
Large number of unrelated active ingredients.
Potential written-description and enablement challenges.
Conventional nature of PVP, PEG, water, surfactants and plasticizers.
Possible obviousness combinations involving known solubilization and alkaline-stabilization techniques.
Drafting inconsistencies and typographical errors.
Expired patent term.

The most defensible historical claim positions would likely have been narrower combinations involving a specific acid-labile drug, alkaline processing at pH 9 or higher, a defined dispersant, PEG or water, and capsule filling. Claim 1 had the broadest commercial reach but also presented the greatest validity and construction risk.

What generic launch risks exist today?

US 6,365,180 creates no present generic-launch prohibition. A generic manufacturer could still face separate risks if its product practices later, unexpired rights involving:

Omeprazole delayed release.
Esomeprazole or other PPI salts.
Enteric coatings.
Softgel or liquid-filled capsule technology.
Specific polymorphs or crystalline forms.
Combination therapies.
Approved methods of use.
Manufacturing processes.

For a product using PVP, PEG, water and an alkaline preparation step, the expired patent remains relevant as prior art and technical history. It may also affect freedom-to-operate analysis by narrowing the scope of later patents that attempt to claim the same formulation concept.

Key Takeaways

US 6,365,180 is a broad formulation-platform patent covering acidic or acid-generating drugs with dispersants and solubilizers.
Its key excipients include PVP, PVP K29-32, hydroxypropylcellulose, hydroxypropylmethylcellulose, cyclodextrin, PEG and water.
The patent specifically reaches omeprazole, NSAIDs, statins, fexofenadine, antibiotics and other listed agents.
Claims 21 and 22 require a surfactant for absorption-rate and therapeutic-onset methods.
Claims 35 through 51 cover alkaline processing, capsule filling and optional enteric coating for acid-labile drugs.
The patent’s U.S. term has ended under the 20-year patent-term framework.
No current Paragraph IV, biosimilar, Orange Book or settlement risk is established for this expired patent.
Any current freedom-to-operate review must focus on later continuation, improvement, formulation, dosage-form, salt, polymorph, method-of-use and manufacturing patents.

FAQs

Does US 6,365,180 cover all omeprazole products?

No. It covers only omeprazole formulations and processes that satisfy the applicable claim limitations, including the specified dispersant, solubilizer, ratio and, for process claims, alkaline pH requirements.

Does an enteric-coated omeprazole capsule infringe this patent?

Not automatically. Enteric coating is an optional limitation in selected claims. The underlying composition and processing limitations must also be met.

Can a company rely on the expiration of US 6,365,180 for a generic launch?

The patent itself does not block launch because its U.S. term has ended. The company must still clear separate later patents covering the same drug, formulation, release profile or manufacturing process.

Is US 6,365,180 a biologic or biosimilar patent?

No. The claims cover small-molecule active agents and pharmaceutical compositions. Biosimilar exclusivity and BPCIA litigation do not apply.

Are PVP and PEG alone enough to trigger infringement?

No. PVP and PEG are only components of the claimed combination. Infringement would require satisfaction of the active-agent, acid-solubility, dispersant-ratio, solubilizer and other applicable limitations.

References

United States Patent No. 6,365,180, “Pharmaceutical compositions and methods,” issued April 2, 2002.
35 U.S.C. §154. Patent term.
35 U.S.C. §271. Infringement of patent.
35 U.S.C. §282. Presumption of validity and defenses.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Regulatory review of pharmaceutical patent listing and certification requirements.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	429210	⤷ Start Trial
Australia	2117399	⤷ Start Trial
Australia	6216800	⤷ Start Trial
Australia	770772	⤷ Start Trial
Brazil	0012488	⤷ Start Trial
Canada	2318128	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,365,180

Summary for Patent: 6,365,180