United States Patent 6,984,403: Azithromycin Formulation Claims, Patent Scope, Expiration and Competitive Landscape

United States Patent No. 6,984,403 protects specific azithromycin oral dosage forms that combine azithromycin multiparticulates with behenate-based glycerides, a poloxamer and an alkalizing agent. The strongest claims target a single-dose, high-dose formulation containing tribasic sodium phosphate and magnesium hydroxide, with azithromycin delivered in multiparticulate form. The patent also claims methods for reducing gastrointestinal side effects and treating bacterial or protozoal infections.

The patent is a formulation and method-of-treatment patent, not a patent on azithromycin itself. Its commercial relevance is concentrated in extended-release or modified-release azithromycin products resembling Pfizer's Zmax oral suspension technology.

What does United States Patent 6,984,403 protect?

The patent has three principal claim groups:

Claim group	Claims	Protected subject matter
Composition claims	1-15	Oral dosage forms containing azithromycin multiparticulates, behenate glycerides, poloxamer and an alkalizing agent
Gastrointestinal side-effect claims	16-32	Contiguous administration of azithromycin with an alkalizing agent to reduce gastrointestinal adverse effects
Infection-treatment claims	33-48	Single-dose treatment of bacterial or protozoal infections using the claimed formulation

The broadest composition claim is claim 1. It requires all of the following:

An effective amount of an alkalizing agent.
Multiparticulates containing about 20% to about 75% azithromycin.
About 25% to about 80% of a glyceride comprising glyceryl monobehenate, glyceryl dibehenate, glyceryl tribehenate, or a mixture.
A poloxamer.

A product that omits any one of those required elements would not literally fall within claim 1. The claims do not cover every azithromycin tablet, capsule, suspension or powder. They require the specified multiparticulate architecture and excipient combination.

How strong is the independent claim scope?

Claim 1: broadest formulation claim

Claim 1 is compositionally broad but technically constrained. It does not require:

A particular azithromycin dose;
A particular dosage form;
A particular alkalizing agent;
Poloxamer 407 specifically;
A specific release profile;
A specific particle size;
Azithromycin dihydrate;
A particular manufacturing process.

The claim does require the multiparticulates to contain both azithromycin and the specified behenate glyceride component, together with a poloxamer. The alkalizing agent may be outside the multiparticulates, which creates a potentially important design-around route.

The percentage limitations appear to apply to the multiparticulate composition. A competing product using a substantially different azithromycin-to-glyceride ratio could avoid literal infringement, subject to construction of the terms "about 20%" and "about 25%" and possible doctrine-of-equivalents arguments.

Claim 8: commercially focused formulation claim

Claim 8 is materially narrower and more commercially specific. It requires:

At least about 200 mg tribasic sodium phosphate;
Multiparticulates containing azithromycin;
A mixture of glyceryl monobehenate, glyceryl dibehenate and glyceryl tribehenate;
Poloxamer 407;
About 1.5 gA to about 4 gA azithromycin.

The abbreviation "gA" refers to grams of azithromycin active, rather than grams of the salt or total formulation. This distinction matters for products using azithromycin dihydrate, because the weighed amount of azithromycin dihydrate exceeds the corresponding active-equivalent amount.

Claim 8 is likely the most relevant claim for a Zmax-type single-dose product. It ties the multiparticulate matrix to a defined buffer system and a high total dose.

Claim 10: narrow combination claim

Claim 10 requires:

300 mg to 400 mg tribasic sodium phosphate;
200 mg to 300 mg magnesium hydroxide;
The azithromycin-behenate-poloxamer multiparticulates of claim 8;
1.5 gA to 4 gA azithromycin.

This claim is narrow in excipient quantities but potentially difficult to design around if a product uses the same buffer system and dose range. A formulation with 299 mg phosphate or 301 mg magnesium hydroxide may raise claim-construction and equivalents issues, depending on the product's actual composition and measurement tolerances.

What formulations are protected by the patent?

The patent covers formulations using a lipid-like multiparticulate matrix based on behenate glycerides. The relevant glycerides are:

Component	Role in claim structure
Glyceryl monobehenate	Permitted alone or in a mixture under claim 1; required as part of the mixture in claim 8
Glyceryl dibehenate	Permitted under claim 1; required in the mixture under claim 8
Glyceryl tribehenate	Permitted under claim 1; required in the mixture under claim 8
Poloxamer	Required by claim 1
Poloxamer 407	Required by claims 2, 8 and 10-12
Tribasic sodium phosphate	One expressly claimed alkalizing agent
Magnesium hydroxide or magnesium oxide	Additional alkalizing components in dependent claims
Azithromycin dihydrate	Expressly claimed in claims 12 and 13

The claims permit multiple dosage forms, including:

Powder for oral suspension;
Unit-dose packet;
Oral suspension;
Tablet;
Capsule.

The patent therefore reaches beyond a liquid product. A solid oral product could infringe if it contains the claimed multiparticulates and alkalizing agent.

How do the claims address gastrointestinal side effects?

Claims 16-32 claim a method for reducing the frequency of gastrointestinal side effects associated with azithromycin administration. The method requires:

Administering the claimed oral dosage form;
Administering it contiguously with an alkalizing agent;
Achieving a lower frequency of gastrointestinal side effects than an equal dose of azithromycin administered without the alkalizing agent.

The comparison language is significant. The claim contains a comparative efficacy limitation, not merely a requirement to administer an antacid. An enforcement case would likely require evidence addressing:

The comparator azithromycin dose;
The identity and amount of the alkalizing agent;
The timing of administration;
The gastrointestinal adverse-event endpoint;
The relevant patient population;
The statistical or clinical basis for the claimed reduction.

Claims 29-32 extend the method to immediate-release azithromycin, sustained-release azithromycin and azithromycin multiparticulates. Those claims do not eliminate the formulation limitations inherited from claim 16 and its dependencies.

What infection-treatment methods are protected?

Claims 33-48 cover treatment of bacterial or protozoal infection with a single dose of the claimed oral dosage form.

The principal treatment limitations include:

Limitation	Claims
Mammalian patient	33-48
Human patient	34-43
Single-dose administration	36, 41 and dependent claims
Adult dose of about 250 mgA to 7 gA	35
Adult dose of 1.5 gA to 4 gA	37
Adult dose of 1.5 gA to 3 gA	38
Adult dose of 1.8 gA to 2.2 gA	39
Child dose of 30 to 90 mgA/kg	40
Child dose of 45 to 75 mgA/kg	42
Child dose of about 60 mgA/kg	43

The pediatric claims apply to children weighing 30 kg or less. A single administration of approximately 60 mgA/kg is the narrowest and most commercially recognizable pediatric dosing concept in the claim set.

The infection claims are not limited to one named pathogen. They cover bacterial or protozoal infections, but infringement still requires administration of the claimed formulation and satisfaction of the single-dose and dose-range limitations where applicable.

When does United States Patent 6,984,403 lose exclusivity?

The ordinary patent term is calculated from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and any applicable pediatric extension under U.S. law. The patent's publicly associated priority date is May 18, 2001. On that basis, the unadjusted 20-year term would run to May 18, 2021, before any statutory extensions or adjustments.

Event	Date or implication
Earliest associated priority date	May 18, 2001
Patent issuance	January 10, 2006
Unadjusted 20-year term	May 18, 2021
Possible pediatric extension	Up to six additional months if statutory requirements were met
Relevant terminal date	Must be confirmed from the patent front page and USPTO term records

The issue date does not determine the expiration date. A later-issued patent with a 2001 filing basis does not receive a fresh 20-year term beginning in 2006. Any patent-term adjustment shown on the issued patent must be added to the calculated term, subject to terminal disclaimers and other statutory constraints. The controlling record is the USPTO patent-term data and the FDA Orange Book listing, if the patent was listed for an approved product (USPTO, 2006; FDA, 2024).

What is the Orange Book status of United States Patent 6,984,403?

The patent's practical regulatory significance depends on whether it was listed against an approved azithromycin product and which FDA use codes or product claims were associated with the listing.

For an NDA product, Orange Book listing can create a Paragraph IV notice and a potential 30-month stay under the Hatch-Waxman framework. A patent may be relevant to an ANDA even if its claims cover a formulation or method of use rather than the active ingredient itself.

The following distinctions matter:

Issue	Significance
Composition patent listing	May require an ANDA applicant to certify against the patent
Method-of-use listing	May be addressed through a section viii statement if the ANDA omits the patented use
Expired patent	Does not block approval, although it may remain relevant to historical litigation
Unlisted patent	May support ordinary patent litigation but usually does not create the same Orange Book certification mechanism
Product-specific use code	Determines whether a proposed label overlaps the listed method

The claim text alone does not establish the patent's current Orange Book listing, use code or any Paragraph IV certification. Those facts must be read from the FDA's current Orange Book and the relevant ANDA records.

Which companies are challenging the patent?

The supplied claim set does not identify an ANDA challenger, Paragraph IV notice, district-court complaint or settlement agreement. No challenger can be reliably identified from the patent number and claims alone.

For commercial diligence, the relevant search should cover:

FDA Orange Book patent listings for the applicable azithromycin NDA;
ANDA litigation under 21 U.S.C. § 355(j);
PACER complaints involving the patent number;
Federal Circuit decisions involving claim construction or validity;
Paragraph IV notices disclosed in company SEC filings;
Settlement agreements reported under the Medicare Modernization Act.

A patent may have no reported Paragraph IV litigation even if it was historically important. Conversely, an ANDA dispute may proceed under a different patent in the same product family.

What is the patent landscape for azithromycin?

Azithromycin has a layered patent landscape rather than a single blocking patent.

Active ingredient and core compound patents

The foundational azithromycin compound and antibiotic patents are old and generally no longer the principal barrier to generic entry. The commercial barriers have shifted toward:

Modified-release delivery;
Multiparticulate matrices;
Taste masking;
Pediatric suspensions;
High-dose single administration;
Excipient combinations;
Manufacturing consistency;
Product-specific regulatory exclusivity.

Formulation patents

Patent 6,984,403 is strongest against products that reproduce the following formulation concept:

High-dose azithromycin;
Multiparticulate delivery;
Behenate glyceride matrix;
Poloxamer, particularly poloxamer 407;
Alkalizing buffer;
Single-dose administration.

A generic company using a conventional immediate-release azithromycin tablet or a conventional aqueous suspension would have a stronger noninfringement position if it avoids the claimed multiparticulate matrix.

Method-of-use patents

The side-effect reduction claims and infection-treatment claims create method-of-use exposure. A generic applicant may attempt to avoid that exposure through:

A label that omits the patented use;
A section viii statement;
An alternative dosing schedule;
A product that does not contain the claimed formulation;
A formulation that does not use the claimed alkalizing system.

The strength of a method claim depends on whether the patented use is required by the proposed label or induced by the product's marketing and prescribing instructions.

Manufacturing and process barriers

The patent claims supplied do not contain detailed process limitations. They focus on the final dosage form and treatment method. Process risk therefore depends on other patents, trade secrets and manufacturing know-how involving:

Formation of azithromycin multiparticulates;
Uniform distribution of behenate glycerides;
Poloxamer incorporation;
Particle-size control;
Suspension reconstitution;
Stability during storage;
Batch-to-batch dose uniformity.

Avoiding this patent does not necessarily eliminate manufacturing risk. A competing product may still require a separate freedom-to-operate analysis for process and particle-engineering patents.

How does this patent compare with conventional azithromycin products?

Product type	Likely relevance of Patent 6,984,403
Conventional azithromycin immediate-release tablet	Usually lower risk if it lacks the claimed multiparticulates and behenate glycerides
Conventional azithromycin capsule	Usually lower risk for the same reason
Standard azithromycin oral suspension	Depends on whether it contains the claimed multiparticulate matrix
High-dose single-dose suspension	Higher relevance, particularly with phosphate and magnesium buffer
Zmax-type extended-release suspension	Highest technical overlap
Pediatric single-dose multiparticulate product	High risk if it uses the claimed excipient architecture
Azithromycin product using a different lipid carrier	Potential design-around, subject to equivalents analysis
Product using no alkalizing agent	Potentially avoids claims 1-15, but may still implicate other patents

What generic launch risks exist?

Before patent expiry

The main risks were:

Paragraph IV litigation;
A 30-month FDA approval stay;
Preliminary-injunction efforts;
Induced-infringement claims based on labeling;
Difficulty designing around both the composition and method claims;
Regulatory uncertainty over whether the proposed product was therapeutically equivalent to the reference product.

After patent expiry

Once the patent term ends, the patent no longer provides an enforceable exclusion right against new products, subject to any valid extended term. Commercial barriers remain in:

FDA approval requirements;
Bioequivalence or comparative clinical requirements;
Product development cost;
Manufacturing scale-up;
Stability data;
Market demand for single-dose azithromycin;
Competition from low-cost immediate-release products.

For a generic entrant, the formulation patent is most relevant when the target product is an extended-release or high-dose product requiring a multiparticulate technology. It is less important for an ordinary azithromycin tablet or suspension that does not reproduce the claimed architecture.

What revenue exposure was associated with the patent?

The patent's revenue exposure was tied primarily to the Zmax-type single-dose azithromycin product rather than the entire azithromycin market. Conventional azithromycin products could continue to compete or enter independently if they did not practice the claims.

The revenue assessment should therefore separate:

Sales of the specific extended-release product;
Sales of immediate-release azithromycin;
Pediatric suspension sales;
Hospital and outpatient use;
Products using alternative delivery technologies.

A patent covering the delivery platform does not automatically protect all sales of the active ingredient. Its financial value depends on whether the protected formulation was commercially important and whether competing products could enter with materially different dosage forms.

Key Takeaways

Patent 6,984,403 is directed to azithromycin multiparticulate formulations and related treatment methods.
Claim 1 requires azithromycin, behenate glycerides, a poloxamer and an alkalizing agent.
Claims 8 and 10 focus on a high-dose formulation using poloxamer 407, tribasic sodium phosphate and magnesium hydroxide.
The patent covers both composition and method-of-treatment subject matter.
Claims 16-32 require a gastrointestinal side-effect reduction comparison against an equal azithromycin dose without the alkalizing agent.
Claims 33-48 focus on single-dose treatment of bacterial or protozoal infections, including adult and pediatric dosing ranges.
The apparent unadjusted 20-year term runs from a 2001 filing basis, producing a May 2021 expiration date before any adjustment or extension.
The patent is most relevant to Zmax-type extended-release or high-dose multiparticulate products.
Conventional azithromycin tablets and suspensions may avoid infringement if they lack the claimed multiparticulate and behenate-glyceride architecture.
Current Orange Book status, Paragraph IV activity and any settlement history require product-specific FDA and court-record verification.

Frequently Asked Questions

Does Patent 6,984,403 cover all azithromycin products?

No. It requires a defined multiparticulate formulation containing azithromycin, behenate glycerides and a poloxamer, together with an alkalizing agent in the dosage form.

Is azithromycin dihydrate required?

No. Azithromycin dihydrate is expressly claimed in claims 12 and 13, but it is not required by the broadest claim 1.

Can a generic avoid the patent by using an immediate-release tablet?

Potentially. A conventional immediate-release tablet that lacks the claimed multiparticulates and behenate glyceride matrix would have a strong literal noninfringement position under the supplied claims.

Does the patent cover a 60 mg/kg pediatric dose?

It does when the other limitations are satisfied. Claims 23-26 and 40-43 address pediatric dosing, including approximately 60 mgA/kg for a child weighing 30 kg or less.

Is the patent still a barrier to FDA approval?

That depends on the verified expiration date, any term adjustment or extension, the Orange Book listing and the proposed product's formulation and label. The patent's apparent unadjusted term ended in 2021.

Sources

U.S. Patent and Trademark Office. (2006). United States Patent No. 6,984,403, Azithromycin formulations.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Zmax azithromycin extended-release oral suspension prescribing information.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	2218	⤷ Start Trial
Argentina	045630	⤷ Start Trial
Austria	407663	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,984,403

Summary for Patent: 6,984,403