US Patent 8,357,394: Amoxicillin Once-Daily Product Claims, Patent Scope, and Generic Entry Risk

US Patent No. 8,357,394 protects a specific once-daily amoxicillin delivery architecture rather than amoxicillin itself. The independent claim requires three separate dosage forms in one 24-hour product: an immediate-release portion, a delayed-release portion coated with a methacrylic acid copolymer, and a second delayed-release portion having both a methacrylic acid copolymer layer and a hypromellose acetate succinate layer. The product must release the three portions at different times and achieve total amoxicillin Cmax in less than about 12 hours.

The patent is directed to the formulation technology associated with Moxatag, a 775 mg extended-release amoxicillin product marketed by MiddleBrook Pharmaceuticals. Its commercial importance depends on whether an accused generic reproduces the three-part release design, the specified coating sequence, and the pharmacokinetic limitations. A generic can avoid literal infringement by using a materially different release mechanism, but bioequivalence to the reference product may constrain practical design options.

What does US Patent 8,357,394 protect?

The patent protects a once-daily amoxicillin product containing three independently formulated dosage forms:

Required component	Claim requirement	Technical function
First dosage form	Immediate release	Initial amoxicillin exposure
Second dosage form	Amoxicillin coated with a methacrylic acid copolymer dispersion	Delayed release after polymer-controlled dissolution
Third dosage form	Amoxicillin with a first methacrylic acid copolymer layer and second hypromellose acetate succinate layer	Further delayed or staged release
Product timing	Each dosage form initiates release at a different time	Pulsatile or sequential exposure
Pharmacokinetics	Total amoxicillin Cmax occurs in less than about 12 hours	Limits the release profile
Dosing	Total amoxicillin dose is administered for a 24-hour interval	Once-daily treatment

The claim uses “comprising,” which generally makes the claims open-ended. An accused product may contain additional excipients, coatings, dosage units, or processing aids and still fall within the claim if all required limitations are present.

The patent does not broadly claim:

Amoxicillin as a molecule.
Every extended-release amoxicillin tablet.
Every once-daily amoxicillin regimen.
A single delayed-release amoxicillin formulation.
A conventional sustained-release matrix tablet without the claimed three-form structure.
A product using only one coating system.

The central inventive concept is the combination of three distinct amoxicillin release populations in one daily product.

How do the claims of US 8,357,394 differ in scope?

Claim 1: Core product claim

Claim 1 is the principal infringement risk. It requires proof of all of the following:

A once-daily amoxicillin product.
First, second, and third amoxicillin dosage forms.
At least one amoxicillin antibiotic and a pharmaceutically acceptable carrier in each dosage form.
An immediate-release first dosage form.
A delayed-release second dosage form coated with a methacrylic acid copolymer dispersion.
A delayed-release third dosage form with:
- a first methacrylic acid copolymer dispersion layer; and
- a second hypromellose acetate succinate layer.
Different release-initiation times for all three dosage forms.
Total amoxicillin Cmax in less than about 12 hours.
The full daily dose in the product.

The claim is a product claim. It does not expressly require a tablet, capsule, bead, pellet, multiparticulate, or particular physical configuration. A capsule containing different coated pellets could potentially satisfy the claim, as could a tablet containing separate granule populations.

Claim 2: Dose limitation

Claim 2 limits the total amoxicillin dose to approximately 775 mg to 1,550 mg.

This range captures a 775 mg once-daily product and a 1,550 mg daily product. A product below 775 mg or above 1,550 mg would not literally satisfy claim 2, but it could still infringe claim 1 if the remaining limitations are met.

The use of “about” creates a potential claim-construction issue around the boundaries. The commercially important reference point is 775 mg, which corresponds to Moxatag extended-release tablets.[2]

Claim 3: Component proportions

Claim 3 requires each dosage-form population to represent 10% to 90% of the product.

The claim does not specify whether the percentages are measured by:

total product weight;
total amoxicillin content;
dosage-unit count;
pellet or granule population; or
another formulation basis.

The specification and prosecution history would be important in determining the proper measurement method. As written, the three ranges can overlap and do not require the percentages to be equal or to total exactly 100% unless the product definition supplies that interpretation.

Claim 4: 45/30/25 formulation split

Claim 4 narrows claim 3 to the following distribution:

Dosage form	Product percentage
Immediate release	45%
First delayed release	30%
Second delayed release	25%

This is the most compositionally specific claim in the set. A generic using a different split may avoid literal infringement of claim 4 while remaining exposed under claims 1 or 3.

Claim 5: Pharmacodynamic exposure

Claim 5 requires serum amoxicillin concentration at or above the MIC90 for the infecting bacterial pathogen for at least five hours during a 24-hour interval.

This limitation raises several proof issues:

The relevant MIC90 may vary by pathogen.
The claim is patient- and pathogen-dependent.
The product must maintain the concentration threshold for at least five hours, but not necessarily continuously at one fixed value across all pathogens.
In an ANDA case, the applicant’s bioequivalence data, labeling, formulation description, and pharmacokinetic profile could become relevant to infringement analysis.

Claim 5 does not require a specific Cmax, AUC, Tmax, or half-life. It focuses on time above MIC90.

Claim 6: Excipients

Claim 6 adds:

microcrystalline cellulose;
povidone; and
polyoxyl 35 castor oil.

These excipients are common pharmaceutical formulation materials. The claim is narrower than claim 1 but may be commercially relevant if the reference formulation and a generic use the same excipient package.

An accused product does not need to use the same excipients to infringe claim 1. Claim 6 is vulnerable to design-around through substitution of functionally similar excipients, unless the substitute formulation still satisfies the broader claims.

Claim 7: Amoxicillin as the only antibiotic

Claim 7 requires amoxicillin to be the only antibiotic in all three dosage forms.

The claim does not prohibit non-antibiotic ingredients. It also does not exclude pharmaceutical excipients, stabilizers, coating materials, buffers, or release modifiers. The limitation is directed to antibiotic identity, not to complete compositional exclusivity.

What formulation technology is protected?

The patent protects a multiparticulate, staged-release architecture. The coatings are central to the claim structure.

Methacrylic acid copolymer coating

Methacrylic acid copolymers are pH-responsive enteric or delayed-release polymers. They can remain relatively insoluble in the stomach and dissolve at higher intestinal pH, depending on polymer grade and formulation conditions.

The claim does not identify a particular commercial polymer grade. The phrase “a methacrylic acid copolymer dispersion” is broader than a named product, but the scope may depend on the specification’s description and the prosecution history.

Hypromellose acetate succinate layer

Hypromellose acetate succinate, commonly known as HPMCAS, is also used as an enteric or delayed-release polymer. Claim 1 requires the third dosage form to contain both coating systems in sequence:

methacrylic acid copolymer dispersion; then
hypromellose acetate succinate.

The order is significant. A product using HPMCAS first and methacrylic acid copolymer second presents a noninfringement argument based on the ordered claim language, subject to claim construction and equivalents analysis.

Three release-initiation times

The claim requires each dosage form to initiate release at a different time. This is more restrictive than requiring different release rates or different completion times.

A formulation in which two populations begin releasing simultaneously but finish at different times may challenge literal infringement. Conversely, small analytical differences in release initiation may create disputes over the meaning of “different times.”

How does US 8,357,394 compare with conventional amoxicillin products?

Product type	Immediate release	Delayed release	Three release populations	Once daily	Potential claim 1 risk
Conventional amoxicillin capsule	Yes	No	No	Usually no	Low
Conventional amoxicillin suspension	Yes	No	No	Usually no	Low
Single extended-release matrix tablet	Usually	May be	No	Possibly	Moderate to low
Single enteric-coated dosage form	No or limited	Yes	No	Possibly	Low to moderate
Three-population multiparticulate product	Yes	Yes	Yes	Yes	High
Moxatag-type formulation	Yes	Yes	Yes	Yes	High

The patent estate is strongest against products that copy the reference product’s release architecture. It is weaker against products using a different technology, such as:

osmotic delivery;
hydrophilic matrix release;
ion-exchange resins;
a single coated population;
a two-pulse formulation;
covalently modified or prodrug approaches;
a different enteric polymer sequence; or
a conventional twice-daily immediate-release regimen.

What is the relationship between US 8,357,394 and Moxatag?

Moxatag is an extended-release amoxicillin tablet approved by the FDA for once-daily treatment of certain infections, including pharyngitis and tonsillitis caused by susceptible Streptococcus pyogenes.[2] The product contains 775 mg of amoxicillin and is administered once daily.

The formulation described in the Moxatag prescribing information is based on immediate- and delayed-release components that produce an extended exposure profile. The product is not interchangeable with conventional immediate-release amoxicillin products without an approved regulatory basis.[2]

US Patent 8,357,394 is commercially relevant because its claims map onto the product’s staged-release design. The patent should be analyzed with related MiddleBrook amoxicillin patents, including US Patent No. 7,022,337, rather than as an isolated document. The earlier patent family members may contain overlapping claims directed to once-daily amoxicillin dosage forms, release profiles, coating systems, and pharmacokinetic performance.[1][3]

What is the patent expiration and exclusivity position?

The patent was issued on January 22, 2013. Its practical exclusivity date depends on the applicable priority chain, patent-term adjustment, terminal disclaimers, patent-term extension, pediatric exclusivity, and any Orange Book listing.

Event	Date or status
Patent issued	January 22, 2013
Patent owner associated with commercial product	MiddleBrook Pharmaceuticals, Inc.
Reference product	Moxatag 775 mg extended-release tablet
FDA approval of Moxatag	2008
Patent term basis	20 years from the relevant nonprovisional filing date, subject to adjustment or extension
Pediatric exclusivity	Must be assessed separately from patent expiration
Regulatory exclusivity	Must be distinguished from patent term
Orange Book status	Requires review of the current FDA Orange Book patent table

The 20-year patent term is not calculated simply from the grant date. A continuation patent can issue years after the original application while retaining an earlier effective term date. Patent term adjustment can extend the calculated term, while a patent-term extension under 35 U.S.C. § 156 can apply to an approved drug-related patent if statutory requirements are satisfied.[4]

FDA Orange Book listings do not themselves create patent rights. They affect ANDA certification and notice procedures. A listed patent can trigger a Paragraph IV notice and a 30-month stay if the NDA holder or patent owner timely files an infringement action.[5]

What is the Orange Book status of Moxatag?

Moxatag’s Orange Book position should be evaluated across four separate categories:

Listed patents for the approved drug.
Expiration dates reported by FDA.
Whether the patent is eligible for Paragraph IV certification.
Whether the product has active commercial status.

The FDA Orange Book identifies patents submitted by NDA sponsors for approved drug products. It does not guarantee that every listed patent is valid, enforceable, or infringed.[5]

For US 8,357,394, the critical diligence questions are:

Whether the patent was listed against NDA 022049.
Whether the listing covered the 775 mg extended-release product.
Whether the FDA-listed expiration date differs from the basic 20-year term.
Whether a generic applicant filed a Paragraph IV certification.
Whether litigation triggered a statutory 30-month stay.
Whether any settlement agreement was submitted under the FDA’s patent-settlement reporting process.

A current Orange Book record and USPTO Patent Center file history are controlling for present status. Patent databases may show the grant, assignment, maintenance, and term data but do not replace the FDA’s listing record or the prosecution history.[1][5]

Which companies challenged Moxatag patents?

Public generic competition for amoxicillin is extensive, but most conventional amoxicillin products do not necessarily challenge the Moxatag formulation claims. A company seeking approval for a generic equivalent of the 775 mg extended-release product would likely need to address listed patents through one of four mechanisms:

Paragraph I certification;
Paragraph II certification;
Paragraph III certification; or
Paragraph IV certification.

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or will not be infringed. The ANDA applicant must provide notice to the NDA holder and patent owner. A timely patent lawsuit can trigger a 30-month stay under the Hatch-Waxman framework.[6]

No company should be treated as a confirmed challenger solely because it markets ordinary amoxicillin. The relevant competitive set is limited to applicants pursuing an extended-release amoxicillin product that references the Moxatag NDA or seeks approval for an equivalent 775 mg once-daily product.

What generic launch scenarios exist?

Scenario 1: No equivalent extended-release ANDA

A generic manufacturer may continue selling immediate-release amoxicillin without addressing the patent if it does not seek approval for the patented once-daily product. This is the lowest litigation-risk scenario.

Scenario 2: Design-around extended-release product

A manufacturer may pursue an extended-release product using a different release system. The applicant would still need to satisfy FDA requirements for safety, efficacy, labeling, and bioequivalence or another applicable pathway. A formulation that avoids one or more required limitations may reduce patent exposure.

Scenario 3: Paragraph IV challenge

An applicant may challenge US 8,357,394 and related patents on grounds such as:

lack of novelty;
obviousness;
inadequate written description;
lack of enablement;
indefiniteness;
noninfringement;
improper claim construction; or
expiration or unenforceability.

The most material noninfringement positions would likely involve the coating sequence, the presence of three distinct dosage forms, the timing of release initiation, or the pharmacokinetic limitations.

Scenario 4: Launch after patent expiration

If the patent and any applicable pediatric or regulatory exclusivity have expired, an approved equivalent could launch without a Paragraph IV-related 30-month barrier. Other listed patents could still affect timing.

How strong is the patent estate?

The estate has meaningful commercial strength but narrow technical boundaries.

Strength factor	Assessment
Product specificity	Strong against close Moxatag copies
Active-ingredient protection	None; amoxicillin is long-established
Formulation protection	Strong where three release populations are reproduced
Coating protection	Significant because the third population requires a specific two-layer sequence
Pharmacokinetic limitations	Potentially difficult to prove and design around
Generic substitution risk	High for a true equivalent; lower for conventional amoxicillin
Prior-art exposure	Likely material because multiparticulate and enteric-release systems were established technologies
Manufacturing barrier	Moderate; coating uniformity and release timing can be difficult to reproduce
Regulatory barrier	Higher than for conventional immediate-release amoxicillin
Biosimilar risk	Not applicable

The patent does not create biosimilar exposure because amoxicillin is a chemically synthesized small molecule, not a biologic. Competition would arise through the ANDA pathway or, for a materially different product, another FDA drug-approval route.[6]

What manufacturing and IP barriers affect generic entry?

The technical challenge is not merely mixing amoxicillin with an enteric polymer. A competing product must control:

particle or pellet size;
amoxicillin loading;
coating weight gain;
polymer dispersion uniformity;
layer order;
coating defects;
dissolution at different pH levels;
release initiation time;
total exposure;
Cmax and Tmax;
stability during storage; and
dose uniformity across the three populations.

The patent’s coating limitations can create a direct formulation barrier. A generic applicant may be able to avoid the claims by using a different architecture, but that approach can create a separate regulatory problem if the altered product no longer matches the reference product’s performance.

What litigation and settlement issues should be reviewed?

A complete diligence review should include:

USPTO Patent Center prosecution history;
assignment records;
maintenance-fee status;
terminal-disclaimer filings;
patent-term-adjustment calculation;
FDA Orange Book entries;
FDA Drugs@FDA approval history;
Paragraph IV notices;
district-court complaints and claim-construction orders;
Federal Circuit decisions;
ANDA settlement agreements;
FTC settlement-reporting records; and
product-discontinuation notices.

The most important litigation issues would likely concern whether “three dosage forms” requires three physically separate populations, how “different times” is measured, whether the polymer limitations require a particular coating composition or grade, and whether the pharmacokinetic limitations are inherent in the product or must be demonstrated independently.

Key Takeaways

US 8,357,394 is a formulation patent, not an amoxicillin compound patent.
Claim 1 requires immediate release plus two distinct delayed-release amoxicillin populations.
The third population must have a methacrylic acid copolymer layer followed by HPMCAS.
Claim 4 narrows the product to a 45%/30%/25% distribution.
Claim 5 adds a five-hour serum-concentration requirement tied to MIC90.
Claim 6 adds microcrystalline cellulose, povidone, and polyoxyl 35 castor oil.
Claim 7 requires amoxicillin to be the only antibiotic.
The patent is most relevant to Moxatag-type once-daily extended-release products.
Conventional immediate-release amoxicillin products are outside the principal technical target.
Generic risk is highest for a 775 mg once-daily product that reproduces the three-population coating architecture.
Biosimilar risk does not apply.
Current enforceability, Orange Book listing, and launch timing require confirmation from the live FDA and USPTO records.

FAQs

Is US 8,357,394 a patent on Moxatag?

It is a formulation patent that is technically aligned with the Moxatag once-daily extended-release amoxicillin product. The FDA Orange Book must be checked to confirm whether it is listed against the Moxatag NDA.

Can a generic use a different enteric polymer?

Potentially. A product using a different polymer may avoid literal infringement of the methacrylic acid copolymer or HPMCAS limitations, but the full claim language, equivalents doctrine, and prosecution history must be analyzed.

Does a 775 mg immediate-release amoxicillin product infringe this patent?

Not based on the stated claims alone. Claim 1 requires three dosage forms, including two delayed-release forms and different release-initiation times.

Does the patent cover twice-daily amoxicillin?

The claims are directed to a product containing the total dose for a 24-hour dosing interval. A conventional twice-daily immediate-release regimen would not ordinarily satisfy the claimed once-daily product structure.

What is the principal invalidity risk?

The principal technical risk is obviousness based on prior-art combinations involving multiparticulate dosage forms, enteric polymers, sequential release, and once-daily antibiotic pharmacokinetics. The strength of that challenge depends on the full prior-art record and the patent’s prosecution history.

References

United States Patent and Trademark Office. (2013). U.S. Patent No. 8,357,394, Once-a-day amoxicillin formulation.
U.S. Food and Drug Administration. (2008). Moxatag (amoxicillin extended-release tablets) prescribing information.
United States Patent and Trademark Office. (2006). U.S. Patent No. 7,022,337, Once-daily amoxicillin formulation.
United States Code. (2023). 35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
United States Code. (2023). 21 U.S.C. § 355; 35 U.S.C. § 271(e).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pragma	MOXATAG	amoxicillin	TABLET, EXTENDED RELEASE;ORAL	050813-001	Jan 23, 2008		DISCN	Yes	No	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006321782	⤷ Start Trial
Australia	2006351475	⤷ Start Trial
Canada	2635378	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 8,357,394