United States Patent 9,327,028: Acetylcysteine Overdose-Treatment Claims, Scope, and Patent Landscape

US Patent No. 9,327,028 protects selected methods for treating acetaminophen overdose with intravenous acetylcysteine. Its central subject is not the acetylcysteine molecule, the vial, or the infusion pump. The patent targets a treatment protocol combining a 300 mg/kg loading course, continuation with a three-bag regimen, and, for certain claims, liver-enzyme monitoring or low-chelator compositions.

The broadest apparent independent claim is claim 7. It requires a 300 mg/kg acetylcysteine course over 20 or 21 hours followed by continued treatment using a 150/50/100 mg/kg three-bag regimen. Claim 1 is narrower because it also requires AST or ALT measurement and a treatment-continuation decision.

What does US Patent 9,327,028 protect?

US 9,327,028 protects a method-of-treatment sequence with the following required elements:

Element	Claim requirement
Disease	Acetaminophen overdose
Patient	Patient in need of treatment
Active ingredient	Acetylcysteine
Route	Intravenous administration
Initial total dose	300 mg/kg
Initial duration	20 or 21 hours
Continuation	Continued acetylcysteine administration
Continuation regimen	Three-bag regimen
Three-bag doses	150 mg/kg over 60 minutes, 50 mg/kg over four hours, and 100 mg/kg over 16 hours
Monitoring	AST or ALT measurement under claim 1
Composition limitation	Less than 0.05% EDTA or less than 0.05% chelating agents under dependent claims
Diluent limitation	5% dextrose, 0.45% sodium chloride, 0.90% sodium chloride, or water for injection under claim 4
Alternative initial regimen	200 mg/kg over four hours followed by 100 mg/kg over 16 hours under claims 5 and 10

The patent therefore covers a clinical-use protocol rather than a composition per se. A product manufacturer would not infringe merely by making or selling acetylcysteine. Liability would turn on use, labeling, instructions, induced infringement, or direct administration of the claimed regimen.

The patent is directed to acetylcysteine, also known as N-acetylcysteine or NAC, administered for acetaminophen-induced hepatic injury. The claimed protocol corresponds to the established loading and maintenance-dose structure used in intravenous NAC therapy, but adds continuation and monitoring conditions that define the patented treatment sequence.

Which claims are independent and which are dependent?

Claims 1 and 7 are the independent method claims.

Claim 1: monitored continuation method

Claim 1 requires:

Intravenous administration of 300 mg/kg acetylcysteine over 20 or 21 hours.
Measurement of AST or ALT after that administration.
A determination whether therapy should continue based on the measurement.
Continued administration through a three-bag regimen.
The specified 150/50/100 mg/kg continuation schedule.

The monitoring language is material. A protocol that administers the same doses but does not measure AST or ALT, or does not make the continuation decision based on the result, presents a stronger non-infringement position against claim 1.

Claim 7: broader continuation method

Claim 7 omits the AST/ALT measurement and the express decision-making step. It requires the dosing sequence and continuation with the three-bag regimen.

This makes claim 7 the principal enforcement risk. A hospital protocol could potentially fall within claim 7 even if treatment decisions are based on other clinical criteria, provided the claimed dose and timing sequence are used.

Claims 1 and 7 overlap substantially, but they do not have identical scope. Claim 7 is broader as to monitoring. Claims 2 through 6 depend from claim 1, while claims 8 through 11 depend from claim 7.

How do the 2-bag and 3-bag regimens fit within the claims?

The patent claims both a 2-bag initial regimen and a 3-bag initial regimen, but the continuation limitation remains important.

Claim	Initial 300 mg/kg course	Continued treatment	Monitoring
1	20 or 21 hours; method does not specify the initial bag structure in the independent claim	150/50/100 mg/kg three-bag regimen	AST or ALT required
5	200 mg/kg over four hours, then 100 mg/kg over 16 hours	Inherits claim 1 continuation	AST or ALT required
6	150 mg/kg over 60 minutes, then 50 mg/kg over four hours, then 100 mg/kg over 16 hours	Inherits claim 1 continuation	AST or ALT required
7	300 mg/kg over 20 or 21 hours	150/50/100 mg/kg three-bag regimen	Not required
10	200 mg/kg over four hours, then 100 mg/kg over 16 hours	Inherits claim 7 continuation	Not required
11	150/50/100 mg/kg three-bag regimen	Inherits claim 7 continuation	Not required

The claim language creates a potential construction issue. The initial course and the continuation course use the same aggregate 300 mg/kg amount in several embodiments. A court would likely examine whether “continuing” means extending treatment after completion of the initial course, repeating the same dose structure, or applying a protocol in which the initial and continuation descriptions overlap.

That issue matters because standard NAC practice normally describes the 300 mg/kg dose as a complete 20- or 21-hour course. The patent claims an additional continuation regimen after that course, especially where liver injury persists.

What formulations are protected by US 9,327,028?

The formulation limitations are narrow and subordinate to the method claims.

Low-EDTA and low-chelator claims

Claims 2 and 8 require less than 0.05% EDTA. Claims 3 and 9 broaden the chemical category to less than 0.05% chelating agents.

These claims do not claim all acetylcysteine formulations. They require:

Intravenous acetylcysteine;
The claimed overdose-treatment protocol; and
The specified concentration threshold.

A formulation containing no EDTA would generally satisfy the “less than 0.05% EDTA” limitation, assuming the other claim elements are met. A formulation containing another chelating agent could avoid the EDTA-specific claim while still raising issues under the broader chelating-agent claim.

Diluent claim

Claim 4 requires preparation in one of four aqueous vehicles:

5% dextrose;
0.45% sodium chloride;
0.90% sodium chloride; or
Water for injection.

The claim does not cover every possible diluent. A different vehicle may avoid claim 4, but it would not avoid the independent claim if all other elements are present.

The formulation claims are therefore narrower than the treatment claims and are unlikely to provide standalone protection against a competing acetylcysteine product unless that product is used according to the claimed dosing protocol.

What is the FDA regulatory status of acetylcysteine injection?

Intravenous acetylcysteine is FDA-approved for reducing the risk of hepatic injury after acetaminophen overdose. Acetadote, associated with Cumberland Pharmaceuticals, was approved under NDA 021539. FDA labeling describes intravenous administration and the established weight-based dosing structure for acetaminophen toxicity.[2]

FDA approval does not itself establish infringement. The relevant question is whether an approved product’s label directs the claimed regimen. A label that recommends only a standard 20- or 21-hour course may not expressly practice the continuation limitations. A label that instructs clinicians to continue treatment using the claimed three-bag schedule presents greater induced-infringement risk.

What is the Orange Book status of US 9,327,028?

Orange Book listing and patent ownership are separate issues. A patent may be enforceable without being listed in the Orange Book, while an Orange Book-listed patent must satisfy FDA listing requirements tied to the approved drug and its labeling.

For acetylcysteine products, the relevant Orange Book analysis should distinguish among:

Patents listed against Acetadote NDA 021539;
Patents covering the active ingredient or formulation;
Method-of-use patents covering acetaminophen overdose treatment; and
Patents whose claimed methods correspond to the approved labeling.

US 9,327,028 is a method patent. Its commercial relevance depends heavily on whether its claims read on the FDA-approved labeling for the reference product and whether the patent was timely submitted and accepted for listing. The patent’s existence alone does not establish current Orange Book listing status.[3]

An ANDA applicant confronting a listed method-of-use patent could use a Paragraph IV certification, a section viii statement where the patented method is carved out, or both, depending on the approved labeling and the scope of the listed claims.[4]

When does US 9,327,028 lose exclusivity?

US 9,327,028 issued on May 3, 2016. Its enforceable term is governed by the patent term rules applicable to its filing and priority chain. For a utility patent, the baseline term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimer, and any applicable patent-term extension.[5]

The patent is therefore not analyzed by its issue date. The relevant expiration date must be taken from the USPTO patent record and the complete priority and continuation chain. A continuation patent can have a later issue date but still expire on the parent application’s term date.

The patent’s practical exclusivity can end earlier through:

A successful invalidity or noninfringement judgment;
A terminal disclaimer;
A narrowing settlement;
Failure to pay maintenance fees;
A successful Paragraph IV challenge; or
Commercial entry using a non-infringing label or regimen.

Which companies are likely to challenge the patent?

Potential challengers include manufacturers of generic injectable acetylcysteine, including companies with approved or pending abbreviated applications for acetylcysteine injection. The principal challenge routes are:

Route	Relevance
Paragraph IV certification	Used if the applicant asserts that the patent is invalid, unenforceable, or not infringed
Section viii statement	Used to omit a patented method from the proposed label where permitted
ANDA litigation	May trigger a 30-month stay if statutory conditions are satisfied
Declaratory judgment	May be used where an actual controversy exists
Post-grant review or inter partes review	Timing and eligibility depend on the patent and statutory deadlines
Label redesign	Can remove continuation instructions or other patented-use directions

A generic applicant has several possible design-around positions:

Use a conventional single 20- or 21-hour course without the claimed continuation;
Avoid the claimed AST/ALT decision sequence;
Use a dosing schedule outside the stated timing windows;
Use a different diluent;
Use a formulation outside the low-chelator limitations; or
Carve out the patented continuation method from labeling.

The strongest patent challenge would target the combination of prior-art dosing protocols and prior-art clinical practice. The individual doses are familiar in NAC treatment. The patentability argument therefore turns on the claimed combination of initial completion, laboratory assessment, continuation, and specific infusion sequence.

How strong is the patent estate for acetylcysteine overdose treatment?

The estate is stronger as a method-of-use portfolio than as a molecule or composition portfolio.

Protection category	Strength assessment
Acetylcysteine molecule	Weak or unavailable because NAC is an old active ingredient
Standard 300 mg/kg dose	Limited standalone exclusivity because the regimen is widely known
Three-bag schedule	Potentially relevant, but vulnerable to prior-art and label-scope challenges
AST/ALT-guided continuation	Stronger claim differentiation under claim 1
Low-EDTA composition	Narrow and formulation-dependent
Low-chelator composition	Broader than the EDTA claim but still dependent on treatment use
Diluent selection	Narrow, with multiple possible design-around vehicles
Manufacturing process	Not covered by the supplied claims
Device or delivery system	Not covered by the supplied claims

The estate’s commercial value depends on whether the patent blocks the reference product’s marketed indication and whether generic companies can omit the patented continuation instructions. Because the claims are method claims, a label carve-out may materially reduce infringement exposure without requiring a different active ingredient.

What patent litigation and settlement risks affect generic entry?

The supplied claim set does not identify a litigation docket, settlement agreement, or Paragraph IV notice. The principal legal risks are nevertheless clear.

A patent owner would likely argue that a generic label induces physicians and hospitals to perform the claimed continuation regimen. A generic applicant would likely respond that:

The claimed continuation is not required by the proposed label;
The initial and continuation courses are clinically distinct;
The claims are anticipated by known NAC protocols;
The continuation limitation is indefinite or unsupported;
The claims improperly extend protection over routine clinical management; or
The composition and diluent limitations are absent.

A settlement could permit entry before patent expiration while restricting label language, distribution, or use in specific indications. In pharmaceutical litigation, the settlement terms, entry date, authorized-generic provisions, and any payment arrangement often matter more commercially than the patent’s face expiration date.

What generic launch scenarios exist?

Scenario 1: No continuation language

A generic label provides only the conventional 300 mg/kg NAC course and does not instruct clinicians to continue with the claimed three-bag regimen. This creates the strongest design-around position against claims 1 and 7.

Scenario 2: Three-bag dosing without patented continuation

The label describes the 150/50/100 mg/kg regimen as the initial treatment but does not characterize it as continuation after a completed 20- or 21-hour course. This may avoid the sequential limitation, subject to claim construction and actual use.

Scenario 3: Full label overlap

The label adopts the 300 mg/kg course, AST/ALT monitoring, treatment continuation, and the claimed 150/50/100 mg/kg sequence. This presents the highest induced-infringement exposure.

Scenario 4: Hospital-use continuation

Even with a narrow generic label, hospitals may continue treatment under institutional protocols. The patent owner could investigate direct administration by healthcare providers and inducement theories against manufacturers or distributors.

How does US 9,327,028 compare with competing patent categories?

US 9,327,028 differs from patents directed to NAC formulations or manufacturing methods.

Patent category	Typical protected subject	Relation to 9,327,028
Formulation patent	Stability, concentration, preservatives, EDTA, pH, container	9,327,028 covers only selected composition limitations within a treatment method
Method-of-use patent	Treatment of overdose or hepatic injury	9,327,028 is primarily in this category
Manufacturing patent	Synthesis, purification, sterilization, filling	Not covered by supplied claims
Device patent	Infusion bag, pump, tubing, dosing controller	Not covered
Regulatory exclusivity	FDA approval rights	Separate from patent rights
Biosimilar exclusivity	Biologic reference-product exclusivity	Not applicable because acetylcysteine is a small molecule

Biosimilar risk is effectively absent. Acetylcysteine is a small-molecule drug regulated through the NDA/ANDA framework, not the biosimilar pathway under the Public Health Service Act.

What licensing deals affect the patent landscape?

Cumberland Pharmaceuticals has been associated with Acetadote commercialization. A commercial license, distribution agreement, or acquisition of product rights does not automatically transfer ownership of US 9,327,028. Patent ownership, exclusive licensing, FDA sponsorship, and product distribution must be examined separately.

No licensing term should be inferred solely from product branding. A generic manufacturer may obtain a license to a patent, enter a settlement, or rely on a carve-out without acquiring any ownership interest in the patent estate.

Key Takeaways

US 9,327,028 is a method-of-treatment patent for intravenous NAC therapy in acetaminophen overdose.
Claim 7 is the broadest apparent independent claim because it omits AST/ALT monitoring.
Claim 1 is narrower but adds a clinically meaningful laboratory-monitoring and continuation-decision requirement.
The patent does not broadly claim acetylcysteine, acetylcysteine injection, or the NAC molecule.
Claims 2, 3, 8, and 9 narrow protection to low-EDTA or low-chelator compositions.
Claim 4 narrows protection to four specified aqueous diluents.
Claims 5 and 10 cover the 2-bag 200/100 mg/kg initial regimen.
Claims 6 and 11 cover the 3-bag 150/50/100 mg/kg regimen.
Generic entry risk depends primarily on label language and whether the continuation sequence can be carved out.
FDA approval, Orange Book listing, patent enforceability, and induced infringement are separate questions.
Biosimilar competition is not relevant because acetylcysteine is a small molecule.
The patent estate is stronger as a protocol and continuation-treatment estate than as a formulation or manufacturing estate.

FAQs About US 9,327,028

Does US 9,327,028 cover oral acetylcysteine?

No. The supplied claims require intravenous administration. Oral NAC products fall outside the express route limitation.

Does a generic acetylcysteine vial infringe the patent automatically?

No. The claims require use in a specific overdose-treatment protocol. Manufacturing or selling acetylcysteine alone does not satisfy every claimed method element.

Is AST or ALT testing required for every infringement theory?

No. AST or ALT measurement is required by claim 1 and its dependents. Claim 7 and its dependents do not include that monitoring limitation.

Can a generic avoid the patent by using a different diluent?

A different diluent may avoid claim 4, but it does not by itself avoid claims 1 or 7. The independent claims do not require the four diluents listed in claim 4.

Is the 2-bag regimen independently protected?

Claims 5 and 10 recite the 2-bag 200/100 mg/kg initial regimen. Those claims remain dependent on the respective independent claim and therefore also require the specified continuation treatment and other inherited limitations.

References

United States Patent and Trademark Office. (2016). U.S. Patent No. 9,327,028, Methods for treating acetaminophen overdose.
U.S. Food and Drug Administration. (n.d.). Acetadote (acetylcysteine) injection prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
Patent Act, 35 U.S.C. §§ 154, 156, 271, and 282.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Apotex	ACETADOTE	acetylcysteine	INJECTABLE;INTRAVENOUS	021539-001	Jan 23, 2004	AP	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				COMPOSITION AND METHOD FOR PROVIDING A REDUCTION IN SIDE EFFECTS FOR HUMAN PATIENTS IN NEED OF ACETYLCYSTEINE THERAPY	⤷ 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	2011281035	⤷ Start Trial
China	103038356	⤷ Start Trial
European Patent Office	2596112	⤷ Start Trial
Malaysia	173215	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2012012640	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,327,028

Which drugs does patent 9,327,028 protect, and when does it expire?

Summary for Patent: 9,327,028