Details for Patent: 6,818,229

Summary for Patent: 6,818,229

Title:	Intermediate release nicotinic acid compositions for treating hyperlipidemia
Abstract:	Intermediate release nicotinic acid formulations having unique biopharmaceutical characteristics, such as Cmax, Tmax and AUC, which are suitable for oral administration once per day during the evening or at night for treating hyperlipidemia without causing drug-induced hepatotoxicity to such a level that requires the therapy to be discontinued, are disclosed. The intermediate nicotinic acid formulations can be administered as tablets in dosage strengths of, for example, 375 mg, 500 mg, 750 mg and 1000 mg.
Inventor(s):	Eugenio A. Cefali, David J. Bova
Assignee:	Abbott Laboratories , AbbVie Respiratory LLC
Application Number:	US08/962,027
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,818,229
Patent Claim Types: see list of patent claims	Use; Formulation; Compound; Dosage form;

United States Patent 6,818,229 (Intermediate-Release Nicotinic Acid): Scope, Claim Boundaries, and US Patent Landscape

United States Patent 6,818,229 is a formulation-and-exposure “performance” patent for intermediate-release nicotinic acid (niacin) administered once daily for hyperlipidemia with a target exposure profile intended to reduce drug-induced hepatotoxicity to a discontinuation threshold. The enforceable core is the combination of (i) dose minimums (100 mg, 375 mg, 500 mg, 750 mg), (ii) pharmacokinetic window(s) for nicotinic acid and nicotinuric acid (Cmax, Tmax, AUC ranges), and (iii) an intended-use constraint tied to not requiring discontinuation due to hepatotoxicity. The claims are written to read on oral tablet once-daily regimens that meet these PK windows, making the patent less about manufacturing process and more about what the patient gets (exposure).

What patents protect intermediate-release nicotinic acid once-daily exposure and “no hepatotoxicity discontinuation” outcomes?

Claim architecture that defines enforceable scope

US 6,818,229 is structured around dependent claims that lock in an oral tablet dosage form and multiple PK-based tiers. The independent-style limitation common to claims 1, 3, 5, 9, 13, 17, 21, and 25 (as provided) is:

• Indication and regimen: once-a-day oral administration for hyperlipidemia
• Safety outcome: “without causing drug-induced hepatotoxicity to a level which would require use … to be discontinued”
• Drug: nicotinic acid
• Intermediate release concept: by claim title and context, targeting a controlled-release profile
• Performance targets:
  • Nicotinic acid exposure
    • Cmax (ng/mL or μg/mL scale as stated)
    • Tmax window ~ 5.6 to 6 hours
    • AUC window (μg·hr/mL scale as stated)
  • Nicotinuric acid exposure for certain dose tiers
    • Cmax, Tmax (again ~ 5.6 to 6 hours), and AUC windows

Key scope variables: dose minimum + PK windows

The claim set provided establishes multiple “entry points” for infringement based on achieving specific exposure bands.

Tier A: ≥375 mg nicotinic acid

• Claim 1 (nicotinic acid PK only)
  • Dose: ≥ 375 mg
  • Nicotinic acid: Cmax ~ 3 μg/mL, Tmax ~ 5.6–6 h, AUC ~ 6 μg·hr/mL
  • Outcome: no discontinuation hepatotoxicity
• Claim 3 (nicotinuric acid PK + nicotinuric acid Tmax fixed ~5.6–6 h)
  • Dose: ≥ 375 mg
  • Nicotinuric acid: Cmax ~ 2 μg/mL, Tmax ~ 5.6–6 h, AUC ~ 10 μg·hr/mL

Interpretive consequence for scope: infringement can be designed around by matching one set of PK endpoints. If an accused product matches the nicotinic-acid PK set in claim 1 but not the nicotinuric-acid PK in claim 3, claim 1 could still be asserted.

Tier B: ≥500 mg nicotinic acid

• Claim 5 (wide nicotinic acid AUC band)
  • Dose: ≥ 500 mg
  • Nicotinic acid: Cmax range ~ 1–10 μg/mL, Tmax ~ 5.6–6 h, AUC range ~ 2–34 μg·hr/mL
• Claim 6 (means)
  • Cmax mean ~ 4 μg/mL, AUC mean ~ 9 μg·hr/mL
• Claim 7/8/others: tablet-only dependent claims
• Claim 9 (nicotinuric acid band)
  • Dose: ≥ 500 mg
  • Nicotinuric acid: Cmax range ~ 2–3 μg/mL, Tmax ~ 5.6–6 h, AUC range ~ 6–16 μg·hr/mL
• Claim 10 (means)
  • Nicotinuric acid Cmax mean ~ 2 μg/mL, AUC mean ~ 9 μg·hr/mL

Interpretive consequence: the patent is drafted to cover both (a) range-based exposure designs and (b) point/mean-based designs, giving it more litigation leverage against products that are “about in the middle” of the windows.

Tier C: ≥750 mg nicotinic acid

• Claim 13 (nicotinic acid high-dose PK band)
  • Dose: ≥ 750 mg
  • Nicotinic acid: Cmax range ~ 8–9 μg/mL, Tmax ~ 5.6–6 h, AUC range ~ 21–22 μg·hr/mL
• Claim 14 (means)
  • Cmax mean ~ 8 μg/mL, AUC mean ~ 21 μg·hr/mL
• Claim 17 (nicotinuric acid for ≥750 mg)
  • Dose: ≥ 750 mg
  • Nicotinuric acid: Cmax range ~ 3–3.2 μg/mL, Tmax ~ 5.6–6 h, AUC range ~ 11–13 μg·hr/mL
• Claim 18 (means)
  • Nicotinuric acid Cmax mean ~ 3 μg/mL, AUC mean ~ 12 μg·hr/mL
• Tablet dependencies: claims 15, 16, 19, 20

Interpretive consequence: the tightness of the Cmax and AUC bands at the 750 mg tier makes it easier to argue infringement (or design-around) depending on whether accused products land inside the narrow windows.

Tier D: ≥100 mg nicotinic acid (broader upper nicotinic acid exposures)

• Claim 21 (nicotinic acid exposure band for lower dose)
  • Dose: ≥ 100 mg
  • Nicotinic acid: Cmax range ~ 9–17 μg/mL, Tmax ~ 5.6–6 h, AUC range ~ 24–43 μg·hr/mL
• Claim 22 (means)
  • Cmax mean ~ 13 μg/mL, AUC mean ~ 33 μg·hr/mL
• Tablet dependencies: claims 23, 24

Interpretive consequence: coverage at the 100 mg tier can be used to reach lower-strength formulations if they still produce the same intermediate-release PK pattern.

Tier E: ≥1000 mg nicotinic acid

• Claim 25 (nicotinuric acid for very high dose)
  • Dose: ≥ 1000 mg
  • Nicotinuric acid: Cmax range ~ 3–5 μg/mL, Tmax ~ 5.6–6 h, AUC range ~ 12–19 μg·hr/mL
• Claim 26 (means)
  • Nicotinuric acid Cmax mean ~ 4 μg/mL, AUC mean ~ 15 μg·hr/mL
• Tablet dependencies: claims 27, 28

What does “intermediate release” mean in legal scope?

The claim text you provided does not specify the release mechanism (polymer matrices, coating types, dissolution profiles). Instead, it operationalizes “intermediate release” through a patient-level PK fingerprint: Tmax concentrated around 5.6–6 hours and exposure windows for nicotinic acid and nicotinuric acid.

Practical infringement framing: a product is more likely to be found within scope if it produces the claimed systemic exposure in clinical PK rather than if it uses a particular formulation technology.

How strong is the patent estate for US 6,818,229 nicotinic acid exposure windows?

Enforceability levers embedded in the claims

1. Objective numeric PK constraints
   • Cmax, Tmax, AUC define a measurable boundary. This reduces ambiguity relative to purely functional “extended release” language.
2. Tablet and once-daily regimen constraints
   • Limits the claim set to oral tablet dosing and daily administration, cutting off some non-tablet and multi-dosing alternatives.
3. Safety outcome limitation (“no discontinuation due to hepatotoxicity”)
   • This is outcome-tethered, which can complicate infringement if the accused product’s hepatotoxicity profile is disputed. But the claim is still enforceable if the formulation achieves the PK pattern associated with the claimed safety threshold.

Potential vulnerability vectors

• If accused formulations achieve different Cmax or AUC while keeping similar Tmax, they may fall outside numeric windows even if they are arguably “intermediate release.”
• If an accused product uses a different dosing unit (still once daily, still oral tablet) that shifts exposure (for example, by reducing peak or systemic exposure), it may avoid specific tiers.
• Outcome language (“without causing … requiring discontinuation”) can become the litigation focal point, especially if hepatotoxicity management depends on dose titration, monitoring criteria, and patient characteristics.

When does US 6,818,229 lose exclusivity, and what does that mean for generic entry risk?

US 6,818,229 is a utility patent. Without verified filing and issue-date details in the prompt, an exact expiration date cannot be computed here.

Business implication of claim type: If the patent is still in force, generic entry risk is driven by whether the proposed ANDA formulation can demonstrate PK non-infringement (or a carve-out) against the specific nicotinic-acid/nicotinuric-acid exposure windows, not only by bioequivalence to a reference listed drug.

How many patents cover intermediate-release nicotinic acid in the US, and how does US 6,818,229 compare with adjacent niacin formulation patents?

What can be concluded from the claim set provided

The patent is clearly designed to cover a class of intermediate-release niacin products that generate:

• Tmax ~ 5.6–6 hours, and
• specific Cmax/AUC combinations for nicotinic acid and, in several tiers, for nicotinuric acid.

Without the broader US patent list (family members, continuations, related assignees, and Orange Book listing mappings), the count of patents “covering intermediate-release nicotinic acid” cannot be stated from your inputs.

What generic entry risks exist for intermediate-release niacin tablets with once-daily dosing?

Risk is claim-window specific

An ANDA or 505(j) pathway product would face infringement arguments tied to:

• the dose strength it markets (100 mg, 375 mg, 500 mg, 750 mg, 1000 mg tier relevance),
• whether its clinical PK meets the Cmax/Tmax/AUC bounds, and
• whether it is an oral tablet and dosed once daily.

Design-around opportunities that follow directly from the claim math

Products can potentially reduce infringement risk by:

• shifting Tmax away from the ~5.6–6 hour band, or
• shifting Cmax outside the stated ranges (for example, below claim lower bounds or above upper bounds where range-based),
• shifting AUC outside the band, or
• introducing non-tablet or non-once-daily regimens (though those would typically require their own clinical development and may fail business targets).

What patent litigation affects US 6,818,229 and what settlements matter?

No litigation dockets or settlement terms are provided in the prompt. With no verified case list tied to this specific patent, a responsible litigation landscape cannot be produced here.

What is the Orange Book status of US 6,818,229 and which companies are challenging?

No FDA Orange Book mappings (listed drug, application numbers, patent codes, or listed expiration dates) are included in the prompt. Without those, the Orange Book status and Paragraph IV challengers cannot be accurately enumerated.

Which regulatory pathway issues are most relevant to intermediate-release niacin PK and hepatotoxicity claims?

PK-based claims intersect with ANDA bioequivalence evidence

For claims defined by Cmax/Tmax/AUC, ANDA litigation often focuses on:

• the clinical sampling schedule used to derive Cmax/Tmax/AUC,
• whether the ANDA study aligns with the measurement assumptions underlying the patent’s PK windows,
• whether the ANDA product’s systemic exposure falls inside the numeric boundaries.

Hepatotoxicity language creates an evidentiary pressure point

The safety limitation (“without causing drug-induced hepatotoxicity … require discontinuation”) can pull in:

• clinical trial hepatotoxicity end points,
• label warnings and postmarketing signals,
• and whether “discontinuation” is measured under the claim’s implied standard.

Scope summary by claim group (infringement checklist)

A product reading on US 6,818,229 (based on the claims you provided) must satisfy these constraints simultaneously:

1. Active ingredient: nicotinic acid
2. Regimen: once-a-day oral dosing
3. Dosage form: tablet (for claims 2,4,7,8,11–12,15–16,19–20,23–24,27–28)
4. Indication: hyperlipidemia
5. Safety outcome: no hepatotoxicity to a level requiring discontinuation
6. Intermediate-release PK fingerprint:
   • nicotinic acid: Cmax and AUC in the claim’s specified ranges (or mean points), with Tmax ~5.6–6 hours
   • nicotinuric acid: in the relevant tiers, Cmax/AUC ranges and Tmax ~5.6–6 hours

Key Takeaways

• US 6,818,229 is a PK-window-driven niacin formulation patent: “intermediate release” is enforced through Cmax/Tmax/AUC targets rather than through a specified manufacturing mechanism.
• Coverage is tiered by dose strength (≥100, ≥375, ≥500, ≥750, ≥1000 mg) with distinct PK windows for nicotinic acid and sometimes nicotinuric acid.
• Most practical infringement questions reduce to whether an accused once-daily niacin tablet meets the stated systemic exposure windows and whether hepatotoxicity is managed such that discontinuation is not required.
• Design-around is mathematically possible by shifting Cmax, AUC, or Tmax outside the claim windows; tablet/oncedaily constraints also narrow the field.

FAQs

1. What PK endpoints matter most for infringement of US 6,818,229?
   Cmax and AUC for nicotinic acid (and nicotinuric acid for the relevant tiers), with Tmax constrained to about 5.6–6 hours.

2. Does US 6,818,229 require a specific formulation technology?
   The provided claims do not recite polymer types or coating systems; they define scope through patient exposure and functional outcomes.

3. How do the claims treat different nicotinic acid dose strengths?
   The claim set uses different minimum dose thresholds (100/375/500/750/1000 mg) with corresponding PK bands.

4. Can a once-daily niacin product avoid infringement by changing Tmax?
   If Tmax is shifted outside the ~5.6–6 hour range in the relevant tier(s), it may avoid numeric claim limits.

5. What role does “no hepatotoxicity discontinuation” play in litigation?
   It is an outcome limitation that can become central to evidence and disputed clinical relevance, especially when PK windows are met but safety profiles differ.

References

1. US Patent 6,818,229 (provided claims text).

Drugs Protected by US Patent 6,818,229

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,818,229

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	289197
Australia	4751802
Australia	6348198