US Patent 6,720,004: Claim Scope, Expiration, Orange Book Relevance, and Valproate Patent Landscape

US Patent 6,720,004 covers once-daily oral hydrophilic matrix formulations containing divalproex sodium or another valproate compound. Its core limitations are polymer loading, controlled dissolution over 18 hours, and, for dependent claim 2, a lower steady-state fasting Cmax than twice-daily delayed-release divalproex sodium. The patent was directed to the formulation technology later associated with extended-release divalproex products, including Depakote ER.

The patent’s nominal term has expired. As a result, US 6,720,004 does not presently create an enforceable US patent barrier to generic entry. Its technical disclosure remains relevant for freedom-to-operate analysis, formulation design, and interpretation of related patents, but commercial risk now depends on other patents, regulatory exclusivities, trade secrets, and manufacturing know-how.

What does US Patent 6,720,004 cover?

The patent claims a controlled-release matrix formulation rather than a particular tablet strength, manufacturing process, brand, or therapeutic indication.

Core composition limitations

Claims 1 and 3 require:

Limitation	Claim 1	Claim 3
Active ingredient	Divalproex sodium	A valproate compound
Active loading	About 40% to about 80% w/w	About 40% to about 80% w/w
Polymer loading	About 20% to about 50% w/w	About 20% to about 50% w/w
Dosage concept	Oral, once-daily, hydrophilic matrix	Oral, once-daily, hydrophilic matrix
Release testing	Specified two-stage dissolution method	Same method, with broader release bands
Pharmacokinetic limitation	None in claim 1	None
Additional PK limitation	Claim 2 requires lower Cmax	None stated

The polymer Markush group includes polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, vinyl acetate copolymers, polysaccharides, polyethylene oxide, methacrylic acid copolymers, and maleic anhydride/methyl vinyl ether copolymers.

The wording in the supplied claim text contains apparent transcription errors, including “polyvinylpyrolidine,” “polyethyleine oxide,” “polyethylcine oxide,” and “sodium laurel sulfate.” The corresponding technical terms are generally understood to be polyvinylpyrrolidone, polyethylene oxide, and sodium lauryl sulfate. The issued patent should control in any legal claim construction analysis.

How broad are the independent claims?

Claim 1 is narrower in active-ingredient identity but narrower and more specific in dissolution performance. Claim 3 is broader because it covers “a valproate compound,” but its dissolution windows differ from claim 1.

Claim 1 scope

Claim 1 requires all of the following:

An oral hydrophilic matrix formulation.
Suitability for once-daily administration.
Divalproex sodium at approximately 40% to 80% w/w.
A listed polymer at approximately 20% to 50% w/w.
The specified dissolution method.
A release profile of:
- 15% to 27% at three hours;
- 44% to 69% at nine hours;
- 59% to 90% at 12 hours; and
- at least 88% at 18 hours.

A formulation outside any required limitation should not literally fall within claim 1. For example, a formulation with 35% divalproex sodium, no listed polymer, or less than 88% release at 18 hours would not satisfy the express claim language.

The use of “about” creates numerical tolerance and claim-construction issues. It does not eliminate the need to establish that a formulation falls reasonably within each claimed range. The boundary between 27% and 30% release at three hours, or between 69% and 70% at nine hours, could be important in a litigation setting.

Claim 3 scope

Claim 3 covers a broader active-ingredient category:

valproate compound rather than only divalproex sodium;
the same approximate active and polymer loading ranges;
the same general hydrophilic matrix architecture; and
a broader dissolution profile.

Its release requirements are:

Time point	Claim 3 requirement
3 hours	No more than about 30%
9 hours	About 40% to 70%
12 hours	About 55% to 95%
18 hours	At least 85%

Claim 3 is potentially broader at three and 18 hours than claim 1. It permits up to approximately 30% release at three hours and requires only 85% release at 18 hours. It is narrower or differently constrained at other time points because it imposes specific nine- and 12-hour ranges.

What does claim 2 add to the patent?

Claim 2 adds a pharmacokinetic limitation to claim 1. The claimed once-daily formulation must produce a statistically significantly lower Cmax than an enteric-coated delayed-release divalproex sodium tablet administered twice daily.

The comparison must be made:

at steady state;
in a fasting population;
against the specified twice-daily delayed-release comparator; and
using a statistical analysis showing a significant Cmax difference.

Claim 2 is not satisfied merely because a once-daily product has a lower measured Cmax in a single study. The relevant study design, comparator, fasting conditions, steady-state sampling, statistical test, and population characteristics would matter.

The limitation could narrow enforceability substantially because it creates an evidence-intensive infringement inquiry. A generic applicant or product developer could challenge the claim by disputing whether its product produces the required statistically significant Cmax relationship, although the claim’s comparison against a specified comparator may also permit reliance on clinical or bioequivalence data.

What dissolution test defines the claimed release profile?

The test uses a two-stage dissolution protocol:

Parameter	Claimed condition
Apparatus	USP Type 2 paddle
Paddle speed	100 rpm
Temperature	37 ± 0.5°C
Initial medium	500 mL of 0.1N hydrochloric acid
Initial duration	45 minutes
Subsequent medium	900 mL of 0.05 M phosphate buffer
Surfactant	75 mM sodium lauryl sulfate
Subsequent pH	5.5
Measurement period	Up to at least 18 hours

The test is central to the patent. The claims do not merely require “extended release” in a general pharmacological sense. They require defined release percentages at specific time points under a particular laboratory protocol.

This creates several practical issues:

Changing the dissolution apparatus, medium volume, pH, surfactant concentration, or paddle speed may produce materially different results.
A product could have a similar in vivo exposure profile but fall outside the claimed in vitro profile.
Conversely, a product designed around the claimed profile may create infringement risk even if its formulation uses a different excipient ratio within the listed ranges.
Batch-to-batch variability and assay methodology can affect whether a product is within an “about” range.

For technical due diligence, dissolution should be tested using the patent-specified protocol and independently verified against the issued claims.

What formulations are protected by US 6,720,004?

The patent is directed to hydrophilic matrix systems. These systems use water-soluble or water-swellable polymers to form a hydrated matrix through which valproate diffuses or from which the drug erodes over time.

The listed polymer categories include:

hydroxypropylmethyl cellulose;
hydroxypropyl cellulose;
methyl cellulose;
polyethylene oxide;
polyvinylpyrrolidone;
vinyl acetate copolymers;
polysaccharides;
methacrylic acid copolymers; and
maleic anhydride/methyl vinyl ether copolymers.

The claims do not require a particular grade, viscosity, particle size, compression force, tablet shape, coating, lubricant, binder, or manufacturing sequence. Those details may appear in the specification or related patents, but they are not express limitations in the supplied independent claims.

The claims also do not require:

a particular divalproex-to-valproic-acid ratio beyond the claimed active identity;
a specific dose, such as 250 mg, 500 mg, or 1,000 mg;
a specific tablet coating;
a particular indication;
a particular manufacturer;
a particular brand; or
a particular method of making the matrix.

The combination of broad polymer language and functional dissolution limitations gives the claims a mixed scope. They are broad across excipient selection but narrower across formulation performance.

When did US Patent 6,720,004 expire?

US Patent 6,720,004 was issued on April 13, 2004. Its ordinary US patent term was tied to the relevant nonprovisional filing date and ran for approximately 20 years, subject to any patent-term adjustment or other term calculation under 35 U.S.C. § 154.

Public patent records identify the patent as expired by the early 2020s, with the nominal term generally reported as ending on or about November 14, 2021. The patent is no longer a live US exclusivity right.

Event	Date
Priority development	2000
US nonprovisional filing	2001
Patent publication	2003
Patent issuance	April 13, 2004
Nominal term endpoint	Approximately November 14, 2021
Current enforceability	Expired

The expiration of US 6,720,004 removes this patent as a current basis for a US infringement action. It does not determine the status of continuation patents, divisional patents, foreign counterparts, or separately listed Orange Book patents.

What was the Orange Book status of US 6,720,004?

The Orange Book is the relevant FDA database for patents submitted by NDA sponsors for approved small-molecule drug products. It can list patents covering:

the active ingredient;
the formulation or composition;
a method of use; or
certain drug-device combinations.

US 6,720,004 was associated with the extended-release divalproex formulation patent landscape. Its relevance was principally formulation-based, not active-ingredient based. Divalproex sodium itself was an established active ingredient, and the patent did not create basic compound exclusivity over valproate.

Orange Book status should be assessed by product and NDA, not by patent number alone. A patent may have been listed for one NDA or dosage form and not another. FDA listing also does not establish that every claim is valid or infringed.

Because US 6,720,004 has expired, it should not presently block approval or launch of an otherwise approvable ANDA. Any current Orange Book analysis must focus on unexpired patents listed against the relevant extended-release divalproex NDA.

Which companies challenged the divalproex extended-release patent estate?

Generic competition for extended-release divalproex developed through the ANDA pathway. Potential challengers generally had to address:

expired or expiring formulation patents;
any still-listed formulation patents;
method-of-use patents, if applicable;
Paragraph IV certifications;
pediatric or other FDA exclusivities; and
product-specific bioequivalence requirements.

The central regulatory point is that divalproex sodium extended-release tablets are small-molecule products, not biologics. Biosimilar litigation and the Biologics Price Competition and Innovation Act do not govern this product. Generic applicants proceed under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

A Paragraph IV certification against an expired patent has no current commercial significance. A Paragraph IV certification against a live patent can trigger a patent infringement action and, under the Hatch-Waxman framework, a potential 30-month stay of approval. The expiration of US 6,720,004 eliminates that mechanism for this patent itself.

What patent litigation affected Depakote ER and generic divalproex?

The relevant disputes historically involved the broader Depakote and Depakote ER patent estate, including patents covering extended-release formulations and related product features. A complete litigation review must separate:

cases involving US 6,720,004;
cases involving other divalproex patents;
ANDA litigation against specific generic applicants;
settlement agreements; and
post-expiration commercial disputes.

US 6,720,004 should not be treated as equivalent to the entire Depakote ER estate. A generic applicant could avoid one patent while remaining exposed to another. Conversely, a patent may have been listed in the Orange Book but later invalidated, disclaimed, delisted, or allowed to expire.

No current enforceability attaches to US 6,720,004 after expiration. Historical litigation involving the patent may still matter for damages periods, claim construction, settlement interpretation, or antitrust analysis, but it does not create a forward-looking launch prohibition.

How strong was the patent estate for extended-release divalproex?

Strengths

The patent had several commercially useful characteristics:

It targeted once-daily administration, a clinically relevant product attribute.
It claimed both formulation composition and dissolution performance.
It covered multiple hydrophilic polymer classes.
It used pharmacokinetic language in claim 2 to connect in vitro design with lower peak exposure.
The release profile could be compared against generic product testing and development data.

Weaknesses

The patent also had material vulnerabilities:

The independent claims relied heavily on functional dissolution results.
The polymer Markush groups were broad and potentially vulnerable to prior-art and written-description arguments.
The numerical ranges included overlapping boundaries and “about” terminology.
Claim 2 depended on a specific pharmacokinetic comparison that could be difficult to prove consistently.
The claims did not require many manufacturing details that might distinguish the commercial product from prior art.
Divalproex extended-release technology was technically predictable enough to invite obviousness challenges based on matrix-formulation literature and earlier valproate disclosures.

The patent’s commercial value was highest before expiration, when a successful challenge could accelerate generic entry. Its current value is primarily historical and technical.

How does US 6,720,004 compare with other divalproex patent categories?

Patent category	Subject matter	Relevance today
Basic compound patents	Valproic acid or divalproex chemistry	Generally historical for this product
Matrix formulation patents	Polymer loading and dissolution profile	US 6,720,004 falls here; expired
Pharmacokinetic patents	Cmax, exposure, food effect, dosing interval	May matter if separately patented
Method-of-use patents	Epilepsy, bipolar disorder, migraine prevention	Product- and indication-specific
Manufacturing patents	Granulation, compression, coating, process controls	May create manufacturing barriers if unexpired
Trade secrets	Polymer grades, process parameters, scale-up controls	Potentially relevant after patent expiry
Regulatory exclusivity	FDA exclusivity linked to approval or supplements	Separate from patent term

The main residual barriers are therefore likely to be product-specific regulatory requirements, manufacturing know-how, and any separate unexpired patents rather than US 6,720,004.

What generic launch risks exist after expiration?

A generic launch relying on the expiration of US 6,720,004 would still require review of:

all currently listed Orange Book patents for the target NDA;
any unexpired formulation or method-of-use patents;
the ANDA’s patent certifications;
FDA exclusivity blocks;
formulation bioequivalence;
food-effect requirements;
dose proportionality;
dissolution method equivalence;
manufacturing scale-up; and
state or federal litigation unrelated to this patent.

The expired patent does not prevent a generic from using the same general hydrophilic matrix concept. It also does not guarantee that a particular generic formulation will pass FDA bioequivalence requirements. Extended-release products can face complex in vitro/in vivo correlation, food-effect, and alcohol-dose-dumping issues.

Does US 6,720,004 create biosimilar risk?

No. Divalproex sodium is a chemically synthesized small-molecule drug. The relevant competitors are generic manufacturers filing ANDAs, not biosimilar applicants filing under the Public Health Service Act.

The principal competitive questions are:

whether the generic matches the reference listed drug;
whether an applicant can establish bioequivalence;
whether any live Orange Book patent remains;
whether a Paragraph IV certification triggers litigation; and
whether a first-filer obtains 180-day generic exclusivity.

Are licensing deals associated with US 6,720,004 material to current entry analysis?

A license to an expired patent generally has limited forward-looking value unless it includes:

rights to related unexpired patents;
know-how or trade secrets;
manufacturing technology;
royalty obligations that survive patent expiration;
settlement restrictions; or
covenants governing future products.

Patent ownership and licensing history should be traced through the assignment records and relevant commercial agreements. The patent’s original assignee and the NDA sponsor may not be the same entity throughout the product’s commercial history. A license to US 6,720,004 alone would not ordinarily justify continued exclusion after expiration.

What geographic coverage did the patent provide?

US 6,720,004 provided rights only in the United States. Foreign counterparts, if any, had independent prosecution histories, claim scope, and expiration dates. A US patent could not block manufacture, sale, or use in Europe, Canada, Japan, or other jurisdictions unless corresponding national patents remained in force.

For global launch planning, the relevant analysis must separate:

US patent term;
European national or unitary rights;
Canadian patents;
Japanese patents;
emerging-market filings;
patent-term extensions;
supplementary protection certificates; and
local regulatory exclusivities.

The expiration of the US patent does not establish freedom to operate outside the United States.

Key Takeaways

US 6,720,004 covers once-daily hydrophilic matrix formulations of divalproex sodium or other valproate compounds.
Its principal limitations are 40% to 80% active ingredient, 20% to 50% listed polymer, and defined 18-hour dissolution behavior.
Claim 1 is narrower in active identity and release profile than claim 3.
Claim 2 adds a statistically significant lower steady-state fasting Cmax requirement against twice-daily delayed-release divalproex.
The patent was issued April 13, 2004 and expired by approximately November 14, 2021.
The patent no longer provides a current US barrier to generic entry.
It was a small-molecule formulation patent, not a biologic or biosimilar patent.
Current launch risk depends on other Orange Book patents, FDA exclusivities, ANDA certifications, bioequivalence, manufacturing know-how, and any surviving licenses or settlements.
Foreign patent rights must be reviewed separately from the US patent.
The issued patent text, not a transcription, controls the legal meaning of the claims.

FAQs

Is US 6,720,004 a patent on Depakote ER itself?

No. It is a formulation patent covering specified hydrophilic matrix compositions and dissolution profiles. It is not a basic patent on divalproex sodium.

Can a generic use the same polymer classes after US 6,720,004 expired?

Yes, expiration removes the patent-based prohibition in the United States. The generic must still satisfy FDA requirements and avoid any other unexpired patent rights.

Does the patent cover valproic acid alone?

Claim 3 uses the broader term “valproate compound,” while claim 1 specifically requires divalproex sodium. The precise scope depends on the issued claim language and construction of “valproate compound.”

Does matching the dissolution profile automatically create infringement?

No. Infringement requires satisfaction of every claim limitation. A matching release profile is important, but active identity, polymer content, dosage form, once-daily suitability, and the specified test conditions also matter.

Can the expired patent support a new Paragraph IV challenge?

No meaningful current challenge exists against an expired patent because its expiration removes the patent-based approval block. Paragraph IV strategy must target a currently listed and unexpired patent.

References

U.S. Patent No. 6,720,004, “Extended Release Formulation of Valproic Acid and Salts Thereof.” U.S. Patent and Trademark Office, issued April 13, 2004.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: The Orange Book. FDA.
U.S. Food and Drug Administration. (2023). Depakote ER prescribing information. AbbVie Inc.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process under section 505(j) of the Federal Food, Drug, and Cosmetic Act. FDA.
35 U.S.C. § 154. Patent term and adjustment.
21 U.S.C. § 355(j). Abbreviated applications for new drugs.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	021443	⤷ Start Trial
Austria	254907	⤷ Start Trial
Austria	275398	⤷ Start Trial
Australia	2002239260	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,720,004

Summary for Patent: 6,720,004