United States Drug Patent 6,958,326: Scope, Claims, Expiration, and Patent Landscape

U.S. Patent No. 6,958,326 covers estrogen-cyclodextrin granules, particularly ethinyl estradiol complexed with beta-cyclodextrin and combined with drospirenone. The principal commercial relevance was oral contraceptive formulations such as Yasmin and related drospirenone/ethinyl estradiol products. The patent was granted on October 25, 2005, and its 20-year patent term expired in 2021, subject to any applicable patent-term adjustment or extension. It is no longer an unexpired U.S. exclusivity barrier.[1][2]

The patent has three claim groups:

Composition claims directed to stable estrogen-cyclodextrin granules.
Method claims directed to improving estrogen stability through complexation and granulation.
Manufacturing claims directed to liquid granulation and controlled granulate humidity.

The commercial concept is narrow in technology but broad in chemical alternatives. It targets the stability problem associated with low-dose estrogens, especially ethinyl estradiol, in combination oral contraceptive tablets.

What does U.S. Patent 6,958,326 protect?

The independent claims require a specific combination of structural and functional elements.

Claim group	Required elements	Principal limitation
Claim 1	Estrogen-cyclodextrin complex in a granulated preparation; optional excipients	At least 90% of initial estrogen remains after 12 months at 40°C/75% RH; essentially free of PVP
Claim 6	Complex formation followed by granulation	Method must improve estrogen stability and be essentially free of PVP
Claim 7	Loading complex and excipients into granulator; applying liquid; granulating and drying	Granulate relative humidity must not exceed 60% at 20°C to 40°C
Claims 2-5	Estrogen and complex concentration limitations	Includes ethinyl estradiol and beta-cyclodextrin ranges
Claims 8-11	Process and humidity limitations	Humidity thresholds fall to 55%, 45%, 40%, and related subranges
Claims 12-26	Composition species and physical characteristics	Excipients, estrogen identity, progestogen, antioxidant, micronization, particle size
Claims 27-32	Method and process species	Excipient, estrogen, PVP, and fluidized-bed granulation limitations

The word "comprising" makes the composition claims open-ended. A product can contain additional excipients or active ingredients and still fall within the claims if all required elements are present.

How broad are the composition claims?

Claim 1 is the principal composition claim. It requires:

A granulated preparation;
A complex between an estrogen and a cyclodextrin;
Optional excipients;
At least 90% estrogen recovery after 12 months at 40°C and 75% relative humidity; and
A formulation essentially free of polyvinylpyrrolidone, commonly known as PVP or povidone.

The claim does not require ethinyl estradiol specifically. Claims 13-16 expand the relevant chemical classes to include:

Ethinyl estradiol;
Estradiol;
Estradiol sulfamates;
Estradiol valerate;
Estradiol benzoate;
Estrone;
Estrone sulfate;
Alpha-, beta-, and gamma-cyclodextrin; and
Alkylated or acylated cyclodextrin derivatives.

The claim is therefore broad at the genus level but narrower in practical enforcement. A claimant would need to establish both the presence of the estrogen-cyclodextrin complex in a granulated preparation and compliance with the stability limitation.

What ethinyl estradiol and beta-cyclodextrin ratios are covered?

Claims 4 and 5 narrow the composition to ethinyl estradiol and beta-cyclodextrin. They require the estrogen to constitute:

Approximately 5% to 20% by weight of the ethinyl estradiol-beta-cyclodextrin complex under claim 4; or
Approximately 8% to 15% by weight under claim 5.

Claim 17 separately recites an estrogen-to-cyclodextrin molar ratio of approximately 2:1 to 1:10. These are not interchangeable measurements. The percentage limitations are weight-based, while claim 17 is molar.

This distinction matters in product testing. A formulation could satisfy one ratio limitation but not another depending on the molecular weights, degree of cyclodextrin substitution, and assay method.

Does the patent cover drospirenone and ethinyl estradiol products?

Yes, dependent claims 18-23 expressly contemplate estrogen compositions containing a second active ingredient, including a progestogen. The listed progestogens include drospirenone, levonorgestrel, norgestrel, gestodene, dienogest, cyproterone acetate, norethisterone, norethisterone acetate, desogestrel, and 3-keto-desogestrel.

Claims 21-23 are directed to drospirenone, including micronized drospirenone at approximately 0.4% to 20% by weight.

A drospirenone/ethinyl estradiol tablet could therefore fall within the dependent claims if it also contains:

An ethinyl estradiol-beta-cyclodextrin complex;
The complex in a granulated preparation;
The claimed stability profile;
The claimed excipient and PVP conditions; and
Where applicable, micronized drospirenone in the recited concentration.

The presence of drospirenone alone does not establish infringement. The cyclodextrin complex and granulation architecture are central limitations.

What stability requirement does claim 1 impose?

Claim 1 requires that at least 90% by weight of the initial estrogen content remain after 12 months at 40°C and 75% relative humidity.

This is a functional limitation, not merely a statement of intended use. The relevant product would need to be tested under the specified accelerated stability conditions. The following factors would affect claim analysis:

The initial assay value used as the baseline;
The analytical method and degradation-product specification;
Whether the test is performed on the granulated preparation or finished dosage form;
Whether the temperature and humidity are continuously maintained;
Whether "estrogen" means total estrogen, intact active ingredient, or a specific assay peak; and
Whether the test result is evaluated batch-by-batch or as an average.

The limitation gives the claim a technical boundary but also creates proof and claim-construction issues. A challenger could contest whether the test protocol is sufficiently defined or whether the patent specification enables the full scope of all estrogen and cyclodextrin combinations.

What process steps are protected?

Claim 7 protects a liquid granulation process with four core steps:

Loading the estrogen-cyclodextrin complex, optional active ingredients, and excipients into a granulator;
Applying a liquid;
Granulating and drying; and
Producing granules with relative humidity not exceeding 60% at 20°C to 40°C.

Claims 9-11 create stricter humidity embodiments:

Claim	Maximum relative humidity
Claim 7	60%
Claim 9	55%
Claim 10	45%
Claim 11	40%

Claim 32 specifies fluidized-bed granulation. The process claims could have been relevant even where a finished product was difficult to characterize, because infringement could be based on manufacturing records, batch parameters, process validation documents, or technical discovery.

Claim 8 is commercially important because it requires the active complex and any additional active agents to be provided individually rather than premixed with excipients. This limitation may distinguish direct-loading processes from premix-based granulation.

How does the PVP limitation affect infringement?

PVP is a central negative limitation.

Claims 1 and 6 require the composition to be "essentially free" of PVP. Claim 28 permits PVP at no more than 2% by weight in the process context.

This creates two different potential design-around routes:

Use no PVP or only a trace amount, but avoid another required element such as the estrogen-cyclodextrin complex or stability result.
Use PVP above the permitted threshold where the applicable claim requires the composition to be essentially free of PVP.

PVP alone does not necessarily avoid every claim. A process could still face claim 7 exposure if it meets the process steps and humidity limitation, while claim 28 would become relevant to the permitted PVP amount.

The phrase "essentially free" is fact-dependent. Its construction would likely turn on the specification, examples, manufacturing tolerances, and whether PVP is intentionally added or present as a contaminant or carryover material.

What formulations and excipients are protected?

Claim 12 identifies the principal excipient classes:

Starch;
Cellulose;
Hydroxypropylcellulose;
Hydroxypropylmethylcellulose; and
Maltodextrin.

Claim 25 adds antioxidant-containing formulations. Claim 26 requires a mean granule particle size of at least approximately 100 micrometers.

These limitations create multiple formulation layers:

Technical feature	Patent relevance
Cyclodextrin complex	Core drug-delivery and stability element
Granulation	Required by the independent composition and process claims
PVP exclusion	Important negative limitation
Listed cellulose or starch excipients	Dependent-claim narrowing feature
Antioxidant	Dependent composition feature
Mean particle size of at least 100 µm	Physical-property limitation
Fluidized-bed granulation	Process-specific limitation
Granulate RH at or below 40%	Narrowest humidity embodiment

A formulation using an alternative binder, direct compression, roller compaction, spray drying, or a non-granulated cyclodextrin system could avoid some dependent claims. That conclusion would not automatically resolve the independent claims because claim 1 does not limit the excipient to the listed materials.

When did U.S. Patent 6,958,326 lose exclusivity?

Event	Date or status
U.S. patent grant	October 25, 2005
Patent term basis	20 years from the relevant U.S. nonprovisional filing date, subject to adjustment
Expected statutory expiration	2021
Current status	Expired; no current patent exclusionary period
Current Paragraph IV exposure	None against this expired patent
Current biosimilar relevance	None

Patent term is governed principally by 35 U.S.C. §154. A terminal disclaimer, patent-term adjustment, or other prosecution event can alter the final expiration date, but the patent is no longer an enforceable future barrier in the ordinary generic-launch analysis.[2]

The patent should be distinguished from later patents covering drospirenone products, tablet compositions, polymorphs, manufacturing processes, or specific commercial products. Expiration of the '326 patent does not establish that every related patent has expired.

What was the Orange Book status of Patent 6,958,326?

The patent's likely regulatory significance arose from its relationship to branded drospirenone/ethinyl estradiol oral contraceptives. Orange Book-listed patents can require an ANDA applicant to certify under Paragraph III or Paragraph IV, depending on the patent's status and expiration date.[3][4]

Because the '326 patent has expired:

It cannot support a current Paragraph III delay;
It cannot create a current 30-month stay based on a new Paragraph IV notice;
It cannot independently block an ANDA launch;
Its historical listing does not extend the term of related patents; and
Any current launch analysis must focus on unexpired Orange Book patents and regulatory exclusivities for the specific reference-listed drug.

The Orange Book is product-specific. A patent may have been listed for one reference product without being listed for every drospirenone or ethinyl estradiol product.[3]

Which companies challenged related drospirenone products?

Generic competition to Yasmin, Yaz, and related products involved companies including Barr Pharmaceuticals, Watson Pharmaceuticals, Teva, Sandoz, and other ANDA applicants. Historical litigation focused on the broader patent estate for drospirenone/ethinyl estradiol products, including composition and product-specific patents.

The important analytical point is that a generic challenger may have litigated a related patent without litigating the '326 patent. A Paragraph IV case against one patent does not establish that all patents in the same family or product estate were invalidated.

The '326 patent is now expired, so historical litigation has no current blocking effect. Any settlement restrictions tied specifically to this patent would ordinarily have no remaining patent-term leverage after expiration, although contractual provisions can require separate review.

What litigation and settlement issues affected this patent estate?

The relevant litigation questions are:

Was the '326 patent listed for the particular reference product?
Was it asserted against the ANDA applicant?
Was the patent dismissed, invalidated, disclaimed, or settled?
Did a settlement contain a launch date earlier than patent expiry?
Did the settlement cover only the patent or the broader product portfolio?
Did later patents replace its commercial blocking function?

For current diligence, the patent's expiration makes validity litigation economically secondary. The principal residual value is historical: it may explain delayed generic entry, settlement economics, or formulation choices used in legacy products.

No current biosimilar risk exists because the covered products are small-molecule oral medicines, not biologics. FDA biosimilar competition under the Public Health Service Act is therefore not the relevant pathway. Generic competition proceeds through the ANDA framework under the Federal Food, Drug, and Cosmetic Act.[5]

How strong was the patent estate?

The patent had meaningful historical coverage because it combined composition, method, and manufacturing claims.

Strength factor	Assessment
Product coverage	Moderate to strong where the commercial product used the claimed complex and granulation
Chemical breadth	Broad due to multiple estrogen and cyclodextrin alternatives
Stability limitation	Useful technical distinction, but creates testing and proof burdens
PVP limitation	Clear design-around target, subject to construction of "essentially free"
Process coverage	Potentially valuable where manufacturing records establish humidity and granulation conditions
Dependent claims	Stronger technically but narrower commercially
Current enforceability	None after expiration
Current licensing value	Primarily historical or know-how related

The strongest historical position likely arose where a product used all of the following: ethinyl estradiol, beta-cyclodextrin, granulation, low residual humidity, listed excipients, micronized drospirenone, and no meaningful PVP.

The weakest claims from an enforcement perspective are those requiring proof of accelerated stability without a fully standardized testing protocol or those relying on ambiguous terms such as "essentially free."

What generic launch scenarios exist today?

The '326 patent does not create a present U.S. launch barrier. A generic manufacturer can generally pursue:

Direct-compression tablets without an estrogen-cyclodextrin granulate;
Granulated formulations using no cyclodextrin;
Alternative estrogen stabilization systems;
Formulations using a different excipient architecture;
Products with a different granulation endpoint;
Products that do not meet the claimed stability result; or
Products governed by other expired or unexpired patents in the relevant product estate.

The remaining risks are regulatory and portfolio-specific rather than tied to the '326 patent. These include bioequivalence, inactive-ingredient compatibility, dissolution, impurity control, labeling, and any unexpired patents listed for the particular reference-listed drug.

What is the geographic coverage of the patent?

U.S. Patent 6,958,326 provided rights only in the United States. Foreign counterparts, if granted, would have required separate national filings and would have had separate expiration, opposition, renewal, and litigation histories.

The U.S. expiration does not establish freedom to operate in:

The European Union;
The United Kingdom;
Canada;
Japan;
Australia;
Brazil; or
Other national markets.

For a global launch, the relevant family members must be assessed by country. European patent rights can also be affected by unitary patent elections, national validation, supplementary protection certificates, and national revocation proceedings. Those issues do not extend the U.S. patent term.

Key Takeaways

U.S. Patent 6,958,326 covers stable granulated estrogen-cyclodextrin compositions and their manufacture.
The core commercial embodiment is ethinyl estradiol complexed with beta-cyclodextrin, potentially combined with micronized drospirenone.
Claim 1 requires at least 90% estrogen retention after 12 months at 40°C/75% RH and an essentially PVP-free composition.
Claim 7 covers liquid granulation with controlled granulate humidity, with dependent claims reaching 40% RH.
The patent's claims are technically broad but commercially dependent on proving the cyclodextrin complex, granulation, stability, and PVP limitations.
The patent expired in 2021 and is not a current U.S. generic or biosimilar barrier.
Historical litigation involving Yasmin, Yaz, or related products should not be treated as proof that this specific patent was asserted or invalidated.
Current freedom-to-operate analysis must focus on later patents, product-specific Orange Book listings, and jurisdiction-specific rights.

FAQs

Is Patent 6,958,326 a formulation patent or a process patent?

It is both. Claims 1-5 and 12-26 primarily cover compositions. Claims 6-11 and 27-32 cover stability-improvement and granulation processes.

Does every ethinyl estradiol tablet infringe this patent?

No. The tablet must contain the claimed estrogen-cyclodextrin complex in a granulated preparation and satisfy the applicable stability and PVP limitations. Conventional ethinyl estradiol tablets without that structure would not meet the core claim elements.

Does using PVP automatically avoid the patent?

No. PVP may avoid claims requiring an essentially PVP-free composition, but the process claims must be analyzed separately. Claim 28 expressly addresses PVP at concentrations of no more than 2% by weight.

Can the expired patent still affect a generic product filing?

It can remain relevant to historical patent certifications, portfolio analysis, and technical design decisions, but it cannot independently delay a current launch after expiration.

Does the patent cover estrogen implants, patches, or injectable products?

The claims are directed to granulated pharmaceutical preparations and their manufacture. Non-granulated transdermal, implantable, or injectable products would generally fall outside the express architecture of the claims.

References

U.S. Patent No. 6,958,326. (2005). Pharmaceutical compositions comprising an estrogen and a cyclodextrin. United States Patent and Trademark Office.
35 U.S.C. §154. (2024). Contents and term of patents; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
21 C.F.R. §314.53. (2024). Submission of patent information.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and generic drug approvals.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	00610135	Dec 20, 2000

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	032205	⤷ Start Trial
Austria	311204	⤷ Start Trial
Australia	1941802	⤷ Start Trial
Australia	2002219418	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,958,326

Summary for Patent: 6,958,326