United States Patent 5,552,394: Claim Scope, Expiration, Orange Book Relevance, and Generic Entry Analysis

U.S. Patent No. 5,552,394 protects a contraceptive dosing method, not a new chemical entity or a stand-alone tablet composition. Its central limitation is a monophasic estrogen-progestin regimen administered for 23 to 25 consecutive days in a 28-day cycle, with a defined ethinyl estradiol-to-norethindrone acetate ratio and a reduced incidence of breakthrough bleeding after the first cycle. The patent is expired and creates no current U.S. blocking right.

The claim set is most closely aligned with low-dose, 24-day oral contraceptive products containing ethinyl estradiol and norethindrone acetate, including the clinical profile associated with Loestrin 24 Fe-type regimens.

What does U.S. Patent 5,552,394 protect?

The patent protects a method of administering a combined oral contraceptive to reduce breakthrough bleeding. The independent claim requires all of the following:

Limitation	Claim requirement
Therapeutic use	Female contraception
Clinical result	Reduced incidence of breakthrough bleeding after the first cycle
Regimen	Monophasic administration
Cycle structure	23 to 25 consecutive treatment days in a 28-day cycle
Estrogen	Equivalent to approximately 1 to 35 mcg ethinyl estradiol daily
Progestin	Equivalent to approximately 0.025 to 10 mg norethindrone acetate daily
Ratio	Estrogen-to-progestin weight ratio of at least 1:45
Calculation basis	Ethinyl estradiol compared with norethindrone acetate

The claims do not broadly cover every combined oral contraceptive containing estrogen and progestin. A potentially infringing product must satisfy the dosing, ratio, cycle, monophasic, and contraceptive-use limitations.

How does the claim hierarchy narrow patent coverage?

Claims 2 through 12 narrow claim 1 through dose, ratio, duration, or active-ingredient identity.

Claim	Additional limitation	Practical effect
1	Broad regimen with 1 to 35 mcg estrogen and 0.025 to 10 mg progestin; 23 to 25 days; ratio at least 1:45	Broadest method claim
2	Progestin equivalent to 0.5 to 0.75 mg norethindrone acetate	Narrow low-dose progestin subset
3	Ratio at least 1:50	More estrogen-heavy ratio than claim 1
4	Administration for 24 days	Covers a 24-active-day regimen
5	Estrogen is ethinyl estradiol	Removes broader estrogen alternatives
6	Progestin is norethindrone acetate	Removes broader progestin alternatives
7	Progestin equivalent to 0.5 to 1.5 mg norethindrone acetate	Broader progestin range than claim 2
8	Ratio at least 1:50	Ratio limitation without claim 7's dose restriction
9	Administration for 24 days	24-day regimen limitation
10	Estrogen is ethinyl estradiol	Species limitation
11	Progestin is norethindrone acetate	Species limitation
12	Estrogen up to 30 mcg ethinyl estradiol	Narrows the upper estrogen boundary

Claim 1 is the key commercial claim because it captures the general dosing concept. Claims 4 through 6 create the most commercially relevant nested position for a 24-day product containing ethinyl estradiol and norethindrone acetate.

What is the mathematical significance of the 1:45 and 1:50 ratios?

The ratio is calculated by weight as ethinyl estradiol divided by norethindrone acetate.

For example:

Daily dose	EE:NETA ratio	Meets 1:45?	Meets 1:50?
20 mcg EE / 1 mg NETA	1:50	Yes	Yes
30 mcg EE / 1 mg NETA	1:33.3	Yes	Yes
20 mcg EE / 0.75 mg NETA	1:37.5	Yes	No
20 mcg EE / 0.5 mg NETA	1:25	Yes	No
30 mcg EE / 1.5 mg NETA	1:50	Yes	Yes
35 mcg EE / 1 mg NETA	1:28.6	Yes	No

A ratio of at least 1:45 means the amount of norethindrone acetate cannot exceed 45 times the ethinyl estradiol amount when both are expressed in the same units. A ratio of at least 1:50 is more restrictive because it permits no more than 50 parts of progestin for each part of estrogen. In practical terms, the claim language uses a ratio that distinguishes low-estrogen, relatively higher-progestin regimens from the claimed balance.

The 20 mcg ethinyl estradiol/1 mg norethindrone acetate combination satisfies the 1:50 limitation exactly. The 30 mcg/1 mg combination exceeds the ratio threshold and therefore also satisfies it.

What formulations are protected by U.S. Patent 5,552,394?

The patent claims a method of use rather than a tablet formulation. It does not expressly require:

A particular tablet excipient;
An iron-containing placebo;
A specific salt or crystal form;
A particular dissolution profile;
A specific package;
A branded product;
A particular manufacturing process.

A product can practice the claimed method even if its tablet composition differs from the reference product, provided the administered active ingredients and regimen meet the claim limitations.

The claims are therefore distinct from formulation patents that protect:

Extended-release matrices;
Enteric coatings;
Specific tablet layers;
Stabilized hormone combinations;
Iron-containing inactive tablets;
Packaging or calendar-blister systems.

A generic manufacturer could avoid a formulation patent by using a different excipient system, but that would not necessarily avoid a method-of-use claim if the generic labeling directs the same 24-day contraceptive regimen.

How strong is the patent estate for ethinyl estradiol and norethindrone acetate?

The patent estate represented by the provided claims is commercially focused but legally narrow in several respects.

Strengths

The claims combine multiple limitations that correspond to a specific commercial regimen:

Monophasic dosing;
23 to 25 active treatment days;
A 28-day cycle;
Low-dose ethinyl estradiol;
Norethindrone acetate;
A defined weight ratio;
A breakthrough-bleeding outcome.

The combination of these limitations can make literal infringement easier to establish against a product that reproduces the same branded regimen. The nested claims also provide fallback positions if a broader claim is challenged.

Weaknesses

The patent does not claim the active ingredients generally. It does not claim all oral contraceptives, all 24-day regimens, or all products containing ethinyl estradiol and norethindrone acetate.

Potential noninfringement positions include:

Use of a different progestin;
A nonmonophasic regimen;
Fewer than 23 or more than 25 consecutive active days;
A 21-day regimen;
A 28-day regimen with a different active-to-placebo structure;
A dose ratio outside the claimed range;
Labeling that does not direct the claimed method;
A product that does not rely on the claimed breakthrough-bleeding method.

The clinical-result language, "reduced incidence of breakthrough bleeding after the first cycle," also creates a potential claim-construction issue. The claim does not state the comparator, numerical reduction, patient population, or statistical threshold. A court would need to determine whether the phrase is merely a statement of intended result or a substantive method limitation.

When did U.S. Patent 5,552,394 lose exclusivity?

U.S. Patent 5,552,394 is expired. Its enforceable patent term ended years ago under the applicable U.S. patent-term rules. The patent therefore cannot support a current injunction against a generic manufacturer or a new Paragraph IV certification directed to an unexpired patent.

The patent issued on September 3, 1996. Because the patent was issued before the modern patent-term framework was fully reflected in later practice, the term analysis depends on the application’s filing and priority chain, any terminal disclaimer, and any adjustment recorded by the U.S. Patent and Trademark Office. Those issues are historical rather than commercially operative because the patent is no longer enforceable.[1]

Milestone	Date or status
U.S. patent number	5,552,394
Issue date	September 3, 1996
Subject matter	Contraceptive dosing method
Current status	Expired
Current blocking effect	None
Current Paragraph IV significance	None against this patent

What is the Orange Book status of U.S. Patent 5,552,394?

The patent is relevant to the historical Orange Book landscape for combined oral contraceptives containing ethinyl estradiol and norethindrone acetate. Orange Book listing status is tied to an approved drug application and the patent information submitted by the NDA holder. A method-of-use patent may be listed when it claims an approved method of using the drug under the FDA’s patent-listing rules.[2]

The commercial relevance of the patent would have depended on whether:

The patent was listed against the relevant NDA;
The listed use appeared in the approved labeling;
A generic applicant sought approval for that use;
The applicant filed a Paragraph IV certification;
The NDA holder initiated infringement litigation within the statutory period.

Because the patent has expired, its historical Orange Book listing does not create present approval delay or a current 30-month stay. FDA approval of a generic product is no longer blocked by this patent.[2]

What Paragraph IV challenges and litigation affected the patent?

A Paragraph IV certification would have been relevant only while the patent was listed and unexpired. A generic applicant could certify that the patent was invalid, unenforceable, or would not be infringed by the proposed product. If the NDA holder or patent owner sued within 45 days, FDA approval could have been stayed for up to 30 months under the Hatch-Waxman framework.[3]

The claims create several potential historical Paragraph IV positions:

The proposed product does not use 23 to 25 consecutive active days;
The product is not monophasic;
The estrogen-to-progestin ratio falls outside the claimed range;
The labeling does not instruct the claimed method;
The clinical-result language is not met;
The patent is invalid for anticipation or obviousness;
The claims are indefinite because the breakthrough-bleeding limitation lacks an objective standard;
The patent is unenforceable based on conduct during prosecution.

No current litigation exposure arises from Patent 5,552,394 itself because the patent is expired. Any historical suit involving a related NDA, continuation, formulation patent, or later method-of-use patent would need to be analyzed separately. A later patent cannot extend the term of Patent 5,552,394, although it can create an independent barrier.

Does the patent create biosimilar risk?

No meaningful biosimilar issue exists. Ethinyl estradiol and norethindrone acetate are small-molecule active ingredients, and products containing them are approved through abbreviated new drug application or conventional NDA pathways rather than the biosimilar pathway under section 351(k) of the Public Health Service Act.

The relevant competitive threat is generic substitution, not biosimilar substitution. FDA approval depends on pharmaceutical equivalence, bioequivalence, labeling, and applicable patent certifications.[4]

Which products are most exposed to the historical claim scope?

The highest historical exposure applied to products with the following profile:

Product characteristic	Exposure
Monophasic product	High
20 mcg ethinyl estradiol	High
1 mg norethindrone acetate	High
24 active tablets in a 28-day cycle	High
1:50 EE-to-NETA ratio	High
21 active tablets	Lower or outside the stated cycle limitation
Different progestin	Outside claims 5, 6, 10, and 11
Triphasic or multiphasic dosing	Potentially outside the monophasic limitation
30 mcg EE/1 mg NETA	Within the ratio limitations
20 mcg EE/0.5 mg NETA	Within 1:45 but outside 1:50

A generic product with the same active ingredients and a 24-day regimen would have faced the strongest historical method-of-use risk. After expiration, that risk became irrelevant unless a separate patent covered the product.

How does this patent compare with formulation and manufacturing patents?

Patent 5,552,394 is weaker than a formulation patent for blocking a product architecture because it does not require a particular tablet design. It is stronger as a historical product-specific method patent when the generic label copied the protected regimen.

Patent category	What it protects	Relevance today
Method-of-use patent	Dosing regimen and clinical use	Expired for Patent 5,552,394
Formulation patent	Tablet composition or delivery system	Depends on separate patent term
Manufacturing patent	Process or intermediate	May affect supply chain, not necessarily product sale
Packaging patent	Calendar pack or administration system	Usually narrower and design-aroundable
Regulatory exclusivity	FDA approval-based period	Separate from patent term

Manufacturing or formulation patents could theoretically have imposed independent constraints during the commercial life of the product. They would not revive or extend the expired claims of Patent 5,552,394.

What generic launch scenarios existed?

Three principal launch scenarios were available during the patent’s active term.

Paragraph III certification

A generic applicant could acknowledge the patent and defer approval until expiration. This was the lowest litigation-risk route but delayed market entry.

Paragraph IV certification

A generic applicant could challenge validity, enforceability, or infringement. A timely patent suit could trigger the 30-month stay, with launch depending on litigation outcome, settlement terms, or expiration of the stay.

Section viii carve-out

If the patent covered a method of use that the generic applicant did not seek to market, the applicant could attempt to remove the protected use from its labeling. This strategy was difficult where the patented regimen was central to the approved product’s labeling and dosage instructions.[3]

Once the patent expired, an ANDA applicant no longer needed to address it as a blocking unexpired patent. The competitive focus shifted to bioequivalence, commercial manufacturing, distribution, and any separate unexpired patents.

What licensing deals and settlement issues matter?

The provided claims do not establish a licensing agreement, royalty obligation, or settlement. Patent ownership and licensing rights must be determined from assignment records, recorded licenses, court settlements, and agreements involving the relevant NDA holder.

An expired patent cannot support a continuing exclusionary royalty based solely on patent rights unless a separate contractual obligation survived expiration. A settlement involving other patents could remain commercially relevant, but it would not make Patent 5,552,394 enforceable again.

Key Takeaways

Patent 5,552,394 is a method-of-use patent for female contraception.
The core regimen is monophasic estrogen-progestin treatment for 23 to 25 consecutive days in a 28-day cycle.
The claims focus on ethinyl estradiol, norethindrone acetate, dose ranges, and a minimum 1:45 weight ratio.
Claims 4 through 6 most closely target a 24-day regimen containing ethinyl estradiol and norethindrone acetate.
A 20 mcg ethinyl estradiol/1 mg norethindrone acetate regimen meets the 1:50 ratio limitation.
The patent does not claim a chemical entity, tablet excipient system, packaging format, or manufacturing process.
The patent is expired and has no current U.S. blocking effect.
Current generic risk depends on separate unexpired formulation, manufacturing, packaging, or method-of-use patents.
Biosimilar analysis is not applicable because these are small-molecule contraceptive products.
Historical Paragraph IV and Orange Book issues were relevant during the patent’s active term but do not create present exclusivity.

Frequently Asked Questions

Does Patent 5,552,394 cover Loestrin 24 Fe?

Its claim structure is consistent with a 24-day low-dose ethinyl estradiol/norethindrone acetate contraceptive regimen. Whether it covered a specific product depended on the approved labeling, listed patent information, and the product’s exact dosage instructions.

Does a 21-day birth-control regimen infringe Patent 5,552,394?

A 21-day regimen would generally fall outside the express 23-to-25-consecutive-day limitation in claim 1, assuming the product is administered as a 21-day regimen and no separate theory of infringement applies.

Does 30 mcg ethinyl estradiol and 1 mg norethindrone acetate meet the patent ratio?

Yes. The ratio is 30 mcg to 1,000 mcg, or 1:33.3. That satisfies the claimed minimum ratio of 1:45 and the narrower 1:50 ratio limitation.

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

A different progestin would avoid the specific norethindrone acetate limitations in claims 6 and 11. It could still require analysis under claim 1 if the substitute progestin is equivalent to norethindrone acetate within the claim’s scope.

Can an expired method-of-use patent block FDA approval?

No. An expired patent does not impose a current Orange Book stay or prevent approval based on that patent. Separate unexpired patents or regulatory exclusivities can produce different results.

References

United States Patent and Trademark Office. (1996). U.S. Patent No. 5,552,394: Method of contraception.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations (Orange Book).
21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.
U.S. Food and Drug Administration. (2024). Guidance for industry: Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA.

Details for Patent: 5,552,394

Summary for Patent: 5,552,394