United States Drug Patent RE38253: Claim Scope, Expiration, Orange Book Status, and Generic Risk

U.S. Patent RE38,253 covered a 23- or 24-day active oral contraceptive regimen followed by five or four placebo or pill-free days. Its principal commercial relevance was the 24/4 regimen used by Yaz, containing 20 micrograms of ethinylestradiol and 3 mg of drospirenone. The patent also recited alternative estrogen and progestin combinations, including 17β-estradiol and cyproterone acetate.

The patent is expired. Its practical blocking effect on generic entry ended in 2014, subject to the precise terminal-date treatment applied in the applicable patent and regulatory records. RE38,253 did not create a current biosimilar issue because it covers small-molecule oral contraceptive products, not biologics.

What does U.S. Patent RE38,253 protect?

RE38,253 protects a packaged oral contraceptive product with three defining elements:

A specified number of active dosage units, either 23 or 24.
An estrogen-progestin combination in each active unit.
Five or four placebo units, or labeling instructions, corresponding to the 23- or 24-day active phase.

The core regimen is therefore a combination-product and dosing-schedule claim. It is broader than a claim limited to a single branded product because it covers multiple estrogen and progestin alternatives and permits either placebo pills or instructions for pill-free days.

The commercial center of gravity is the 24 active tablets plus four placebo tablets configuration:

Element	Claimed commercial configuration
Active tablets	24
Placebo tablets or pill-free instructions	4
Estrogen	20 micrograms ethinylestradiol
Progestin	Drospirenone, generally 3 mg
Cycle structure	24 active days followed by 4 non-active days
Principal branded association	Yaz

The claim text supplied contains apparent transcription or publication-format problems, including inconsistent drospirenone ranges and the phrase “gestadene gestodene.” Those errors do not change the principal legal concept: the patent claims an extended active-tablet regimen with a short hormone-free interval and specified estrogen/progestin combinations.

How are the RE38,253 claims structured?

Claim 1: Broad combination-product claim

Claim 1 is the principal broad claim. It requires:

23 or 24 active dosage units;
an estrogen selected from a specified 17β-estradiol range or 0.020 mg of ethinylestradiol;
a gestagen selected from the listed drospirenone or cyproterone acetate ranges; and
five or four placebo units, or equivalent instructions, following the active units.

The claim covers both physical packaging and informational indicia. A product could potentially satisfy the “placebo” element through inactive tablets or through labeling that instructs the patient to take no dosage unit during the specified interval.

The claim is not limited to a particular tablet shape, blister configuration, excipient system, manufacturer, or trade name. Its relevant limitations are pharmaceutical composition, dosage, tablet count, and sequence.

Claims 2 through 4: Ethinylestradiol combinations

Claim 2 narrows claim 1 to ethinylestradiol as the estrogen.

Claims 3 and 4 then divide the covered progestins:

Claim 3: ethinylestradiol plus cyproterone acetate.
Claim 4: ethinylestradiol plus drospirenone.

Claim 4 is the most commercially important dependent claim because it maps directly onto the Yaz-type active combination.

Claim 5: Low-dose equivalence formulation

Claim 5 recites a 23- or 24-unit regimen containing:

20 micrograms of ethinylestradiol, or an equivalent 17β-estradiol dose; and
a gestagen dose equivalent to 75 micrograms of gestodene.

This claim introduces a relative potency or dose-equivalence limitation. Such language can create infringement and validity disputes because “equivalent” may require technical evidence concerning progestational activity, assay methodology, and the relevant comparison standard.

The claim also appears to use ranges that differ materially from claim 1. The supplied version lists 2.5 to 3.0 mg of drospirenone and 1 to 2 mg of cyproterone acetate, which is consistent with a Yaz-like drospirenone dose but not with the lower range reproduced in claim 1.

Claim 6: 23 active units and five placebo days

Claim 6 narrows the product to:

23 active dosage units; and
five placebo pills or five days without an active dosage unit.

This is a 23/5 regimen rather than the better-known 24/4 Yaz regimen.

Claim 7: Specific 23/5 Yaz-type regimen

Claim 7 is the narrowest and most commercially specific claim. It recites:

23 active units;
20 micrograms of ethinylestradiol in each active unit;
drospirenone or cyproterone acetate at a dose equivalent to 75 micrograms of gestodene; and
five placebo pills or five non-dosing days.

A product with 24 active tablets and four placebo tablets would not satisfy the literal 23-active-unit limitation in claim 7, although it could fall within other claims.

Claims 8 through 10: 17β-estradiol combinations

Claim 8 narrows the estrogen to 17β-estradiol.

Claims 9 and 10 specify:

17β-estradiol plus cyproterone acetate; or
17β-estradiol plus drospirenone.

These claims expand the technical scope beyond Yaz because Yaz uses ethinylestradiol rather than 17β-estradiol.

What dosage forms and regimens fall within RE38,253?

The claims principally cover oral solid dosage products, although the claims do not appear to require a specific tablet manufacturing process. A product can be exposed if it uses the claimed active and inactive-unit sequence even when it differs in:

tablet color;
blister-card design;
excipients;
coating;
packaging artwork;
tablet shape; or
trade name.

The patent’s schedule limitations are central. A standard 21 active/7 placebo product is outside the literal 23/5 and 24/4 configurations. A 28-day pack with 24 active tablets and four inactive tablets is within the commercial profile addressed by the patent, assuming the active ingredients and doses satisfy the applicable claim.

A continuous-use product with no placebo interval presents a different analysis. It would generally lack the claimed four- or five-day inactive phase, unless the product labeling still directs the claimed sequence.

Regimen	Likely relationship to RE38,253
21 active / 7 placebo	Outside the central 23/5 and 24/4 schedule
23 active / 5 placebo	Directly targeted by claims 1, 5, 6 and 7
24 active / 4 placebo	Directly targeted by claim 1 and related dependent claims
24 active / 4 pill-free days	Covered if the claim’s instruction alternative is satisfied
28 active / 0 placebo	Generally outside the claimed schedule
Continuous dosing	Generally outside the literal placebo-period limitation
24 active / 4 placebo with different excipients	Potentially covered if composition and dose limitations are met

When did RE38,253 lose exclusivity?

RE38,253 expired in 2014. The patent could not provide a current barrier to generic entry after expiration.

The patent’s effective term is governed by the term of the original patent from which the reissue issued. A reissue does not ordinarily restart the patent term. The relevant term also depends on the patent’s priority and filing history, any terminal disclaimer, and any patent-term adjustment or extension reflected in USPTO records. The commercial Orange Book significance of RE38,253 ended when its listed patent term expired.

Milestone	Significance
Original patent family filing	Established the term and priority framework
Reissue issuance	Corrected or revised the original patent; did not create a new 20-year term
FDA listing	Provided notice of the patent for the listed drug
Paragraph IV litigation	Delayed or threatened ANDA approval before expiration
2014 expiration	Removed the patent’s blocking effect

RE38,253 should therefore be treated as a historical exclusivity asset, not a live U.S. enforcement asset.

What was the Orange Book status of RE38,253?

RE38,253 was associated with the U.S. regulatory and patent estate for drospirenone/ethinylestradiol oral contraceptive products, particularly the Yaz product family. The relevant listed-drug sponsor was Bayer-related, with the product marketed under Bayer and affiliated Schering entities during the relevant period.

The patent’s Orange Book function was to identify a patent that an ANDA applicant had to address through one of the statutory certifications:

Paragraph I: no patent information listed;
Paragraph II: patent has expired;
Paragraph III: applicant will wait until expiration; or
Paragraph IV: patent is invalid, unenforceable, or will not be infringed.

Before expiration, an ANDA applicant making a Paragraph IV certification could trigger litigation under the Hatch-Waxman Act. After expiration, the patent could be addressed through a Paragraph II certification or otherwise cease to delay approval.

The patent did not function as a current Orange Book barrier after its expiration. Any remaining regulatory exclusivity had to arise from another listed patent, new-product exclusivity, or a separate FDA statutory protection.

Which products were commercially exposed to RE38,253?

The patent most directly affected products using:

20 micrograms of ethinylestradiol;
approximately 3 mg of drospirenone;
24 active tablets; and
four placebo tablets.

The principal reference product was Yaz, also known in some markets as Yasmin 24/4 or under related Bayer product names depending on jurisdiction and formulation.

Other drospirenone/ethinylestradiol products require a separate claim analysis. Products such as Yasmin generally use a 21/7 schedule and therefore may avoid the schedule limitations even though they share the active ingredients. Products such as Gianvi, Ocella, Loryna, Nikki, and related generic or authorized-generic products more closely track the 24/4 structure.

A product can avoid literal infringement through a different regimen, but changing only branding or excipients would not ordinarily address the central claim limitations.

What other patents protected Yaz and drospirenone/ethinylestradiol products?

RE38,253 was one part of a broader patent estate. The commercially important landscape included at least four categories.

Composition patents

Composition patents covered the combination of drospirenone and ethinylestradiol, including pharmaceutical compositions, dosage strengths, and stability characteristics. U.S. Patent No. 6,787,531 was a key Bayer/Schering patent associated with drospirenone and ethinylestradiol products.

Composition claims can remain relevant even when a regimen patent expires. A generic applicant therefore had to evaluate both:

the chemical composition and dosage formulation; and
the 24/4 administration schedule.

Regimen patents

RE38,253 focused on the number of active units and the reduced hormone-free interval. This was distinct from a patent claiming only the active ingredients.

Regimen patents are commercially valuable when the branded product’s differentiation depends on a nonstandard dosing cycle. Their strength depends on whether the dosage schedule produces an unexpected clinical or pharmacokinetic benefit and whether the prior art disclosed the same active-unit and placebo-unit arrangement.

Formulation and manufacturing patents

Other patent families may cover:

micronized or particle-size-controlled drospirenone;
dissolution or bioavailability characteristics;
solid dispersion or wet-granulation processes;
tablet coating;
stability improvements;
impurity control;
packaging systems; and
manufacturing methods.

These patents can create residual barriers after an active-ingredient or regimen patent expires. They do not automatically block an ANDA product that uses a different manufacturing route and does not practice the claimed formulation.

Regulatory and label patents

A label patent can target a particular indication, dosing instruction, or patient population. For oral contraceptives, the principal label-related risk is usually lower than in therapeutic products with multiple patented indications because contraception is the central use. A generic applicant may use a section viii statement or carve out a patented indication when the FDA and patent claims permit it.

How strong was the RE38,253 patent estate?

The patent was commercially strong before expiration because it aligned closely with a marketed product configuration. Its practical value came from the combination of:

a defined 24/4 schedule;
a commercially important drospirenone/ethinylestradiol product;
broad coverage of placebo pills or pill-free instructions; and
dependent claims focused on the commercially relevant ingredients.

Its vulnerabilities were also identifiable.

Claim-construction vulnerabilities

The claim set contains drafting and transcription irregularities involving:

inconsistent numerical ranges;
“gestadene gestodene” terminology;
alternative dose descriptions;
“selected from” constructions; and
equivalence language.

Those issues could generate disputes over claim meaning, antecedent basis, enablement, and written description. A court would likely construe the claims in light of the issued patent, prosecution history, specification, and any reissue certificate rather than relying on a secondary transcription.

Obviousness risk

The relevant prior art likely included:

conventional 21/7 oral contraceptive regimens;
low-dose ethinylestradiol products;
drospirenone contraceptive compositions;
extended-cycle contraceptive schedules; and
clinical literature concerning shorter hormone-free intervals.

An accused generic could argue that combining known active ingredients with a 23/5 or 24/4 schedule was an obvious optimization. The patent holder could respond that the schedule produced unexpected reductions in follicular activity, breakthrough bleeding, or contraceptive-management advantages.

Infringement risk

Before expiration, a generic product closely matching 24 active tablets, four placebo tablets, 20 micrograms of ethinylestradiol, and approximately 3 mg of drospirenone presented a high literal-infringement risk. A product using a different regimen had a stronger noninfringement position, although other composition patents could remain relevant.

After expiration, infringement risk under RE38,253 became immaterial for U.S. market entry.

Which companies challenged the Yaz patent estate?

The Yaz patent estate was challenged through Hatch-Waxman ANDA litigation involving generic companies seeking approval for drospirenone/ethinylestradiol products. Publicly reported participants in the broader Yaz litigation and generic market included Barr Laboratories, Watson Laboratories, Teva, Mylan, Lupin, and related entities.

The principal legal mechanisms were:

Paragraph IV certifications;
patent-infringement complaints filed within the statutory window;
settlement agreements;
possible authorized-generic arrangements; and
delayed generic launch dates tied to patent expiration or settlement terms.

The exact patent challenged, settlement date, launch date, and product configuration must be analyzed separately for each ANDA. A challenge to a composition patent did not necessarily challenge RE38,253, and a settlement involving one patent did not necessarily resolve every patent in the estate.

What litigation and settlement issues affected generic launch?

Before expiration, litigation risk was concentrated in products that copied the marketed 24/4 regimen. A generic applicant could face:

infringement allegations based on the active ingredients;
separate allegations based on the 24/4 schedule;
formulation patent claims;
Orange Book stay consequences; and
settlement restrictions affecting launch timing.

The 30-month stay under Hatch-Waxman could delay final ANDA approval after timely patent litigation. That stay did not extend the patent term. Once the patent expired, FDA approval could proceed subject to unresolved patents, regulatory exclusivities, labeling requirements, and manufacturing approval.

Settlement terms in pharmaceutical patent cases can include:

a permitted entry date;
a license to manufacture or sell;
restrictions on authorized-generic supply;
launch rights tied to appellate outcomes; and
releases for specified patents or products.

A settlement should not be treated as an admission that the patent was valid or infringed. Its economic effect depends on the entry date and the scope of the release.

Was there biosimilar risk for RE38,253?

No. RE38,253 concerns an oral small-molecule combination product. The relevant competitors proceed through the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not through the biosimilar pathway under section 351(k) of the Public Health Service Act.

The competitive risks were therefore:

generic substitution;
authorized generics;
formulation design-arounds;
alternative active-tablet schedules; and
post-expiration price competition.

Biosimilar concepts such as reference biologic exclusivity, interchangeability, and biosimilar naming are not applicable.

How does RE38,253 compare with the main composition patents?

Issue	RE38,253	Drospirenone/ethinylestradiol composition patents
Primary subject	Dosing schedule and package	Active ingredients and formulation
Key limitation	23/5 or 24/4 sequence	Drospirenone plus ethinylestradiol
Product dependence	High dependence on marketed regimen	Higher dependence on formulation and dose
Design-around path	Change active/placebo schedule	Change formulation, process, or composition
ANDA relevance	Label and regimen analysis	Drug-product and formulation analysis
Current status	Expired in 2014	Must be assessed patent by patent
Biosimilar relevance	None	None

A generic company could avoid RE38,253 by using a noncovered schedule, but that would not necessarily avoid composition or manufacturing patents. Conversely, a product could practice the same active ingredients without infringing the regimen patent if it used a different active/placebo sequence.

What generic launch scenarios existed?

Before expiration, three principal launch strategies were available.

1. Paragraph IV challenge

The applicant could allege that RE38,253 was invalid, unenforceable, or not infringed. This created litigation exposure but could support an earlier launch if the patent was defeated or settled.

2. Noninfringing regimen

The applicant could seek approval for a product with a different active/placebo schedule. This approach reduced risk under RE38,253 but could affect therapeutic equivalence, labeling, physician acceptance, and commercial substitutability.

3. Post-expiration entry

The applicant could wait for patent expiration and enter with a product closely matching the reference product. This reduced patent litigation risk but sacrificed the commercial value of an earlier launch.

After 2014, the third scenario became the normal legal baseline for RE38,253, although other patents and regulatory requirements still required review.

What is the geographic coverage of RE38,253?

RE38,253 is a United States patent. Its enforceability and expiration had no direct legal effect in Europe, Canada, Japan, or other jurisdictions.

The same invention may have been pursued through a related international patent family, but foreign family members required separate analysis of:

national filing dates;
granted claims;
supplementary protection certificates;
pediatric extensions;
opposition or nullity proceedings;
local litigation; and
country-specific expiration dates.

A U.S. expiration did not establish worldwide freedom to operate. For a global launch, the 23/5 or 24/4 regimen, drospirenone/ethinylestradiol composition, and manufacturing process had to be cleared in each target market.

Key Takeaways

RE38,253 is a regimen and combination-product patent centered on 23/5 and 24/4 oral contraceptive schedules.
Its most commercially important embodiment is 24 active tablets containing 20 micrograms of ethinylestradiol and approximately 3 mg of drospirenone, followed by four placebo tablets.
Claims 2 through 4 narrow the invention to ethinylestradiol and specific progestins.
Claims 5 through 7 address dose equivalence and the narrower 23/5 configuration.
Claims 8 through 10 extend the claim set to 17β-estradiol combinations.
The patent expired in 2014 and is no longer a current U.S. barrier to generic entry.
The patent covered a small-molecule drug product, so biosimilar law is not relevant.
Historical generic risk arose from both the regimen patent and separate composition, formulation, and manufacturing patents.
A product could design around RE38,253 by changing the active/placebo schedule, but that would not necessarily avoid other members of the Yaz patent estate.
Foreign family members must be assessed independently.

Frequently Asked Questions

Does RE38,253 cover Yaz specifically?

It covers the principal 24/4 Yaz-type configuration when the product contains the claimed ethinylestradiol and drospirenone doses. The claims are broader than the Yaz brand because they include alternative estrogens, progestins, and regimen formats.

Does a 21/7 drospirenone contraceptive infringe RE38,253?

A conventional 21 active/7 placebo product generally does not satisfy the patent’s 23/5 or 24/4 active-to-placebo schedule limitations. Separate composition patents may still apply.

Can a generic use the same ingredients with 28 active tablets?

A 28-active-tablet product would generally avoid the literal 23/5 and 24/4 limitations, but it requires a separate analysis for composition, formulation, labeling, and other patent claims.

Did the reissue create a new patent term?

No. A reissue generally retains the original patent’s expiration framework. It does not ordinarily provide a new 20-year term calculated from the reissue date.

Is drospirenone itself protected by RE38,253?

The patent does not broadly claim drospirenone as a chemical entity. It claims drospirenone as an ingredient in specified oral contraceptive combinations and dosing schedules. Chemical, composition, formulation, and process protection must be analyzed separately.

References

U.S. Patent and Trademark Office. (2003). U.S. Patent No. RE38,253, Pharmaceutical preparation for contraception. Washington, DC: U.S. Department of Commerce.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information. https://www.uspto.gov/patents/laws/patent-term-calculator
U.S. Food and Drug Administration. (2006). Yaz prescribing information. Bayer HealthCare Pharmaceuticals.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Patent and Trademark Office. (2000). U.S. Patent No. 6,787,531, Pharmaceutical composition comprising drospirenone and ethinylestradiol. Washington, DC: U.S. Department of Commerce.
Federal Circuit. (2012). Bayer Schering Pharma AG v. Lupin, Ltd., 676 F.3d 1316.
Federal Circuit. (2013). Bayer Schering Pharma AG v. Watson Laboratories, Inc., 713 F.3d 1369.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	43 44 462	Dec 22, 1993

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	344038	⤷ Start Trial
Canada	2179728	⤷ Start Trial
China	100377713	⤷ Start Trial
China	1142185	⤷ Start Trial
China	1611222	⤷ Start Trial
Czech Republic	296387	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: RE38253