US Patent 8,617,597: Claim Scope, Drug Product Coverage, and Patent Landscape

US Patent 8,617,597 protects a narrowly defined combination oral contraceptive tablet containing micronized drospirenone, ethinyl estradiol, and an alkaline-earth-metal salt of 5-methyl-(6S)-tetrahydrofolic acid, commonly called levomefolate. The independent claim is a formulation-and-performance claim. A product must satisfy the quantitative composition limits, dissolution requirements, and 12-month stability requirement to fall within literal claim 1.

The claim is commercially relevant to products corresponding to Bayer's drospirenone/ethinyl estradiol/levomefolate products, including formulations marketed under the Beyaz and Safyral brands. Patent claims alone do not establish current Orange Book listing, enforceability, expiration, or litigation status.

What drug product does US 8,617,597 protect?

Claim 1 covers a tablet core containing all of the following:

Required element	Claim limitation
Drospirenone	3 mg, micronized
Ethinyl estradiol	0.02 mg or 0.03 mg
Microcrystalline cellulose	25-36 wt% of tablet-core weight
Lactose monohydrate	52-63 wt% of tablet-core weight
Folate compound	0.42-0.49 mg of an alkaline-earth-metal salt of 5-methyl-(6S)-tetrahydrofolic acid
Drospirenone dissolution	At least 85% dissolved within 30 minutes
Folate dissolution	At least 85% dissolved within 30 minutes
Folate stability	At least 90% remains after 12 months at 25°C and 60% relative humidity
Dosage form	Tablet core

The claim does not protect drospirenone or ethinyl estradiol as chemical compounds. It protects a specific pharmaceutical composition and tablet architecture.

The use of "comprising" makes the claim open-ended. A composition may contain additional excipients or active ingredients unless another claim limitation excludes them. A competitor cannot avoid claim 1 merely by adding an unclaimed excipient.

How broad is independent claim 1?

Claim 1 is technically narrow but commercially meaningful. It combines precise composition ranges with functional performance requirements.

Composition limitations

The claim requires both excipient percentages to be calculated against the total tablet-core weight. The limitation is not based on the weight of the complete coated tablet. A coating therefore should not affect the claimed percentage calculation, provided the percentages are measured against the core.

The excipient ranges are:

Microcrystalline cellulose: 25-36 wt%
Lactose monohydrate: 52-63 wt%

These ranges create a substantial formulation fingerprint. A generic manufacturer using materially different filler levels may have a non-infringement position even if it uses the same active ingredients and strengths.

The folate range is also narrow:

0.42-0.49 mg

The commonly used calcium levomefolate amount in this product class is approximately 0.451 mg, which falls within the claimed range.

Active-ingredient limitations

Claim 1 requires 3 mg of micronized drospirenone. A product containing non-micronized drospirenone would not literally satisfy that limitation, although particle-size characterization and the doctrine of equivalents could become relevant in litigation.

The claim permits either:

0.02 mg ethinyl estradiol; or
0.03 mg ethinyl estradiol.

This allows the claim to cover both lower- and higher-strength ethinyl estradiol versions if all other requirements are met.

Functional dissolution limitations

The claim requires at least 85% dissolution of both drospirenone and the folate salt within 30 minutes. The tests are analyte-specific:

Component	Medium	Apparatus and conditions
Drospirenone	Water	USP XXIX Paddle Method II, 37°C, 50 rpm
Levomefolate salt	0.03% aqueous ascorbic acid solution adjusted to pH 3.5 with 0.05 M phosphate buffer	USP XXIX Paddle Method II, 37°C, 50 rpm

The two dissolution thresholds are separate. Satisfactory drospirenone dissolution does not cure failure of the folate dissolution requirement, and vice versa.

The test conditions are material claim limitations. A product that passes under a different medium, pH, agitation speed, or sampling protocol may not establish literal compliance with claim 1. Conversely, infringement testing would likely focus on the specified conditions rather than a general statement that the tablet is "immediate release."

Stability limitation

The tablet must retain at least 90% of the claimed folate amount after:

12 months;
25°C;
60% relative humidity;
storage in a closed container.

This limitation creates a substantial evidentiary burden. A patent owner would need validated assay data showing the retained amount of the folate salt. A generic applicant could challenge infringement by demonstrating that its formulation does not meet the stability threshold under the claimed conditions.

What do claims 2 through 11 add?

The dependent claims create narrower positions around the estrogen form, folate form, excipient profile, and finished dosage form.

Claim	Additional limitation	Commercial significance
2	Ethinyl estradiol is in an estrogen-beta-cyclodextrin complex	Covers complexed estrogen formulations
3	Ethinyl estradiol is micronized	Covers micronized free ethinyl estradiol
4	Estrogen-beta-cyclodextrin complex is micronized	Narrowest estrogen particle/formulation limitation
5	Folate is the calcium salt	Targets calcium levomefolate products
6	Calcium salt is crystalline	Excludes amorphous or non-crystalline forms from literal scope
7	Calcium salt is Type I crystalline form	Strongest solid-state limitation
8	No vitamin B12	Prevents avoidance by interpreting the claim around a B12-containing folate composition
9	Less than 2 wt% PVP	Limits the binder profile
10	Tablet is coated	Covers a coated dosage form
11	Tablet is film-coated	Narrower coating limitation

Claim 7 is particularly important for solid-state control. A competitor using calcium levomefolate Type II, an amorphous form, or another polymorph may avoid literal infringement of claim 7, but would still need to assess claims 1 and 5.

Claim 8 is unusual because claim 1 is open-ended. Claim 8 narrows the product by excluding vitamin B12, while leaving other additional ingredients permissible.

What formulations are protected by US 8,617,597?

The patent's strongest commercial coverage is directed to tablets with the following profile:

Drospirenone at 3 mg in micronized form.
Ethinyl estradiol at 0.02 mg or 0.03 mg.
Calcium levomefolate at approximately 0.451 mg.
Microcrystalline cellulose and lactose monohydrate within the stated weight ranges.
Rapid dissolution of both hormone and folate components.
Folate stability under long-term controlled storage.
Optional coating, including a film coating.
Optional micronization or cyclodextrin complexing of ethinyl estradiol.
Optional crystalline Type I calcium levomefolate.
Less than 2% PVP and no vitamin B12 under dependent claims 8 and 9.

The patent therefore has greater relevance to a near-copy formulation than to all drospirenone contraceptive products.

Does the patent cover Beyaz and Safyral?

Beyaz and Safyral are the principal commercial products that map most closely to the claimed active-ingredient combination.

Product	Drospirenone	Ethinyl estradiol	Folate	Relationship to claim 1
Beyaz	3 mg	0.02 mg	Calcium levomefolate	Strong product-profile overlap
Safyral	3 mg	0.03 mg	Calcium levomefolate	Strong product-profile overlap
Yaz	3 mg	0.02 mg	None	Does not satisfy folate limitation
Yasmin	3 mg	0.03 mg	None	Does not satisfy folate limitation

The marketed strengths align with the alternative ethinyl estradiol amounts in claim 1. The folate requirement distinguishes the claimed products from Yaz and Yasmin.

Whether a particular marketed tablet satisfies the particle-size, excipient-percentage, dissolution, stability, PVP, or Type I crystal-form limitations requires product-specific technical evidence.

How strong is the patent estate for this formulation?

The patent is strongest against a generic that copies the reference product's formulation and manufacturing controls. Its strength declines as a competitor changes the following variables:

Filler ratios.
Folate salt or solid form.
Drospirenone particle size.
Ethinyl estradiol presentation.
Binder concentration.
Dissolution profile.
Packaging and stability profile.
Tablet-core composition.

The independent claim has several cumulative limitations. A challenger can seek non-infringement based on any missing limitation, but the claim's open-ended structure prevents simple avoidance by adding ingredients.

Primary strength factors

Covers both 0.02 mg and 0.03 mg ethinyl estradiol.
Covers the commercially important 3 mg drospirenone strength.
Uses a specific calcium-levomefolate-compatible formulation.
Includes performance requirements that may correspond to the reference product.
Extends to coated and film-coated tablets through dependent claims.

Primary weakness factors

Narrow excipient ranges.
Required micronized drospirenone.
Required rapid dissolution under defined methods.
Required 12-month folate stability.
Type I crystal-form limitation appears only in a dependent claim.
No claim, on the supplied text, to a broad method of contraception or treatment.

What generic entry risks exist?

A generic applicant could pursue several design-around paths.

Excipient design-around

The most direct path is changing microcrystalline cellulose or lactose monohydrate outside the claimed ranges. Because both ranges are explicit, a formulation with 24% microcrystalline cellulose or 64% lactose monohydrate would have a potential literal non-infringement argument, subject to the actual tablet-core calculation and other asserted claims.

Folate design-around

Potential alternatives include:

A different alkaline-earth-metal salt.
A different crystalline form.
An amorphous form.
A folate amount outside 0.42-0.49 mg.
A formulation containing a different folate species.

These alternatives may avoid claims 5 through 7, but they would still need to address claim 1 if the product uses an alkaline-earth-metal salt within the claimed amount and satisfies the remaining limitations.

Estrogen design-around

A generic could use non-micronized ethinyl estradiol or avoid the beta-cyclodextrin complex. That may avoid claims 2 through 4. It would not necessarily avoid claim 1, which does not expressly require micronized ethinyl estradiol.

Performance design-around

A product that fails the claimed dissolution or stability criteria may avoid literal infringement. This strategy has regulatory consequences because the ANDA product generally must demonstrate pharmaceutical equivalence and comparable performance to the reference product.

PVP and vitamin B12

Claim 9 can be avoided by using at least 2% PVP, although that may affect manufacturability and dissolution. Claim 8 can be avoided by including vitamin B12, but doing so does not avoid claim 1, which is open-ended and does not itself prohibit B12.

What Paragraph IV issues would apply?

A generic applicant seeking approval before patent expiration would typically evaluate whether to:

Certify that the patent is invalid or not infringed under Paragraph IV.
File a Paragraph III certification and defer approval until patent expiration.
Omit a patented method of use, if the relevant patent claims only a method.
Use a formulation design-around.

For this patent, a Paragraph IV position would likely focus on one or more of:

Anticipation or obviousness of the excipient combination.
Obviousness of combining drospirenone, ethinyl estradiol, and levomefolate.
Lack of written description or enablement for the full ranges and functional requirements.
Failure of the accused product to meet the dissolution or stability limitations.
Non-infringement based on particle size, folate form, or tablet-core percentages.

A Paragraph IV notice can trigger Hatch-Waxman litigation and a 30-month stay of FDA approval under the applicable statutory framework, subject to the patent's listing and the timing of the NDA holder's response. The supplied claims do not identify any particular ANDA filer, notice letter, district-court action, settlement, or launch date.

What is the Orange Book status of US 8,617,597?

The patent number and claim text do not establish whether US 8,617,597 is currently listed in the FDA Orange Book, whether it was delisted, or whether an applicable pediatric or regulatory exclusivity period remains. Orange Book listing is an FDA regulatory record separate from the patent document itself.[1]

For a drug-product patent, relevant Orange Book questions include:

Whether the patent was submitted for Beyaz, Safyral, or another NDA.
Whether FDA accepted the patent as a formulation or composition patent.
The listed expiration date.
Whether the listing covers the approved strength, dosage form, or formulation.
Whether an ANDA applicant has submitted a Paragraph IV certification.

The claims are directed to a tablet composition, which is the type of subject matter commonly evaluated for product-patent listing. The claims do not themselves establish that FDA accepted the patent for listing.

What is the patent expiration date?

A precise expiration date cannot be derived from the supplied claims. It requires the patent's earliest effective nonprovisional priority date, any terminal disclaimer, patent-term adjustment, patent-term extension, and relevant USPTO continuity data.

The controlling framework is generally a 20-year term measured from the earliest effective U.S. nonprovisional filing date, subject to statutory adjustments.[2] The issued patent date, December 31, 2013, is not the expiration date.

A business assessment should distinguish among:

Patent term expiration.
FDA regulatory exclusivity.
Orange Book-listed expiration.
Terminal disclaimers.
Pediatric exclusivity.
Any later-issued continuation or divisional patents.

What patent litigation and settlement agreements affect the product?

The supplied information identifies no specific litigation docket, ANDA challenger, consent judgment, or settlement agreement. Patent 8,617,597 should be analyzed with the full family and related product patents because commercial exclusivity may depend on multiple patents covering:

The active combination.
Calcium levomefolate solid forms.
Tablet formulations.
Manufacturing processes.
Dissolution control.
Methods of contraception or folate supplementation.
Packaging and stability.

A single patent may be non-infringed or invalidated without eliminating all generic-entry barriers. Conversely, a later patent may have limited practical value if it is not listed or if its claims are difficult to assert against an ANDA product.

How does this patent compare with broad contraceptive patents?

US 8,617,597 is narrower than a basic compound patent and narrower than a broad method-of-use patent.

Patent category	Typical subject matter	Relative position of US 8,617,597
Compound patent	Drospirenone or ethinyl estradiol molecule	Narrower
Combination patent	Drospirenone plus ethinyl estradiol	More formulation-specific
Formulation patent	Excipients, particle size, dissolution, stability	Direct category
Solid-form patent	Calcium levomefolate polymorph	Partly covered through claims 6 and 7
Method-of-use patent	Contraception or treatment method	Not apparent from supplied claims
Manufacturing patent	Granulation, compression, coating, or process controls	Not apparent from supplied claims

The patent's commercial value depends on whether the reference product uses the claimed formulation and whether an ANDA applicant can obtain approval without reproducing the claimed tablet-core characteristics.

Key Takeaways

US 8,617,597 is a tablet-composition patent, not a broad drospirenone or ethinyl estradiol compound patent.
Claim 1 requires 3 mg micronized drospirenone, 0.02 or 0.03 mg ethinyl estradiol, 0.42-0.49 mg of an alkaline-earth-metal levomefolate salt, and specified microcrystalline cellulose and lactose ranges.
The claim also requires separate 30-minute dissolution thresholds and 12-month folate stability.
Claims 5 through 7 focus on calcium levomefolate, crystallinity, and Type I crystal form.
Claims 8 through 11 address the absence of vitamin B12, PVP concentration, coating, and film coating.
Beyaz and Safyral have the closest commercial profile to the claimed composition.
The most credible generic design-arounds involve excipient ratios, folate form, particle size, dissolution behavior, and stability.
The patent claims do not establish current Orange Book status, exact expiration, litigation status, Paragraph IV activity, or settlement terms.
Commercial freedom to operate requires review of the complete patent family, Orange Book records, FDA exclusivity data, and ANDA litigation history.

FAQs

Does US 8,617,597 cover Yaz?

No. Yaz does not contain the claimed 5-methyl-(6S)-tetrahydrofolic acid salt. It therefore does not satisfy claim 1 as supplied.

Does the patent require calcium levomefolate?

Claim 1 covers an alkaline-earth-metal salt of 5-methyl-(6S)-tetrahydrofolic acid. Claim 5 narrows that scope to the calcium salt. A non-calcium alkaline-earth-metal salt could potentially fall within claim 1 but outside claim 5.

Can a generic avoid the patent by using a different tablet coating?

Not necessarily. Claim 1 is directed to the tablet core, and claim 10 covers a coated tablet. Changing the coating will not avoid claim 1 if the core satisfies every limitation.

Does adding vitamin B12 avoid claim 1?

No. Claim 8 excludes vitamin B12, but claim 1 is open-ended and does not prohibit it. Adding B12 may avoid claim 8 while leaving claim 1 potentially applicable.

Is Type I calcium levomefolate required in every claim?

No. Type I crystalline calcium levomefolate is required only by claim 7. Claim 1 is broader as to the folate salt and does not require the Type I crystal form.

References

U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation guidance.
U.S. Patent No. 8,617,597. (2013). Pharmaceutical composition comprising drospirenone, ethinylestradiol, and a salt of 5-methyl-(6S)-tetrahydrofolic acid. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Beyaz prescribing information.
U.S. Food and Drug Administration. (n.d.). Safyral prescribing information.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Hlthcare	BEYAZ	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022532-001	Sep 24, 2010	AB	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Bayer Hlthcare	SAFYRAL	drospirenone; ethinyl estradiol; levomefolate calcium	TABLET;ORAL	022574-001	Dec 16, 2010	AB	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Details for Patent: 8,617,597

Which drugs does patent 8,617,597 protect, and when does it expire?

Summary for Patent: 8,617,597