Details for Patent: 10,603,281

Which drugs does patent 10,603,281 protect, and when does it expire?

Patent 10,603,281 protects DROSPIRENONE and SLYND and is included in two NDAs.

This patent has sixty-nine patent family members in thirty-one countries.

Summary for Patent: 10,603,281

Title:	Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same
Abstract:	The present invention relates to pharmaceutical compositions and kits comprising pharmaceutical compositions, and methods for administering pharmaceutical compositions comprising active contraceptive drugs in a patient. Specifically, the pharmaceutical compositions may comprise progestogen-only contraceptive (“POC”), such as Drosphirenone.
Inventor(s):	Philippe Perrin, Jose Luis Velada, Dominique Drouin
Assignee:	Laboratorios Leon Farma SA
Application Number:	US16/415,599
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,603,281
Patent Claim Types: see list of patent claims	Use; Composition; Process; Dosage form;

United States Patent 10,603,281: Drospirenone Contraceptive Claims, Scope and Patent Landscape

US Patent No. 10,603,281 protects methods of contraception using an estrogen-free, orally administered drospirenone formulation. Its central limitations are a 2 mg to 6 mg drospirenone dose, defined excipient classes and concentration ranges, controlled drospirenone particle size, and either a dissolution or pharmacokinetic profile.

The patent is closely aligned with the commercial characteristics of Slynd, the 4 mg drospirenone-only oral contraceptive. The broadest claims are method-of-use claims rather than composition claims. A competing product can avoid literal infringement if it omits a required formulation, particle-size, dissolution, pharmacokinetic, or dosing limitation, although the practical risk depends on the product label, manufacturing process and evidence of induced infringement.

What patents protect drospirenone-only oral contraception under US 10,603,281?

US 10,603,281 has two independent claims:

Claim	Core protected subject matter	Key technical limitations
1	Contraceptive method using a drospirenone oral composition	2-6 mg drospirenone; specified binder, filler, glidant and lubricant; d50 of about 1-60 µm; no more than 50% dissolution at 30 minutes; no estrogen
13	Contraceptive method using a drospirenone oral composition	2-6 mg drospirenone; specified excipients; d50 of about 10-60 µm; fasting mean Tmax of 2.2-6 hours; mean Cmax below about 30 ng/mL; AUC0-tlast of at least 300 ng·h/mL; no estrogen

The patent does not claim every drospirenone-only contraceptive. It claims administration of a composition satisfying the recited formulation and performance limitations.

The term "comprising" makes the claims open-ended. A product may contain additional excipients or formulation components and still fall within the claim if it contains the required elements and satisfies the quantitative ranges.

How broad are the independent claims?

Claim 1: formulation and dissolution claim

Claim 1 requires all of the following:

1. A contraception method performed in a patient.
2. Daily administration.
3. A solid oral pharmaceutical composition.
4. Drospirenone in an amount of 2 mg to 6 mg.
5. A binder at 50.0% to 65.0% by weight.
6. A filler at 25.0% to 35.0% by weight.
7. A glidant at 0.2% to 6.0% by weight.
8. A lubricant at 0.2% to 0.6% by weight.
9. Drospirenone particles with a d50 of about 1 µm to about 60 µm.
10. No more than 50% dissolution within 30 minutes under the specified USP XXIII Paddle Method.
11. No estrogen.

The excipient lists are extensive. The binder list includes microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, starches, gums and polyvinyl pyrrolidone. The filler list includes lactose, anhydrous lactose, microcrystalline cellulose, starches, calcium salts, sugars, mannitol and sorbitol.

The claim is technically restrictive despite its broad wording. A competing tablet must satisfy the composition ranges and dissolution limitation simultaneously. A formulation that uses the same drospirenone dose but has a different dissolution profile, particle-size distribution or excipient ratio may fall outside literal claim 1.

Claim 13: pharmacokinetic claim

Claim 13 replaces claim 1's dissolution limitation with a pharmacokinetic profile. The product must produce, under fasting conditions:

• Mean Tmax of approximately 2.2 to 6 hours;
• Mean Cmax below approximately 30 ng/mL; and
• AUC0-tlast of at least 300 ng·h/mL.

Claim 13 also requires a narrower d50 range of about 10 µm to about 60 µm.

This claim creates a product-testing issue. Infringement analysis would likely require reliable pharmacokinetic evidence generated using a sufficiently comparable study design, dose, formulation, fasting protocol and subject population. Small changes in study conditions may affect Tmax, Cmax and AUC results.

What formulations are protected by US 10,603,281?

The patent specifically reaches formulations containing:

Component	Claimed amount	Exemplary materials
Binder	50.0%-65.0% by weight	Microcrystalline cellulose, starches, gums, hydroxypropyl cellulose, PVP
Filler	25.0%-35.0% by weight	Anhydrous lactose, lactose, microcrystalline cellulose, mannitol, starches
Glidant	0.2%-6.0% by weight	Silicon dioxide, talc, powdered cellulose, starches
Lubricant	0.2%-0.6% by weight	Magnesium stearate, calcium stearate, stearic acid, talc
Active ingredient	2-6 mg	Preferably about 4 mg drospirenone

Claim 26 narrows the formulation to microcrystalline cellulose as binder, anhydrous lactose as filler, silicon dioxide as glidant and magnesium stearate as lubricant.

Claim 27 recites an approximately 4 mg formulation containing:

• 4 mg drospirenone;
• 33.02 mg microcrystalline cellulose;
• 17.50 mg anhydrous lactose;
• 0.29 mg silicon dioxide; and
• 0.33 mg magnesium stearate.

The listed excipient amounts total approximately 51.14 mg, excluding any additional tablet components not expressly recited in that dependent claim. The quantitative ranges in claim 1 are calculated against the pharmaceutical composition as a whole, so product-by-product weight accounting is important.

How does the drospirenone particle-size limitation affect infringement?

Particle size is a major technical boundary in the patent.

Claim 1 requires a d50 of about 1 µm to about 60 µm. Claim 13 requires a d50 of about 10 µm to about 60 µm. Claim 7 adds:

• d90 below 100 µm; and
• d10 above 3 µm.

Claim 8 requires particles obtained by milling, crystallization, precipitation, sieving or a combination of those processes. Claim 9 identifies fluid energy mills, ball mills, rod mills, hammer mills, cutting mills and oscillating granulators.

A particle-size challenge would focus on:

• The measurement technique;
• The dispersion medium;
• Whether the measurement is volume-, mass- or number-based;
• The definition of d10, d50 and d90;
• Batch-to-batch variability;
• Whether agglomerates are measured as individual particles;
• The meaning of "about" in the asserted range.

The process limitation in claim 8 is narrower than the particle-size limitation alone. A formulation may satisfy a target d50 but raise a separate question about whether the particles were obtained through one of the expressly listed processes.

What dosing regimens are protected?

Claims 2 through 6 and 14 through 18 cover a 28-day regimen involving:

• Active treatment for 24 to 28 consecutive days;
• Up to four days without active drug;
• Approximately 24-hour intervals between active doses;
• Optional placebo tablets during the inactive interval.

The claims also address missed doses. They cover resuming administration after:

• One missed active dose taken as soon as possible and within about 24 hours; and
• Two or more non-consecutive missed active doses, with each missed dose taken as soon as possible and within about 24 hours.

Claims 3, 4, 15 and 16 narrow the regimen to placebo dosage units and tablet presentations. These claims may be relevant to a generic label that reproduces the branded product's 24 active plus 4 inactive tablet regimen and missed-dose instructions.

The regimen limitations are dependent. A product could potentially implicate claim 1 or claim 13 without practicing every 28-day, placebo or missed-dose limitation.

What method-of-use claims cover tolerability and bleeding outcomes?

Claims 20 through 25 cover asserted clinical advantages of the pharmacokinetic profile.

Claim	Additional limitation
20	Improved pharmacokinetics compared with combined oral contraceptives containing drospirenone
21	Delayed Tmax, reduced Cmax or reduced AUC0-tlast
22	Improved drospirenone tolerance compared with combined oral contraceptives
23	Reduced hyperkalemia, spotting or irregular bleeding
24	Improved bleeding profile compared with conventional progestogen-only contraceptives
25	Reduced unscheduled spotting or bleeding

These claims are difficult to assess solely from the product's ingredients. They depend on comparative pharmacokinetic or clinical evidence. A generic applicant could face a labeling issue if the proposed label includes the same comparative statements or clinical-use instructions.

Claims 20 through 25 may also be vulnerable to definiteness, written-description, enablement or inherency arguments depending on the prosecution history and the factual record. The claims use comparative and outcome-oriented language, while the underlying product must also satisfy the detailed formulation and PK limitations inherited from claim 13.

When does US 10,603,281 lose exclusivity?

The patent's standard term is generally measured from the earliest effective nonprovisional priority date, subject to patent-term adjustment and any applicable patent-term extension. The patent is associated with the drospirenone-only contraceptive product Slynd and was issued on March 31, 2020.

Public patent records should be used to confirm the effective expiration date, patent-term adjustment and any terminal disclaimer. The expiration date cannot be determined reliably from the issued patent number alone without the patent's priority and term data. [1]

The commercial exclusivity analysis must also separate:

• Patent expiration;
• FDA chemical exclusivity;
• Pediatric exclusivity;
• Regulatory review period extension;
• Later-issued formulation or method patents; and
• Any settlement or license affecting generic entry.

For Slynd, patent expiry is more important than biosimilar exclusivity because drospirenone is a small molecule and generic applicants use the ANDA pathway, not the biosimilar pathway.

What is the Orange Book status of US 10,603,281?

Slynd is an FDA-approved drospirenone-only oral contraceptive. The FDA-approved labeling describes 4 mg drospirenone tablets administered as 24 active tablets followed by four inactive tablets. [2]

Patent listing status must be confirmed in the current FDA Orange Book. An Orange Book listing can support a Paragraph IV notice against an ANDA applicant, but listing alone does not establish that every claim is infringed by every generic formulation. The FDA Orange Book generally identifies patents submitted by the NDA holder and does not resolve claim construction or validity.

The relevant regulatory distinction is:

Issue	Business significance
Orange Book listing	May trigger notice and a 30-month stay after a Paragraph IV filing
Patent expiry	Determines the ordinary end of enforceable patent rights
ANDA label	Can create induced-infringement exposure for method claims
Formulation design	Determines whether the generic product meets the structural limitations
Paragraph IV certification	Creates a potential litigation pathway before launch

Which companies are challenging Slynd patents?

A definitive list of challengers requires current FDA, PACER and district-court records. The supplied claims do not identify an ANDA applicant, Paragraph IV notice, litigation docket, settlement or license.

For this patent, the relevant challenger universe consists of generic manufacturers pursuing an ANDA for 4 mg drospirenone tablets. Their principal design-around options would include:

• Altering the binder or filler ratio;
• Using a lubricant outside the claimed range;
• Changing drospirenone particle-size distribution;
• Producing a dissolution profile above the claim 1 threshold;
• Producing a PK profile outside claim 13;
• Omitting the 24/4 regimen from the proposed label where legally permissible; or
• Pursuing a partial label that excludes patented methods.

A Paragraph IV challenge could attack validity based on prior art relating to drospirenone-only contraception, excipient ratios, particle-size control, dissolution behavior, pharmacokinetic targeting, clinical bleeding outcomes or obviousness-type combinations.

How strong is the patent estate for drospirenone-only contraception?

US 10,603,281 has meaningful commercial relevance because it combines a familiar active ingredient with unusually specific formulation and PK limitations.

Strengths

• It maps closely to a 4 mg drospirenone-only tablet.
• It includes both formulation and clinical-use limitations.
• The open "comprising" language permits additional excipients.
• Dependent claims cover common commercial elements, including microcrystalline cellulose, anhydrous lactose, silicon dioxide and magnesium stearate.
• The 24/4 regimen and missed-dose instructions may align with an approved product label.
• Particle-size and PK limitations can create manufacturing and testing burdens for ANDA applicants.

Vulnerabilities

• The independent claims are combination claims with many required limitations.
• Prior art may separately disclose drospirenone-only contraception, oral tablets, conventional excipients and particle-size reduction.
• The percentage ranges may be attacked as optimized routine formulation variables.
• PK limitations can be difficult to prove consistently across studies.
• Method claims require proof that the accused product is administered for contraception.
• A generic applicant may avoid infringement through formulation or labeling changes.
• The patent does not independently claim a composition without the contraception-method requirement.

The strongest practical enforcement position is likely against a product that reproduces the 4 mg tablet composition, particle-size profile, dissolution or PK behavior, and 24 active plus 4 inactive dosing instructions.

How does US 10,603,281 compare with older drospirenone patents?

Older drospirenone patents generally focused on combined oral contraceptives containing estrogen, particularly ethinyl estradiol, or on the chemical compound and earlier formulations. US 10,603,281 is differentiated by its estrogen-free method, drospirenone particle size, excipient architecture, dissolution behavior and targeted PK profile.

Patent category	Typical subject matter	Relevance to 10,603,281
Compound patents	Drospirenone and related steroid compounds	Primarily historical; generally less relevant to current product blocking rights
Combined contraceptive patents	Drospirenone plus estrogen	Separate from the estrogen-free claims
Slynd formulation patents	4 mg drospirenone tablet, excipients and particle size	Directly relevant
Slynd method patents	24/4 administration and tolerability or bleeding outcomes	Directly relevant where listed and unexpired
Manufacturing patents	Milling, crystallization and particle control	May create separate supply-chain restrictions
Regulatory exclusivity	FDA approval and statutory exclusivity	Separate from patent enforceability

What manufacturing and IP barriers affect generic entry?

A generic entrant must address more than the active ingredient. The principal technical barriers are:

1. Consistent drospirenone particle-size distribution.
2. Control of d10, d50 and d90 values.
3. Tablet excipient percentages within or outside the claimed ranges.
4. Dissolution testing under the specified paddle method.
5. Fasting PK performance.
6. Labeling for contraception and missed doses.
7. Ability to use a non-infringing manufacturing process.
8. Potentially separate patents covering formulation, process or dosing.

The most effective design-around may be a formulation that remains bioequivalent for FDA purposes but falls outside the claimed particle-size or excipient ranges. That approach requires careful coordination between formulation development, bioequivalence testing, patent certification and proposed labeling.

What generic launch risks exist?

Launch scenario	Patent risk	Commercial implication
Paragraph III certification	Acceptance of patent validity and noninfringement until expiry	Delayed but lower litigation risk
Paragraph IV certification	Immediate challenge to validity or infringement	Litigation likely if the patent is listed and unexpired
Section viii carve-out	Exclusion of patented method language	Depends on whether remaining label supports approval and marketability
Formulation design-around	Reduced literal infringement risk	May require new development and PK work
At-risk launch	Exposure to damages and injunction	High financial and operational risk
Authorized generic or license	Contractual access to protected product	Depends on deal terms and launch date

For a small-molecule oral contraceptive, biosimilar risk is not the relevant framework. The principal risk is ANDA-based generic entry, coupled with Orange Book patent litigation and potential state or federal induced-infringement claims.

What patent litigation and settlement issues matter?

The supplied record does not establish a current litigation or settlement involving US 10,603,281. A complete enforcement assessment requires the current docket, Orange Book listing data, Paragraph IV notices and any settlement filings.

The legally important questions are:

• Whether the patent is listed against the relevant Slynd NDA;
• Whether a generic applicant has certified Paragraph IV;
• Whether the NDA holder filed suit within 45 days;
• Whether a 30-month stay applies;
• Whether the asserted claims survived claim construction and validity challenges;
• Whether the parties entered a licensed or delayed-entry settlement;
• Whether the settlement includes a generic launch date, authorized-generic restrictions or supply terms.

Key Takeaways

• US 10,603,281 covers methods of contraception using estrogen-free oral drospirenone formulations.
• Claims 1 and 13 are the principal independent claims.
• Claim 1 relies on excipient percentages, particle size and dissolution.
• Claim 13 relies on particle size and fasting PK parameters.
• The patent is closely aligned with a 4 mg drospirenone-only product administered in a 24 active/4 inactive regimen.
• Claims 2-6 and 14-18 cover regimen, placebo and missed-dose instructions.
• Claims 20-25 target comparative PK, tolerability and bleeding outcomes.
• The patent is not a biosimilar barrier. Generic applicants would use the ANDA pathway.
• The principal design-around opportunities involve excipient ratios, particle-size distribution, dissolution, PK behavior and labeling.
• Current Orange Book, patent-term, litigation and settlement status must be verified against the latest FDA and court records.

FAQs

Does US 10,603,281 claim the Slynd tablet itself?

No. The independent claims are drafted as methods of providing contraception. The claims require administration of a qualifying composition, although dependent claims closely describe a commercial tablet formulation.

Can a generic use 4 mg drospirenone and avoid the patent?

Potentially, but the dose alone is not determinative. The generic would need to assess the excipient ranges, particle-size limitations, dissolution or PK requirements, and proposed contraception labeling.

Does the patent cover drospirenone combined with estrogen?

No. The claims expressly require that the pharmaceutical composition not contain an estrogen.

Are the placebo tablets independently protected?

No. The placebo limitations appear in dependent claims tied to the 28-day active dosing regimen. They do not create an independent composition claim for placebo tablets.

Is a different drospirenone particle-size measurement automatically non-infringing?

No. The result depends on the claim construction of particle-size terms, the measurement method and whether the accused product falls within the applicable "about" range. [1]

Sources

1. United States Patent and Trademark Office. (2020). US Patent No. 10,603,281, methods of providing contraception using drospirenone.
2. U.S. Food and Drug Administration. (2019). Slynd (drospirenone) tablets: Prescribing information.

Drugs Protected by US Patent 10,603,281

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Exeltis Usa Inc	DROSPIRENONE	drospirenone	TABLET, CHEWABLE;ORAL	216285-001	Jun 29, 2022		DISCN	Yes	No						PREVENTION OF PREGNANCY IN FEMALES OF REPRODUCTIVE AGE
Exeltis Usa Inc	SLYND	drospirenone	TABLET;ORAL	211367-001	May 23, 2019		RX	Yes	Yes						PREVENTION OF PREGNANCY IN FEMALES OF REPRODUCTIVE AGE

International Family Members for US Patent 10,603,281

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2588114		CA 2020 00023	Denmark
European Patent Office	2588114		2020C/518	Belgium
European Patent Office	2588114		19/2020	Austria
European Patent Office	2588114		C202030026	Spain