United States Patent 10,500,216: Mifepristone Food-Effect Claims, Scope, Validity, and Patent Landscape

U.S. Patent No. 10,500,216 protects a narrow method of administering mifepristone to a patient with Cushing's syndrome. The independent claim requires all of the following: a 1,200 mg daily oral dose, administration within 30 minutes after a meal, treatment for at least seven days, increased Cmax and AUC compared with fasted administration, and an AUC increase of at least 44%. The patent is therefore a regimen and pharmacokinetic-use patent, not a composition-of-matter patent covering mifepristone itself.

The principal commercial risk is directed at products used according to the claimed fed-dose regimen. The principal validity issues are likely to involve prior disclosure of mifepristone administration with food, the objective significance of the 44% AUC threshold, claim construction, and whether the claimed pharmacokinetic result is sufficiently tied to the required treatment steps.

What does U.S. Patent 10,500,216 protect?

The patent protects a food-effect method for improving mifepristone absorption in patients with Cushing's syndrome. Claim 1 combines treatment, dose, timing, duration, and pharmacokinetic-result limitations.

Limitation	Requirement in claim 1	Scope significance
Active ingredient	Mifepristone	Excludes other glucocorticoid-receptor antagonists
Patient population	Patient suffering from Cushing's syndrome	Limits infringement to the specified disease population
Route	Oral	Excludes intravenous, transdermal, implantable, and other routes
Dose	1,200 mg per day	Doses materially below or above 1,200 mg may fall outside the literal claim
Food timing	Within 30 minutes after consuming a meal	Creates a narrow administration window
Duration	At least seven days	Requires a treatment course, subject to interpretation of single-dose language in dependent claim 3
Pharmacokinetics	Increased Cmax and AUC versus fasted administration	Requires a fed-versus-fasted comparison
AUC threshold	At least 44% increase	Adds an objective quantitative limitation
Therapeutic objective	Increasing mifepristone absorption	Links the regimen to the claimed pharmacokinetic effect

The claim does not require a particular formulation, tablet excipient, manufacturer, tablet strength, or brand product. A generic or alternative formulation could infringe if it is administered in the claimed manner and produces the claimed pharmacokinetic result.

How should the independent claim be construed?

Claim 1 is a method-of-treatment claim with a compound pharmacokinetic limitation. Each limitation must generally be satisfied for direct infringement.

Dose limitation

The phrase "an oral dose of mifepristone of 1200 mg per day" is likely to be read as a daily dosage amount rather than necessarily a single 1,200 mg tablet. A regimen using multiple tablets that collectively delivers 1,200 mg per day could satisfy the dose limitation.

A regimen delivering 600 mg twice daily may raise a closer construction issue. The total daily dose is 1,200 mg, but the claim also refers to administration "within 30 minutes after consuming a meal." If both doses are administered after meals, literal infringement is more plausible than if only one dose is fed and the other is fasted. A once-daily 1,200 mg regimen presents the clearest infringement case.

Food-timing limitation

"Within 30 minutes after consuming a meal" is narrower than a general instruction to take mifepristone with food. A label directing administration with meals but not specifying the 30-minute window may create a weaker literal-infringement case, although the actual prescribing and administration practice could still be relevant to induced infringement.

The claim does not specify meal size, fat content, caloric content, or composition. Unless the specification limits "meal" more narrowly, ordinary food consumed as a meal would likely be sufficient.

Seven-day limitation

The patient must receive the regimen for at least seven days. A one-time fed administration does not satisfy claim 1. A patient who begins the regimen but stops before seven days may not satisfy the duration limitation, although inducement analysis can focus on the instructions and expected use.

Pharmacokinetic limitations

The claim requires that fed administration increase both Cmax and AUC compared with administration in the fasted state. It also requires an AUC increase of at least 44%.

The comparison is not necessarily against the patient's historical fasted exposure. It is more naturally read as a comparison between the claimed fed regimen and the corresponding fasted regimen. The patent may therefore require clinical or pharmacokinetic evidence showing the relevant exposure relationship.

The 44% threshold is important. An accused product or regimen may use the same dose and meal timing but avoid literal infringement if the relevant AUC increase is below the threshold. That defense depends on the appropriate reference condition, patient population, sampling design, and statistical treatment.

What do dependent claims 2 through 4 add?

Claim	Added limitation	Practical effect
2	Patient is male	Narrows the population to male patients
3	Mifepristone is administered as a single dose	Likely targets once-daily administration, but may create ambiguity with the seven-day requirement
4	Patient suffers from Cushing's disease	Narrows the broader Cushing's syndrome population to Cushing's disease

Claim 3 requires careful construction. Claim 1 requires administration for at least seven days, while claim 3 specifies administration as a "single dose." The commercially sensible interpretation is likely a single daily dose repeated for at least seven days. If "single dose" were read as a one-time administration, claim 3 would conflict with claim 1 and would have limited practical effect.

Claim 4 is narrower than claim 1 because Cushing's disease is generally a form of Cushing's syndrome caused by pituitary adrenocorticotropic hormone secretion. The claim does not cover every endogenous or exogenous cause of Cushing's syndrome.

What is the patent's geographic scope and expected expiration?

U.S. Patent 10,500,216 provides protection only in the United States. It does not establish rights in Europe, Japan, China, Canada, or other jurisdictions. Parallel international rights would require separate national or regional patents.

The patent's enforceable term is based on the U.S. patent-term statute and the relevant priority and nonprovisional filing dates, subject to patent-term adjustment and any applicable patent-term extension. The grant date, December 2019, does not itself determine the expiration date. The exact expiration date must be taken from the USPTO patent record and the continuity data for the patent family. [1]

Because the claim concerns mifepristone administration for Cushing's syndrome, its commercial term may overlap with other Korlym-related patents and FDA regulatory exclusivities. Patent expiration, Orange Book delisting, and FDA exclusivity are separate issues.

What patents protect mifepristone and Korlym?

Mifepristone's basic chemical structure is long outside ordinary small-molecule patent exclusivity. The relevant U.S. landscape instead consists of secondary patents covering:

Use of mifepristone for Cushing's syndrome.
Dosing and titration regimens.
Administration with food.
Pharmacokinetic exposure and absorption.
Formulations and tablet compositions.
Manufacturing processes and intermediates.
Other therapeutic uses, including reproductive-health indications.

U.S. Patent 10,500,216 is technically distinct from a composition-of-matter patent. It does not prevent every sale of mifepristone. It targets a defined method of use involving food, dose, timing, duration, and measured exposure.

The commercial product associated with the Cushing's syndrome indication is Korlym, whose active ingredient is mifepristone. FDA labeling and the Orange Book should be reviewed together because the label can disclose the relevant administration instructions, while the Orange Book identifies patents submitted for the approved drug product and indication. [2, 3]

What is the Orange Book status of U.S. Patent 10,500,216?

The claim text alone does not establish whether Patent 10,500,216 is currently listed in the Orange Book, whether it is listed against the relevant Korlym NDA, or whether it has been delisted. Orange Book status is an FDA database issue, separate from patent validity and enforceability.

If listed, the patent could be relevant to an abbreviated new drug application that relies on the Korlym labeling or seeks approval for the relevant Cushing's syndrome use. A generic applicant would need to assess whether a Paragraph IV certification is required or whether the proposed label can carve out the protected method.

A method patent may be listed only if it satisfies the FDA's statutory and regulatory listing requirements. FDA listing does not confirm that the claims are valid or infringed. [3, 4]

When does mifepristone lose exclusivity?

Mifepristone does not have a single exclusivity-loss date. The relevant dates may include:

Exclusivity layer	What determines the end date
Chemical patent protection	Expiration of any valid composition patent
Method-of-use patents	Expiration of Cushing's syndrome, dosing, or food-effect patents
Formulation patents	Expiration of tablet or delivery-system claims
FDA new-drug exclusivity	Statutory exclusivity tied to the NDA approval
Pediatric exclusivity	Potential six-month extension if awarded
Regulatory restrictions	FDA requirements governing dispensing and distribution
Litigation stays	A Paragraph IV suit may trigger a statutory stay of approval

A generic launch decision therefore cannot rely on the expiration date of Patent 10,500,216 alone. It must account for all Orange Book-listed patents, the approved label, regulatory exclusivity, and any litigation settlement.

What Paragraph IV challenges could target this patent?

A generic applicant could challenge the patent through a Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed. The most relevant theories would be the following.

Anticipation

An anticipation challenge would require one prior-art reference to disclose every limitation, including:

1,200 mg per day;
oral administration;
administration within 30 minutes after a meal;
treatment for at least seven days;
a Cmax increase;
an AUC increase;
an AUC increase of at least 44%;
treatment of a patient with Cushing's syndrome.

A general disclosure that mifepristone should be taken with food may not anticipate the precise 30-minute window and 44% AUC threshold unless those details are disclosed directly and unambiguously.

Obviousness

Obviousness is a more substantial risk if the prior art disclosed:

mifepristone treatment for Cushing's syndrome;
use of 1,200 mg daily;
administration with food;
known food-related increases in mifepristone exposure; and
routine pharmacokinetic testing.

The patentee's strongest response would likely rely on the specific magnitude of the AUC increase, the clinical importance of the food effect, and any evidence that the claimed regimen produced an unexpected or clinically useful result.

Written description and enablement

The patent must support the claimed 44% increase across the claim's full scope. Potential issues include whether the specification provides sufficient data across different meals, patient characteristics, formulations, disease severities, and treatment durations.

The claim is relatively narrow in dose and timing but broad in meal composition and formulation. That breadth can create an enablement issue if the food effect varies materially with those factors.

Indefiniteness

Potential construction issues include:

the meaning of "meal";
the reference condition for the fed-versus-fasted comparison;
whether the 44% increase is an individual-patient or population-level result;
how "single dose" operates with a seven-day regimen; and
whether "increasing absorption" imposes a separate limitation beyond increased AUC.

These issues do not automatically invalidate the claims, but they affect litigation risk and the reliability of infringement testing.

What formulation patents protect mifepristone?

Patent 10,500,216 does not require a particular formulation. It therefore differs from a formulation patent that claims:

a specific tablet composition;
particle size or polymorph;
excipient ratios;
dissolution characteristics;
controlled release;
stability properties; or
a manufacturing process.

A generic manufacturer could avoid a formulation patent by changing the composition, but that strategy would not necessarily avoid Patent 10,500,216 if the generic product is still administered at 1,200 mg within 30 minutes after a meal for at least seven days and produces the claimed exposure increase.

Conversely, avoiding the patented fed regimen may not avoid separate formulation or method-of-use patents. Patent clearance must be performed claim by claim across the complete family and Orange Book listing.

What patent litigation affects mifepristone generic entry?

A Paragraph IV lawsuit involving an Orange Book-listed patent can delay FDA approval for up to 30 months, subject to statutory exceptions and court developments. A settlement may establish a licensed entry date, a permitted label, or restrictions on the generic's marketing conduct. [4]

The supplied information does not establish:

whether Patent 10,500,216 has been asserted;
whether a Paragraph IV notice has been served;
whether litigation is pending or concluded;
whether a settlement agreement exists; or
whether a generic has an agreed entry date.

Those facts cannot be inferred from the claim language or patent number.

How strong is the patent estate for this mifepristone regimen?

The claim has meaningful commercial specificity but limited breadth.

Strengths

It identifies a precise dose used in the approved Cushing's syndrome treatment context.
The 44% AUC threshold creates an objective infringement marker.
The claim covers administration practice rather than a particular branded tablet.
A generic using the same label instructions could face method-of-use exposure.

Weaknesses

The claim depends on a food-effect relationship that may have been observed or suggested in clinical pharmacology literature.
The 30-minute timing requirement may be difficult to prove in ordinary clinical practice.
The AUC threshold can require patient-level or population-level pharmacokinetic evidence.
A label carve-out or alternative administration instruction could reduce induced-infringement exposure.
The claim does not block mifepristone products used for other indications or at other doses.

The patent is strongest against a product whose labeling expressly directs 1,200 mg daily administration after a meal and whose clinical use predictably follows that instruction. It is weaker against a product with a different dose, a different food instruction, a carved-out Cushing's indication, or evidence that the 44% AUC threshold is not met.

What generic launch scenarios exist?

Launch scenario	Risk profile
Generic copies Korlym labeling, including fed administration	High exposure to method-of-use claims
Generic uses 1,200 mg daily but omits or changes food instructions	Lower literal risk, with induced-infringement questions
Generic uses a materially different dose	Potentially outside claim 1
Generic seeks a Cushing's indication but carves out the patented method	Regulatory and infringement analysis required
Generic launches after patent expiration	Patent risk reduced, subject to other patents and exclusivities
Generic launches under litigation settlement	Governed by settlement terms and permitted-label restrictions

A skinny-label strategy is not automatically sufficient. If the remaining label, physician instructions, promotional materials, or product design encourage the patented regimen, induced-infringement allegations may remain possible.

Does biosimilar risk apply to mifepristone?

No. Mifepristone is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an ANDA for a generic drug, not a biosimilar application under the Public Health Service Act.

The principal regulatory issues are therefore bioequivalence, labeling, patent certifications, manufacturing compliance, and any applicable restricted-distribution requirements. [2, 4]

Key Takeaways

U.S. Patent 10,500,216 is a narrow mifepristone method-of-use patent.
Claim 1 requires 1,200 mg daily, oral administration, administration within 30 minutes after a meal, at least seven days of treatment, and an AUC increase of at least 44% versus fasting.
The patent does not claim mifepristone itself or a specific tablet formulation.
Claims 2 and 4 narrow the patient population to male patients and patients with Cushing's disease, respectively.
Claim 3 is best read as a single daily dose repeated for at least seven days, although its wording creates a claim-construction issue.
The main validity risks are obviousness based on known mifepristone food effects, anticipation, enablement, and ambiguity surrounding the pharmacokinetic comparison.
Generic exposure is highest where the proposed label reproduces the 1,200 mg fed-dose regimen.
Mifepristone is subject to generic, not biosimilar, competition.
Patent expiration, Orange Book listing, Paragraph IV activity, litigation, and settlement terms cannot be determined from the supplied claims alone.

FAQs

Can a generic avoid Patent 10,500,216 by using a different meal?

Possibly, but not automatically. The claim does not specify meal composition. A different meal may still satisfy the claim if it is administered within 30 minutes and produces the required pharmacokinetic increase.

Does taking mifepristone with food automatically infringe the patent?

No. The claim also requires a 1,200 mg daily dose, at least seven days of treatment, increased Cmax and AUC, and an AUC increase of at least 44%.

Is the 44% AUC threshold measured in every patient?

The claim text does not specify whether the threshold is an individual-patient requirement or a population pharmacokinetic result. The specification, prosecution history, and expert evidence would control the interpretation.

Can the patent cover a generic tablet with different excipients?

Yes. The claim is not limited to a particular formulation. A different formulation can still fall within the claim if the claimed administration regimen and pharmacokinetic result are present.

Does FDA approval establish infringement?

No. FDA approval and patent infringement are separate questions. Approval may create practical exposure if the approved label directs the patented method, but only a legal analysis of the claims and actual conduct determines infringement.

References

United States Patent and Trademark Office. (n.d.). U.S. Patent No. 10,500,216, patent term and prosecution records.
U.S. Food and Drug Administration. (n.d.). Korlym (mifepristone) prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Code, 21 U.S.C. §§ 355(j), 355(c)(3)(E), 355(j)(5)(B)(iii); 35 U.S.C. §§ 154, 271(e).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Corcept Therap	KORLYM	mifepristone	TABLET;ORAL	202107-001	Feb 17, 2012	AB	RX	Yes	Yes	10,500,216	⤷ Start Trial				TREATING CUSHING'S SYNDROME	⤷ 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: 10,500,216

Which drugs does patent 10,500,216 protect, and when does it expire?

Summary for Patent: 10,500,216