US Patent 9,943,526: Scope, Claims, Expiration, Orange Book Status, and Mifepristone Patent Landscape

US Patent 9,943,526 protects a pharmacokinetic dosing method for treating Cushing's syndrome with mifepristone. Its central limitation is repeated plasma-level testing and dose adjustment to achieve mifepristone concentrations above 1,631 ng/mL. The patent does not broadly claim mifepristone for Cushing's syndrome, a 300 mg tablet, or a fixed dosing regimen. It claims a treatment protocol tied to a specific plasma concentration threshold.

The principal commercial risk is method-of-use infringement by a generic sponsor that markets mifepristone for Cushing's syndrome with labeling that instructs physicians to measure plasma mifepristone and increase the dose when concentrations are 1,631 ng/mL or lower.

What patent is US 9,943,526?

US Patent 9,943,526 B2 is titled "Methods for treating Cushing's syndrome." The patent is associated with Corcept Therapeutics, the developer and marketer of Korlym, the mifepristone product approved for certain patients with endogenous Cushing's syndrome.

Field	Description
Patent	US 9,943,526 B2
Title	Methods for treating Cushing's syndrome
Patent type	Utility patent
Technology	Mifepristone dose optimization using plasma concentration testing
Therapeutic area	Endogenous Cushing's syndrome
Active ingredient	Mifepristone
Core threshold	Greater than 1,631 ng/mL
Core treatment duration	At least seven daily doses over at least seven days
Additional maintenance period	Up to six months under claim 9
Primary commercial product	Korlym
Patent holder associated with product	Corcept Therapeutics
US patent term	Nominally tied to the earliest effective nonprovisional priority date; the family is generally reported as extending into 2029

The patent's enforceable term must be confirmed against the USPTO patent-term-adjustment record, terminal-disclaimer record, and any applicable corrections. Patent expiration is separate from FDA regulatory exclusivity.

What does claim 1 of US 9,943,526 cover?

Claim 1 is a multi-step method claim with several cumulative limitations. A practicing party must satisfy each material limitation for literal infringement.

Claim 1 limitation analysis

Limitation	Required conduct
Patient population	The patient must be suffering from Cushing's syndrome
Exclusion	The patient must not already be suffering from a condition indicated for treatment with mifepristone
Initial treatment	At least seven daily doses must be administered over at least seven days
Dose structure	Each initial daily dose contains an initial amount of mifepristone
Testing	The patient's plasma mifepristone level must be tested
Threshold branch 1	If the level is greater than 1,631 ng/mL, treatment continues with the existing daily dose
Threshold branch 2	If the level is 1,631 ng/mL or lower, the daily amount must be increased
Repetition	Testing and the applicable dose decision must be repeated
Result	Dose adjustment must achieve plasma levels greater than 1,631 ng/mL

The claim is therefore narrower than a conventional titration claim. It requires:

A defined minimum pretreatment period.
Plasma concentration testing.
A numerical threshold.
Continued treatment when the level exceeds the threshold.
Increased dosing when the level does not exceed the threshold.
Repeated implementation of the testing and adjustment cycle.

A physician who merely increases Korlym from 300 mg to 600 mg based on clinical response, glucose control, or cortisol-related symptoms would not necessarily practice claim 1. The claim requires plasma mifepristone testing and use of the 1,631 ng/mL threshold.

How do claims 2 through 9 narrow the patent?

Claims 2 through 9 add administration, dose, duration, testing-device, and maintenance limitations.

Claim	Additional limitation	Commercial significance
2	Initial seven or more daily doses are administered orally	Targets oral Korlym treatment
3	Initial daily dose is at least 300 mg	Covers the labeled starting strength
4	Initial daily dose is at least 600 mg	Covers higher starting regimens
5	Initial daily dose is at least 900 mg	Covers aggressive titration
6	Initial daily dose is at least 1,200 mg	Covers the labeled maximum daily dose
7	Treatment continues for at least 28 daily doses over at least 28 days	Extends the claim to a four-week course
8	Testing uses a plasma sampling collection device and a device suitable for detecting plasma mifepristone	Adds sample-collection and detection-system requirements
9	Plasma levels are maintained above 1,631 ng/mL for up to six months	Covers longer-term optimized treatment

Claims 3 through 6 are particularly relevant to Korlym because the FDA-approved labeling provides a 300 mg starting dose and permits weekly increases up to 1,200 mg per day based on clinical response and tolerability. The FDA label does not, by itself, establish that routine plasma mifepristone monitoring is required. [1]

What is the scope of the 1,631 ng/mL limitation?

The threshold is the claim's principal technical distinction. The claim does not cover every dose that produces a therapeutic response. It requires the treatment protocol to be directed toward achieving plasma mifepristone levels greater than 1,631 ng/mL.

The threshold creates several potential infringement questions:

Whether the plasma assay must produce a precise quantitative result.
Whether a test result at exactly 1,631 ng/mL triggers dose escalation.
Whether a result above 1,631 ng/mL permits continuation without increasing the dose.
Whether testing must occur after seven days of treatment.
Whether every later test must lead to the claimed continue-or-increase decision.
Whether a physician's undocumented clinical practice can establish the required treatment steps.
Whether a product label that recommends monitoring would induce infringement even if some physicians do not perform the test.

The claim expressly treats a result of 1,631 ng/mL or lower as insufficient. The required target is therefore strictly greater than 1,631 ng/mL.

What formulations are protected by US 9,943,526?

US 9,943,526 is not principally a formulation patent. Its claims are directed to treatment steps and pharmacokinetic optimization.

The patent does not, based on the claims supplied, require:

A particular tablet excipient.
A specific coating.
A particular particle-size distribution.
A controlled-release profile.
A specific salt or polymorph.
A particular tablet strength.
A defined dissolution profile.
A particular manufacturing process.

Claim 2 limits administration to oral treatment, but oral administration alone does not create formulation protection. A generic oral mifepristone tablet could potentially avoid formulation-specific patents while still raising risk under this patent if its proposed labeling directs the claimed plasma-monitoring and dose-adjustment protocol.

Does the patent cover the FDA-approved Korlym dosing regimen?

The FDA-approved Korlym label recommends a 300 mg once-daily starting dose. The dosage may be increased in 300 mg increments, generally at intervals of at least one week, up to 1,200 mg once daily, based on clinical response and tolerability. [1]

That regimen overlaps with several elements of claims 3 through 6 and claim 7. The overlap is incomplete because the label's standard dosing instructions do not necessarily require:

Measuring plasma mifepristone concentrations.
Using 1,631 ng/mL as the decision threshold.
Increasing the dose whenever plasma levels are 1,631 ng/mL or lower.
Maintaining levels above 1,631 ng/mL for up to six months.

The practical strength of the patent depends heavily on the wording of an ANDA label, physician instructions, specialty-pharmacy materials, and risk-management materials. A generic label that omits the patented use may reduce direct inducement risk, but it does not eliminate all litigation exposure if the product is commercially used for the patented indication.

What is the Orange Book status of US 9,943,526?

Korlym is an FDA-approved drug product containing mifepristone. Orange Book-listed patents can impose certification obligations on an ANDA applicant under the Hatch-Waxman Act. An applicant generally must certify against listed patents, including by filing a Paragraph IV certification when it contends that a listed patent is invalid, unenforceable, or not infringed. [2]

The relevant Orange Book issues are:

Issue	Analysis
Listed drug	Korlym tablets
NDA holder	Corcept Therapeutics
Relevant pathway	ANDA certification under 21 U.S.C. § 355(j)
Patent category	Method-of-use patent
Product protection	Not a simple composition-of-matter claim
Litigation trigger	Notice of Paragraph IV certification to the patent owner and NDA holder
Potential stay	A timely infringement action can trigger the statutory 30-month stay, subject to statutory exceptions
Label strategy	A generic sponsor may seek a section viii carve-out for patented use where legally available

The Orange Book list must be evaluated together with the exact approved use codes. An Orange Book listing does not prove that every claim is valid, enforceable, or infringed. It determines the regulatory certification framework.

When does US 9,943,526 lose exclusivity?

The patent's nominal family term is generally reported as extending into January 2029, based on the earliest effective priority date associated with the relevant Corcept patent family. The operative expiration date must account for USPTO patent-term adjustment and any terminal disclaimer.

The exclusivity timeline is separate from patent expiry:

Protection	Approximate status
FDA approval of Korlym	2012
New chemical entity exclusivity	Expired
Patent protection under method patents	Extends beyond regulatory exclusivity
US 9,943,526	Reported to extend into 2029
Generic launch	Dependent on patent certifications, litigation, settlement, and any carve-out

Mifepristone also has separate FDA-approved uses and products. Mifeprex, used under a different FDA approval for medication abortion, should not be treated as interchangeable with Korlym's Cushing's syndrome indication for patent analysis. The products contain the same active ingredient but have different approved uses, sponsors, dosing frameworks, and regulatory histories.

Which companies are challenging Korlym exclusivity?

A Paragraph IV challenge would be commercially significant because Korlym has a specialized indication, a limited prescriber base, and a method-of-use patent estate. The principal risk would come from an ANDA sponsor seeking approval for mifepristone tablets with a Cushing's syndrome indication or with labeling that can be used to support that indication.

The relevant challenger categories are:

A conventional generic manufacturer filing an ANDA for mifepristone tablets.
A specialty pharmaceutical company pursuing a limited-distribution launch.
A sponsor attempting a section viii carve-out that omits the patented dosing method.
A company challenging the patent through an inter partes review or other validity proceeding.

Publicly reported litigation and settlement terms must be matched to the specific patent number. A generic challenge against another Korlym patent does not automatically establish a challenge to US 9,943,526.

What invalidity arguments are most relevant?

The patent's claim structure creates several potential validity issues.

Written description and enablement

The claims require achieving a plasma concentration above 1,631 ng/mL across patients with Cushing's syndrome. A challenger could argue that the specification does not adequately support the full scope of the claimed population, dose range, testing methods, treatment duration, and repeated adjustment protocol.

Enablement risk increases if the patent requires extensive experimentation to determine:

The dose needed for each patient.
The relationship between dose and plasma exposure.
The reliability of the 1,631 ng/mL threshold.
The appropriate interval between tests.
The safety of maintaining concentrations above the threshold for six months.

Anticipation

Earlier clinical studies, protocols, or publications could be relevant if they disclose all elements, including the specific threshold and the repeated decision rule. A reference that discloses mifepristone treatment and plasma monitoring but not the 1,631 ng/mL threshold would not necessarily anticipate claim 1.

Obviousness

A challenger could combine:

Known mifepristone use in Cushing's syndrome.
Pharmacokinetic monitoring.
Dose escalation based on measured drug levels.
Routine therapeutic-drug-monitoring principles.
Clinical data correlating exposure with response.

The patent owner would likely argue that the specific threshold and treatment algorithm produced a non-obvious optimization and that prior art did not direct clinicians to maintain levels above 1,631 ng/mL.

Indefiniteness

Potential disputes include the meaning of:

"Initial amount."
"Daily doses."
"Testing the plasma mifepristone levels."
"Achieve" and "maintain."
"Up to six months."
"Condition indicated for treatment with mifepristone."

The threshold itself is numerically definite. The broader operational language may generate claim-construction disputes.

How strong is the patent estate for Korlym?

US 9,943,526 is strongest against a generic label that expressly recommends plasma mifepristone testing and dose escalation above 1,631 ng/mL. It is weaker against a label limited to standard clinical titration based on tolerability and clinical response.

Risk factor	Assessment
Numerical threshold	Strong claim differentiation
Product-specific limitation	No, the claim covers a method rather than a unique product
Oral tablet coverage	Added by claim 2
Starting-dose coverage	Claims 3 through 6 cover 300 mg to 1,200 mg
Monitoring burden	Creates proof and inducement issues
Label-based enforcement	Important, particularly for ANDA products
Formulation barrier	Limited under the supplied claims
Manufacturing barrier	No material manufacturing limitation appears in the supplied claims
Biosimilar relevance	None; mifepristone is a small molecule, not a biologic
Generic substitution risk	Depends on indication labeling and patent certification

The estate's commercial value comes from its position around the approved indication rather than from manufacturing exclusivity. A generic may be able to develop a chemically equivalent tablet while still facing method-of-use litigation.

What generic launch scenarios exist?

Scenario 1: Full Cushing's syndrome label

A generic sponsor seeks an indication for Cushing's syndrome and includes plasma monitoring or dose adjustment tied to the 1,631 ng/mL threshold. This presents the highest risk of literal infringement and induced infringement.

Scenario 2: Cushing's syndrome label without the patented monitoring method

The sponsor seeks approval for mifepristone treatment of Cushing's syndrome but relies on clinical response and tolerability for dose adjustment. This may reduce exposure under claims 1 and 9, although other Korlym patents could remain relevant.

Scenario 3: Section viii carve-out

The sponsor omits the patented Cushing's syndrome use and markets only for a non-patented indication, if the FDA-approved labeling and applicable patent listings permit the carve-out. Commercial substitution into Cushing's syndrome may still create litigation risk.

Scenario 4: Paragraph IV litigation and settlement

The sponsor certifies that US 9,943,526 is invalid, unenforceable, or not infringed. Corcept may sue within the statutory period, potentially delaying approval while the litigation proceeds. A settlement could provide a negotiated entry date, subject to antitrust review and regulatory requirements.

Key Takeaways

US 9,943,526 is a pharmacokinetic method-of-use patent for mifepristone treatment of Cushing's syndrome.
Its core limitation is achieving plasma mifepristone levels greater than 1,631 ng/mL through repeated testing and dose adjustment.
The patent does not broadly claim all mifepristone treatment, all Korlym tablets, or a specific formulation.
Claims 3 through 6 cover initial daily doses of at least 300 mg, 600 mg, 900 mg, and 1,200 mg.
Claim 9 extends protection to maintenance above the threshold for up to six months.
The FDA Korlym label overlaps with the dose and duration limitations but does not necessarily require the patented plasma-monitoring algorithm.
The reported patent term extends into 2029, subject to the official USPTO term calculation.
The principal generic risk is a Paragraph IV challenge involving a Cushing's syndrome label or labeling that induces the claimed monitoring and dose-adjustment method.
Biosimilar analysis is not applicable because mifepristone is a small-molecule drug.
Formulation and manufacturing barriers are not the principal protections in the supplied claims.

FAQs About US Patent 9,943,526 and Korlym

Does US 9,943,526 cover a 300 mg mifepristone tablet?

It can cover treatment using an initial 300 mg daily dose under claim 3, but only when the remaining claim 1 limitations are satisfied, including plasma testing and dose adjustment based on the 1,631 ng/mL threshold.

Can a generic avoid US 9,943,526 by using the same mifepristone molecule?

Not necessarily. The patent is a method-of-use patent. A generic may use the same active ingredient and still face infringement risk if its labeling induces the patented Cushing's syndrome dosing protocol.

Is monitoring mifepristone plasma levels required by the FDA Korlym label?

The standard Korlym label provides dose escalation based on clinical response and tolerability. It does not establish the same requirement as claim 1 to test plasma levels and target concentrations greater than 1,631 ng/mL. [1]

Does US 9,943,526 protect medication-abortion use of mifepristone?

No. The supplied claims are directed to treating Cushing's syndrome and exclude a patient already suffering from a condition indicated for treatment with mifepristone. Medication-abortion products and indications involve separate FDA approvals and regulatory records.

Is US 9,943,526 a biosimilar patent?

No. Mifepristone is a small-molecule active pharmaceutical ingredient. A competing product would generally proceed through an ANDA or another small-molecule pathway, not the biosimilar pathway under the Public Health Service Act.

References

U.S. Food and Drug Administration. (2024). Korlym (mifepristone) tablets, prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
United States Patent and Trademark Office. (2018). U.S. Patent No. 9,943,526: Methods for treating Cushing's syndrome. U.S. Department of Commerce.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term information. U.S. Department of Commerce.

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	9,943,526	⤷ 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: 9,943,526

Which drugs does patent 9,943,526 protect, and when does it expire?

Summary for Patent: 9,943,526