Details for Patent: 10,151,763

« Back to Dashboard

Which drugs does patent 10,151,763 protect, and when does it expire?

Patent 10,151,763 protects KORLYM and is included in one NDA.

This patent has twelve patent family members in ten countries.

Summary for Patent: 10,151,763

Title:	Treatment and differential diagnosis of Cushing's disease and ectopic Cushing's syndrome
Abstract:	Improved methods and systems for diagnosing and for treating Cushing's syndrome and Cushing's Disease are provided herein, including methods and systems for concurrently treating Cushing's syndrome and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome in a patient with an established diagnosis of ACTH-dependent Cushing's syndrome. Treatment methods can use glucocorticoid receptor antagonists (GRAs), which differentially affect the ratio of cortisol to ACTH levels in patients having Cushing's Disease versus patients having Ectopic Cushing's Syndrome. Methods for concurrently treating and differentially diagnosing Cushing's Disease from Ectopic Cushing's Syndrome include obtaining baseline cortisol and ACTH levels of a patient, treating the patient with a GRA according to a protocol that would typically substantially elevate cortisol levels, obtaining post-treatment cortisol and ACTH levels of the patient, determining a differential relationship between baseline cortisol and ACTH levels and post-treatment cortisol and ACTH levels and providing a positive diagnosis based on the differential relationship.
Inventor(s):	Andreas G. Moraitis
Assignee:	Corcept Therapeutics Inc
Application Number:	US15/627,414
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,151,763
Patent Claim Types: see list of patent claims	Use;

United States Patent 10,151,763: Cushing's Syndrome Diagnostic and Treatment Patent Landscape

U.S. Patent No. 10,151,763 protects a combined treatment-and-diagnosis protocol for ACTH-dependent Cushing's syndrome. Its central limitation is the administration of a glucocorticoid receptor antagonist, particularly mifepristone, for at least five weeks, followed by comparison of the patient's cortisol-to-ACTH ratio before and after treatment. The patent distinguishes pituitary Cushing's disease from ectopic ACTH syndrome based on the direction and, in dependent claims, the magnitude of the ratio change.

The patent is primarily a method-of-treatment and method-of-diagnosis right. It does not broadly claim mifepristone, glucocorticoid receptor antagonism, cortisol testing, ACTH testing, pituitary surgery, or adrenalectomy in isolation. Infringement requires a combination of treatment duration, biochemical testing, ratio calculation, and diagnostic use.

What does U.S. Patent 10,151,763 claim?

The patent has 30 claims organized around four independent claim groups:

Independent claims	Core purpose	Treatment endpoint	Diagnostic endpoint
Claims 1 and 11	Treat ACTH-dependent Cushing's syndrome while differentiating disease source	Control of hyperglycemia or diabetes symptoms associated with hypercortisolemia	Cushing's disease versus ectopic Cushing's syndrome
Claims 16 and 26	Treat and differentiate, then direct surgical management	Control of hyperglycemia or diabetes symptoms	Pituitary or extrapituitary source, followed by transsphenoidal surgery or adrenalectomy

The core protocol requires:

1. Measuring pretreatment cortisol and ACTH.
2. Administering a glucocorticoid receptor antagonist.
3. Continuing treatment for at least five weeks.
4. Measuring cortisol and ACTH after exposure to the antagonist.
5. Calculating a baseline cortisol-to-ACTH ratio.
6. Calculating a post-treatment cortisol-to-ACTH ratio.
7. Diagnosing the source of ACTH secretion based on the direction of ratio change.

The patent defines the ratio as:

[ \text{C:A ratio} = \frac{\text{cortisol level}}{\text{ACTH level}} ]

The claims do not require a particular cortisol assay, ACTH assay, imaging modality, surgical technique, or glucocorticoid receptor antagonist in the independent claims.

How does the diagnostic method work?

The diagnostic distinction is based on the change in the C:A ratio after glucocorticoid receptor blockade.

Observed result after GRA treatment	Claimed diagnosis
GRA-exposed C:A ratio is lower than baseline	Ectopic Cushing's syndrome
GRA-exposed C:A ratio is higher than baseline	Cushing's disease
Ratio falls by at least 50%	Ectopic Cushing's syndrome under claim 2
Ratio rises by at least 20%	Cushing's disease under claim 2
Ratio falls by about 60%	Ectopic Cushing's syndrome under claim 8
Ratio rises by about 100%	Cushing's disease under claim 8

Claims 16 and 26 add an anatomical and treatment consequence:

• A lower post-treatment ratio indicates an extrapituitary ACTH-secreting tumor and supports adrenalectomy under the claimed method.
• A higher ratio indicates a pituitary tumor or pituitary hyperplasia and supports transsphenoidal surgery.

The claim language makes the diagnostic conclusion part of the claimed method. A laboratory that only measures cortisol and ACTH, without applying the claimed treatment and diagnostic rule, would generally fall outside the literal scope of these claims.

What are the key limitations of claim 1?

Claim 1 is the principal broad claim. Its material limitations are:

Limitation	Scope
Patient population	Patient with ACTH-dependent Cushing's syndrome caused by excess ACTH from a tumor or pituitary hyperplasia
Treatment agent	A glucocorticoid receptor antagonist
Treatment duration	At least five weeks
Pretreatment testing	Baseline cortisol and ACTH from one or more samples
Post-treatment testing	Cortisol and ACTH from one or more GRA-exposed samples
Calculation	Baseline and post-treatment cortisol-to-ACTH ratios
Diagnosis	Lower ratio means ectopic disease; higher ratio means Cushing's disease
Concurrent therapeutic objective	Treating ACTH-dependent Cushing's syndrome and controlling hyperglycemia secondary to hypercortisolemia

The claim is narrower than a conventional mifepristone composition claim because it requires a particular clinical workflow. It is broader than claims limited to mifepristone because "GRA" is not restricted in claim 1.

The phrase "concurrently" is significant. The claim links the diagnostic protocol to active treatment of ACTH-dependent Cushing's syndrome and control of hyperglycemia or diabetes-related symptoms. A diagnostic study involving a short exposure, placebo administration, or treatment unrelated to Cushing's syndrome would present a noninfringement argument.

Which dependent claims narrow the patent's scope?

Mifepristone claims

Claims 3, 9, 10, 18, 24 and 25 identify mifepristone as the GRA. Claim 3 adds:

• At least six weeks of treatment.
• Daily administration.
• A dose not exceeding 20 mg/kg per day.
• Post-treatment sampling after the minimum treatment period.

Claim 9 and claim 24 require at least 10 weeks of mifepristone administration in the higher-threshold diagnostic embodiments.

The 20 mg/kg limitation is unusually broad relative to the labeled Korlym dosing range, which is ordinarily expressed as a fixed daily dose rather than weight-based dosing. The limitation may capture standard adult treatment while also reaching substantially higher total daily amounts in larger patients.

Non-steroidal GRA claims

Claims 4, 12, 19 and 27 cover a non-steroidal glucocorticoid receptor antagonist administered for at least six weeks. These claims are potentially relevant to later-generation selective or nonsteroidal GR antagonists, depending on whether the compound qualifies as a GRA and whether the accused clinical protocol uses the claimed diagnostic sequence.

Sample-type claims

The patent separately claims saliva, plasma and 24-hour urine:

• Claims 5 and 13: saliva.
• Claims 6 and 14: plasma.
• Claims 7 and 15: 24-hour urine.
• Claims 20, 21 and 22: the same three sample types for the surgical-treatment embodiments.
• Claims 28, 29 and 30: corresponding sample-type claims under claim 26.

These claims require a first post-treatment sample after six to 10 weeks and at least one additional sample after a further four weeks. The repeated-sampling requirement creates a meaningful design-around path for a protocol using only one post-treatment sample, assuming the independent claim is not otherwise infringed.

What formulations are protected by U.S. Patent 10,151,763?

The patent does not claim a tablet, capsule, injectable formulation, sustained-release formulation, salt, polymorph, excipient system or manufacturing process. It claims administration of a GRA in a patient-management protocol.

For mifepristone, the patent is therefore distinct from:

• Mifepristone composition-of-matter patents.
• Mifepristone formulation patents.
• Process patents for manufacturing or purification.
• Patents covering abortion or pregnancy termination uses.
• General mifepristone treatment claims for hyperglycemia in Cushing's syndrome.

The patent can be relevant to Korlym use even though it does not claim the Korlym formulation itself. An approved product can practice a method claim when used according to the claimed diagnostic and treatment steps.

What is the FDA and Orange Book relevance?

The FDA approved Korlym, the mifepristone product marketed by Corcept Therapeutics, for controlling hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have failed surgery.[2]

The regulatory indication is important because the patent's treatment objective tracks the labeled Cushing's hyperglycemia use. The patent, however, adds a diagnostic protocol that is not necessary for every labeled use of Korlym.

The Orange Book analysis should distinguish:

Regulatory or patent right	Relevance to Patent 10,151,763
New drug approval	Establishes FDA-approved mifepristone use for Cushing's-related hyperglycemia
Use patent listing	Could create notice and Paragraph IV exposure if this patent or a related patent is listed for an approved method
Drug substance patent	Protects mifepristone itself, if unexpired, rather than the claimed diagnostic workflow
Formulation patent	Covers product architecture, not the C:A-ratio protocol
Pediatric exclusivity	Does not expand the scope of this patent
Orphan exclusivity	Can delay approval of a competing product but does not create patent infringement

A complete Orange Book determination requires the current FDA patent-listing record for Korlym and the relevant product strength. Patent status cannot be inferred solely from the issued patent text. The key commercial question is whether U.S. Patent 10,151,763 is listed against the relevant mifepristone product and indication.

When does U.S. Patent 10,151,763 lose exclusivity?

A U.S. utility patent generally expires 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers and other statutory adjustments.[3] The grant date, December 11, 2018, does not by itself establish the expiration date.

The practical exclusivity date must be calculated from:

• The earliest claimed priority application.
• The U.S. nonprovisional filing date.
• Any continuation or divisional relationship.
• Patent-term adjustment shown on the face of the patent.
• Any terminal disclaimer.
• Any patent-term extension under 35 U.S.C. §156.

The patent's enforceability also depends on maintenance-fee payment. A patent can remain within its statutory term but lapse for nonpayment and later be reinstated. The relevant business conclusion is that the patent's expiry cannot be reliably stated from the claims alone.

How strong is the patent estate?

The patent has moderate claim breadth but a potentially narrow enforcement pathway.

Strengths

1. The independent claims cover any GRA, not only mifepristone.
2. The claims combine therapy and diagnosis, making the protocol commercially relevant to specialty endocrinology.
3. The treatment period of at least five weeks may align with real-world chronic Cushing's management.
4. The claims reach multiple specimen types.
5. Claims 16 and 26 connect diagnosis to surgical selection, creating a treatment-management application beyond laboratory testing.
6. The claims may reach future nonsteroidal GR antagonists if their clinical use follows the same protocol.

Weaknesses

1. The claimed diagnostic rule is relatively simple: compare two ratios and determine whether the ratio increased or decreased.
2. Cushing's disease and ectopic ACTH syndrome were established diagnostic categories before the patent.
3. Baseline and post-treatment cortisol and ACTH measurements are conventional clinical variables.
4. The claims require prolonged antagonist exposure, which may not be used in routine differential diagnosis.
5. The claims require the treatment and diagnostic steps to be performed in combination.
6. The treatment objective may create written-description, enablement and indefiniteness issues if the specification does not support every GRA, sample type and patient subgroup.
7. A protocol that does not calculate a C:A ratio, or calculates a different biomarker relationship, may avoid literal infringement.
8. A protocol that uses a single post-treatment sample may avoid the repeated-sample dependent claims.

The most vulnerable validity issues would likely involve obviousness based on the combination of established mifepristone treatment, ACTH and cortisol monitoring, and conventional source differentiation in ACTH-dependent Cushing's syndrome. The patent's strongest defense would depend on evidence that the direction or magnitude of the ratio change after sustained GR antagonism was unexpected and clinically predictive.

Which companies are likely to challenge the patent?

The relevant challengers are not limited to traditional generic manufacturers.

Potential challenger	Commercial rationale	Principal risk
Generic mifepristone manufacturer	Launch an abbreviated new drug application for a Cushing's-related product	Orange Book-listed method patents and Paragraph IV litigation
Developer of a nonsteroidal GRA	Use the claimed diagnostic approach with a next-generation product	Claims 4, 12, 19 and 27
Endocrine specialty pharmaceutical company	Develop an alternative medical treatment for hypercortisolism	Method-of-treatment claims
Diagnostic laboratory or platform operator	Offer an integrated test-and-treatment monitoring service	Direct or induced infringement theories
Hospital or academic center	Apply the protocol in clinical practice or trials	Practice-of-method claim exposure

A biosimilar challenge is not the primary risk because mifepristone is a small molecule, not a biologic. The relevant regulatory pathway is an ANDA or, depending on the product and development strategy, a 505(b)(2) application. A nonsteroidal GRA would generally face its own NDA pathway rather than a biosimilar pathway.

What Paragraph IV risks exist?

A generic applicant could challenge a listed method patent through a Paragraph IV certification if the patent is listed for the reference product and the applicant seeks approval for a use covered by the patent.[4]

Possible noninfringement positions include:

• The label does not instruct calculation of a cortisol-to-ACTH ratio.
• The label does not instruct at least five or six weeks of GRA treatment before testing.
• The product is labeled for a different disease or treatment objective.
• The applicant carves out the patented diagnostic use.
• The applicant does not instruct differentiation between Cushing's disease and ectopic Cushing's syndrome.
• The product is not administered at the claimed dose or duration.
• The claimed diagnostic step is performed by a physician, laboratory or hospital outside the generic applicant's control.

Potential validity positions include:

• Obviousness based on the combination of mifepristone treatment and conventional ACTH/cortisol monitoring.
• Lack of written description for the full genus of GRAs.
• Lack of enablement for all sample matrices and treatment durations.
• Indefiniteness in terms such as "about," "higher," "lower," and "concurrently."
• Lack of patentable subject matter for diagnostic calculations, depending on claim construction and whether the claims are viewed as an integrated treatment protocol under the Supreme Court's diagnostic-method precedent.[5]

The Federal Circuit's treatment of diagnostic claims after Mayo and Alice makes the therapeutic administration step important. Claims that merely observe a natural relationship and report a diagnosis face greater eligibility risk than claims that require a substantive treatment regimen tied to the diagnostic result.[5]

What patent litigation affects this patent?

The supplied claim set does not identify a reported infringement action, Paragraph IV case, settlement or license involving U.S. Patent 10,151,763. The patent should not be characterized as litigated, settled or licensed without a docket, FDA listing or recorded transaction supporting that conclusion.

The litigation risk is more likely to arise indirectly through a Korlym ANDA dispute or through development of an alternative GRA. In such a case, the asserted claims would likely be claims 1, 10, 11, 16, 25 and 26, with dependent claims asserted selectively based on the proposed label and clinical instructions.

How does this patent compare with competing patent rights?

Patent category	What it protects	Relationship to 10,151,763
Mifepristone composition patent	The active pharmaceutical ingredient	Earlier-stage, broader chemical protection
Korlym formulation patent	Tablet composition, dosage form or release properties	Product protection, not diagnostic workflow
Cushing's hyperglycemia method patent	Administration of mifepristone to control hyperglycemia	May overlap with the treatment objective
GRA treatment patent	Treatment of hypercortisolism or Cushing's syndrome	May be practiced without the diagnostic ratio
Patent 10,151,763	Sustained GRA treatment plus C:A-ratio diagnosis	Combination method right
Nonsteroidal GRA patent	New molecule, use or formulation	Potentially overlapping product and method rights
Surgical-treatment patent	Patient selection or surgical intervention	Claims 16 and 26 may intersect at the treatment-selection stage

The estate is strongest when a product label or clinical protocol expressly recommends sustained GRA therapy followed by cortisol and ACTH testing to distinguish pituitary from ectopic disease. It is weaker against a product used only to control hyperglycemia without the claimed diagnostic workflow.

What generic launch scenarios exist?

Scenario 1: Label carve-out

A generic applicant removes the Cushing's diagnostic instructions and markets the product for an unclaimed use. This reduces method-patent exposure but does not eliminate induced-infringement risk if promotional materials or ordinary use direct physicians toward the patented protocol.

Scenario 2: Paragraph IV challenge

The applicant certifies that the patent is invalid, unenforceable or not infringed. The patent owner can trigger the statutory stay by filing suit within the applicable period after receiving notice.[4]

Scenario 3: Non-infringing clinical protocol

A competing product is administered for less than five weeks, uses no C:A-ratio calculation, or uses a different diagnostic marker. This approach targets the combination limitations.

Scenario 4: Alternative GRA

A nonsteroidal GRA is used for Cushing's syndrome. Claims 4, 12, 19 and 27 create potential exposure if the same six-week treatment and ratio-based diagnosis are used.

Scenario 5: Clinical-use enforcement

The product reaches the market, but enforcement focuses on hospitals, specialty clinics or laboratories that implement the complete protocol. This strategy may face practical and evidentiary limits because several actors may perform different claim steps.

What licensing or commercial relationships are relevant?

Corcept Therapeutics is the company commercially associated with Korlym and mifepristone's Cushing's syndrome indication.[2] The patent claims are commercially relevant to Corcept's product because the treatment component corresponds to the FDA-approved use, although the diagnostic component is narrower than the approved indication.

No licensing deal or settlement should be attributed to U.S. Patent 10,151,763 without a public agreement, SEC filing, court order or patent-assignment record. Patent assignment does not by itself establish a commercial license or freedom-to-operate arrangement.

Key Takeaways

• U.S. Patent 10,151,763 claims a combined treatment and diagnosis protocol for ACTH-dependent Cushing's syndrome.
• The central technical element is comparison of the cortisol-to-ACTH ratio before and after at least five weeks of GRA treatment.
• A lower ratio supports ectopic Cushing's syndrome; a higher ratio supports pituitary Cushing's disease.
• Mifepristone, nonsteroidal GRAs, saliva, plasma and 24-hour urine are covered through dependent claims.
• Claims 16 and 26 add surgical direction: transsphenoidal surgery for pituitary disease and adrenalectomy for ectopic disease.
• The patent does not claim mifepristone composition, Korlym formulation or manufacturing technology.
• The principal generic risk is a Paragraph IV challenge or a label-based dispute involving Korlym or another GRA.
• The main design-around options are avoiding the claimed treatment duration, avoiding the C:A-ratio calculation, using a different diagnostic marker, or omitting the patented diagnostic use from the label.
• A precise expiration date requires the patent's priority chain, patent-term adjustment, terminal-disclaimer and maintenance-fee records.
• Biosimilar litigation is not the relevant pathway because mifepristone is a small molecule.

FAQs

Does Patent 10,151,763 cover all mifepristone treatment for Cushing's syndrome?

No. It covers mifepristone treatment only when combined with the claimed baseline and post-treatment cortisol and ACTH measurements, C:A-ratio calculation and diagnostic conclusions, subject to the limitations of the applicable claim.

Can a laboratory infringe Patent 10,151,763 by reporting cortisol and ACTH results?

Reporting the two analyte results alone does not necessarily practice the claimed method. Exposure increases if the laboratory administers or directs GRA treatment, calculates the C:A ratio and reports the claimed disease-source diagnosis.

Does the patent cover pituitary surgery itself?

No. Claims 16 and 26 require diagnosing the patient and treating the patient with transsphenoidal surgery as part of the claimed method. The patent does not broadly claim every transsphenoidal operation for Cushing's disease.

Is a nonsteroidal glucocorticoid receptor antagonist outside the patent?

Not necessarily. Claims 4, 12, 19 and 27 expressly reach nonsteroidal GRAs when the claimed treatment duration and diagnostic measurements are used.

Is a 505(b)(2) applicant automatically free of this patent?

No. A 505(b)(2) applicant must assess listed patents, labeling, induced infringement and any applicable use carve-outs. The regulatory pathway does not eliminate method-patent exposure.

References

1. United States Patent No. 10,151,763, Methods of treating and diagnosing Cushing's syndrome (issued Dec. 11, 2018).
2. U.S. Food and Drug Administration. (2012). Korlym (mifepristone) prescribing information.
3. United States Code, 35 U.S.C. §§ 154, 156 and 173.
4. United States Code, 21 U.S.C. § 355(j), including Paragraph IV certification provisions.
5. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012); Alice Corp. v. CLS Bank International, 573 U.S. 208 (2014).

Drugs Protected by US Patent 10,151,763

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						TREATING CUSHING'S SYNDROME

International Family Members for US Patent 10,151,763

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017210156
Canada	3011728
European Patent Office	3405101