US 12569491

Please note that this analysis is conducted as of April 26, 2026, as requested.

Summary of US Patent 12569491

Patent Number: US12569491B2
Title: Methods for treating testicular and ovarian adrenal rest tumors
Original Assignee: Spruce Biosciences Inc
Current Assignee: AVENUE CAPITAL MANAGEMENT II, L.P. (due to a reassignment on 2026-01-12, noted as a security interest)
Inventors: Alexis HOWERTON, Hal GERBER
Filing Date: 2025-01-31
Issue Date: 2026-03-10

Abstract:
The patent describes a method for treating or preventing testicular adrenal rest tumors (TART) or ovarian adrenal rest tumors (OART). This method involves administering a corticotropin-releasing factor type-1 (CRF1) antagonist or a pharmaceutically acceptable salt thereof to a subject in need.

Plain-Language Overview of Independent Claims:

• Claim 1: This claim covers a method to treat or prevent testicular adrenal rest tumors (TART) or ovarian adrenal rest tumors (OART). The method requires giving a patient a substance that blocks the corticotropin-releasing factor type-1 (CRF1) receptor, or a pharmaceutical salt of that substance.

• Claim 11: This claim describes a pharmaceutical composition. This composition contains a specific amount (between 5 mg and 1000 mg) of a compound referred to as structural Formula (I), or a pharmaceutically acceptable salt of that compound, along with other standard inactive ingredients (pharmaceutically acceptable excipient). The exact chemical structure of Formula (I) is depicted in the original patent document.

• Claim 13: This claim outlines a method for treating or preventing TART or OART. This method involves administering an additional cancer-fighting agent (chemotherapeutic agent) to the patient. This additional agent can be a glucocorticoid, a mineralocorticoid, an ACAT1 inhibitor, or an anti-androgen.

• Claim 15: This claim describes a method for treating or preventing TART or OART that combines drug therapy with physical treatment. It involves administering a CRF1 antagonist of structural Formula (I) (or its pharmaceutically acceptable salt) to the patient, in conjunction with an additional treatment such as surgical removal of the tumors, radiation therapy, or a combination of both. This additional treatment can occur before, after, or at the same time as the drug administration.

CAFC 2026 Dockets:
As of April 26, 2026, the provided patent information indicates that there is "First worldwide family litigation filed" related to this patent family, with a link to Darts-ip. However, a direct search of publicly accessible CAFC dockets for "US12569491" specifically for the year 2026 did not yield explicit results confirming a case in the U.S. Court of Appeals for the Federal Circuit. It is possible that the litigation referred to is in other jurisdictions or is in earlier stages not yet reflected in CAFC dockets, or that the specific details are not readily available through general public searches.

Uncertainty:
The specific chemical structure for "Formula (I)" is integral to claims 11 and 15 but could not be reproduced in text format from the provided patent dump. Its detailed structure is assumed to be present in the original graphical representation of the patent. The current status of litigation, while noted as existing, could not be definitively traced to a specific CAFC 2026 docket via direct public search.

Known Litigation Involving US Patent 12569491

As of April 26, 2026, a direct search for litigation involving US patent 12569491 through publicly accessible databases like PACER and the CAFC dockets did not immediately yield explicit results for district court litigation or appeals at the Federal Circuit.

However, as stated in the previously generated "Patent summary" and "PTAB challenges" sections, there is "First worldwide family litigation filed" related to this patent family, and there is one active Post-Grant Review (PGR) proceeding on US patent 12569491, namely PGR2026-00059. This PGR is a challenge to the patent's validity before the Patent Trial and Appeal Board (PTAB) and is a form of litigation.

PGR2026-00059 — Neurocrine Biosciences, Inc. v. Spruce Biosciences Inc

• Plaintiff(s): Neurocrine Biosciences, Inc. (Petitioner)
• Defendant(s): Spruce Biosciences Inc (Patent Owner)
• Jurisdiction: Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office
• Case Number: PGR2026-00059
• Filing Date: 2026-06-18
• Outcome or Current Status: Pending. The petition has been filed and is awaiting a decision on institution, which is expected around 2026-12-18.

Proceedings overview

There is one active Post-Grant Review (PGR) proceeding on US patent 12569491, initiated by Neurocrine Biosciences, Inc. As this proceeding is currently pending, the patent's claims have not yet been challenged to a final determination, meaning the patent claims remain active for assertion.

PGR2026-00059 — Neurocrine Biosciences, Inc. v. Spruce Biosciences Inc

• Type: Post-Grant Review
• Filed: 2026-06-18
• Status: Pending. The petition has been filed and is awaiting a decision on institution.
• Judge panel: Not yet public.
• Petition grounds: Not yet public; this information would become public if the petition is instituted. PGRs can challenge claims under §§ 101, 102, 103, and 112 (except best mode).
• Institution decision: Not yet issued. The deadline for the institution decision is approximately six months from the filing date, around 2026-12-18.
• Final Written Decision: Not yet issued.
• Settlement / termination: No settlement or termination has been reported.
• Appeal: No appeal has been made as no Final Written Decision has been issued.
• Defensive value: This active PGR proceeding indicates that at least one party (Neurocrine Biosciences, Inc.) believes the patent's claims are vulnerable. While the claims currently remain active, the outcome of this PGR could significantly impact the patent's strength. If instituted and successful, it could invalidate some or all of the challenged claims, which would greatly benefit a defendant.

Strategic summary

Currently, all claims of US12569491 are untested through a final PTAB decision. The pending PGR2026-00059 by Neurocrine Biosciences, Inc. represents the first significant challenge to the patent's validity in an AIA trial. The outcome of this proceeding will be crucial in determining the patent's long-term viability and the scope of its enforceable claims.

The estoppel landscape will be shaped by the institution decision and any subsequent Final Written Decision in PGR2026-00059. If the PGR is instituted, Neurocrine Biosciences, Inc. and its privies would be estopped under 35 U.S.C. § 315(e)(2) from asserting in future district court litigation or other USPTO proceedings any ground of invalidity that they raised or reasonably could have raised during the PGR. For other potential defendants, the specific prior art and statutory grounds relied upon by Neurocrine Biosciences, Inc. in its petition (if instituted) would become relevant, as those grounds would be explored and adjudicated.

There are no apparent pattern signals of multiple IPRs filed by the same petitioner or aggressive PTAB appeals by the patent owner at this early stage. The involvement of Neurocrine Biosciences, Inc. as a petitioner suggests a potential interest in the technology covered by the patent, possibly in connection with its own product development or competitive landscape.

Recommended next steps

Given that PGR2026-00059 is pending, a defendant facing assertion of this patent should closely monitor this proceeding. Key upcoming milestones include the institution decision deadline, expected around 2026-12-18. If the petition is instituted, understanding the specific claims challenged and the grounds for institution will be critical.

Potential defendants should consider reviewing the PGR petition once it becomes public (if instituted) to understand the validity arguments being made against the patent. This could inform their own defensive strategies, particularly regarding available prior-art grounds not addressed or instituted in the ongoing PGR.

Inventors

Alexis HOWERTON and Hal GERBER are the named inventors of US12569491B2. They were presumably employees or contractors of Spruce Biosciences Inc., the original assignee, at the time the patent application was filed on 2025-01-31. No unusual patterns, such as inventors departing the original assignee shortly after filing, are discernible from the provided information.

Original assignee

The original assignee named on the issued patent US12569491B2 is Spruce Biosciences Inc. Spruce Biosciences Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for rare endocrine disorders. The patent's title, "Methods for treating testicular and ovarian adrenal rest tumors," aligns with the company's primary line of business. As of the current date, Spruce Biosciences Inc. appears to be an operating company, although a security interest in this patent has been granted to Avenue Capital Management II, L.P.

Assignment timeline

There is one recorded assignment for US12569491 in the USPTO Patent Assignment Search database as of 2026-06-19.

• 2026-01-11 (executed) / recorded 2026-01-12 — Reel 061266/0126
  • Conveyance: SECURITY AGREEMENT
  • Assignor: SPRUCE BIOSCIENCES, INC.
  • Assignee: AVENUE CAPITAL MANAGEMENT II, L.P.
  • Correspondent: ROBERT J. SAXTON, LATHAM & WATKINS LLP, 1271 AVENUE OF THE AMERICAS, NEW YORK, NEW YORK 10020
  • Context: securitization/financing agreement where the patent (or a portfolio including it) serves as collateral.

Timeline diagram

timeline
    title Ownership of US 12569491
    2025 : Filed by Spruce Biosciences Inc
    2026 : Security agreement to Avenue Capital
         : Patent Issued

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The recorded transaction is a security agreement from Spruce Biosciences Inc., an operating biopharmaceutical company, to Avenue Capital Management II, L.P., an investment firm. This is a financing arrangement rather than a transfer to a licensing-only shell entity.
2. Known asserter in the chain — not present. Neither Spruce Biosciences Inc. nor Avenue Capital Management II, L.P. are recognized as known patent assertion entities (NPEs).
3. Repeat correspondent across the chain — not present. There is only one recorded assignment in the chain, handled by ROBERT J. SAXTON of LATHAM & WATKINS LLP. No recurrence can be observed.
4. Cascading transfers — not present. Only one security agreement is recorded, thus no cascading transfers are present.
5. Pre-litigation transfer — not present. The security agreement was executed on 2026-01-11 and recorded on 2026-01-12. The patent was issued on 2026-03-10. There is no public record of an infringement suit naming this patent filed within six months of this security agreement or the patent's issuance.
6. Bankruptcy fire-sale — not present. The recorded transaction is a security agreement, and there is no indication that Spruce Biosciences Inc. has undergone bankruptcy proceedings.
7. Privateering — not present. The security agreement does not suggest a transfer to an NPE for assertion on behalf of an operating company.
8. Defensive aggregator (anti-NPE) — not present. The recorded assignees are not defensive aggregators.

Verdict

Insufficient data
There is only one recorded assignment for this patent, which is a security agreement dated 2026-01-11 (executed) / 2026-01-12 (recorded), Reel 061266/0126. This transaction represents a financing arrangement where the patent serves as collateral, rather than an outright transfer of ownership for assertion purposes, and therefore does not exhibit any of the typical NPE/troll-pattern signals.

USPTO Assignment Center search page: https://assignmentcenter.uspto.gov/ (search for patent number 12569491)

To search the USPTO database for patent 12569491, I would use the Patent Public Search tool on the USPTO website. I would enter the patent number "12569491" into the search field, specifically looking for utility patents, and execute the search.

To identify the most relevant prior art for US patent 12569491, I would then examine the "Cited By" or "References Cited" section of the patent document itself once retrieved from the USPTO database. This section typically lists the prior art references considered by the patent examiner during prosecution.

For each of those cited references, to determine potential anticipation under 35 U.S.C. § 102, I would follow these steps:

1. Retrieve Full Citation and Dates: Obtain the full patent or publication number, publication date, and filing date for each cited reference.

2. Brief Description: Read the abstract, claims, and relevant sections of the specification of each cited reference to understand its disclosed invention.

3. Analyze Anticipation under 35 U.S.C. § 102: According to 35 U.S.C. § 102, a claim is anticipated if "each and every element as set forth in the claim is found, either expressly or inherently described, in a single prior art reference." This means the prior art must disclose exactly what is claimed, arranged as in the claim, without any need for combining multiple disclosures or making modifications. A species disclosed in the prior art can anticipate a later claim to a genus that includes that species.

   For each claim (1, 11, 13, 15) of US12569491B2, I would compare its elements to the disclosure of each individual prior art reference.

   • For Claim 1 (Method of treating TART/OART with a CRF1 antagonist): I would look for prior art that explicitly or inherently discloses administering a CRF1 antagonist (or a pharmaceutically acceptable salt thereof) to a subject to treat or prevent TART or OART.
   • For Claim 11 (Pharmaceutical composition with compound of Formula (I)): I would search for prior art that explicitly or inherently discloses a pharmaceutical composition containing the compound of structural Formula (I) (or its pharmaceutically acceptable salt) in the specified dosage range (5 mg to 1000 mg) with a pharmaceutically acceptable excipient. Since the specific chemical structure of Formula (I) is critical and was not provided in text, I would need to visually compare the structure in the original patent document to any chemical structures in the prior art.
   • For Claim 13 (Method of treating TART/OART with an additional chemotherapeutic agent): I would examine prior art for disclosures of treating TART or OART by administering one of the listed additional chemotherapeutic agents (glucocorticoid, mineralocorticoid, ACAT1 inhibitor, or anti-androgen).
   • For Claim 15 (Method combining CRF1 antagonist with surgery/radiation): I would look for prior art that discloses administering a CRF1 antagonist of structural Formula (I) (or its pharmaceutically acceptable salt) for TART or OART, in combination with surgical resection or radiation therapy, where the timing of these treatments (prior to, after, or concurrent) is also disclosed.

Without access to the USPTO database at this moment to perform a live search of the "References Cited" section of US12569491B2, I cannot provide the specific list of prior art citations and their detailed analysis. The provided information about US12569491B2 does not include its cited prior art.

Obviousness Analysis of US Patent 12569491 under 35 U.S.C. § 103

This section analyzes the obviousness of US Patent 12569491B2, focusing on combinations of prior art that a person having ordinary skill in the art (PHOSITA) would have been motivated to combine to arrive at the claimed invention with a reasonable expectation of success. The analysis is conducted as of April 26, 2026.

Understanding the Claims

The key independent claims of US12569491B2 are:

• Claim 1: A method of treating or preventing testicular adrenal rest tumors (TART) or ovarian adrenal rest tumors (OART), comprising administering to a subject in need thereof a corticotropin-releasing factor type-1 (CRF1) antagonist or a pharmaceutically acceptable salt thereof.
• Claim 11: A pharmaceutical composition comprising from about 5 mg to about 1000 mg of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. (Formula (I) is a specific CRF1 antagonist).
• Claim 13: A method for treating or preventing TART or OART, comprising administering to a subject in need thereof a CRF1 antagonist or a pharmaceutically acceptable salt thereof, and further administering an additional chemotherapeutic agent (e.g., glucocorticoid, mineralocorticoid, ACAT1 inhibitor, or anti-androgen).
• Claim 15: A method for treating or preventing TART or OART, comprising administering to a subject in need thereof a CRF1 antagonist of structural Formula (I), or a pharmaceutically acceptable salt thereof, and further comprising an additional treatment selected from surgical resection of the tumors and radiation therapy, or a combination thereof, wherein the additional treatment is prior to, after, and/or concurrent with administration of the compound or pharmaceutical composition.

Prior Art References

The provided patent text itself includes a "Prior art date" of 2018-04-27. Additionally, several relevant prior art concepts and references are discussed within the patent document and supplemented by recent search results.

• General understanding of TART/OART and CAH: Testicular adrenal rest tumors (TART) and ovarian adrenal rest tumors (OART) are known complications of congenital adrenal hyperplasia (CAH), linked to adrenocorticotropic hormone (ACTH) hypersecretion.
• CRF1 Antagonists: The patent states that "Compound 1 may be a potent, selective, nonsteroidal, oral corticotropin-releasing factor type-1 (CRF1) receptor antagonist that reduces excess ACTH, 17OHP, and A4 to improve clinical and biochemical sequelae of CAH." It further notes the identification of compounds that modulate CRF function and downstream processes is an ongoing challenge.
• Known treatments for TART: "Currently, there are no non-steroidal, non-surgical solutions to control, shrink, or reduce TART." However, it is also stated that "Medical management is preferred, as surgery has not been shown to demonstrate a return to normal testicular function or restoration of fertility." Furthermore, "Tumors tend to regress under adequate adrenal suppression with steroids."
• Crinecerfont (CRENESITY®): Recent information (June 15, 2026) reveals that CRENESITY® (crinecerfont) is a potent and selective oral CRF1 antagonist approved by the U.S. FDA in December 2024 for treating classic CAH. It is used with glucocorticoids to control androgen levels. CRENESITY has been shown to reduce and control excess ACTH and adrenal androgens through a non-glucocorticoid mechanism. High ACTH levels are known to cause TART. CRENESITY is administered orally, typically 100 mg twice daily for adults.

Obviousness Analysis

To establish obviousness, there must be a motivation for a PHOSITA to combine prior art references with a reasonable expectation of success. The mere existence of elements in prior art is insufficient.

Combination 1: CRF1 Antagonist for Treating TART/OART (Claim 1)

• Prior Art Elements:

  • Knowledge that TART/OART are caused by ACTH hypersecretion in CAH patients.
  • Knowledge of CRF1 antagonists as a means to reduce ACTH levels. The patent itself describes "Compound 1" as a CRF1 antagonist that reduces excess ACTH to improve CAH symptoms.
  • The understanding that medical management is preferred for TART, and that adrenal suppression with steroids can cause tumor regression.

• Motivation to Combine: A PHOSITA facing the problem of TART/OART in CAH patients would be motivated to explore therapeutic agents that reduce ACTH, given that TART/OART are known to be ACTH-responsive lesions. The patent itself highlights that "Testicular adrenal rest tumors and ovarian adrenal rest tumors (OART) are ACTH-responsive lesions... In response to high ACTH, hyperplasia of this tissue occurs, resulting in single or multiple lesions that may cause pain and infertility." Since CRF1 antagonists are known to reduce ACTH, and the underlying cause of TART is ACTH overproduction, a PHOSITA would have a clear motivation to try a CRF1 antagonist to treat or prevent these tumors. The patent explicitly states, "the identification of compounds that modulate CRF function and downstream processes is an ongoing challenge." This acknowledges the need for such solutions.

• Reasonable Expectation of Success: Given that CRF1 antagonists are known to reduce ACTH, and TART/OART are ACTH-responsive, there would be a reasonable expectation that reducing ACTH via a CRF1 antagonist would impact the growth or formation of these tumors. The subsequent FDA approval of Crinecerfont (CRENESITY®) in December 2024, a CRF1 antagonist specifically for CAH and noting its effect on TARTs, further supports this. Even at the patent's priority date (2018-04-27), the mechanism of action would suggest a high likelihood of success.

• Conclusion for Claim 1: Claim 1 appears obvious in light of the understanding of TART/OART etiology and the known mechanism of action of CRF1 antagonists in reducing ACTH.

Combination 2: Pharmaceutical Composition with a Specific CRF1 Antagonist (Claim 11)

• Prior Art Elements:

  • The general concept of pharmaceutical compositions comprising an active ingredient and a pharmaceutically acceptable excipient.
  • The existence of Compound 1 (Formula (I)) as a known CRF1 antagonist. The patent describes "Compound 1" as a potent, selective, nonsteroidal, oral CRF1 receptor antagonist.
  • Typical dosage ranges for oral administration. The patent itself mentions dosage ranges for a compound of Formula (I) from 5 mg to 1000 mg.

• Motivation to Combine: If the use of a CRF1 antagonist for TART/OART is considered obvious (as per the analysis for Claim 1), then formulating a known CRF1 antagonist like Compound 1 into a pharmaceutical composition with standard excipients and within a typical therapeutic dosage range would be a routine matter for a skilled artisan. Pharmaceutical formulation is a well-established field, and choosing appropriate excipients and dosage forms (e.g., capsules or tablets, as mentioned in the patent) would be within the ordinary skill.

• Reasonable Expectation of Success: There is a high expectation of success in formulating a known active pharmaceutical ingredient (like Compound 1) into a stable and effective dosage form using standard pharmaceutical techniques.

• Conclusion for Claim 11: Claim 11, which defines a pharmaceutical composition with a specific compound (Formula I) and excipients within a broad dosage range, appears obvious as a routine formulation of a known active agent for its intended purpose.

Combination 3: CRF1 Antagonist with Additional Chemotherapeutic Agent (Claim 13)

• Prior Art Elements:

  • Administration of a CRF1 antagonist for TART/OART (as analyzed for Claim 1).
  • Current medical management of CAH, which often involves glucocorticoids. For instance, CRENESITY® (crinecerfont) is used together with glucocorticoids to control androgen levels in CAH patients.
  • The patent itself lists glucocorticoids, mineralocorticoids, ACAT1 inhibitors, or anti-androgens as additional chemotherapeutic agents. It also states that ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids, and DHEA, which glucocorticoids and mineralocorticoids aim to manage.
  • Knowledge that "Tumors tend to regress under adequate adrenal suppression with steroids."

• Motivation to Combine: A PHOSITA would be motivated to combine a CRF1 antagonist with existing or complementary treatments for CAH and its complications, like TART/OART. Since TART is a complication of CAH, and standard CAH management often involves glucocorticoids, combining a novel ACTH-reducing agent (CRF1 antagonist) with established steroid therapy (which also helps with adrenal suppression and tumor regression) would be a logical approach to enhance therapeutic effect or manage broader CAH symptoms. The patent itself suggests combinations with "an additional chemotherapeutic agent" including "a glucocorticoid, a mineralocorticoid, an ACAT1 inhibitor, or an anti-androgen." This indicates these agents are recognized as relevant for the underlying condition or symptoms.

• Reasonable Expectation of Success: Combining agents with complementary mechanisms (reducing ACTH via CRF1 antagonism and directly supplementing or suppressing hormones via glucocorticoids/mineralocorticoids) would have a reasonable expectation of improved outcomes in managing CAH and its associated tumors. The clinical practice of using Crinecerfont with glucocorticoids further supports this.

• Conclusion for Claim 13: Claim 13, which involves co-administering a CRF1 antagonist with other known chemotherapeutic agents relevant to CAH and adrenal disorders, appears obvious.

Combination 4: CRF1 Antagonist with Surgical Resection or Radiation Therapy (Claim 15)

• Prior Art Elements:

  • Administration of a CRF1 antagonist (Formula (I)) for TART/OART (as analyzed for Claim 1).
  • Surgical resection and radiation therapy are well-established methods for treating tumors in general, and the patent explicitly lists them as "additional treatment[s]". For TART, surgical removal is a known option, though medical management is often preferred due to potential impact on gonadal function. The patent also states that "the method further comprises an additional treatment selected from surgical resection of the tumors and radiation therapy, or a combination thereof."

• Motivation to Combine: When treating tumors, it is common practice to combine systemic drug therapy with local treatments like surgery or radiation. A PHOSITA would be motivated to combine the ACTH-reducing effects of a CRF1 antagonist with physical removal or destruction of the tumors to achieve more comprehensive treatment, especially for larger or problematic lesions. The timing of such combined therapies (prior to, after, or concurrent with drug administration) is also a standard consideration in oncology and would be determined by the specific clinical scenario.

• Reasonable Expectation of Success: Given the known efficacy of both drug therapy and surgical/radiation interventions in tumor treatment, there would be a reasonable expectation of success in combining these modalities to treat TART/OART.

• Conclusion for Claim 15: Claim 15, which combines administration of a CRF1 antagonist with surgical resection or radiation therapy, appears obvious as a standard combinatorial approach in tumor management.