DCT
1:25-cv-00059
Neurocrine Biosciences Inc v. Spruce Biosciences Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Neurocrine Biosciences, Inc. (Delaware)
- Defendant: Spruce Biosciences, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Latham & Watkins LLP
- Case Identification: 1:25-cv-00059, D. Del., 01/14/2025
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a corporation organized and existing under the laws of Delaware and therefore resides in the district.
- Core Dispute: Plaintiff seeks a declaratory judgment that Defendant’s patent is invalid for lacking sufficient written description to support its broad claims.
- Technical Context: The technology involves corticotropin-releasing factor type 1 (CRF1) receptor antagonists, a class of drugs used to treat congenital adrenal hyperplasia (CAH), a rare genetic disease.
- Key Procedural History: The complaint notes that the Patent Trial and Appeal Board (PTAB) recently issued Final Written Decisions finding all claims of two related patents from the same family (’908 and ’201 patents) invalid for lack of written description. The complaint states that the patent-in-suit (’557 patent) shares the same specification and alleged defects. Defendant has since filed for Director Review of the PTAB’s decisions.
Case Timeline
| Date | Event |
|---|---|
| 2017-08-14 | ’557 Patent Priority Date |
| 2019-04-18 | Parent application for patent family originally filed with claims limited to tildacerfont |
| 2020-12-01 | Related U.S. Patent No. 10,849,908 issues |
| 2021-05-18 | Related U.S. Patent No. 11,007,201 issues |
| 2021-05-28 | Neurocrine files Petition for Post-Grant Review of the ’908 patent |
| 2022-05-31 | U.S. Patent No. 11,344,557 issues |
| 2024-10-15 | Related U.S. Patent No. 12,115,166 issues |
| 2024-11-26 | PTAB issues Final Written Decision finding ’908 patent claims invalid |
| 2024-11-27 | PTAB issues Final Written Decision finding ’201 patent claims invalid |
| 2024-12-10 | Spruce announces it is "winding down" investment in tildacerfont for CAH |
| 2024-12-13 | FDA approves Neurocrine’s CRENESSITY™ (crinecerfont) for CAH |
| 2024-12-20 | Neurocrine commercially releases CRENESSITY™ |
| 2024-12-26 | Spruce files for Director Review of PTAB Final Written Decisions |
| 2025-01-14 | Complaint for Declaratory Judgment filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,344,557 - “Corticotropin Releasing Factor Receptor Antagonists”
The Invention Explained
- Problem Addressed: The patent addresses the treatment of congenital adrenal hyperplasia (CAH), a condition involving hormonal imbalances ('557 Patent, col. 9:35-41). In CAH, deficiencies in enzymes like 21-hydroxylase disrupt cortisol production, leading to an overproduction of androgens driven by elevated levels of adrenocorticotropic hormone (ACTH) ('557 Patent, col. 11:3-25). Standard treatments often involve high doses of glucocorticoids, which carry risks of significant side effects ('557 Patent, col. 11:46-49).
- The Patented Solution: The invention proposes a method for treating CAH by administering a "CRF1 receptor antagonist." This antagonist is intended to block the CRF1 receptor, thereby reducing ACTH levels and, consequently, the overproduction of androgens and other hormone precursors like 17-hydroxyprogesterone (17-OHP) ('557 Patent, Abstract; col. 11:53-64). The specification identifies a specific compound, referred to as "Compound 1" (tildacerfont), and provides clinical data showing its effect on reducing ACTH and 17-OHP levels in patients ('557 Patent, col. 2:36-40; col. 43:45-67; Figs. 2-3).
- Technical Importance: This approach offered a potential alternative or adjunct to high-dose steroid therapy by targeting a key upstream regulator (CRF) in the hormonal cascade that causes CAH symptoms, aiming to normalize hormone levels with a different mechanism of action (Compl. ¶20).
Key Claims at a Glance
- The complaint identifies independent Claim 1 as exemplary (Compl. ¶34).
- Essential elements of Claim 1 are:
- A method for treating congenital adrenal hyperplasia (CAH) in a human.
- The method comprises administering a therapeutically-effective amount of a CRF1 receptor antagonist or a pharmaceutically acceptable salt thereof.
- The administration results in the reduction of an adrenocorticotropic hormone (ACTH) level in the human by at least about 10% from baseline.
- The administration also results in the reduction of a 17-hydroxyprogesterone (17-OHP) level in the human by at least about 10% from baseline.
- The complaint challenges all claims of the '557 patent (Compl. ¶68).
III. The Accused Instrumentality
Product Identification
CRENESITY™ (crinecerfont), Plaintiff Neurocrine's own product (Compl. ¶1).
Functionality and Market Context
- Crinecerfont is a "first-in-class adjunctive therapy" for classic CAH, acting as a corticotropin-releasing factor type 1 (CRF1) receptor antagonist (Compl. ¶1). It is the first new treatment for classic CAH in over 70 years and is intended to allow patients to take lower doses of glucocorticoids while managing androgen levels (Compl. ¶¶1, 20-21).
- The complaint alleges that Spruce, the Defendant, has failed in its own attempts to develop a CRF1 receptor antagonist for CAH (tildacerfont) and has announced it is "winding down" its investment in that program (Compl. ¶¶2, 27). The complaint includes a screenshot of Spruce's development pipeline, showing tildacerfont as its only drug candidate and listing indications other than CAH (Compl. ¶24, p. 9). Neurocrine alleges that because Spruce has no competing product, its patent portfolio is being used to improperly "extract money" from Neurocrine (Compl. ¶¶11, 50).
IV. Analysis of Infringement Allegations
This is a declaratory judgment action for invalidity, not a direct suit for infringement. Neurocrine alleges that an actual controversy exists because Spruce's broad patent claims are directed at Neurocrine's CRENESSITY™ product, creating an immediate risk of an infringement suit (Compl. ¶¶47, 54, 61). The complaint does not contain a traditional infringement claim chart. The following table summarizes Neurocrine’s stated basis for the controversy by outlining how its CRENESSITY™ product aligns with the elements of the '557 patent’s exemplary claim. The complaint's central argument is that while CRENESSITY™ may fall within the literal scope of the broad claims, those claims are invalid for lack of written description (Compl. ¶¶39-40, 67). The complaint reproduces the text of Claim 1 of the ’557 patent, which broadly claims a method of treating CAH with a "CRF1 receptor antagonist" (Compl. ¶34, p. 12).
| Claim Element (from Independent Claim 1) | Alleged CRENESSITY™ Functionality (Basis for DJ Controversy) | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating congenital adrenal hyperplasia (CAH) in a human... | CRENESSITY™ is an FDA-approved adjunctive therapy for classic CAH. | ¶1, ¶21 | col. 48:62-64 |
| ...comprising administering to the human a therapeutically-effective amount of a CRF1 receptor antagonist... | CRENESSITY™ (crinecerfont) is identified as a "first-in-class ... CRF1 receptor antagonist therapy." | ¶1 | col. 48:64-66 |
| ...wherein an adrenocorticotropic hormone (ACTH) level in the human is reduced by at least about 10% from baseline... | While not explicitly quantified for CRENESSITY™ in the complaint, its mechanism as a CRF1 receptor antagonist is alleged to reduce downstream hormones like ACTH. | ¶17 | col. 49:1-3 |
| ...and wherein a 17-hydroxyprogesterone (17-OHP) level is reduced in the human by at least about 10% from baseline. | The complaint does not provide specific data for CRENESSITY™ but alleges that as a CRF1 antagonist, it is intended to "reduce excessive androgens." | ¶20 | col. 49:1-3 |
- Identified Points of Contention:
- Scope Questions: The central issue is one of validity, not infringement. The primary question for the court is whether the patent's disclosure of a single species (tildacerfont, "Compound 1") provides adequate written description to support a claim covering the entire genus of "CRF1 receptor antagonist" compounds for treating CAH (Compl. ¶¶37, 39, 67). To illustrate the subsequent broadening of claims, the complaint provides an image of an original claim from the parent application, which was limited to the specific chemical structure of tildacerfont (Compl. ¶35, p. 13).
- Technical Questions: A key question will be whether the disclosed properties and clinical results of tildacerfont are representative of the entire claimed genus of CRF1 receptor antagonists. The complaint alleges they are not, pointing to tildacerfont's clinical failures in contrast to crinecerfont's success (Compl. ¶¶2, 38).
V. Key Claim Terms for Construction
The construction of the following term is central to the written description and validity dispute.
- The Term: "CRF1 receptor antagonist"
- Context and Importance: Practitioners may focus on this term because the entire case hinges on its proper scope. Neurocrine argues that, in the context of the '557 patent, this term cannot validly encompass the entire functional genus of compounds that antagonize the CRF1 receptor. Instead, it argues the patent's disclosure only supports a scope limited to the single disclosed chemical structure, tildacerfont (Compl. ¶¶37, 39). The resolution of this term's scope will likely determine the patent's validity.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain language of Claim 1 uses the broad functional term "CRF1 receptor antagonist" without any structural limitations that would narrow it to a specific compound or chemical class ('557 Patent, col. 49:1-3).
- Evidence for a Narrower Interpretation: The specification discloses only a single chemical structure for a CRF1 receptor antagonist, "Compound 1" (tildacerfont), and all accompanying examples and clinical data relate solely to that compound ('557 Patent, col. 2:36-40; col. 43:45-67). The complaint alleges that during prosecution of a parent patent, Spruce argued tildacerfont had "unexpected result[s]" and "significant and practical advantage" over other CRF1 antagonists, which may be used to argue the inventors did not consider their invention to be representative of the entire genus (Compl. ¶38).
VI. Other Allegations
No indirect or willful infringement is alleged in this declaratory judgment action.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of validity and scope: Does the patent’s disclosure of a single chemical species (tildacerfont) provide sufficient written description under 35 U.S.C. § 112 to support claims covering the entire functional genus of "CRF1 receptor antagonist" therapies for CAH?
- A key evidentiary question will be the persuasive weight of related PTAB proceedings: To what extent will the court be influenced by the PTAB’s Final Written Decisions that invalidated claims in two parent patents—which share the same specification as the '557 patent—on the identical ground of lack of written description?
- A central legal question will be one of prosecution history estoppel and written description: Can Spruce defend its broad genus claims after allegedly arguing for patentability based on the "unexpected" and "different" properties of its single disclosed compound compared to other members of the same genus?