Details for Patent: 11,827,600

Which drugs does patent 11,827,600 protect, and when does it expire?

Patent 11,827,600 protects DAYBUE STIX and DAYBUE and is included in two NDAs.

Protection for DAYBUE STIX has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has thirteen patent family members in twelve countries.

Summary for Patent: 11,827,600

Title:	Crystalline forms of trofinetide
Abstract:	This disclosure provides crystalline forms of trofinetide and trofinetide hydrate, pharmaceutical compositions comprising crystalline forms of trofinetide and trofinetide hydrate, methods of making crystalline forms of trofinetide or trofinetide hydrate, and methods of treating a disease, condition, or disorder in a subject comprising administering a composition comprising crystalline forms of trofinetide or trofinetide hydrate to the subject.
Inventor(s):	Matthew Peterson, Marlon Carlos, Martin Bernard Catherine Bousmanne, Cecilia Betti, David T. JONAITIS, Lisa M. McCracken, Lisa M. GROVE
Assignee:	Acadia Pharmaceuticals Inc
Application Number:	US17/862,865
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Device;

US Patent 11,827,600: Trofinetide Crystal Form Claims, Scope and Patent Landscape

US Patent 11,827,600 protects a crystalline hydrate form of trofinetide, the active pharmaceutical ingredient in Acadia Pharmaceuticals' Daybue. The patent is directed primarily to the solid-state form, its analytical fingerprints, pharmaceutical compositions, aqueous preparations, kits, therapeutic use and a specified ethanol-mediated crystallization process. It is not a broad patent on trofinetide itself.

The commercial risk is concentrated in the crystalline active ingredient and products manufactured from that form. A competing manufacturer that uses a different solid form, anhydrous trofinetide or a non-infringing manufacturing route could present a different analysis, although downstream composition, formulation and method-of-use patents may still apply.

What does US Patent 11,827,600 protect?

The independent claims cover crystalline trofinetide hydrate with approximately two to four water molecules per trofinetide molecule:

Claim group	Protected subject matter
Claim 1	Crystalline trofinetide.xH2O, where x is about 2 to about 4, identified by one or more analytical characteristics
Claims 2-4	Powder X-ray diffraction and d-spacing profiles
Claims 5-6	FT-Raman and low-frequency Raman profiles
Claim 7	Solid-state carbon-13 NMR profile
Claim 8	Differential scanning calorimetry melting behavior
Claims 9-10	Infrared and near-infrared spectra
Claims 11-12	Narrower hydrate ranges, including approximately three waters
Claim 13	Pharmaceutical composition containing the crystal and excipient
Claim 14	Aqueous formulation containing the dissolved crystal
Claim 15	Method of preparing the aqueous formulation by admixing crystal and water
Claim 16	Kit containing the crystal and dissolution instructions
Claims 17-18	Treatment of specified neurological disorders, including Rett syndrome
Claim 19	Method of making the crystal using aqueous trofinetide, ethanol, cooling and isolation

The central legal limitation is the crystalline hydrate identity. The patent does not claim every trofinetide product, every trofinetide formulation or every method of treating Rett syndrome.

How broad is claim 1 of US 11,827,600?

Claim 1 is broad in structure but narrow in subject matter. It uses nine alternative analytical definitions, including PXRD, Raman, solid-state NMR, DSC, IR and NIR characteristics. The claim can be satisfied by one listed analytical characterization or by a combination.

The principal elements are:

1. The material must be crystalline trofinetide.
2. It must contain approximately two to four equivalents of water.
3. It must exhibit at least one of the specified analytical signatures.
4. The analytical values must fall within the stated tolerances.

The claim is therefore a product claim defined through physical characteristics. It does not require a particular synthesis route, therapeutic indication, dosage strength or excipient.

Why the alternative analytical limitations matter

The use of "or" between the analytical alternatives expands the claim. An accused product may infringe if it meets only the claimed PXRD pattern, even if it does not match every Raman, NMR or DSC feature.

Claims 2 through 10 provide narrower positions. They may be important in litigation because they give the patent owner multiple ways to define the same solid form. Claims 2 and 3 are particularly significant because PXRD is a standard solid-form identification method and is commonly used for pharmaceutical quality control.

What does the hydrate range cover?

Claim 1 covers approximately 2 to approximately 4 waters of hydration. Claim 11 narrows the range to approximately 2.5 to approximately 3.5, while claim 12 centers the claim on approximately three waters.

The word "about" creates a factual boundary question. A product containing a measured water content outside the literal range could still raise infringement issues depending on the analytical method, measurement error, claim construction and prosecution history. The claims do not define a single exact stoichiometric composition in the way a claim to a fixed trihydrate would.

What are the strongest claims in US Patent 11,827,600?

Claims 2, 3, 4, 7 and 19 are the most commercially important.

Claims 2 and 3: PXRD-defined crystal

Claim 2 requires characteristic peaks around 6.7-6.8, 11.4-11.5, 12.6 and 13.7-13.8 degrees 2-theta. Claim 3 adds peaks at 22.3, 23.6, 25.3 and 28.1 degrees.

PXRD is likely to be the primary infringement and quality-control test because it is reproducible, widely used in solid-form analysis and directly compares a defendant's material against the claimed pattern.

Claim 7: solid-state NMR

Claim 7 requires a set of 19 carbon-13 solid-state NMR peaks. Solid-state NMR can distinguish polymorphs, hydrates and amorphous material, but it is more specialized and less likely than PXRD to be the first routine screening method in a generic manufacturing investigation.

Claim 19: crystallization process

Claim 19 covers a process with three defined steps:

1. Adding ethanol to an aqueous trofinetide solution at about 25°C.
2. Cooling the solution to about 0°C.
3. Isolating the resulting solid.

This is a process claim rather than a product claim. It could be relevant where a generic manufacturer uses the same solvent and cooling sequence. It is less useful against a manufacturer that produces the same hydrate through a different crystallization process unless the resulting product claims are also infringed.

What formulations are protected by US Patent 11,827,600?

The patent reaches several product and preparation categories.

Claim	Formulation or use	Commercial relevance
13	Composition containing crystalline trofinetide hydrate and pharmaceutically acceptable excipient	Covers drug product containing the claimed crystal
14	Aqueous formulation in which the crystal is dissolved in water	Directly relevant to an oral liquid product
15	Preparation of the aqueous formulation by mixing crystal and water	Covers a specified preparation step
16	Kit with crystal and instructions for dissolution	Could cover a powder-plus-water presentation
17	Treatment of traumatic brain injury, neurodevelopmental disorders, Rett syndrome, Fragile X syndrome or autism spectrum disorder	Method-of-use protection
18	Treatment of Rett syndrome	Narrower, commercially focused use claim

The formulation claims do not require a particular concentration, pH, preservative, flavor, container or dosing schedule. Claim 14 is therefore potentially broad for an aqueous product, but it remains dependent on use of the claimed crystalline hydrate.

Does the patent cover Daybue?

Daybue is an oral trofinetide solution approved by the FDA for the treatment of Rett syndrome in adults and pediatric patients aged two years and older. The FDA approval was granted in March 2023. [1]

US Patent 11,827,600 is relevant to Daybue because its claims cover:

• The crystalline trofinetide hydrate used as the starting active ingredient.
• Pharmaceutical compositions containing that crystal.
• Aqueous formulations made by dissolving the crystal in water.
• Treatment of Rett syndrome with the composition.

The patent does not, based on the supplied claims, require the full commercial Daybue formulation. It does not expressly recite a specific strength, excipient system, flavor profile or bottle configuration.

When does US Patent 11,827,600 expire?

US Patent 11,827,600 was granted on January 2, 2024. Public patent records identify the patent as a trofinetide crystalline-form patent associated with Neuren Pharmaceuticals Limited and its licensed commercial relationship with Acadia Pharmaceuticals.

Its nominal patent term is expected to run into approximately 2040, subject to the patent's earliest effective nonprovisional or international filing date, patent-term adjustment, terminal disclaimer and any applicable patent-term extension. The grant date is not the expiration date.

The patent term is separate from FDA regulatory exclusivity. Daybue's initial FDA orphan-drug exclusivity provides seven years of protection from approval for the same orphan indication, subject to statutory exceptions. That period runs from the 2023 approval and is distinct from patent rights. [1] [2]

What is the Orange Book status of US Patent 11,827,600?

The Orange Book is the relevant FDA publication for patents submitted for approved small-molecule drug products. Daybue is a small-molecule product, so generic applicants would generally use the ANDA pathway and address listed patents through patent certifications.

A patent covering a crystalline active ingredient may be eligible for Orange Book listing if it claims the drug substance, drug product or approved method of use and satisfies FDA listing requirements. The practical significance of US 11,827,600 depends on whether it is listed against the approved Daybue product and which claims are identified as relevant to the approved indication.

If listed, an ANDA applicant could be required to provide a Paragraph IV certification alleging that the patent is invalid, unenforceable or will not be infringed. A Paragraph IV notice could trigger a 30-month stay of FDA approval if the patent owner or NDA holder files suit within the statutory period. [3]

What Paragraph IV challenges and litigation affect trofinetide?

No Paragraph IV challenger or final district-court decision can be established from the supplied claim text alone. The principal potential litigation pathway is an ANDA challenge involving:

• Invalidation of the crystal-form claims for anticipation or obviousness.
• Non-infringement based on a different polymorph, hydrate state or amorphous form.
• Non-infringement based on analytical characteristics outside the claimed ranges.
• Non-infringement of claim 19 through use of a different crystallization process.
• Invalidity or indefiniteness challenges directed to "about" water content and analytical tolerances.
• Written-description or enablement challenges to the alternative characterization methods.

A generic applicant could also pursue a Paragraph III certification and defer launch until the relevant patent expires, or develop a formulation that avoids the listed crystal form.

How strong is the patent estate for trofinetide?

US Patent 11,827,600 is strongest against a generic using the same crystalline hydrate. Its strength is lower against a competitor that can lawfully select another solid form and demonstrate non-infringement.

Risk category	Assessment	Reason
Same crystalline hydrate	High	Multiple independent analytical routes and dependent claims identify the material
Different polymorph	Moderate to high defense potential	Product claims depend on the claimed physical form
Anhydrous trofinetide	Potentially outside this patent	The claims require xH2O with approximately two to four waters
Amorphous trofinetide	Potentially outside this patent	The claims are directed to crystalline material
Alternative crystallization route	Potentially outside claim 19	Process claim requires ethanol addition, aqueous solution and cooling
Same crystal in a different excipient system	Limited defense	Claim 13 is not tied to a specific excipient
Rett syndrome indication	Overlap remains possible	Claims 17 and 18 cover use of the patented composition for Rett syndrome

The estate has a layered structure: solid-form claims, formulation claims, kit claims, manufacturing claims and method-of-use claims. That structure improves enforcement options but does not eliminate design-around opportunities.

Which companies are challenging trofinetide exclusivity?

Acadia Pharmaceuticals is the commercial sponsor of Daybue, while Neuren Pharmaceuticals is the originating research and intellectual-property holder under the parties' licensing arrangement. [4]

No approved generic trofinetide product or trofinetide biosimilar exists. Biosimilar analysis is not applicable because trofinetide is a synthetic small molecule, not a biologic. Any competitor would generally pursue an ANDA or another small-molecule regulatory pathway rather than a biosimilar application.

The competitive landscape is therefore divided between:

• Generic manufacturers evaluating an ANDA and solid-form design-around.
• Specialty pharmaceutical companies developing alternative Rett syndrome treatments.
• Sponsors pursuing different mechanisms or non-trofinetide formulations.
• Contract manufacturers capable of producing or avoiding the claimed hydrate.

What generic launch scenarios exist?

Scenario 1: Same hydrate, Paragraph IV challenge

A generic uses the patented crystalline hydrate and challenges the patent. This is the highest infringement exposure and would likely produce a patent litigation dispute if the patent is Orange Book listed.

Scenario 2: Different solid form

A generic develops an anhydrous, alternative polymorphic or amorphous trofinetide form. This could avoid claim 1 if the material does not meet the claimed hydration and analytical limitations. The applicant would still need to assess other trofinetide patents.

Scenario 3: Same active ingredient, different manufacturing route

A generic avoids claim 19 by using a solvent system or temperature profile that does not meet the claimed process. This strategy does not avoid claims 1 or 13 if the final product is the patented hydrate.

Scenario 4: Formulation substitution

A generic uses a different formulation, such as a tablet, capsule or alternative liquid system. This may avoid some formulation-specific claims but could remain exposed to the crystal composition claim and method-of-use claims.

What manufacturing and IP barriers does the patent create?

The practical barrier is solid-form control. A manufacturer must control:

• Water activity and hydrate stoichiometry.
• Ethanol-to-water ratio.
• Cooling rate and seeding conditions.
• Isolation temperature.
• Drying conditions.
• Storage humidity.
• Conversion between crystalline and amorphous material.
• PXRD and spectroscopic release specifications.

A process that produces the same hydrate through a different route may avoid claim 19 but still infringe the product claims. Conversely, a process that follows the claimed ethanol and cooling sequence but produces a different solid may raise process-infringement questions without necessarily infringing the product claims.

How does this patent compare with a conventional trofinetide composition patent?

A conventional trofinetide composition patent would generally claim the active ingredient, a composition, a dosage form or a therapeutic method without requiring a particular crystal structure. US 11,827,600 is narrower because it depends on the hydrate and its physical signatures, but it can be more difficult to design around when the approved product uses that form as its manufacturing precursor.

Patent type	Scope	Main vulnerability
Trofinetide composition patent	Broad active ingredient or formulation coverage	Prior art and obviousness
Method-of-use patent	Treatment of a defined disease	Indication carve-outs and invalidity
Formulation patent	Specific liquid, tablet or excipient system	Alternative formulation
US 11,827,600	Specific crystalline hydrate and related products/processes	Alternative solid form or route

Key Takeaways

• US Patent 11,827,600 is a crystalline-form patent for trofinetide.xH2O, centered on approximately two to four waters of hydration.
• Claim 1 uses alternative PXRD, Raman, NMR, DSC, IR and NIR definitions, giving the patent multiple product-identification routes.
• Claims 13-16 extend protection to compositions, aqueous formulations, preparation methods and kits.
• Claims 17-18 cover treatment of Rett syndrome and other specified neurological disorders.
• Claim 19 covers a specific ethanol-assisted crystallization process.
• The highest infringement risk is a generic using the same trofinetide hydrate found in the patented product.
• Anhydrous, amorphous or alternative polymorphic trofinetide may provide a design-around route, subject to other patents.
• Trofinetide is a small molecule; biosimilar risk does not apply.
• Generic competition would normally proceed through the ANDA and Paragraph IV framework.
• The patent's nominal term is expected to extend into approximately 2040, subject to the official patent-term calculation and any applicable adjustments.

FAQs

Is US Patent 11,827,600 a patent on Daybue itself?

It is not a blanket patent on every Daybue product. It claims a specific crystalline trofinetide hydrate and products, uses and processes involving that form.

Can a generic use trofinetide without infringing US Patent 11,827,600?

Potentially. A generic may seek a different hydrate, polymorph, amorphous form or manufacturing route. The result depends on whether the final material meets the claim limitations and whether other trofinetide patents apply.

Does claim 19 cover every process for making trofinetide crystals?

No. Claim 19 requires adding ethanol to an aqueous trofinetide solution at about 25°C, cooling to about 0°C and isolating the resulting solid.

Are the PXRD peaks in claim 1 cumulative?

No. Claim 1 is written with alternative characterization options. A product may satisfy the claim through one listed analytical profile or a combination, subject to claim construction and proof.

Does FDA orphan exclusivity replace the patent protection?

No. FDA orphan exclusivity and patent rights are separate. Orphan exclusivity restricts approval of the same drug for the same orphan indication for the statutory period, while the patent can restrict making, using, selling or importing the claimed invention.

References

1. U.S. Food and Drug Administration. (2023). FDA approves first treatment for Rett syndrome. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-rett-syndrome

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

3. U.S. Food and Drug Administration. (n.d.). ANDA submissions: Content and format of an ANDA. https://www.fda.gov/drugs/generic-drugs/abbreviated-new-drug-application-anda

4. Acadia Pharmaceuticals Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission. https://www.sec.gov/edgar.shtml

Drugs Protected by US Patent 11,827,600

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Acadia Pharms Inc	DAYBUE STIX	trofinetide	FOR SOLUTION;ORAL	219884-001	Dec 11, 2025		RX	Yes	Yes					Y
Acadia Pharms Inc	DAYBUE STIX	trofinetide	FOR SOLUTION;ORAL	219884-002	Dec 11, 2025		RX	Yes	Yes					Y
Acadia Pharms Inc	DAYBUE STIX	trofinetide	FOR SOLUTION;ORAL	219884-003	Dec 11, 2025		RX	Yes	Yes					Y
Acadia Pharms Inc	DAYBUE	trofinetide	SOLUTION;ORAL	217026-001	Mar 10, 2023		RX	Yes	Yes					Y

International Family Members for US Patent 11,827,600

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2022309740
Brazil	112023026559
Canada	3224298
Chile	2024000086
China	117460415
China	121591830
Colombia	2023017186