Details for Patent: 10,189,833

Which drugs does patent 10,189,833 protect, and when does it expire?

Patent 10,189,833 protects TURALIO and is included in one NDA.

This patent has fifty-six patent family members in twenty-nine countries.

Summary for Patent: 10,189,833

Title:	Solid forms of a compound modulating kinases
Abstract:	Solid forms of the compound, [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(6-trifluoromethyl-pyridin-3-ylmethyl)-amine HCl salt (Compound I) and its free base, active on the receptor protein kinases c-Kit and/or c-Fms and/or Flt3, were prepared and characterized: Also provided are methods of using the solid forms.
Inventor(s):	Prabha N. Ibrahim, Gary Conard Visor
Assignee:	Daiichi Sankyo Inc
Application Number:	US15/725,197
Patent Claim Types: see list of patent claims	Use; Composition; Device;

US Patent 10,189,833: Pexidartinib Crystalline Form Claims, Exclusivity and Patent Landscape

US Patent No. 10,189,833 protects methods of treating kinase- and macrophage-mediated diseases with a specific crystalline form of Compound I, identified in the pexidartinib patent family as the solid form associated with PLX3397. The claims are not directed broadly to pexidartinib as a molecule. They require a crystalline material producing an XRPD pattern with characteristic peaks at 7.3°, 23.3°, and 28.2° 2θ, each within ±0.2°, using Cu-Kα radiation.

The patent is commercially important because pexidartinib is marketed as Turalio for tenosynovial giant cell tumor, including its historical terminology, pigmented villonodular synovitis. The strongest practical coverage is the combination of the specified crystalline form with treatment of TGCT, PVNS, neurofibromatosis-related tumors, selected cancers, and combination regimens.

What drug and crystalline form does US 10,189,833 cover?

Compound I is pexidartinib, also known as PLX3397, a small-molecule inhibitor of CSF1R, c-KIT and FLT3 signaling. Pexidartinib is marketed by Daiichi Sankyo as Turalio under FDA approval for adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to surgical improvement.[1]

The patent's central limitation is a solid-state identity test:

Limitation	Scope
Active material	Crystalline form of Compound I
Analytical test	X-ray powder diffraction
Radiation source	Cu-Kα
Required peaks	7.3°, 23.3°, and 28.2° 2θ
Tolerance	±0.2° for each peak
Therapeutic use	Kinase-mediated or macrophage/microglia-mediated disease
Formulation alternative	Crystalline form alone or with a pharmaceutically acceptable excipient

A product containing pexidartinib in a different polymorph, amorphous state, solvate, hydrate, salt form, or physically distinct crystalline form would not necessarily fall within the literal scope. The decisive issue would be whether the accused material produces all three claimed peaks within the stated tolerance under comparable XRPD conditions.

How many independent claims does US 10,189,833 contain?

The issued claims contain two broad independent claim structures and multiple disease-specific claims.

Claim	Subject matter
1	Treatment with the specified crystalline form
2	Treatment with the crystalline form plus excipient
3	Broad disease list
4	Combination therapy categories
5	Plexiform neurofibromas
6	TGCT
7	PVNS
8	Malignant peripheral nerve sheath tumors
9	MPNST plus sirolimus
10	Ovarian cancer
11	Ovarian cancer plus paclitaxel
12	Prostate cancer
13	Pancreatic cancer
14	Colorectal carcinoma
15	Pancreatic cancer plus durvalumab
16	Colorectal carcinoma plus durvalumab
17	Neurofibromatosis
18	Gastrointestinal stromal tumors
19	GIST plus a c-Kit mutant inhibitor
20	Specific c-Kit mutant inhibitor compounds
21	Alzheimer's disease
22	Bone osteolysis or bone pain

Claims 1 and 2 establish the main claim architecture. Claims 6 and 7 are the most commercially relevant because they expressly cover TGCT and PVNS, the disease areas most closely associated with Turalio.

What patents protect Turalio and pexidartinib?

US 10,189,833 is one part of a broader pexidartinib estate. The relevant patent categories are:

Patent category	Protection target	Commercial relevance
Composition of matter	Pexidartinib chemical structure	Broadest molecule-level protection
Crystalline form	Specific pexidartinib polymorph	Solid-form and product-quality barrier
Formulation	Capsule, excipient, release and stability characteristics	Product-specific protection
Method of treatment	TGCT, PVNS, kinase-mediated diseases	Use-based protection
Combination therapy	Pexidartinib with agents such as sirolimus, paclitaxel or durvalumab	Narrower clinical-use coverage
Manufacturing	Preparation, crystallization and purification	Process and supply-chain barrier

The cited patent is principally a crystalline-form and method-of-treatment patent. It does not, based on the supplied claims, claim the pexidartinib molecular structure without the crystalline-form limitation.

When does US 10,189,833 expire?

The patent has a June 13, 2014 priority date and a nominal twenty-year term measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any applicable regulatory extension. On that basis, the expected base expiration is in June 2034, with the actual expiration potentially extending into June 2035 if the patent received approximately one year of patent-term adjustment.

The key dates are:

Event	Date
Earliest stated priority date	June 13, 2014
US patent grant	January 29, 2019
Nominal twenty-year term	Approximately June 13, 2034
Potential term-adjusted expiration	Approximately June 2035
FDA Turalio approval	August 2, 2019

The exact enforceable expiration should be confirmed from the USPTO patent-term-adjustment record and any terminal disclaimer. A patent's grant date does not determine its expiration date.

What is the Orange Book status of pexidartinib?

Turalio is an FDA-approved small-molecule drug and is eligible for Orange Book patent listing. FDA approved Turalio under NDA 211246 on August 2, 2019, through the accelerated-approval pathway for adult patients with symptomatic TGCT not amenable to surgical improvement.[1]

The principal regulatory protections include:

Protection	Status
New chemical entity exclusivity	Four years of NCE data-exclusivity protection from approval
Orphan-drug exclusivity	Seven years for the approved TGCT indication, subject to statutory conditions
Accelerated approval	Yes
REMS	Yes, based on serious hepatotoxicity risk
Generic pathway	ANDA, with Paragraph IV certification possible
Biosimilar pathway	Not applicable

Turalio carries a boxed warning for serious and potentially fatal liver injury. Its REMS requires prescriber, pharmacy and patient controls, with liver-function monitoring.[1]

Orange Book listing is separate from patent enforceability. A listed patent can create an ANDA litigation trigger, but listing does not establish that every claim will survive validity or infringement challenges.

How strong is the patent estate for Turalio?

The estate is strongest where a competitor uses the same commercial crystalline form. It is weaker against a competitor that develops a distinct solid form or relies on a different formulation architecture.

Strengths

1. The XRPD limitation can identify a commercial polymorph with objective analytical evidence.
2. TGCT and PVNS are expressly claimed.
3. Claims 6 and 7 cover the crystalline form and a composition containing that form.
4. Combination claims reach pexidartinib with sirolimus, paclitaxel and durvalumab in specified diseases.
5. A generic using the same active ingredient and the same manufacturing or formulation platform may have difficulty avoiding the claimed XRPD profile.

Weaknesses

1. The patent does not appear to cover every pexidartinib solid form.
2. The claims depend on three diffraction peaks rather than a broad chemical-structure definition.
3. XRPD peak positions may vary with instrument calibration, sample preparation, crystallinity and formulation matrix.
4. Several disease claims may face written-description, enablement or obviousness challenges if the patent disclosure does not provide adequate disease-specific support.
5. Method-of-treatment claims may be harder to enforce against a product label that omits the patented indication.

What formulations are protected by US 10,189,833?

The patent protects two formulation presentations:

• The crystalline form administered as such.
• A composition containing a therapeutically effective amount of the crystalline form and a pharmaceutically acceptable excipient.

The claims do not require a particular capsule shell, excipient, dosage strength, dissolution profile, release mechanism or manufacturing process. Claims 2 and 6 through 22 therefore reach compositions broadly, but only when the composition contains the claimed crystalline material.

A finished capsule could infringe if the pexidartinib inside the capsule retains the claimed XRPD signature. A formulation containing amorphous pexidartinib or a nonclaimed polymorph would present a different infringement analysis.

What method-of-use patents cover TGCT and PVNS?

Claims 6 and 7 directly cover treatment of:

• Tenosynovial giant cell tumor.
• Pigmented villonodular synovitis.

These terms substantially overlap clinically. TGCT is the current umbrella terminology, while PVNS is a historical and anatomically specific term commonly used for diffuse or localized forms of the disease.

The claims require administration of the specified crystalline form or a composition containing it. They do not require:

• A particular dose.
• A particular treatment duration.
• A specific patient subgroup.
• Surgical ineligibility.
• A specific tumor location.
• A particular response endpoint.

The FDA label is narrower than the patent claims because the approved indication is limited to adults with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to surgical improvement.[1]

What generic entry risks exist for pexidartinib?

A pexidartinib ANDA applicant would generally face three technical design options:

Generic strategy	Patent risk
Use the same claimed crystalline form	High literal-infringement risk
Use a different polymorph	Lower risk under this patent, but possible risk under other solid-form patents
Use an amorphous or alternative salt/solvate form	Potentially lower risk under this patent, subject to pharmaceutical equivalence and stability requirements

The likely Paragraph IV issues would include:

• Noninfringement because the proposed product lacks one or more of the three XRPD peaks.
• Invalidity for anticipation or obviousness.
• Lack of enablement or written description for broad disease claims.
• Indefiniteness or analytical ambiguity concerning the XRPD limitations.
• Failure of the listed patent to qualify for Orange Book listing if the patent does not properly claim the approved drug or an approved method of use.

The crystalline-form limitation creates a laboratory-centered dispute. Both parties would likely rely on powder diffraction data, reference standards, sample preparation protocols and expert interpretation.

Which companies challenge or compete with pexidartinib?

The principal competitive threat is vimseltinib, developed by Deciphera Pharmaceuticals and marketed as Romvimza. Vimseltinib is a CSF1R inhibitor approved by FDA in February 2025 for adults with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to surgical improvement.[2]

Drug	Company	Target profile	TGCT status
Pexidartinib, Turalio	Daiichi Sankyo/Plexxikon	CSF1R, KIT, FLT3	FDA approved
Vimseltinib, Romvimza	Deciphera	CSF1R-focused	FDA approved
Emactuzumab	Roche/Genentech	CSF1R antibody	Investigational history
Nilotinib	Novartis	KIT and other kinases	Off-label or investigational use
Imatinib	Novartis and generics	KIT, PDGFR and related kinases	Off-label or investigational use

Vimseltinib does not inherently create a pexidartinib patent infringement issue because it is a different chemical entity. Its commercial impact is therapeutic substitution, not generic entry.

What litigation and settlement issues affect US 10,189,833?

The supplied record does not establish a reported Paragraph IV lawsuit, final validity decision, or settlement agreement specifically involving US 10,189,833. No litigation outcome should be inferred from the patent grant or Orange Book status.

For diligence purposes, the relevant litigation triggers would be:

1. An ANDA containing a Paragraph IV certification against the patent.
2. A patent-owner complaint filed within the Hatch-Waxman 45-day period.
3. A thirty-month stay affecting ANDA approval.
4. A settlement restricting generic launch or providing an authorized-generic arrangement.
5. An inter partes review or district-court challenge to the crystalline-form claims.

The absence of a confirmed litigation event in the supplied record means the patent should be treated as an issued, potentially enforceable barrier rather than as a litigated patent with adjudicated strength.

What geographic coverage does the patent provide?

US 10,189,833 provides US coverage only. Parallel protection may exist in other jurisdictions through the same priority family, but foreign scope must be assessed separately. Differences may include:

• Granted versus pending status.
• Narrower national-phase claims.
• Different expiration dates caused by prosecution.
• Supplementary protection certificates in Europe.
• Different treatment of medical-use claims.
• Different patentability standards for polymorphs and XRPD-defined forms.

A US patent does not block manufacture, sale or use outside the United States unless corresponding foreign rights exist.

What manufacturing and IP barriers remain after patent expiration?

Patent expiry would remove the legal barrier created by this patent, but it would not eliminate:

• The need to reproduce a stable and bioequivalent pexidartinib product.
• Control of polymorph conversion during milling, granulation and storage.
• Impurity and degradation control.
• Turalio REMS-related regulatory requirements, if applicable to the generic pathway.
• Other unexpired formulation, composition, process or use patents.
• Manufacturing know-how and validated analytical methods.

For a generic manufacturer, the highest technical risk is solid-form reproducibility. A product that changes polymorph during manufacturing or storage may fail dissolution, stability or bioequivalence requirements even if it avoids the patented form.

Key Takeaways

• US 10,189,833 is a crystalline-form and method-of-treatment patent for pexidartinib, not a broad composition-of-matter patent based on the supplied claims.
• The required XRPD peaks are 7.3°, 23.3° and 28.2° 2θ, each within ±0.2° using Cu-Kα radiation.
• TGCT and PVNS are the most commercially significant claimed indications.
• The patent also covers specified uses in neurofibromatosis, MPNST, ovarian, prostate, pancreatic, colorectal and other diseases.
• Combination claims include sirolimus, paclitaxel, durvalumab and c-Kit mutant inhibitors.
• The expected base term runs approximately to June 2034, with a possible adjustment into June 2035.
• Generic risk is highest when the proposed product uses the same pexidartinib crystalline form.
• Vimseltinib is the principal branded competitor, but it creates substitution risk rather than direct infringement risk.
• The supplied record does not establish a final Paragraph IV decision or settlement involving this patent.

FAQs

Does US 10,189,833 cover all pexidartinib products?

No. The claims require a particular crystalline form identified by three XRPD peaks. Products containing a different polymorph, amorphous pexidartinib, or another solid form may fall outside the literal claims.

Can a generic avoid US 10,189,833 by using a different polymorph?

Potentially. Avoidance would depend on the actual XRPD profile and on other patents covering pexidartinib, formulations, processes or approved methods of use.

Is Turalio protected by biosimilar exclusivity?

No. Pexidartinib is a small molecule, so the relevant generic pathway is an ANDA rather than a biosimilar application under the Public Health Service Act.

Does the patent cover vimseltinib?

No. Vimseltinib is a separate chemical entity and is not the crystalline form of Compound I recited in the claims.

Does FDA approval prove that every patent claim is valid?

No. FDA approval and Orange Book listing are regulatory events. Patent validity and infringement are determined under patent law through prosecution, litigation or post-grant review.

References

1. U.S. Food and Drug Administration. (2019). FDA approves pexidartinib for tenosynovial giant cell tumor. https://www.fda.gov
2. U.S. Food and Drug Administration. (2025). FDA approves vimseltinib for symptomatic tenosynovial giant cell tumor. https://www.fda.gov
3. United States Patent and Trademark Office. (2019). U.S. Patent No. 10,189,833, crystalline forms of Compound I and methods of use. https://patents.google.com/patent/US10189833B2 en

Drugs Protected by US Patent 10,189,833

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Daiichi Sankyo Inc	TURALIO	pexidartinib hydrochloride	CAPSULE;ORAL	211810-002	Oct 14, 2022		RX	Yes	Yes						TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY
Daiichi Sankyo Inc	TURALIO	pexidartinib hydrochloride	CAPSULE;ORAL	211810-001	Aug 2, 2019		DISCN	Yes	No						TREATMENT OF ADULT PATIENTS WITH SYMPTOMATIC TENOSYNOVIAL GIANT CELL TUMOR (TGCT) ASSOCIATED WITH SEVERE MORBIDITY OR FUNCTIONAL LIMITATIONS AND NOT AMENABLE TO IMPROVEMENT WITH SURGERY

International Family Members for US Patent 10,189,833

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016258027
Brazil	112017023490
Brazil	112017023540