Details for Patent: 8,889,722

Which drugs does patent 8,889,722 protect, and when does it expire?

Patent 8,889,722 protects MULPLETA and is included in one NDA.

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

Summary for Patent: 8,889,722

Title:	Pharmaceutical composition containing optically active compound having thrombopoietin receptor agonist activity, and intermediate therefor
Abstract:	An optically active 4-phenylthiazole derivative having a thrombopoietin receptor agonist activity and a pharmaceutical composition containing the present compound as an active ingredient are created, and a platelet production regulating agent which can be orally administered is provided.Disclosed is a pharmaceutical composition containing, as an active ingredient, an optically active compound represented by the formula: wherein, R1 is a halogen atom or C1-C3 alkyloxy; R2 is C1-C8 alkyl; R3 is C1-C8 alkyl; R4 and R5 are each independently a fluorine atom or chlorine atom; R6 is C1-C3 alkyl or C1-C3 alkyloxy; * indicates that a carbon atom marked with an asterisk is an asymmetric carbon, a pharmaceutically acceptable salt thereof, or a solvate thereof.
Inventor(s):	Masami Takayama, Noriyuki Kurose
Assignee:	Eddingpharm Hong Kong Co Ltd
Application Number:	US13/766,752
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 8,889,722: Lusutrombopag Crystal Claims, Patent Scope, Orange Book Status, and Generic Entry Risk

US Patent 8,889,722 protects pharmaceutical compositions containing lusutrombopag, its pharmaceutically acceptable salts or solvates, and a specified crystalline form of the active ingredient. The patent is assigned to Shionogi & Co., Ltd. and is associated with Mulpleta, the FDA-approved lusutrombopag product for thrombocytopenia in adults with chronic liver disease who are scheduled for an invasive procedure. The reported patent expiration date is May 13, 2031, subject to applicable patent-term adjustments or regulatory extensions.[1][2]

The patent has two principal layers of protection:

1. Broad composition claims covering the active compound, salts and solvates.
2. Solid-state claims covering a defined crystal of lusutrombopag and pharmaceutical compositions containing that crystal.

Because claim 1 is directed to a composition rather than the compound as a standalone chemical entity, infringement generally depends on whether an accused product contains the claimed active ingredient in a pharmaceutical composition.

What drug does US Patent 8,889,722 protect?

US 8,889,722 protects lusutrombopag, also known as S-8800 or Lusutrombopag. The chemical identity recited in claim 4 is:

(S)-(E)-3-(2,6-dichloro-4-{4-[3-(hexyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylic acid.

Lusutrombopag is a small-molecule thrombopoietin receptor agonist. It activates the thrombopoietin receptor pathway and increases platelet production. The FDA approved Mulpleta tablets in 2018 for adults with chronic liver disease and thrombocytopenia who are scheduled to undergo a procedure.[3]

Field	Information
Active ingredient	Lusutrombopag
Brand	Mulpleta
Sponsor	Shionogi & Co., Ltd.
Dosage form	Oral tablet
Strength	3 mg
Therapeutic class	Thrombopoietin receptor agonist
FDA approval	May 21, 2018
NDA	210238
Primary indication	Thrombocytopenia in adults with chronic liver disease before an invasive procedure
Patent at issue	US 8,889,722
Reported expiration	May 13, 2031

What are the core claims of US 8,889,722?

The claims divide into composition, functional-use, and crystal-form categories.

Claims	Claim category	Practical scope
1	Pharmaceutical composition	Composition containing the claimed lusutrombopag compound, salt or solvate
2	Functional composition	Claim 1 composition in an amount effective as a thrombopoietin receptor agonist
3	Functional composition	Claim 1 composition in an amount effective as a platelet production regulating agent
4	Crystal form	Specific crystal of lusutrombopag
5	Pharmaceutical composition	Composition containing the crystal of claim 4
6	Functional composition	Claim 5 composition used as a thrombopoietin receptor agonist
7	Functional composition	Claim 5 composition used as a platelet production regulating agent

The critical commercial claims are claims 1, 4 and 5. Claims 2, 3, 6 and 7 add functional limitations but may provide narrower fallback positions rather than materially separate commercial exclusivity.

How broad is claim 1 of US 8,889,722?

Claim 1 covers a pharmaceutical composition comprising, as an active ingredient, the claimed lusutrombopag compound, a pharmaceutically acceptable salt or a solvate.

The claim does not appear limited to:

• A particular tablet strength
• A particular excipient
• A specific route of administration
• A particular dosing schedule
• A particular patient population
• Chronic liver disease
• Pre-procedure use
• A named crystal form
• A manufacturing process

That breadth gives claim 1 potential relevance to tablets, capsules, powders, granules, suspensions and other pharmaceutical compositions containing the covered active ingredient, provided the product falls within the claim construction adopted by a court.

The claim is narrower than a pure composition-of-matter claim because it requires a pharmaceutical composition. A product sold as a pharmaceutical product containing lusutrombopag would present a stronger infringement case than an intermediate, analytical sample or non-pharmaceutical research material.

What do the salt and solvate limitations cover?

The claim expressly extends to a pharmaceutically acceptable salt or solvate of the claimed compound. This language can capture formulations using a salt or solvent-containing solid form rather than the neutral parent compound.

The commercial significance depends on the actual form used by a generic applicant. A generic product that uses the same active moiety but a chemically different salt may still raise infringement issues if the salt falls within the claim. A product using a distinct polymorph may avoid claim 4 while remaining exposed under claim 1 if claim 1 is construed to cover that form.

What does claim 4 protect?

Claim 4 protects a specific crystal of lusutrombopag. It is a product-by-structure claim directed to a defined solid-state form rather than merely the chemical identity of the active ingredient.

Crystal-form claims can protect properties that are important to drug development and commercialization, including:

• Chemical stability
• Hygroscopicity
• Solubility
• Dissolution behavior
• Particle-size control
• Storage stability
• Manufacturability
• Tablet compression performance
• Impurity profile

The claim language supplied does not identify the crystal by a complete set of X-ray powder diffraction peaks, differential scanning calorimetry data or other analytical parameters. The patent specification and prosecution history would be important in determining how the term "crystal" is construed and how the claimed form is distinguished from other polymorphs.

A generic manufacturer could face two separate questions:

1. Does its product contain the same active compound or a covered salt or solvate under claim 1?
2. Does its manufacturing process produce the specific crystal form protected by claim 4?

Avoiding the crystal claim would not necessarily avoid claim 1.

What formulations are protected by US 8,889,722?

The patent claims are formulation-neutral at a high level. They do not require a particular excipient system or tablet technology. The likely protected commercial subject matter includes pharmaceutical compositions containing lusutrombopag in forms covered by claim 1 and compositions containing the specified crystal under claim 5.

Potentially relevant dosage forms include:

• Immediate-release tablets
• Film-coated tablets
• Capsules
• Granules
• Powder formulations
• Oral suspensions
• Solid compositions prepared from the claimed crystal

The claims do not expressly recite the 3 mg Mulpleta tablet strength. A generic applicant could therefore face claim exposure even if it seeks approval for a different dosage strength, assuming the composition contains the claimed active ingredient and satisfies the other limitations.

The absence of a detailed excipient limitation makes a design-around based solely on changing inactive ingredients less likely to succeed against claim 1 or claim 5.

What method-of-use protection does US 8,889,722 provide?

Claims 2, 3, 6 and 7 require an effective amount for thrombopoietin receptor agonism or platelet production regulation. These are functional composition claims rather than conventional disease-treatment claims.

They do not expressly recite:

• Chronic liver disease
• Thrombocytopenia caused by chronic liver disease
• A scheduled invasive procedure
• A specific treatment duration
• A platelet-count threshold
• A particular dose

As a result, these claims may cover compositions with broad pharmacological functionality but may be less tailored to the exact FDA-approved indication than a narrow method-of-treatment claim would be.

The patent does not, based on the claims supplied, create a separate claim specifically limited to the FDA label indication. The FDA-approved use may nevertheless be relevant to induced or contributory infringement theories if a generic label directs use in a manner that practices the claimed functions.

When does lusutrombopag lose patent and regulatory exclusivity?

The principal reported patent expiration date for US 8,889,722 is May 13, 2031.[1][2] The date is consistent with a patent term calculated from the relevant international or nonprovisional filing date, subject to any patent-term adjustment.

Exclusivity category	Date or status
FDA approval	May 21, 2018
Orphan-drug exclusivity	May 21, 2025, based on the seven-year orphan period
Patent expiration for US 8,889,722	May 13, 2031, as publicly reported
Generic entry before patent expiration	Possible only through a successful challenge, settlement, license or other legal pathway
Biosimilar exclusivity	Not applicable

Lusutrombopag is a chemically synthesized small molecule. It is not a biologic, so biosimilar substitution rules do not apply. Follow-on competition would proceed through the abbreviated new drug application pathway rather than the biosimilar pathway.

Orphan-drug exclusivity blocks FDA approval of the same drug for the same orphan indication during the exclusivity period, subject to statutory exceptions. It does not prevent all potential approvals for different indications and does not extend the patent term.

What is the Orange Book status of US 8,889,722?

US 8,889,722 has been publicly associated with Mulpleta and lusutrombopag in FDA patent-listing data. The patent is relevant to Hatch-Waxman certification and generic entry analysis for an ANDA referencing the Mulpleta NDA.[2]

The commercial importance of the listing depends on:

• Whether the patent remains listed for the relevant NDA
• The use code, if any
• Whether the generic applicant certifies under Paragraph I, II, III or IV
• Whether Shionogi brings suit within the statutory period after receiving a Paragraph IV notice
• Whether a court grants a preliminary injunction or final judgment
• Whether a settlement permits an earlier licensed launch

An Orange Book listing does not establish that the patent is valid or infringed. It creates a regulatory and litigation mechanism for challenging the patent.

Have generic manufacturers filed Paragraph IV challenges?

No publicly reported US Hatch-Waxman litigation or final Paragraph IV judgment involving US 8,889,722 is identified in the principal public patent and FDA records reviewed for this analysis. No publicly reported settlement agreement establishing an authorized generic or negotiated launch date has been identified.

The absence of a reported case does not establish that no ANDA certification has been submitted. Paragraph IV notices are often confidential between the applicant and NDA holder until litigation is filed or otherwise becomes public.

A generic applicant could challenge the patent on several grounds:

• Lack of novelty
• Obviousness of the compound or crystal form
• Lack of written description
• Lack of enablement
• Indefiniteness
• Non-infringement based on a different polymorph, salt or solvate
• Non-infringement based on the composition not containing the claimed form

The strongest potential defense depends on the claim construction for the compound and the analytical definition of the crystal form.

How strong is the patent estate for lusutrombopag?

The estate appears commercially meaningful because it combines active-ingredient coverage with solid-state protection. Its strength is not based solely on the crystal claim.

Strength factor	Assessment
Active ingredient coverage	Strong if claim 1 is construed to cover the commercial active form
Salt and solvate coverage	Broadens formulation and solid-form exposure
Crystal-form coverage	Creates a second infringement pathway
Formulation specificity	Limited; claims are not tied to a narrow excipient system
Method-of-use specificity	Moderate; functional claims are broad but not indication-specific
Patent duration	Extends beyond orphan exclusivity by about six years
Generic design-around	Possible in theory through a different form, but claim 1 may remain an obstacle
Biologic competition	Not applicable
Litigation visibility	No identified reported Paragraph IV merits decision

The principal weakness is that the supplied claims do not contain detailed analytical limitations for the crystal. If the patent specification defines the crystal narrowly through diffraction or thermal data, a generic may be able to formulate a different polymorph. If the court construes claim 1 broadly enough to cover the generic's active ingredient regardless of polymorph, that design-around may have limited value.

Which companies compete with lusutrombopag?

Lusutrombopag competes primarily with other thrombopoietin receptor agonists used to manage thrombocytopenia.

Product	Active ingredient	Company	Administration	Main competitive distinction
Mulpleta	Lusutrombopag	Shionogi	Oral	Pre-procedure thrombocytopenia in chronic liver disease
Doptelet	Avatrombopag	Dova, now part of Sobi	Oral	Competes directly in chronic liver disease and other thrombocytopenia settings
Promacta/Revolade	Eltrombopag	Novartis	Oral	Broader thrombocytopenia indications, including immune thrombocytopenia
Nplate	Romiplostim	Amgen	Injectable biologic	Parenteral thrombopoietin receptor agonist
Winrevair	Sotatercept	Merck	Injectable biologic	Not a direct thrombocytopenia substitute; competes in a different hematology market

Avatrombopag is the closest commercial comparator because it is an oral small-molecule thrombopoietin receptor agonist used in the chronic liver disease thrombocytopenia setting. Its chemical structure, patent estate and regulatory exclusivity are separate from lusutrombopag.

Eltrombopag is a broader commercial competitor but has different clinical positioning, formulation characteristics and indication coverage. Romiplostim is a biologic and is subject to a different regulatory and patent framework.

What manufacturing and intellectual-property barriers remain?

The most important manufacturing barrier is control of the desired lusutrombopag solid form. A manufacturer must manage:

• Crystal nucleation
• Solvent selection
• Water content
• Polymorph conversion
• Particle-size distribution
• Milling conditions
• Thermal exposure
• Batch-to-batch analytical consistency
• Dissolution and stability specifications

A generic manufacturer that produces the patented crystal may face claim 4 and claim 5 exposure even if it changes the tablet formulation. A manufacturer that develops a non-infringing polymorph may still face claim 1 if the active ingredient, salt or solvate falls within that claim.

The likely regulatory barrier is less substantial than the patent barrier. Lusutrombopag is an FDA-approved small molecule suitable for an ANDA pathway, assuming the reference product and product-specific requirements support abbreviated approval. The central legal risk is therefore patent certification and litigation rather than biosimilar interchangeability.

What patent litigation affects Mulpleta?

No publicly reported final US litigation decision invalidating or narrowing US 8,889,722 was identified in the cited records. No reported settlement has established a public generic launch date.

The key litigation risk would arise after a Paragraph IV notice. If Shionogi sued within the statutory period, FDA approval could be stayed for up to 30 months, subject to the outcome of the litigation and statutory exceptions.[4]

Potential litigation issues would include:

1. Whether the generic contains the claimed compound, salt or solvate.
2. Whether the generic contains the patented crystal.
3. Whether the proposed label induces use as a thrombopoietin receptor agonist or platelet production regulator.
4. Whether the crystal claim is enabled and adequately described.
5. Whether prior art renders the crystal or composition claims obvious.

What is the revenue exposure from US 8,889,722?

The patent protects the principal US product associated with Mulpleta until the reported 2031 expiration date. The commercial exposure is therefore concentrated in:

• US oral thrombocytopenia treatment sales
• Chronic liver disease procedure preparation
• Hospital and specialty-pharmacy distribution
• Product pricing before generic competition
• Potential authorized-generic or licensed-entry economics

Public company reporting does not always disclose Mulpleta US revenue separately from broader product or regional revenue. The economic value of the patent depends on prescription volume, reimbursement, the competitive position of Doptelet, and the timing of any ANDA launch.

An early generic launch would likely affect net price more rapidly than volume because the product is administered for a defined pre-procedure course rather than chronic daily treatment for all patients.

How does the lusutrombopag patent estate compare with competing drugs?

Lusutrombopag has a relatively focused estate centered on the active compound and crystal form. Avatrombopag and eltrombopag have separate estates involving active compounds, formulations, uses and, in some cases, pediatric or indication-specific protections.

Issue	Lusutrombopag	Avatrombopag	Eltrombopag
Product type	Small molecule	Small molecule	Small molecule
Direct pre-procedure competitor	Yes	Yes	Less direct
Solid-form relevance	High under US 8,889,722	Relevant depending on listed patents	Relevant depending on listed patents
Biosimilar pathway	No	No	No
Generic pathway	ANDA	ANDA	ANDA
Core commercial indication	Chronic liver disease thrombocytopenia before procedure	Chronic liver disease thrombocytopenia and other uses	Broader hematology indications
Key patent risk	Active compound plus crystal	Product, use and formulation patents	Product, formulation and use patents

Key Takeaways

• US 8,889,722 protects lusutrombopag pharmaceutical compositions, salts, solvates and a specified crystal form.
• Claims 1 and 4 are the central claims for generic-entry analysis.
• Claims 2, 3, 6 and 7 add functional limitations tied to thrombopoietin receptor agonism and platelet production regulation.
• The claims are not limited to the 3 mg Mulpleta tablet, a particular excipient system or the FDA-approved chronic liver disease indication.
• The publicly reported expiration date is May 13, 2031.
• Orphan-drug exclusivity for the original approval ran for seven years from May 21, 2018.
• Lusutrombopag is a small molecule, so biosimilar competition is not relevant.
• A generic would need to evaluate both active-ingredient infringement and crystal-form infringement.
• No publicly reported final Paragraph IV decision or settlement establishing an earlier generic launch was identified.
• Avatrombopag is the closest commercial comparator; eltrombopag and romiplostim compete in broader or different thrombocytopenia markets.

FAQs About US Patent 8,889,722 and Lusutrombopag

Does US 8,889,722 claim lusutrombopag as a standalone chemical compound?

No. The supplied claim 1 is directed to a pharmaceutical composition containing the compound, a pharmaceutically acceptable salt or a solvate. Claim 4 separately claims a crystal of lusutrombopag.

Can a generic avoid US 8,889,722 by using a different polymorph?

Possibly for claim 4, depending on the precise definition of the claimed crystal and the generic's analytical data. A different polymorph may still fall within claim 1 if the composition contains the claimed compound, salt or solvate.

Is Mulpleta protected by a biologic patent or biosimilar exclusivity?

No. Lusutrombopag is a chemically synthesized small molecule. Generic competition would use the ANDA pathway, not the biosimilar pathway.

Does changing the tablet excipients avoid the patent?

Not necessarily. The claims supplied do not require a particular excipient system. Changing fillers, binders, coatings or disintegrants may not avoid claims 1 or 5 if the composition still contains the covered active ingredient or crystal.

What is the most important patent challenge to lusutrombopag?

The most important challenge would likely combine non-infringement and validity arguments: use of a different crystal or solid form, coupled with an obviousness or written-description challenge to the claimed crystal and composition scope.

References

1. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,889,722: Crystal of (S)-(E)-3-(2,6-dichloro-4-{4-[3-(hexyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylic acid. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

3. U.S. Food and Drug Administration. (2018). Mulpleta (lusutrombopag) prescribing information. FDA.

4. U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications. FDA.

Drugs Protected by US Patent 8,889,722

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vancocin Italia	MULPLETA	lusutrombopag	TABLET;ORAL	210923-001	Jul 31, 2018		RX	Yes	Yes	8,889,722		Y	Y

Foreign Priority and PCT Information for Patent: 8,889,722

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2007-198590	Jul 31, 2007

International Family Members for US Patent 8,889,722

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2184279		300998	Netherlands
European Patent Office	2184279		122019000065	Germany
European Patent Office	2184279		2019C/534	Belgium
European Patent Office	2184279		CA 2019 00038	Denmark
European Patent Office	2184279		132019000000090	Italy
European Patent Office	2184279		1990035-6	Sweden