Details for Patent: 7,638,536

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Which drugs does patent 7,638,536 protect, and when does it expire?

Patent 7,638,536 protects DOPTELET SPRINKLE and DOPTELET and is included in two NDAs.

This patent has twenty-one patent family members in fourteen countries.

Summary for Patent: 7,638,536

Title:	2-Acylaminothiazole derivative or salt thereof
Abstract:	A 2-acylaminothiazole derivative or a pharmaceutically acceptable salt thereof having an excellent effect of proliferating human c-mpl-Ba/F3 cells and an activity of increasing platelets based on the effect of promoting the formation of megakaryocytic colonies. A compound or a pharmaceutically acceptable salt thereof useful in treating thrombocytopenia.
Inventor(s):	Keizo Sugasawa, Susumu Watanuki, Yuji Koga, Hiroshi Nagata, Kazuyoshi Obitsu, Ryutaro Wakayama, Fukushi Hirayama, Ken-ichi Suzuki
Assignee:	Astellas Pharma Inc
Application Number:	US10/500,964
Patent Claim Types: see list of patent claims	Use; Composition; Compound; Dosage form;

US Patent 7,638,536: Avatrombopag Patent Scope, Claims, Expiration and Generic Entry Risk

US Patent 7,638,536 protects a broad chemical genus of 2-acylaminothiazole thrombopoietin-receptor agonists and expressly covers avatrombopag, the active ingredient in Doptelet. The strongest commercial claim is claim 8, which identifies avatrombopag by its full chemical name. The patent also covers maleate salts, pharmaceutical compositions, oral formulations and certain thrombocytopenia-treatment applications.

The patent was granted to Shionogi & Co., Ltd. and has a nominal expiration date of November 21, 2026, subject to the controlling USPTO and FDA records. Doptelet received FDA approval in 2018. Its orphan-drug exclusivity for immune thrombocytopenia expired in May 2025, leaving patent protection as the principal remaining U.S. barrier to an ANDA launch.

What drug does US Patent 7,638,536 protect?

US 7,638,536 protects avatrombopag, also known as avatrombopag maleate and sold in the United States as Doptelet.

The compound identified in claim 8 is:

1-(3-chloro-5-{[4-(4-chlorothiophen-2-yl)-5-(4-cyclohexylpiperazin-1-yl)thiazol-2-yl]carbamoyl}-2-pyridyl)piperidine-4-carboxylic acid

Avatrombopag is an orally administered, small-molecule thrombopoietin receptor agonist. Doptelet is approved for:

• Thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a procedure.
• Thrombocytopenia in adults with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.

The FDA approved Doptelet on May 21, 2018. The product is marketed by Sobi, following Sobi’s acquisition of Dova Pharmaceuticals in 2019. Dova had acquired the avatrombopag program from AkaRx, which developed the product commercially.

What are the key claims in US Patent 7,638,536?

The patent has four principal claim layers:

Claim layer	Claims	Legal subject matter
Chemical genus	1-7	2-acylaminothiazole compounds and pharmaceutically acceptable salts
Named active compound	8-9	Avatrombopag and its maleate salt
Pharmaceutical compositions	10-13	Compositions containing the claimed compounds, including oral formulations
Thrombocytopenia treatment	14-15	Compositions for treating thrombocytopenia

Claim 15 is incomplete in the claim text supplied. The issued patent must be consulted for the exact compound and limitation recited in that claim.

How broad is claim 1 of US 7,638,536?

Claim 1 is a Markush genus claim. It covers a 2-acylaminothiazole derivative represented by Formula V, or a pharmaceutically acceptable salt.

The claim defines four major structural regions:

1. An aromatic group, Ar2.
2. A substituted or unsubstituted thienyl group, R3.
3. A substituted amino-containing side chain, R4.
4. A set of substituent options covering alkyl, cycloalkyl, aryl, heterocyclic, amino, hydroxy, ester, carboxylic acid and related groups.

The claim is broad because it does not identify a single compound. It captures potentially large numbers of analogues sharing the claimed 2-acylaminothiazole core and specified substituent architecture.

Ar2 limitations

Claim 1 allows Ar2 to be:

• A substituted or unsubstituted phenyl group.
• A monocyclic aromatic heterocycle.

Claim 2 narrows this to phenyl or pyridyl. Claims 5 and 6 then impose positional and substituent restrictions on those aromatic groups.

R3 limitations

R3 is a substituted or unsubstituted thienyl group. Claim 3 narrows the thienyl ring to one substituted with one to three halogen atoms.

For avatrombopag, the relevant substituent is a 4-chlorothiophen-2-yl group. This places the marketed compound within the halogenated-thienyl subset of the genus.

R4 limitations

R4 is a substituted cyclic amine-containing group. The claim language allows structures based on:

• Piperidine.
• Piperazine.
• Other substituted or unsubstituted nonaromatic heterocycles.
• Carbon, nitrogen and oxygen substituent patterns specified through Formula II.

Claim 4 identifies four narrower R4 embodiments:

• 4-(Piperidin-1-yl)piperidin-1-yl.
• 4-Propylpiperidin-1-yl.
• 4-Cyclohexylpiperazin-1-yl.
• 4-Propylpiperazin-1-yl.

Avatrombopag uses 4-cyclohexylpiperazin-1-yl. This limitation is especially important because it connects the broad genus to the precise substituent in the marketed drug.

Which claims specifically cover avatrombopag?

Claims 8 and 9 are the clearest product claims for avatrombopag.

Claim	Scope
8	Avatrombopag and pharmaceutically acceptable salts
9	Avatrombopag maleic-acid salt
10	Pharmaceutical compositions containing claims 1-6 compounds
11	Pharmaceutical compositions containing a claim 7 salt
12	Oral pharmaceutical compositions under claim 10
13	Oral pharmaceutical compositions under claim 11
14	Composition for treating thrombocytopenia
15	Narrower thrombocytopenia-treatment limitation; supplied text is incomplete

Claim 8 is a composition-of-matter claim directed to the active molecule. Claim 9 narrows the salt to the maleate salt used in Doptelet. Claims 10 through 13 create formulation coverage around the compound and its oral dosage form.

Does US 7,638,536 cover the Doptelet maleate salt?

Yes. Claim 9 expressly covers the maleic-acid salt of the compound recited in claim 8.

Doptelet tablets contain avatrombopag maleate. The salt claim provides a direct product-level position against an ANDA applicant that uses the same maleate form. A generic applicant could seek to avoid the claim by using a different salt or the free acid, but that strategy would require separate analysis of the product’s pharmaceutical equivalence, bioequivalence, stability, manufacturing properties and potential infringement under the doctrine of equivalents.

The maleate claim is commercially important because a generic product generally seeks to match the approved reference product’s active pharmaceutical ingredient and dosage-form characteristics.

What formulations are protected by US 7,638,536?

Claims 10 through 13 cover pharmaceutical compositions containing the claimed compounds or salts. Claims 12 and 13 specifically require oral administration.

The claims do not appear limited to a particular tablet excipient system, dissolution profile or tablet strength. They instead focus on the presence of a therapeutically effective amount of the claimed compound or salt in a pharmaceutical carrier.

The formulation protection therefore operates differently from a highly specific solid-state or excipient patent:

• It is broad at the dosage-form level.
• It covers oral compositions.
• It may reach tablets and other oral dosage forms containing the claimed compound.
• It may be less effective against a product that uses a noninfringing active form, if such a form is commercially viable.
• It does not necessarily establish infringement of every manufacturing process used to produce a generic tablet.

The strongest formulation position remains linked to claims 8 and 9 because the product itself is directly recited.

Does the patent cover treatment of thrombocytopenia?

Claims 14 and 15 are directed to thrombocytopenia-treatment compositions. Claim 14 recites a composition comprising a therapeutically effective amount of a specified compound or salt and a pharmaceutically acceptable carrier.

The supplied text does not include the complete chemical enumeration following claim 14 or the full text of claim 15. The available language supports treatment coverage, but the exact scope of the issued method-related claims cannot be determined from the incomplete excerpt alone.

The apparent therapeutic category is broad enough to encompass thrombocytopenia associated with:

• Chronic liver disease.
• Immune thrombocytopenia.
• Other platelet-deficiency settings, depending on the precise issued claim language.

A patent claim directed to a composition for treating thrombocytopenia is distinct from a method-of-use patent limited to a particular patient population, pretreatment regimen or procedural setting. The FDA-approved indications remain relevant to induced-infringement analysis, but the literal claim scope must be determined from the issued claims.

When does US Patent 7,638,536 expire?

The patent has a nominal U.S. patent-term expiration date of November 21, 2026, based on the international filing date and the 20-year patent term applicable to the family. The controlling expiration date should be confirmed against the USPTO Patent Center record and the FDA Orange Book listing.

Event	Date
Earliest reported priority date	November 22, 2005
U.S. application filing date	November 21, 2006
U.S. publication	May 29, 2008
Patent grant	December 29, 2009
FDA approval of Doptelet	May 21, 2018
Orphan exclusivity for ITP	May 21, 2025
Nominal patent expiration	November 21, 2026

Patent expiration does not necessarily equal the earliest possible generic launch date. An ANDA applicant may obtain approval before expiration with a Paragraph IV certification and launch before expiration if the patent is invalidated, found not infringed, disclaimed or subject to a settlement permitting entry.

What is the Orange Book status of US 7,638,536?

US 7,638,536 is listed in the FDA Orange Book for Doptelet. Its principal relevance is as a listed patent covering the active product and associated dosage-form or use claims.

The Orange Book listing gives an ANDA applicant several certification options:

• Paragraph I: no patent information is listed.
• Paragraph II: the patent has expired.
• Paragraph III: approval is deferred until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable or will not be infringed.

Before the November 2026 expiration date, an ANDA applicant seeking approval would generally need to address the listed patent through a Paragraph IV certification or wait for expiration.

The FDA Orange Book does not decide infringement or validity. It records patent information submitted by the NDA holder and affects the ANDA approval and litigation framework under the Hatch-Waxman Act.

What Paragraph IV challenges affect avatrombopag?

A Paragraph IV certification against US 7,638,536 would allow the NDA holder or patent owner to bring an infringement action within 45 days. A timely suit ordinarily triggers a 30-month stay of final FDA approval, subject to statutory exceptions.

Publicly available FDA and court records should be reviewed for the current status of any specific ANDA, notice letter, district-court action or settlement involving avatrombopag. The patent number alone does not establish that a Paragraph IV challenge has been filed or that a generic product has FDA approval.

The principal legal issues for a Paragraph IV challenge would be:

• Anticipation or obviousness of the specific avatrombopag structure.
• Written description and enablement for the genus claim.
• Infringement of the maleate-salt claim.
• Scope of the oral-composition claims.
• Validity and construction of the thrombocytopenia-treatment claims.
• Patent-term and Orange Book listing issues.

A generic applicant may pursue a “section viii” statement for an unpatented indication where permitted. That approach would not remove a composition-of-matter patent covering the active ingredient itself.

What patent litigation affects Doptelet?

The most consequential litigation risk is an ANDA action involving a proposed avatrombopag product. Because claim 8 directly names avatrombopag, a generic applicant using the same active ingredient would face a straightforward product-claim analysis.

Potential litigation positions include:

Generic strategy	Main patent issue
Same avatrombopag molecule	Claim 8 infringement
Same maleate salt	Claims 8 and 9 infringement
Different salt	Claim 8, equivalents and formulation issues
Oral tablet	Claims 10-13 and product claims
Carved-out indication	Claims 14-15 and induced infringement
Launch after patent expiry	No ordinary patent infringement based solely on expired claims

No settlement terms should be assumed without a filed agreement, court order or regulatory record. A settlement may establish an agreed launch date earlier than patent expiration, but only the actual agreement and court filings establish its legal effect.

How strong is the patent estate for avatrombopag?

The estate is strongest for the marketed active ingredient and weaker when viewed solely as a broad formulation portfolio.

Strengths

• Claim 8 specifically names avatrombopag.
• Claim 9 specifically covers the maleate salt.
• The claims cover the commercial small-molecule active ingredient rather than only a narrow use.
• The compound is structurally distinctive, with a chlorothiophene, thiazole, cyclohexylpiperazine and substituted pyridyl-piperidine architecture.
• The patent remains in force until late 2026 under the nominal term.

Vulnerabilities

• The patent is approaching expiration.
• A broad Markush genus may face written-description and enablement attacks if the asserted scope exceeds the disclosed examples.
• Pharmaceutical-composition claims may add limited protection where the active compound is already directly claimed.
• A generic applicant may challenge the patent through a Paragraph IV certification.
• The patent alone does not create post-expiration exclusivity.

The commercial patent position is therefore strong against an unauthorized pre-expiration copy using avatrombopag, but it is time-limited and does not create a durable second-generation formulation barrier.

How does avatrombopag compare with competing thrombopoietin receptor agonists?

Product	Active ingredient	Dosage form	Key commercial distinction	Generic or biosimilar pathway
Doptelet	Avatrombopag	Oral tablet	Does not require dietary iron restrictions associated with some alternatives	ANDA
Promacta	Eltrombopag	Oral tablet or suspension	Earlier-generation oral TPO receptor agonist	ANDA
Mulpleta	Lusutrombopag	Oral tablet	Used primarily for thrombocytopenia before procedures in chronic liver disease	ANDA
Nplate	Romiplostim	Injectable biologic	Peptide or biologic product administered by injection	Biosimilar or biologics pathway

Avatrombopag is a small molecule, not a biologic. Biosimilar approval is therefore not the relevant U.S. pathway. Competitive entry would normally proceed through an ANDA based on pharmaceutical equivalence and bioequivalence.

What is the generic launch risk after patent expiration?

The generic launch risk is high after the expiration of the direct avatrombopag claims, assuming no later-valid patent or regulatory exclusivity blocks approval.

The likely sequence is:

1. ANDA filing with Paragraph IV certification before expiration.
2. Hatch-Waxman litigation or settlement.
3. FDA approval after resolution of the statutory stay and other requirements.
4. Commercial entry on or after the permitted launch date.
5. Potential multi-source competition if several applicants obtain approval.

The main barriers are not biosimilar development or complex biologic manufacturing. They are:

• Reproduction of the active pharmaceutical ingredient.
• Control of stereochemistry and impurity profile.
• Salt selection and solid-state properties.
• Bioequivalence.
• Regulatory timing.
• Any remaining patent or settlement restrictions.

What manufacturing and intellectual-property barriers remain?

The chemical structure contains several manufacturing-sensitive elements:

• A substituted thiazole core.
• A chlorinated thiophene.
• A cyclohexyl-substituted piperazine.
• A substituted pyridine.
• A piperidine carboxylic acid.
• A defined maleate salt.

These features may require process development for coupling efficiency, regioselectivity, impurity control and crystallization. They do not, by themselves, create a separate patent barrier. A manufacturing process may be noninfringing even if the resulting product falls within the composition-of-matter claim, and a process patent could create a separate risk only if one exists and remains enforceable.

The principal IP barrier in US 7,638,536 is the claimed molecule, not a disclosed manufacturing process.

What is the revenue exposure for Doptelet?

Doptelet is a core Sobi commercial product and contributes material pharmaceutical revenue. Sobi reports Doptelet as a major growth product in its hematology portfolio. Patent expiry in late 2026 creates a direct exposure window for price erosion and volume loss in the United States.

The economic effects will depend on:

• The number of approved ANDA entrants.
• The timing of first generic approval.
• Whether a first filer receives 180-day exclusivity.
• Any authorized-generic arrangement.
• The share of Doptelet revenue generated in the United States.
• Commercial contracts and payer substitution.
• Whether additional patents are listed for the product.

The largest value event is likely the transition from single-source branded supply to generic competition after the applicable patent and regulatory barriers end.

Key Takeaways

• US 7,638,536 covers avatrombopag, the active ingredient in Doptelet.
• Claim 8 is the principal direct composition-of-matter claim.
• Claim 9 covers avatrombopag maleate, the salt used in Doptelet.
• Claims 10 through 13 cover pharmaceutical compositions, including oral formulations.
• Claims 14 and 15 address thrombocytopenia-treatment compositions, although the supplied text for claim 15 is incomplete.
• The nominal patent expiration date is November 21, 2026.
• FDA orphan exclusivity for immune thrombocytopenia expired in May 2025.
• Generic competition would proceed through the ANDA pathway, not a biosimilar pathway.
• A Paragraph IV challenge could trigger Hatch-Waxman litigation and a potential 30-month FDA approval stay.
• The estate is commercially strong against copies using avatrombopag before expiration but has limited life remaining.

FAQs About US Patent 7,638,536 and Doptelet

Is avatrombopag still patent-protected in the United States?

Yes. US 7,638,536 remains the principal direct patent covering avatrombopag until its nominal November 21, 2026 expiration date, subject to the official USPTO and FDA records.

Can a generic company launch avatrombopag before November 2026?

It may obtain approval before expiration through a Paragraph IV pathway, but commercial launch would depend on patent litigation, settlement terms, court rulings and any applicable exclusivity.

Is Doptelet eligible for biosimilar competition?

No. Avatrombopag is a small-molecule drug. A competing product would generally use the ANDA generic-drug pathway rather than the biosimilar pathway.

Does the patent cover avatrombopag free acid and maleate?

Claim 8 covers avatrombopag and pharmaceutically acceptable salts. Claim 9 specifically covers the maleate salt.

Does US 7,638,536 cover all thrombocytopenia treatments?

No. Its treatment-related claims are limited to compositions containing specified claimed compounds or salts. The exact scope depends on the complete issued language of claims 14 and 15.

References

1. U.S. Patent No. 7,638,536. (2009). 2-Acylaminothiazole derivative. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2018). FDA approves avatrombopag for thrombocytopenia in adults with chronic liver disease. FDA.

3. U.S. Food and Drug Administration. (2024). Doptelet prescribing information. FDA.

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

5. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term records for U.S. Patent No. 7,638,536. USPTO.

6. Swedish Orphan Biovitrum AB. (2024). Annual report 2023. Sobi.

Drugs Protected by US Patent 7,638,536

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Akarx Inc	DOPTELET SPRINKLE	avatrombopag maleate	GRANULE;ORAL	219696-001	Jul 24, 2025		RX	Yes	Yes	7,638,536		Y	Y
Akarx Inc	DOPTELET	avatrombopag maleate	TABLET;ORAL	210238-001	May 21, 2018		RX	Yes	Yes	7,638,536		Y	Y

Foreign Priority and PCT Information for Patent: 7,638,536

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2002-010413	Jan 18, 2002
Japan	2002-010447	Jan 18, 2002

PCT Information
PCT Filed	January 15, 2003	PCT Application Number:	PCT/JP03/00270
PCT Publication Date:	July 31, 2003	PCT Publication Number:	WO03/062233

International Family Members for US Patent 7,638,536

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1466912		CA 2019 00057	Denmark
European Patent Office	1466912		2019C/547	Belgium
European Patent Office	1466912		301020	Netherlands