US Patent 6,525,060: Ticagrelor Compound Scope, Claims, Expiration, and Patent Landscape

US Patent 6,525,060 is a foundational AstraZeneca patent covering triazolotriazine and triazolopyrimidine antiplatelet compounds, including ticagrelor, the active ingredient in Brilinta. Its principal genus claim covers substituted cyclopentane nucleoside analogues bearing a triazolopyrimidine core, a cyclopropylamine substituent, and selected thioalkyl groups. The patent issued on February 25, 2003, and its US patent term expired in 2020, subject to any applicable patent-term adjustment or pediatric exclusivity.

The patent remains commercially important because it identifies the original compound class and contains claims directed to ticagrelor itself, pharmaceutical compositions, post-myocardial-infarction treatment, stroke treatment, intermediates, and manufacturing chemistry. It is no longer an enforceable barrier to US generic entry, but its disclosure remains relevant to validity, obviousness, written-description, and freedom-to-operate analyses involving later patents.

What drug does US Patent 6,525,060 protect?

US 6,525,060 protects compounds in the triazolo[4,5-d]pyrimidine class, including ticagrelor.

Ticagrelor is the compound corresponding to the claimed structure:

A triazolo[4,5-d]pyrimidine nucleus.
A 5-position propylthio substituent.
A 7-position amino substituent derived from trans-2-(3,4-difluorophenyl)cyclopropylamine.
A substituted cyclopentane diol at the 3-position.
A 5-position hydroxymethyl or 2-hydroxyethoxy substituent.

The compound is a reversible P2Y12 platelet receptor antagonist. AstraZeneca markets ticagrelor in the United States under the Brilinta brand.

The claims supplied by the user correspond closely to the chemical and therapeutic disclosure associated with ticagrelor and related analogues. The patent does not use the modern INN name "ticagrelor" in the claims. Instead, it claims the compound by stereochemically defined chemical structure.

How broad is claim 1 of US 6,525,060?

Claim 1 is a Markush genus claim covering a large family of stereochemically defined triazolopyrimidine compounds.

The principal variables are:

Variable	Claimed scope
R1	C3-C5 alkyl, optionally substituted with one or more halogens
R2	Phenyl, optionally substituted with one or more fluorine atoms
R3 and R4	Both hydroxy
R	CH2OH, OCH2CH2OH, or a bond
Salt and solvate status	Pharmaceutically acceptable salts, solvates, and solvates of salts

The structural core disclosed by the claims contains:

A cyclopentane or related carbocyclic sugar mimic.
A triazolo[4,5-d]pyrimidine heterocycle.
An amino-cyclopropyl aryl substituent.
A thioalkyl or related substituent.
Multiple hydroxyl groups that provide the nucleoside-analogue character.

Claim 1 is narrowed by three express provisos:

If X is CH2 or a bond, R1 cannot be propyl.
If X is CH2 and R1 is 3,3,3-trifluoropropyl, butyl, or pentyl, R2 must be fluorinated.
If X is OCH2CH2 and R1 is propyl, R2 must be fluorinated.

These provisos are significant. They prevent the broad language from covering certain combinations of an unsubstituted phenyl group, a propylthio group, and particular side-chain configurations. In a claim-construction or invalidity analysis, the provisos would be treated as substantive limitations rather than drafting surplusage.

Does claim 1 cover ticagrelor?

Yes. Ticagrelor falls within the claim 1 genus and is expressly identified by the species recited in claim 5.

The ticagrelor configuration is generally represented as:

R1: propyl
R2: 3,4-difluorophenyl
R: OCH2CH2OH
R3 and R4: hydroxy
Defined stereochemistry at the cyclopentane and cyclopropyl centers

The claim 5 species corresponding to ticagrelor is:

"[1S-(1α,2α,3β(1S,2R),5β)]-3-[7-[[2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-cyclopentane-1,2-diol."

The combination of propylthio and 3,4-difluorophenyl satisfies the claim 1 proviso applicable to the OCH2CH2OH configuration.

What do dependent claims 2 through 5 cover?

Claim 2: thioalkyl selection

Claim 2 narrows R1 to:

3,3,3-trifluoropropyl
Butyl
Propyl

This claim removes other C3-C5 alkyl possibilities that may fall within claim 1, including certain pentyl and halogenated variants not expressly recited in claim 2.

Claim 3: aryl selection

Claim 3 limits R2 to:

Phenyl
4-fluorophenyl
3,4-difluorophenyl

The 3,4-difluorophenyl embodiment is commercially important because it is part of ticagrelor. Claim 3 excludes other fluorinated phenyl patterns that might otherwise fall within the broader "one or more fluorine atoms" language of claim 1.

Claim 4: side-chain selection

Claim 4 limits R to:

CH2OH
OCH2CH2OH

These are the two principal hydroxyalkyl substituents in the claim set. Ticagrelor uses the OCH2CH2OH embodiment.

Claim 5: expressly named drug-like species

Claim 5 recites nine specific compounds or compound classes. The list includes:

3,3,3-trifluoropropylthio analogues.
Propylthio analogues.
Butylthio analogues.
Phenyl, 4-fluorophenyl, and 3,4-difluorophenyl cyclopropylamine analogues.
Hydroxymethyl and hydroxyethoxy cyclopentane analogues.

Claim 5 provides a direct species claim for ticagrelor and several close analogues. This substantially improves the patent's position against an argument that the broad genus lacks adequate support for the commercial compound, although enforceability would still depend on the full prosecution record and any later validity challenge.

What do claims 6, 7, and 14 cover?

Claim 6: pharmaceutical compositions

Claim 6 covers a pharmaceutical composition containing a claim 1 compound with:

A pharmaceutically acceptable diluent.
An adjuvant.
A pharmaceutically acceptable carrier.

The claim is broad and does not require a particular dosage form, excipient, strength, release profile, tablet architecture, or manufacturing process. It could encompass tablets, capsules, solutions, suspensions, and other conventional dosage forms if they contain a covered compound.

Claim 6 does not, by itself, create a detailed formulation patent. It is a compound-containing composition claim. Later formulation patents would typically require narrower limitations, such as specific excipients, particle size, polymorph, dissolution profile, coating, or manufacturing conditions.

Claim 7: post-myocardial-infarction treatment

Claim 7 covers administering a claim 1 compound to a patient suffering from post-myocardial infarction.

This is a method-of-treatment claim. It is narrower than a general cardiovascular-use claim but broad in its omission of:

Dose.
Frequency.
Duration.
Route of administration.
Combination therapy.
Patient biomarker.
Specific time interval after infarction.

The claim could be relevant to ticagrelor's use in patients with a history of myocardial infarction, although an infringement analysis would require comparing the accused labeling and actual use with the claim's patient and treatment limitations.

Claim 14: stroke treatment

Claim 14 covers treatment of stroke with a claim 1 compound.

This is a separate method-of-treatment claim. It does not require the post-myocardial-infarction condition in claim 7. The claim's breadth is offset by potential issues concerning:

Whether the claimed use was adequately supported by the specification.
Whether the method was enabled across the full compound genus.
Whether a later product label instructs the claimed use.
Whether the relevant use is direct or induced infringement.

What do claims 8 through 13 cover?

Claims 8 through 13 expand the patent beyond finished drug compounds.

Claim 8: manufacturing process

Claim 8 covers a process that reacts:

A formula II compound containing the carbocyclic nucleoside portion and a leaving group.
A formula III compound containing the cyclopropyl aryl amine.
A base.
An inert solvent.
Ambient or elevated temperature.

The process also covers subsequent operations, including:

Functional-group conversion.
Deprotection.
Salt formation.
Solvate formation.

This is a coupling-process claim. It can be relevant to manufacturing freedom to operate even where a final ticagrelor compound claim has expired, but only if the accused process falls within every process limitation. A process using a different coupling order, different leaving group, different solvent system, or different reaction mechanism may avoid literal infringement.

Claims 9 through 13: intermediates and protected derivatives

These claims cover protected carbocyclic intermediates, amino and bromo triazolopyrimidine intermediates, ester intermediates, sulfone analogues, acetate derivatives, and hydroxyethoxy precursors.

The intermediates include:

Acetonide-protected cyclopentane compounds.
Bromo-substituted heterocyclic intermediates.
7-amino intermediates.
Propylthio, butylthio, and 3,3,3-trifluoropropylthio compounds.
Methyl ester and acetate derivatives.
Hydroxyethoxy precursors.
Propylsulfonyl oxidation products.

These claims have two practical functions:

They protect chemical building blocks that may be used in the synthesis of ticagrelor or related analogues.
They provide fallback positions if a final-product claim is challenged.

The intermediate claims are not coextensive with ticagrelor. Several listed compounds have protected hydroxyl groups, leaving groups, halogens, esters, or different oxidation states. A manufacturer can infringe an intermediate claim without making the finished drug, although the patent's expiration eliminates current US enforcement of these claims.

When did US Patent 6,525,060 expire?

US 6,525,060 issued on February 25, 2003. Its ordinary US patent term ran approximately 20 years from the relevant nonprovisional filing date, producing an expiration in May 2020. FDA Orange Book records identify the patent as expiring on May 9, 2020. Any pediatric exclusivity associated with the product would have extended regulatory protection for six months, but not the underlying patent term.[1][2]

Event	Date or status
US patent application	Filed before issuance; associated with the AstraZeneca triazolopyrimidine family
Patent issuance	February 25, 2003
Patent number	US 6,525,060
Patent holder or original applicant	AstraZeneca group entity
FDA product associated with compound	Brilinta, ticagrelor
Listed patent expiration	May 9, 2020
Current patent status	Expired in the United States
Pediatric exclusivity	Potentially extended FDA marketing protection, not patent enforceability

The practical result is that US 6,525,060 no longer blocks manufacture, sale, or importation of ticagrelor on its own.

What was the Orange Book status of ticagrelor?

The Orange Book listed US 6,525,060 for Brilinta and identified it as a drug-substance or drug-product patent associated with ticagrelor. The listing was important during the period when generic applicants filed abbreviated new drug applications and submitted Paragraph IV certifications.

Orange Book listing does not establish that a patent is valid or infringed. It triggers the Hatch-Waxman notice and litigation framework when a generic applicant certifies that a listed patent is invalid, unenforceable, or not infringed.[1]

After expiration of US 6,525,060, later-listed patents became more important to the timing of generic entry. Those patents may cover:

Ticagrelor formulations.
Specific dosage forms.
Crystalline or solid-state forms.
Manufacturing processes.
Therapeutic uses.
Dosing regimens or patient populations.

The original compound patent should therefore be separated from later Orange Book-listed patents in any current launch analysis.

Did ticagrelor generic applicants file Paragraph IV challenges?

Generic applicants seeking approval before expiration of US 6,525,060 could use a Paragraph IV certification against the patent. A Paragraph IV certification asserts that the listed patent is invalid, unenforceable, or would not be infringed by the proposed generic product.[3]

The principal commercial consequences were:

AstraZeneca could file a patent-infringement action within 45 days of receiving notice.
FDA approval could be stayed for up to 30 months, subject to statutory exceptions.
The first substantially complete Paragraph IV filer could potentially receive 180-day generic exclusivity.
Litigation would focus on claim construction, validity, and the relationship between the proposed generic product and the claimed ticagrelor structure.

Because US 6,525,060 has expired, a new Paragraph IV challenge to that patent is no longer a meaningful basis for delaying approval. Current applicants would focus on unexpired Orange Book patents, if any remain listed for the relevant ticagrelor product and dosage form.

What patent litigation affected the ticagrelor market?

Ticagrelor litigation primarily arose from ANDA filings seeking approval before expiration of AstraZeneca's listed patents. The litigation risk centered on:

Direct infringement of the ticagrelor compound claims.
Validity of the Markush genus and expressly claimed species.
Obviousness based on prior P2Y12 antagonists and nucleoside analogues.
Written description and enablement for the stereochemically complex genus.
Later patents directed to formulations, dosage strengths, or methods of use.

The patent's broad chemical scope would have made a conventional small-molecule generic difficult to design around while the patent was enforceable. A generic applicant generally could not avoid infringement by changing excipients or tablet shape if the active ingredient remained ticagrelor. The principal route to early entry was therefore a successful validity or noninfringement challenge, a settlement, or a license.

Public litigation databases and FDA records should be reviewed separately for each ANDA defendant because filing dates, asserted patents, settlement terms, and launch dates differed by applicant. A litigation result involving a later formulation patent does not necessarily determine the validity of US 6,525,060.

Were there settlement agreements or licensing deals?

The supplied claims do not identify settlement agreements or licenses. Public patent records establish ownership and prosecution history, but they do not by themselves establish the commercial terms of any Hatch-Waxman settlement.

The commercially relevant distinction is:

A license or settlement may authorize an agreed generic launch date.
A consent judgment may resolve litigation without invalidating the patent.
A patent expiration ends the exclusionary right regardless of whether earlier litigation settled.
Confidential settlement provisions may not appear in the patent file.

For current competition analysis, the expiration of US 6,525,060 is more important than any historical settlement involving that patent.

How strong was the patent estate for ticagrelor?

Strengths

The patent had several structural strengths:

It included a broad Markush genus.
It recited ticagrelor as a specific species.
It covered pharmaceutically acceptable salts and solvates.
It included a pharmaceutical composition claim.
It included post-myocardial-infarction and stroke treatment claims.
It covered intermediates and a manufacturing process.
The compound was structurally distinctive, limiting simple chemical design-around options.

Weaknesses

The principal vulnerabilities were typical of an early small-molecule compound patent:

The genus contained many stereochemical and substituent combinations.
The broad claim depended on the adequacy of the specification's examples and guidance.
Provisos created complex claim boundaries.
Method claims could face limitations based on label wording and actual use.
Process claims required proof that the accused manufacturing route met each process limitation.
Later generic litigation could raise obviousness arguments based on known antiplatelet pharmacophores and nucleoside mimics.

The estate was strongest against a product containing ticagrelor itself during the patent term. It was less effective against unrelated P2Y12 antagonists, noninfringing manufacturing routes, or products entering after patent expiration.

How does US 6,525,060 compare with later ticagrelor patents?

Patent category	Typical protected subject matter	Relevance to generic entry
US 6,525,060	Ticagrelor and related compound genus; compositions; methods; intermediates; process	Core compound barrier; expired in 2020
Later compound patents	New salts, polymorphs, stereochemical forms, or analogues	May block particular versions if valid and listed
Formulation patents	Tablets, excipients, dissolution, particle properties, dosage forms	Can delay or complicate ANDA approval
Method-of-use patents	Cardiovascular, post-MI, stroke, or dosing applications	Relevant to labeling and induced-infringement analysis
Process patents	Specific synthesis, purification, or crystallization routes	Relevant to API suppliers and supply chains
Regulatory exclusivity	New clinical evidence, pediatric exclusivity, or qualified uses	May restrict approval independently of patent rights

The core patent should not be treated as the complete ticagrelor estate. A current freedom-to-operate review must map each proposed API process, dosage form, strength, label, and jurisdiction against the later patent family.

What generic entry risks exist after expiration?

The main US barriers after expiration of US 6,525,060 are regulatory and secondary-patent issues rather than the original compound claim.

Potential risks include:

A listed formulation patent covering the proposed dosage form.
A method-of-use patent implicated by the proposed label.
A process patent covering the API synthesis.
A patent on a solid form or impurity profile.
FDA requirements for bioequivalence and product-specific labeling.
ANDA litigation involving later-listed patents.
Supply-chain exposure if the API manufacturer uses a patented route in another jurisdiction.

A standard immediate-release ticagrelor tablet containing the same active moiety generally cannot be designed around the expired compound claim by changing inactive ingredients. The design-around analysis instead focuses on unexpired secondary patents and the manufacturing route.

What is the geographic coverage of US 6,525,060?

US 6,525,060 provides rights only in the United States. The underlying invention was prosecuted through an international patent family, with corresponding applications or patents in other jurisdictions.

Foreign equivalents must be analyzed independently because:

Patent claims differ by jurisdiction.
Prosecution amendments may narrow foreign claims.
Patent-term calculations differ.
Supplementary protection certificates may affect European rights.
Some foreign patents may have expired earlier or later than the US patent.
Litigation outcomes are jurisdiction-specific.

A US patent expiration does not establish freedom to operate in Europe, Japan, China, Canada, or other markets.

Key Takeaways

US 6,525,060 is a foundational AstraZeneca patent for ticagrelor and related triazolopyrimidine compounds.
Claim 1 is a broad Markush genus defined by thioalkyl, fluorinated phenyl, hydroxy, and hydroxyalkyl variables.
Claim 5 expressly recites ticagrelor as a specific stereochemically defined compound.
Claims 6, 7, and 14 cover compositions, post-myocardial-infarction treatment, and stroke treatment.
Claim 8 covers a key coupling process; claims 9 through 13 cover protected intermediates and synthetic precursors.
The US patent issued on February 25, 2003, and expired in May 2020.
The patent no longer independently blocks US generic ticagrelor entry.
Current commercial risk depends on later Orange Book patents, formulation rights, method-of-use claims, process patents, and FDA approval requirements.
Foreign equivalents require separate expiration and claim-scope analysis.
Historical Paragraph IV litigation involving this patent is no longer a current patent-term barrier, although it remains relevant to the product's competitive history.

Frequently Asked Questions

What is the active ingredient covered by US 6,525,060?

The principal commercial active ingredient is ticagrelor, marketed in the United States as Brilinta by AstraZeneca.

Is US Patent 6,525,060 still enforceable?

No. The patent's US term expired in 2020, subject to the precise statutory term calculation and any separate regulatory exclusivity.

Does the patent cover ticagrelor salts and solvates?

Yes. Claim 1 expressly includes pharmaceutically acceptable salts, solvates, and solvates of such salts.

Can a generic avoid US 6,525,060 by using different excipients?

No, not during the patent term if the generic contains a claimed ticagrelor compound. Different excipients would generally not avoid a compound claim. The patent's expiration removes that barrier today.

Does expiration of US 6,525,060 eliminate all ticagrelor patent risk?

No. Later patents may cover formulations, solid forms, manufacturing methods, or therapeutic uses. Those rights must be reviewed separately for the proposed product and launch strategy.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Patent and Trademark Office. (2003). U.S. Patent No. 6,525,060: Triazolopyrimidine compounds and their use as pharmaceuticals. https://patents.google.com/patent/US6525060
U.S. Food and Drug Administration. (2015). Hatch-Waxman amendments and patent certification procedures. FDA. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/hatch-waxman-amendments
AstraZeneca Pharmaceuticals LP. (2011). Brilinta (ticagrelor) prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/
United States Code, 35 U.S.C. §§ 154, 271, and 282. (2024). Patent term, infringement, and presumptions of validity. Cornell Legal Information Institute. https://www.law.cornell.edu/uscode/text/35

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	9804211	Dec 04, 1998
Sweden	9901271	Apr 09, 1999

PCT Information
PCT Filed	December 02, 1999	PCT Application Number:	PCT/SE99/02256
PCT Publication Date:	June 15, 2000	PCT Publication Number:	WO00/34283

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1135391	⤷ Start Trial	C300485	Netherlands	⤷ Start Trial
European Patent Office	1135391	⤷ Start Trial	CA 2011 00013	Denmark	⤷ Start Trial
European Patent Office	1135391	⤷ Start Trial	PA2011004	Lithuania	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,525,060