# United States Drug Patent 6,130,208: Claim Scope, Expiration, Orange Book Status, and Competitive Patent Landscape

U.S. Patent No. 6,130,208 protects pharmaceutical compositions containing a defined nucleotide analog and one or more glass-forming additives. The patent also covers dried and reconstituted dosage forms, sucrose-modified formulations, manufacturing processes, and therapeutic use in platelet aggregation disorders, acute coronary syndromes, percutaneous transluminal coronary angioplasty, and angina.

The patent is a formulation and method-of-use patent. It does not, based on the supplied claims, claim the nucleotide analog as a chemical entity by itself. Its commercial value therefore depends on whether a marketed product uses the claimed nucleotide analog in a glass-forming, dried or reconstituted composition.

What does U.S. Patent 6,130,208 protect?

The patent protects a composition containing two required elements:

A nucleotide analog within the genus defined by formula (I).
At least one glass-forming additive.

Claim 1 is the principal composition claim. Claims 2 through 5 narrow the formulation. Claims 6, 8 and 9 cover medical uses. Claim 7 covers preparation of the dried formulation.

Claim	Subject matter	Commercial relevance
1	Nucleotide analog plus one or more glass-forming additives	Core formulation claim
2	Freeze-dried, spray-dried or vacuum-dried form	Covers solid pharmaceutical presentation
3	Reconstituted composition	Covers product after preparation for administration
4	Composition further containing a modifying agent	Adds formulation flexibility
5	Modifying agent is sucrose	Narrower sucrose embodiment
6	Treatment of platelet aggregation disorders	Broad therapeutic-use claim
7	Process using freezing and drying or spray-drying	Manufacturing-process claim
8	Treatment of acute coronary syndromes and use in PTCA	Cardiovascular method-of-use claim
9	Treatment of angina	Narrower cardiovascular use claim

The use of “comprising” in claim 1 makes the claim open-ended. A formulation can contain additional active ingredients, excipients, buffers, stabilizers or carriers and still fall within the claim if it contains the required nucleotide analog and glass-forming additive.

How broad is claim 1 of U.S. Patent 6,130,208?

Claim 1 is broad in formulation structure but limited by the chemical genus and the glass-forming-additive requirement.

Chemical scope of the nucleotide analog

The claimed nucleotide analog is defined by a formula in which:

R1 and R2 are independently hydrogen or halogen;
R3 and R4 are independently phenyl or substituted C1-6 alkyl;
substitutions may include OR5, C1-6 alkylthio, NR6R7, phenyl, COOR8 or halogen;
R5 through R8 are independently hydrogen or C1-6 alkyl; and
X is an acidic moiety.

The claim also covers pharmaceutically acceptable salts.

The missing structural drawing designated “##STR6##” is material to a complete Markush-group analysis. The text identifies the permissible substituents but does not show the chemical backbone, ring system, nucleotide attachment points or the position of the acidic moiety. Those features determine whether a commercial nucleotide analog falls within the claimed genus.

On the supplied wording, the claim is directed to a defined class of nucleotide-like platelet aggregation inhibitors rather than to every nucleotide analog. A product must satisfy both the structural formula and the formulation limitations.

Glass-forming additives

“Glass forming additives” is a functional formulation limitation. The term generally covers excipients that produce or stabilize an amorphous glassy matrix during freeze-drying, spray-drying or vacuum drying. Likely candidates include sugars, polyols and related stabilizing excipients, but the patent specification controls the precise construction.

Claim 1 does not require sucrose. Sucrose appears only in claim 5. A formulation using another qualifying glass-forming additive could therefore fall within claim 1 while avoiding claim 5.

Pharmaceutically acceptable salts

The salt language expands claim coverage to salt forms of the nucleotide analog. A sodium, potassium, ammonium or other pharmaceutically acceptable salt may be covered if the underlying compound satisfies the structural formula and the finished composition contains a qualifying glass-forming additive.

What formulations are protected by U.S. Patent 6,130,208?

Claims 2 through 5 cover several dosage-form and excipient configurations.

Freeze-dried formulations

Claim 2 expressly covers a freeze-dried composition. This is the most commercially important embodiment if the nucleotide analog is unstable in aqueous solution or requires storage as a powder for later injection.

A product can potentially fall within claim 2 if it contains:

the claimed nucleotide analog;
one or more glass-forming additives; and
a freeze-dried presentation.

Claim 7 separately covers the process of mixing the ingredients, freezing the mixture and drying the frozen material.

Spray-dried and vacuum-dried formulations

Claim 2 also covers spray-dried and vacuum-dried products. These alternatives prevent a competitor from avoiding the claim merely by selecting a drying process other than lyophilization.

The process claim is narrower than the composition claim in one respect: it requires mixing the ingredients and using freezing and drying or spray-drying. A manufacturer using a different production route may avoid claim 7 while still infringing a composition claim if the resulting product meets the limitations of claim 1 or claim 2.

Reconstituted products

Claim 3 covers the composition in reconstituted form. This is important for injectable products supplied as a powder and reconstituted with a diluent before administration.

A reconstituted product may present separate infringement questions concerning:

the identity of the nucleotide analog;
the concentration of glass-forming additive remaining after reconstitution;
whether the reconstituted product is legally the same claimed composition; and
whether the reconstitution step changes the formulation enough to avoid a claim limitation.

Sucrose-containing products

Claim 5 narrows claim 4 by requiring sucrose as the modifying agent. A product containing sucrose and another qualifying glass-forming additive may fall within both the broader composition claim and the sucrose-specific claim.

A product without sucrose can still infringe claims 1 through 4 if it uses another modifying agent or satisfies the broader glass-forming-additive limitation.

How do the method-of-use claims affect infringement risk?

Claims 6, 8 and 9 cover administration of the claimed composition for cardiovascular indications.

Claim	Indication or procedure	Scope
6	Platelet aggregation disorder	Broadest therapeutic-use claim
8	Acute coronary syndromes and PTCA	More specific cardiovascular use
9	Angina	Specific disease-use claim

These claims require administration of a pharmaceutical composition “as defined in claim 1.” The method claims therefore incorporate the composition limitations. Administration of the nucleotide analog alone, without the claimed glass-forming formulation, would not satisfy the literal language of these claims.

The method claims may create liability risks for a manufacturer, distributor or healthcare provider depending on the applicable indirect-infringement facts, product labeling, promotional activity and prescribing behavior. A generic applicant could attempt to avoid method-of-use exposure through a section viii labeling carve-out, but that strategy would not avoid composition claims directed to the product itself.

When did U.S. Patent 6,130,208 lose exclusivity?

U.S. Patent No. 6,130,208 is an early-generation patent issued in 2000. Its enforceable term was based on the post-1995 twenty-year patent-term regime, measured from the applicable earliest nonprovisional or international filing date, subject to any patent-term adjustment.

The patent’s core term expired in approximately 2018. The controlling date is the expiration and adjustment data recorded by the USPTO patent file, not the issue date. The patent is therefore not a current blocking patent for ordinary U.S. commercialization.

Event	Approximate timing
Earliest priority period	Late 1990s
U.S. filing and prosecution	Late 1990s
Patent issued	September 2000
Base twenty-year term endpoint	Approximately 2018
Current enforceability	Expired by term

An expired patent cannot support a new U.S. infringement action for post-expiration conduct. It may still matter as prior art, as a family-history document, or as evidence of formulation development, but it does not create current patent exclusivity.

What is the Orange Book status of U.S. Patent 6,130,208?

U.S. Patent 6,130,208 should not be treated as a current Orange Book barrier solely because it concerns a cardiovascular nucleotide analog formulation.

The Orange Book lists patents identified by an NDA holder for a specific approved drug product. Listing depends on the sponsor’s submission, FDA acceptance of the listing, the patent type, and the drug-product relationship. A patent can be technically relevant to a drug yet absent from the current Orange Book.

For an approved platelet inhibitor supplied as a lyophilized or reconstituted product, the relevant current patents would usually be later patents covering:

the active compound or salt;
specific injectable formulations;
dosing regimens;
treatment timing during PCI or ACS;
stability or container systems; and
manufacturing or purification methods.

Because U.S. Patent 6,130,208 is expired, it would not provide current Orange Book exclusivity even if it had historically been listed. The FDA Orange Book and the sponsor’s patent-certification history are the controlling sources for current listing status. [U.S. Food and Drug Administration, 2024a]

Which companies are challenging the patent?

No Paragraph IV challenge can be established from the claim text alone. Paragraph IV activity is tied to an ANDA, an identified listed patent and litigation filed under the Hatch-Waxman framework.

For an expired patent, a current Paragraph IV challenge has limited practical value. An ANDA applicant would not need to wait for expiration of U.S. Patent 6,130,208, although the applicant could still address the patent in its certification strategy if the patent remained listed in a relevant Orange Book record.

The principal litigation risk would instead come from later, unexpired patents associated with the marketed nucleotide analog or its approved product. A patent-family review must separate:

expired formulation patents;
active-ingredient patents;
formulation patents with remaining term;
method-of-use patents;
regulatory exclusivity; and
patents listed for the specific NDA product.

Does the patent create biosimilar risk?

No. Biosimilar law applies to biological products licensed under the Public Health Service Act. A chemically synthesized nucleotide analog is regulated as a small-molecule drug and would generally be challenged through the ANDA pathway, not through a biosimilar application under section 351(k). [FDA, 2024b]

The relevant competitive threat is therefore generic entry, not biosimilar entry.

What generic launch scenarios exist?

The patent itself presents no current generic-launch barrier because its term has ended. Commercial launch risk depends on later patents and FDA exclusivity associated with the marketed product.

Scenario 1: Formulation design-around

A competitor could use:

a liquid formulation;
a non-glass-forming stabilizer system;
a different drying technology;
a different salt or pH system; or
a formulation that does not contain the claimed nucleotide analog genus.

This approach would target the limitations of claim 1 rather than challenge validity.

Scenario 2: Paragraph IV challenge to later patents

If later patents remain listed for the reference product, an ANDA applicant could file a Paragraph IV certification and seek a 30-month stay dispute under the Hatch-Waxman framework. The relevant litigation would concern those later patents, not the expired ’208 patent. [21 U.S.C. § 355]

Scenario 3: Paragraph III or expiration-based launch

An ANDA applicant could certify that relevant listed patents have expired or will expire before launch. This route avoids the need to prove invalidity or noninfringement.

Scenario 4: Non-infringing labeled use

For method-of-use patents, an applicant may attempt to remove patented indications from the proposed labeling. That strategy does not eliminate exposure under product or formulation patents.

How strong is the patent estate for the claimed technology?

The expired ’208 patent has no current exclusionary strength, but its original claim architecture was commercially meaningful.

Factor	Assessment
Composition breadth	Broad, subject to the structural genus and glass-forming limitation
Chemical-entity protection	Not established by the supplied claims
Formulation protection	Meaningful for dried or reconstituted products
Process protection	Narrower and easier to design around
Method-of-use protection	Dependent on use of the claimed composition
Current enforceability	None after term expiration
Generic barrier today	Low from this patent alone
Biosimilar relevance	None
Prior-art value	Potentially significant for later formulation claims

The strongest original protection was likely claim 1 because it covered any qualifying composition containing the claimed nucleotide analog and glass-forming additive. Claim 2 added commercially important dried presentations. Claim 7 was more vulnerable to process substitution, while claims 6, 8 and 9 depended on proving use of the claimed formulation for the recited indication.

What geographic coverage does the patent provide?

U.S. Patent 6,130,208 provides U.S. rights only. Patent protection in Europe, Japan, Canada or other jurisdictions would require separate national or regional patents in the same family.

The expiration of the U.S. patent does not establish the status of foreign counterparts. Foreign family members may have:

different filing dates;
different claim scope;
terminal disclaimers;
opposition or revocation history;
supplementary protection certificates; or
earlier expiration.

A global freedom-to-operate review therefore must analyze the full priority family rather than rely on the U.S. patent number.

What manufacturing and intellectual-property barriers remain?

The ’208 patent’s manufacturing claims focus on mixing, freezing and drying or spray-drying. Those claims could have affected a manufacturer using a conventional lyophilized production process during the patent term.

Current manufacturing barriers are more likely to arise from later patents covering:

sterile filtration;
crystallization or purification of the nucleotide analog;
control of degradation products;
container-closure systems;
reconstitution time;
concentration and dosing;
stability under refrigerated storage; and
commercial-scale lyophilization.

Expired formulation patents can also remain relevant as technical prior art against later patents that attempt to claim similar stabilizer systems or drying processes.

Key Takeaways

U.S. Patent 6,130,208 is a formulation patent covering a nucleotide analog combined with one or more glass-forming additives.
The core claim is open-ended because it uses “comprising.”
The patent covers freeze-dried, spray-dried, vacuum-dried and reconstituted compositions.
Sucrose is a narrower embodiment, not a requirement of the core claim.
Claims 6, 8 and 9 cover treatment of platelet disorders, ACS, PTCA and angina using the claimed composition.
Claim 7 covers a specific preparation process and is more susceptible to process design-around.
The patent’s U.S. term expired in approximately 2018.
It does not create a current generic or biosimilar barrier.
Current commercial risk must be assessed against later patents listed for the relevant approved drug product.
The missing structural drawing for formula (I) prevents a complete chemical-genus comparison against any particular nucleotide analog.
Foreign patent-family status cannot be inferred from the U.S. patent alone.

FAQs

Is U.S. Patent 6,130,208 a compound patent?

No. The supplied claims are directed to pharmaceutical compositions, methods of treatment and a manufacturing process. The claims do not independently claim the nucleotide analog as a chemical compound.

Can a liquid formulation avoid U.S. Patent 6,130,208?

Potentially. The principal claims require one or more glass-forming additives, and claim 2 requires a dried form. A liquid formulation without a qualifying glass-forming additive may avoid the literal scope, subject to the full specification and doctrine-of-equivalents analysis.

Does the patent cover every P2Y12 inhibitor?

No. The nucleotide analog must fall within the specific formula (I) genus, and the composition must contain a glass-forming additive. The claims do not cover unrelated platelet inhibitors such as clopidogrel, prasugrel, ticagrelor or abciximab merely because they treat platelet disorders.

Can a generic applicant ignore the patent because it is expired?

For current U.S. launch purposes, an expired patent does not block entry. The applicant must still assess later patents, FDA exclusivity, labeling restrictions and any other enforceable intellectual-property rights associated with the reference product.

Does expiration of the U.S. patent mean all foreign counterparts expired?

No. Foreign counterparts require separate analysis. Their terms, prosecution histories, claims and supplementary protection rights may differ from the U.S. patent.

References

U.S. Patent and Trademark Office. (2000). U.S. Patent No. 6,130,208, pharmaceutical compositions comprising a nucleotide analog. Washington, DC: U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations. Silver Spring, MD: U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024b). Purple Book: Database of licensed biological products. Silver Spring, MD: U.S. Department of Health and Human Services.
21 U.S.C. § 355. Abbreviated applications and patent certifications.
35 U.S.C. §§ 154, 156. Patent term and patent-term extension.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	9702680	Jul 11, 1997

PCT Information
PCT Filed	June 29, 1998	PCT Application Number:	PCT/SE98/01287
PCT Publication Date:	January 21, 1999	PCT Publication Number:	WO99/02542

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	013157	⤷ Start Trial
Austria	340801	⤷ Start Trial
Australia	8362598	⤷ Start Trial
Brazil	9810703	⤷ Start Trial
Canada	2295628	⤷ Start Trial
China	1263533	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,130,208

Summary for Patent: 6,130,208