United States Drug Patent 6,114,313: Scope, Claims, Expiration, and Cangrelor Patent Landscape

U.S. Patent No. 6,114,313 protects pharmaceutical formulations containing a defined class of nucleotide analogs, mannitol, and sodium chloride or a polyol. The central commercial embodiment is cangrelor, the intravenous P2Y12 platelet-inhibitor marketed as Kengreal. The patent does not principally claim cangrelor as a molecule. It claims stabilized, dried, and reconstitutable pharmaceutical compositions containing cangrelor or structurally related nucleotide analogs.

The strongest coverage is concentrated in claims 1, 3, 5, 7, 8, 10, 11, and 13. Claim 3 identifies cangrelor specifically. Claims 7 through 10 add manufacturing and product-quality limitations involving drying, reconstitution, pH, and residual water. Claims 11 and 13 create process exposure for manufacturers using the claimed excipient and drying sequence.

What drug does U.S. Patent 6,114,313 protect?

The patent covers formulations of nucleotide analogs that inhibit platelet aggregation, with cangrelor as the principal identified compound.

The compound in claim 3 is:

N-[2-(methylthio)ethyl]-2-[(3,3,3-trifluoropropyl)thio]-5'-adenylic acid, monoanhydride with dichloromethylenebisphosphonic acid.

This compound is cangrelor, also known as AR-C69931MX and cangrelor tetrasodium in its marketed pharmaceutical form. Cangrelor is an intravenous, direct-acting P2Y12 receptor antagonist used to reduce thrombotic cardiovascular events in patients undergoing percutaneous coronary intervention when oral P2Y12 therapy is not practical or desirable (U.S. Food and Drug Administration [FDA], 2015).

The patent’s claim architecture is formulation-focused:

Patent subject	Covered by U.S. 6,114,313?
Cangrelor molecule in isolation	No, not directly
Defined nucleotide analog class in a pharmaceutical composition	Yes
Cangrelor with mannitol	Yes
Cangrelor with sorbitol or another polyol	Yes
Cangrelor with sodium chloride	Yes
Lyophilized cangrelor formulation	Yes
Spray-dried or vacuum-dried formulation	Yes
Reconstituted formulation	Yes
pH approximately 6 to 10	Yes, when incorporated through claim 9
Water content below 5% by weight	Yes, when incorporated through claim 10
Treatment of platelet aggregation disorder	Yes, under claim 12
Manufacturing process using the claimed drying operations	Yes, under claims 11 and 13

What is the claim scope of U.S. Patent 6,114,313?

The patent has three functional claim groups: composition claims, manufacturing claims, and treatment claims.

How broad is independent claim 1?

Claim 1 requires four principal elements:

A pharmaceutical composition.
A nucleotide analog having the specified structural formula.
Mannitol.
A modifying additive that is sodium chloride or a polyol.

The claim is not limited to cangrelor. Its Markush structure covers a broader family of nucleotide analogs defined by substituents R1 through R8 and an acidic moiety X.

The relevant chemical variables are:

Variable	Claimed alternatives
R1 and R2	Hydrogen or halogen
R3 and R4	Phenyl or substituted C1-C6 alkyl
R5-R8	Hydrogen or C1-C6 alkyl
X	An acidic moiety
Modifying additive	Sodium chloride or a polyol
Required excipient	Mannitol

A composition that lacks mannitol falls outside claim 1, even if it contains cangrelor and sodium chloride. A composition containing mannitol but no sodium chloride or polyol also falls outside claim 1. The claim therefore requires both the core excipient and one of the specified modifying additives.

What does claim 2 add?

Claim 2 narrows the chemical genus by requiring:

Halogen substitution at R1 and R2;
An alkyl or alkylthio-substituted alkyl group at R3;
An alkyl or haloalkyl group at R4; and
X to be phosphonic acid, sulfonic acid, or carboxylic acid.

Cangrelor is within this narrower class. Claim 2 is important because claim 12 depends on claim 2, not merely on claim 1.

What does claim 3 cover?

Claim 3 identifies cangrelor by chemical name. It is the most commercially significant composition limitation in the patent.

Claim 3 remains a formulation claim. It does not claim cangrelor in every pharmaceutical or nonpharmaceutical context. A competing product would need to include the specified cangrelor compound in a composition that also satisfies the limitations inherited from claim 1, including mannitol and sodium chloride or a polyol.

What do claims 4 and 5 protect?

Claim 4 requires the modifying additive to be a polyol. Claim 5 narrows the polyol to sorbitol.

These claims create separate infringement routes:

Cangrelor plus mannitol and sorbitol may fall within claims 1, 3, 4, and 5.
Cangrelor plus mannitol and sodium chloride may fall within claims 1 and 3 but not claim 5.
Cangrelor plus mannitol and another qualifying polyol may fall within claims 1 and 4 but not necessarily claim 5.

What does claim 6 add?

Claim 6 requires at least 1% by weight of mannitol. The claim provides a quantitative limitation that can be tested through product composition, batch records, formulation specifications, or analytical testing.

A formulation containing trace mannitol below 1% by weight would not satisfy claim 6, although it could still satisfy claim 1 if all other limitations are met.

What do claims 7 through 10 protect?

These claims target solid-state and finished-product characteristics:

Claim 7: freeze-dried, spray-dried, or vacuum-dried form.
Claim 8: reconstituted form.
Claim 9: pH of about 6 to about 10.
Claim 10: water content below 5% by weight.

The combination is directed to an injectable product supplied as a dry powder and reconstituted before administration. The claims are commercially relevant because cangrelor is supplied for intravenous preparation rather than as a conventional oral tablet.

“About” in claim 9 introduces a range-construction issue. The legally relevant pH boundary would depend on intrinsic evidence, prosecution history, specification examples, and ordinary pharmaceutical practice. A product at pH 6.0 to 10.0 is the obvious target, but values near the boundaries would require claim-construction analysis.

How do the process claims affect generic manufacturers?

Claims 11 and 13 create process exposure separate from the finished-composition claims.

Claim	Process limitation
11	Mix ingredients, then freeze and dry the frozen mixture or spray the mixture
13	Mix nucleotide analog, mannitol, and sodium chloride or polyol, then use lyophilization, vacuum drying, or spray drying

Claim 13 is particularly relevant to generic injectable manufacturers because it expressly names the formulation ingredients and drying operations. A generic sponsor could attempt to avoid literal infringement by:

Using a different stabilizing excipient;
Omitting mannitol;
Using a different drying or concentration process;
Marketing a liquid formulation;
Using a formulation outside the claimed nucleotide-analog structure; or
Demonstrating that the final composition does not satisfy the inherited claim limitations.

Process avoidance is not automatically sufficient. A court could consider equivalents, and the product itself may still infringe composition claims even if the manufacturing process differs.

What is the scope of claim 12 for platelet aggregation treatment?

Claim 12 covers treating a platelet aggregation disorder with a therapeutically effective amount of the composition defined in claim 2.

The claim is narrower than a general method-of-use claim for cangrelor. It requires the claimed composition, including the structural restrictions in claim 2. A method using cangrelor in an unclaimed formulation would not necessarily fall within claim 12.

The likely clinical field includes:

Percutaneous coronary intervention;
Acute coronary syndromes;
Prevention of platelet-mediated arterial thrombosis; and
Situations requiring immediate and reversible P2Y12 inhibition.

The claim does not appear limited to a particular procedure, patient population, dose, infusion duration, or clinical endpoint. Its principal limitation is the composition administered.

What formulation technology is protected?

The patent is directed to improving the handling and pharmaceutical performance of unstable or difficult-to-formulate nucleotide analogs.

The protected formulation concept combines:

Cangrelor or a related nucleotide analog;
Mannitol as a bulking or stabilizing excipient;
Sodium chloride or a polyol as a modifying additive; and
Drying into a low-water solid suitable for reconstitution.

The water-content limitation in claim 10 is commercially significant. Reducing residual water can improve storage stability, reduce degradation, and support a shelf-stable injectable product. The claim does not require a particular vial, stopper, diluent, concentration after reconstitution, or administration device.

What is the patent expiration date for U.S. Patent 6,114,313?

U.S. Patent 6,114,313 issued on September 5, 2000 (U.S. Patent No. 6,114,313, 2000). Its enforceable term must be determined from the patent’s earliest effective U.S. nonprovisional filing or priority date, together with any applicable patent-term adjustment, patent-term extension, terminal disclaimer, and regulatory extension.

The key legal point is that the patent is not governed solely by the issue date. For modern U.S. patents, the baseline term is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156.

The patent’s remaining commercial relevance therefore depends on:

The earliest effective filing date;
Any patent-term adjustment recorded by the USPTO;
Any FDA patent-term extension;
The Orange Book listing history for Kengreal;
Whether a terminal disclaimer applies; and
Whether continuation or related patents provide later-dated protection.

The patent itself should not be treated as an automatically current barrier merely because it is listed in historical patent databases. FDA Orange Book records and the USPTO Patent Center file history control the current status analysis (FDA, n.d.; U.S. Patent and Trademark Office [USPTO], n.d.).

What is the Orange Book status of cangrelor and Kengreal?

Kengreal was approved by FDA in June 2015 under NDA 207558 for intravenous use in patients undergoing PCI (FDA, 2015).

For Orange Book purposes, the relevant analysis is narrower than a general patent search. A patent must be evaluated for:

Listing against the approved NDA;
The specific dosage form and route;
Patent-use-code language;
Expiration or delisting status;
Whether the patent covers the active ingredient, formulation, method of use, or drug product; and
Whether a generic applicant must certify under Paragraph III, Paragraph IV, or another applicable pathway.

U.S. Patent 6,114,313 is best characterized as a formulation and method patent. It is not a classic compound patent claiming cangrelor in all forms. Its practical significance depends on whether the listed product uses the claimed mannitol-plus-modifying-additive formulation and whether the relevant patent term remains enforceable.

Which companies challenged or could challenge the patent?

Publicly identifiable commercial risk centers on generic injectable manufacturers rather than biosimilar developers. Potential parties include companies with sterile injectable manufacturing capabilities, such as Fresenius Kabi, Hikma, Sagent, Teva, Pfizer, and other ANDA sponsors. A company becomes a legal challenger only if it files an ANDA with a Paragraph IV certification or otherwise creates an actionable controversy.

The principal challenge theories would be:

Challenge theory	Likely target
Anticipation	Earlier formulation disclosure containing mannitol and the required additive
Obviousness	Combining known nucleotide-analog stabilization methods with mannitol and sodium chloride or a polyol
Lack of written description	Breadth of the Markush genus and support for all substituent combinations
Lack of enablement	Full scope of the broad chemical and formulation combinations
Indefiniteness	“About” pH range and boundaries of “polyol” or “modifying additive”
Noninfringement	Different excipients, liquid formulation, different drying route, or different water content
Invalidity based on prosecution history	Narrowing amendments or surrendered subject matter

No biosimilar pathway applies to cangrelor because cangrelor is a chemically synthesized small-molecule drug, not a biologic. The relevant regulatory route is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under section 351(k) of the Public Health Service Act.

How strong is the patent estate for cangrelor?

U.S. Patent 6,114,313 has meaningful formulation specificity but limited molecule-wide coverage.

Strengths

Claim 3 identifies cangrelor directly.
The formulation requires excipients commonly suited to sterile injectable products.
Claims cover both product and manufacturing process.
Drying and reconstitution claims align with the commercial presentation of cangrelor.
Claim 10 adds a measurable residual-water limitation.
Claim 12 links the formulation to platelet aggregation treatment.

Vulnerabilities

The patent does not broadly claim cangrelor as a compound.
A competitor may design around mannitol, sodium chloride, or polyol requirements.
A liquid or alternative solid formulation may avoid the drying claims.
The Markush genus may face written-description or enablement scrutiny if asserted broadly.
The “about 6 to about 10” pH limitation may create boundary disputes.
Patent-term status is critical because the patent issued more than two decades ago.

The estate is therefore stronger against a copycat of the original Kengreal formulation than against every possible cangrelor product.

How does U.S. Patent 6,114,313 compare with compound and method patents?

Patent category	Scope	Strategic value
Compound patent	Cangrelor molecule or closely defined chemical class	Broadest product barrier
Formulation patent	Cangrelor with mannitol and sodium chloride or polyol	Protects commercial dosage form
Process patent	Mixing and lyophilization, spray drying, or vacuum drying	Can complicate generic manufacturing
Method-of-use patent	Treatment using the claimed formulation	Relevant to induced or contributory infringement
Device patent	Vial, reconstitution system, or delivery apparatus	May create separate product barriers

U.S. Patent 6,114,313 should be analyzed as one layer of the cangrelor estate, not as a complete substitute for compound, salt, dosage, polymorph, manufacturing, or clinical-use patents.

What generic launch scenarios exist for cangrelor?

Scenario 1: Paragraph III certification

A generic applicant acknowledges the patent and waits until the listed patent expires. This is the lowest-litigation route but delays launch.

Scenario 2: Paragraph IV certification

The applicant asserts that the patent is invalid, unenforceable, or not infringed. The patent owner may file suit within the statutory period, triggering the Hatch-Waxman stay under applicable conditions.

Scenario 3: Formulation design-around

The applicant develops a cangrelor product without the claimed combination of mannitol and sodium chloride or polyol. This approach may avoid literal infringement but must account for other listed patents and regulatory sameness requirements.

Scenario 4: Alternative dosage form

A liquid, non-dried, or differently stabilized product could avoid claims 7, 11, and 13. The product would still need to satisfy FDA requirements for pharmaceutical equivalence, stability, sterility, strength, and labeling.

Scenario 5: Litigation settlement

The parties could resolve a Paragraph IV dispute through a license, delayed-entry agreement, or other settlement. The commercial effect would depend on entry timing, authorized-generic rights, royalties, and restrictions on formulation changes.

What revenue exposure does the patent create?

Kengreal is a hospital-administered product used in interventional cardiology. Its revenue exposure is narrower than that of a chronic oral antiplatelet because sales depend on procedure volume, hospital formularies, inventory practices, and competitive use of oral P2Y12 agents.

The patent’s economic value is tied to the commercial injectable formulation. If a generic manufacturer can enter with a noninfringing cangrelor formulation, the patent may not prevent competition even if cangrelor demand remains clinically stable.

Key commercial variables include:

Kengreal net sales;
Share of PCI procedures using intravenous cangrelor;
Hospital contracting;
Generic sterile-injectable capacity;
FDA approval timing;
Patent listing and expiration;
Availability of alternative P2Y12 inhibitors; and
Whether the manufacturer controls later-expiring formulation or use patents.

Key Takeaways

U.S. Patent 6,114,313 is principally a formulation patent, not a broad cangrelor compound patent.
Claim 3 specifically identifies cangrelor.
The core combination is cangrelor or a related nucleotide analog, mannitol, and sodium chloride or a polyol.
Claims 7 through 10 cover dried, reconstituted, pH-controlled, and low-water formulations.
Claims 11 and 13 create separate process risks for lyophilization, spray drying, and vacuum drying.
Claim 12 is a method-of-treatment claim limited to the composition defined in claim 2.
Generic risk is concentrated in sterile injectable manufacturers pursuing formulation design-arounds or Paragraph IV challenges.
Biosimilar risk does not apply because cangrelor is a small-molecule drug.
The patent’s current blocking power depends on verified USPTO term data, FDA Orange Book status, and any later cangrelor patents.
The strongest infringement case would involve a Kengreal-like cangrelor formulation using mannitol and sodium chloride or a qualifying polyol.

Frequently Asked Questions

Does U.S. Patent 6,114,313 claim cangrelor itself?

No. Claim 3 identifies cangrelor, but it does so within a pharmaceutical-composition claim that inherits the mannitol and sodium chloride or polyol limitations of claim 1.

Can a generic cangrelor avoid the patent by removing mannitol?

Potentially. Removing mannitol may avoid claim 1 and its dependent claims, but the generic would need to evaluate other formulation, process, compound, and method patents.

Does the patent cover Kengreal after reconstitution?

Yes, claim 8 expressly covers the reconstituted form, provided the formulation satisfies the limitations inherited from the preceding claims.

Is cangrelor subject to biosimilar competition?

No. Cangrelor is a small-molecule nucleotide analog. Competition would proceed through the generic-drug framework, primarily an ANDA, rather than the biosimilar pathway.

What is the main litigation vulnerability of this patent?

The principal vulnerability is its limited formulation scope. A competitor may argue that a product using different excipients, a different physical form, or a different manufacturing route does not meet the required limitations.

References

Food and Drug Administration. (2015). Kengreal (cangrelor) prescribing information. U.S. Department of Health and Human Services.

Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

U.S. Patent No. 6,114,313. (2000). Pharmaceutical compositions. United States Patent and Trademark Office.

U.S. Patent and Trademark Office. (n.d.). Patent Center and patent-term information. U.S. Department of Commerce.

35 U.S.C. §§ 154, 156, 271, 282.

21 U.S.C. § 355(j).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	9604795	Dec 20, 1996

PCT Information
PCT Filed	December 11, 1997	PCT Application Number:	PCT/SE97/02068
PCT Publication Date:	July 02, 1998	PCT Publication Number:	WO98/28009

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1007094	⤷ Start Trial	15C0060	France	⤷ Start Trial
Argentina	010377	⤷ Start Trial
Austria	221787	⤷ Start Trial
Australia	5351598	⤷ Start Trial
Australia	758857	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,114,313

Summary for Patent: 6,114,313