US Patent 8,133,879: CVT-3146 Formulation Claims, Patent Scope, and Regadenoson IP Landscape

US Patent 8,133,879 protects specific liquid formulations of CVT-3146, the active pharmaceutical ingredient later commercialized as regadenoson. The patent does not broadly claim regadenoson as a molecule. Its core protection requires a combination of regadenoson, a sodium phosphate buffer, EDTA, propylene glycol, and a controlled pH. The broadest independent claims also require defined propylene glycol ranges and, for claim 13, suitability for intravenous single-bolus administration.[1]

The commercially relevant formulation is closely aligned with the claimed combination of 400 micrograms of regadenoson in an aqueous, buffered solution containing propylene glycol and EDTA. The principal enforcement value therefore lies in formulation substitution risk, not in blocking manufacture of regadenoson API itself.

What does US Patent 8,133,879 protect?

The patent protects pharmaceutical compositions containing CVT-3146 with five material requirements:

Required element	Claim requirement
Active ingredient	CVT-3146, chemically identified as a substituted adenosine analog
Liquid carrier	Water, distilled water, de-ionized water, saline, buffer, or combinations
Buffer	At least one sodium phosphate buffer
Chelating agent	EDTA
Cosolvent	Propylene glycol at about 5% to about 25% w:v
pH	About 6 to about 8
Route, in claim 13	Intravenous administration as a single bolus injection

The claims are formulation claims. They do not claim:

The CVT-3146 chemical entity in isolation;
Every dosage form containing regadenoson;
Oral, inhaled, transdermal, or depot formulations without the claimed excipients;
Any formulation that uses a non-phosphate buffer;
Any formulation that omits EDTA;
Any formulation with propylene glycol outside the claimed range, subject to possible equivalents analysis.

The claim set is internally layered. Claim 1 establishes the broad formulation architecture, while claims 2 through 9 add concentration, dose, pH, buffer, and excipient limitations. Claim 10 is a separate independent claim directed to a narrower fixed formulation. Claim 13 is another independent claim that adds intravenous bolus use.

How do the independent claims differ?

Claim 1: broadest composition claim

Claim 1 requires:

CVT-3146;
A permitted liquid carrier;
Sodium phosphate buffer;
EDTA;
Propylene glycol at about 5% to about 25% w:v; and
pH from about 6 to about 8.

Claim 1 does not require water specifically. Saline or another listed liquid carrier can satisfy the carrier limitation. It also does not require a particular CVT-3146 concentration or a specific dose.

A competing product containing 100 micrograms/mL of regadenoson, 15% propylene glycol, EDTA, sodium phosphate buffer, and pH 7 would fall squarely within claim 1 if the remaining formulation elements are present.

Claim 10: fixed commercial-style formulation

Claim 10 narrows the composition to:

Water;
Sodium phosphate buffer;
0.1% EDTA;
15% w:v propylene glycol; and
pH of about 7.

Claim 10 does not state a CVT-3146 concentration. Claim 12 supplies a dependent limitation of 100 micrograms/mL.

This claim is narrower than claim 1 but potentially more commercially significant because it corresponds closely to a defined product formulation. A product that uses the same excipient system but changes the CVT-3146 concentration may still infringe claim 10, because concentration is not required by the independent claim itself.

Claim 13: intravenous single-bolus formulation

Claim 13 covers a composition meeting the claim 1 formulation requirements that “may be administered intravenously as a single bolus injection.”

This creates two related issues. First, the product must have the claimed formulation characteristics. Second, it must be suitable for the stated intravenous administration. The claim is not limited to a particular dose or injection volume.

A product labeled solely for infusion rather than bolus administration presents a stronger noninfringement position under the express wording of claim 13, although claims 1 and 10 could remain relevant because they do not contain the bolus limitation.

What formulations are protected by US 8,133,879?

The dependent claims create several formulation-specific protection zones.

Claim	Added limitation	Commercial significance
1	Propylene glycol about 5%-25% w:v; pH about 6-8	Broad formulation combination
2	Propylene glycol about 8%-20% w:v	Intermediate range
3	Propylene glycol 15% w:v	Key fixed-cosolvent embodiment
4	CVT-3146 10-1000 micrograms	Dose-defined composition
5	Liquid carrier is water	Aqueous formulation
6	pH 7	Neutral-pH embodiment
7	Sodium phosphate buffer at 100 mM	Defined buffer strength
8	400 micrograms CVT-3146	Commercial-dose embodiment
9	15% propylene glycol, 100 mM phosphate, pH 7, 0.1% EDTA	Highly specific formulation
10	Water, phosphate buffer, 0.1% EDTA, 15% propylene glycol, pH about 7	Independent fixed formulation
11	100 mM phosphate buffer	Narrower claim 10 embodiment
12	100 micrograms/mL CVT-3146	Concentration-defined embodiment
13	Intravenous single-bolus administration	Route and administration-mode claim

Claim 9 is especially narrow but commercially important. It captures the formulation profile most closely associated with a ready-to-use regadenoson injection. Claim 10 is broader than claim 9 in one respect because it does not require 100 mM phosphate buffer, but it requires water and 0.1% EDTA.

How would literal infringement be assessed?

Literal infringement requires every limitation of at least one asserted claim to be present in the accused product.

For claim 1, the principal screening questions are:

Does the product contain CVT-3146?
Is sodium phosphate present as a buffer?
Is EDTA present?
Is propylene glycol present at approximately 5%-25% w:v?
Is the pH approximately 6-8?
Is the formulation liquid and does it contain a qualifying carrier?

A formulation with 15% propylene glycol and pH 7 would satisfy the numerical limitations directly. A formulation using citrate, acetate, histidine, or tromethamine instead of sodium phosphate would avoid the literal sodium-phosphate limitation, even if the substitute buffer performed the same function.

A formulation that uses polyethylene glycol, glycerol, ethanol, or another cosolvent instead of propylene glycol would likewise avoid literal infringement of the propylene glycol limitation. The risk would then turn on claim construction and possible doctrine-of-equivalents arguments.

The term “about” creates numerical boundaries that may require expert and prosecution-history evidence. A product at 4.5% or 25.5% propylene glycol cannot be classified solely from the claim text. The relevant analysis would consider specification disclosure, examples, prosecution arguments, and any amendments made during examination.

Does the patent claim the regadenoson molecule itself?

No. The claims supplied are directed to compositions. The chemical identity of CVT-3146 defines the active ingredient, but the patent does not claim CVT-3146 standing alone.

This distinction affects generic and follow-on competition:

A manufacturer may be able to make regadenoson API without infringing these composition claims.
A finished injectable product can still infringe if it uses the claimed excipient system.
An alternative finished product may avoid the patent by changing the buffer, cosolvent, chelator, pH, or route.
A process patent, compound patent, polymorph patent, or separate method-of-use patent would need independent analysis.

The patent therefore creates a formulation barrier rather than a complete API barrier.

What is the Orange Book relevance of US 8,133,879?

Patent 8,133,879 may be relevant to an approved regadenoson injection only if it has been submitted to FDA for listing against the relevant drug product and appears in the applicable Orange Book records. The claims alone do not establish Orange Book listing status.

For an ANDA applicant, the commercial implications depend on the listing and certification record:

Scenario	Regulatory consequence
Patent listed and unexpired	Paragraph IV certification may be required for a patent the applicant believes is invalid, unenforceable, or not infringed
Patent listed but expired	The patent generally does not block approval on an exclusivity basis
Patent not listed	It ordinarily does not create a standard Orange Book Paragraph IV approval block
Formulation patent listed	A generic may need to address the formulation claims even if the API claims are absent
Method-of-use patent only	A section viii statement may be relevant if the ANDA omits the patented use

A Paragraph IV certification can trigger patent litigation under Hatch-Waxman. The 30-month stay and approval timing depend on the date of notice, litigation filing, patent listing, and the specific statutory framework applicable to the ANDA.

When does US 8,133,879 lose exclusivity?

The patent’s enforceable expiration date cannot be established from the claim text alone. The controlling calculation requires the complete USPTO prosecution record, including:

Nonprovisional filing date;
Priority claims;
Patent term adjustment;
Terminal disclaimers;
Any patent-term extension;
Reexamination or post-grant changes;
Continuation or divisional relationships.

A nominal expiration calculation based only on the issue number or the apparent priority date is not sufficient. The expiration date should be taken from the USPTO patent-term data and checked against Orange Book records if the patent is listed for an approved product.[2,3]

FDA approval of the reference product does not by itself establish that this patent has remaining exclusivity. Regulatory exclusivity and patent term are separate. New chemical entity exclusivity, three-year clinical-investigation exclusivity, pediatric exclusivity, and patent rights can have different end dates.

What is the competitive landscape for regadenoson injection?

Regadenoson is an adenosine A2A receptor agonist used as a pharmacologic stress agent in myocardial perfusion imaging. The FDA-approved reference product, Lexiscan, is an intravenous injection. Its labeled formulation includes regadenoson with inactive ingredients including propylene glycol, EDTA, phosphate salts, and water.[4]

The competitive landscape has four relevant layers:

API competition

Regadenoson API manufacturing is distinct from finished-product formulation. The patent claims supplied do not prevent API production by themselves.

Finished injectable competition

The most direct risk involves generic or follow-on injections using the same or substantially similar excipient system. A generic applicant may challenge the formulation claims through Paragraph IV or design around them.

Formulation design-around competition

Potential design-around routes include:

Replacing sodium phosphate with another buffer;
Removing or replacing EDTA;
Using a different cosolvent;
Adjusting propylene glycol below or above the claimed range;
Changing pH outside the claimed range;
Using a different administration format.

Each change can affect solubility, stability, tonicity, tolerability, container compatibility, and regulatory comparability.

Regulatory and manufacturing barriers

Even where a design-around avoids literal infringement, the applicant must show that the revised formulation is acceptable for intravenous use. Changes to excipients can create CMC requirements involving stability, degradation products, extractables and leachables, sterility, particulate matter, and container closure integrity.

These technical requirements can make a formulation patent commercially relevant even when the active ingredient itself is available from multiple sources.

How strong is the patent estate based on these claims?

The claim estate is strongest against products that copy the full excipient architecture. Its principal strengths are:

A broad independent formulation claim;
Multiple fallback claims;
Coverage of both concentration ranges and fixed values;
Separate protection for water-based formulations;
A dedicated intravenous bolus claim;
Coverage of the commercially important 15% propylene glycol embodiment.

The main vulnerabilities are:

Dependence on a specific combination of known pharmaceutical excipients;
Potential obviousness arguments based on prior art formulation screening;
Numerical ambiguity around “about”;
Possible written-description or enablement disputes for the full 5%-25% range;
Ease of designing around one or more required excipients;
Lack of direct protection for the active ingredient.

The strongest assertion targets are likely products containing regadenoson, sodium phosphate, EDTA, and approximately 15% propylene glycol at near-neutral pH. Products using a different buffer or cosolvent present substantially lower literal-infringement risk.

What litigation and settlement issues should be monitored?

A complete litigation assessment requires docket-level review of federal court cases, PTAB proceedings, FDA patent listings, and ANDA certifications. The supplied claims do not identify any litigation, settlement agreement, license, or Paragraph IV notice.

Relevant monitoring categories are:

ANDA filings for regadenoson injection;
Paragraph IV notices directed to the formulation claims;
Hatch-Waxman complaints and 30-month-stay dates;
PTAB petitions challenging validity;
License or supply agreements involving the reference-product sponsor;
Orange Book delisting or patent-listing disputes;
Generic launches following a covenant not to sue or settlement.

No biosimilar pathway applies because regadenoson is a small-molecule drug, not a biologic. Competition proceeds primarily through the ANDA pathway rather than the abbreviated biologics license application pathway.

Key Takeaways

US Patent 8,133,879 is a formulation patent for CVT-3146, not a broad compound patent.
Claim 1 requires regadenoson, sodium phosphate buffer, EDTA, propylene glycol at about 5%-25% w:v, and pH about 6-8.
Claims 9 and 10 target a commercial-style aqueous formulation containing 15% propylene glycol and 0.1% EDTA near pH 7.
Claim 13 adds intravenous single-bolus suitability.
A generic can potentially design around the patent by changing the buffer, chelator, cosolvent, pH, or administration format.
The patent’s commercial strength depends on Orange Book listing, remaining term, prosecution history, and the formulation used by the competing product.
The claims do not independently block manufacture or sale of regadenoson API.
Biosimilar risk is not applicable; the relevant pathway is generic ANDA competition.
Exact expiration, listing, litigation, licensing, and settlement status require the USPTO, FDA Orange Book, court docket, and regulatory records rather than the claim text alone.

FAQs

Does changing the regadenoson dose avoid patent infringement?

Not necessarily. Claim 1 does not require a specific dose. Claims 4 and 8 add dose limitations but do not restrict the scope of claim 1. A product using a different dose can still infringe claim 1 if all formulation elements are present.

Does a citrate-buffered regadenoson injection fall within the claims?

A citrate-buffered product would not literally satisfy the sodium phosphate buffer limitation. The product could still face an equivalents argument, but the literal claim analysis would favor noninfringement.

Does the patent cover a prefilled syringe?

The claims do not specify a vial, syringe, cartridge, or other container. A prefilled syringe can fall within the claims if its formulation contains all required ingredients and properties.

Can a generic use propylene glycol at 3%?

A 3% formulation would be outside the express 5%-25% range in claim 1. The final analysis would depend on how the court construes “about” and whether an equivalents theory is asserted.

Is an IV infusion covered by claim 13?

Claim 13 expressly refers to administration as a single bolus injection. An infusion may not satisfy that limitation, but claims 1 and 10 do not contain the same route or administration-mode restriction.

References

U.S. Patent No. 8,133,879, claims 1-13. United States Patent and Trademark Office.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/patents/laws/patent-term-adjustment
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (2008). Lexiscan (regadenoson) injection prescribing information. AstraZeneca Pharmaceuticals LP.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2003259264	⤷ Start Trial
Canada	2492855	⤷ Start Trial
China	1671399	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,133,879

Summary for Patent: 8,133,879