US Patent 8,106,029: Regadenoson Claims, Scope, Expiration and Patent Landscape

US Patent 8,106,029 protects a specific clinical use of regadenoson, the active ingredient in Lexiscan. Its core requirement is administration of a single intravenous bolus containing regadenoson in a near-neutral formulation, at a dose capable of increasing average coronary peak flow velocity by approximately 16.5 to 105 cm/sec. Claim 12 extends the method to myocardial perfusion imaging with a radionuclide.

The patent does not broadly claim the regadenoson molecule, every regadenoson formulation, or every use of regadenoson. Its enforceable scope depends on the combined presence of the drug, formulation conditions, IV bolus administration, coronary-flow effect, and, for claim 12, radionuclide imaging.

What patent is US 8,106,029?

Item	Information
Patent	US 8,106,029 B2
Subject	Methods of producing coronary vasodilation and performing myocardial perfusion imaging
Active ingredient	Regadenoson
Inventive focus	Single IV bolus administration of a pH-controlled regadenoson composition producing a defined coronary flow response
Priority date	May 16, 2005
Nonprovisional filing	May 16, 2006
Patent grant	February 7, 2012
Patent owner history	CV Therapeutics, later associated with Gilead Sciences and Astellas commercial rights
Nominal patent term	May 16, 2026, before any applicable patent-term adjustment or disclaimer
Product relevance	Lexiscan, regadenoson injection
FDA approval of Lexiscan	2008

The patent is a method-of-treatment patent. It is not principally a composition-of-matter patent. The chemical identity of regadenoson is recited to define the active ingredient, but the claims require a specific therapeutic administration and physiological result. [1][2]

What does claim 1 of US 8,106,029 protect?

Claim 1 requires all of the following:

A human patient in need of coronary vasodilation.
A single intravenous bolus dose.
A pharmaceutical composition containing regadenoson.
At least one pharmaceutical excipient.
A composition pH from approximately 6 to 8.
A dose sufficient to increase average coronary peak flow velocity by approximately 16.5 to 105 cm/sec.

The claim is narrower than a claim to “administering regadenoson intravenously.” A potentially infringing product or treatment must satisfy the formulation, administration, and functional limitations together.

Claim 1 limitation analysis

Claim element	Scope and commercial significance
“Human in need thereof”	Limits the claim to treatment of a human patient, rather than in vitro testing or animal use.
“Single intravenous bolus dose”	Excludes ordinary infusion regimens and repeated-dose protocols unless the facts establish a single bolus within the claim’s meaning.
Regadenoson	Covers the specified A2A adenosine receptor agonist, including its identified chemical form.
Pharmaceutical excipient	Broadly captures inactive formulation ingredients.
pH about 6 to about 8	A significant formulation limitation. Products outside this range may avoid literal infringement, subject to equivalence analysis.
Increase in average coronary peak flow velocity	A functional and quantitative limitation requiring the claimed physiological effect.
About 16.5 to about 105 cm/sec	Defines the claimed response range. The term “about” introduces a numerical boundary issue requiring claim construction and clinical evidence.

The claim is therefore a combination claim. A generic manufacturer would not avoid the claim merely by changing a buffer if the resulting composition remains within pH 6 to 8 and produces the claimed coronary flow response. Conversely, a formulation outside the pH range may create a meaningful noninfringement position, although the patentee could assert the doctrine of equivalents.

How do claims 2 through 11 narrow the patent?

Claims 2 through 11 add formulation, concentration, dose, timing, and pharmacodynamic limitations. They create fallback positions if claim 1 is challenged.

Claim	Additional limitation
2	Water, saline, buffer, dextrose in water, or combinations
3	Dibasic sodium phosphate, dibasic sodium phosphate dihydrate, monobasic sodium phosphate monohydrate, or combinations
4	Dibasic sodium phosphate plus monobasic sodium phosphate monohydrate
5	EDTA
6	Propylene glycol at about 5% to 25% w:v
7	Propylene glycol at about 8% to 20% w:v
8	Regadenoson amount of about 10 to 500 micrograms
9	Regadenoson dose of about 0.05 to 60 micrograms/kg
10	Administration over approximately 10 to 20 seconds
11	Coronary peak flow velocity increase of approximately 16.5 to 77.0 cm/sec

What formulation does the patent most closely cover?

Claims 4 through 7 track a formulation containing:

Regadenoson;
a phosphate buffer system;
EDTA; and
propylene glycol, particularly at 8% to 20% w:v.

The FDA-approved Lexiscan formulation contains regadenoson in an aqueous vehicle with excipients that include phosphate salts, propylene glycol, and edetate disodium. The labeled product is administered as a 0.4 mg/5 mL IV bolus over approximately 10 seconds, followed by a saline flush. [2]

The overlap between the patent claims and the approved product is strongest for claims 4 through 10. A product with the same or materially equivalent excipient system, pH, dose, and administration time would present a concentrated infringement risk.

What does claim 12 protect?

Claim 12 covers a method of performing myocardial perfusion imaging that combines:

A single IV bolus of the claimed regadenoson composition;
Administration of at least one radionuclide; and
Imaging of the myocardium at least concomitantly with the administration steps.

This claim is directed to the diagnostic workflow rather than coronary vasodilation alone. It requires both the regadenoson administration and radionuclide imaging components.

Claims 13 and 14 cover alternative timing arrangements:

Claim 13: regadenoson and radionuclide administered simultaneously.
Claim 14: regadenoson and radionuclide administered separately.

Claim 15 requires myocardial imaging to begin no sooner than approximately one minute after regadenoson administration. This limitation is narrower than the broader timing language in claim 12.

Why claim 12 matters for generic entry

A generic product may be used primarily as a pharmacologic stress agent in myocardial perfusion imaging. If the ANDA labeling directs or encourages the patented dosing and imaging sequence, the applicant may face induced-infringement allegations even if the product label does not reproduce the patent claims word for word.

The key risk is not only the composition. It is the labeled method of use. An ANDA applicant would generally need to address the listed method-of-use patent through a Paragraph IV certification, a section viii statement, or another regulatory strategy depending on the patent listing and the proposed labeling. [3][4]

What is the relationship between US 8,106,029 and Lexiscan?

Lexiscan is an FDA-approved regadenoson injection used as a pharmacologic stress agent in radionuclide myocardial perfusion imaging. Regadenoson selectively activates the adenosine A2A receptor and produces coronary vasodilation, allowing perfusion imaging without exercise stress in appropriate patients. [2]

The approved use aligns closely with the central limitations of US 8,106,029:

Lexiscan characteristic	Relationship to claim scope
Regadenoson active ingredient	Required by claims 1 and 12
IV bolus administration	Required by claims 1 and 12
Single 0.4 mg dose	Within claim 8’s 10 to 500 microgram range
Approximately 10-second administration	Within claim 10
Near-neutral formulation pH	Within claim 1
Phosphate-buffered formulation	Covered by claims 3 and 4
Propylene glycol and EDTA	Covered by claims 5 through 7
Myocardial perfusion imaging	Covered by claim 12
Radionuclide administration	Required by claim 12

The patent is therefore highly product-relevant even though it does not claim the active molecule in isolation.

When does US 8,106,029 lose exclusivity?

The nominal expiration date is May 16, 2026, based on the earliest nonprovisional filing date of May 16, 2006 and the 20-year patent term under 35 U.S.C. §154. The actual enforceable date must account for any patent-term adjustment, terminal disclaimer, maintenance-fee status, and any applicable patent-term extension. [1][5]

Milestone	Date
Earliest priority	May 16, 2005
Nonprovisional filing	May 16, 2006
Grant	February 7, 2012
Nominal expiration	May 16, 2026
Relevant regulatory exclusivity	Separate from patent term and dependent on FDA exclusivity records

Patent expiration does not itself establish immediate generic availability. FDA approval timing, other listed patents, litigation settlements, regulatory exclusivity, and manufacturing readiness can alter the practical launch date.

What is the Orange Book status of US 8,106,029?

The Orange Book is the relevant FDA source for patents submitted by the new drug application holder and listed against an approved product. A method-of-use patent can be listed when it claims an approved use reflected in the product labeling. [3]

For Lexiscan, the commercial and regulatory analysis should separate four categories:

Patents listed against the reference product.
Patents that have expired.
Patents remaining in force through May 2026.
Unlisted patents that may still support a separate infringement action but do not automatically create an Orange Book certification obligation.

US 8,106,029 is strategically important because its claims correspond to the labeled use of Lexiscan. Its relevance to an ANDA challenge depends on the FDA’s current listing record, the specific approved indication, and whether later-issued continuation patents remain listed.

Which companies are challenging Lexiscan exclusivity?

The principal competitive threat is from ANDA applicants seeking to market regadenoson injection. A Paragraph IV challenge would assert that the listed patent is invalid, unenforceable, or not infringed. A section viii statement would seek approval for uses that omit the patented method, if the FDA listing and labeling structure permit that approach.

The most material legal issues would be:

Whether the proposed product’s pH is within the claimed range;
Whether the product contains the claimed phosphate, EDTA, and propylene glycol excipients;
Whether the proposed dose and administration time fall within claims 8 through 10;
Whether the label directs myocardial perfusion imaging with a radionuclide;
Whether the coronary-flow increase limitation is inherently met by the proposed product;
Whether the claim is invalid for anticipation or obviousness in view of earlier regadenoson clinical and formulation disclosures.

A generic applicant could challenge the patent through a Paragraph IV certification, an inter partes review, district-court litigation, or a combination of proceedings. The practical value of an invalidity challenge increases as the patent approaches its May 2026 nominal expiration.

How strong is the patent estate for regadenoson?

US 8,106,029 has moderate-to-strong product linkage but narrower legal breadth than a composition-of-matter patent.

Strengths

The claims map closely to the labeled Lexiscan administration.
Claims 2 through 10 provide multiple formulation and dosing fallbacks.
The formulation limitations correspond to the commercial product.
Claim 12 captures the principal diagnostic use of regadenoson.
The patent contains both treatment and imaging claim categories.

Weaknesses

The patent does not broadly claim regadenoson as a molecule.
The claims require a specific IV bolus protocol.
The pH and excipient limitations create design-around opportunities.
The coronary-flow velocity limitation may create proof and claim-construction disputes.
A generic label could potentially omit or carve out a patented use, depending on FDA treatment of the listed method.
The remaining term is limited compared with a newly issued composition patent.

The strongest infringement case would involve a product that duplicates Lexiscan’s formulation, 0.4 mg bolus, approximately 10-second administration, pH range, and myocardial perfusion imaging instructions.

What generic launch scenarios exist?

Scenario 1: Full-label generic launch after patent expiry

A generic applicant launches an equivalent regadenoson injection after the patent expires and after addressing all other listed patents and regulatory barriers. This is the lowest litigation-risk pathway but may delay commercial entry until the full patent estate is cleared.

Scenario 2: Paragraph IV launch before expiration

The applicant certifies that US 8,106,029 is invalid, unenforceable, or not infringed. The patent holder may sue within the statutory period, potentially triggering a 30-month FDA approval stay under the Hatch-Waxman framework. [4]

Scenario 3: Carved-out labeling

The applicant removes or narrows a patented method of use. This strategy is more difficult if the proposed product is intended primarily for the same myocardial perfusion imaging indication and the remaining label still encourages the patented administration sequence.

Scenario 4: Formulation design-around

The applicant changes pH, excipient composition, propylene glycol concentration, administration duration, or another claim element. This may reduce literal infringement exposure but must preserve stability, sterility, tolerability, and pharmacodynamic performance.

What patent litigation affects regadenoson?

Litigation risk is concentrated in ANDA litigation against the Lexiscan patent estate. The relevant causes of action would include:

35 U.S.C. §271(e)(2) infringement based on the ANDA filing;
Declaratory judgments of noninfringement or invalidity;
Induced infringement based on proposed labeling;
Preliminary or permanent injunctive relief;
Settlement agreements providing delayed entry, licenses, or other commercial terms.

The patent’s method claims make the proposed generic label central to the case. Discovery would likely focus on the formulation batch records, pH specifications, excipient ranges, dose instructions, clinical pharmacology, and the applicant’s labeling strategy.

No broad conclusion that a specific company has settled, launched, or prevailed should be drawn solely from the patent text. Those conclusions require the corresponding district-court docket, FDA approval record, and Orange Book listing.

How does US 8,106,029 compare with a molecule patent?

Attribute	US 8,106,029	Regadenoson composition-of-matter patent
Protected subject	Clinical administration and imaging methods	Chemical compound or broad compound class
Infringement proof	Requires treatment facts, formulation, dose, and effect	Usually focuses on product identity
Design-around potential	Relatively meaningful	Usually limited
Relevance to Lexiscan label	Very high	High
Generic litigation focus	Label, formulation, dose, and use	Chemical identity
Term value near expiry	Narrowing as alternatives emerge	Usually stronger until expiry

US 8,106,029 is most valuable as a product-specific method patent. Its commercial force comes from the close alignment between the claims and Lexiscan’s labeled administration, not from broad control over all regadenoson chemistry.

Does biosimilar risk apply to regadenoson?

No. Regadenoson is a chemically synthesized small molecule, not a biologic. The relevant competitive pathway is an ANDA for a generic drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Public Health Service Act. [4]

The principal risks are generic substitution, Paragraph IV litigation, formulation design-around, and post-expiration price erosion. Biosimilar interchangeability and biologic reference-product exclusivity are not applicable.

What manufacturing and IP barriers remain?

The manufacturing barriers are lower than for a biologic but still commercially relevant. A competing manufacturer must establish:

Chemical synthesis and impurity control for regadenoson;
Sterile injectable manufacturing;
Consistent pH control;
Stability of the phosphate-buffered formulation;
Compatibility with propylene glycol and EDTA;
Container-closure integrity;
Sterility assurance and particulate control;
Bioequivalence or applicable clinical pharmacology support.

The patent barriers are concentrated in the formulation and administration combination. A manufacturer can reduce patent exposure by altering one or more claim elements, but the resulting product must remain pharmaceutically acceptable and clinically equivalent.

Key Takeaways

US 8,106,029 is a regadenoson method-of-treatment and myocardial-imaging patent.
Claim 1 requires a single IV bolus, pH 6 to 8, an excipient, and a defined coronary peak flow response.
Claims 4 through 7 closely track the Lexiscan formulation containing phosphate buffer, EDTA, and propylene glycol.
Claims 8 through 10 cover the commercial dose range and approximately 10-second administration.
Claim 12 protects use of the formulation with radionuclide myocardial perfusion imaging.
The nominal expiration date is May 16, 2026, before any applicable term adjustment or disclaimer.
The patent does not broadly claim regadenoson as a molecule.
Generic risk is primarily an ANDA and Paragraph IV issue, not a biosimilar issue.
The strongest infringement case involves a generic product and label that reproduce Lexiscan’s formulation, dose, timing, and imaging use.
The principal design-around options are pH, excipient composition, concentration, administration timing, and labeling.

FAQs

Can a generic regadenoson product avoid US 8,106,029 by changing the pH?

Potentially. A pH outside the approximately 6 to 8 range could avoid literal infringement of claim 1, but the patentee may argue that the change is insubstantial under the doctrine of equivalents. The product must also meet injectable-drug quality and stability requirements.

Does US 8,106,029 cover regadenoson administered by infusion?

The independent claims require a single IV bolus dose. An infusion regimen does not literally satisfy that limitation, although the infringement analysis would depend on the actual administration protocol and any asserted equivalents.

Is the 0.4 mg Lexiscan dose within the patent claims?

Yes. A 0.4 mg dose equals 400 micrograms, which falls within claim 8’s approximately 10 to 500 microgram range. It also falls within the claimed weight-based range for many adult patients.

Can a generic applicant use the same regadenoson formulation for a non-imaging indication?

A non-imaging label may reduce claim 12 risk, but it does not eliminate claim 1 risk if the product is administered as the claimed IV bolus and produces the claimed coronary vasodilation response.

Is US 8,106,029 a patent on Lexiscan’s active ingredient?

No. It is principally a patent on specified methods of administering regadenoson and using the administration protocol in myocardial perfusion imaging. A separate composition-of-matter patent would be needed to claim the active ingredient broadly.

References

United States Patent and Trademark Office. (2012). US Patent No. 8,106,029 B2: Methods of producing coronary vasodilation.
U.S. Food and Drug Administration. (2023). Lexiscan (regadenoson) injection prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and patent certifications.
United States Code. (2024). 35 U.S.C. §154: Contents and term of patent; provisional rights.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005295437	⤷ Start Trial
Canada	2583185	⤷ Start Trial
China	101076343	⤷ Start Trial
European Patent Office	1802317	⤷ Start Trial
Japan	2008517063	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,106,029

Summary for Patent: 8,106,029