United States Patent RE40640: Claim Scope, Expiration, Orange Book Status, and Microfoam Patent Landscape

U.S. Patent RE40640 is an expired reissue patent covering injectable sclerosing microfoam, particularly foam made with polidocanol, sodium tetradecyl sulfate, or other sclerosants and an oxygen-containing gas. Its central commercial concept overlaps with the technology later used for polidocanol foam products, including Varithena. The patent’s U.S. enforceable term ended in December 2014, subject to confirmation from the USPTO maintenance and term records. It therefore does not currently block generic, compounded, or branded microfoam products.

The strongest historical claims were claims 21 through 40 because they define the gas component as oxygen or a mixture of oxygen and carbon dioxide and identify specific sclerosants. Claims 1 through 20 are materially broader but face greater validity and construction risks because they use open-ended language such as “any sclerosing substance” and “injectable microfoam for therapeutic uses.” [1]

What does U.S. Patent RE40640 protect?

RE40640 protects injectable therapeutic microfoam containing a sclerosing substance. The claims cover both:

The microfoam composition itself; and
Methods of injecting the microfoam into vessels for phlebologic, angiologic, proctologic, or esophageal-varix treatment.

The patent is not limited to treatment of varicose veins. Its asserted scope extends to several vascular and proctologic indications, although the technical and commercial center of gravity is sclerotherapy for venous disease.

Core claim architecture

Claim group	Subject matter	Main limitation
Claims 1-8	Injectable microfoam compositions	Sclerosing substance, including polidocanol and sodium tetradecyl sulfate
Claims 9-20	Treatment methods	Injection into vessels for phlebologic, angiologic, proctologic, or variceal treatment
Claims 21-25	Injectable microfoam compositions	Listed sclerosant plus oxygen or oxygen/carbon dioxide gas
Claims 26-30	Phlebologic treatment methods	Injection of the claim 21 composition
Claims 31-35	Angiologic treatment methods	Injection of the claim 21 composition
Claims 36-40	Esophageal-varix treatment methods	Injection of the claim 21 composition

Claims 21 through 40 appear to be the operative reissue claim set most relevant to modern polidocanol foam products. They require a gas component consisting essentially of oxygen or a mixture of oxygen and carbon dioxide. The claims also permit, but do not universally require, a substance with foaming capacity.

What substances are covered by RE40640?

The claims identify eight principal categories of sclerosants:

Polidocanol, also known as lauromacrogol 400
Sodium tetradecyl sulfate
Hypertonic glucosated solutions
Hypertonic glucosaline solutions
Chromated glycerol
Ethanolamine oleate
Sodium morrhuate
Iodated solutions

Claims 2 and 22 specifically narrow the composition to polidocanol. Claims 3 and 24 specifically narrow it to sodium tetradecyl sulfate.

The dependent claims do not require every listed sclerosant to be present. The phrase “at least one sclerosing substance chosen from” permits a composition containing one or more members of the listed group. A product containing polidocanol and sodium tetradecyl sulfate could fall within the literal language of the composition claims if the other limitations were satisfied.

Foaming agents

Claims 23, 25, 28, 30, 33, 35, and 38-40 address a separate optional feature: a substance with foaming capacity. The listed examples are:

Polysorbate 20
Polysorbate 80
Polygeline

Because claim 23 says the microfoam “further comprises” a foaming substance, claim 21 does not necessarily require one of these additives. The patent therefore has two conceptual embodiments:

Foam generated from the sclerosant and gas system; and
Foam that also contains an identified surfactant or foaming agent.

How broad are claims 1 through 20?

Claims 1 through 20 are broad in therapeutic and compositional language.

Claim 1 recites:

“Prepared or extemporaneously prepared injectable microfoam for therapeutic uses ... prepared with any sclerosing substance.”

This language potentially reaches:

Factory-prepared foam;
Foam generated immediately before administration;
Foam made with a sclerosant not expressly listed in the dependent claims;
Therapeutic injection into a wide range of vessels.

Claims 9 through 20 then apply the microfoam to particular treatment categories. Claims 9-11 cover phlebologic treatment, claims 12-14 cover esophageal varices, claims 15-17 cover proctologic treatment, and claims 18-20 cover angiologic treatment.

The principal weakness of this claim group is breadth. “Any sclerosing substance” may create written-description, enablement, or indefiniteness issues if the specification does not support the full genus. “Microfoam” and “therapeutic uses” also require interpretation based on the specification, prosecution history, and technical understanding at the relevant filing date.

Claims 21 through 40 reduce some of those risks by adding a defined gas system and an enumerated sclerosant group.

What is the importance of the oxygen and carbon dioxide limitation?

The gas limitation is the key technical restriction in claims 21 through 40.

The composition must contain a gas component that:

Consists essentially of oxygen; or
Consists essentially of oxygen and carbon dioxide.

“Consists essentially of” generally permits incidental components that do not materially alter the basic and novel characteristics of the claimed composition. It is narrower than “comprising,” but broader than “consisting of.”

A product using nitrogen, air, or another gas as the principal gas component could avoid the literal gas limitation, depending on the composition and claim construction. A product using oxygen alone or oxygen combined with carbon dioxide would fall within the central gas definition if the remaining limitations were met.

This limitation is commercially significant because FDA-approved polidocanol foam products have used oxygen and carbon dioxide gas systems. The FDA label for Varithena describes a polidocanol injectable foam product generated from polidocanol and an oxygen/carbon dioxide gas mixture. [2]

What formulation patents protect modern polidocanol foam products?

RE40640 is a foundational microfoam patent, but it is not the only relevant patent family. Later patents generally focus on:

Canister-based foam generation;
Gas composition and gas-to-liquid ratios;
Foam stability;
Bubble-size distribution;
Polidocanol concentration;
Delivery devices;
Storage and administration;
Treatment of incompetent veins;
Manufacturing and quality-control methods.

For Varithena, later BTG and Provensis patent families became more commercially relevant than RE40640 after its expiration. These patents were associated with the product’s formulation, delivery system, and clinical use rather than only the broad concept of injecting sclerosant foam.

Foundational versus later patent protection

Technology layer	RE40640 relevance	Later patent relevance
Sclerosant in injectable foam	Directly covered	Often narrowed to polidocanol formulations
Oxygen or oxygen/carbon dioxide gas	Directly covered in claims 21-40	Further optimized in product-specific patents
Extemporaneous preparation	Expressly covered	May be distinguished by device and process claims
Canister delivery	Not fully defined by the supplied claims	Common subject of later product patents
Foam stability and bubble size	Broadly implicated	More likely claimed in later formulation patents
Indication-specific treatment	Covered broadly	Later patents may target venous anatomy and dosing
Manufacturing process	Limited in supplied claims	Separate process and device families may apply

A freedom-to-operate review for a current product must therefore separate the expired foundational patent from unexpired product-specific patents.

When did RE40640 lose exclusivity?

RE40640’s patent term was tied to the term of the underlying original patent and did not restart when the patent was reissued. The relevant priority and filing history places the effective U.S. term in December 2014. A reissue patent does not receive a new 20-year term merely because the reissue certificate issued later. [3]

Event	Timing
Earliest U.S. priority or filing history	December 1994
Original U.S. patent issued	1997
Reissue patent RE40640 issued	2009
Expected patent-term endpoint	December 2014
Current enforceability	Expired

The precise expiration date should be read from the USPTO term calculation and patent record rather than inferred solely from the reissue issue date. Patent-term adjustment, terminal disclaimers, or other record-specific events can affect the final date. The commercial conclusion remains unchanged: RE40640 is no longer an enforceable U.S. exclusion right.

What is the Orange Book status of RE40640?

RE40640 should not be treated as a current Orange Book barrier to an FDA approval or generic launch.

Varithena was approved by FDA under NDA 205098 in 2013 for the treatment of incompetent veins in the superficial venous system. [2] Orange Book protection for the product has historically depended on later, product-specific patents rather than the expired RE40640 patent. FDA’s Orange Book identifies approved drug products, patents submitted by NDA holders, and regulatory exclusivity information. [4]

RE40640’s practical Orange Book significance is historical:

It helped establish the early patent position for injectable sclerosant microfoam.
It is not a current patent term blocking an ANDA.
It does not create a present-day 30-month stay under Hatch-Waxman.
It should not be confused with later patents listed for polidocanol foam products.

What Paragraph IV challenges and generic entry risks exist?

A Paragraph IV certification against RE40640 would have little present commercial value because the patent has expired. A generic applicant would instead focus on unexpired patents listed for the relevant reference product.

For a polidocanol foam product, the main regulatory and patent risks may include:

Later formulation patents covering the approved foam composition;
Device patents covering a canister or foam-generation system;
Method-of-use patents covering treatment of incompetent veins;
Labeling restrictions and induced-infringement theories;
FDA requirements for demonstrating bioequivalence or equivalent clinical performance;
Manufacturing controls for foam stability, bubble size, and gas composition.

A generic product could pursue an ANDA if it can match the reference product’s dosage form and route while addressing listed patents. A 505(b)(2) application could be relevant where the proposed product differs in formulation, delivery device, concentration, or clinical use.

Generic launch scenarios

Scenario	RE40640 impact	Principal remaining risk
Polidocanol liquid injection	No current blocking effect	Separate formulation and labeling patents
Polidocanol foam using oxygen/carbon dioxide	Historical relevance only	Later Varithena patents and device claims
Foam using nitrogen or air	Likely outside claims 21-40 gas limitation	Other formulation, safety, and regulatory issues
Compounded extemporaneous foam	RE40640 term expired	State pharmacy law, FDA compounding rules, product quality
Sodium tetradecyl sulfate foam	RE40640 term expired	Alternative patent families and clinical evidence

Which companies developed or commercialized the technology?

The early microfoam technology is associated with inventor Juan Cabrera Garrido and related patent ownership connected to the Cabrera/Provensis development program. Provensis developed Varithena, and BTG later acquired the relevant business and commercialized the product. Boston Scientific acquired BTG in 2019 for approximately $4.2 billion. [5]

Company	Role
Juan Cabrera Garrido and related inventors	Early microfoam inventorship
Provensis Ltd.	Development and commercialization of polidocanol foam technology
BTG International Ltd.	Later owner and commercial sponsor of Varithena
Boston Scientific Corp.	Acquired BTG and its portfolio, including Varithena-related assets
Generic manufacturers	Potential ANDA or 505(b)(2) entrants, subject to later patents

Varithena revenue has not generally been reported as a separately disclosed product line in Boston Scientific’s public financial reporting. Revenue exposure should therefore be assessed through the company’s venous-interventions business rather than a standalone product figure.

What patent litigation affects the microfoam market?

The principal litigation risk for modern polidocanol foam products has shifted from RE40640 to later patents.

BTG pursued patent litigation involving Varithena-related patents against generic pharmaceutical companies, including Amneal. The Federal Circuit addressed issues arising from BTG’s patent enforcement against an ANDA challenger in BTG International Ltd. v. Amneal Pharmaceuticals LLC. [6] Those disputes involved later Varithena-related patent rights and should not be treated as active litigation over the expired RE40640 patent.

The practical litigation categories are:

Patent infringement actions after Paragraph IV certifications;
Declaratory-judgment actions concerning listed formulation patents;
Claim-construction disputes over gas composition and foam characteristics;
Validity challenges based on prior art foam-generation techniques;
Induced-infringement claims based on approved labeling;
Settlement agreements that delay or define generic entry.

No current enforcement action can revive RE40640. Any present litigation value lies in the patent families that followed it.

How strong is the RE40640 patent estate?

RE40640 was commercially important but is now legally weak because the patent has expired.

Factor	Assessment
Original technical concept	Strong historical significance
Breadth of independent claims	Broad
Specificity of claims 21-40	Moderate to strong historically
Dependence on gas composition	Material limitation
Dependence on listed sclerosants	Narrows scope and improves clarity
Current enforceability	None after expiration
Current Orange Book leverage	None as an enforceable patent
Design-around potential during term	Available through gas, formulation, and process changes
Biosimilar relevance	None

During its term, the patent could have reached products using polidocanol or sodium tetradecyl sulfate in oxygen-containing foam. After expiration, it functions primarily as prior art against later patents and as a historical reference for claim construction and obviousness analysis.

Does biosimilar risk apply to polidocanol foam?

No. Polidocanol is a chemically synthesized small molecule, not a biologic. The relevant regulatory pathway is generally an ANDA under section 505(j) or, in some cases, a 505(b)(2) application. The section 351(k) biosimilar pathway does not apply.

The competitive landscape is therefore determined by:

Generic-drug approval;
Formulation and device patents;
Reference-product exclusivity;
Clinical and pharmaceutical-equivalence requirements;
Manufacturing capability.

What geographic coverage does RE40640 provide?

RE40640 provides rights only in the United States. Corresponding foreign applications and patents may have existed in Europe and other jurisdictions, but their status must be evaluated separately by country.

Patent expiration is jurisdiction-specific. A U.S. expiration does not establish that corresponding rights in the European Union, United Kingdom, Canada, Japan, or other markets have also expired. The relevant analysis requires review of each national or regional patent register, including any supplementary protection certificate or national term adjustment.

Key Takeaways

RE40640 covers injectable therapeutic microfoam containing a sclerosing substance.
The listed sclerosants include polidocanol and sodium tetradecyl sulfate.
Claims 21-40 require oxygen or an oxygen/carbon dioxide gas component.
The patent covers composition claims and methods for phlebologic, angiologic, proctologic, and esophageal-varix treatment.
The reissue did not create a new patent term.
The U.S. patent term ended in December 2014.
RE40640 is not a current Orange Book barrier to generic entry.
Current commercial risk resides in later patents covering Varithena’s formulation, device, manufacturing process, and methods of use.
Polidocanol foam is subject to generic-drug, not biosimilar, competition.
Boston Scientific inherited BTG’s Varithena-related intellectual-property portfolio through its 2019 acquisition of BTG.
The typographical errors in claims 27, 29, 31, 36, and related claims should be checked against the issued reissue certificate and USPTO image file. The certified patent text controls.

FAQs

Can a company commercialize polidocanol foam without infringing RE40640?

Yes, RE40640 is expired. A current product must still be screened against later unexpired formulation, device, manufacturing, and method-of-use patents.

Does RE40640 cover foam made with nitrogen?

Claims 21-40 require oxygen or oxygen combined with carbon dioxide. Nitrogen-based foam may avoid those gas limitations, although claims 1-20 and other patent families require separate analysis.

Is sodium tetradecyl sulfate foam covered by the patent?

Historically, yes. Claims 3, 11, 14, 17, 20, 24, and 29-34 expressly address sodium tetradecyl sulfate. Those claims are no longer enforceable because the patent has expired.

Is an extemporaneously prepared foam within the claimed scope?

Yes. The claims expressly cover foam that is “prepared or extemporaneously prepared.” That limitation had potential significance during the patent term but does not create a current exclusion right.

Does FDA approval of Varithena prove infringement of RE40640?

No. FDA approval establishes regulatory status, not patent infringement. Varithena’s approval is relevant to product composition and gas technology, while infringement depends on claim limitations and the applicable patent term.

References

United States Patent and Trademark Office. (2009). U.S. Patent No. RE40,640, Microfoam for use in the treatment of varicose veins.
U.S. Food and Drug Administration. (2013). Varithena (polidocanol injectable foam) prescribing information, NDA 205098.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration guidance.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
Boston Scientific Corporation. (2019). Boston Scientific completes acquisition of BTG plc.
BTG International Ltd. v. Amneal Pharmaceuticals LLC, 923 F.3d 1063 (Fed. Cir. 2019).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Spain	9301413	Jun 23, 1993

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	179598	⤷ Start Trial
Australia	7001294	⤷ Start Trial
Germany	69418286	⤷ Start Trial
Denmark	0656203	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE40640

Summary for Patent: RE40640