US Patent 10,369,264: Claim Scope, Exclusivity, and Patent Landscape for Delcath-Style Percutaneous Hepatic Perfusion

US Patent 10,369,264 protects an integrated regional chemotherapy system combining three technical elements: a double-balloon vascular isolation catheter, an extracorporeal hemoperfusion circuit, and a hemocompatible polymer-coated carbon adsorbent with tightly defined physical properties. The claims are directed primarily to kits and systems for delivering melphalan or other small-molecule chemotherapy to the liver while reducing systemic exposure.

The patent is strongest against products that use all of the following in combination:

A double-balloon isolation or aspiration catheter.
Extracorporeal blood withdrawal and return.
A filter containing polymer-coated carbon cores.
Carbon cores with a pore volume of approximately 1.68 to 2.17 cc/g.

The patent does not broadly cover every hepatic chemotherapy procedure, every melphalan delivery system, or every activated-carbon hemoperfusion filter. Its enforceable scope depends on the interaction of the catheter, circuit, filter media, and specified adsorbent characteristics.

What does US Patent 10,369,264 cover?

The patent covers kits and systems capable of delivering a small-molecule chemotherapeutic agent to a patient while filtering the drug from blood before the blood returns to systemic circulation.

Independent claim 1 is a combination claim directed to a kit. Independent claim 15 is another kit claim focused on delivery to the liver. Independent claim 20 is a system claim covering the catheter circuit and filter apparatus.

Claim group	Claim numbers	Principal subject matter
General kit	1-14	Double-balloon catheter, filter, coated carbon media, and chemotherapy agent
Liver-treatment kit	15-19, 25-28	Isolation-aspiration catheter, liver delivery, extracorporeal circuit, infusion catheter
Integrated system	20-24	Percutaneous inferior vena cava catheter, balloons, fenestrations, flow machine, filter, and return catheter

The claims are drafted as combination claims. A product that has only the coated-carbon filter, or only the double-balloon catheter, would not necessarily fall within the literal scope of the independent claims.

What are the essential elements of independent claim 1?

Claim 1 requires a “kit of parts capable of being assembled” containing:

A double-balloon catheter.
A filter housing with an inlet and outlet.
Extraction media inside the housing.
Hemocompatible polymer-coated carbon cores.
Carbon-core pore volume of approximately 1.68 to 2.17 cc/g.

The claim does not expressly require melphalan. Melphalan hydrochloride appears in dependent claims 7 and 14. Accordingly, claim 1 can cover kits intended for other small-molecule chemotherapeutic agents if the remaining limitations are met.

The phrase “capable of being assembled” broadens the claim beyond a fully integrated commercial device. Components may be packaged separately, provided the kit is objectively configured for assembly into the claimed treatment system.

How do claims 15 and 20 expand the patent scope?

Claim 15 requires a kit for delivering chemotherapy to the liver and replaces the generic “double balloon catheter” language with an “isolation-aspiration catheter” comprising two balloons.

Claim 20 is structurally more detailed. It requires:

A catheter inserted percutaneously into the inferior vena cava.
A hemo-compatible tube.
A main lumen for outflowing blood.
Two fixedly spaced balloons.
Fenestrations between the balloons.
Separate lumina for balloon inflation and deflation.
A filter apparatus containing the specified carbon cores.
A flow machine.
A sheath or return catheter.

Claim 20 therefore has a narrower but more technically specific infringement profile. A competing system may avoid claim 20 by using a different catheter architecture, a single balloon, occlusion devices that are not balloons, or a flow path that does not use the claimed lumen and fenestration arrangement. It may still face claims 1 or 15 if the kit satisfies those broader limitations.

What physical properties of the carbon cores are protected?

The dependent claims define a narrow adsorbent specification.

Property	Claimed range	Claims
Pore volume	About 1.68-2.17 cc/g	1, 15, 20
Particle diameter	About 0.45-1.15 mm	2, 21, 25
Apparent density	About 0.19-0.20 g/cc	3, 22, 26
Median micropore diameter	About 9.3-10.5 angstroms	4, 23, 27
Median mesopore diameter	About 30-156 angstroms	5, 24, 28

These limitations are important because they create both an infringement boundary and a design-around opportunity. A competing filter with the same catheter and chemotherapy configuration may reduce literal infringement risk by using carbon media outside one or more claimed ranges.

The practical legal question is how the measurements are performed. Pore volume, apparent density, micropore diameter, and mesopore diameter can vary with test method, sample preparation, moisture content, degassing conditions, and calculation model. A validity or infringement dispute would likely focus on the patent’s specification, testing protocol, intrinsic evidence, and expert reproducibility.

What polymer coatings are covered?

Claims 10-12 require a semipermeable polymer coating selected from:

Cellulose.
Methacrylate polymers.
Combinations of those materials.

Claim 11 specifies:

PMMA.
PEMA.
PHEMA.
Combinations.

Claim 12 narrows the coating to PHEMA, or polyhydroxyethyl methacrylate.

The coating limitation is central to the patent’s differentiation from conventional activated-carbon hemoperfusion. A bare carbon adsorbent would not satisfy the express polymer-coating limitation. A coating based on a different polymer family may avoid literal infringement, although the doctrine of equivalents could become relevant if the alternative performs substantially the same function in substantially the same way.

The coating appears intended to maintain blood compatibility while allowing the carbon core to remove chemotherapy from circulating blood. The claims do not require a particular coating thickness, degree of crosslinking, coating uniformity, or surface chemistry.

Is melphalan required for infringement?

No. Melphalan hydrochloride is required only by dependent claims 7, 14, and 17.

The broad independent claims refer to a “small molecule chemotherapeutic agent.” Claim 16 lists several examples, including:

Melphalan.
Doxorubicin.
5-fluorouracil.
Floxuridine.
Cisplatin.
Oxaliplatin.
Topotecan.
Mitomycin C.
Cyclophosphamide.
Methotrexate.
Vincristine.
Bleomycin.
FAMT.

A system using melphalan hydrochloride would fall within the melphalan-specific dependent claims if the other limitations are satisfied. A system using a different listed agent could implicate claim 16, but only in combination with the claim 15 limitations.

What is the relationship to HEPZATO and PHP therapy?

The claims correspond closely to the technical architecture used in percutaneous hepatic perfusion, commonly known as PHP. Delcath Systems commercializes HEPZATO KIT, which combines melphalan hydrochloride with a delivery and filtration procedure for patients with unresectable uveal melanoma metastatic to the liver.

The FDA approved HEPZATO in August 2023 under the accelerated approval pathway. The product is used with a proprietary delivery system that isolates the liver circulation, administers melphalan, withdraws hepatic venous blood, filters the chemotherapy, and returns treated blood to the patient (FDA, 2023).

The patent claims are broader in some respects than the approved indication because they cover small-molecule chemotherapy generally and recite multiple possible drugs. FDA approval, however, does not establish patent infringement. Patent scope depends on claim limitations, product configuration, and use.

What is the FDA regulatory status?

Item	Status
Product	HEPZATO KIT
Active drug	Melphalan hydrochloride
Sponsor	Delcath Systems, Inc.
FDA pathway	Accelerated approval
Approval date	August 14, 2023
Indication	Unresectable hepatic-dominant metastatic uveal melanoma without extrahepatic disease or with limited extrahepatic disease
Delivery method	Percutaneous hepatic perfusion with extracorporeal filtration
Key regulatory risk	Procedure-related complications, systemic melphalan exposure, hematologic toxicity, and vascular complications

The HEPZATO label imposes substantial procedural requirements, including use by trained personnel in an appropriate facility. The commercial system is therefore protected by more than drug patents. The regulatory package, physician training, hospital infrastructure, catheter technology, and extracorporeal filtration procedure create additional market barriers (FDA, 2023).

What patents protect the broader PHP platform?

A complete freedom-to-operate review should separate at least four patent clusters:

Catheter and vascular-isolation patents

These cover:

Double-balloon catheters.
Inferior vena cava isolation.
Hepatic venous blood withdrawal.
Fenestrated catheter tubes.
Balloon inflation lumina.
Return catheters and sheaths.

Claims 20-24 of US 10,369,264 are positioned in this cluster.

Filter and adsorbent patents

These cover:

Polymer-coated carbon.
Hemocompatible coatings.
Carbon particle size.
Pore volume.
Micropore and mesopore distributions.
Cartridge and dual-cartridge configurations.

Claims 1-14 and 20-28 are principally directed to this cluster.

Treatment-method patents

Separate patent families may cover:

Regional delivery of melphalan.
Isolated hepatic perfusion.
Chemotherapy dosing.
Blood-flow rates.
Treatment sequencing.
Patient selection.
Use in liver metastases or uveal melanoma.

US 10,369,264 is not primarily a method-of-treatment patent. Its claims are directed to kits and systems.

Drug and formulation patents

Melphalan hydrochloride is an established cytotoxic drug. Patent value in the HEPZATO platform is therefore concentrated in the delivery system, procedure, filtration technology, and regulatory product configuration rather than in basic composition-of-matter protection for melphalan.

When does US Patent 10,369,264 lose exclusivity?

The statutory patent term generally ends 20 years after the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other USPTO adjustments (35 U.S.C. §§ 154, 156).

The expiration date cannot be determined reliably from the claims alone. Patent number 10,369,264 identifies the issued patent but does not, by itself, establish:

The earliest effective nonprovisional filing date.
Patent-term adjustment.
Patent-term extension.
Terminal disclaimer status.
Whether the patent claims priority through a chain of continuations.
Whether a later reissue or disclaimer affects enforceability.

The controlling records are the USPTO patent center file history and the face of the issued patent. The FDA Orange Book is not necessarily the controlling source for this device-and-procedure patent because Orange Book listing is generally directed to patents submitted for approved drug products, including drug substance, drug product, and method-of-use patents (FDA, 2024).

What is the Orange Book status?

US 10,369,264 should not be assumed to be an Orange Book-listed patent merely because it relates to HEPZATO or melphalan delivery.

Orange Book listing depends on whether the patent is submitted by the new-drug application holder and meets FDA listing requirements. A patent directed primarily to a catheter, filter apparatus, extracorporeal circuit, or kit may not qualify for listing against an abbreviated new drug application in the same way as a drug composition or method-of-use patent.

For HEPZATO, the relevant regulatory exclusivities and patent listings must be reviewed in the FDA Orange Book entry for the specific NDA. Device patents may remain commercially important without appearing in the Orange Book.

Are Paragraph IV challenges likely?

A Paragraph IV certification is available when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. The practical relevance of Paragraph IV depends on whether the patent is listed for the approved drug product and whether an ANDA pathway is available.

For US 10,369,264, the principal obstacles are:

The claims cover a combination of a drug-delivery catheter and extracorporeal filter.
The product is administered through a complex procedure rather than a conventional oral or injectable generic pathway.
The claims include device and kit limitations that may not map cleanly onto a drug-only ANDA.
A generic applicant may seek a design-around rather than challenge every claim.
HEPZATO’s accelerated approval and specialized hospital procedure reduce the immediate likelihood of a conventional generic substitution.

A Paragraph IV challenge would be more likely against a listed melphalan formulation or method-of-use patent than against a system claim requiring a specific filter medium and catheter architecture.

What generic-entry risks exist?

The principal entry scenarios are different from ordinary small-molecule generic entry.

Entry scenario	Risk to the patented platform	Commercial likelihood
Generic melphalan alone	Low for system claims	Limited substitution value
Alternative melphalan delivery system	Medium	Depends on clinical and regulatory acceptance
Competing double-balloon catheter	Medium to high	Requires compatible filtration and clinical workflow
Alternative carbon filter	High design-around potential	Must match performance and blood-compatibility requirements
Biosimilar entry	Not applicable to melphalan	Melphalan is a small molecule, not a biologic
Full competing PHP system	High regulatory and clinical barriers	Requires substantial development and hospital adoption

There is no biosimilar pathway for melphalan hydrochloride. The relevant competitive threat is a generic drug, a competing drug-device combination, or a redesigned regional perfusion system.

How strong is the patent estate?

US 10,369,264 has meaningful commercial value but a narrower legal profile than a composition-of-matter patent.

Strengths

Combines the catheter and filtration components in a single claim.
Covers kits, reducing the importance of whether components are sold assembled.
Includes melphalan-specific dependent claims.
Protects physical properties of the adsorbent media.
Covers dual filter-cartridge arrangements.
Captures the clinically relevant hepatic isolation and blood-return workflow.
Makes a simple substitution of a conventional hemoperfusion cartridge more difficult.

Weaknesses

Independent claims require multiple technical elements.
The patent does not broadly cover melphalan itself.
Carbon-core ranges create design-around options.
Polymer coating limitations may exclude alternative hemocompatible materials.
Measurement disputes may affect pore-volume and density limitations.
A product using a different isolation mechanism may avoid claim 20.
The “kit of parts” format may create questions about component combination, intended use, and divided infringement in some commercial arrangements.

The strongest assertion case would involve a commercial package containing a two-balloon hepatic isolation catheter, melphalan, extracorporeal blood circulation, and a filter using carbon cores within the claimed physical ranges.

Which companies are challenging the platform?

No verified public record establishing a current Paragraph IV challenger, district-court invalidity action, or settlement involving US 10,369,264 is established by the claim text alone.

The competitive landscape is more likely to involve:

Alternative regional chemotherapy systems.
Other extracorporeal adsorption technologies.
Localized liver-directed therapies.
Transarterial radioembolization.
Transarterial chemoembolization.
Hepatic arterial infusion.
Surgical resection or ablation for selected disease.
Drug-device combinations targeting liver-dominant metastases.

The relevant competitor may not need to copy the patented system. It can compete by using a different vascular-isolation design, a different adsorbent, a non-extracorporeal approach, or a different local-delivery modality.

What manufacturing and IP barriers matter?

The filter media is a meaningful manufacturing barrier because the claims require a defined combination of:

Carbon particle size.
Apparent density.
Pore volume.
Micropore distribution.
Mesopore distribution.
Hemocompatible polymer coating.

Producing carbon that satisfies the adsorption-performance requirements while maintaining blood compatibility and acceptable pressure drop is more difficult than producing ordinary activated carbon.

Other barriers include:

Consistent coating of granular carbon.
Prevention of particle shedding.
Sterilization compatibility.
Cartridge packing density.
Flow uniformity.
Hemolysis control.
Chemical stability.
Validation of drug clearance.
Integration with a high-flow extracorporeal circuit.
Clinical training and procedural support.

The patent does not necessarily block every alternative manufacturing route. A competitor may pursue non-carbon adsorbents, different polymer systems, different pore distributions, or a filter located outside the claimed circuit configuration.

What geographic coverage does the patent provide?

US 10,369,264 provides rights in the United States only. It does not establish protection in Europe, Japan, China, Australia, Canada, or other jurisdictions.

International protection must be assessed through the patent family and national-stage filings. The relevant review should identify:

PCT application and publication.
European regional-phase applications.
Canadian, Australian, Japanese, and Chinese counterparts.
Continuations and divisionals.
Granted claims in each jurisdiction.
Local expiration dates.
Patent-term adjustments or supplementary protection mechanisms.
Litigation and opposition proceedings.

The US claims may differ materially from foreign claims. In particular, the scope of filter-media parameters, catheter structure, and melphalan use may have been narrowed during prosecution in individual jurisdictions.

What litigation and settlement issues should be reviewed?

For diligence, the relevant records are:

USPTO Patent Center prosecution history.
PACER district-court filings.
PTAB inter partes review and post-grant review records.
Federal Circuit decisions.
FDA Orange Book patent listings.
FDA Purple Book records, although biosimilar records are not relevant to melphalan.
Delcath SEC filings.
License agreements and collaboration disclosures.
Patent-family records in Google Patents, Espacenet, and WIPO Patentscope.

The highest-risk disputes would involve:

Whether a competitor’s carbon media falls within the claimed physical ranges.
Whether a polymer coating is “hemocompatible” and within the claimed polymer class.
Whether separately sold components form a claimed kit.
Whether a competing catheter has the required two-balloon and fenestration structure.
Whether a filter cartridge is arranged in parallel as required by claim 9.
Whether the product is used for delivery of a covered chemotherapeutic agent.
Whether the asserted claims are enabled across the full ranges.
Whether prior art discloses the combination of regional chemotherapy and extracorporeal adsorption.

No settlement terms should be inferred without a filed agreement, court order, SEC disclosure, or other primary record.

Key Takeaways

US 10,369,264 is a combination patent for regional hepatic chemotherapy delivery and extracorporeal drug filtration.
Its core protection is the combination of a double-balloon catheter and a filter containing polymer-coated carbon cores.
The principal adsorbent limitation is a pore volume of approximately 1.68 to 2.17 cc/g.
Dependent claims add particle size, apparent density, micropore diameter, mesopore diameter, polymer identity, cartridge arrangement, and melphalan.
The patent is relevant to the HEPZATO/PHP platform but does not protect melphalan itself.
The patent is not a biosimilar patent and should not automatically be treated as an Orange Book-listed drug patent.
The principal design-around routes are alternative filter media, alternative polymer coatings, different pore characteristics, and different vascular-isolation architectures.
Patent-term and Orange Book conclusions require the official USPTO and FDA records, not the claim text alone.

FAQs

Does US 10,369,264 cover a standard activated-carbon hemoperfusion filter?

No. The independent claims require a combination involving a double-balloon catheter or equivalent claimed system architecture, and the extraction media must comprise hemocompatible polymer-coated carbon cores with specified pore volume.

Can a competitor avoid the patent by using uncoated activated carbon?

Potentially, if the product does not meet the polymer-coating limitation. The competitor would still need to assess other patent families covering the catheter, treatment method, filter structure, or regional perfusion procedure.

Does using doxorubicin instead of melphalan avoid infringement?

Not necessarily. The independent claims are not limited to melphalan. Dependent claim 16 identifies doxorubicin and other chemotherapeutic agents, subject to the remaining limitations of claim 15.

Are HEPZATO patents automatically listed in the Orange Book?

No. Listing depends on FDA eligibility and submission for the relevant NDA. A patent focused on a catheter, filter, or extracorporeal system may not qualify for listing in the same manner as a drug composition or method-of-use patent.

Is a competing hepatic perfusion system a biosimilar?

No. Melphalan is a small-molecule drug. A competing product would ordinarily involve generic-drug, 505(b)(2), device, combination-product, or independent clinical-development pathways rather than the biosimilar framework.

References

Delcath Systems, Inc. (n.d.). U.S. Patent No. 10,369,264: [Patent record and claims]. United States Patent and Trademark Office.
Food and Drug Administration. (2023, August 14). FDA grants accelerated approval to melphalan flufenamide? FDA.
Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
United States Code. (2024). 35 U.S.C. § 156: Extension of patent term.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Delcath Systems Inc	HEPZATO	melphalan hydrochloride	POWDER;INTRA-ARTERIAL	201848-001	Aug 14, 2023		RX	Yes	Yes	10,369,264	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2776086	⤷ Start Trial
European Patent Office	3241576	⤷ Start Trial
European Patent Office	3590561	⤷ Start Trial
European Patent Office	4242176	⤷ Start Trial
Spain	2728280	⤷ Start Trial
Spain	2750846	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,369,264

Which drugs does patent 10,369,264 protect, and when does it expire?

Summary for Patent: 10,369,264