US Patent 10,583,207: Claim Scope, Definity Coverage, Patent Expiration and Generic Entry Risk

US Patent 10,583,207 protects a specific process for preparing and using lipid-encapsulated perfluoropropane microspheres in ultrasound imaging. Its core limitations are the lipid composition, the substantially nonaqueous propylene glycol and/or glycerol vehicle, the approximately 10:82:8 molar ratio of DPPA:DPPC:MPEG5000-DPPE, and use of the activated microspheres for imaging. The patent is closely aligned with the formulation and activation platform used for perflutren lipid microsphere products such as Definity.

The claims are method claims rather than broad composition claims. A competitor may avoid literal infringement by changing the lipid ratio, replacing a listed excipient, using a different gas, altering the activation sequence, or omitting the claimed ultrasound-imaging steps. Those design-arounds may still face other patents covering perflutren formulations, vial activation, manufacturing, or clinical use.

What does US Patent 10,583,207 cover?

The patent covers methods that combine four technical features:

A perfluoropropane gas phase.
A lipid shell containing:
- DPPA, or dipalmitoylphosphatidic acid;
- DPPC, or dipalmitoylphosphatidylcholine; and
- MPEG5000-DPPE, a polyethylene glycol-linked phospholipid.
A substantially nonaqueous vehicle containing propylene glycol and/or glycerol.
Activation, administration and ultrasound imaging.

The independent claims are claims 1 and 11.

Claim	Independent or dependent	Principal limitation
1	Independent	Adds an aqueous diluent to a nonaqueous lipid mixture before activation, then administers the microspheres and obtains an ultrasound image
2	Dependent	Lipid concentration of about 0.1-10 mg/mL
3	Dependent	DPPA, DPPC, MPEG5000-DPPE, propylene glycol and glycerol as the essential components
4	Dependent	Combined lipid-to-solvent weight ratio of about 1:100:100 to 1:600:700
5	Dependent	Average microsphere diameter of about 1.0-2.0 microns
6	Dependent	Concentration greater than 10^8 microspheres/mL after activation
7	Dependent	Concentration greater than 10^8 microspheres/mL
8	Dependent	Agitation for 20-45 seconds
9	Dependent	DPPA, DPPC, MPEG5000-DPPE and propylene glycol without glycerol
10	Dependent	Combined lipid-to-propylene glycol weight ratio of about 1:100 to 1:600
11	Independent	Activates the nonaqueous composition in contact with perfluoropropane gas before administration and imaging
12-22	Dependent	Concentration, particle size, dilution, solvent composition and post-activation concentration

The claims do not cover every lipid-coated ultrasound contrast agent. They are directed to a narrow formulation and process combination.

How do claims 1 and 11 differ?

Claim 1 requires the aqueous diluent to be added to the nonaqueous mixture before activation:

“forming a combined mixture by adding an aqueous diluent ... and activating the combined mixture”

Claim 11 is broader in sequence. It requires activation of the composition containing the nonaqueous mixture and perfluoropropane gas, but it does not require an aqueous diluent before activation. Claims 13, 15, 18, 19, 21 and 22 address adding an aqueous diluent before administration.

This creates two principal infringement pathways:

Process pathway	Potential claim exposure
Aqueous diluent added before activation	Claim 1 and its dependent claims
Activation before aqueous dilution	Claim 11 and potentially claims 13, 15, 18, 19, 21 or 22
No aqueous dilution at any stage	Claim 11 remains potentially relevant
Dry or lyophilized formulation reconstituted by a different process	Depends on whether the reconstituted product and activation sequence satisfy the claim limitations

Claim 11 is commercially important because it does not require pre-activation dilution. A manufacturer cannot necessarily avoid the patent by moving dilution after activation.

What formulation is protected by US 10,583,207?

The central formulation contains DPPA, DPPC and MPEG5000-DPPE at approximately a 10:82:8 molar ratio. The ratio is a material limitation in both independent claims.

Lipid composition

Component	Claimed function or significance
DPPC	Principal phospholipid shell component
DPPA	Anionic phospholipid component
MPEG5000-DPPE	PEGylated phospholipid associated with shell stabilization and circulation behavior
Propylene glycol	Nonaqueous vehicle
Glycerol	Optional co-vehicle in claims 1-4 and 14-15

The phrase “about 10:82:8” provides some numerical tolerance. The scope will depend on how a court construes “about” in light of the specification, examples and prosecution history. A formulation materially outside the disclosed range may avoid literal infringement, although the doctrine of equivalents could remain relevant.

Solvent limitations

Claims 1 and 11 require the nonaqueous mixture to contain less than 5% w/w water. This limitation is important because it distinguishes the claimed pre-activation formulation from an aqueous lipid dispersion.

Claims 3 and 14 require a mixture consisting essentially of the three named lipids, propylene glycol and glycerol. Claims 9 and 10 provide a glycerol-free alternative based on propylene glycol.

“Consisting essentially of” generally permits components that do not materially affect the basic and novel characteristics of the formulation. The legal effect depends on the patent specification and prosecution record. A formulation containing additional surfactants, buffers or stabilizers could create a claim-construction dispute.

What particle-size and concentration limitations are covered?

Claims 5, 6, 7, 16, 17 and 20 add performance specifications:

Average diameter of approximately 1.0-2.0 microns.
Concentration greater than 10^8 microspheres/mL after activation.

These claims can be difficult to assess without a defined measurement method. Particle-size distributions may vary according to:

Sampling time after activation;
Instrument and analytical technique;
Whether the measurement is number-weighted, volume-weighted or intensity-weighted;
Dilution before analysis; and
Microsphere stability after activation.

The concentration limitation is measured after activation, not necessarily after administration. A product that meets the concentration threshold immediately after activation but falls below it after dilution may still satisfy the claim if the tested process produces the claimed post-activation concentration.

Does the patent cover Definity?

The technical subject matter is strongly associated with the Definity platform. Definity is a perflutren lipid microsphere ultrasound contrast agent marketed by Lantheus Medical Imaging. Perflutren is octafluoropropane, also known as perfluoropropane or C3F8. The FDA-approved product uses lipid-coated microspheres and is activated by agitation before intravenous administration.[2]

The patent claims should not be treated as a blanket statement that every Definity use infringes. A product-by-product analysis must compare:

The actual lipid composition;
The DPPA:DPPC:MPEG5000-DPPE ratio;
Water content before activation;
Propylene glycol and glycerol concentrations;
Activation sequence;
Particle-size distribution;
Microsphere concentration; and
The accused clinical-use protocol.

A marketed product may practice the claims even if its label does not reproduce every manufacturing detail. Conversely, a generic manufacturer may argue that its process uses materially different excipient concentrations or an altered activation sequence.

What is the patent’s legal status and expiration date?

US Patent 10,583,207 was issued on March 10, 2020.[1] The patent’s enforceable term is generally governed by 35 U.S.C. § 154 and is ordinarily 20 years from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers and applicable priority rules.[3]

The issue date alone does not establish the expiration date. The exact expiration analysis requires the patent’s continuity data, earliest effective filing date, terminal-disclaimer status and any patent-term adjustment. The claims supplied do not contain that information.

Event	Date or status
Patent issued	March 10, 2020
Patent number	US 10,583,207
Patent type	Utility patent
Claim type	Method of preparation, administration and ultrasound imaging
Statutory term	Generally 20 years from the earliest effective nonprovisional filing date
Patent-term adjustment	Must be confirmed from USPTO Patent Center
Patent-term extension	Must be confirmed from FDA and USPTO records
Terminal disclaimer	Must be confirmed from the prosecution and assignment records

The patent is not automatically entitled to FDA patent-term extension merely because it relates to an approved contrast agent. Patent-term extension applies only if the statutory requirements are met and the patent is identified in the relevant regulatory record.

Is US 10,583,207 listed in the Orange Book?

Orange Book listing and patent enforceability are separate issues. The FDA lists patents for approved drug products when the NDA holder submits patents that meet the applicable listing requirements. Method-of-use patents can be listed with a use code. Manufacturing-process patents generally receive different treatment and may not be eligible for listing merely because they relate to an approved product.[4]

For Definity, the relevant regulatory product is NDA 021064. The Orange Book analysis should determine:

Whether US 10,583,207 is listed against NDA 021064;
Whether the listing is for a method of use, formulation, or another category;
Whether an FDA use code maps to the ultrasound-imaging method claimed in the patent;
Whether the patent was listed before or after an ANDA filing; and
Whether the listing has been withdrawn, delisted or remains active.

The claim language combines manufacturing steps with administration and imaging. That hybrid structure may affect Orange Book listing treatment and Paragraph IV relevance. A patent’s presence in the Orange Book does not establish that every claim is valid or infringed.

What Paragraph IV risks exist for generic Definity?

A generic applicant seeking approval of a perflutren lipid microsphere product could face several certification positions:

Certification	Commercial effect
Paragraph I	No relevant patent information is listed
Paragraph II	Listed patent has expired
Paragraph III	Applicant will wait until patent expiration
Paragraph IV	Patent is invalid, unenforceable or not infringed
Section viii statement	Applicant omits a patented method of use from labeling

For US 10,583,207, a Paragraph IV challenge would likely focus on:

Anticipation by earlier lipid microsphere preparation methods.
Obviousness based on known DPPC/DPPA/PEG-lipid shells and nonaqueous polyol vehicles.
Lack of written description for the claimed ratio and process combinations.
Enablement of the full scope of “about” ranges and “consists essentially of” formulations.
Noninfringement based on a different water content, solvent ratio, activation sequence or lipid ratio.
Patent eligibility or claim-construction issues associated with the medical-use steps, although conventional treatment-method claims generally receive different treatment from diagnostic-only claims.

The most credible generic design-around would be a formulation that uses the same gas but changes the lipid ratio and avoids the claimed propylene glycol/glycerol composition. A second route would use a different shell chemistry or a different activation process. A third route would rely on a label that omits any use corresponding to the patented imaging method, subject to the induced-infringement and product-labeling analysis.

No Paragraph IV challenge, ANDA litigation matter or settlement agreement can be established from the claim text alone. Those events must be confirmed through FDA Orange Book records, FDA litigation records, PACER and SEC disclosures.

Which competing ultrasound contrast agents have different patent risks?

US 10,583,207 is most relevant to perfluoropropane lipid microspheres. Competing agents use materially different gases or shell systems.

Product	Active gas or agent	Principal sponsor or manufacturer	Relationship to US 10,583,207
Definity	Perflutren, or octafluoropropane	Lantheus Medical Imaging	Closest technical overlap
Lumason/SonoVue	Sulfur hexafluoride	Bracco	Different gas and formulation platform
Optison	Perflutren in a human serum albumin shell	GE HealthCare	Different shell technology
Sonazoid	Perfluorobutane	GE HealthCare in relevant markets	Different gas and lipid formulation

Lumason/SonoVue is not an obvious literal match because it uses sulfur hexafluoride rather than perfluoropropane. Optison uses a protein-based shell rather than the claimed DPPA/DPPC/MPEG5000-DPPE lipid shell. Sonazoid uses perfluorobutane and a different formulation platform.[2,5]

The patent therefore creates a more targeted barrier around perflutren lipid microsphere technology than around ultrasound contrast imaging generally.

How strong is the patent estate?

US 10,583,207 has meaningful commercial relevance because it claims a process associated with an established product platform. Its strength is concentrated rather than broad.

Factors supporting enforcement value

Both independent claims cover administration and ultrasound imaging.
Claim 11 does not require aqueous dilution before activation.
The 10:82:8 lipid ratio identifies a specific commercial formulation space.
The patent includes alternative glycerol-containing and glycerol-free embodiments.
Dependent claims add commercially measurable particle-size and concentration limitations.

Factors limiting scope

The claims require perfluoropropane.
The claims require a particular three-lipid system.
The nonaqueous mixture must contain less than 5% water.
The claims depend on specific polyol vehicles.
The claims are process-and-use claims, not unrestricted composition claims.
Several limitations may require proprietary manufacturing and analytical evidence to prove.

The patent is strongest against a manufacturer that deliberately reproduces the claimed Definity-type formulation and activation process. It is weaker against products using another gas, another shell, a materially different lipid ratio, or a fully aqueous preparation process.

What manufacturing and intellectual-property barriers remain?

A generic competitor must solve more than patent clearance. Perflutren microsphere products require control of:

Gas loading and retention;
Lipid-shell formation;
Particle-size distribution;
Microsphere concentration;
Activation reproducibility;
Container closure and vial performance;
Sterility and particulate control;
Stability before and after activation; and
Clinical performance under ultrasound imaging conditions.

A noninfringing formulation that fails to match the reference product’s acoustic response, stability or safety profile may face FDA bioequivalence and product-quality obstacles. For complex injectable products, a generic applicant may need extensive comparative characterization even when the active gas and broad dosage form are the same.

What litigation or settlement agreements affect the patent?

The supplied claim text does not identify litigation, a settlement, a covenant not to sue, a license, or a terminal disclaimer. No such event should be inferred from issuance of the patent or its relationship to Definity.

A complete freedom-to-operate review should treat the patent as one layer in a broader portfolio that may include:

Earlier lipid-microsphere composition patents;
Perflutren formulation patents;
Vial activation and reconstitution patents;
Manufacturing-process patents;
Method-of-use patents for specific imaging applications; and
Regulatory exclusivity or market-protection rights.

Patent expiration does not eliminate regulatory, trade-secret or manufacturing barriers.

What is the commercial exposure?

Definity is the principal commercial product potentially exposed to this patent family because it uses perflutren lipid microspheres. The business exposure depends on:

Whether the patent is listed for the product;
Whether a generic applicant uses the claimed formulation process;
Whether other unexpired patents cover the same product;
Whether a Paragraph IV notice triggers litigation;
Whether the patent has a terminal disclaimer or earlier expiration; and
Whether a generic product receives approval with a full or carve-out label.

Revenue exposure should not be estimated from US 10,583,207 alone. The commercial risk is portfolio-based. A generic may clear this patent but remain blocked by another listed patent, or it may avoid a listed method claim through labeling while still requiring a different formulation process.

Key Takeaways

US 10,583,207 protects methods using lipid-encapsulated perfluoropropane microspheres for ultrasound imaging.
The central formulation is DPPA:DPPC:MPEG5000-DPPE at approximately 10:82:8 mol %, in propylene glycol and/or glycerol.
The nonaqueous mixture must contain less than 5% water.
Claim 1 requires aqueous dilution before activation; claim 11 does not.
Dependent claims cover lipid concentration, solvent ratios, particle size, microsphere concentration and activation time.
The patent is technically closest to Definity and other perflutren lipid microsphere products.
Lumason/SonoVue, Optison and Sonazoid use materially different gas or shell platforms.
The patent issued March 10, 2020.
An exact expiration date cannot be derived from the claims. It depends on the earliest effective filing date, patent-term adjustment, terminal disclaimers and any patent-term extension.
Paragraph IV, Orange Book and litigation conclusions require a verified review of FDA, USPTO and court records.
The principal generic design-around options are changing the lipid ratio, replacing the polyol vehicle, using a different shell or gas, or modifying the activation sequence.

FAQs

Does US 10,583,207 claim perflutren itself?

No. The claims are directed to methods using lipid-encapsulated perfluoropropane microspheres. Perflutren is the drug substance commonly associated with octafluoropropane, but the patent claims require additional formulation, activation, administration and imaging elements.

Can a generic use the same perflutren gas but a different lipid shell?

Potentially. A different shell may avoid literal infringement if it does not contain DPPA, DPPC and MPEG5000-DPPE in the claimed combination and approximate ratio. Other patents and FDA comparability requirements could still apply.

Does a 20-45 second activation time appear in the independent claims?

No. The 20-45 second agitation period appears in dependent claim 8. A process can potentially fall within claim 1 or claim 11 without satisfying claim 8.

Does adding water after activation avoid the patent?

Not necessarily. Claim 11 does not require aqueous dilution before activation, and several dependent claims expressly address aqueous dilution before administration. Post-activation dilution alone does not establish noninfringement.

Is a biosimilar pathway relevant to Definity?

No. Definity is a drug product rather than a biologic for purposes of the biosimilar pathway. A competing product would generally proceed through an abbreviated drug-approval route, subject to FDA classification and product-specific requirements.

References

United States Patent and Trademark Office. (2020). U.S. Patent No. 10,583,207.
U.S. Food and Drug Administration. (2023). Definity (perflutren lipid microsphere) injectable suspension prescribing information. Lantheus Medical Imaging, Inc.
Patent Act, 35 U.S.C. § 154.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Lumason, Optison and Sonazoid prescribing information.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Lantheus Medcl	DEFINITY	perflutren	INJECTABLE;INTRAVENOUS	021064-001	Jul 31, 2001		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				METHOD OF USING THE DRUG SUBSTANCE/DRUG PRODUCT FOR ULTRASOUND IMAGING	⤷ Start Trial
Lantheus Medcl	DEFINITY RT	perflutren	INJECTABLE;INTRAVENOUS	021064-002	Nov 17, 2020		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				METHOD OF USING THE DRUG SUBSTANCE/DRUG PRODUCT FOR ULTRASOUND IMAGING	⤷ 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
Australia	2015374286	⤷ Start Trial
Australia	2022201065	⤷ Start Trial
Brazil	112017013787	⤷ Start Trial
Canada	2972423	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,583,207

Which drugs does patent 10,583,207 protect, and when does it expire?

Summary for Patent: 10,583,207