US Patent 11,266,750: Claim Scope, Definity Manufacturing Coverage, Patent Landscape, and Generic Entry Risk

US 11,266,750 is directed to a manufacturing-controlled method for ultrasound contrast imaging using lipid-encapsulated perfluorocarbon microspheres. Its commercial relevance is strongest for Definity, the Lantheus perflutren lipid microsphere product, because the claimed excipient system, 10:82:8 phospholipid ratio, perfluoropropane gas, and impurity controls correspond closely to the Definity formulation and manufacturing process.[1][2]

The patent does not broadly claim every ultrasound contrast agent or every perflutren product. It claims an end-to-end process that requires specified raw-material impurity limits, a phospholipid formulation, microsphere activation with perfluorocarbon gas, administration to a subject, and ultrasound imaging. A competing product that uses a different lipid shell, gas, impurity profile, or manufacturing sequence may avoid literal infringement.

What does US Patent 11,266,750 claim?

The patent has two independent method claims, claims 1 and 5. Claims 2 through 4 depend from claim 1, while claims 6 through 8 depend from claim 5.

Claim group	Primary impurity limitation	Formulation limitation	Gas limitation
Claims 1-4	Calcium only	MPEG5000-DPPE, DPPA, DPPC and propylene glycol	Any perfluorocarbon gas; perfluoropropane in claim 4
Claims 5-8	Combined calcium and magnesium	MPEG5000-DPPE, DPPA, DPPC and propylene glycol	Any perfluorocarbon gas; perfluoropropane in claim 8

Both independent claims require the following sequence:

Selecting MPEG5000-DPPE with the specified impurity concentration.
Combining it with DPPA, DPPC and propylene glycol.
Producing a phospholipid solution below the specified impurity threshold.
Combining that solution with an aqueous solution.
Activating the resulting suspension with perfluorocarbon gas.
Forming lipid-encapsulated gas microspheres.
Administering the microspheres to a subject.
Obtaining an ultrasound image.

The claims therefore combine product-composition limitations with process and clinical-use limitations. They are not simple composition claims.

What formulations are protected by US 11,266,750?

The protected formulation uses four specified components:

DPPA, or dipalmitoylphosphatidic acid;
DPPC, or dipalmitoylphosphatidylcholine;
MPEG5000-DPPE, a polyethylene glycol-modified phospholipid; and
Propylene glycol.

Claims 2 and 6 require a molar ratio of:

Component	Mole percentage
DPPA	10%
DPPC	82%
MPEG5000-DPPE	8%

The 10:82:8 ratio is a dependent limitation. A process using the same excipients but a different ratio may fall outside claims 2 and 6, while still potentially infringing claims 1 or 5 if all other limitations are satisfied.

The patent does not expressly require glycerin, sodium chloride, a particular vial configuration, a specific dose, or a particular imaging indication in the claims supplied. Those features may appear in the specification or regulatory labeling, but they do not narrow the quoted independent claims unless incorporated through claim construction.

How do the calcium and magnesium limitations affect claim scope?

The impurity limitations are the central technical feature.

Claim 1 calcium pathway

Claim 1 requires:

MPEG5000-DPPE calcium concentration below 115 ppm; and
final phospholipid solution calcium concentration below 0.7 ppm.

Claim 3 adds raw-material specifications:

DPPA calcium below 780 ppm;
DPPC calcium below 90 ppm; and
propylene glycol calcium below 0.7 ppm.

Claim 3 does not replace the requirements of claim 1. It adds limitations. A defendant must therefore satisfy both the claim 1 solution threshold and the claim 3 component thresholds to infringe claim 3.

Claim 5 combined-calcium-and-magnesium pathway

Claim 5 uses combined calcium and magnesium concentration instead of calcium alone:

MPEG5000-DPPE combined calcium and magnesium below 115 ppm; and
final phospholipid solution combined calcium and magnesium below 0.7 ppm.

Claim 7 adds combined impurity limits for DPPA, DPPC and propylene glycol.

The claim 5 pathway may reach materials that satisfy a combined-metal limit but would not satisfy a calcium-only analysis under the same testing methodology. Conversely, a material with low calcium but excessive magnesium could fail claim 5 while satisfying claim 1.

Potential construction issues

Several terms are likely to matter in an infringement dispute:

"Selecting" may require evidence that the manufacturer deliberately chose material meeting the threshold, rather than that the material happened to satisfy it.
"Having a calcium concentration" raises questions about the analytical method, sampling point, batch averaging and detection limits.
"Phospholipid solution" and "phospholipid suspension" identify distinct manufacturing stages.
"Activating" may refer to the operational step that generates the gas microspheres, such as mechanical agitation or vial activation.
"Perfluorocarbon gas" is broader than perfluoropropane. Claims 4 and 8 narrow the gas to perfluoropropane.
"Administering ... to a subject" and "obtaining an ultrasound image" require clinical-use conduct, not only manufacture.

Because the claims use open transitional and process language, adding unclaimed excipients or process steps would not necessarily avoid infringement.

How strong is the patent estate for Definity and perflutren lipid microspheres?

US 11,266,750 has meaningful but narrow protection.

Strength factor	Assessment
Technical specificity	High. The claims identify named phospholipids, propylene glycol, metal thresholds and a defined microsphere process.
Coverage of the commercial formulation	Potentially strong if the accused process uses the claimed raw materials and thresholds.
Breadth against alternative products	Limited. Different shell lipids, gases or impurity controls may avoid the claims.
Detectability	Moderate to high. Ingredient identity and final metal concentrations can be tested, but process sequence and supplier selection require records.
Manufacturing leverage	High. The claims target process control rather than only the finished product.
Vulnerability to design-around	Moderate. A competitor may alter lipid ratios, impurity specifications, analytical controls or gas composition.
Clinical-use leverage	Moderate. The imaging and administration steps may create inducement or divided-infringement issues.

The patent is most commercially important where a competitor attempts to reproduce the Definity platform using the same phospholipid architecture and low-metal raw-material controls. It is less important to competing products such as sulfur hexafluoride lipid microspheres or protein-shell perflutren agents.

How does US 11,266,750 compare with competing ultrasound contrast agents?

The principal U.S. ultrasound contrast agents occupy different technical and patent positions.

Product	Active gas or agent	Shell or carrier	Relationship to US 11,266,750
Definity	Perflutren, commonly perfluoropropane	Phospholipid shell	Closest technical overlap
Lumason/SonoVue	Sulfur hexafluoride	Phospholipid shell	Different gas; likely outside claims requiring perfluorocarbon gas
Optison	Perflutren	Human serum albumin shell	Different shell architecture
Abbreviated or follow-on products	Product-dependent	Product-dependent	Risk depends on process and formulation similarity

Definity is a lipid-encapsulated perflutren microsphere. Lumason uses sulfur hexafluoride, which is not a perfluorocarbon gas. Optison uses an albumin-based shell rather than the DPPA/DPPC/MPEG5000-DPPE system. Those distinctions reduce direct overlap with the quoted claims.[2][3][4]

The patent is therefore not a platform monopoly over ultrasound contrast imaging. It is a targeted estate around one class of phospholipid microsphere production and use.

When does US 11,266,750 lose exclusivity?

The patent issued on March 8, 2022.[1] A U.S. utility patent ordinarily has a term measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension.[5]

The grant date alone does not establish the expiration date. The quoted claims also do not establish:

the earliest effective priority date;
patent-term adjustment;
any terminal disclaimer;
patent-term extension; or
whether the patent is part of a continuation chain with different term effects.

The legally operative expiration date must therefore be taken from the USPTO patent record and the patent’s term calculation. A post-grant expiration analysis should not rely on a simple 20-year calculation from the issue date.

What is the Orange Book status of US 11,266,750?

The claims are method claims, not claims limited to a drug product, drug substance or drug-device presentation. Orange Book listing depends on whether the patent is submitted for an approved NDA and whether it claims the approved drug, a method of use, or another qualifying subject under FDA listing rules.[6]

For Definity, the relevant regulatory product is Lantheus’s perflutren lipid microsphere injection, approved under NDA 021064.[2] A patent covering manufacturing impurity controls may not automatically appear as an Orange Book-listed method-of-use patent. Even if listed, the patent’s commercial effect would depend on the listed use code, the proposed generic label and the scope of any Paragraph IV certification.

A manufacturing-process patent can remain relevant without an Orange Book listing. It may be asserted under ordinary patent infringement provisions against manufacturing, importing, selling or using a product made by a patented process. The Hatch-Waxman pathway does not eliminate ordinary process-patent enforcement.

What Paragraph IV challenges and generic entry risks exist?

The direct generic risk is more limited than the risk associated with a broad composition patent.

A generic applicant seeking approval of a perflutren lipid microsphere product could pursue several strategies:

Generic strategy	Risk under US 11,266,750
Use the same DPPA/DPPC/MPEG5000-DPPE system and 10:82:8 ratio	High risk under claims 2 or 6 if impurity limits also match
Use the same excipients but a different lipid ratio	Possible risk under claims 1 or 5
Use different phospholipids	Lower literal-infringement risk
Use perfluoropropane with a non-claimed shell	Lower risk if the four claimed excipients are absent
Use a different perfluorocarbon gas	Claims 1 and 5 may still be relevant; claims 4 and 8 would not apply
Manufacture outside the United States and import the product	Potential process-patent risk under 35 U.S.C. § 271(g), depending on whether the product is made by the patented process
Avoid the claimed low-metal specifications	Potential design-around, subject to product quality and regulatory comparability

The patent does not claim every generic perflutren formulation. A Paragraph IV certification would require analysis of the specific Orange Book listing, proposed labeling and manufacturing process. If the patent is not listed, a generic applicant may still face conventional infringement litigation, but the statutory Orange Book stay mechanism may not apply to this patent.

What patent litigation affects US 11,266,750?

The claim text alone does not establish an active infringement case, settlement or license involving US 11,266,750. The patent discloses no settlement terms or license grant in the claims.

The most likely dispute theories would involve:

Literal infringement: whether the accused process uses each named excipient and meets each concentration threshold.
Claim construction: whether "selecting" requires intentional procurement or merely use of qualifying material.
Analytical proof: whether calcium and magnesium measurements are reliable and comparable across batches.
Process evidence: whether the accused product was made by the claimed sequence.
Inducement: whether product labeling directs administration and ultrasound imaging in a manner satisfying the method claims.
Validity: whether the impurity thresholds and process sequence were obvious in view of prior microsphere manufacturing techniques.

The strongest evidence for a patentee would usually be supplier specifications, certificates of analysis, batch records, manufacturing instructions and elemental-analysis data. Product testing alone may establish the final solution threshold but may not prove every upstream selection step.

What prior-art and invalidity issues are most important?

The likely validity pressure points are technical rather than conceptual.

Anticipation

An anticipation challenge would need one reference disclosing all required elements, including:

the four named formulation components;
the relevant calcium or combined calcium/magnesium limits;
the final solution threshold below 0.7 ppm;
aqueous suspension formation;
perfluorocarbon activation;
lipid-encapsulated microsphere formation; and
administration and ultrasound imaging.

A reference disclosing Definity-type microspheres but not the impurity thresholds may not anticipate the claims.

Obviousness

The most plausible obviousness theory would combine:

known Definity or perflutren lipid-microsphere formulations;
known phospholipid ratios;
known purification or low-metal raw-material controls; and
known effects of divalent-metal impurities on microsphere stability or performance.

The patentee’s strongest response would focus on whether the specific numerical thresholds produced an unexpected improvement in microsphere stability, activation, acoustic response, shelf life or batch consistency. The commercial and technical record supporting that relationship will be more important than the mere existence of low-metal ingredients.

Enablement and written description

The claims require tight analytical values, particularly a final calcium or combined calcium/magnesium concentration below 0.7 ppm. The specification must provide sufficient testing methodology and process guidance to reproduce those limits across relevant batches. The risk increases if the specification reports only isolated examples or lacks a validated method for measuring trace metals at the claimed level.

What geographic coverage does the patent provide?

US 11,266,750 provides U.S. patent rights only. It can reach:

manufacture in the United States;
use in the United States;
sale or offer for sale in the United States;
importation into the United States; and
in some circumstances, products imported after manufacture abroad by a patented process.

It does not directly block manufacture or sale in Europe, Japan, China, Canada or other jurisdictions. Foreign counterparts must be reviewed separately for claim scope, prosecution amendments, expiration and enforceability. A U.S. process patent may still create supply-chain risk when an overseas manufacturer exports the resulting product into the United States.

What manufacturing and intellectual-property barriers does the patent create?

The practical barrier is process replication. A competitor may need to secure:

low-calcium MPEG5000-DPPE;
low-calcium DPPA and DPPC;
low-metal propylene glycol;
validated trace-metal analytical methods;
controlled aqueous processing;
perfluorocarbon gas activation equipment; and
microsphere quality controls.

The patent adds legal risk to that technical burden. Even if a competitor can reproduce the finished microsphere performance, it may still infringe if its manufacturing records show the claimed raw-material thresholds and process steps.

The most credible design-around options are:

changing the phospholipid components;
using a different molar ratio;
changing the perfluorocarbon gas;
using a different solvent or excipient system;
controlling impurities through a different process without selecting materials at the claimed thresholds; or
using a non-lipid shell.

Each design-around must be evaluated against regulatory comparability requirements. A technically clean patent design-around may require a new formulation or a more substantial FDA submission.

Key Takeaways

US 11,266,750 is a narrow, process-centered patent covering low-metal manufacture and clinical use of lipid-encapsulated perfluorocarbon microspheres.
Claims 1 and 5 are the principal independent claims. Claim 1 measures calcium; claim 5 measures combined calcium and magnesium.
Claims 2 and 6 protect the 10:82:8 DPPA:DPPC:MPEG5000-DPPE ratio.
Claims 4 and 8 narrow the gas to perfluoropropane.
The patent is most relevant to Definity and closely related perflutren lipid microsphere products.
Lumason and Optison use materially different technical platforms and present lower direct overlap.
The patent does not establish a broad monopoly over ultrasound contrast agents or perflutren generally.
Generic risk depends heavily on the proposed manufacturing process, impurity specifications, labeling and any Orange Book listing.
The operative expiration date requires the USPTO term record, including priority, patent-term adjustment and any terminal disclaimer.
The principal litigation issues are trace-metal measurement, process proof, claim construction, obviousness and the relationship between manufacturing conduct and the claimed imaging method.

FAQs About US Patent 11,266,750

Does US 11,266,750 cover Definity itself?

It may cover a process used to manufacture Definity-type microspheres, but it is not a simple product-composition claim. Infringement depends on whether the accused process satisfies every required ingredient, impurity threshold, activation step and imaging limitation.

Does the patent cover sulfur hexafluoride ultrasound contrast agents?

Claims 1 and 5 require a perfluorocarbon gas. Sulfur hexafluoride is generally classified as a sulfur fluoride gas rather than a perfluorocarbon, so Lumason-type products present a materially different infringement analysis.

Can a generic avoid the patent by changing the DPPA-to-DPPC ratio?

Changing the ratio may avoid dependent claims 2 and 6, but it would not necessarily avoid independent claims 1 and 5. The generic would need to avoid all limitations of at least one asserted independent claim.

Is this a biosimilar patent risk?

No. Definity is a drug product containing perflutren lipid microspheres, not a biologic for which biosimilar approval under section 351(k) would ordinarily be the primary pathway. A follow-on applicant would more likely evaluate a generic, hybrid or other abbreviated drug-approval strategy.

Can the patent be enforced against an overseas manufacturer?

Potentially. U.S. law can reach importation of a product made abroad by a patented process under specific circumstances. The analysis depends on the actual foreign manufacturing steps and whether the imported product is materially made by the patented process.

References

U.S. Patent No. 11,266,750, Methods of ultrasound contrast imaging using lipid-encapsulated gas microspheres (U.S. Patent and Trademark Office 2022).
U.S. Food and Drug Administration. (n.d.). Definity (perflutren lipid microsphere) injectable suspension: Prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Lumason (sulfur hexafluoride lipid-type A microspheres) for injectable suspension: Prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Optison (perflutren protein-type A microspheres) injectable suspension: Prescribing information. FDA.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation. USPTO.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.

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	11,266,750	⤷ 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	11,266,750	⤷ 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	2017291815	⤷ Start Trial
Brazil	112018074469	⤷ Start Trial
Canada	3025580	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,266,750

Which drugs does patent 11,266,750 protect, and when does it expire?

Summary for Patent: 11,266,750