United States Patent 11,395,856 (Composition of DPPA/DPPC/PEG5000-DPPE in Propylene Glycol or Glycerol with Perfluorocarbon Gas): Scope, Claim-Building Blocks, and US Patent Landscape
Executive summary
U.S. Patent 11,395,856 claims a low-water, non-aqueous phospholipid mixture (DPPA, DPPC, and/or PEG5000-DPPE) in propylene glycol and/or glycerol combined with a perfluorocarbon gas, with ≤5% w/w water. It also claims methods to form lipid-encapsulated perfluorocarbon gas microspheres (LIPFGMs) via adding glycerol/propylene glycol/aqueous diluent followed by activation, and administration of the resulting microspheres. The enforceable core is the combination of (i) specific phospholids, (ii) specific non-aqueous solvents, (iii) specific water constraint, and (iv) gas presence, then downstream formulation/method steps that reuse that constrained intermediate.
What is the scope of US Patent 11,395,856 and what is it really protecting?
Direct answer: The patent protects (1) a specific storage/formulation intermediate that is a non-aqueous phospholipid-perfluorocarbon mixture with ≤5% w/w water, and (2) downstream assembly and use of lipid-encapsulated perfluorocarbon gas microspheres produced by activating that intermediate with added aqueous diluent.
Claim 1 “composition” is the primary bottleneck
Claim 1 defines the critical physical and compositional constraints that most design-arounds must address simultaneously:
- Phospholipids limited to:
- DPPA and/or DPPC (as “one or more phospholipids selected from DPPA, DPPC and PEG5000-DPPE”)
- PEG5000-DPPE (specified by name)
- Non-aqueous mixture solvents limited to:
- propylene glycol and/or glycerol
- Perfluorocarbon gas present in the composition
- Water constraint:
- non-aqueous mixture comprises ≤5% w/w water
- Implied context:
- The composition is a mixture intended as a precursor to ultrasound contrast agent microspheres.
Practical scope: A product formulation, kit component, or manufacturing intermediate that meets all elements of Claim 1 is within the composition claim.
Claims 2, 5, 6, 7, 8, 9 narrow the boundary conditions
Key narrowing features:
- Claim 2: water is <5% w/w
- Claim 5: phospholipid concentration ~0.9 to ~7.5 mg/mL
- Claim 6: phospholipid concentration fixed at ~3.75 mg/mL
- Claim 7: <5% impurities after room temperature storage for ~3 months
- Claim 8: perfluorocarbon gas is perfluoropropane (PFP)
- Claim 9: PEG5000-DPPE is “MPEG5000-DPPE” (a naming equivalence)
These create multiple “landing zones” where partial overlap may still avoid infringement if a feature is not met, but full coverage tends to align with the specific DPPA/DPPC/PEG5000-DPPE + propylene glycol/glycerol + low-water + perfluorocarbon combination.
Which claim elements are likely to be litigated in the US for 11,395,856?
Direct answer: The litigated focus typically concentrates on (i) water level, (ii) whether the exact phospholipid(s) are used, (iii) whether propylene glycol and/or glycerol are used as the non-aqueous vehicle, and (iv) whether a perfluorocarbon gas is present in the claimed mixture at the relevant step.
Element-by-element infringement pressure points
| Claim element |
Where it shows up |
Typical evidence in litigation |
| DPPA/DPPC/PEG5000-DPPE selection |
Claim 1 |
phospholipid identity assays (HPLC/LC-MS), lot COAs, stability profiles |
| Vehicle is propylene glycol and/or glycerol |
Claim 1 |
composition charts, solvent percentages, extraction/analysis |
| ≤5% w/w water |
Claim 1 (and Claim 2) |
Karl Fischer titration, drying/handling logs, packaging moisture migration data |
| Perfluorocarbon gas present |
Claim 1 |
gas composition in headspace or encapsulated phase; process records |
| Phospholipid mg/mL ranges |
Claims 5/6 |
concentration measurement |
| Impurities <5% after 3 months RT storage |
Claim 7 |
stability study methods, impurity profiling |
| PFP gas |
Claim 8 |
gas identity confirmation |
| PEG5000-DPPE naming |
Claim 9 |
structural identity confirmation and mapping of synonym |
| “Forming” method steps |
Claims 10-12 |
process instructions, manufacturing batch records, device settings |
What is the “non-aqueous low-water phospholipid gas composition” limitation and how narrow is it?
Direct answer: The composition claim is narrower than many general contrast agent patents because it locks the solvent system to propylene glycol and/or glycerol and locks water to ≤5% w/w in the “non-aqueous mixture” that contains the phospholipid and the perfluorocarbon gas.
Why the ≤5% w/w water limitation matters
In practice, water is the highest-friction design-around variable because it:
- changes lipid hydration state and viscosity,
- affects activation behavior in forming microspheres,
- creates a measurable quantitative threshold.
A competing process that uses higher water content in the precursor intermediate may seek to position itself outside Claim 1 even if the final microspheres are similar.
How do Claims 10–12 expand coverage beyond the composition?
Direct answer: The method claims extend the estate to manufacturing steps and administration of LIPFGMs made using the claimed composition.
Claim 10 (method of forming ultrasound contrast agent formulation)
- Adds glycerol and/or propylene glycol and/or an aqueous diluent to the Claim 1 composition to form an ultrasound contrast agent formulation.
This is written to cover a step where the Claim 1 composition is the starting material, and additional components are added to reach a workable “formulation” condition prior to activation.
Claim 11 (activating to form lipid-encapsulated perfluorocarbon gas microspheres)
- After forming the formulation, “activating” produces lipid-encapsulated perfluorocarbon gas microspheres.
The claim is not limited to a specific apparatus type in your text excerpt; “activating” typically captures sonication/agitation/shaking/microfluidics depending on how the specification defines it.
Claim 12 (method of using microspheres)
- Covers:
- forming microspheres using the steps:
- adding aqueous diluent to the Claim 1 composition to form a mixture, and
- activating to form microspheres
- administering to a subject.
This is the classic bridge from product-by-process style manufacturing to direct medical use.
What formulations are explicitly covered (and what is not clearly covered from the claim text)?
Direct answer: Explicitly covered formulations are those that:
- contain DPPA, DPPC and/or PEG5000-DPPE,
- are dissolved/dispersed in propylene glycol and/or glycerol,
- contain perfluorocarbon gas, and
- have ≤5% w/w water.
Covered gas and lipid specifics
- Perfluoropropane is explicitly covered via Claim 8.
- PEG5000-DPPE equivalence via Claim 9 expands interpretive reach.
Not explicit from the claims you provided
Your claim excerpt does not explicitly list:
- other phospholipids (e.g., DSPC, DPPE, egg lecithin, or cholesterol),
- polymeric surfactants,
- a mandated particle size distribution,
- surfactant identity, shell thickness, or number of production steps,
- specific ultrasound activation device parameters.
If competitors use different lipid systems or solvents, the claim boundary becomes the primary defense lever.
How many distinct “claim lanes” exist in US 11,395,856?
Direct answer: The claim set creates multiple independent lanes where a product can satisfy infringement even if another parameter differs. At least these lanes exist:
- Composition lane (Claim 1): the full combination (DPPA/DPPC/PEG5000-DPPE + propylene glycol/glycerol + perfluorocarbon gas + ≤5% w/w water).
- Water lane (Claims 2): same lane with tighter water (<5%).
- Concentration lane (Claims 5/6): phospholipid mg/mL window or a single point.
- Stability/impurity lane (Claim 7): impurity threshold after RT 3 months.
- Gas lane (Claim 8): PFP specifically.
- Method lane (Claims 10–12): using the Claim 1 composition as the input for forming and administering LIPFGMs.
What US patent landscape surrounds 11,395,856: related contrast agent families and likely blocking patents?
Direct answer: The patent text you provided is consistent with a well-known class of lipid-encapsulated perfluorocarbon ultrasound contrast agents that use DPPC/DPPA and PEGylated phospholipids and form gas microspheres by activation. In such estates, the surrounding US landscape usually clusters into:
- (A) phospholipid selection and PEGylation (stabilization and circulation),
- (B) perfluorocarbon gas encapsulation and shell formation,
- (C) manufacturing/activation processes (mixing order, solvent system, hydration/water control),
- (D) formulation vehicles and lyophilized or non-aqueous precursors, and
- (E) method-of-use (ultrasound imaging indications).
However, producing a numbered, accurate list of which specific US patents cite or are cited by 11,395,856, and identifying assignees, expiration dates, and Orange Book mappings requires the official bibliographic record and prosecution history, and those are not present in the prompt.
Orange Book status and generic entry risk for a product tied to 11,395,856
Direct answer: No Orange Book status, listed drug, or NDA/BLA linkage is provided in the prompt. Without the drug product identity connected to U.S. Patent 11,395,856, a correct Orange Book mapping and Paragraph IV risk assessment cannot be completed.
How to assess freedom-to-operate from the claim text alone
Direct answer: From the claim text provided, a clearance analysis should treat water content, solvent system, phospholipid identity, and presence of perfluorocarbon gas in the precursor mixture as the four most decisive infringement toggles.
Design-around levers (high-level, claim-logic based)
- Increase water above the asserted “≤5% w/w” in the relevant non-aqueous precursor mixture.
- Replace one or more of DPPA, DPPC, and PEG5000-DPPE with a lipid system outside Claim 1’s “selected from” set.
- Replace propylene glycol and/or glycerol with a different non-aqueous vehicle (or adjust formulation so the relevant “non-aqueous mixture” is not in PG/Glycerol).
- Form microspheres via a process that does not start from the Claim 1 composition (for process claims), though the method-of-use claim is harder to avoid if the final administerable microspheres are made as claimed.
Key Takeaways
- Primary protection: A non-aqueous precursor composition containing DPPA, DPPC, and/or PEG5000-DPPE in propylene glycol and/or glycerol, with perfluorocarbon gas and ≤5% w/w water.
- Downstream coverage: The patent adds manufacturing steps for producing lipid-encapsulated perfluorocarbon gas microspheres via adding PG/glycerol/aqueous diluent and activating, plus administration to a subject.
- Litigation focus: The most enforceable, testable variables are water content, lipid identity, vehicle solvents, and the gas-containing precursor character.
- Landscape gap: A precise US patent landscape (other US patents, citations, assignees, expiration, litigation, Orange Book listings) cannot be enumerated from the prompt alone.
FAQs
-
Does Claim 1 cover formulations where water is exactly 5% w/w?
Yes, “equal to or less than 5% w/w” includes 5%.
-
Is perfluoropropane required for all of Claim 1?
No. Claim 8 specifically narrows perfluoropropane; Claim 1 covers “a perfluorocarbon gas” generally.
-
Can a formulation with DPPC only infringe if it does not include DPPA or PEG5000-DPPE?
Likely yes under Claim 1 if DPPC is included because it is within the allowed “one or more phospholipids selected from DPPA, DPPC and PEG5000-DPPE.”
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Do Claims 10–12 require the precursor to be the exact Claim 1 composition?
Yes, Claim 10 and Claim 12 are written to add components to “the composition of claim 1,” and Claim 12 recites forming microspheres using steps that begin with that composition.
-
If impurities exceed 5% after 3 months at room temperature, does infringement still exist?
Claim 7 is a dependent limitation; infringement of Claim 7 would not attach, but infringement of independent Claim 1 may still occur if Claim 1 is satisfied.
References
- United States Patent 11,395,856. Claimed subject matter as provided in the prompt.
