United States Patent 9,789,210: Scope, Claims, and U.S. Patent Landscape for Ultrasound Contrast Microspheres
What is the technical core of US 9,789,210?
US 9,789,210 claims ultrasound contrast imaging methods that require making and using lipid-encapsulated gas microspheres formed by activating a phospholipid suspension with a perfluorocarbon gas. The method is constrained by (i) a specific lipid composition (DPPA/DPPC/MPEG5000-DPPE in a defined molar ratio) and (ii) tightly specified calcium impurity limits in both the selected MPEG5000-DPPE ingredient and the final phospholipid solution, plus optional manufacturing environment controls (claims 2) and analytical methods for verifying calcium (claims 3-6).
The claims are written as a “make microspheres, administer, image” workflow, with the main claim-differentiators being calcium thresholds, impurity assay methods, and manufacturing conditions.
What do the independent claims require (Claims 1 and 2)?
Claim 1 (composition + calcium limits + process)
Claim 1 requires all of the following:
- Activating a phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres.
- The phospholipid suspension comprises a phospholipid solution in propylene glycol containing:
- DPPA, DPPC, and MPEG5000-DPPE
- Mole % ratio: 10:82:8 (DPPA:DPPC:MPEG5000-DPPE)
- Calcium concentration constraints
- MPEG5000-DPPE selected as having calcium < 115 ppm
- Phospholipid solution calcium concentration < 0.7 ppm
- Administering the lipid-encapsulated gas microspheres to a subject.
- Obtaining an ultrasound image of the subject.
In short: the independent claim is an imaging method where the microspheres are formed from a specific DPPA/DPPC/MPEG5000-DPPE molar recipe in propylene glycol, and the formulation must meet defined calcium impurity specifications.
Claim 2 (adds manufacturing controls)
Claim 2 depends on Claim 1’s overall method structure and adds formulation-preparation constraints:
- The phospholipid solution is made under:
- methanol- and toluene-free condition
- methyl t-butyl ether-free condition
- The lipid and impurity constraints remain:
- DPPA/DPPC/MPEG5000-DPPE molar ratio 10:82:8
- MPEG5000-DPPE selected as having calcium < 115 ppm
- Phospholipid solution calcium concentration < 0.7 ppm
In short: Claim 2 is the same claimed method, tightened by a defined solvent/processing environment for preparing the phospholipid solution.
What are the dependent claim add-ons (Claims 3-9)?
Calcium assay limitations (Claims 3-6)
- Claim 3: calcium concentration determined using atomic absorption spectroscopy (AAS).
- Claim 5: calcium concentration determined using ICP-MS.
- Claim 4: same as Claim 3 but in the context of Claim 2.
- Claim 6: same as Claim 5 but in the context of Claim 2.
These claims convert the calcium limits from purely compositional constraints into constraints tied to a specific verification technique, which can matter in both infringement proof and invalidity arguments.
Specific numeric sub-limits for calcium by component (Claims 7-8)
- Claim 7: calcium concentration limits:
- DPPA calcium < 780 ppm
- DPPC calcium < 90 ppm
- propylene glycol calcium < 0.7 ppm
- Claim 8: same as Claim 7 for Claim 2.
This is a “component-by-component impurity” refinement that can narrow the practical scope to manufacturing routes that keep calcium low in each input stream and excipient.
MPEG5000-DPPE ingredient sub-limit (Claim 9)
- Claim 9: MPEG5000-DPPE is selected as having calcium < 115 ppm.
This does not appear to add a new threshold beyond what is already in Claim 1/2’s selection language, but it reinforces it in a dedicated dependent claim position (useful in claim strategy, fallback positioning, and potential claim construction issues).
How the claim scope is shaped: the “must-haves” and the “differentiators”
US 9,789,210 is not claiming “any ultrasound contrast using gas microspheres.” It is claiming a targeted method with a stacked set of constraints:
Must-haves (central to independent claim scope)
- Lipid-encapsulated gas microspheres formed by perfluorocarbon activation
- DPPA/DPPC/MPEG5000-DPPE present at 10:82:8 (mole %)
- Dispersion medium: propylene glycol
- Calcium thresholds:
- MPEG5000-DPPE < 115 ppm
- Final phospholipid solution < 0.7 ppm
- Use in ultrasound imaging in a subject (administer microspheres, then image)
Differentiators that narrow or create fallback
- Claim 2: solvent/process exclusions (methanol-free, toluene-free, methyl t-butyl ether-free)
- Claims 3-6: verification method for calcium (AAS or ICP-MS)
- Claims 7-8: component-level calcium sub-limits (DPPA, DPPC, propylene glycol)
- Claim 9: reinforces MPEG5000-DPPE calcium criterion
What is the infringement-relevant claim structure (method + formulation constraints)?
Because all claims are method claims, infringement analysis turns on whether an accused product’s formulation and preparation satisfy the claim constraints and whether the accused actor performs the administer-and-image steps.
Key practical points for infringement mapping:
- The “microspheres” must be lipid-encapsulated gas microspheres formed by perfluorocarbon activation.
- If a competitor’s microspheres are formed via different chemistry or do not involve the claimed activation scheme, they can fall outside scope.
- Lipid molar ratio and components are explicit.
- The claim requires DPPA + DPPC + MPEG5000-DPPE at 10:82:8.
- Calcium impurity thresholds are explicit and tied to specific entities.
- MPEG5000-DPPE selection threshold is separate from the final solution threshold.
- Claim 2 creates a processing-environment limitation.
- Even if calcium thresholds are met, using methanol/toluene/methyl t-butyl ether in preparation can be outside Claim 2 (but not necessarily outside Claim 1).
- Claims 3-6 make the assay part of the claimed method.
- In practice, an accused workflow may meet calcium thresholds using other assays; that could matter for literal infringement of assay-dependent claims.
Where the patent landscape pressure points usually sit for this kind of claim
Even without external citations in this response, the claim architecture indicates what the prior art and design-around targets typically look like in this area:
1) Gas-filled lipid microsphere ultrasound formulations
This claim family sits in a mature space: lipid-shelled perfluorocarbon microspheres for ultrasound contrast. The landscape competitive risk usually comes from earlier filings that disclose:
- perfluorocarbon gas in lipid shells,
- DPPC-like lipids,
- PEGylated lipids,
- and methods of imaging.
US 9,789,210 tries to differentiate with the specific lipid blend (DPPA/DPPC/MPEG5000-DPPE at 10:82:8) and calcium impurity controls.
2) Impurity/trace metal specifications as formulation differentiation
The explicit calcium limits and component-by-component constraints indicate differentiation via manufacturing quality attributes. In many ultrasound contrast programs, calcium and metal ions impact:
- dispersion stability,
- particle integrity,
- osmolality-related behavior,
- and potentially in vivo performance.
Accordingly, prior art that:
- targets “low calcium,” “low divalent cations,” or “trace metal control,”
- or uses defined limits validated by AAS/ICP-MS,
would be directly relevant to novelty and obviousness arguments.
3) Ingredient manufacturing constraints and solvent exclusions
Claim 2’s solvent-free conditions for methanol, toluene, and methyl t-butyl ether signal a second differentiation vector. Prior art that uses alternative solvent systems or claims solvent removal and cleanliness could overlap.
4) Analytical method claims
Because Claims 3-6 lock in AAS or ICP-MS as the calcium determination method, the landscape of earlier filings that include trace metal specification testing and identify analytic methods (AAS/ICP-MS/ICP-OES) is directly relevant to claim validity and design-around.
What parts of the claim set create the most freedom for design-arounds
The claim set creates multiple ways to avoid literal infringement, but each comes with practical tradeoffs.
Design-around levers
- Change lipid composition off the 10:82:8 molar ratio
- Any deviation can avoid literal infringement of independent claims that require the exact ratio.
- Use different PEG-lipid
- Claim language requires MPEG5000-DPPE specifically. Alternative PEG chain lengths or different PEG-lipids can steer outside.
- Meet imaging via different formulation route
- Claims require activating with perfluorocarbon gas to form lipid-encapsulated gas microspheres. Different particle construction can avoid.
- Meet calcium limits but avoid the claim’s assay-dependent steps
- This can matter for Claims 3-6, depending on how verification is performed and documented.
- For Claim 2 only: use manufacturing that includes methanol/toluene/methyl t-butyl ether
- That can avoid Claim 2 while potentially still falling under Claim 1 if the calcium thresholds and ratio are met.
Design-around risk concentration
If an accused product matches:
- the same DPPA/DPPC/MPEG5000-DPPE ratio,
- uses propylene glycol,
- uses perfluorocarbon activation,
- and meets the same calcium impurity thresholds,
then the only remaining levers are typically the solvent/process constraints in Claim 2 and the assay method limitations in Claims 3-6.
Key claim-to-competitor mapping checklist (for U.S. landscape screening)
Use this as a search and diligence framework on U.S. filings and granted patents around lipid-shelled perfluorocarbon ultrasound agents:
| Screening element |
US 9,789,210 requirement |
Search/landmark focus |
| Particle type |
lipid-encapsulated gas microspheres made by perfluorocarbon activation |
“perfluorocarbon gas activation” + “lipid shell” + “microspheres” |
| Lipid components |
DPPA + DPPC + MPEG5000-DPPE |
“DPPA” + “MPEG5000-DPPE” + “DPPC” combinations |
| Lipid ratio |
10:82:8 (mole %) |
patents with explicit mol% ranges and exact recipes |
| Vehicle |
propylene glycol |
formulations listing propylene glycol as dispersion medium |
| Calcium limits |
MPEG5000-DPPE <115 ppm; solution <0.7 ppm |
trace metal specs: calcium, “divalent cations,” “metal ions” |
| Manufacturing solvent controls |
methanol-free, toluene-free, methyl t-butyl ether-free |
solvent-system patents and “free” conditions |
| Analytical method |
AAS or ICP-MS for calcium |
claims that specify AAS/ICP-MS in QC or method steps |
| Component calcium sub-limits |
DPPA<780 ppm; DPPC<90 ppm; propylene glycol<0.7 ppm |
multi-input impurity spec patents |
What is the business meaning of the claim scope right now
- The claims are likely to protect formulation quality attributes (calcium control and defined lipid selection) rather than only a generic imaging method.
- The numeric thresholds and assay-dependent dependents can make the patent valuable in product lifecycle management, especially where competitors must demonstrate trace metal control to meet regulatory and performance targets.
- The strongest commercial leverage usually appears when a competitor’s product formulation is close to the claimed recipe and the calcium specifications are achievable only via specific purification and control strategies that resemble the claimed limits.
Key Takeaways
- US 9,789,210 claims a specific method: make lipid-encapsulated gas microspheres by activating a phospholipid suspension with perfluorocarbon gas, administer to a subject, then obtain an ultrasound image.
- The independent scope is anchored on a defined lipid system: DPPA/DPPC/MPEG5000-DPPE at 10:82:8 (mole %) in propylene glycol, plus calcium impurity specifications (MPEG5000-DPPE < 115 ppm; final solution calcium < 0.7 ppm).
- Claim 2 adds processing constraints: the phospholipid solution must be made methanol-free, toluene-free, and methyl t-butyl ether-free.
- Dependent claims refine proof and fallback through assay method limitations (AAS or ICP-MS) and component-level calcium thresholds (DPPA, DPPC, propylene glycol).
- For U.S. landscape work, the search should focus on (i) identical lipid recipes, (ii) trace calcium/divalent ion specs, (iii) analytical methods for calcium, and (iv) solvent-free manufacturing claims.
FAQs
1) Is US 9,789,210 limited to perfluorocarbon gas microspheres?
Yes. The method requires activating the phospholipid suspension with a perfluorocarbon gas to form lipid-encapsulated gas microspheres.
2) What is the lipid molar ratio in the independent claims?
The phospholipid solution must contain DPPA, DPPC, and MPEG5000-DPPE in a mole % ratio of 10:82:8.
3) What are the calcium limits that define the main novelty in the claims?
The claims require MPEG5000-DPPE calcium < 115 ppm and phospholipid solution calcium < 0.7 ppm.
4) Does Claim 2 restrict the solvents used to make the phospholipid solution?
Yes. Claim 2 requires the phospholipid solution be made under methanol-free and toluene-free and methyl t-butyl ether-free conditions.
5) Do the dependent claims restrict how calcium must be measured?
Yes. Claims 3-6 limit determination of calcium to atomic absorption spectroscopy and/or ICP-MS.
References
No sources cited.
