United States Patent 5,213,804: Scope, Claim Map, and US Patent Landscape
US Patent 5,213,804 covers “sterically stabilized” liposomes using an amphipathic polymer-derivatized lipid (PEG or biodegradable polymer analogs) at defined molar fraction and particle-size range, with an asserted functional outcome: extended liposome blood lifetime (24 hours after IV dosing) and enhanced tumor localization by extravasation. The independent claim set is split across (i) a liposome composition (claim 1), (ii) a liposome formulation for tumor targeting with anthracyclines (claim 7), and (iii) end-to-end methods covering manufacturing (claim 8) and tumor localization in vivo (claim 11), plus an explicit treatment use case for breast/colon carcinoma (claim 13).
What is the legal scope of claim 1 (composition for solid-tumor localization)?
Core invention requirements (claim 1)
Claim 1 requires all of the following elements:
A. Lipid architecture
- Liposomes “composed of vesicle-forming lipids”
- Plus between 1 and 20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, where the polymer is limited to:
- polyethyleneglycol (PEG), or
- polylactic acid, or
- polyglycolic acid, or
- polylactic acid/polyglycolic acid copolymers.
B. Particle size window
- “selected mean particle diameter” in the range about 0.07 to 0.12 microns.
C. Payload form
- The “compound in liposome-entrapped form” (payload must be entrapped in the liposomes, not merely associated).
D. Pharmacokinetic-like functional requirement
- A liposome blood lifetime, measured 24 hours after IV injection, that is “several times greater” than the blood lifetime of liposomes “in the absence of the derivatized lipid.”
- This is a comparative functional limitation: the claimed liposomes must outperform an internal comparator lacking the derivatized lipid.
Claim 1 scope implications
- The scope is not limited to a specific vesicle-forming lipid matrix (no egg-phospholipid vs hydrogenated phospholipid requirement stated in the claim text you provided). It is primarily determined by:
1) polymer-derivatized amphipathic lipid mol%,
2) particle size,
3) entrapped payload,
4) a 24h blood lifetime performance target relative to non-derivatized-lipid controls.
- “Several times greater” is a numeric ambiguity in the claim language provided. The legal breadth depends on how the specification defines the comparator and threshold for “several times.”
How do the dependent claims narrow the claim 1 baseline?
Claim 2: PEG identity and molecular weight
- Hydrophilic polymer = PEG
- Molecular weight 1,000 to 5,000 daltons.
Scope effect: narrows polymer chemistry and PEG chain length.
Claim 3: biodegradable polymer alternatives
- Hydrophilic polymer = polylactic acid, polyglycolic acid, or copolymers.
Scope effect: keeps PEG out; retains biodegradables only.
Claim 4: anti-tumor + entrapped fraction
- Compound is an anti-tumor agent
- At least about 80% of the compound is liposome-entrapped.
Scope effect: adds a payload loading/entrapment fraction threshold.
Claim 5: anthracyclines + concentration threshold
- Anti-tumor agent = anthracycline antibiotic
- Drug concentration in liposomes > 50 μg compound per μmole liposome lipid.
Scope effect: adds a quantitative loading requirement tied to lipid molar basis.
Claim 6: specific anthracyclines
- Anthracycline is selected from doxorubicin, epirubicin, daunorubicin, including pharmacologically acceptable salts and acids.
Scope effect: narrows the drug identity.
Claim 7: composition tailored to anthracyclines (independent)
Claim 7 overlaps heavily with claim 1 but is tightened to the anthracycline use case and adds explicit payload thresholds:
- Polymer-derivatized amphipathic vesicle-forming lipid derivatized with polyethyleneglycol (PEG) (not the broader polymer genus of claim 1).
- Size range about 0.07 to 0.12 microns.
- Drug: at least about 80% entrapped.
- Drug concentration > 50 μg agent/μmole liposome lipid.
- Again, functional requirement: 24h blood lifetime several times greater than liposomes lacking the derivatized lipid.
Scope effect: claim 7 is a more commercially actionable formulation claim: PEG only, plus explicit quantitative loading/entrapment and size.
Claim 8: preparation method (manufacturing scope)
Method claim 8 covers preparing an IV-administered tumor-localizing liposome composition by entrapping an agent, requiring:
- Lipid composition with 1-20 mole percent of the polymer-derivatized amphipathic vesicle-forming lipid (polymer genus as in claim 1),
- Average size 0.07-0.12 microns,
- 24h blood lifetime several times greater versus non-derivatized-lipid liposomes.
Scope effect: gives a process hook to production, but it is still tied to product characteristics (size and blood lifetime).
Claim 9: remote loading across an ion/pH gradient
- If agent is an anthracycline antibiotic
- Entrapping includes “loading the agent into preformed liposomes by remote loading across an ion or pH gradient”
- Final concentration > 50 μg agent/μmole liposome lipid.
Scope effect: constrains entrapment method and loading method mechanics.
Claim 10: anthracycline selection
- doxorubicin, epirubicin, daunorubicin; salts and acids.
Claim 11: method of localizing in vivo (extravasation and time course)
Claim 11 adds dosing and localization metrics:
- Prepares liposomes meeting:
- derivatized amphipathic lipid at 1-20 mole%,
- size 0.07-0.12 microns,
- “blood lifetime, as measured by the percent of a liposome marker present in the blood 24 hours after IV” is several times greater versus absence of derivatized lipids.
- contains compound entrapped.
- IV injects in “amount effective” to localize therapeutically effective quantity in solid tumor.
- Achieves localization of liposomes in solid tumor 48 hours after IV that is “substantially greater” than liposomes lacking derivatized lipid.
Scope effect: adds the 48h localization advantage and injective dosing intent/efficacy.
Claim 12: PEG MW narrowing for claim 11
- PEG molecular weight 1,000-5,000 daltons.
Claim 13: treatment method (breast or colon carcinoma)
Claim 13 converts the formulation/localization concept into a therapeutic use with explicit composition thresholds:
- Breast or colon carcinoma
- Anthracycline drug entrapped in liposomes meeting:
- 24h blood lifetime several times greater (marker-based measure in blood),
- size 0.07-0.12 microns,
- concentration > 50 μg drug/μmole lipid,
- at least 80% entrapped,
- IV dosing in an amount effective to localize therapeutically effective quantity of agent in carcinoma.
Scope effect: ties to oncology indication and retains all formulation constraints.
Claim 14: PEG MW + drug identity
- PEG MW 1,000-5,000 daltons
- drug selected from doxorubicin, epirubicin, daunorubicin; salts and acids.
Claim 15: composition mirror (anthracycline selection)
- Like claim 7, drug identity constraint to doxorubicin/epirubicin/daunorubicin.
What is the claim map in table form (scope-by-claim)?
| Claim |
What it protects |
Polymer on derivatized amphipathic lipid |
Mol% |
Particle size |
Entrapment % / concentration |
Functional PK/target limits |
| 1 |
Composition for tumor localization |
PEG or PLA or PGA or PLA/PGA copolymer |
1-20 mol% |
0.07-0.12 μm (mean diameter) |
Entrapped payload; no explicit % |
24h blood lifetime several-times vs no derivatized lipid |
| 2 |
Composition dependent |
PEG only |
1-20 mol% (implied) |
0.07-0.12 μm |
As claim 1 |
As claim 1 |
| 3 |
Composition dependent |
PLA, PGA, PLA/PGA only |
1-20 mol% |
0.07-0.12 μm |
As claim 1 |
As claim 1 |
| 4 |
Composition dependent |
As claim 1 |
1-20 mol% |
0.07-0.12 μm |
≥80% entrapped |
As claim 1 |
| 5 |
Composition dependent |
As claim 1 |
1-20 mol% |
0.07-0.12 μm |
Anthracycline; concentration >50 μg/μmole lipid |
As claim 1 |
| 6 |
Composition dependent |
As claim 1 |
1-20 mol% |
0.07-0.12 μm |
Specific anthracyclines |
As claim 1 |
| 7 |
Composition (PEG-specific anthracycline) |
PEG only |
1-20 mol% |
0.07-0.12 μm (avg size) |
≥80% entrapped and >50 μg/μmole lipid |
24h blood lifetime several-times vs no derivatized lipid |
| 8 |
Method of preparing |
Polymer genus as claim 1 |
1-20 mol% |
0.07-0.12 μm |
Entrapped agent; no explicit % |
Requires 24h blood lifetime several-times vs no derivatized lipid |
| 9 |
Preparation method (anthracycline remote loading) |
As claim 8 (implied by claim 9’s dependency on claim 8) |
1-20 mol% |
0.07-0.12 μm |
remote loading; final conc >50 μg/μmole lipid |
As claim 8 |
| 10 |
Drug selection |
As claim 9 |
1-20 mol% |
0.07-0.12 μm |
Specific anthracyclines |
As claim 9 |
| 11 |
Method of localizing in vivo |
Polymer genus as claim 1 |
1-20 mol% |
0.07-0.12 μm |
Contains compound entrapped |
24h blood marker several-times; 48h tumor localization “substantially greater” |
| 12 |
Method dependent |
PEG MW 1,000-5,000 Da |
1-20 mol% |
0.07-0.12 μm |
As claim 11 |
As claim 11 |
| 13 |
Treatment method |
Polymer genus as claim 11 |
1-20 mol% |
0.07-0.12 μm |
>50 μg/μmole lipid; ≥80% entrapped |
24h blood marker several-times; localization in breast/colon carcinoma |
| 14 |
Treatment dependent |
PEG MW 1,000-5,000 Da |
1-20 mol% |
0.07-0.12 μm |
Specific anthracyclines |
As claim 13 |
| 15 |
Composition dependent |
As claim 7 |
1-20 mol% |
0.07-0.12 μm |
Specific anthracyclines |
As claim 7 |
Where are the highest infringement-risk design constraints?
In practice, the claim language creates a multi-factor “must-match” test. The highest-risk parameters are:
1) Polymer-derivatized amphipathic lipid at 1-20 mol%
- Avoiding infringement by using polymer-free steric stabilization or using different polymer architectures could fall outside, but the claim is anchored to “derivatized amphipathic vesicle-forming lipid” plus a specific polymer genus.
2) Particle size 0.07-0.12 microns
- Tight nanorange; “mean particle diameter” vs “average size” appear as slightly different phrasing across claims, but both center on the same window.
3) 24h blood lifetime performance as a comparative functional limitation
- This is the claims’ core differentiation: the liposomes must persist longer in blood than the same system without the derivatized lipid, with measurement tied to marker presence in blood for certain methods.
4) Anthracycline-specific payload limits in the anthracycline claims
- ≥80% entrapped and >50 μg/μmole lipid.
- Doxorubicin/epirubicin/daunorubicin identity limits on multiple dependents.
5) Remote loading via ion or pH gradient (for claim 9)
- If manufacturing uses different loading mechanics, claim 9 could be avoided while composition and method-of-localization claims remain possible.
What is the US patent landscape around this technology class?
This patent landscape analysis is limited to what can be proven from the claim text provided. The requested landscape cannot be completed to a reliable, citation-backed map of related US patents, families, claim overlaps, or prosecution history without authoritative bibliographic and patent-document data.
Given only claim text, the defendable “landscape” is the set of claim-to-claim technical neighbors inside the same patent:
- Composition layer: claim 1 and claim 7 define the formulation perimeter (polymer type, mol%, size, entrapped payload, and 24h blood lifetime).
- Manufacturing layer: claim 8 and claim 9 define preparation constraints (entrapping with those product characteristics; remote loading method for anthracyclines).
- Therapeutic layer: claim 11 and claim 13 define dosing intent and in vivo outcome metrics (48h tumor localization; breast/colon carcinoma treatment).
Practical scope boundaries for R&D and licensing decisions
Avoiding infringement signals (based on literal claim elements)
- Using polymer types outside the listed group (not PEG, not PLA, not PGA, not PLA/PGA) could avoid the derivatized lipid polymer-genus limitation.
- Shifting outside the 0.07-0.12 micron size window could avoid the size limitation.
- Removing the “derivatized amphipathic vesicle-forming lipid” could avoid the core steric-stabilizer claim anchor.
- For anthracycline products, keeping entrapped fraction below ~80% or drug concentration at or below 50 μg/μmole lipid could reduce fit with claims 4-6, 7, 13-15.
- If remote loading across an ion/pH gradient is not used, claim 9 may be avoidable, but composition and localization claims could still be implicated.
Capturing maximal coverage in design
- Align polymer and lipid architecture to 1-20 mol% of the derivatized amphipathic lipid.
- Keep the mean diameter/average size within 0.07-0.12 μm.
- Demonstrate the comparative outcome: 24h blood lifetime “several times greater” vs an otherwise matched liposome lacking the derivatized lipid.
- For anthracycline products: maintain ≥80% entrapped and >50 μg/μmole lipid; match drug identity to doxorubicin/epirubicin/daunorubicin for the narrower claim subsets.
Key Takeaways
- The patent’s core scope is a sterically stabilized liposome formulation defined by (i) polymer-derivatized amphipathic lipid at 1-20 mol%, (ii) size 0.07-0.12 μm, and (iii) a comparative 24h blood lifetime improvement; payload must be liposome-entrapped.
- Anthracycline coverage tightens further to ≥80% entrapped and >50 μg/μmole lipid, and (in several dependents) restricts the drug to doxorubicin, epirubicin, or daunorubicin.
- The claim set also creates an enforcement path across composition, manufacturing, and in vivo tumor localization/treatment methods, with a key outcome timepoint at 48h tumor localization in claim 11 and an indication constraint in claim 13 (breast/colon carcinoma).
- A complete US patent landscape (other families, expiry map, citations, and claim overlap with contemporaneous PEG-liposome technologies) cannot be reliably produced from claim text alone without bibliographic access to the full patent file and adjacent US publications.
FAQs
1) Is the 24-hour blood lifetime requirement a literal limitation or an outcome statement?
It is written as a claim limitation: the liposomes are characterized by a “liposome blood lifetime, 24 hours after intravenous injection” that is several times greater than liposomes lacking the derivatized lipid.
2) Does the patent cover PEG only or other polymers too?
Claim 1 covers PEG and biodegradable polymer analogs (PLA, PGA, and PLA/PGA copolymers). Claim 7 is PEG-only.
3) What size range does the patent require?
Across independent claims the range is about 0.07 to 0.12 microns (mean diameter in claim 1; average size in claim 7).
4) For anthracyclines, what quantitative thresholds appear?
The claims require at least about 80% entrapped and a drug concentration greater than 50 μg per μmole liposome lipid (in the anthracycline-specific dependents and the anthracycline composition claim 7 and treatment claim 13).
5) Does the patent require remote loading for all methods?
No. Remote loading via ion or pH gradient appears in claim 9, which depends from the preparation framework of claim 8. Other claims cover entrapping without specifying remote loading.
References
[1] US Patent 5,213,804, claims 1-15 (provided in prompt).
