US Patent 5,536,729: Scope of Rapamycin + Surfactant/Ethanol/Phospholipid Solvent Compositions and Capsule Formulations
What does US 5,536,729 claim?
US 5,536,729 claims pharmaceutical compositions that solubilize or formulate rapamycin using a defined solvent system built from (i) a surfactant, (ii) a phospholipid solution with specified phospholipid weight fraction, and (iii) in dependent claim set 11-14, an ethanol co-solvent. The claims also extend into solid oral dosage forms via capsules.
The independent claim set is effectively two composition frameworks:
1) Solvent system with surfactant + phospholipid solution (no ethanol requirement)
- Claim 1: rapamycin + surfactant + phospholipid solution with phospholipid at 40-75 wt%
- Capsule coverage appears in claims 9 and 10.
2) Solvent system with surfactant + ethanol + phospholipid solution
- Claim 11: rapamycin + surfactant + absolute ethanol + phospholipid solution, including phospholipid at 40-75 wt%
- Claims 13 and 14 provide narrowed numeric exemplars.
Claim-by-claim scope (what is inside and what is excluded)
Independent claim: Claim 1 (surfactant + phospholipid solution)
Claim 1 requires, per 100 mL of composition:
- Rapamycin: 0.01 g to 5.0 g
- Surfactant: 0.05% to 10% by volume
- Phospholipid solution: 75% to 99.95% by volume
- Phospholipid concentration in that solution: 40% to 75% by weight
Key scope drivers
- The formulation is defined by volumetric percentages of the solvent system and weight fraction of phospholipid in that solvent solution.
- There is no ethanol requirement in claim 1. Any ethanol presence would be outside the strict “solvent system comprising” structure unless the ethanol is tolerated within the listed ranges without breaking the %-by-volume constraints.
Practical reading
- A product matches claim 1 if it uses a solvent system where the bulk is a phospholipid solution at 40-75 wt% phospholipid, with a minor surfactant fraction in 0.05-10 vol%, and rapamycin at 0.01-5 g per 100 mL.
Dependent claim: Claim 2 (lecithin as the phospholipid)
Claim 2 narrows claim 1 by specifying:
- The phospholipid solution is a lecithin solution.
Scope impact
- Claim 1 is open-ended regarding phospholipid source as long as it is within the 40-75 wt% phospholipid concentration range.
- Claim 2 is a subset: lecithin only.
Dependent claims: 3-8 (numerical subranges and fixed ratios)
These claims carve out specific compositions within the claim 1 framework.
Claim 3 (per 100 mL)
- Rapamycin: 0.03 g to 1.0 g
- Surfactant: 0.10 mL to 5 mL per 100 mL (equivalently 0.10% to 5% v/v if treated as volume)
- Phospholipid solution: 90 to 99.95 mL per 100 mL
- Phospholipid in solution: 40% to 70 wt%
Claim 4 (per 100 mL)
- Rapamycin: 0.03 g to 0.8 g
- Surfactant: 0.10 mL to 5 mL
- Phospholipid solution: 95 to 99.9 mL of a 50% phospholipid solution
Claim 5 (per 100 mL)
- Rapamycin: 0.05 g to 0.5 g
- Surfactant: 0.5 mL to 5 mL
- Phospholipid solution: 95 to 99.5 mL of a 50% phospholipid solution
Claim 6 (per 25 mL)
- Rapamycin: 0.025 g
- Surfactant: 0.270 g (note: mass specified for surfactant here, unlike earlier volume-based language)
- Phospholipid solution: q.s. to 25 mL of a 50% phospholipid solution
Claim 7 (per 25 mL)
- Rapamycin: 0.125 g
- Surfactant: 0.270 g
- Phospholipid solution: q.s. to 25 mL of 50% phospholipid solution
Claim 8 (per 100 mL)
- Rapamycin: 1.0 g
- Surfactant: 1.0 mL
- Phospholipid solution: q.s. to 100 mL of 50% phospholipid solution
Scope impact (how to use these in landscape analysis)
- Claims 4 and 5 lock the phospholipid solution to 50% phospholipid (wt%).
- Claims 6 and 7 introduce mass-based surfactant specification (0.270 g), which can materially affect infringement analysis if competitors specify surfactant in volume or in a different concentration.
- Claim 8 is a high-rapamycin-per-100 mL point (1.0 g) with a fixed surfactant volume (1.0 mL) and 50% phospholipid solution to q.s.
Dependent claims: 9-10 (capsule packaging of claim 1 composition)
Claim 9
- Composition of claim 1 in a pharmaceutically acceptable starch capsule.
Claim 10
- Composition of claim 1 in a pharmaceutically acceptable gelatin capsule.
Scope impact
- These claims cover the same formulation (as defined by claim 1) but framed inside specific capsule matrices.
- If a competitor uses the same solvent system but uses a different capsule type (e.g., HPMC), these claims do not directly cover.
Independent claim: Claim 11 (surfactant + absolute ethanol + phospholipid solution)
Claim 11 requires, per 100 mL composition:
- Rapamycin: 0.01 g to 5.0 g
- Surfactant: 0.05% to 10% by volume
- Absolute ethanol: 0.1% to 50% by volume
- Phospholipid solution: 40% to 99.85% by volume
- Phospholipid in solution: 40% to 75% by weight
Key scope drivers
- Ethanol is a required co-solvent within the claim 11 solvent system definition.
- The phospholipid solution volumetric range in claim 11 (40 to 99.85%) is broader than claim 1’s (75 to 99.95%), reflecting ethanol’s role in reducing the phospholipid fraction needed for solubilization.
Dependent claims: 12-14 (lecithin and specific numeric embodiments)
Claim 12
- Phospholipid solution is lecithin.
Claim 13 (per 100 mL)
- Rapamycin: 2.0 to 3.0 g
- Surfactant: 3% to 7.5% by volume
- Absolute ethanol: 5% to 20% by volume
- Phospholipid solution: 40% to 92% by volume
- Phospholipid content in solution: 40% to 60 wt%
Claim 14 (per 100 mL)
- Rapamycin: 2.5 g
- Surfactant: 5.0 mL
- Absolute ethanol: 12.67 mL
- Phospholipid solution: q.s. to 100 mL (given as 50% phospholipid solution by omission but aligned with claim 14’s numeric structure)
Scope impact
- Claim 13 is a concentrated rapamycin embodiment paired with relatively high surfactant and ethanol fractions, with phospholipid at 40-60 wt%.
- Claim 14 is a fixed point formulation useful for assessing direct copying or “near-identical” designs in filings that list explicit component volumes.
How broad is the claimed space? (quantitative coverage map)
Rapamycin load
Across claims 1 and 11 (independent frameworks):
- 0.01 g to 5.0 g per 100 mL
Within narrower embodiments:
- Claim 3: 0.03 to 1.0 g
- Claim 4: 0.03 to 0.8 g
- Claim 5: 0.05 to 0.5 g
- Claim 13: 2.0 to 3.0 g
- Claim 14: 2.5 g
Surfactant
- Independent claim 1: 0.05 to 10 vol%
- Independent claim 11: 0.05 to 10 vol%
- Claim 3: 0.10 to 5 mL per 100 mL
- Claim 13: 3 to 7.5 vol%
- Claims 6-7: surfactant specified as 0.270 g per 25 mL
Phospholipid solution concentration (wt%)
- Independent claim 1 and 11: 40% to 75 wt%
- Claim 3: 40% to 70 wt%
- Claim 13: 40% to 60 wt%
- Claims 4-5 and 6-8 (explicitly): 50% phospholipid solution
Ethanol (only in claim 11 framework)
- Claim 11: 0.1% to 50 vol%
- Claim 13: 5% to 20 vol%
Patent landscape implications: where competition tends to cluster
Without additional bibliographic metadata (publication number, priority date, family members, and related claims), only the scope logic of US 5,536,729 can be mapped. The landscape for rapamycin formulations typically clusters around:
1) Solubilization vehicles and their component definitions
- This patent fixes a three-part architecture: rapamycin + surfactant + phospholipid solution, with ethanol in the second independent claim set.
2) Concentration windows and “compositions comprising” drafting
- The numeric ranges are broad, particularly for rapamycin load (0.01-5.0 g per 100 mL) and ethanol (0.1-50%). Broad windows increase overlap risk for generic developers whose formulations use a phospholipid-based vehicle plus surfactant and often ethanol.
3) Phospholipid species constraints
- Claim 2 and 12 (lecithin) create an additional infringement hook for lecithin-based systems even if the general phospholipid could be broader.
4) Dosage packaging constraints (capsule type)
- Claims 9 and 10 narrow to starch or gelatin capsules. Competitors using different capsule shells can avoid those specific dependent claims, though they may still fall under broader composition claims if the claims are asserted.
Scope risk checklist for infringement screening
Use the following claim-structure logic to classify a candidate formulation quickly:
A. Does it meet the rapamycin loading window?
- Per 100 mL: 0.01 to 5.0 g (claim 1/11)
B. Does it use a solvent system that contains the required components?
- For claim 1: surfactant + phospholipid solution (no ethanol required)
- For claim 11: surfactant + absolute ethanol + phospholipid solution
C. Are the component ratios within the specified ranges?
- Surfactant: 0.05-10 vol%
- Phospholipid solution:
- Claim 1: 75-99.95 vol%
- Claim 11: 40-99.85 vol%
- Ethanol (claim 11 only): 0.1-50 vol%
- Phospholipid content within solution: 40-75 wt%
D. Is the phospholipid lecithin?
- If yes, claim 2 and 12 become relevant.
E. Is the product a starch or gelatin capsule formulation?
- If yes, claims 9 and 10 become relevant.
Key Takeaways
- US 5,536,729 claims two main formulation families: (i) rapamycin with surfactant and phospholipid solution and (ii) rapamycin with surfactant, absolute ethanol, and phospholipid solution.
- The most important numeric constraints are rapamycin load (0.01-5.0 g/100 mL), surfactant (0.05-10 vol%), phospholipid content in the phospholipid solution (40-75 wt%), and in the ethanol family the ethanol window (0.1-50 vol%).
- Lecithin and capsule shell dependencies (claims 2, 12, 9, 10) create additional infringement hooks when products use those specific materials.
- Specific embodiment claims (4-8 and 13-14) are useful for identifying “copy-close” formulations using 50% phospholipid solution and defined rapamycin and solvent amounts.
FAQs
1) What is the core formulation technology covered?
Rapamycin formulated in a defined solvent system containing surfactant and a phospholipid solution with specified phospholipid weight fraction. A second family also requires absolute ethanol.
2) Does the patent require ethanol in all claims?
No. Ethanol is required only in claim 11 and its dependent claim set (11-14), not in claim 1 and its dependent claims (1-10).
3) How does phospholipid concentration get defined?
By weight percent within the phospholipid solution: typically 40% to 75 wt%, with narrower limits in some dependent claims (e.g., 40-70 wt% and 40-60 wt%).
4) What capsule types are specifically claimed?
A composition of claim 1 in either a starch capsule (claim 9) or a gelatin capsule (claim 10).
5) Which claim windows are likely easiest to design around?
Design-around options are primarily through moving outside the phospholipid solution volumetric fraction and/or phospholipid wt%, or removing absolute ethanol where claim 11 is asserted, or using capsule shells other than starch/gelatin where those dependent claims are targeted.
References
[1] United States Patent 5,536,729 (claims as provided in prompt).
