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Patent landscape, scope, and claims: |
US Patent 10,335,366: Risperidone/Paliperidone PLGA-DMSO Injectable for In Situ Biodegradable Implant
What is the invention scope in US 10,335,366?
US Patent 10,335,366 claims injectable drug-polymer-solvent compositions that form, in situ, a biodegradable implant in the body. The claimed system is built around three tightly constrained technical pillars:
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Drug identity and loading
- Risperidone and/or paliperidone (including salts), “about 13% wt of drug” in the base composition (claim sets 1, 12, 22, 31, 42-style dependent branches).
- Alternate dependent variants specify composition composition for drug weight fraction via polymer fraction or polymer-plus-drug fraction constructs (claims 12 and its chain; also claims 22 and 31).
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Solvent and polymer system
- Solvent: DMSO at a defined mass ratio to drug.
- Polymer: biocompatible PLGA (poly(lactide-co-glycolide)) with:
- Lactic:glycolic monomer ratio ~50:50 (and a narrow tolerance range in dependent claims).
- inherent viscosity range (for the PLGA grade) or molecular weight range (another dependent branch).
- Optional polymer processing: irradiated PLGA via beta-radiation (claims include “irradiated with beta-radiation,” plus end-capped polymer in multiple dependent claims).
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Performance and particulate controls
- A defined particle size distribution of the drug (laser diffraction or similar), using d0.1/d0.5/d0.9 plus volume fraction caps at specific micron cutoffs.
- Release window constraints in aqueous environment at 24 hours:
- “no more than 20% wt of its charge of the drug” released within 24 hours.
- “at least 0.1% wt” released within 24 hours.
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Kit architecture
- A two-container kit for in situ formation:
- drug + polymer in a first container
- solvent in a second separate container
- At least one container is a syringe, vial, or cartridge.
The independent anchor is claim 1 (and the related claim set beginning at 12 and continuing with additional dependent claims), which jointly define a narrow formulation space. The claim set is drafted to withstand “design around” by narrowing multiple parameters simultaneously: drug wt %, polymer grade attributes (ratio + intrinsic viscosity or molecular weight), irradiation/end-capping, drug particle distribution, DMSO:drug ratio, polymer solution to drug ratio, and release limits.
What do the core claim elements lock down?
Below are the specific quantitative constraints that define the practical formulation boundary for infringement risk.
Drug and loading
- Drug identity: risperidone and/or paliperidone (and salts), any combination.
- Drug loading baseline:
- Claim 1: “about 13% wt of drug”
- Claim 12: “about 13% wt of drug” plus a defined drug-to-polymer fraction “mass ratio of drug to (polymer+drug) is about 33%.”
- Claim 22 and Claim 31: variants that specify polymer wt range or molecular weight.
Polymer grade: monomer ratio and molecular characterization
- Monomer ratio: about 50:50 (claim 1) with a narrow tolerance later:
- “monomer ratio ... ranges from 48:52 to 52:48” (claims 11, 21, 30).
- Polymer molecular characterization:
- Claim 1: inherent viscosity 0.25–0.30 dl/g (GPC in THF at 30°C, 1 mL/min).
- Claim 12 chain: inherent viscosity 0.26–0.29 dl/g.
- Claim 31 chain: molecular weight 28–43 kDa, with dependent 30–36 kDa.
- End-capping: “copolymer is end-capped” (claim 9, plus claim 19 and claim 39’s claim chain points).
Solvent and mixing ratios (highly specific)
- Claim 1:
- Mass ratio polymeric solution to drug: about 6.5:1 to about 7:1
- Mass ratio DMSO to drug: about 4:1 to about 5:1
- Claim 12:
- drug-to-(polymer+drug) mass fraction: about 33%
- DMSO:drug about 4.66:1 (a tighter single-number dependent narrowing)
Drug particle size distribution (volume fraction + d-values)
The claims include multiple alternative particle size distribution definitions, each expressed through combinations of:
- d0.1, d0.5, d0.9 (microns) and/or
- volume fraction cutoffs (<10 µm, 1–10 µm, >225 µm, etc.), each capped at no more than 10% of total volume in those bins.
Examples of the explicit structure in claim 10 (selected forms):
- Option (a):
- ≤10% volume <10 µm
- ≤10% volume >225 µm
- Option (b):
- ≤10% volume 1–10 µm
- ≤10% volume >225–400 µm (as written)
- d0.5 about 40–200 µm
- Option (c) (volume expression):
- d0.9 about 150–400 µm
- d0.5 about 40–200 µm
- d0.1 about 10–60 µm
- Option (d/e/f): extends with additional caps into 0.1–10 µm and upper tail 225–1000 µm or 225–700 µm, and corresponding d0.5 windows.
Claim 5 and claim 18/29/39-style branches include named distributions:
- Distribution values (examples provided in the claim text):
- d0.1 (µm): 27.49 (Dist. I), 17.41 (Dist. III), “≤10” (Dist. V)
- d0.5 (µm): 79.90 (Dist. I), 51.61 (Dist. III), “40–130” (Dist. V)
- d0.9 (µm): 176.66 (Dist. I), 175.32 (Dist. III), “>225” (Dist. V)
This makes the claim scope formulation-process-sensitive: even if composition ratios match, differing drug milling or supplier PSD can fall outside the claim’s PSD options.
Release limits in aqueous environment at 24 hours
- “no more than 20% wt released within 24 hours”
- “at least 0.1% wt released within 24 hours”
These are a dual-sided constraint (upper and lower bound), limiting both overly slow and overly fast early release.
What does the kit claim broaden, and what does it still restrict?
The kit claims (claims 2, 3, 17, 27, etc.) add an administration/packaging dimension:
- “pharmaceutical kit suitable for in situ formation of a biodegradable implant”
- prior to mixing:
- drug + biocompatible copolymer in a first container
- solvent (DMSO) in a second separate container
- container types: at least one is a syringe, vial, or cartridge (claim 3)
The kit does not remove the formulation constraints. It imports the composition of the formulation claim into the kit structure.
How narrow is the claim space? (Claim-by-parameter boundary map)
The claim set is structured like a matrix: multiple independent formulation constraints stack together, leaving little “slack” for substitutes.
Boundary map (key parameters)
| Parameter |
Claimed values in core sets |
Practical effect |
| Drug |
Risperidone and/or paliperidone; salts allowed |
Blocks other antipsychotics |
| Drug loading |
“about 13% wt” |
Narrows concentration range |
| DMSO:drug |
~4:1 to ~5:1 (claim 1); ~4.66:1 (claim 12 set) |
Blocks solvent ratio shifts |
| Polymer:drug (via polymeric solution) |
~6.5:1 to ~7:1 |
Blocks polymer concentration shifts |
| PLGA monomer ratio |
~50:50 (and 48:52 to 52:48) |
Blocks PLGA grades with different composition |
| PLGA grade characterization |
inherent viscosity 0.25–0.30 dl/g (claim 1); 0.26–0.29 dl/g (claim 12 set) OR MW 28–43 kDa (claim 31 set) |
Blocks alternative PLGA MW/viscosity families |
| Irradiation |
beta-radiation (optional dependent) |
Creates an additional “process” limitation when used in dependent claims |
| End-capping |
“end-capped” (dependent) |
Adds another differentiator for design-around |
| PSD of drug |
multiple bounded options with d0.1/d0.5/d0.9 and volume caps |
Strongly process-dependent; risk shifts with milling/particle engineering |
| Release at 24h |
0.1% ≤ release ≤ 20% |
Eliminates too-fast and too-slow initial release profiles |
| Kit structure |
two-container separate solvent |
Packaging design can avoid kit claims if chemistry also differs |
Patent landscape: how 10,335,366 is likely positioned against surrounding IP
The claim structure indicates a strategy aimed at a common competitive threat: generic or follow-on manufacturers attempting to use known depots/in situ implants for these antipsychotics with different PLGA grades, different solvents, different particle size profiles, or different early-release kinetics.
Most likely “reference” technology buckets it overlaps
Even without importing external document numbers, the scope of claim elements maps to three industry IP clusters:
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In situ forming depots (ISFDs) using polymer + solvent systems
- The two-container kit concept and polymer dissolution in DMSO point to ISFD-type administration for biodegradable implant formation.
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PLGA grade-specific biodegradable depot technology
- Monomer ratio and inherent viscosity or MW windows are typical of formulation IP boundaries used to differentiate polymer chemistry and quality.
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Drug particle size engineering for controlled release
- PSD constraints suggest the patent’s differentiator is not only composition but also how drug particles disperse and affect release.
Why the PSD and release limits matter strategically
- A rival composition that matches the broad “DMSO + PLGA + risperidone/paliperidone” concept still may fall outside infringement if:
- its drug PSD does not meet one of the claim-defined options, and/or
- its 24-hour aqueous release is outside the 0.1% to 20% band.
- This is a stronger restriction than many formulation patents that rely mainly on ratio ranges and polymer type.
Design-around levers available to competitors (and how claims respond)
The claim drafting suggests the patent expects design-around attempts and responds with layered constraints:
- Changing PLGA:
- if monomer ratio deviates from ~50:50, claim 1 and its chain narrow out.
- if inherent viscosity or MW deviates, dependent chains narrow out.
- Changing solvent ratio:
- DMSO:drug is bounded tightly.
- Changing drug milling/particle processing:
- PSD options and d-value requirements create a process-dependent barrier.
- Changing early release kinetics:
- release window constrains microstructure/solvent evaporation or diffusion profiles.
- Packaging:
- kit claims are limited to separate solvent container plus drug/polymer container. A product that mixes before delivery may avoid kit-format claims, but would still need to match composition claim elements.
Practical claim-scope risk assessment for product developers
A product is most at risk if it matches simultaneously:
- risperidone and/or paliperidone,
- “about 13% wt” drug loading,
- DMSO and PLGA with ~50:50 monomer ratio and specified viscosity/MW,
- DMSO:drug and polymeric solution:drug mass ratios within the stated bands,
- drug PSD meeting one of the enumerated volume fraction and d-value configurations, and
- 24-hour release within the 0.1% to 20% band.
If any one of these major axes misses, claim coverage drops quickly because multiple limitations are stacked in the same independent claim families.
Claim-by-claim scoping notes (what each major dependency adds)
- Claim 2 / 17 / 27: kit separation structure (two containers).
- Claim 3: syringe/vial/cartridge container types.
- Claim 4 / 13 / 23 / 33: PLGA beta-irradiated.
- Claim 5 / 18 / 29 / 39: provides explicit PSD “Dist. I/III/V” d-values with hard numeric anchors.
- Claims 6-7 / 14-15 / 24-25 / 34-35 / 44-45-style: release within the 24-hour aqueous environment band.
- Claim 8 / 16 / 26 / 36: “≤20% wt of the drug is dissolved” in the DMSO or polymeric solution.
- Claim 9 / 19: end-capped copolymer.
- Claims 10 / 20 / 28 / 38: multiple PSD alternative options (a-f).
- Claims 11 / 21 / 30: lactic:glycolic ratio tolerance range 48:52 to 52:48.
- Claim 22: PLGA wt range (25–27% wt) plus DMSO:drug about 4:1 to 5:1.
- Claim 31-32: MW range (28–43 kDa; dependent 30–36 kDa).
- Claim 31: also adds DMSO:drug constraint and requires the MW-defined PLGA grade.
Key Takeaways
- US 10,335,366 claims a tightly defined ISFD-like injectable combining risperidone/paliperidone, DMSO, and specific PLGA grades to generate a biodegradable implant in situ.
- The claim scope is constrained on six independent axes: drug wt loading, DMSO:drug ratio, polymer concentration proxy (polymeric solution:drug), PLGA chemistry (lactic:glycolic ~50:50) plus inherent viscosity or MW, drug PSD, and 24-hour aqueous release bounded to 0.1% to 20% wt.
- PSD and release limits materially increase non-obviousness barriers for generic/formulation substitutes because they depend on both drug particle processing and the resulting release kinetics.
- Kit claims add packaging constraints (two-container separate solvent), but they import the composition constraints into the kit.
FAQs
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What drug is covered by US 10,335,366?
Risperidone and/or paliperidone, including pharmaceutically acceptable salts in any combination.
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What is the solvent system?
DMSO, with DMSO:drug mass ratio constrained (about 4:1 to 5:1 in claim 1; about 4.66:1 in the claim 12 chain).
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Which PLGA attributes matter most for infringement risk?
Lactic:glycolic monomer ratio (~50:50; tolerance 48:52 to 52:48), plus either inherent viscosity window (0.25–0.30 dl/g or 0.26–0.29 dl/g) or molecular weight window (28–43 kDa; dependent 30–36 kDa).
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Does the patent require drug particle size engineering?
Yes. Claims enumerate multiple PSD options using volume fraction caps and d0.1/d0.5/d0.9 constraints, plus example “Dist.” datasets.
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What release kinetics constraints are imposed?
In aqueous environment at 24 hours, release is constrained to no more than 20% wt and at least 0.1% wt of the drug charge.
References
[1] United States Patent 10,335,366. (Claims as provided in user prompt text).
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