Details for Patent: 10,456,360

Which drugs does patent 10,456,360 protect, and when does it expire?

Patent 10,456,360 protects ONIVYDE and is included in one NDA.

This patent has thirty-nine patent family members in nineteen countries.

Summary for Patent: 10,456,360

Title:	Stabilizing camptothecin pharmaceutical compositions
Abstract:	Irinotecan phospholipid liposomes with improved storage stability are provided, with related methods of treatment and manufacture. The irinotecan liposomes can have reduced formation of lyso-phosphatidylcholine (lyso-PC) during storage, and prior to administration to a patient.
Inventor(s):	Daryl C. Drummond, Dmitri B. Kirpotin, Mark Eamon Hayes, Charles Noble, Kevin Kesper, Antoine M. Awad, Douglas J. Moore, Andrew J. O'brien
Assignee:	Ipsen Biopharm Ltd
Application Number:	US15/768,352
Patent Claim Types: see list of patent claims	Use; Composition; Process; Dosage form;

Executive summary US Drug Patent 10,456,360 claims a tightly defined, storage-stabilized liposomal irinotecan formulated with irinotecan sucrose octasulfate (SOS) encapsulated in liposomes made from DSPC + cholesterol + MPEG-terminated DSPE and stabilized to limit lyso-phosphatidylcholine (lyso-PC) generation during refrigerated storage (2–8°C) while also requiring specific encapsulation performance (encapsulation fraction and time/temperature durability) and process controls (loading via above-phospholipid transition temperature contact, plus pH adjustment to 7.25–7.50). The independent claim is effectively a “composition + manufacturing method” tethered to a defined formulation architecture and multiple quantitative performance gates (lyso-PC <20 mol% at early storage; low lyso-PC at 9–12 months; ≥98% encapsulated after 6 months; controlled particle size ~110 nm; buffer and ionic strength windows; defined SOS sulfate concentration 0.4–0.5 M and optional tighter 0.45–0.48 M). Downstream claims narrow further to specific size measurement methods, unilamellarity, exact drug loading, and the specific ammonium SOS counterion embodiments (triethylammonium or diethylammonium) with ppm-level constraints on residual counterions.

H1: US Patent 10,456,360 scope and claim-by-claim patent landscape for storage-stabilized liposomal irinotecan (SOS, DSPC/cholesterol/MPEG-DSPE, lyso-PC control, pH 7.25–7.50)

What does US 10,456,360 actually claim: a composition with process and performance limitations?

The claim set is structured so that infringement is not limited to “liposomal irinotecan with PEG-lipids,” but requires meeting a combination of structural features, stability outcomes, and manufacturing/process parameters.

Independent claim 1: core scope elements (all required)

A. Drug form / cargo identity

• Encapsulated cargo is irinotecan sucrose octasulfate (SOS), i.e., a substituted ammonium salt of SOS (counterion selected later in dependent claims).
• SOS sulfate concentration in the loading step (step (a)) is 0.4 to 0.5 M.

B. Liposome composition architecture

• Liposomes comprise:
  • DSPC
  • cholesterol
  • methoxy-terminated polyethylene glycol-distearoylphosphatidyl ethanolamine
• In particular, the formulation requires a weight ratio corresponding to:
  • 500 g ± 10% by weight irinotecan moiety per mol total phospholipids.
• A storage stabilization requirement constrains degradation:
  • during first 6 months at 2–8°C, lyso-PC is < 20 mol% (relative to total phospholipids).

C. Manufacturing process steps are embedded into the claim

• (a) Form DSPC/cholesterol/MPEG-DSPE liposomes and encapsulate a substituted ammonium salt of SOS with 0.4–0.5 M sulfate.
• (b) Contact liposomes with an irinotecan solution at a temperature above the transition temperature of the phospholipids, forming liposomes encapsulating the SOS salt inside.
• (c) Obtain storage stabilized composition by adjusting pH of the step-(b) preparation to 7.25–7.50.

D. Performance outcomes baked into the claim Dependent claims include hard performance thresholds, and the independent claim includes the early stability gate (lyso-PC threshold at 0–6 months).

Practical reading for scope US 10,456,360 functions as an IP barrier against:

• “Generic” liposomal irinotecan that uses different lipid systems (non-DSPC, non-cholesterol, non-MPEG-DSPE), different internal salts/counterions, different pH windows, or different loading regimes that fail the lyso-PC suppression metric.
• Products that match the high-level concept (liposomal irinotecan + PEG + DSPC) but do not meet the specific stabilization mechanism outcome tied to lyso-PC generation and the pH/loading constraints.

Which claim limitations are the “hard gates” versus “easy substitutes”?

The independent claim is broad in concept but narrow in execution: multiple quantitative requirements make “design-around” difficult without altering the stabilization profile or the internal sulfate chemistry.

Hard gates (high design-around cost)

1. DSPC/cholesterol/MPEG-DSPE scaffold (and implicit functional role of the phospholipid transition behavior in step (b)).
2. Loading chemistry requiring encapsulation of SOS with 0.4–0.5 M sulfate in step (a), and then irinotecan-contact above the phospholipid transition temperature.
3. pH adjustment to 7.25–7.50 after loading.
4. Early stability: lyso-PC during first 6 months at 2–8°C must be <20 mol% (relative to total phospholipids).
5. Downstream dependent thresholds include:
   • <1 mg/mL lyso-PC after 6 months (claim 16)
   • <20 mol% lyso-PC after 9–12 months (claim 5)
   • ≥98% encapsulated after 6 months (claim 6)
   • Particle size window and measurement method (claims 2, 10, 27–29)

Easier substitutes (if you can avoid claim coverage)

• Specific buffer identity (HEPES) and concentration window (claim 7) and sodium chloride (claim 8) are dependent and can be changed if you aim to avoid those narrower claims.
• Specific unilamellar vs not (claims 3, 11, 14, 26, plus unilamellar tie-ins).
• Exact irinotecan equivalent concentration 4.3 mg/mL (claim 4) if you keep other elements.
• Tight counterion controls (triethylammonium / diethylammonium) and residual counterion ppm constraints are dependent (claims 17–20) and may be avoidable if the salt identity differs while still meeting the core SOS encapsulation requirement in claim 1.

How do the dependent claims narrow the formulation: lyso-PC, particle size, encapsulation, and buffer/ionic strength?

What is claimed about storage stability via lyso-PC formation?

• Claim 1: <20 mol% lyso-PC vs total phospholipids during the first 6 months at 2–8°C.
• Claim 5: <20 mol% lyso-PC after 9–12 months at 2–8°C.
• Claim 16: <1 mg/mL lyso-PC after 6 months at 2–8°C. These three claims create layered stability coverage: both relative molar measure and absolute mg/mL measure at different timepoints.

What is claimed about encapsulation efficiency?

• Claim 6: ≥98% of irinotecan encapsulated within liposomes after 6 months at 2–8°C.

What is claimed about particle size and how it must be measured?

• Claim 2: 110 nm ±20% volume-weighted mean size; method is DLS cumulants.
• Claim 10: 95–115 nm by quasi-elastic light scattering.
• Claims 27, 28, 29: size determined by cumulants method for the specific size-dependent claim groupings.
• Claim 13: pH ~7.25 with size about 110 nm and quasi-elastic light scattering.
• Claims 2/10/13/20 tie size ranges to other formulation variables (pH, counterion ppm).

What is claimed about liposome lamellarity?

• Claim 3: unilamellar liposomes (depending on claim 2).
• Claim 11: unilamellar liposomes (depending on claim 10).
• Claim 14 and 26: unilamellar variants for other claim groupings.

What is claimed about buffer and salts?

• Claim 7: HEPES aqueous buffer at 2–20 mM.
• Claim 8: NaCl 130–160 mM.
• Claim 12: explicit composition amounts:
  • 6.81 mg DSPC/mL
  • 2.22 mg cholesterol/mL
  • 0.12 mg MPEG-2000-DSPE/mL
  • 4.05 mg/mL HEPES buffer
  • 8.42 mg sodium chloride/mL

These dependencies matter because a product can mimic structural lipids and cargo but still fail these dependent claim windows, potentially escaping those narrower claims.

When does the claimed formulation “lose exclusivity”: patent expiration and key timing issues?

US 10,456,360 is a US patent and would generally expire 20 years from its earliest non-provisional effective filing date, subject to possible patent term adjustment or extension. Without the priority/filing history, no exact expiration date can be stated from the claim text alone. The exclusivity timeline is therefore not fully computable from the information provided.

What patents protect SOS-liposomal irinotecan in the US: how does claim coverage map to other likely patent types?

Within the claim architecture of US 10,456,360, the landscape is best understood as overlapping patent categories:

1) Composition-of-matter (formulation identity)

Protected items implied by claim 1:

• SOS-irinotecan salt in liposomes
• DSPC/cholesterol/PEG-lipid architecture
• specific internal sulfate concentration during preparation
• stabilization outcome measured via lyso-PC formation
• pH window for storage stabilized state

2) Process-by-step limitations (method constraints as infringement hooks)

Because claim 1 includes steps (a)–(c), a competitor’s process can matter:

• Using DSPC transition temperature-based loading and controlling the internal sulfate salt concentration.
• pH adjusting the loaded dispersion to 7.25–7.50.

3) Secondary method outcomes (particle size and encapsulation performance)

Dependent claims create additional infringement entry points where manufacturers often document specs:

• DLS cumulants size distribution
• quasi-elastic light scattering values
• encapsulation fraction after aging
• lyso-PC levels quantified at defined aging intervals.

How broad is infringement risk: would a “close” liposomal irinotecan infringe?

A close generic or follow-on must clear all limitations tied to claim 1 for independent claim coverage. The most common failure points for “close” products would be:

• Different phospholipid (using HSPC or DOPC instead of DSPC)
• Different PEG-lipid (non-MPEG-terminated DSPE or non-ethanolamine PEG-lipid)
• Different loading salt identity or sulfate concentration (not 0.4–0.5 M sulfate in the internal SOS salt step)
• Different pH adjustment (outside 7.25–7.50)
• Lyso-PC stabilization failure (greater than 20 mol% during first 6 months at 2–8°C)

Even if a competitor hits liposome composition and SOS identity, failing the lyso-PC control would likely avoid at least the independent claim and any dependent claims tied to stability specs.

What design-arounds are most plausible given the claim structure?

Based on the claim set alone, the strongest design-around levers are:

1. Avoid the lyso-PC threshold by changing lipid oxidation/hydrolysis dynamics (but then risk triggering other claims depending on which stability metric is met).
2. Move pH outside 7.25–7.50 (while still keeping the product stable and acceptable).
3. Alter the internal SOS salt prep to avoid the sulfate concentration window 0.4–0.5 M.
4. Switch away from DSPC to a different phospholipid with a different transition behavior, undermining the “above transition temperature” loading requirement tied to the DSPC system.
5. Change the PEG-lipid architecture (not MPEG-terminated DSPE or different PEG chain class, which could remove literal coverage of the required methoxy-terminated PEG-distearoylphosphatidyl ethanolamine).

Counterion changes (triethylammonium/diethylammonium) are narrower dependent levers and do not, on their own, remove claim 1 coverage because claim 1 already requires a “substituted ammonium salt of SOS” without limiting counterion identity.

How many distinct invention “threads” are embedded in the claims?

US 10,456,360 contains multiple claim threads that can exist as separate inventive contributions:

1. SOS salt encapsulation concept for liposomal irinotecan.
2. DSPC/cholesterol/MPEG-DSPE formulation with a specific lipid ratio tied to irinotecan moiety loading.
3. Shelf-life stabilization by limiting lyso-PC formation at defined storage conditions.
4. A combined loading method using temperature above phospholipid transition temperature.
5. A post-loading pH adjustment window (7.25–7.50).
6. Analytical/quality gates: particle size by specific scattering method, encapsulation rate after aging, and lyso-PC quantification thresholds.

What “claim chart” mapping would look like (infringement checklist)

A practical infringement checklist for claim 1 would require the target product/process to show:

• Cargo: irinotecan SOS (as substituted ammonium salt) encapsulated in liposomes.
• Internal sulfate concentration: SOS salt prepared with 0.4–0.5 M sulfate in step (a).
• Lipid composition: DSPC + cholesterol + methoxy-terminated MPEG-DSPE (with the specified ratio corresponding to 500 g ±10% irinotecan moiety per mol total phospholipids).
• Manufacturing temperature/time: loading step occurs at temperature above phospholipid transition temperature.
• pH: final composition has pH 7.25–7.50.
• Stability: lyso-PC remains <20 mol% vs total phospholipids over first 6 months at 2–8°C.

If any of these elements cannot be met, claim 1 literal infringement risk decreases sharply. Dependent claims then add further tight constraints (size distribution, unilamellarity, buffer composition, exact drug concentration, counterion ppm, etc.).

Key Takeaways

• US 10,456,360 is centered on storage-stabilized liposomal irinotecan using irinotecan sucrose octasulfate (SOS) cargo in DSPC/cholesterol/MPEG-DSPE liposomes, with explicit stabilization performance via lyso-PC suppression during 2–8°C storage.
• Claim 1 is not just a composition-of-matter; it also requires process steps (temperature above transition temperature loading and pH adjustment to 7.25–7.50) and a defined internal SOS sulfate concentration (0.4–0.5 M).
• Dependent claims add measurable product specs that become infringement “targets” for quality dossiers: particle size (~110 nm by specific methods), ≥98% encapsulation after aging, unilamellarity, HEPES/NaCl windows, and counterion residual control (triethylammonium/diethylammonium ppm).
• For a competitor, the most credible design-around levers implied by the claims are pH outside 7.25–7.50, non-DSPC or non-matching PEG-lipid architecture, altered internal sulfate concentration, and failure to meet the lyso-PC suppression gate.

FAQs

1) Does US 10,456,360 cover any liposomal irinotecan with PEG and DSPC?
No. Coverage requires SOS cargo with specific internal preparation parameters and a pH adjustment to 7.25–7.50, plus lyso-PC suppression during refrigerated storage.

2) What is the most important stability metric in the claims?
lyso-phosphatidylcholine (lyso-PC), constrained to <20 mol% (and in a dependent claim, <1 mg/mL) under defined storage conditions.

3) Are process parameters required for infringement under claim 1?
Yes. Claim 1 includes manufacturing steps (encapsulation of the SOS salt with specified sulfate concentration; contacting above phospholipid transition temperature; pH adjustment).

4) What particle size range does the patent tie to the claimed formulation?
About 110 nm ±20% (DLS cumulants) and, in another dependent claim, 95–115 nm by quasi-elastic light scattering, with measurement-method dependent language.

5) Do the triethylammonium/diethylammonium limitations apply to claim 1?
They appear only in dependent claims (claims 17–20). Claim 1 requires a substituted ammonium SOS salt but does not, in the independent claim, restrict to triethylammonium or diethylammonium.

References

1. US Patent 10,456,360 (claims provided in prompt).

Drugs Protected by US Patent 10,456,360

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ipsen	ONIVYDE	irinotecan hydrochloride	INJECTABLE, LIPOSOMAL;INTRAVENOUS	207793-001	Oct 22, 2015		RX	Yes	Yes	10,456,360		Y

Foreign Priority and PCT Information for Patent: 10,456,360

PCT Information
PCT Filed	October 15, 2016	PCT Application Number:	PCT/US2016/057247
PCT Publication Date:	April 20, 2017	PCT Publication Number:	WO2017/066726

International Family Members for US Patent 10,456,360

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016340153
Australia	2022203167
Brazil	112018006922