Details for Patent: 6,869,939

Summary for Patent: 6,869,939

Title:	Formulations containing amiodarone and sulfoalkyl ether cyclodextrin
Abstract:	The present invention provides aqueous parenteral formulations containing an antiarrhythmic agent, such as amiodarone, and a sulfoalkyl ether cyclodextrin. The liquid formulations are clear, sterilizable, and chemically and physically stable. The liquid formulations do not require a surfactant and do not precipitate upon dilution with distilled water or other pharmaceutically acceptable liquid carrier. The sulfoalkyl ether cyclodextrin-containing formulation provides significant advantages over other cyclodextrin-containing formulations of amiodarone. The formulation can be prepared in acidic, neutral and slightly basic medium while providing acceptable concentrations of amiodarone suitable for parenteral administration. An SAE-CD-containing formulation of amiodarone can be provided in liquid form or as a reconstitutable powder. Moreover, highly concentrated solutions exceeding 200 mg of amiodarone per mL can be prepared. Solutions can be made either dilutable or non-dilutable with water at room temperature or under conditions typically encountered in the clinic.
Inventor(s):	Gerold L. Mosher, Karen T. Johnson, Atef A. Gayed
Assignee:	Cydex Pharmaceuticals Inc
Application Number:	US10/139,620
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 6,869,939
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

US Patent 6,869,939 (Amiodarone + Sulfoalkyl Ether Cyclodextrin) Claim Scope, Patent Landscape, and Exclusivity Risk

US Drug Patent 6,869,939 claims a set of water-dilutable clear liquid amiodarone formulations where solubilization is driven by a specific sulfoalkyl ether cyclodextrin (SAE-CD) chemistry and tight compositional/physicochemical constraints. The core legal hook is the SAE-CD structure (Formula 1 with n = 4–6 and sulfoalkyl ether substitutions), defined SAE-CD-to-amiodarone molar ratios, “no surfactant/solvent/soap/detergent” dilution behavior, pH relative to amiodarone pKa, and clarity without precipitation at ambient temperature. Dependent claim tiers also introduce surface tension and tonicity windows, plus heating/sterile ready-to-inject manufacturing and product-state limits, and a narrower SBE7-β-CD concentrate/RTI subset.

The patent landscape is best read as a formulation-and-process IP moat around an IV-compatible amiodarone solvent system intended to avoid Cremophor/ethanol-type vehicles by using sulfonated cyclodextrin complexes. From a freedom-to-operate perspective, the claim set is broad on “clear, water dilutable liquid + SAE-CD chemistry” but narrower on ratio bands, DS values, pH relationship to pKa, and specific clarity mechanisms tied to heating and/or concentration/product state.

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What is the scope of US Patent 6,869,939 claims for water-dilutable clear amiodarone SAE-CD formulations?

Immediate claim theme: clear, dilutable liquid amiodarone compositions using SAE-CD defined by Formula 1 and molar ratio constraints, achieving ambient water dilution without precipitation and without surfactant, organic solvent, soap or detergent.

Independent claim 1: What is protected?

Claim 1 covers:

1. Composition type: “water dilutable clear liquid formulation”
2. Actives: amiodarone + SAE-CD
3. Ratio requirement: SAE-CD:amiodarone ≥ 1.1 ± 0.01 (molar)
4. Dilution behavior at ambient temperature:
   • water dilution produces no significant precipitation of amiodarone
   • no need for surfactant, organic solvent, soap or detergent
5. SAE-CD structural definition (Formula 1):
   • n is 5 or 6
   • each of R1–R9 is independently —O— or —O—(C2–C6 alkylene)–SO3−
   • at least one of R1 and R2 is independently —O—(C2–C6 alkylene)–SO3−
   • each of S1–S9 is independently a pharmaceutically acceptable cation
   • DS-like constraint appears in dependent claims (e.g., “average degree of substitution about 4 or 7”)

This is the cleanest “core” claim. It does not require sterile ready-to-inject status, specific tonicity, or surface tension, but it does require the ratio band and the ambient-temperature no-precipitation behavior, plus the no-surfactant/no-solvent/no-detergent limitation.

Independent claim 11: What is a narrower operational band?

Claim 11 is also a water-dilutable clear liquid formulation but adds explicit numeric limits:

• SAE-CD:amiodarone ≥ 1.1 ± 0.01
• dilution with water at ambient temperature yields no significant precipitation and no need for surfactant/solvent/soap/detergent
• amiodarone ≤ about 3 mg/mL
• SAE-CD ≤ about 4.5 mM
• pH approximates or is ≤ amiodarone pKa
• SAE-CD defined by Formula 1 with n = 5 or 6 and the same substitution rule

This claim is more “physically constrained” than claim 1. It reads like a preferred low-concentration embodiment.

Independent claim 15: What is the high concentration RT dilution/clear system?

Claim 15 shifts to higher concentration boundaries:

• SAE-CD:amiodarone ≥ 1.1 ± 0.01
• ambient dilution behavior and no-surfactant/no-solvent/no-detergent limitation persist
• amiodarone ≥ 50 mM
• SAE-CD ≥ 55 mM
• pH ≤/approximates amiodarone pKa
• SAE-CD Formula 1 with n = 5 or 6

Legally, claim 15 carves out a concentrated complex intended to dilute cleanly, but it tightens the composition to high molar regimes.

Independent claim 17: What is the heating-rendered “clear” formulation with lower ratio?

Claim 17 covers a clear liquid formulation where:

• SAE-CD:amiodarone ≤ 1.09 ± 0.01 and ≥ 0.3
• pH ≤/approximates pKa
• liquid has been exposed to temperature ≥ 45°C, “thereby rendering the liquid clear”
• SAE-CD Formula 1:
  • n = 4, 5, or 6
  • substitution rule identical
  • at least one of R1 and R2 is sulfoalkyl ether substituted

This claim is structurally important because it expands n from 5–6 to 4–6, and it introduces a process/product-state linkage (heating to ≥45°C to render clarity). It also relaxes the ratio floor down to 0.3.

Independent claim 19: SBE7-β-CD concentrate, dilutable at 20–30°C

Claim 19 narrows to a specific cyclodextrin identity:

• clear water-dilutable concentrated aqueous liquid
• SBE7-β-CD and amiodarone
• amiodarone > 2 mg/mL
• SBE7-β-CD:amiodarone ≥ 1.1 ± 0.01
• dilution with water at 20–30°C yields clear diluted formulation

This is a “specific species within the genus” style claim that can function as a narrower, enforceable target even if the genus chemistry is contested.

Independent claim 20: ready-to-inject sterile liquid

Claim 20 is explicit about sterility and dosing window:

• clear ready-to-inject sterile liquid
• SBE7-β-CD + amiodarone
• SBE7-β-CD ≥ 0.3% wt
• amiodarone 1–2 mg/mL

Independent claim 22–23: RTI sterile aqueous liquid with numeric composition ceilings

Claim 22:

• RTI sterile aqueous
• SAE-CD ≥ 0.3% wt
• amiodarone about 0.482 to 100.8 mg/mL
• SAE-CD Formula 1:
  • n = 4, 5, or 6
• SAE-CD-to-amiodarone range is not explicitly restated in claim 22’s text as a ratio, but the structural definition is present.

Claim 23 introduces a stricter ceiling structure:

• RTI sterile aqueous
• SAE-CD ≤ about 0.055 M
• amiodarone ≤ about 0.05 M
• SAE-CD:amiodarone ≤ about 1.09 ± 0.01 and ≥ about 0.3
• heating prep aspects appear in claims 24–26

Independent claim 27: water dilutable clear aqueous liquid with amiodarone ≤50 mM

Claim 27 is essentially a “mid concentration” aqueous dilutable boundary:

• SAE-CD:amiodarone ≥ 1.1 ± 0.01
• ambient dilution no precipitation and no surfactant/solvent/soap/detergent
• amiodarone ≤ 50 mM
• pH ≤/approximates pKa
• SAE-CD Formula 1 with n = 4, 5, or 6

Independent claim 29: method claim for preparation with heating

Claim 29 covers:

• providing amiodarone + SAE-CD + aqueous carrier
• SAE-CD:amiodarone ≥ 0.3 and < about 1.09 ± 0.1
• heating ≥ 45°C
• SAE-CD chemistry limited to Formula 1 with n = 4, 5, or 6

This is the manufacturing lever, particularly relevant for process infringement theories targeting the “clarity by heating” pathway.

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Which elements of the claims create the biggest infringement risk for generics or alternate formulations?

The infringement risk concentrates where alternatives are unlikely to match all constraints simultaneously.

1) SAE-CD structural requirement (Formula 1)

The claims require sulfoalkyl ether cyclodextrin with:

• sulfonated ether substituents (R groups)
• at least one sulfoalkyl ether in R1 or R2
• pharmaceutically acceptable counter-cations S1–S9
• and specific ring size n depending on claim family:
  • n = 5 or 6 (claims 1/11/15)
  • n = 4, 5, or 6 (claims 17/21/22/23/27/29)

A competing cyclodextrin without the specified sulfoalkyl ether architecture is an immediate design-around vector.

2) No-surafactant/no-solvent/no-soap/no-detergent limitation

In claims 1, 11, 15, 17 (and claim 27), the composition is defined as requiring no surfactant, organic solvent, soap or detergent to enable ambient water dilutability without precipitation. If a competitor relies on those excipients, they may avoid infringement even if they achieve similar clarity and solubilization.

Claim 5 does add “further comprising” solubilizing agent, antioxidants, buffering agents, etc., so the “no surfactant/no solvent” language is not a blanket bar on any additive; it is a bar on needing those classes to accomplish the specified behavior. That distinction matters for workaround formulation strategy.

3) Ratio windows with tight tolerance bands

Multiple claims use:

• ≥ 1.1 ± 0.01 (molar) for the “core” genus family (claims 1/11/15/19/21/27)
• 0.3 to ≤ 1.09 ± 0.01 for the lower-ratio/heating clarity family (claims 17/23)

This creates a boundary that can be engineered around if a formulation stays outside those molar ranges, assuming the SAE-CD structure still matches.

4) pH relationship to amiodarone pKa

Claims require pH that “approximates or is less than the pKa of amiodarone.” If a competitor runs pH above that relationship, even with the same SAE-CD and ratios, they can fall outside literal scope. This also impacts method-to-product alignment because a process for making a final pH state can be targeted.

5) “Clear” and ambient dilution without precipitation

Clear liquid plus no significant precipitation on ambient dilution is the functional limitation that will be used both in enforcement and in any validity/enablement disputes. It also creates measurable test criteria for infringement/non-infringement assessments.

6) Surface tension and tonicity windows (dependent claims 9–10, 14)

Claims 9–10, 14 add:

• surface tension > 50 dynes/cm when amiodarone ≤10 mg/mL
• tonicity 280–500 mOsm when amiodarone ≤10 mg/mL
• claim 14 combines both

If a competitor’s system produces lower surface tension or tonicity outside range, they may avoid the dependent-claim coverage, but still risk independent-claim infringement.

7) Heating state linkage (claims 17 and 24–26)

Claim 17 ties clarity to exposure at ≥45°C. Claims 24–26 repeat heating steps at ≥30°C to prepare the RTI formulations. This creates a process-state hook: even if final product meets chemistry/ratio, failure to perform the heating steps could defeat process-related claims while leaving product claims potentially intact, depending on whether product claims cover the state regardless of how clarity was achieved.

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How many claim categories does US 6,869,939 cover (composition types, ratios, and product states)?

Claim cluster	Composition state	Key ratio band (molar SAE-CD:amiodarone)	SAE-CD n value	Notable added constraints
Claims 1, 11, 12, 13, 9–10, 2–3	Water dilutable clear liquid	≥ 1.1 ± 0.01	n = 5–6	ambient dilution no precipitation; pH ≤/approx pKa; optional surface tension/tonicity; amiodarone and SAE-CD numeric bands in dependent claims
Claims 15, 16	Water dilutable clear liquid, high conc	≥ 1.1 ± 0.01	n = 5–6	amiodarone ≥50 mM; SAE-CD ≥55 mM; pH ≤/approx pKa
Claims 17, 18	Clear liquid after heating	0.3 to ≤ 1.09 ± 0.01	n = 4–6	clarity rendered by ≥45°C exposure; pH ≤/approx pKa; optional dilution into heated carrier with surfactant/solvent/complexing agents allowed in diluted step (claim 18)
Claims 19, 20	SBE7-β-CD concentrate and RTI	≥ 1.1 ± 0.01	SBE7-β-CD species	amiodarone >2 mg/mL; RTI: SBE7-β-CD ≥0.3% wt; amiodarone 1–2 mg/mL
Claims 21, 22, 23, 24–26	SAE-CD RTI sterile aqueous	varies; key ceiling in 23	n = 4–6	21: water dilutable; 22: RTI with range amiodarone up to 100.8 mg/mL; 23: SAE-CD ≤0.055 M and amiodarone ≤0.05 M; 23 uses ratio 0.3–1.09 ±0.01; 24–26 include heating prep steps
Claims 27, 28	Water dilutable clear aqueous	≥ 1.1 ± 0.01	n = 4–6	amiodarone ≤50 mM; SAE-CD ≤55 mM (dep. 28); pH ≤/approx pKa
Claim 29	Method of preparation	0.3 to < 1.09 ± 0.1	n = 4–6	heating at ≥45°C yields clear liquid

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What formulations are protected by the patent beyond the “generic” genus language? (SBE7-β-CD and DS subsets)

SBE7-β-CD is explicitly claimed

Claims 19 and 20 specify “SBE7-β-CD” with defined wt% and mg/mL values. If a competitor uses a sulfoalkyl ether cyclodextrin that is not SBE7-β-CD, they may avoid those specific claims, but still face genus claims if the SAE-CD structure matches Formula 1.

Average degree of substitution appears as a dependent design feature

Claims 4 and 12 require:

• average degree of substitution about 4 or 7

This is a narrow dependent filter. In practice, DS can be used as a manufacturing fingerprint. If a competitor’s SAE-CD has DS outside “about 4 or 7,” they could avoid those dependent-claim embodiments while potentially still infringing independent claims that do not recite DS.

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How does US 6,869,939 relate to FDA formulations and Orange Book status for amiodarone products?

No FDA labeling, product identity, Orange Book listing, or approval pathway details are provided in the record you supplied. Under the constraints, a complete and accurate Orange Book-linked status mapping cannot be produced from the claim text alone.

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What generic entry risks exist for amiodarone clear SAE-CD dilutable products?

This patent is structured to protect against straightforward “solubilizer swap” strategies:

1. Cyclodextrin-type excipients must match structural Formula 1 with sulfoalkyl ether substitution and the required n values depending on claim family.
2. Ambient water dilution behavior without precipitation is a functional barrier.
3. No surfactant/solvent/soap/detergent requirement blocks certain emulsion or micellar workaround vehicles unless their presence is not “needed” for the specified behavior and claim interpretation does not treat them as required.
4. Ratio and pH relationship create a measurable formulation design space.

The sharpest competitive risk is for a product positioned as:

• “Cremophor-free / solvent-free” amiodarone
• using sulfonated cyclodextrins
• engineered to be dilutable with water at room temperature
• and tuned into the provided molar ratio and pH relationship windows.

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What manufacturing and process claims could matter for infringement (heating to render clarity)?

Heating clarity process hook

• Claim 17: “exposed to temperature ≥45°C thereby rendering… clear”
• Claim 29: heating ≥45°C after mixing to the lower ratio band

This supports enforcement arguments where:

• competitor manufacturing includes a heating step in the recited range, and
• the product clarity outcome is tied to that step.

Dependent claims 24–26 add “prepared by heating… at temperature ≥30°C” for certain RTI formulations. That provides additional procedural anchoring for process-based theories.

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How does the claim set compare with alternative cyclodextrin amiodarone approaches?

Within the patent’s own logic:

• The patent is focused on sulfoalkyl ether cyclodextrins with sulfonate ether functionality.
• It is not drafted around neutral cyclodextrins (e.g., unmodified β-CD) without sulfonate ether substitutions.
• It relies on solubilization complexes that support:
  • clear appearance
  • dilution stability
  • acceptable tonicity/surface tension for injection use (dependent limits)

A competitor using a different cyclodextrin family or a mixed-solvent system risks falling outside either:

• Formula 1 structural boundaries, or
• the “no surfactant/organic solvent/soap/detergent need” limitation.

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Key Takeaways

• US 6,869,939 protects a platform: amiodarone + SAE-CD in water-dilutable clear liquids with ambient dilution stability and no need for surfactants/solvents/soaps/detergents, driven by specific SAE-CD sulfoalkyl ether chemistry (Formula 1).
• The enforceable scope is anchored by (i) SAE-CD structure, (ii) SAE-CD:amiodarone molar ratio bands with tight tolerances, (iii) pH ≤/approx amiodarone pKa, and (iv) functional clarity/no-precipitation behavior.
• The claim set splits into:
  • high-ratio (≥1.1 ±0.01) water-dilutable families with n=5–6 (claims 1/11/15),
  • lower-ratio (0.3 to ≤1.09 ±0.01) heating-rendered clarity families with n=4–6 (claims 17/29, and 23),
  • SBE7-β-CD specific concentrate and RTI embodiments (claims 19–20).
• Dependent constraints add measurable injection-relevant product attributes: surface tension, tonicity, DS subsets, ionic strength caps, and sterile RTI state.
• From a design-around perspective, the most direct levers are: SAE-CD structural substitution pattern (Formula 1), n value, molar ratio band placement, and pH control, with process heating step choices affecting method/process claim exposure.

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FAQs

1) What SAE-CD structure is required by US 6,869,939?
The claims require SAE-CD defined by Formula 1 with n = 5 or 6 in the core independent claims, expanding to n = 4–6 in the lower-ratio/heating and broader RTI family. The cyclodextrin must carry sulfoalkyl ether groups where at least one of R1 or R2 is —O—(C2–C6 alkylene)–SO3−, with pharmaceutically acceptable counter-cations (S1–S9).

2) How narrow is the SAE-CD-to-amiodarone ratio limitation?
The patent uses tight bands: ≥ 1.1 ±0.01 for the primary water-dilutable genus claims, and a complementary range 0.3 to ≤1.09 ±0.01 for heating-rendered clarity claims.

3) Does the patent require a specific pH relative to amiodarone pKa?
Yes. Multiple claims require pH that approximates or is less than the pKa of amiodarone.

4) Are heating steps part of the protection?
Yes. The patent contains process/product-state linkage: one key family requires exposure to ≥45°C to “render” the formulation clear, and additional heating-prep limitations appear for certain RTI claims.

5) What additional product attributes are claimed for injection-relevant performance?
Dependent claims include surface tension thresholds and tonicity windows, plus ionic strength constraints (excluding amiodarone and SAE-CD).

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References (APA)

1. US Patent 6,869,939, “Water dilutable clear liquid amiodarone formulations comprising sulfoalkyl ether cyclodextrins (SAE-CD).” Claims provided in the prompt.

Drugs Protected by US Patent 6,869,939

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,869,939

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	535239
Australia	2003234285
Canada	2483774
Cyprus	1112527
Denmark	1501496