Details for Patent: 8,410,077

Which drugs does patent 8,410,077 protect, and when does it expire?

Patent 8,410,077 protects NEXTERONE, BAXDELA, EVOMELA, CARNEXIV, NOXAFIL, SESQUIENT, and ZULRESSO, and is included in seven NDAs.

This patent has thirty-one patent family members in thirteen countries.

Summary for Patent: 8,410,077

Title:	Sulfoalkyl ether cyclodextrin compositions
Abstract:	SAE-CD compositions are provided, along with methods of making and using the same. The SAE-CD compositions comprise a sulfoalkyl ether cyclodextrin having an absorption of less than 0.5 A.U. due to a drug-degrading agent, as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
Inventor(s):	Vincent ANTLE
Assignee:	Cydex Pharmaceuticals Inc
Application Number:	US12/613,103
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,410,077
Patent Claim Types: see list of patent claims	Use; Composition; Device;

United States Patent 8,410,077: Scope, Claim Construction, Expiration and SAE-CD Patent Landscape

US Patent 8,410,077 protects high-purity sulfoalkyl ether cyclodextrin compositions, particularly sulfobutyl ether-beta-cyclodextrin sodium, known commercially as Captisol. Its central limitations are low phosphate content, controlled average degree of substitution, low ultraviolet absorbance associated with drug-degrading impurities, and, in process claims, repeated treatment with phosphate-free activated carbon. The patent is directed primarily to excipient quality and manufacturing controls rather than a particular active pharmaceutical ingredient.

The patent issued April 2, 2013. Its commercial relevance is concentrated in Captisol-containing injectable and oral pharmaceutical products, but it is not an active-ingredient patent and is not ordinarily an Orange Book-listed patent.

What does US Patent 8,410,077 protect?

The patent has four principal protection groups:

Protection group	Claims	Core subject matter
Purified SAE-CD composition	1-20	SAE-CD with phosphate below 100 ppm and low UV absorbance
Manufacturing process	21-28, 64-71	Aqueous sulfoalkylation, separation, and repeated phosphate-free activated-carbon treatment
SAE-CD pharmaceutical compositions	29-63, 72-76	SAE-CD combined with an excipient and/or active agent
Narrow high-purity embodiments	14-20	Tighter impurity and absorbance limits, including DS of 6-7.1 or 6.5-7

The patent does not claim a specific drug such as voriconazole, remdesivir, posaconazole, sugammadex, or melphalan. It claims a quality-defined excipient and products containing that excipient.

What is the core technical concept?

The core concept is that SAE-CD can contain trace manufacturing residues or degradation-promoting impurities that compromise the stability of a co-formulated drug. The patent uses analytical absorbance as a proxy for the concentration of those impurities.

The central composition limitations are:

• SAE-CD average degree of substitution of 4.5 to 7.5 in claims 1 and 2.
• Sulfobutyl ether cyclodextrin as the expressly identified SAE-CD in claims 3 and 4.
• Phosphate concentration below 100 ppm.
• Absorbance below 0.5 A.U. at 245-270 nm.
• Testing at 300 mg/mL or 500 mg/mL in a 1 cm cell.
• More restrictive absorbance thresholds below 0.2 A.U. in dependent claims 5, 6, 14, 19 and 20.
• Color-related absorbance below 0.2 A.U. or 0.1 A.U. at 320-350 nm in claims 6, 14 and 15.

The concentration and optical path limitations matter. A sample that passes an absorbance threshold at 300 mg/mL may fail when tested at 500 mg/mL. A supplier or downstream manufacturer cannot evaluate the claims using a routine dilute-solution specification without reproducing the claimed test conditions.

How should the independent claims be construed?

Claims 1 and 2: broad composition claims with degree-of-substitution limits

Claims 1 and 2 cover an SAE-CD composition having:

1. An average degree of substitution of 4.5 to 7.5;
2. Less than 100 ppm phosphate; and
3. Absorbance below 0.5 A.U. due to a drug-degrading agent.

Claim 1 uses a 300 mg/mL test concentration. Claim 2 uses 500 mg/mL.

These claims are broad because they do not require:

• Sulfobutyl ether specifically;
• Sodium as the counterion;
• A particular cyclodextrin starting material;
• A named drug;
• A specific activated-carbon treatment;
• The additional impurity limits in claim 7.

The strongest commercial reading is that a qualifying Captisol-type material can fall within claims 1 or 2 even if it is made by a process different from the process recited in claims 21-28.

Claims 3 and 4: broader SAE-CD identity, narrower chemical species

Claims 3 and 4 remove the average-degree-of-substitution requirement but specify sulfobutyl ether cyclodextrin. They still require:

• Less than 100 ppm phosphate; and
• Absorbance below 0.5 A.U. at 245-270 nm.

These claims may capture sulfobutyl ether cyclodextrin materials outside the 4.5-7.5 degree-of-substitution range, provided the absorbance and phosphate requirements are met.

This creates a potential overlap between claims 1-2 and claims 3-4. A material with a degree of substitution of 6.5-7.0 may satisfy both groups.

Claims 19 and 20: commercially important high-purity Captisol claims

Claims 19 and 20 are narrower and potentially more valuable in commercial enforcement. They require:

• Sulfobutyl ether cyclodextrin;
• Average degree of substitution of 6 to 7.1;
• Less than 100 ppm phosphate; and
• Absorbance below 0.2 A.U. at 245-270 nm.

The claims apply at either 300 mg/mL or 500 mg/mL.

These limitations align closely with the commercially relevant Captisol material, commonly described as sulfobutyl ether-beta-cyclodextrin sodium with an average degree of substitution near seven. The claims could therefore be more significant against a competing supplier selling a high-purity, high-substitution sulfobutyl ether cyclodextrin rather than against a drug manufacturer using a different excipient.

Claims 21 and 64: product-by-process claims

Claims 21 and 64 require a composition produced by a process involving:

• Aqueous reaction of cyclodextrin and a sulfoalkylating agent in the presence of an alkalizing agent;
• Separation of unwanted components;
• Treatment of the partially purified solution with phosphate-free activated carbon at least twice; and
• The claimed absorbance result.

Claims 21 and 64 differ mainly in the test concentration:

• Claim 21: 300 mg/mL.
• Claim 64: 500 mg/mL.

The process steps include ultrafiltration, diafiltration, centrifugation, extraction, solvent precipitation and dialysis. The claims also cover repeated batch treatment and flow-through or recycling treatment.

Because these are product-by-process claims, infringement analysis may focus on whether the accused product has the claimed product characteristics and whether the process language is legally treated as limiting in the relevant proceeding. A manufacturer using a different purification process may still face risk if the claim is construed to cover the resulting composition based on the claimed structural and analytical characteristics.

What impurity limits are protected?

Claim 7 introduces a multi-impurity profile:

Impurity or residual component	Claim 7 limit
Sulfoalkylating agent	Less than 20 ppm
Underivatized cyclodextrin	Less than 0.5 wt.%
Alkali metal halide salt	Less than 1 wt.%
Hydrolyzed sulfoalkylating agent	Less than 0.25 wt.%

Claims 14-16 narrow these limits further.

Parameter	Claim 14	Claim 15	Claim 16
Phosphate	<50 ppm	<10 ppm	<5 ppm
Sulfoalkylating agent	<10 ppm	<2 ppm	<250 ppb
Underivatized cyclodextrin	<0.2 wt.%	<0.1 wt.%	<0.1 wt.%
Alkali metal halide salt	<0.5 wt.%	<0.2 wt.%	<0.05 wt.%
Hydrolyzed sulfoalkylating agent	<0.1 wt.%	<0.08 wt.%	<0.08 wt.%
Color absorbance	<0.2 A.U.	<0.1 A.U.	Not recited
Test wavelength	320-350 nm	320-350 nm	Not recited

The claims create a layered specification strategy. Claims 1-4 establish broad compositional protection. Claims 14-16 protect more demanding quality grades that may be used for sensitive injectable products.

What manufacturing methods are covered?

The process claims focus on impurity reduction after sulfoalkylation.

Activated-carbon purification

Claims 21-25 and 64-68 cover:

• Phosphate-free particulate or powdered activated carbon;
• Addition of carbon to the partially purified aqueous SAE-CD solution;
• Separation of carbon from the solution;
• Repetition of the treatment at least once;
• Flow-through treatment and recycling;
• Use of different carbon masses in successive passes;
• Approximately 12% activated carbon by weight of SAE-CD;
• Treatment for at least two hours;
• An SAE-CD-to-carbon weight ratio of 8.3:1 to 8.5:1.

The phrase "phosphate-free" is important. Activated carbon and process-contact materials containing phosphate could prevent literal satisfaction of the process claims, although the composition claims may remain relevant if the final material has less than 100 ppm phosphate and meets the absorbance limits.

Thermal degradation of excess sulfoalkylating agent

Claims 26, 27, 69 and 70 cover degradation of excess sulfoalkylating agent by heating the reaction milieu:

• 60°C to 80°C for 6 to 72 hours; or
• 75°C to 80°C for 6 to 72 hours.

These claims target process controls intended to reduce residual sulfoalkylating agent and related hydrolysis products before final purification.

Ultrafiltration

Claims 28 and 71 specify ultrafiltration with a molecular-weight cutoff of about 1,000 daltons. A manufacturer using a different molecular-weight cutoff may avoid this dependent claim while remaining exposed to broader composition or process claims.

When does US Patent 8,410,077 lose exclusivity?

Event	Date
Patent issued	April 2, 2013
Patent number	US 8,410,077 B2
Expected ordinary US patent-term endpoint	2027, subject to the patent’s recorded term adjustment
Regulatory exclusivity	No drug-specific exclusivity created by this patent

The patent is a pre-2013 US patent governed by the 20-year term from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any applicable terminal disclaimer. The relevant commercial planning date is therefore in 2027, rather than the issue date.

Patent expiration does not remove quality, regulatory or know-how barriers. A competitor may still need to qualify a noninfringing SAE-CD source, demonstrate impurity control, establish drug compatibility and obtain sponsor-specific regulatory acceptance.

What is the Orange Book status of US 8,410,077?

US 8,410,077 is not a conventional Orange Book drug-product patent.

The FDA Orange Book lists patents submitted for approved drug products, including patents covering an active ingredient, formulation, composition of matter or method of use. US 8,410,077 claims an excipient composition and generic pharmaceutical compositions containing that excipient. It does not identify a particular NDA product, active ingredient, dosage regimen or approved method of use.

Consequences include:

• No ordinary Orange Book patent listing for Captisol as an excipient.
• No direct Paragraph IV certification against this patent merely because an ANDA applicant uses Captisol.
• No Hatch-Waxman 30-month stay based solely on this patent unless a drug sponsor separately and validly lists a qualifying patent for a specific approved product.
• Potential conventional patent litigation under 35 U.S.C. §§ 271 and 281 if a supplier or manufacturer is accused of making, using or selling a covered composition.

A drug product using Captisol can have separate Orange Book patents covering the active ingredient, formulation, dosage form or method of treatment. Those product-specific patents must be analyzed independently.

Which companies are most exposed to this patent?

Ligand Pharmaceuticals and Captisol

CyDex Pharmaceuticals developed and commercialized Captisol. Ligand Pharmaceuticals acquired CyDex in 2011 and has continued to commercialize Captisol and related cyclodextrin technology. Ligand is the principal commercial entity associated with the Captisol platform and its patent portfolio.

Public filings generally report Captisol-related commercial activity at the platform or product level, not revenue attributable to US 8,410,077 specifically. The patent’s economic value is therefore linked to continued use of Captisol in approved and pipeline drug products, supply agreements and technical qualification requirements.

Drug manufacturers

Companies using sulfobutyl ether-beta-cyclodextrin in injectable or oral formulations may face risk if their purchased material meets the claimed thresholds. Key Captisol-containing or Captisol-associated products have included products involving:

• Voriconazole;
• Posaconazole;
• Remdesivir;
• Sugammadex;
• Ziprasidone;
• Other poorly water-soluble or formulation-sensitive active agents.

Use of an excipient in an approved product does not itself prove infringement. The relevant question is whether the sourced composition satisfies the claim limitations, including phosphate, absorbance and, for process claims, manufacturing history.

Competing excipient suppliers

The most direct competitor risk concerns suppliers of:

• Sulfobutyl ether cyclodextrin;
• Sulfoalkyl ether-beta-cyclodextrin;
• Alternative sodium sulfobutyl ether cyclodextrin grades;
• Custom SAE-CD materials for parenteral formulations.

A supplier can reduce risk by using a different cyclodextrin derivative, a different average degree of substitution, or a manufacturing process that produces material outside the claimed analytical profile. Those strategies may create formulation, toxicology or regulatory disadvantages.

How strong is the patent estate?

The patent is strongest when all of the following are present:

• Sulfobutyl ether cyclodextrin;
• Average degree of substitution between 6 and 7.1;
• Very low phosphate;
• Low absorbance at 245-270 nm;
• Use in a pharmaceutical formulation;
• Manufacturing with repeated phosphate-free activated-carbon treatment.

Its strength is lower where:

• The SAE-CD has a degree of substitution outside the claimed range;
• The material is not sulfobutyl ether cyclodextrin;
• Phosphate exceeds 100 ppm;
• The drug-degrading-agent absorbance exceeds 0.5 A.U.;
• The supplier uses a different purification route;
• The accused product cannot be shown to have been produced using the claimed process.

Potential validity pressure points

The analytical limitations create potential construction and validity issues:

1. "Drug-degrading agent" is functional and not tied to a single chemical identity.
2. "Due to" may require attribution between measured absorbance and a particular impurity.
3. The claims specify wavelength ranges rather than a single wavelength.
4. Absorbance depends on concentration, pH, solvent, cell path length and instrument conditions.
5. Product-by-process limitations may create disputes over whether the process or only the resulting product limits claim scope.
6. The very broad downstream composition claims may face written-description, enablement or obviousness arguments depending on the asserted claim and prosecution history.

These issues do not make the patent commercially weak. They increase the importance of certificate-of-analysis data, retained samples, validated analytical methods and supplier audit records.

What generic entry risks exist?

Generic drug applicants

The principal risk is indirect. An ANDA applicant may avoid this patent by:

• Using a non-SAE-CD solubilizer;
• Using a different SAE-CD grade;
• Purchasing material with a specification outside the claimed ranges;
• Formulating without Captisol;
• Demonstrating that the active product does not use a composition satisfying the relevant claim.

The applicant still must address drug-specific patents and regulatory requirements. Avoiding US 8,410,077 may require reformulation and new stability data.

Biosimilar applicants

Biosimilar risk is limited. SAE-CD is a small-molecule excipient, not a biologic active ingredient. The Biologics Price Competition and Innovation Act does not create a biosimilar pathway issue for the excipient itself. A biologic formulation containing SAE-CD could face ordinary formulation patent issues, but US 8,410,077 does not create biosimilar exclusivity.

Generic launch scenarios

Scenario	Patent risk
Generic uses Captisol purchased from the patent holder	Commercial license and supply terms may reduce practical risk
Generic uses third-party SAE-CD within the claimed specifications	Highest composition-claim risk
Generic uses SAE-CD outside DS and absorbance limits	Reduced literal infringement risk
Generic uses a different solubilizer	Lowest risk under this patent, but reformulation risk increases
Generic uses a process copied from the patent disclosure	Elevated process-claim risk
Generic uses a different purification process but produces qualifying material	Composition-claim risk remains

What licensing and settlement issues matter?

The key commercial issue is whether Captisol access is controlled through supply and licensing arrangements rather than patent litigation alone. Ligand and its predecessors have commercialized Captisol through collaborations, supply agreements and technology arrangements with pharmaceutical companies.

A supply agreement may provide practical freedom to operate for a customer, but it does not necessarily establish a license for every patent family or every geographic jurisdiction. Agreement-specific covenants, field-of-use restrictions, minimum purchase commitments and sublicensing rights can materially change the risk analysis.

No broadly reported US Paragraph IV settlement is associated specifically with US 8,410,077. That absence is consistent with the patent’s excipient focus and its apparent lack of ordinary Orange Book listing. Any confidential supply or license settlement would not be visible from the patent record.

What geographic coverage does the SAE-CD patent landscape have?

US 8,410,077 provides US protection only. The relevant international landscape may include counterpart applications directed to:

• SAE-CD composition quality;
• Sulfoalkylation processes;
• Activated-carbon purification;
• Captisol formulations;
• Specific drug products using Captisol.

Freedom to operate must be assessed separately in the European Union, Japan, China, South Korea, Canada and other manufacturing or sales jurisdictions. Expiration in the United States does not terminate foreign counterparts, and a manufacturing step performed abroad may still create US exposure if the resulting product is imported or sold in the United States.

Key Takeaways

• US 8,410,077 is an excipient-quality and manufacturing patent, not an active-ingredient patent.
• The central commercial target is high-purity sulfobutyl ether cyclodextrin, particularly Captisol-type material.
• Claims 1-4 use phosphate and UV-absorbance limits to define broad purified compositions.
• Claims 19 and 20 narrow the protected space to sulfobutyl ether cyclodextrin with a degree of substitution of 6-7.1 and absorbance below 0.2 A.U.
• Claims 21-28 and 64-71 cover repeated treatment with phosphate-free activated carbon, thermal degradation of residual sulfoalkylating agent and ultrafiltration.
• The ordinary patent-term endpoint is in 2027, subject to the recorded patent-term adjustment and any terminal disclaimer.
• The patent is not ordinarily an Orange Book-listed patent and does not independently create a Paragraph IV certification obligation.
• Biosimilar risk is minimal because SAE-CD is an excipient rather than a biologic active ingredient.
• The principal enforcement risk falls on competing SAE-CD suppliers and pharmaceutical manufacturers using material that meets the claimed analytical profile.
• The principal design-around options are alternative excipients, different SAE-CD chemistry, or material outside the claimed degree-of-substitution, phosphate and absorbance ranges.
• Captisol supply, licensing and technical qualification may remain commercially relevant after patent expiration because regulatory and manufacturing barriers can outlast patent rights.

FAQs About US Patent 8,410,077

Does US 8,410,077 cover Captisol?

Yes. Captisol is a commercial sulfobutyl ether-beta-cyclodextrin sodium product, and Captisol-type material can fall within the composition claims when it satisfies the claimed degree-of-substitution, phosphate and absorbance limits.

Can a pharmaceutical company infringe the patent by buying Captisol?

Potentially. Use of a purchased excipient can create infringement exposure if the material satisfies the composition limitations and the company makes, uses or sells a covered pharmaceutical composition. A supplier license does not automatically grant rights to every downstream user unless the agreement provides them.

Is a phosphate-containing activated carbon process outside the patent?

It may avoid the process claims requiring phosphate-free activated carbon, but the final product could still fall within the composition claims if it contains less than 100 ppm phosphate and meets the absorbance limitations.

Does patent expiration eliminate the need for Captisol regulatory qualification?

No. Patent expiration removes patent exclusivity but does not eliminate the need to qualify the excipient, demonstrate pharmaceutical-grade manufacture, establish impurity controls and generate formulation stability data.

Can a competitor avoid the patent by changing the average degree of substitution?

Changing the average degree of substitution may avoid claims 1, 2 and 17-20 if the resulting material falls outside the specified ranges. Claims 3 and 4 do not require a stated average degree of substitution, so a sulfobutyl ether cyclodextrin material may remain exposed to those claims if it satisfies the phosphate and absorbance limitations.

References

1. CyDex Pharmaceuticals, Inc. (2013). Sulfoalkyl ether cyclodextrin compositions and methods of making same (U.S. Patent No. 8,410,077 B2). United States Patent and Trademark Office.

2. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

4. U.S. Food and Drug Administration. (n.d.). Inactive Ingredient Database. https://www.accessdata.fda.gov/scripts/sda/sdIndex.cfm?product=Inactive%20Ingredient%20Database

5. Ligand Pharmaceuticals Incorporated. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.

Drugs Protected by US Patent 8,410,077

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Baxter Hlthcare	NEXTERONE	amiodarone hydrochloride	INJECTABLE;INJECTION	022325-002	Nov 16, 2010		RX	Yes	Yes			Y
Baxter Hlthcare	NEXTERONE	amiodarone hydrochloride	INJECTABLE;INJECTION	022325-003	Nov 16, 2010		RX	Yes	Yes			Y
Melinta	BAXDELA	delafloxacin meglumine	POWDER;INTRAVENOUS	208611-001	Jun 19, 2017		RX	Yes	Yes			Y
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes			Y
Lundbeck Pharms Llc	CARNEXIV	carbamazepine	SOLUTION;INTRAVENOUS	206030-001	Oct 7, 2016		DISCN	Yes	No			Y
Merck Sharp Dohme	NOXAFIL	posaconazole	SOLUTION;INTRAVENOUS	205596-001	Mar 13, 2014		DISCN	Yes	No			Y

International Family Members for US Patent 8,410,077

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2009241858
Brazil	PI0905080
Canada	2702603
Canada	2771879
China	101959508
China	105288650