Details for Patent: 7,758,890

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Summary for Patent: 7,758,890

Title:	Treatment using dantrolene
Abstract:	Low volume safe for injection formulations of dantrolene yield significant advantages over the currently approved and marketed dantrolene for MH threatening anesthetic crisis. Once dantrolene can be made immediately available to patients triggered of MH, the anesthesiologist will be able to focus exclusively on the management of the patient's physiologic status in this complex and evolving crisis, not on the laborious and time consuming reconstitution process of the rescue agent. Additionally, a safe for injection low volume formulation of dantrolene can be made widely available to non-anesthesiologist practitioners who have occasion to use dantrolene intravenously in the treatment of other potentially life threatening conditions, including in the field. The low volume, safe for injection formulations of dantrolene, as well as other formulations of dantrolene, have significant advantages over currently used approaches to the prevention and treatment of pumphead, and other neurological, cognitive and motor dysfunction incident to iatrogenically or trauma induced situations of altered blood flow, including those incurred during surgical procedures involving CPB or related procedures, as well as those incurred during non-normothermic episodes caused iatrogenically or by disease.
Inventor(s):	David Anderson, Benjamin G. Cameransi, JR., Vincent M. Conklin
Assignee:	Lyotropic Therapeutics Inc
Application Number:	US10/788,413
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,758,890
Patent Claim Types: see list of patent claims	Composition; Formulation;

US Patent 7,758,890: Dantrolene Sodium Formulation Claims, Patent Scope, and Generic Entry Risk

US Patent No. 7,758,890 protects a low-volume, injectable dantrolene sodium formulation designed to replace conventional reconstitution-heavy products used for malignant hyperthermia. Its core combination is dantrolene sodium, a water-soluble polysorbate, sorbitol or mannitol, water, and submicron-to-micron particle control in a colloidal dispersion.

The patent is formulation-specific. It does not broadly claim dantrolene sodium, the treatment of malignant hyperthermia, or every injectable dantrolene product. Infringement generally requires a liquid formulation with the claimed excipients, concentration or dose-volume relationship, particle-size limitation, and intravenous safety characteristics.

The patent’s commercial relevance is closely tied to Ryanodex, an FDA-approved 250-mg dantrolene sodium product marketed by Eagle Pharmaceuticals. The principal commercial protection is expected to run through approximately February 2026, subject to the applicable patent-term calculation and any regulatory exclusivity or later-listed patents.

What does US Patent 7,758,890 protect?

The patent protects low-volume aqueous colloidal dispersions of dantrolene sodium that are suitable for intravenous injection. The independent claims require the following elements:

Claim element	Requirement
Active ingredient	Dantrolene sodium
Concentration	30-80 mg/mL or 10-60 mg/mL in claims 1-18
Alternative dose-volume format	3-150 mL provides approximately 500 mg in claims 19-21
Surfactant	A water-soluble polysorbate
Polyol	Sorbitol or mannitol
Carrier	Water
Physical form	Colloidal dispersion of dantrolene sodium particles in water
Particle size	Less than about 2 microns average diameter
Administration	Safe for intravenous administration
Optional excipient	Polyvinylpyrrolidone, or PVP
Commercial dose	250-300 mg in claim 16; 250 mg in claim 17
Bolus administration	Single injection in less than one minute under claim 16
Preferred concentration	50 mg/mL under claim 18

The independent claims are claims 1 and 19. Claims 2-18 depend from claim 1. Claims 20 and 21 depend from claim 19.

The patent therefore has two principal claim architectures:

1. A concentration-based formulation claim covering specified dantrolene concentrations.
2. A dose-volume claim covering a liquid quantity that delivers approximately 500 mg in 3-150 mL.

How should the concentration ranges in claim 1 be interpreted?

Claim 1 recites dantrolene sodium at a concentration "in the range of 30-80 mg/ml or in the range of 10-60 mg/ml." Read literally, the union of those ranges covers 10-80 mg/mL because the two ranges overlap from 30-60 mg/mL.

The drafting creates two practical issues:

• The narrower 30-80 mg/mL range is fully contained within the broader combined range.
• A formulation at 10-29.99 mg/mL may fall within the 10-60 mg/mL alternative but outside the 30-80 mg/mL alternative.
• A formulation above 60 mg/mL may fall within the 30-80 mg/mL alternative but outside the 10-60 mg/mL alternative.

A product at 50 mg/mL, including the marketed Ryanodex concentration, falls within both ranges and separately falls within claim 18.

The concentration limitation is only one part of the claim. A competing formulation at 50 mg/mL would not necessarily infringe unless it also satisfies the polysorbate, sorbitol-or-mannitol, aqueous colloidal-dispersion, particle-size, and intravenous-safety limitations.

What are the most important dependent claims?

Claims 2 and 20: "consisting essentially of" formulations

Claims 2 and 20 use "consists essentially of." This language may exclude additional ingredients that materially affect the basic and novel characteristics of the formulation while permitting ingredients that do not materially alter those characteristics.

The basic formulation characteristics likely include:

• Low-volume injectable delivery
• Aqueous colloidal dispersion
• Dantrolene sodium particle-size control
• Intravenous safety
• Stabilization or solubilization using polysorbate and sorbitol or mannitol

A competing formulation containing an additional buffer, preservative, tonicity agent, or stabilizer would require a fact-specific analysis. The presence of an additional excipient does not automatically avoid a "consisting essentially of" claim.

Claims 4, 5, and 21: PVP-containing formulations

Claims 4, 5, and 21 add polyvinylpyrrolidone. These claims narrow the scope to formulations containing PVP, but they can provide a separate infringement path where PVP is used as a stabilizer, dispersant, or particle-growth inhibitor.

Claims 5 and 21 are narrower because they combine PVP with "consisting essentially of" language.

Claims 6-8: particle-size requirements

These claims create progressively different particle-size limitations:

Claim	Particle-size limitation
1	Average particle diameter below about 2 microns
6	At least 95% of particles no more than 0.8 microns
7	At least 95% of particles no more than 0.45 microns
8	No particles more than 2 microns

Claims 6 and 7 are distribution-based claims. They require measurement of at least 95% of the particles against the stated threshold. Claim 8 is an absolute upper-limit claim and may be more difficult to establish experimentally because a single particle exceeding 2 microns could be material.

The claims raise measurement questions involving:

• Number-based versus volume-based particle distributions
• Wet-state versus dry-state measurement
• Dynamic light scattering, laser diffraction, microscopy, or another method
• Whether agglomerates are measured as particles
• Whether the test is performed before or after storage, dilution, shaking, or administration

Particle-size testing is likely to be central to any technical due-diligence or Paragraph IV dispute.

Claims 9 and 18: mannitol ratio and concentration

Claim 9 limits mannitol to no more than 30 mg per milligram of dantrolene. This is a broad ratio limitation. Claim 18 specifies 50 mg/mL dantrolene sodium.

A 250-mg dose at 50 mg/mL requires 5 mL of formulation. That dose-volume relationship corresponds closely to the low-volume commercial use case described in the patent.

Claims 12-17: low-volume administration

These claims address the amount of liquid used to administer a therapeutic dose:

• Claim 12 covers a quantity sufficient to deliver a therapeutic dose.
• Claim 13 specifies 3-150 mL.
• Claim 14 narrows the volume to 10 mL or less.
• Claim 15 narrows the volume to 5 mL or less.
• Claim 16 covers 250-300 mg delivered by a single bolus injection in less than one minute.
• Claim 17 narrows claim 16 to 250 mg.

These limitations are commercially significant because conventional dantrolene products often require substantially larger reconstitution volumes and multiple vials. A generic could attempt to avoid claims 14-17 by using a higher volume while remaining within broader claims 1 or 13.

What formulations are protected by US 7,758,890?

The claims cover a formulation profile rather than a single precise recipe. The following table summarizes likely claim exposure.

Formulation design	Likely claim position
50 mg/mL dantrolene sodium, polysorbate, mannitol, water, sub-2-micron particles	High exposure under claims 1 and 18
50 mg/mL with PVP added	High exposure under claims 1, 4, and 18; possible exposure under claim 5
10-29.99 mg/mL with required excipients and particle size	Potential exposure under claim 1
60-80 mg/mL with required excipients and particle size	Potential exposure under claim 1
Dantrolene sodium in a true solution rather than colloidal dispersion	Potential design-around, subject to factual characterization
Dantrolene sodium with a non-polysorbate surfactant only	Potential design-around
Dantrolene sodium with glucose or another polyol instead of sorbitol or mannitol	Potential design-around
Formulation with particles averaging 2 microns or larger	Potential design-around, but may affect injectability and safety
High-volume formulation outside the stated dose-volume ranges	May avoid narrower claims but not necessarily claim 1
Intramuscular-only product	Potential design-around to the intravenous limitation, subject to claim construction and product labeling

The most difficult elements to design around simultaneously are likely the required polysorbate, sorbitol-or-mannitol excipient, aqueous carrier, and controlled particle size. Those limitations define the formulation platform.

How strong is the patent estate for the low-volume dantrolene formulation?

The strength of US 7,758,890 depends on claim construction, prior art, and the relationship between the issued claims and later patents. Based on the supplied claims, the estate has meaningful commercial coverage but is not absolute.

Strengths

• It covers the formulation architecture associated with low-volume intravenous dantrolene.
• It includes both concentration and dose-volume claim formats.
• It has fallback claims for PVP, mannitol ratio, 50 mg/mL concentration, sub-0.8-micron and sub-0.45-micron particle distributions, and 250-mg bolus delivery.
• Several claim limitations correspond to measurable product characteristics.
• The claims cover both broad formulation concepts and clinically relevant commercial configurations.

Vulnerabilities

• The formulation requires multiple limitations to be met in combination.
• The "less than about 2 microns" limitation may raise indefiniteness or measurement-method issues.
• The overlapping concentration ranges create drafting and claim-construction questions.
• Prior art may include earlier dantrolene suspensions, colloidal dispersions, polysorbate formulations, particle-size reduction methods, or injectable compositions.
• A competitor may pursue a different surfactant, polyol, delivery route, physical form, or concentration.
• "Safe for intravenous administration" may require interpretation through the specification, examples, regulatory record, and ordinary technical meaning.

The strongest enforcement position would generally involve a product that reproduces the commercial profile: 50 mg/mL dantrolene sodium in a small-volume aqueous formulation containing polysorbate and mannitol, with controlled submicron particles.

When does US Patent 7,758,890 lose exclusivity?

US Patent 7,758,890 was granted on July 20, 2010. The patent’s expected expiration is approximately February 2026 based on the patent-family priority and term information commonly associated with the low-volume dantrolene estate. The precise enforceable date depends on the official USPTO patent-term calculation, including any patent-term adjustment and terminal disclaimer information.

Event	Date or status
Patent	US 7,758,890
Grant date	July 20, 2010
Technology	Low-volume injectable dantrolene sodium formulation
Commercial product associated with the technology	Ryanodex
Expected patent expiration	Approximately February 2026
Regulatory exclusivity	Separate FDA analysis required; patent expiration does not itself determine FDA exclusivity
Post-expiration risk	Generic or alternative formulation entry, subject to remaining patents and regulatory approval

Patent expiration does not automatically permit immediate generic launch. A generic sponsor must still address FDA approval requirements, listed patents, regulatory exclusivity, manufacturing readiness, and any litigation settlement restrictions.

What is the Orange Book status of the dantrolene product?

Ryanodex is an FDA-approved dantrolene sodium product. Its labeling identifies a 250-mg vial for intravenous use after reconstitution or preparation according to the approved product instructions. FDA Orange Book treatment depends on the specific product listing, active patent listings, and the date of review.

Patent 7,758,890 should be evaluated against:

• The current Orange Book listing for the relevant dantrolene sodium product
• Any later-issued formulation patents listed for the same product
• Patent delistings, expiration updates, and pediatric exclusivity
• Whether the reference product is approved under an NDA and whether an ANDA applicant must make Paragraph I, II, III, or IV certifications

A patent can remain enforceable even if it is not currently listed in the Orange Book. Conversely, Orange Book listing creates an ANDA notice and litigation framework but does not establish validity or infringement.

Which companies are challenging the dantrolene formulation patents?

The supplied claim set does not identify a Paragraph IV notice, ANDA applicant, district-court action, or settlement agreement. No company-specific challenge can be stated from the claim text alone.

A complete challenge analysis would normally review:

1. FDA Orange Book patent listings.
2. ANDA Paragraph IV notices.
3. FDA litigation information where available.
4. PACER district-court complaints and judgments.
5. Federal Circuit appeals.
6. Patent assignments and licenses.
7. Product-specific settlement agreements.

The absence of an identified challenger in the supplied material should not be treated as evidence that no challenge exists.

What patent litigation affects US 7,758,890?

The supplied information contains no litigation docket, complaint, claim-construction order, invalidity decision, or settlement involving US 7,758,890. Accordingly, a case-specific litigation conclusion cannot be made from the claims alone.

The likely litigation issues would include:

Literal infringement

A plaintiff would need to show that the accused product satisfies each required element, including:

• Dantrolene sodium
• Water-soluble polysorbate
• Sorbitol or mannitol
• Water carrier
• Colloidal dispersion
• Particle-size limitation
• Intravenous safety
• Applicable concentration or dose-volume limitation

Doctrine of equivalents

A formulation that uses a chemically or functionally similar excipient may create a doctrine-of-equivalents issue. Prosecution-history estoppel, dedication, claim vitiation, and foreseeability would limit that theory.

Validity

Potential validity grounds could include:

• Anticipation by earlier injectable dantrolene formulations
• Obviousness based on known dantrolene compositions and particle-size reduction
• Indefiniteness of particle-size and "safe for intravenous administration" language
• Written-description or enablement challenges
• Double-patenting in relation to related applications

How does the patent compare with conventional dantrolene products?

Attribute	Conventional dantrolene formulation	Low-volume formulation claimed by US 7,758,890
Physical presentation	Often powder requiring reconstitution	Liquid colloidal dispersion
Administration burden	Multiple preparation steps and vials	Low-volume injection
Dantrolene concentration	Lower after reconstitution in many legacy products	10-80 mg/mL claim ranges; 50 mg/mL preferred claim
Particle engineering	Less central to commercial description	Explicit sub-2-micron limitation
Excipients	Product-specific	Polysorbate plus sorbitol or mannitol
250-mg dose volume	Potentially high	As low as approximately 5 mL at 50 mg/mL
Regulatory relevance	Existing dantrolene safety and efficacy history	New formulation, administration, and safety profile

The patent’s commercial value arises from reducing preparation volume and administration time during a medical emergency. The claims translate that product objective into concentration, particle-size, excipient, and volume limitations.

What generic entry risks exist for Ryanodex?

At-risk launch before patent expiration

A generic sponsor could file an ANDA with a Paragraph IV certification against an Orange Book-listed patent. The patent holder could then bring an infringement action within the statutory period, potentially triggering a 30-month stay of ANDA approval under the Hatch-Waxman framework.

The commercial risk depends on:

• Whether 7,758,890 remains listed
• Whether other patents cover the product
• The filing date of the ANDA
• The strength of the proposed noninfringement and invalidity positions
• Any 30-month stay
• The availability of a section viii carve-out for method-of-use claims
• Whether the generic uses the same concentration and excipient architecture

Entry after expiration

After expiration, a generic could enter if FDA approval is available and no other unexpired patent blocks the product. The principal post-expiration risks are:

• Later-issued formulation patents
• Manufacturing-process patents
• Device or container patents
• Regulatory exclusivity
• Settlement-based launch restrictions
• Manufacturing scale-up and sterile-product validation

Design-around entry

The clearest technical design-around strategies would target one or more claim limitations:

• Use a non-polysorbate surfactant.
• Use a polyol other than sorbitol or mannitol.
• Develop a true solution rather than a colloidal dispersion.
• Alter the particle-size distribution.
• Use a concentration outside the relevant range.
• Increase dose volume beyond narrower low-volume claims.
• Change the route of administration.

Each strategy must be assessed against product performance. Avoiding the patent may undermine the low-volume, rapid intravenous administration characteristics that create the product’s commercial value.

Does the patent cover method of use or only formulation?

US 7,758,890, based on the supplied claims, is a composition patent. The claims do not expressly require treatment of malignant hyperthermia, exertional heat stroke, neuroleptic malignant syndrome, or another named disease.

The patent does contain administration-related limitations, including intravenous administration, therapeutic-dose volume, and rapid bolus injection. Those limitations describe how the composition is configured or administered, but they do not convert the claims into conventional patient-treatment method claims.

A separate method-of-use patent could create additional Orange Book or litigation exposure. The supplied claims do not identify such a patent.

Are biosimilar risks relevant to dantrolene sodium?

No. Dantrolene sodium is a small-molecule active pharmaceutical ingredient, not a biologic. Biosimilar pathways under the Biologics Price Competition and Innovation Act do not apply.

Competitive entry would generally proceed through an ANDA, a 505(b)(2) application, or, depending on the product and formulation differences, another applicable FDA pathway. The main legal framework is generic drug approval and patent certification, not biosimilar interchangeability.

What manufacturing and intellectual-property barriers remain?

The patent claims impose technical requirements that can be difficult to reproduce consistently at commercial scale:

• Stable dispersion of poorly water-soluble dantrolene sodium
• Control of particle-size distribution
• Prevention of agglomeration during storage
• Sterile processing or aseptic manufacture
• Injectable excipient compatibility
• Dose uniformity
• Physical stability after handling
• Rapid and reliable administration
• Container-closure compatibility
• Analytical validation for submicron particles

Particle-size control may be a manufacturing barrier even where it is not ultimately a legal barrier. A product that avoids the claims by allowing larger particles may encounter injectability, stability, or safety problems.

Manufacturing know-how may also be protected through trade secrets or related patents covering milling, precipitation, homogenization, dispersion stabilization, sterilization, or filling processes. The supplied claims do not identify those process rights.

How should investors and licensing teams value the patent?

The patent has the highest value where the protected formulation is difficult to substitute without losing the product’s emergency-use advantages. Relevant commercial variables include:

• Product sales before and after patent expiry
• Hospital adoption and emergency-department use
• Competitor approval timing
• Number of viable ANDA applicants
• Remaining Orange Book patents
• Manufacturing complexity
• Price erosion after generic entry
• Contracting and group-purchasing exposure
• The percentage of sales dependent on the protected 250-mg, low-volume presentation

Revenue exposure should be modeled by scenario:

Scenario	Commercial effect
No approved generic before February 2026	Continued branded pricing until expiry
One approved generic at or near expiry	Moderate initial price erosion
Multiple approved generics	Faster price and market-share erosion
Successful Paragraph IV launch	Earlier erosion and litigation expense
Design-around product	Slower entry if clinical or manufacturing development is required
Later patent blocking entry	Extended protection if valid and enforceable

Key Takeaways

• US 7,758,890 is a formulation patent for low-volume intravenous dantrolene sodium.
• Its core limitations are dantrolene sodium, water, a water-soluble polysorbate, sorbitol or mannitol, a colloidal aqueous dispersion, and particles below about 2 microns on average.
• Claims 6-8 add narrower particle-size protections, while claims 14-18 target commercially important low-volume and 250-mg bolus configurations.
• A 50-mg/mL formulation is expressly covered by claim 18 and falls within the concentration ranges in claim 1.
• PVP-containing formulations are separately addressed by claims 4, 5, and 21.
• The patent is directed to composition and administration characteristics, not a general dantrolene treatment method.
• Dantrolene is a small molecule, so biosimilar analysis is not relevant.
• The expected patent expiration is approximately February 2026, subject to the official patent-term calculation.
• Generic risk depends on the current Orange Book listing, any later Ryanodex patents, Paragraph IV activity, litigation, and settlement terms.
• The most commercially exposed design is a 250-mg, approximately 5-mL, 50-mg/mL aqueous dantrolene formulation using polysorbate and mannitol with submicron particles.

FAQs

Can a dantrolene product avoid US 7,758,890 by using a different surfactant?

Potentially. The claims require a water-soluble polysorbate. A formulation using only a different surfactant may avoid literal infringement, but the formulation would still require separate analysis under the doctrine of equivalents and any related patents.

Does a 250-mg dantrolene vial automatically infringe the patent?

No. The dose alone is insufficient. The product must also satisfy the applicable concentration, excipient, aqueous-dispersion, particle-size, and intravenous-use limitations.

Is a 5-mL dantrolene injection covered by the patent?

A 5-mL product delivering 250 mg would be a high-risk configuration if it uses approximately 50 mg/mL dantrolene sodium with polysorbate, mannitol or sorbitol, water, and sub-2-micron particles. Claims 15-18 are particularly relevant.

Can an ANDA applicant carve out the intravenous administration limitations?

A section viii statement may be available only where the relevant patented use can be omitted from the proposed labeling and the remaining approved uses support the application. Composition claims cannot generally be avoided through a labeling carve-out.

Does patent expiration eliminate all Ryanodex market protection?

No. Expiration of US 7,758,890 may remove one patent barrier, but later-listed patents, regulatory exclusivity, manufacturing patents, device rights, litigation settlements, or approval timing may still affect entry.

References

1. United States Patent and Trademark Office. (2010). U.S. Patent No. 7,758,890, low volume dantrolene formulations.
2. U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2014). Ryanodex (dantrolene sodium) prescribing information. Eagle Pharmaceuticals, Inc.
4. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application approvals and patent certification requirements.
5. United States Code, 35 U.S.C. §§ 154, 271, and 281-285.
6. United States Code, 21 U.S.C. § 355.

Drugs Protected by US Patent 7,758,890

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 7,758,890

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2004262507
Canada	2516667
European Patent Office	1435781