Details for Patent: 8,496,973

Which drugs does patent 8,496,973 protect, and when does it expire?

Patent 8,496,973 protects NITHIODOTE and SODIUM THIOSULFATE and is included in two NDAs.

This patent has thirty-two patent family members in eleven countries.

Summary for Patent: 8,496,973

Title:	Sodium thiosulfate-containing pharmaceutical compositions
Abstract:	Provided herein are pharmaceutically acceptable sodium thiosulfate and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-purgable organic carbon in a sodium thiosulfate-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium thiosulfate. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium thiosulfate.
Inventor(s):	Craig Sherman, Catherine Marie Smith, Kevin Robert Wirtz, Erich Schulze
Assignee:	Hope Medical Enterprises Inc
Application Number:	US12/831,331
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,496,973
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 8,496,973: Claim Scope, Validity Risks, Exclusivity and Sodium Thiosulfate Patent Landscape

US Patent 8,496,973 protects a defined pharmaceutical-grade sodium thiosulfate pentahydrate material and compositions made with that material. Its strongest commercial coverage is concentrated in sterile intravenous sodium thiosulfate solutions containing 250 mg/mL sodium thiosulfate pentahydrate, potassium chloride, boric acid, sodium hydroxide and water. The patent does not broadly cover all sodium thiosulfate products or all uses of sodium thiosulfate.

The patent’s central limitation is quality-based. A potentially infringing product must satisfy a large group of impurity, assay, microbial, endotoxin, solvent, physical-property and formulation specifications. Those limitations create meaningful noninfringement opportunities for competitors but also raise claim-construction, enablement and written-description issues.

The patent was granted July 30, 2013. Based on the stated 2010 priority date, the nominal expiration date is November 9, 2031, subject to patent-term adjustment, patent-term extension, terminal disclaimer or other prosecution-specific modifications. The claims supplied do not establish current enforceability, Orange Book listing status, terminal disclaimers or litigation outcomes.

What does US Patent 8,496,973 cover?

The patent has four principal coverage groups:

Coverage group	Claims	Commercial significance
Pharmaceutical-grade sodium thiosulfate pentahydrate	1-3	Covers the material itself when it meets the full specification
Compositions containing the material	4-8	Extends coverage to formulations using the specified grade
Sterile intravenous solutions	9-13	Narrowest but commercially most important formulation claims
Therapeutic methods	14-16	Covers selected uses, including cyanide poisoning and sequential nitrite/thiosulfate treatment

The patent is therefore not a conventional active-ingredient patent. Sodium thiosulfate was known before this patent. The claimed distinction is the pharmaceutical-grade quality profile, combined with selected compositions, sterile IV formulations and methods of use.

What limitations define claim 1?

Claim 1 is an unusually dense product-by-specification claim. It requires sodium thiosulfate pentahydrate to satisfy all listed limitations, including:

• No greater than about 10 ppm non-purgeable organic carbon.
• No greater than about 0.01% carbonate.
• No greater than about 0.05 ppm mercury.
• No greater than about 2 ppm aluminum.
• No greater than about 0.003% selenium.
• 98% to 102% sodium thiosulfate on an anhydrous basis, measured by ion chromatography.
• 32% to 37% water.
• Heavy metals no greater than about 10 ppm.
• Chloride no greater than about 200 ppm.
• Sulfide no greater than about 0.001%.
• Iron no greater than about 0.002%.
• Calcium no greater than about 0.01%.
• Potassium no greater than about 0.005%.
• Sulfite no greater than about 0.1%.
• Sulfate no greater than about 0.5%.
• Arsenic no greater than about 3 ppm.
• Lead no greater than about 0.001%.
• Total aerobic microbial count no greater than about 100 CFU/g.
• Yeast and mold count no greater than about 20 CFU/g.
• Bacterial endotoxins no greater than about 0.02 EU/mg.
• Nitrogen compounds no greater than about 0.002%.
• Insoluble matter no greater than about 0.005%.
• Residual anti-caking agent no greater than about 0.01%.
• Organic volatile impurities within ICH Q3C limits.
• A colorless 10% aqueous solution at 25°C.
• A pH of approximately 6.0 to 8.0 for that solution.
• Odorless crystals.

A product that exceeds any one required threshold may avoid literal infringement of claim 1, although the doctrine of equivalents could become relevant depending on the limitation and prosecution history. The phrase “about” introduces numerical tolerance questions. The practical scope will depend on analytical method variability, specification-defined test methods and the prosecution record.

How does the assay limitation affect infringement?

The assay limitation requires 98% to 102% sodium thiosulfate on an anhydrous basis measured by ion chromatography. This is narrower than a generic pharmacopeial assay requirement if the competing product uses a different analytical method or reports assay on a different basis.

A competitor may have noninfringement positions based on:

1. A different assay method.
2. A result outside the claimed range.
3. A water content outside 32% to 37%.
4. One or more impurity concentrations above the claimed threshold.
5. A different physical form or hydrate state.
6. Failure to meet the color, pH or odor limitations.

The claim does not appear to require a specific manufacturing process. A competitor could therefore use a different purification, crystallization or drying process and still infringe if the resulting material meets every limitation.

What do claims 2 and 3 add?

Claims 2 and 3 require positive identification tests for sodium and thiosulfate, respectively. These are dependent claims and add limited commercial differentiation because sodium thiosulfate pentahydrate ordinarily would be expected to identify positively for both ions.

The claims may provide fallback positions if claim 1 is challenged. Their value depends on the identification test used, whether the test is specified in the patent or pharmacopeia, and whether the identification limitations impose meaningful additional structure.

What pharmaceutical compositions are protected?

Claim 4 covers a pharmaceutical composition containing the claimed pharmaceutical-grade sodium thiosulfate pentahydrate and one or more pharmaceutically acceptable carriers or excipients. Because claim 4 repeats the quality requirements of claim 1, the composition must contain sodium thiosulfate meeting the full impurity and quality profile.

Claim 5 lists multiple administration routes:

• Oral
• Parenteral
• Inhalation
• Nasal
• Intravesical
• Vaginal
• Rectal
• Sublingual
• Ophthalmic
• Topical

Claim 6 narrows the composition to a single dosage form. Claim 7 identifies water as an excipient. Claim 8 requires an isotonic agent and one or more pH-adjusting agents.

These claims reach well beyond the commercial IV product, but their enforceability depends on whether the claimed quality profile and formulation are present in the accused product. The administration-route language does not independently protect a therapeutic use unless the product is actually formulated for that route.

What IV formulation does claim 9 protect?

Claim 9 covers a sterile composition suitable for IV administration containing:

Component	Claimed concentration
Sodium thiosulfate pentahydrate	250.0 mg/mL
Potassium chloride	About 4.40 mg/mL
Boric acid	About 2.80 mg/mL
Sodium hydroxide	pH adjustment
Water	Pharmaceutical vehicle

Claim 10 restates the core sterile aqueous solution. Claim 11 permits additional boric acid and sodium hydroxide sufficient to achieve an injectable pH. Claim 12 recites a package-scale composition containing:

• 12.5 grams sodium thiosulfate pentahydrate.
• 140 mg boric acid.
• 220 mg potassium chloride.

Claim 13 covers a sterile aqueous solution prepared by combining sodium thiosulfate pentahydrate, boric acid, potassium chloride, sodium hydroxide and water.

How narrow are claims 9 through 13?

Claims 9 through 13 are materially narrower than claims 1 and 4. They require a particular IV formulation architecture and, in several cases, specific concentrations. A competing IV product may avoid literal infringement by changing:

• Sodium thiosulfate concentration.
• Potassium chloride concentration or identity.
• Boric acid concentration or identity.
• pH-adjusting agent.
• Sterility presentation.
• Container configuration.
• Manufacturing sequence.
• Reconstitution method.
• Final dosage volume.

A formulation containing the same ingredients at materially different concentrations may not satisfy claims 9, 10 or 12. Claim 13 is potentially broader because it focuses on the ingredients and preparation, but it still requires a sterile aqueous solution intended for IV injection.

What methods of use are covered?

Claim 14 covers administering the claimed pharmaceutical-grade sodium thiosulfate pentahydrate to treat:

• Platinum-induced ototoxicity.
• Platinum-induced nephrotoxicity.
• Cyanide poisoning.
• Calciphylaxis.
• Vascular calcification associated with atherosclerosis.
• Fungal infection of the skin, nailbeds or nails.

Claim 15 narrows claim 14 to cyanide poisoning. Claim 16 covers sequential IV administration of:

1. A sterile aqueous solution containing the claimed sodium thiosulfate pentahydrate; and
2. A sterile aqueous solution containing sodium nitrite.

The method claims require use of the claimed pharmaceutical-grade material. Administration of ordinary sodium thiosulfate that does not meet claim 1’s quality specifications may not literally infringe.

How important is claim 16 for cyanide products?

Claim 16 is commercially relevant to sodium nitrite/sodium thiosulfate cyanide antidote products. It does not broadly cover every cyanide treatment. It requires sequential IV administration, the claimed sodium thiosulfate material and a separate sterile sodium nitrite solution.

Potential design-around positions include:

• Administering the agents in a different sequence.
• Using a combined product rather than sequential solutions, depending on claim construction.
• Using sodium thiosulfate that does not meet claim 1.
• Using an alternative cyanide antidote.
• Challenging whether the treatment protocol is performed by a relevant party.
• Challenging whether the claimed quality limitations are met.

The doctrine of divided infringement could become relevant if different entities provide or administer the two solutions, depending on the factual arrangement and applicable case law.

When does US Patent 8,496,973 lose exclusivity?

Event	Date or status
Earliest stated priority	November 9, 2010
Nonprovisional filing	2011, based on the patent family record associated with the grant
Grant	July 30, 2013
Nominal 20-year term endpoint	November 9, 2031
Patent-term adjustment	Must be confirmed from the USPTO patent record
Patent-term extension	Not established from the supplied claims
Maintenance fees	Must be confirmed from USPTO maintenance-fee records
Terminal disclaimer	Must be confirmed from the prosecution file

The grant date does not determine expiration. For a utility patent, the ordinary term generally runs 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments.[2] A provisional priority filing does not itself start the 20-year term.

The patent may lose enforceability before the nominal expiration date if maintenance fees are not paid or if a court invalidates the relevant claims. Conversely, patent-term adjustment could extend the term beyond the ordinary endpoint.

Is US Patent 8,496,973 listed in the Orange Book?

The claims alone do not establish Orange Book listing status. Orange Book listing depends on whether the patent was submitted for an approved drug product, whether FDA accepted the listing, the relevant NDA, and whether the patent covers the drug substance, drug product or an approved method of use.[3]

The patent’s composition and method claims could be relevant to an NDA product containing injectable sodium thiosulfate. That does not mean the patent is necessarily listed. A patent can be enforceable without being Orange Book-listed, and an Orange Book-listed patent can remain vulnerable to Paragraph IV litigation.

The principal FDA-linked products relevant to this technology include cyanide-antidote sodium thiosulfate products and sodium thiosulfate products used for platinum-induced ototoxicity. FDA approval of a product does not itself establish infringement of this patent.

What Paragraph IV challenges could target this patent?

A generic applicant could challenge the patent through an Abbreviated New Drug Application if the reference product and listed patent structure support a Paragraph IV certification. Possible grounds include:

Anticipation

A challenger could argue that earlier sodium thiosulfate material, pharmaceutical specifications or IV solutions disclose every limitation of the asserted claim. The dense impurity profile makes anticipation difficult unless a single prior-art reference discloses the complete combination.

Obviousness

Obviousness is a more plausible challenge. A challenger could combine:

• Known pharmaceutical-grade sodium thiosulfate.
• Pharmacopeial purity requirements.
• Known control limits for heavy metals, microbial load and endotoxins.
• Existing IV formulations.
• Known sodium nitrite/thiosulfate cyanide protocols.

The patent holder would likely argue that the precise combination of impurity limits, analytical controls, physical properties and sterile formulation was not routine and produced a material suitable for pharmaceutical injection.

Indefiniteness

The terms “about,” “pharmaceutical grade,” “suitable for intravenous administration,” “colorless,” “odorless” and “sufficient to achieve a pH suitable for injection” may create indefiniteness arguments if the specification does not provide objective boundaries or testing procedures.

Written description and enablement

The specification must support the full breadth of claims 5 and 14. Claim 5 reaches numerous administration routes, while claim 14 covers several distinct diseases and toxicities. A challenger could argue that the patent does not adequately support the entire genus or enable treatment across all listed conditions.

Double patenting

Any continuation, divisional or related patent covering the same sodium thiosulfate composition or formulation could create obviousness-type double-patenting issues, particularly if a terminal disclaimer was not filed.

What patent landscape surrounds sodium thiosulfate?

The relevant landscape has four technical clusters.

Pharmaceutical-grade material patents

These patents focus on impurity control, assay, hydrate form, crystallinity, stability and production methods. US 8,496,973 sits primarily in this cluster. Its protection is product-defined rather than process-defined.

Sterile injectable formulation patents

These patents cover concentration, excipients, pH, isotonicity, packaging, sterility and stability. Claims 9 through 13 fall into this category. Competitors are most exposed when they use the same 250 mg/mL concentration with potassium chloride and boric acid.

Cyanide antidote patents

This cluster covers sodium nitrite and sodium thiosulfate combinations, sequential administration, dosing regimens and emergency-use packaging. Claim 16 is directed to this area.

Platinum-induced ototoxicity patents

This cluster is associated with sodium thiosulfate administered to pediatric oncology patients receiving platinum chemotherapy. Commercial products approved for this use may have separate formulation, dosing, timing and method-of-use patents distinct from US 8,496,973.[4]

Biosimilar risk is not applicable because sodium thiosulfate is a small-molecule inorganic salt, not a biologic. The relevant competition is generic, authorized-generic and competing branded injectable entry.

Which companies are most relevant?

The commercial landscape includes:

Company or product category	Relevance
Hope Pharmaceuticals and related sodium thiosulfate cyanide-antidote products	Historical commercial relevance to sodium nitrite/sodium thiosulfate treatment
Fennec Pharmaceuticals and Pedmark	Sodium thiosulfate product for platinum-induced ototoxicity
Generic injectable manufacturers	Potential competitors for sodium thiosulfate injection and cyanide-antidote products
Pharmaceutical-grade API suppliers	Potential suppliers or challengers concerning the claim 1 quality profile
Contract manufacturers	Relevant to sterile formulation, fill-finish and analytical release testing

The competitive risk is product-specific. A manufacturer selling sodium thiosulfate API may face claim 1 exposure if the API meets every specification. A finished-product manufacturer may face claims 4 and 9 through 13 if its formulation uses that API and matches the claimed composition.

How strong is the patent estate?

The estate has moderate structural strength but uneven practical breadth.

Strengths

• Claim 1 covers the pharmaceutical-grade material itself.
• The claim combines many quality attributes, making complete anticipation more difficult.
• Claims 9 through 13 identify a commercially recognizable IV formulation.
• Claim 16 addresses the established sequential cyanide-antidote protocol.
• The patent can potentially reach API suppliers and finished-product manufacturers.

Weaknesses

• Every limitation in claim 1 must be satisfied.
• Many limitations are quality specifications that may vary by batch and analytical method.
• “About” and qualitative terms create construction issues.
• Broad administration-route and disease claims may face written-description or enablement challenges.
• Sodium thiosulfate, sterile injection and cyanide treatment were known technologies before the patent.
• A competitor may redesign the formulation or source material outside one or more claimed thresholds.

The most defensible commercial claims are likely the narrower IV composition claims if the accused product uses the recited concentrations and excipients. The broadest claim, claim 1, may be valuable against suppliers but is also the most exposed to analytical disputes and prior-art attacks.

What generic launch scenarios exist?

Launch scenario	Patent exposure
API with materially different impurity profile	Lower claim 1 risk, subject to all-test results
API meeting all claim 1 specifications	High claim 1 and claim 4 risk
IV product at 250 mg/mL with potassium chloride and boric acid	Highest exposure to claims 9-13
IV product with different excipients	Reduced literal exposure to claims 9-13
Cyanide product using sodium nitrite and sodium thiosulfate sequentially	Potential claim 16 exposure
Cyanide product using a different antidote protocol	Lower claim 16 exposure
Oral or topical sodium thiosulfate	Possible claim 4 or 5 exposure if the material meets claim 1
Product for platinum ototoxicity using nonconforming sodium thiosulfate	Potential method noninfringement position

A Paragraph IV filing would likely focus on invalidity and noninfringement in parallel. The product developer would need batch-level testing against each numerical limitation, not only a conventional assay and identity test.

What manufacturing and geographic barriers matter?

The patent does not require a particular manufacturing process, so process substitution alone does not avoid infringement. The main operational barrier is the ability to produce and consistently release material meeting the full impurity profile, microbial limits, endotoxin limit, water range and physical-property requirements.

Geographic coverage is limited to the United States patent. Commercial activities performed entirely outside the United States are not governed by US patent infringement rules, although importation into the United States, manufacture for US sale and components made abroad for combination in the United States can create exposure under 35 U.S.C. §§ 271(a), 271(b), 271(c) and 271(g), depending on the facts.[5]

Key Takeaways

1. US 8,496,973 is primarily a pharmaceutical-grade material and formulation patent, not a basic sodium thiosulfate composition-of-matter patent.
2. Claim 1 requires simultaneous satisfaction of numerous impurity, assay, microbial, endotoxin, solvent, physical and pH limitations.
3. Claims 9 through 13 create the clearest risk for a 250 mg/mL sterile IV product containing potassium chloride and boric acid.
4. Claim 16 is relevant to sequential IV sodium nitrite/sodium thiosulfate treatment for cyanide poisoning.
5. The nominal expiration date is November 9, 2031, subject to USPTO-record adjustments and enforceability events.
6. The claims supplied do not establish Orange Book listing, maintenance-fee status, terminal disclaimers or litigation disposition.
7. Generic entrants have potential design-around options involving impurity specifications, analytical methods, excipients, concentrations, administration sequence and product presentation.
8. Biosimilar risk is not applicable. The competitive threat is from generic API and injectable manufacturers.

FAQs

Can a company sell sodium thiosulfate without infringing US Patent 8,496,973?

Potentially. A product that fails at least one required claim 1 limitation may avoid literal infringement, but the full product specification and prosecution history must be analyzed.

Does a different manufacturing process avoid this patent?

Not necessarily. The principal claims are product and formulation claims. A different process does not avoid infringement if the resulting material or solution satisfies the claimed limitations.

Does the patent cover sodium thiosulfate for all medical indications?

No. Claim 14 lists specific indications. Claims 15 and 16 focus on cyanide poisoning. The patent does not broadly claim every therapeutic use of sodium thiosulfate.

Could a 250 mg/mL sodium thiosulfate injection avoid claims 9 through 13?

It may, if it changes a required excipient, concentration, pH-adjusting system, sterility configuration or other limitation. The exact formulation and claim construction control.

Is sodium thiosulfate subject to biosimilar competition?

No. Sodium thiosulfate is a small-molecule inorganic salt. Competition generally proceeds through generic-drug, NDA, authorized-generic or competing branded-product pathways rather than the biosimilar pathway.

References

1. United States Patent No. 8,496,973, “Pharmaceutical grade sodium thiosulfate and methods of making and using same” (July 30, 2013).
2. United States Code, 35 U.S.C. § 154.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
4. U.S. Food and Drug Administration. (2022). Pedmark (sodium thiosulfate) prescribing information.
5. United States Code, 35 U.S.C. §§ 271(a)-(g).

Drugs Protected by US Patent 8,496,973

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Hope Pharms	NITHIODOTE	sodium nitrite; sodium thiosulfate	SOLUTION, SOLUTION;INTRAVENOUS, INTRAVENOUS	201444-001	Jan 14, 2011		RX	Yes	Yes			Y	Y		TREATMENT OF ACUTE CYANIDE POISONING THAT IS JUDGED TO BE LIFE THREATENING
Hope Pharms	SODIUM THIOSULFATE	sodium thiosulfate	SOLUTION;INTRAVENOUS	203923-001	Feb 14, 2012		RX	Yes	Yes			Y	Y		TREATMENT OF ACUTE CYANIDE POISONING THAT IS JUDGED TO BE LIFE THREATENING

International Family Members for US Patent 8,496,973

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010270605
Canada	2767168
Denmark	2451435
European Patent Office	2451435