Details for Patent: 11,753,301

Which drugs does patent 11,753,301 protect, and when does it expire?

Patent 11,753,301 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: 11,753,301

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-purgeable 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:	US18/108,803
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,753,301
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 11,753,301: Sodium Thiosulfate Patent Scope, Claims, Exclusivity and Generic Risk

US Patent 11,753,301 protects a defined pharmaceutical-grade sodium thiosulfate active ingredient, processes for producing that material, aqueous injectable compositions, and therapeutic use of those compositions. The patent is directed primarily to product quality and formulation characteristics rather than to sodium thiosulfate as a chemical compound.

The commercial relevance is highest for Fennec Pharmaceuticals' PEDMARK, a sterile intravenous sodium thiosulfate product approved to reduce the risk of cisplatin-associated ototoxicity in pediatric patients. The strongest practical claims are claims 1, 5, 12-15 and 22. Claims 17-21 are broader method-of-treatment claims but may face greater validity and infringement challenges because sodium thiosulfate has long-standing use in several listed conditions.

What is US Patent 11,753,301?

US Patent 11,753,301 is titled "Pharmaceutical Grade Sodium Thiosulfate." The patent issued on August 29, 2023. The patent claims a highly purified sodium thiosulfate material with specified chemical, elemental, microbiological and pharmaceutical quality attributes.

Item	Patent information
Patent	US 11,753,301 B2
Title	Pharmaceutical grade sodium thiosulfate
Issue date	August 29, 2023
Technology	Pharmaceutical-grade sodium thiosulfate, manufacturing process and injectable compositions
Principal commercial relevance	PEDMARK sodium thiosulfate injection
Dosage form implicated by the claims	Sterile aqueous solution for intravenous injection
Patent term	Nominally extending into 2039, subject to the recorded patent-term adjustment
Patent type	Composition-of-matter quality specification, process, formulation and method-of-use claims

The patent is not a basic compound patent. Sodium thiosulfate has been known and used medically for decades, including as an antidote for cyanide poisoning. The patent instead attempts to distinguish pharmaceutical-grade material by imposing a cumulative set of impurity, potency, microbial, endotoxin, solvent and physical-property limitations.

What does claim 1 protect?

Claim 1 protects pharmaceutical-grade sodium thiosulfate meeting all listed limitations. The claim requires the material to satisfy each of the following categories:

1. Assay and identity:

   • 98% to 102% sodium thiosulfate on an anhydrous basis.
   • Measurement by ion chromatography.
   • A colorless 10% aqueous solution.
   • pH between approximately 6.0 and 8.0.

2. Organic and inorganic impurities:

   • Non-purgeable organic carbon no greater than approximately 10 ppm.
   • Mercury no greater than approximately 0.05 ppm.
   • Aluminum no greater than approximately 2 ppm.
   • Selenium no greater than approximately 0.003% by weight.
   • Arsenic no greater than approximately 3 ppm.
   • Lead no greater than approximately 0.001% by weight.
   • Total heavy metals no greater than approximately 10 ppm.

3. Process-related ionic impurities:

   • Chloride no greater than approximately 200 ppm.
   • Sulfide no greater than approximately 0.001%.
   • Iron no greater than approximately 0.002%.
   • Calcium no greater than approximately 0.01%.
   • Potassium no greater than approximately 0.005%.
   • Sulfite no greater than approximately 0.1%.
   • Sulfate no greater than approximately 0.5%.

4. Pharmaceutical quality attributes:

   • Microbial aerobic count no greater than 100 CFU/g.
   • Yeast and mold count no greater than 20 CFU/g.
   • Bacterial endotoxins no greater than 0.02 EU/mg.
   • Nitrogen compounds no greater than 0.002%.
   • Insoluble matter no greater than 0.005%.
   • Residual anti-caking agent no greater than 0.01%.
   • Organic volatile impurities within ICH Q3C limits.

A competitor would need to practice every limitation to infringe literally. Failure to meet one numerical threshold may avoid literal infringement of claim 1, although the doctrine of equivalents could remain relevant depending on the difference and prosecution history.

The claim is technically narrow because it contains many cumulative specifications. It is commercially significant because a finished injectable manufacturer may purchase or internally manufacture sodium thiosulfate that satisfies the claimed specifications even if the finished product has a different label or indication.

How do claims 2 and 3 narrow the patent scope?

Claim 2 narrows claim 1 by reducing the non-purgeable organic carbon limit from approximately 10 ppm to approximately 8 ppm.

Claim 3 requires anhydrous sodium thiosulfate. The independent quality claim therefore covers both anhydrous and hydrated material through claim 1, while claim 3 creates a narrower anhydrous subgenus.

The anhydrous limitation matters because sodium thiosulfate is commonly handled as sodium thiosulfate pentahydrate. A manufacturer may avoid claim 3 by using the pentahydrate, but that does not necessarily avoid claim 1, claim 5 or claim 22 if the material and finished product meet those claims' limitations.

What manufacturing process is protected by claim 4?

Claim 4 covers a process for preparing the claimed pharmaceutical-grade sodium thiosulfate. The process requires:

1. Contacting sodium sulfite with sulfur in a solvent.
2. Filtering the resulting reaction mixture.
3. Concentrating the filtered solution.
4. Exposing the solution to activated carbon.
5. Filtering the activated-carbon-treated solution.
6. Crystallizing sodium thiosulfate from the solution.

The claim is a process claim, not merely a result-by-process claim. A competing manufacturer using a different purification sequence may have a strong noninfringement position even if its final sodium thiosulfate meets the same quality specifications.

The activated-carbon and crystallization steps are particularly important. They provide a process route for reducing organic carbon and other impurities while producing pharmaceutical-grade crystals. A process that uses different adsorbents, membrane purification, ion exchange, recrystallization conditions or starting materials may fall outside claim 4.

What formulations are protected by claims 5 through 16?

Claims 5 through 16 cover pharmaceutical compositions containing the claimed sodium thiosulfate material in an aqueous pharmaceutically acceptable carrier.

Claim 5 is broad in dosage-form terms. It covers a composition containing the specified sodium thiosulfate and an aqueous carrier. Claim 6 narrows the carrier to sterile water for injection.

Claim 8 lists multiple administration routes:

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

Claim 9 narrows the composition to parenteral administration, and claim 10 requires a single dosage form.

Claims 11 through 15 are more commercially focused. They cover an injectable composition with an isotonic agent and pH-adjusting agents. Claim 12 identifies:

• Potassium chloride at approximately 4.40 mg/mL.
• Boric acid at approximately 2.80 mg/mL.
• Sodium hydroxide.
• Sterility.
• Suitability for intravenous administration.

Claims 13 through 15 then specify the sodium thiosulfate concentration and batch quantities:

Claim	Limitation
12	Sterile intravenous solution with potassium chloride, boric acid and sodium hydroxide
13	Approximately 250 mg/mL sodium thiosulfate pentahydrate on an anhydrous basis
14	Approximately 140 mg boric acid and 220 mg potassium chloride
15	Approximately 12.5 g sodium thiosulfate pentahydrate on an anhydrous basis

These limitations closely track the commercial presentation of PEDMARK, which is supplied as a concentrated sodium thiosulfate injection. The formulation claims therefore have greater product-specific relevance than the broader route-of-administration claims.

What does claim 22 protect?

Claim 22 is an independent composition claim directed to a sterile solution for intravenous injection prepared by combining:

• The claimed pharmaceutical-grade sodium thiosulfate.
• Boric acid.
• Potassium chloride.
• Sodium hydroxide.
• Water.

Unlike claim 12, claim 22 does not recite the same detailed concentrations for boric acid and potassium chloride. That makes claim 22 potentially broader with respect to formulation quantities, provided the formulation contains the claimed sodium thiosulfate quality profile and the specified ingredients.

Claim 23 covers anhydrous sodium thiosulfate in the claim 22 formulation. Claim 24 covers sodium thiosulfate pentahydrate.

Claims 22 through 24 are likely the most important claims for an injectable product that uses the same excipient system but changes concentration, batch size or presentation.

What therapeutic uses are covered by claims 17 through 21?

Claim 17 covers administration of the claimed composition to treat or prevent:

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

Claims 18 through 21 narrow that broad claim to cyanide poisoning and platinum-induced ototoxicity, with certain claims requiring anhydrous sodium thiosulfate.

The platinum-induced ototoxicity claims are the most commercially relevant because they correspond to the approved use of PEDMARK. The cyanide-poisoning claim is less differentiated from historic sodium thiosulfate use and may encounter prior-art and obviousness arguments.

The fungal-infection and vascular-calcification limitations expand the patent beyond the approved pediatric oncology indication. Their practical enforceability depends on the asserted composition claim, the prescribed treatment protocol and the evidence that the accused product meets every quality limitation.

What is the Orange Book status of US 11,753,301?

The patent is relevant to the FDA-approved PEDMARK product and has been associated with the product's patent protection in FDA regulatory and commercial disclosures. The Orange Book question is product-specific: a patent is listed against an approved drug only when the sponsor identifies it as covering the drug, its formulation or an approved method of use under FDA listing rules.

The relevant regulatory distinction is:

Regulatory issue	Assessment
Product	PEDMARK sodium thiosulfate injection
NDA holder	Fennec Pharmaceuticals
FDA approval	September 2022
Approved use	Reduction of cisplatin-associated ototoxicity risk in pediatric patients with localized, nonmetastatic solid tumors
Small-molecule or biologic	Small molecule
Biosimilar pathway	Not applicable
Likely abbreviated pathway	ANDA under section 505(j)
Relevant patent challenge	Paragraph IV certification if an ANDA applicant seeks approval before patent expiry
Orphan exclusivity	Relevant to the approved indication, subject to the FDA exclusivity record

PEDMARK is not a biologic. A competitor would not file a biosimilar application under the Public Health Service Act. A generic applicant would generally use an ANDA and address listed patents through Paragraph I, II, III or IV certifications.

When does PEDMARK lose exclusivity?

PEDMARK's commercial protection has several separate components.

Patent exclusivity

US 11,753,301 is expected to provide protection into approximately 2039 based on its filing and priority history, subject to the official patent-term calculation and any patent-term adjustment. The patent's claims are not limited to the FDA-approved indication. A noninfringing product may still be possible if the competitor uses sodium thiosulfate that falls outside the claimed impurity profile or a formulation that avoids the claimed excipient combination.

Orphan-drug exclusivity

PEDMARK received approval for a pediatric oncology use that has been associated with orphan-drug protection. Orphan-drug exclusivity generally lasts seven years from approval for the same approved use. For a September 2022 approval, the relevant period would generally run into September 2029, subject to the FDA's designation and approval records.

Orphan exclusivity does not block every sodium thiosulfate product. It primarily restricts FDA approval of the same drug for the same orphan indication, subject to statutory exceptions.

Clinical investigation exclusivity

Because sodium thiosulfate was previously known, PEDMARK's regulatory protection is not equivalent to the five-year exclusivity generally associated with a new chemical entity. Any three-year exclusivity associated with new clinical investigations would depend on the FDA's specific exclusivity determination and would not necessarily block all sodium thiosulfate ANDAs.

How strong is the patent estate?

The patent is strongest against a competitor that reproduces the commercial product's combination of:

• Pharmaceutical-grade sodium thiosulfate.
• Very low organic carbon.
• Controlled heavy metals and elemental impurities.
• Low sulfate, sulfite and chloride.
• Low bioburden and endotoxin.
• Sterile water-based intravenous formulation.
• Boric acid, potassium chloride and sodium hydroxide.
• Approximately 250 mg/mL concentration.
• Use for cisplatin-associated ototoxicity.

Its principal strength is the combination of raw-material specifications and finished-product formulation limitations. A competitor cannot avoid the patent merely by changing the product name or using a different label if its material and formulation still satisfy the claims.

Its principal weakness is claim breadth relative to the age of sodium thiosulfate. Sodium thiosulfate itself is old. A challenger could argue that the impurity thresholds are routine pharmaceutical specifications, that the purification steps are obvious process controls, or that the claimed excipient combination would have been expected for an injectable formulation.

Key validity pressure points

Issue	Potential challenge
Written description	Whether the specification supports every listed numerical threshold and combination
Enablement	Whether the full range of impurity limits can be reliably achieved without undue experimentation
Obviousness	Whether known sodium thiosulfate purification and injectable formulation practices render the claims obvious
Indefiniteness	Meaning of terms such as "about," "pharmaceutical grade" and "heavy metal content"
Analytical variability	Reproducibility of ppm, CFU/g and endotoxin measurements
Infringement proof	Whether a competitor's raw material satisfies all cumulative specifications
Method claims	Whether the accused use corresponds to the claimed condition and composition

Which companies are challenging US 11,753,301?

The supplied claim set does not identify an ANDA applicant, Paragraph IV notice letter, district-court complaint or settlement agreement involving US 11,753,301. No challenger can be identified from the patent claims alone.

The likely competitive groups are:

1. Existing sodium thiosulfate injection suppliers serving the cyanide-antidote and hospital markets.
2. Generic manufacturers seeking an ANDA for a sodium thiosulfate injection.
3. Contract manufacturers capable of producing pharmaceutical-grade sodium thiosulfate.
4. Developers seeking a lower-cost alternative to PEDMARK for pediatric cisplatin patients.

A generic applicant could pursue several design-around strategies:

• Use sodium thiosulfate with a specification outside at least one claim 1 threshold.
• Avoid the boric acid and potassium chloride combination.
• Use a different pH-adjustment system.
• Use a different concentration or dosage presentation.
• Manufacture through a process that does not use the claimed activated-carbon sequence.
• Seek approval for cyanide poisoning rather than the patented ototoxicity indication, subject to listed-use and regulatory restrictions.

What generic launch risks exist?

Generic launch risk is material but product-dependent.

Scenario	Risk under US 11,753,301
Exact PEDMARK formulation and raw material	High
Same excipients with different quantities	Moderate to high, particularly under claim 22
Sodium thiosulfate injection for cyanide poisoning using different excipients	Moderate
Conventional sodium thiosulfate injection with untested impurity profile	Unclear until analytical testing
Nonsterile pharmaceutical-grade bulk sodium thiosulfate	Lower for formulation claims, but claim 1 may remain relevant
Product using a different purification process	Lower under claim 4, but composition claims remain relevant
Product outside the claimed impurity specifications	Potentially lower, subject to FDA quality requirements
Biosimilar product	Not applicable

A Paragraph IV challenge would likely focus on invalidity of the cumulative quality limitations, noninfringement based on one or more specifications, and the distinction between the patented product and older sodium thiosulfate injections.

Does the patent create a manufacturing or licensing barrier?

Yes. The patent can create a commercial barrier for manufacturers that do not control pharmaceutical-grade sodium thiosulfate production. The process claim may also affect contract-manufacturing arrangements where the supplier uses sodium sulfite, sulfur, activated carbon and crystallization in the claimed sequence.

The most defensible licensing position would cover:

• Access to the claimed raw material.
• Use of the PEDMARK-like injectable formulation.
• Pediatric cisplatin ototoxicity indications.
• Supply of finished sterile product.
• Territory-specific rights outside the United States.

No licensing agreement or settlement involving US 11,753,301 is established by the supplied information. Fennec's commercial partnerships, distribution arrangements or manufacturing agreements should not be treated as patent licenses unless the relevant agreement expressly grants patent rights.

How does this patent compare with ordinary sodium thiosulfate patents?

US 11,753,301 differs from conventional sodium thiosulfate patents in four ways:

Feature	US 11,753,301	Conventional sodium thiosulfate protection
Chemical compound	Old active ingredient	May cover preparation or use
Main protection	Purity and pharmaceutical quality profile	Often therapeutic use or manufacturing
Formulation	Sterile aqueous injectable with specified excipients	May be broad or product-specific
Enforcement evidence	Analytical testing and batch records	Product labels, use evidence or process discovery

The patent is therefore a quality-and-formulation patent estate rather than a fundamental chemical patent. Its commercial value depends on how closely a competitor's product resembles the claimed PEDMARK raw material and formulation.

Key Takeaways

• US 11,753,301 claims pharmaceutical-grade sodium thiosulfate defined by a dense set of impurity, potency, microbiological and physical-property limits.
• Claim 4 protects a sodium sulfite and sulfur process that includes activated-carbon treatment and crystallization.
• Claims 12-15 closely track a sterile intravenous formulation containing sodium thiosulfate, boric acid, potassium chloride and sodium hydroxide.
• Claim 22 may be broader than claims 12-15 because it does not specify the same excipient concentrations.
• Claims 17-21 cover several therapeutic uses, with platinum-induced ototoxicity being the most commercially important.
• The patent is relevant to PEDMARK and is expected to provide protection into approximately 2039, subject to the official patent-term calculation.
• PEDMARK's orphan-drug protection is generally relevant through approximately 2029 for the approved indication.
• Sodium thiosulfate is a small molecule, so biosimilar risk does not apply. The principal regulatory competitor would be an ANDA applicant.
• The most credible design-around paths involve impurity specifications, formulation excipients, process sequence and indication.
• The patent is strongest against an exact or near-exact PEDMARK copy and weaker against legacy cyanide-antidote products using different materials or formulations.

FAQs About US Patent 11,753,301

Does US 11,753,301 cover all sodium thiosulfate products?

No. It covers sodium thiosulfate products that satisfy the complete claimed quality profile or fall within one of the specific formulation, process or method claims.

Is sodium thiosulfate pentahydrate covered?

Yes. Claim 24 expressly covers sodium thiosulfate pentahydrate in the claimed sterile intravenous composition. Claim 3 separately covers anhydrous material within the claim 1 composition.

Can a generic avoid the patent by changing the concentration?

Possibly, but concentration changes alone may not avoid claim 22, which does not recite the same detailed concentrations as claims 12-15. The generic would need to assess every limitation of each asserted claim.

Does the patent cover cyanide antidote products?

Potentially. Claim 17 and claim 18 recite treatment of cyanide poisoning using the claimed pharmaceutical composition. Older sodium thiosulfate products may avoid infringement if their raw material or formulation does not meet the claimed limitations.

Is a Paragraph IV challenge likely for this patent?

A Paragraph IV challenge is legally available to an ANDA applicant seeking approval before patent expiry. The strength of such a challenge would depend on the patent's Orange Book listing, the applicant's proposed product, analytical specifications, prior art and the prosecution history.

Sources

1. U.S. Patent and Trademark Office. (2023). U.S. Patent No. 11,753,301 B2: Pharmaceutical grade sodium thiosulfate.

2. U.S. Food and Drug Administration. (2022). PEDMARK (sodium thiosulfate) injection prescribing information.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Orange Book.

4. International Council for Harmonisation. (2023). ICH Q3C(R3): Impurities: Guideline for residual solvents.

5. U.S. Food and Drug Administration. (2024). Approved drug product exclusivity and patent information resources.

Drugs Protected by US Patent 11,753,301

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 SERIOUS OR LIFE-THREATENING
Hope Pharms	SODIUM THIOSULFATE	sodium thiosulfate	SOLUTION;INTRAVENOUS	203923-001	Feb 14, 2012		RX	Yes	Yes			Y	Y		SODIUM THIOSULFATE INJECTION IS INDICATED FOR SEQUENTIAL USE WITH SODIUM NITRITE FOR THE TREATMENT OF ACUTE CYANIDE POISONING THAT IS JUDGED TO BE SERIOUS OR LIFE-THREATENING

International Family Members for US Patent 11,753,301

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