US Patent 10,596,190: Scope, Claims, Expiration, and Sodium Thiosulfate Patent Landscape

US Patent 10,596,190 protects a narrow method of administering sodium thiosulfate after cisplatin to reduce hearing loss in very young pediatric patients with localized, non-metastatic tumors. The claim requires specific patient age, cisplatin exposure, sodium thiosulfate dosing, approximately six-hour timing, a quantified ototoxicity benefit, defined audiometric endpoints, and no substantive impairment of relapse-free or overall survival.

The patent is relevant to Fennec Pharmaceuticals’ PEDMARK, a sodium thiosulfate product approved by the FDA in 2022 to reduce the risk of cisplatin-associated ototoxicity in pediatric patients with localized, non-metastatic solid tumors.[1]

What does US Patent 10,596,190 protect?

US Patent 10,596,190 protects a treatment protocol rather than sodium thiosulfate as a chemical compound. Its independent claim requires the combined administration of:

Claim element	Required limitation
Patient	Pediatric patient about 5 years of age or younger
Cancer	Localized and non-metastatic tumor
Platinum drug	Cisplatin
Cisplatin dose	About 1-5 mg/kg or about 10-300 mg/m² per cycle
Cisplatin schedule	One to five administration days per cycle
Protective agent	Sodium thiosulfate
Sodium thiosulfate dose	About 5-25 g/m²
Timing	After each cisplatin dose, about six hours later
Treatment objective	At least 50% better reduction in ototoxicity than without sodium thiosulfate
Hearing endpoint	One or more specified audiometric criteria
Baseline	Hearing change measured against pre-treatment baseline
Oncologic outcome	No substantive effect on relapse-free survival or overall survival

The claim is cumulative. A method that omits a required limitation generally would not literally infringe claim 1, even if it uses sodium thiosulfate to reduce cisplatin-related hearing loss.

How narrow is claim 1 of US 10,596,190?

Claim 1 is narrower than the broad clinical concept of using sodium thiosulfate with cisplatin.

The most important narrowing limitations are:

The patient must be about five years of age or younger.
The tumor must be localized and non-metastatic.
Cisplatin must be administered within specified dose and cycle ranges.
Sodium thiosulfate must be administered after each cisplatin dose.
The interval must be about six hours.
The reduction in ototoxicity must satisfy at least one listed hearing-loss definition.
The administration must not substantively affect relapse-free or overall survival.

A pediatric protocol involving a 10-year-old patient, a metastatic tumor, carboplatin rather than cisplatin, or sodium thiosulfate administered at a materially different time may fall outside the literal wording of claim 1. The doctrine of equivalents could still be relevant, but it would depend on prosecution history, claim construction, and the facts of a particular case.

What are the technical scope and infringement pressure points?

Patient age

The claim is directed to a patient “about 5 years of age and under.” “About” creates potential claim-construction issues near the age boundary. The clearest infringement risk is for patients aged five years or younger. The term does not necessarily cover the broader FDA-approved population, which includes pediatric patients from one month to less than 18 years of age.[1]

Tumor status

The tumor must be localized and non-metastatic. This limitation is commercially important because PEDMARK’s FDA indication also focuses on pediatric patients with localized, non-metastatic solid tumors.[1]

A patient with metastatic disease, recurrent disease, or a tumor whose staging is unresolved presents a different infringement analysis. Documentation of disease status would likely matter in a method-of-treatment dispute.

Cisplatin dose and schedule

The claim covers either:

approximately 1-5 mg/kg per cycle; or
approximately 10-300 mg/m² per cycle.

Cisplatin must be administered on one to five days per cycle. The claim does not require a particular tumor type, route of cisplatin administration, or total number of cycles.

The broad 10-300 mg/m² range captures many pediatric cisplatin regimens. The alternative weight-based range may create a separate route to infringement where dosing is recorded by body weight rather than body surface area.

Sodium thiosulfate timing

The claim requires sodium thiosulfate after each cisplatin dose and approximately six hours after cisplatin. This is a central design-around issue.

A regimen using sodium thiosulfate before cisplatin, immediately after cisplatin, or only after selected cycles may avoid literal infringement if the timing or “each dose” limitations are not met. Whether a shorter or longer interval remains “about six hours” would depend on ordinary clinical practice, intrinsic patent evidence, prosecution history, and expert testimony.

Ototoxicity measurement

The claim includes several audiometric definitions. These include:

a 20 dB loss at one frequency;
a 10 dB loss at two consecutive frequencies;
loss of response at three consecutive test frequencies;
bilateral high-frequency hearing-loss grades based on 8,000 Hz, 4,000 Hz, 2,000 Hz, or 1,000 Hz thresholds; and
alternative hearing-loss grades based on hearing levels above 4,000 Hz, at 4,000 Hz and above, or at lower frequencies.

The use of multiple alternatives broadens the types of clinical hearing data that may satisfy the claim. It also creates evidentiary complexity. A patent holder would need to show that the accused treatment produced the claimed reduction under at least one qualifying metric.

“At least 50% better” reduction

The phrase “at least 50% better” is potentially outcome-determinative. It appears to require a comparative benefit against a patient not receiving sodium thiosulfate, but the claim does not expressly define whether the comparison is:

relative risk reduction;
absolute percentage-point reduction;
reduction in the proportion of patients with hearing loss;
reduction in hearing-threshold change; or
another statistical measure.

This language may be challenged as indefinite or construed through the specification and prosecution record. Clinical-study data from the relevant pediatric trials would likely be important to claim interpretation and infringement analysis.

When does US Patent 10,596,190 expire?

The patent issued on March 24, 2020. Its underlying priority date is reported as March 15, 2013. On a standard 20-year term calculation from the earliest effective nonprovisional priority date, the base expiration is expected in March 2033, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.[2]

Event	Date or status
Earliest reported priority	March 15, 2013
Patent issuance	March 24, 2020
Base 20-year expiration estimate	March 15, 2033
Patent-term adjustment	Must be confirmed in the USPTO patent record
Patent-term extension	No extension is established by the claim text
Commercial product associated with the technology	PEDMARK, sodium thiosulfate

The legally operative expiration date is the USPTO term calculation, not the simple 20-year estimate. Any freedom-to-operate opinion should use the patent’s terminal disclaimer and patent-term-adjustment data.

What is the FDA and Orange Book status of the protected product?

The FDA approved PEDMARK, sodium thiosulfate injection, on September 20, 2022, under NDA 214701. The approved use is to reduce the risk of ototoxicity associated with cisplatin in pediatric patients one month of age and older with localized, non-metastatic solid tumors.[1]

Regulatory issue	Status
Product	PEDMARK
Active ingredient	Sodium thiosulfate
Sponsor	Fennec Pharmaceuticals Inc.
NDA	214701
FDA approval	September 20, 2022
FDA indication	Reduction of cisplatin-associated ototoxicity in pediatric patients with localized, non-metastatic solid tumors
Dosage form	Intravenous injection
Small-molecule pathway	ANDA pathway, not biosimilar pathway
Regulatory exclusivity	New clinical investigation exclusivity and pediatric-exclusivity issues require current FDA Orange Book confirmation

PEDMARK is not a biologic, so biosimilar substitution rules do not apply. A competitor would generally pursue an abbreviated new drug application, subject to applicable patent certifications and any regulatory exclusivity.

The Orange Book status of US 10,596,190 depends on current FDA listing data. The patent claim is a method-of-use claim, making a section viii “label carve-out” theoretically relevant if an ANDA applicant removes the patented use from its labeling. That strategy may be difficult where the approved product’s principal commercial use is the patented ototoxicity-reduction indication.

How does the patent compare with the FDA-approved indication?

The FDA label covers a broader age range than claim 1.

Issue	US 10,596,190 claim 1	FDA PEDMARK indication
Age	About 5 years and under	One month and older, pediatric population
Disease status	Localized, non-metastatic tumor	Localized, non-metastatic solid tumor
Platinum agent	Cisplatin	Cisplatin
Timing	About six hours after each cisplatin dose	Label-specific administration instructions
Clinical objective	At least 50% better ototoxicity reduction	Reduce risk of cisplatin-associated ototoxicity
Survival limitation	No substantive effect on relapse-free or overall survival	Supported by clinical evidence and labeling

The patent therefore does not cover every patient within the FDA-approved age range on its face. It has particular importance for the youngest pediatric population, where cisplatin-associated hearing loss is a major clinical concern.

What other patents protect sodium thiosulfate otoprotection?

The relevant landscape includes three patent categories:

Method-of-use patents

These claims cover administering sodium thiosulfate with cisplatin or another platinum-based chemotherapy to reduce ototoxicity. US 10,596,190 is in this category.

The principal claim variables are:

patient age;
tumor localization and metastatic status;
cisplatin dose;
sodium thiosulfate dose;
administration interval;
hearing-loss definition;
survival outcome; and
specific pediatric cancer population.

Formulation and product patents

Separate rights may cover pharmaceutical formulations of sodium thiosulfate, including concentration, excipients, pH, container systems, stability, and ready-to-use injectable presentations. These rights can create commercial barriers even when a method claim is avoided.

For an ANDA applicant, formulation patents may be more difficult to avoid than method claims if the proposed product must match the reference listed drug’s dosage form, concentration, or inactive-ingredient profile.

Clinical and manufacturing rights

Additional protection may concern:

sterile manufacture of sodium thiosulfate injection;
impurity control;
storage and stability;
dosing kits or co-packaged administration systems;
use with specific platinum regimens; and
pediatric oncology protocols.

A complete clearance review must evaluate the entire patent family, continuations, divisionals, terminal disclaimers, and foreign counterparts rather than US 10,596,190 alone.

Which companies are challenging the patent?

No established biosimilar challenge exists because sodium thiosulfate is a small molecule. A generic applicant would use the ANDA process and could submit:

a paragraph III certification, accepting delay until patent expiration;
a paragraph IV certification, alleging invalidity, unenforceability, or non-infringement; or
a section viii statement carving out a patented method of use.

Publicly identifying a paragraph IV challenger requires current FDA Orange Book data, ANDA litigation filings, and district-court or Federal Circuit dockets. The patent number and claim text alone do not establish that a generic company has filed a challenge.

What patent litigation and settlement risks exist?

The main litigation theories would be:

Risk area	Likely issue
Infringement	Whether the accused protocol meets every dosing, timing, age, tumor-status, and hearing-outcome limitation
Invalidity	Written description, enablement, anticipation, obviousness, indefiniteness, and patentable subject matter
Claim construction	Meaning of “about,” “after,” “about six hours,” “at least 50% better,” and “substantively affect”
Regulatory overlap	Whether an ANDA label induces use covered by the patent
Settlement	Delayed generic entry, licensed entry, or label carve-out
Injunction	Potential under the Hatch-Waxman framework after a paragraph IV notice

The survival limitation may create a substantial factual burden. The patent does not merely require administration of sodium thiosulfate; it requires that the treatment not substantively impair relapse-free or overall survival compared with a control pediatric patient.

How strong is the patent estate?

US 10,596,190 has meaningful commercial value because it aligns closely with the clinical use underlying PEDMARK. Its strength is highest where the product is used:

in very young children;
for localized, non-metastatic tumors;
with cisplatin;
at covered dose levels;
with sodium thiosulfate administered about six hours later; and
under the labeled ototoxicity-reduction protocol.

Its principal weaknesses are claim breadth and proof requirements. The age limitation narrows coverage. The “at least 50% better” and “substantively affect” limitations may require clinical and statistical evidence. The multiple hearing criteria broaden coverage but may create claim-construction and measurement disputes.

The estate is stronger when supported by related continuation patents covering broader pediatric populations, alternative dosing intervals, formulations, or specific clinical regimens. It is weaker if US 10,596,190 is treated in isolation and no enforceable continuation or formulation claims remain in force.

What generic launch scenarios exist?

Paragraph III launch

A generic applicant could accept the patent and delay launch until the enforceable patent term ends. This is the lowest litigation-risk pathway but postpones market entry.

Paragraph IV challenge

A challenger could argue that:

the claim is obvious in view of prior cisplatin otoprotection studies;
the clinical benefit is not adequately described across the full claimed range;
“at least 50% better” is indefinite;
the survival limitation lacks adequate written description or enablement; or
the proposed product or label does not practice every claim limitation.

Section viii carve-out

A label carve-out could remove the patented ototoxicity-reduction indication. This strategy has limited commercial value if the product’s principal demand is generated by that indication and if physicians may still prescribe the generic for the patented use.

Design-around

A competitor could investigate:

administration at a materially different interval;
alternative sodium thiosulfate dosing;
use in an older pediatric population;
use in metastatic disease;
administration after selected rather than every cisplatin dose; or
a different documented treatment objective.

Each design-around would require review of related patents and potential equivalents liability.

Key Takeaways

US 10,596,190 is a method-of-treatment patent for sodium thiosulfate otoprotection after cisplatin.
Claim 1 is limited to very young pediatric patients, localized non-metastatic tumors, specified cisplatin and sodium thiosulfate doses, and approximately six-hour post-cisplatin administration.
The claim requires a quantified hearing benefit and no substantive adverse effect on relapse-free or overall survival.
The estimated base expiration is March 15, 2033, subject to USPTO term calculations.
The FDA-approved PEDMARK population is broader than the age range expressly recited in claim 1.
Generic competitors face an ANDA pathway, not a biosimilar pathway.
Paragraph IV, section viii, and design-around strategies are the principal generic-entry routes.
The most important legal uncertainties concern “about six hours,” “at least 50% better,” and “substantively affect.”
Formulation, continuation, manufacturing, and related method-of-use patents may materially expand the effective commercial estate.

FAQs

Does US 10,596,190 cover all uses of sodium thiosulfate in children?

No. The claim is limited to a defined cisplatin regimen, young pediatric patients, localized non-metastatic tumors, specified timing and dosing, and qualifying hearing outcomes.

Is PEDMARK protected by a composition-of-matter patent?

US 10,596,190 is not a composition-of-matter claim. It protects a method of using sodium thiosulfate. Separate formulation or product patents may provide additional protection.

Can a generic sodium thiosulfate product launch before 2033?

Potentially. A generic applicant could pursue a successful paragraph IV challenge, use a valid section viii carve-out, avoid the asserted claims, or enter under a settlement. A simple approval does not establish freedom to market for the patented use.

Does the patent cover patients older than five years?

Claim 1 expressly targets patients “about 5 years of age and under.” Older patients may be covered by other claims or related patents, but claim 1 alone does not clearly reach the full FDA-labeled pediatric population.

Is sodium thiosulfate a biosimilar product?

No. Sodium thiosulfate is a small-molecule drug. A competing product would generally use the ANDA framework rather than the biosimilar pathway.

References

U.S. Food and Drug Administration. (2022). PEDMARK: Sodium thiosulfate injection prescribing information. FDA.
United States Patent and Trademark Office. (2020). U.S. Patent No. 10,596,190, Methods for reducing ototoxicity in pediatric patients receiving platinum-based chemotherapy. USPTO.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. FDA.
U.S. Code, 35 U.S.C. §§ 154, 156, and 271.
U.S. Code, 21 U.S.C. § 355(j).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Fennec Pharms Inc	PEDMARK	sodium thiosulfate	SOLUTION;INTRAVENOUS	212937-001	Sep 20, 2022		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial			Y	A METHOD OF REDUCING OTOTOXICITY IN A HUMAN PEDIATRIC PATIENT ABOUT 5 YEARS OF AGE OR UNDER WITH LOCALIZED MEDULLOBLASTOMA COMPRISING ADMINISTERING SODIUM THIOSULFATE ABOUT SIX HOURS AFTER ADMINISTRATION OF CISPLATIN	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2018374850	⤷ Start Trial
Brazil	112020010726	⤷ Start Trial
Canada	3082838	⤷ Start Trial
China	112955157	⤷ Start Trial
European Patent Office	3716987	⤷ Start Trial
Israel	274645	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,596,190

Which drugs does patent 10,596,190 protect, and when does it expire?

Summary for Patent: 10,596,190