United States Drug Patent 10,117,848: Claim Scope, Etripamil Formulation Protection, and Patent Landscape

US Patent No. 10,117,848 protects high-concentration aqueous nasal formulations of the S-enantiomer of etripamil, particularly an acetate salt formulation containing approximately 350 mg/mL of drug. Its claims also cover two-pump nasal delivery systems, acute treatment of paroxysmal supraventricular tachycardia (PSVT), and a defined manufacturing process using acidification, EDTA, heating, stirring, and pH adjustment.[1]

The patent is directed primarily to the commercial dosage form rather than to etripamil as a chemical entity. A competing product could avoid direct infringement by changing the salt, concentration, delivery volume, pump configuration, process sequence, or treatment method, although the practical freedom-to-operate analysis depends on the full patent family and related continuation patents.

What drug and formulation does US Patent 10,117,848 protect?

Compound I is etripamil, also known as MSP-2017, a short-acting calcium-channel blocker developed for rapid termination of PSVT. The asserted commercial formulation is the acetate salt of the S-enantiomer of etripamil in an aqueous nasal spray.

The core technical problem addressed by the patent is delivering a large dose in a small nasal volume. The claims cover a formulation that:

Feature	Claimed scope
Route	Nasal administration
Dosage form	Aqueous solution
Drug form	Free base, pharmaceutically acceptable salt, racemate, or enantiomer
Broad concentration	150-600 mg/mL
Preferred concentration	350 mg/mL +/- 25 mg/mL
Water content	40%-85% w/v
Broad pH	3.0-6.0
Narrow pH	4.4-4.6, including 4.5 +/- 0.1
Acid options	Acetic acid or methanesulfonic acid; sulfuric acid in narrower claims
Stabilizer	Chelating agent, including EDTA
Delivery system	No more than four, and preferably no more than two, pump sprays
Narrow pump dose	100 microliters per spray
Narrow drug dose	35 mg per spray, 70 mg total
Indication	Cardiac arrhythmia, stable angina, or migraine; narrower claims cover PSVT

The patent therefore reaches both formulation composition and product configuration. A product may infringe multiple claim categories at the same time if it uses the claimed concentration, salt, pH, EDTA system, and two-spray delivery format.

How are the independent claims structured?

US 10,117,848 has seven important independent claim groups.

Claim 1: broad aqueous composition

Claim 1 covers an aqueous nasal composition containing compound I, a salt, free base, racemate, or enantiomer at 150-600 mg/mL.

This is the broadest composition claim. It does not require:

the S-enantiomer;
the acetate salt;
EDTA;
a particular pH;
a particular pump;
a particular indication; or
a specific manufacturing process.

A competing nasal formulation containing a different pharmaceutically acceptable salt could remain within claim 1 if the active moiety is compound I and the concentration is within the claimed range.

Claims 2-11: composition limitations

Claims 2-11 narrow claim 1 by adding the following features:

the S-enantiomer;
350 mg/mL +/- 25 mg/mL;
40%-85% water;
pH 4.5 +/- 1.5;
0.5-1.5 molar equivalents of acetic acid;
0.5-1.5 molar equivalents of methanesulfonic acid;
a chelating agent;
EDTA;
a pharmaceutically acceptable excipient; and
homogeneity at room temperature.

Claims 6 and 7 are alternative acid limitations. A formulation using acetic acid may fall within claim 6, while one using methanesulfonic acid may fall within claim 7. The claims do not require both acids.

Claims 12-14: nasal delivery system

Claims 12-14 protect a delivery system containing the claimed aqueous composition in a unit dosage form.

The key limitations are:

no more than four single-pump spray doses under claim 12;
no more than two single-pump spray doses under claim 13; and
no more than 200 microliters administered to each nostril under claim 14.

These claims connect the formulation to the commercial device. A formulation sold in a bottle or container without the claimed pump or dosage configuration may raise a different infringement analysis than a finished nasal spray product.

Claims 15-17: treatment methods

Claim 15 covers nasal administration of the claimed composition to treat:

cardiac arrhythmia;
stable angina; or
migraine.

Claim 16 narrows cardiac arrhythmia to PSVT, atrial fibrillation, or ventricular tachycardia. Claim 17 requires administration of 150-200 microliters.

These method claims create a different risk profile from composition claims. A generic manufacturer may face direct product claims even if its labeling omits a patented indication. Method-of-use exposure depends on the product label, promotional conduct, physician behavior, and applicable induced-infringement principles.

Claims 18-20: manufacturing process

Claims 18-20 cover a multistep process involving:

adding an acidic solution to etripamil free base;
adding EDTA;
heating and mechanically stirring until the drug disperses;
adjusting pH to 3.5-5.5; and
diluting to at least 300 mg/mL.

Claim 19 identifies acetic acid and methanesulfonic acid as first acids. Claim 20 identifies acetic acid, sulfuric acid, and methanesulfonic acid as second acids.

The process claims are significant because they may reach manufacturing operations even when the finished product is difficult to distinguish analytically. Their enforceability depends on whether the accused process performs each required step, including the order of addition and the use of heating and mechanical stirring.

Claims 21-39: commercial formulation and PSVT claims

Claims 21-39 create a dense set of narrower fallback positions. The most commercially important claims are:

claim 21: acetate salt of the S-enantiomer;
claim 22: acetate salt of the S-enantiomer at 350 mg/mL +/- 25 mg/mL;
claim 24: pH 4.5 +/- 0.1;
claim 27: EDTA;
claim 29: two pump doses, each containing 35 mg;
claim 30: two 100-microliter doses;
claim 32: PSVT treatment using the acetate S-enantiomer at 350 mg/mL +/- 25 mg/mL;
claim 33: 70 mg administered;
claim 38: the narrow manufacturing sequence; and
claim 39: final concentration of 350 mg/mL.

Claims 22, 29, 30, 32, and 33 closely track the commercial product configuration associated with Cardamyst.

What is the strongest patent claim in US 10,117,848?

The strongest commercial combination is the cluster formed by claims 22, 24, 27, 29, 30, 32, and 33.

That combination requires:

the acetate salt;
the S-enantiomer;
approximately 350 mg/mL;
a pH close to 4.5;
EDTA;
two 100-microliter sprays;
35 mg per spray; and
70 mg total for PSVT.

These claims are narrower than claim 1 but map more closely to the marketed product. Narrow claims generally have a smaller literal scope, but they may be more resilient against prior-art attacks if the precise combination was not previously disclosed.

Claim 1 has the broadest literal reach. Its main vulnerability is prior art involving high-concentration nasal delivery of etripamil or closely related compounds. Claims 38 and 39 have a separate vulnerability: a process challenger could argue that the sequence, acid selection, heating conditions, or dilution step was known or obvious.

What formulation features are protected?

The patent protects a combination of physical, chemical, and operational parameters.

Concentration

The 150-600 mg/mL range is unusually important. A product at 149 mg/mL or above 600 mg/mL would fall outside the literal range of claim 1, subject to doctrine-of-equivalents issues. A product at 325-375 mg/mL falls within the preferred 350 mg/mL +/- 25 mg/mL limitation.

The concentration limitation is likely measured by the amount of compound dissolved per milliliter of final composition. Salt-versus-free-base measurement can become material if the product label or manufacturing record reports drug content on different molecular-weight bases.

Salt and stereochemistry

The broad claims cover the free base, pharmaceutically acceptable salts, racemates, and enantiomers. The later claims focus on the acetate salt of the S-enantiomer.

A product using the R-enantiomer or racemate may avoid the narrow S-enantiomer claims but could remain within claim 1, depending on the identity of compound I and the concentration.

pH and acids

The patent uses overlapping pH ranges:

3.5-5.5 in the process claims;
3.0-6.0 through claim 5;
4.4-4.6 in claim 24; and
4.4-4.6 in claim 37.

The narrow pH claims are particularly relevant to product testing. A formulation that drifts outside the range during storage could raise questions about infringement at manufacture, sale, or use, depending on the claim and the relevant jurisdiction.

EDTA and chelation

EDTA is not required by the broadest composition claim. It becomes relevant in dependent composition claims and the manufacturing claims. A formulation using another chelator may avoid the EDTA-specific claims but could remain within claim 8 if the substitute qualifies as a chelating agent.

When does US Patent 10,117,848 lose exclusivity?

The patent issued on November 6, 2018.[1] The statutory expiration date is determined from the earliest effective nonprovisional or international filing date, not from the grant date. Patent-term adjustment, terminal disclaimers, patent-term extension, and regulatory exclusivity can change the effective commercial protection period.

The claim text alone does not establish the exact expiration date. The controlling records are the USPTO Patent Center application history and the patent-term information maintained by the USPTO.[2]

FDA approval does not itself extend this patent. Separate Hatch-Waxman protections may apply to the approved product, including:

five-year new chemical entity exclusivity if applicable;
three-year exclusivity for a qualifying new clinical investigation;
pediatric exclusivity if awarded; and
listed patents in the Orange Book.

Cardamyst received FDA approval for acute termination of PSVT in adults in December 2024.[3] FDA exclusivity and Orange Book listings must be evaluated separately from US 10,117,848.

What is the Orange Book status of US 10,117,848?

A patent is Orange Book-relevant only if the NDA holder lists it for the approved drug product and FDA accepts the listing under applicable requirements. The patent’s existence does not prove that it is listed.

For Cardamyst, the relevant Orange Book analysis should distinguish:

Issue	Relevance
Active ingredient patent	Protects etripamil as a chemical entity, if listed
Formulation patent	May cover the 350 mg/mL nasal solution
Device or delivery patent	May cover the pump and dose configuration
Method-of-use patent	May cover PSVT treatment
Process patent	Usually has limited direct Orange Book relevance unless tied to the approved product
Regulatory exclusivity	Can block approval independently of patent expiration

The Orange Book listing, patent-use codes, and any delisting or correction history are controlling for Paragraph IV timing.[4]

Are Paragraph IV challenges or generic lawsuits public?

A Paragraph IV challenge would require a generic applicant to certify that a listed patent is invalid, unenforceable, or not infringed. The claim set creates several possible challenge theories:

concentration ranges were anticipated or obvious;
high-concentration nasal delivery was predictable;
EDTA and acidification were routine formulation choices;
the acetate S-enantiomer lacked unexpected results;
the pump configuration was an obvious dosage-device selection; or
the manufacturing sequence was obvious from conventional salt-formation processes.

The patent owner would likely respond that the claimed combination solves a delivery problem involving unusually high drug loading, nasal tolerability, stability, homogeneity, and rapid systemic exposure.

A complete litigation conclusion requires the current PACER and USPTO records. The supplied claims do not establish whether a Paragraph IV notice, ANDA filing, district-court action, or settlement agreement exists.

How strong is the patent estate for etripamil?

US 10,117,848 is a focused formulation patent with several layers of protection:

Estate layer	Strength in relation to commercial product
Broad composition	High reach, greater prior-art exposure
S-enantiomer and acetate salt	Strong product alignment
350 mg/mL concentration	Strong commercial alignment
pH and EDTA	Useful fallback limitations
Two-pump delivery system	Strong finished-product coverage
70 mg PSVT method	Direct alignment with approved use
Manufacturing process	Potentially important but harder to prove
Active-ingredient patents	Must be assessed separately

The estate is more defensible as a product-specific combination than as a broad monopoly over nasal etripamil. A competitor that changes several variables simultaneously, such as salt, concentration, pH, and pump dose, would materially improve its design-around position.

What generic launch scenarios exist?

Scenario 1: Same formulation and same device

This presents the highest infringement risk. A product using acetate S-etripamil at approximately 350 mg/mL in two 100-microliter sprays would likely implicate the narrow composition and delivery claims.

Scenario 2: Different concentration

A formulation below 150 mg/mL or above 600 mg/mL could avoid claim 1, but it would need to preserve dose delivery, solubility, nasal tolerability, and pharmacokinetics. A concentration between 150 and 600 mg/mL remains exposed.

Scenario 3: Different salt

A different salt may avoid acetate-specific claims but remain exposed to claim 1 and other broad claims covering pharmaceutically acceptable salts.

Scenario 4: Different stereochemical form

The racemate or R-enantiomer may avoid S-enantiomer claims. Claim 1 remains relevant because it expressly covers racemates and enantiomers.

Scenario 5: Different pump configuration

More than two sprays, a different volume, or a non-pump delivery system may avoid claims 12-14 and 29-30. Composition and method claims could remain applicable.

Scenario 6: Different manufacturing process

A process that avoids the claimed acid addition order, EDTA step, heating, or mechanical stirring may reduce process-claim exposure without avoiding composition claims.

What licensing and competitive issues matter?

Milestone Pharmaceuticals is the developer associated with etripamil and Cardamyst. The commercial competitive landscape includes:

branded etripamil nasal spray;
hospital-administered intravenous adenosine;
intravenous or oral calcium-channel blockers;
beta blockers and other acute rhythm-control strategies; and
future generic or alternative intranasal calcium-channel blocker products.

No licensing arrangement can be inferred from the claim text. Any analysis of sublicenses, co-development rights, manufacturing agreements, or royalty burdens requires the relevant SEC filings, assignment records, and transaction documents.

Key Takeaways

US 10,117,848 protects high-concentration aqueous nasal etripamil formulations.
The commercial center of gravity is the acetate salt of the S-enantiomer at about 350 mg/mL.
Claims 22, 24, 27, 29, 30, 32, and 33 closely track a 70-mg, two-spray PSVT product.
Claim 1 is the broadest composition claim and covers 150-600 mg/mL formulations using the free base, salts, racemate, or enantiomers.
The patent separately covers delivery systems, PSVT treatment, and a defined EDTA-containing manufacturing process.
A design-around may be possible through changes to concentration, salt, stereochemistry, pH, pump volume, dosing format, or manufacturing sequence.
The exact patent expiration date, Orange Book status, Paragraph IV activity, litigation record, and settlement position cannot be established from the claim text alone.
Cardamyst was FDA-approved in December 2024 for acute termination of PSVT in adults, making the narrow product and method claims commercially important.

FAQs

Is US 10,117,848 a patent on etripamil itself?

No. The supplied claims primarily cover aqueous nasal formulations, delivery systems, PSVT treatment methods, and manufacturing processes. Separate patents may protect the active ingredient or other etripamil uses.

Does a different etripamil salt automatically avoid infringement?

No. The broad claims cover pharmaceutically acceptable salts and free base. A different salt may avoid acetate-specific claims while remaining within claim 1.

Does changing the nasal spray volume avoid the patent?

It may avoid claims requiring two 100-microliter sprays or no more than 200 microliters per nostril. It does not automatically avoid the independent composition claims.

Can a generic use the same 70-mg dose with a different concentration?

Potentially, but the product would need to avoid the 150-600 mg/mL range and the narrower 350 mg/mL claims. The alternative concentration must also satisfy FDA equivalence and product-performance requirements.

Does EDTA create the primary infringement risk?

EDTA is important to several dependent and process claims, but it is not required by the broadest composition claim. A formulation without EDTA could still infringe claims based on concentration, drug form, and nasal administration.

References

United States Patent and Trademark Office. (2018). U.S. Patent No. 10,117,848, claims 1-39.
United States Patent and Trademark Office. (n.d.). Patent Center: U.S. Patent No. 10,117,848.
U.S. Food and Drug Administration. (2024). Cardamyst prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. Orange Book.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Milestone Pharms Usa	CARDAMYST	etripamil	SPRAY;NASAL	218571-001	Dec 12, 2025		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y			TREATMENT OF A CARDIAC ARRHYTHMIA	⤷ 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	2016249030	⤷ Start Trial
Brazil	112017021620	⤷ Start Trial
Canada	2982622	⤷ Start Trial
Canada	3203288	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,117,848