Details for Patent: 11,464,752

Which drugs does patent 11,464,752 protect, and when does it expire?

Patent 11,464,752 protects EMERPHED and is included in one NDA.

This patent has thirteen patent family members in nine countries.

Summary for Patent: 11,464,752

Title:	Compositions comprising ephedrine or an ephedrine salt and methods of making and using same
Abstract:	The present disclosure provides compositions comprising ephedrine sulfate ready for immediate use in a clinical setting, and methods of making and using same.
Inventor(s):	Shahid Ahmed
Assignee:	Nexus Pharmaceuticals LLC
Application Number:	US17/381,770
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,464,752
Patent Claim Types: see list of patent claims	Composition; Process;

US Patent 11,464,752: Ephedrine Sulfate Prefilled Syringe Patent Scope, Validity and Generic Entry Risk

US Patent No. 11,464,752 protects a preservative-free, ready-to-use ephedrine sulfate product in a syringe or other single-use container. The core combination is 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, water, an initial pH of about 4.5 to 7, and defined stability after accelerated or long-term storage. The patent also covers terminal sterilization in the filled container, including heating at approximately 122°C for 15 minutes.[1]

The strongest commercial protection is concentrated in claims 1, 5 and 10. Claims 2 through 4, 6, 7 and 11 through 16 add manufacturing, container, particulate, endotoxin, stereoisomer and stability limitations.

What does US Patent 11,464,752 protect?

The patent protects a drug product rather than ephedrine sulfate as a chemical compound. Its principal subject matter is the combination of:

Protected feature	Claims
Ephedrine sulfate concentration of 5 mg/mL	1, 5, 10
Sodium chloride concentration of 9 mg/mL	1, 5, 10
Water-based composition	1, 5, 10
No preservative	1, 5, 10
Initial pH of approximately 4.5 to 7	1, 5, 10
Stability after 12 months at 25°C/60% RH or six months at 40°C/75% RH	1, 5, 10
Ephedrine concentration at least 95% of labeled concentration	1, 5, 10
pH change within 0.5 pH unit	1, 8-10, 14-15
Bacterial endotoxin level not exceeding 7 EU/mg	1
(+)-1S,2R-ephedrine not exceeding 0.5%	5
Terminal sterilization inside the filled container	2, 6, 12
Heating at approximately 122°C for approximately 15 minutes	3, 7, 13
Filtration before filling	4
Single-use container or syringe	1, 5, 10-11
Particulate matter of no more than 6,000 particles at least 10 μm	16

The claims do not cover every ephedrine injection. A product must satisfy the specified formulation, packaging and performance limitations to fall within the primary claim set.

How do the independent claims differ?

Claim 1: syringe, endotoxin and stability claim

Claim 1 requires a packaged syringe containing a sterilized ready-to-use ephedrine composition. It includes the formulation, initial pH and post-storage requirements, plus a bacterial endotoxin limit.

This is the most demanding independent claim from an evidentiary perspective because infringement requires proof of the endotoxin limitation and the specified stability characteristics. A competitor could avoid literal infringement if its product exceeds 7 EU/mg, although that design choice could create regulatory or quality concerns.

Claim 5: syringe, stereoisomer and stability claim

Claim 5 also requires a packaged syringe containing 5 mg/mL ephedrine sulfate and 9 mg/mL sodium chloride. Instead of the endotoxin limitation, it requires the level of (+)-1S,2R-ephedrine to be no more than 0.5%.

This claim is directed at stereochemical purity and degradation or epimerization control. It may be important where terminal heat sterilization affects the stereoisomeric profile of ephedrine.

Claim 10: broader single-use container claim

Claim 10 covers a packaged ready-to-use single-use container, not only a syringe. It requires the same core formulation and stability profile but does not require the endotoxin or stereoisomer limitation found in claims 1 and 5.

Claim 10 is likely the broadest commercial claim because it can reach a vial, cartridge or other single-use presentation if the remaining limitations are met. Claim 11 narrows the claim back to a syringe.

What formulations are protected by US 11,464,752?

The protected formulation is a simple isotonic ephedrine sulfate composition:

• Ephedrine sulfate: 5 mg/mL
• Sodium chloride: 9 mg/mL
• Water
• No preservative
• Initial pH: approximately 4.5 to 7

The claims do not expressly require a buffer, antioxidant, chelating agent or other stabilizer. The absence of a preservative is an affirmative limitation. A formulation containing a preservative would not literally satisfy the independent claims.

The concentration limitations are material. A product containing 5 mg/mL ephedrine base rather than 5 mg/mL ephedrine sulfate would raise a claim-construction issue because the claims identify ephedrine sulfate specifically. A 5 mg/mL concentration with a different salt, such as ephedrine hydrochloride, would not literally meet the ephedrine sulfate limitation.

The phrase “about” applies to the pH range and sterilization conditions. It gives the patent holder potential flexibility around exact pH and temperature values, but it does not eliminate the requirement for a meaningful relationship to the claimed range or process.

What stability requirements must a competing product meet?

The patent uses two alternative storage protocols:

Storage condition	Required result
25°C and 60% relative humidity for 12 months	Ephedrine sulfate at least 95% of packaged concentration
25°C and 60% relative humidity for 12 months	pH within 0.5 pH units of initial pH, where required by the claim
40°C and 75% relative humidity for six months	Ephedrine sulfate at least 95% of packaged concentration
40°C and 75% relative humidity for six months	pH within 0.5 pH units of initial pH, where required by the claim
Same conditions	(+)-1S,2R-ephedrine no more than 0.5%, under claim 5
Same conditions	Bacterial endotoxin no more than 7 EU/mg, under claim 1
Same conditions	No more than 6,000 particles at least 10 μm, under claim 16

The alternative wording means the claim may be satisfied by performance under either stated storage protocol, depending on the exact claim construction and prosecution history. A challenger would likely examine whether “or” creates two independent testing routes or whether the specification and prosecution record impose a narrower interpretation.

Stability testing is central to infringement. A formulation that initially matches the claimed composition but fails the stability thresholds would not satisfy the product claims as written.

Does the patent cover terminal sterilization?

Yes. Dependent claims cover terminal sterilization after the composition has been placed into the sealed syringe or single-use container.

The most specific process limitation is heating the sealed container at approximately 122°C for approximately 15 minutes. Claim 3 depends on claim 2, claim 7 depends on claim 6, and claim 13 depends on claim 12. These claims therefore require the underlying product and process limitations inherited from the applicable independent claim.

The patent does not make terminal sterilization a requirement of every independent claim. Claims 1, 5 and 10 are product claims. A product could potentially fall within those claims even if it was sterilized by another method, provided the product satisfies the claimed characteristics. Conversely, a process that uses terminal sterilization but produces a different formulation may avoid infringement of the product claims.

How strong is the patent estate?

The patent has meaningful product protection but a relatively narrow technical target. Its strength depends on whether a competing product uses the same concentration and packaging combination.

Strength factors

1. The claims combine formulation, container and shelf-life performance. A competitor cannot avoid the patent merely by matching the initial formulation if the product also meets the stability limitations.
2. Claim 10 reaches single-use containers beyond syringes.
3. The claims cover both long-term and accelerated storage conditions.
4. The patent addresses commercially important attributes: ready-to-use presentation, preservative-free formulation and terminal sterilization.
5. The claims include measurable quality attributes that can be tested through product samples and regulatory filings.

Weakness factors

1. The core formulation is narrowly defined at 5 mg/mL ephedrine sulfate and 9 mg/mL sodium chloride.
2. Concentration changes may provide a direct design-around route.
3. The claims do not cover the active ingredient broadly.
4. The patent does not, on the supplied claims, cover every manufacturing method, delivery device or ephedrine dosage form.
5. The stability limitations may create enablement, written-description and indefiniteness issues if the specification does not support the full scope of the claimed ranges and storage outcomes.
6. The use of “about” and functional stability limitations may generate claim-construction disputes.

The patent is stronger against a matching ready-to-use 5 mg/mL prefilled syringe than against a vial, ampoule or formulation using a materially different concentration or excipient system.

What patent litigation and Paragraph IV risks exist?

The supplied claims do not identify any Paragraph IV notice, ANDA litigation, settlement agreement or court decision involving US 11,464,752. The patent number alone does not establish that it is listed in the FDA Orange Book or that it has been asserted against a generic applicant.

For an ANDA applicant, the main certification questions would be:

• Whether the patent is listed for the reference drug product.
• Whether the proposed product uses the claimed 5 mg/mL ephedrine sulfate and 9 mg/mL sodium chloride formulation.
• Whether the proposed container is a syringe or another single-use container.
• Whether stability data meet the claimed pH and concentration thresholds.
• Whether the product is terminally sterilized in the filled container.
• Whether the product meets the endotoxin, stereoisomer and particulate limitations.

A Paragraph IV challenge could rely on invalidity, noninfringement or both. The most likely invalidity theories would involve obviousness over earlier ready-to-use ephedrine formulations, prefilled syringe technology, isotonic saline compositions and terminal sterilization processes. Anticipation would require a single prior-art reference disclosing the complete combination, including the claimed stability results.

What is the Orange Book status?

Orange Book listing must be confirmed against the specific approved NDA and product presentation. A formulation and container patent can be eligible for listing if it claims the drug product or an approved method of use, but process-only claims generally are not listed under FDA Orange Book rules.[2]

The supplied claims are primarily drug-product claims. Claims 1, 5 and 10 may present an Orange Book listing basis if they correspond to an approved ephedrine sulfate syringe or single-use container. Claims directed solely to filtration or terminal sterilization would present a weaker listing basis because they are process limitations.

Orange Book status also depends on the NDA holder’s submission and FDA’s listing decision. Patent grant status and Orange Book listing status are separate issues.

When does US Patent 11,464,752 lose exclusivity?

The patent grant date was November 8, 2022. The statutory term for a modern U.S. utility patent generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers.[3]

The exact expiration date cannot be established from the claims alone. Based on the patent’s 2022 grant and apparent 2019-era filing profile, the unadjusted term would ordinarily extend into approximately 2039. The authoritative date is the USPTO patent-term calculation, not the grant date.

FDA regulatory exclusivity is separate from patent exclusivity. A product may have no remaining FDA exclusivity while retaining unexpired patent claims, or may retain FDA exclusivity after a patent expires.

What generic launch scenarios are most credible?

Scenario	Likely patent exposure
5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, preservative-free prefilled syringe	High
Same formulation in another single-use container	High under claim 10
Same formulation in a multidose container	Lower, because single-use packaging is required
Different ephedrine concentration	Potential design-around
Different salt of ephedrine	Potential design-around
Preserved formulation	Potential design-around
Different pH outside the claimed range	Potential design-around
Formulation failing the claimed stability thresholds	Potential noninfringement position
Same product made by aseptic filling rather than terminal sterilization	Does not necessarily avoid product claims
Same formulation with terminal sterilization at materially different conditions	May avoid the narrow process claims but not necessarily the product claims

The principal commercial risk is therefore presentation-specific. A generic or competing manufacturer that follows the same ready-to-use syringe architecture faces greater exposure than one that changes concentration, container type or formulation.

How does US 11,464,752 compare with ordinary ephedrine injection products?

Traditional ephedrine sulfate injection products are often supplied in vials or ampoules and may require withdrawal into a syringe before administration. The patent targets a different product configuration: a ready-to-use, single-use, preservative-free presentation that reduces preparation steps.

Attribute	Conventional ephedrine injection	Claimed product
Presentation	Often vial or ampoule	Syringe or single-use container
Preparation	May require withdrawal	Ready to use
Preservative	Product-specific	None
Ephedrine sulfate concentration	Product-specific	5 mg/mL
Sodium chloride	Product-specific	9 mg/mL
Terminal sterilization in final container	Product-specific	Expressly covered in dependent claims
Stability performance	Product-specific	Defined by claim thresholds

The patent’s commercial value is linked to the delivery system and shelf-life profile rather than to ephedrine sulfate itself.

Key Takeaways

• US 11,464,752 is a formulation, packaging and stability patent for ready-to-use ephedrine sulfate.
• The core formulation is 5 mg/mL ephedrine sulfate in 9 mg/mL sodium chloride, with water, no preservative and an initial pH of approximately 4.5 to 7.
• Claims 1 and 5 focus on syringes; claim 10 extends protection to a broader single-use container category.
• Stability, endotoxin, stereoisomer and particulate limits are material claim elements.
• Terminal sterilization at approximately 122°C for 15 minutes is protected only in dependent process claims.
• The strongest infringement risk concerns a competing 5 mg/mL preservative-free ephedrine sulfate prefilled syringe.
• A different concentration, salt, container configuration or formulation may provide a design-around strategy.
• Paragraph IV activity, litigation, settlement and Orange Book listing cannot be inferred from the patent claims alone.
• The patent’s unadjusted term likely reaches approximately 2039, subject to the USPTO term calculation and any patent-term adjustment or extension.

FAQs

Does US 11,464,752 cover ephedrine sulfate vials?

Claim 10 can reach a single-use container other than a syringe, but the product must satisfy the claimed formulation and stability requirements. A vial that is multidose or contains a different formulation may fall outside the claims.

Does the patent cover ephedrine hydrochloride?

No. The claims identify ephedrine sulfate. Ephedrine hydrochloride would not literally satisfy that limitation.

Can a manufacturer avoid the patent by changing the sterilization method?

Changing sterilization may avoid claims limited to terminal sterilization, but it may not avoid the independent product claims if the resulting product still satisfies their formulation, container and stability limitations.

Are the pH and stability limits likely to be tested in ANDA litigation?

Yes. Product samples, stability protocols, batch records, regulatory submissions and analytical data would be relevant to whether the accused product meets the claimed pH, concentration and impurity thresholds.

Does patent expiration automatically permit immediate generic launch?

No. Launch timing also depends on Orange Book listing, FDA approval, regulatory exclusivity, court orders, settlement terms and any other unexpired patent or regulatory barrier.

References

1. United States Patent and Trademark Office. (2022). U.S. Patent No. 11,464,752, stable ephedrine compositions.
2. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations.
3. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension provisions.

Drugs Protected by US Patent 11,464,752

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Nexus	EMERPHED	ephedrine sulfate	SOLUTION;INTRAVENOUS	213407-002	Feb 28, 2023		RX	Yes	Yes	11,464,752		Y
Nexus	EMERPHED	ephedrine sulfate	SOLUTION;INTRAVENOUS	213407-001	Apr 17, 2020	AP1	RX	Yes	Yes	11,464,752		Y

International Family Members for US Patent 11,464,752

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2020276619
Canada	3140043
China	113825500