US Patent 11,478,436: Claim Scope, Exclusivity, Litigation Risk, and Ephedrine Sulfate Patent Landscape

US Patent 11,478,436 protects specific methods for administering a sterile, preservative-free, ready-to-use ephedrine sulfate injection. Its independent claims do not broadly cover ephedrine sulfate, ephedrine sulfate compositions, or all ready-to-use presentations. They require a defined combination of formulation, packaging, manufacturing, stability, and administration steps. The strongest commercial risk is directed to a 5 mg/mL preservative-free ephedrine sulfate product in a ready-to-use container that is injected without dilution.

The patent is most relevant to manufacturers of ephedrine sulfate injection products, hospital-use injectable suppliers, 505(b)(2) applicants, and generic or authorized-generic developers seeking to commercialize pre-mixed ephedrine sulfate.

What does US Patent 11,478,436 protect?

The patent claims methods of administering ephedrine sulfate to a patient with hypotension or an elevated risk of hypotension. The claims combine clinical-use limitations with detailed product and manufacturing requirements.

Claim group	Principal subject matter	Key limitations
Claims 1-3	Administration of ephedrine sulfate in saline or dextrose	5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride or 5% dextrose, no preservative, sterile ready-to-use product, drawing into a syringe, no dilution, injection
Claims 4-10	Administration of saline-based product	5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, no preservative, water, vial filling, sealing, terminal sterilization
Claims 11-18	Endotoxin limitations	Endotoxin thresholds from not more than 7 EU/mg to not more than 0.2 EU/mg
Claims 19-21	Accelerated-stability version of claims 1-3	pH remains within 0.5 pH units after six months at 40°C and 75% relative humidity
Claims 22-25	Endotoxin limitations for claims 19-21	Endotoxin thresholds after accelerated storage

The patent is therefore a hybrid method patent. It claims how the product is used, but defines the product through formulation, manufacturing, container, sterilization, and stability characteristics. [1]

How broad are the independent claims?

What does claim 1 require?

Claim 1 requires every one of the following:

A subject has hypotension or an elevated risk of developing hypotension.
The product contains:
- 5 mg/mL ephedrine sulfate;
- 9 mg/mL sodium chloride or 5% dextrose;
- no preservative.
The product is sterile, shelf-stable, and ready to use.
The product is drawn from a sealed container into a syringe.
The product is not diluted after drawing.
The product is injected into the subject.
The product was made by:
- combining ephedrine sulfate, sodium chloride or dextrose, and water;
- forming a solution with an initial pH;
- membrane filtration;
- placing the filtered solution into a container;
- sealing the container.
After 12 months at 25°C and 60% relative humidity, the pH remains within 0.5 pH units of the initial pH.

Claim 1 covers two formulation branches:

5 mg/mL ephedrine sulfate with 9 mg/mL sodium chloride; or
5 mg/mL ephedrine sulfate with 5% dextrose.

The claim does not require a vial specifically. It refers to a sealed container. A syringe, cartridge, ampoule, or other sealed presentation could potentially satisfy the container limitation if the remaining requirements are met.

What does claim 4 require?

Claim 4 is narrower in formulation and manufacturing scope but uses the transitional phrase “consisting essentially of.” It requires:

5 mg/mL ephedrine sulfate;
9 mg/mL sodium chloride;
no preservative;
water;
a sterile premixed pharmaceutical product;
drawing the composition into a syringe;
injecting it without an express “no dilution” limitation;
filling vials;
sealing the vials; and
terminally sterilizing the sealed vials.

Claims 5 and 6 narrow the process further by requiring coated rubber stoppers and terminal sterilization at approximately 122°C for approximately 15 minutes.

The phrase “consisting essentially of” generally permits additional ingredients that do not materially affect the basic and novel characteristics of the claimed composition. The commercial significance is that excipients or processing aids may create claim disputes if they materially affect stability, pH, sterilization performance, or the intended ready-to-use characteristics.

What does claim 19 add?

Claim 19 tracks claim 1 but substitutes accelerated stability for the long-term stability requirement. The product must maintain its pH within 0.5 pH units after six months at 40°C and 75% relative humidity.

Claims 1 and 19 create two different stability pathways:

Claim	Stability condition	Duration
Claim 1	25°C / 60% relative humidity	12 months
Claim 19	40°C / 75% relative humidity	6 months

A product could satisfy one pathway without necessarily satisfying the other, depending on its stability profile and test data.

What formulations are protected by US Patent 11,478,436?

The principal protected formulation is a preservative-free, ready-to-use ephedrine sulfate injection at 5 mg/mL.

Formulation	Included in independent claim 1 or 19?	Included in claim 4?
5 mg/mL ephedrine sulfate + 9 mg/mL sodium chloride	Yes	Yes
5 mg/mL ephedrine sulfate + 5% dextrose	Yes	No
Ephedrine sulfate at another concentration	No	No
Product containing a preservative	No	No
Product requiring dilution before administration	Likely outside claims 1 and 19; claim 4 requires separate analysis	Potentially outside, depending on complete method
Premixed sterile vial	Yes if all other limitations are met	Yes
Prefilled syringe	Potentially, if it is drawn from a sealed container into a syringe as claimed	Not necessarily, because claim 4 requires drawing from a sterile premixed product into a syringe

The claims do not cover every preservative-free ephedrine sulfate product. Concentration, diluent, container, manufacturing process, stability, and administration practice must be assessed together.

How do the dependent claims strengthen the patent?

Claims 2, 3, 10, and 20 narrow the pH range or specify pH adjustment:

Initial pH of approximately 4.5 to 7;
use of sodium hydroxide or acetic acid to reach the initial pH.

Claims 11-18 and 22-25 add bacterial endotoxin limits. These claims create a descending series:

Endotoxin limitation	Relative claim breadth
Not more than 7 EU/mg	Broadest endotoxin limitation
Not more than 1.7 EU/mg	Narrower
Not more than 1 EU/mg	Narrower
Not more than 0.2 EU/mg	Narrowest

The endotoxin claims are important because the thresholds are product-performance limitations measured after specified storage periods. A manufacturer may avoid a particular dependent claim by failing to meet its endotoxin threshold, but that does not necessarily avoid the corresponding independent claim.

What manufacturing processes are protected?

The patent does not claim a generic sterile manufacturing process. It claims process features tied to a defined ephedrine sulfate product.

Membrane filtration

Claims 1 and 19 require membrane filtration after solution formation and before filling. A product made solely through another sterilization route may present a noninfringement position against these claims, although the product may still fall within claim 4 if the vial-filling and terminal-sterilization limitations are met.

Terminal sterilization

Claim 4 requires terminal sterilization after vial sealing. Claim 6 specifies heating at approximately 122°C for approximately 15 minutes.

This limitation can be commercially significant. A product made by aseptic processing without terminal sterilization may avoid claim 4 if no equivalent claim construction applies. Conversely, a product that is filtered, filled, sealed, and terminally sterilized could implicate both the filtration-based and terminal-sterilization claim groups, depending on the precise process.

Packaging

Claim 5 requires coated rubber stoppers. A vial using an uncoated stopper may avoid claim 5 but remain within claim 4. A non-vial container may avoid claim 4 while remaining potentially relevant to claims 1 or 19.

When does US Patent 11,478,436 lose exclusivity?

The patent issued on November 1, 2022. Its precise expiration date depends on the earliest effective nonprovisional priority date, patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable statutory calculations. The claims supplied do not establish those dates.

For a US utility patent, the ordinary term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and patent-term extension under 35 U.S.C. §§ 154 and 156. Patent expiration does not necessarily coincide with FDA exclusivity or the date on which a generic may launch.

A complete exclusivity analysis should distinguish:

Exclusivity category	Relevance
Patent term	Controls enforceable patent rights
FDA new-drug exclusivity	May restrict certain applications independently of patent rights
Orphan-drug exclusivity	Relevant only if granted for the applicable indication
180-day generic exclusivity	Relevant to a first Paragraph IV challenger
Pediatric exclusivity	Can add six months to qualifying periods

What is the Orange Book status of US Patent 11,478,436?

A method-of-treatment patent may be listed in the Orange Book only if it satisfies FDA listing requirements for an approved drug product and is submitted by the NDA holder or authorized party. The claims in Patent 11,478,436 are method claims, not composition claims or claims directed solely to a manufacturing process.

If listed, the patent would most naturally be relevant to a drug product containing ephedrine sulfate injection at the claimed concentration and presentation. Orange Book listing does not establish infringement. It affects the regulatory pathway and may trigger a Paragraph IV notice and the possibility of a 30-month stay under the Hatch-Waxman framework. [2]

The patent number alone does not establish current listing status, an unexpired listing, or whether an NDA holder submitted the patent for a particular ephedrine sulfate product.

Which companies are challenging US Patent 11,478,436?

A Paragraph IV challenge cannot be inferred from the claims. It requires an ANDA filer to certify that the patent is invalid, unenforceable, or will not be infringed, followed by notice to the patent owner and NDA holder.

Potential challengers would likely include:

generic injectable manufacturers;
505(b)(2) applicants developing ready-to-use ephedrine sulfate;
suppliers of prefilled syringes or premixed vials;
companies seeking to substitute ephedrine sulfate products in hospital formularies.

A product that uses a different concentration, requires dilution, contains a preservative, uses dextrose instead of saline, or is made without the claimed process steps may have a stronger design-around position. A product that copies the 5 mg/mL preservative-free saline presentation and uses the claimed container and stability profile presents greater Paragraph IV and infringement exposure.

What patent litigation affects ephedrine sulfate injection?

The supplied claim text does not identify a litigation caption, district court case, International Trade Commission investigation, settlement agreement, or Paragraph IV notice involving Patent 11,478,436.

The primary litigation issues would likely be:

Whether the accused product satisfies the 5 mg/mL concentration requirement.
Whether the product contains 9 mg/mL sodium chloride or 5% dextrose.
Whether “no preservative” is satisfied.
Whether the accused process includes membrane filtration.
Whether the product was terminally sterilized after vial sealing.
Whether administration occurs without dilution.
Whether the product meets the specified pH stability limitation.
Whether process limitations can be proven for an accused commercial product.
Whether the claims are anticipated or obvious over earlier ephedrine sulfate formulations and hospital compounding practices.
Whether the claims improperly combine known formulation, sterilization, and administration steps.

Because the claims require multiple cumulative limitations, litigation may focus on one missing element rather than the entire patent.

How strong is the patent estate for ephedrine sulfate?

Strengths

The claims are tied to a commercially useful ready-to-use injectable presentation.
The formulation is simple and clinically recognizable.
The no-dilution limitation maps directly onto hospital workflow.
Stability and endotoxin limitations may distinguish the claimed product from extemporaneous compounding.
Claims 1 and 19 cover both long-term and accelerated stability conditions.
The dependent claims create fallback positions for pH, sterilization, packaging, and endotoxin levels.

Weaknesses

The independent claims are method claims rather than broad composition claims.
The claims require proof of multiple manufacturing and stability facts.
The formulation ingredients are conventional pharmaceutical components.
The process limitations may create noninfringement opportunities.
A competitor may pursue a different concentration, diluent, container, sterilization route, or administration protocol.
The obviousness analysis may combine known ephedrine sulfate injection formulations with standard sterile manufacturing and stability practices.

The estate is strongest against a directly substitutable 5 mg/mL preservative-free, ready-to-use saline product manufactured and administered in the claimed manner. It is weaker against conventional diluted ephedrine sulfate, preservative-containing products, different concentrations, or products made through materially different processes.

How does Patent 11,478,436 compare with generic launch scenarios?

Launch scenario	Apparent risk
5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, preservative-free vial, no dilution	High
Same formulation but aseptically processed without terminal sterilization	Moderate; claim 4 risk may decrease, claims 1 and 19 require separate analysis
5 mg/mL ephedrine sulfate in 5% dextrose	High under claims 1 and 19 if process and stability limitations are met
5 mg/mL product requiring dilution before injection	Lower against claims 1 and 19; claim 4 requires detailed review
Different ephedrine sulfate concentration	Lower
Product containing a preservative	Lower
Conventional pharmacy-compounded ephedrine sulfate	Lower if it lacks shelf-stability, sealed-container, and claimed process limitations
Prefilled syringe manufactured without drawing from a separate sealed container	Potentially lower, subject to claim construction

What licensing and commercial issues matter?

A licensee would need to determine whether the rights cover:

the drug product;
the manufacturing process;
a specific FDA-approved presentation;
hospital use;
prefilled syringes;
saline and dextrose formulations;
geographic territories outside the United States.

The claims are US method claims. They do not, by themselves, establish rights in Europe, Canada, Japan, or other jurisdictions. Foreign protection would require corresponding national or regional patents with surviving claims.

Commercial exposure depends on the substitutability of the protected product. A ready-to-use ephedrine sulfate vial can reduce preparation steps, dilution errors, and pharmacy labor. That creates a meaningful commercial incentive to design around or license the patent, particularly for hospital injectable suppliers and 505(b)(2) applicants.

Key Takeaways

US Patent 11,478,436 is directed to administration methods for ready-to-use ephedrine sulfate injection.
The core formulation is 5 mg/mL ephedrine sulfate without a preservative.
Claim 1 and claim 19 cover saline and dextrose alternatives.
Claim 4 is narrower and focuses on a saline vial made by filling, sealing, and terminal sterilization.
The patent includes long-term and accelerated pH-stability requirements.
Dependent claims add endotoxin, pH, stopper, filtration, and sterilization limitations.
The strongest infringement risk concerns a product that closely replicates the 5 mg/mL preservative-free saline presentation and its manufacturing process.
A change in concentration, diluent, sterilization method, container, preservative status, or administration workflow may support a design-around position.
Patent expiration, Orange Book listing, Paragraph IV activity, litigation, and settlement status cannot be established from the claim text alone.

FAQs About US Patent 11,478,436

Does Patent 11,478,436 claim ephedrine sulfate itself?

No. The independent claims are directed to methods of administering ephedrine sulfate using specified sterile, ready-to-use products and manufacturing characteristics.

Does the patent cover ephedrine sulfate that is diluted before use?

Claims 1 and 19 expressly require that the product not be diluted after it is drawn from the sealed container. A product administered after dilution presents a potentially stronger noninfringement position against those claims.

Can a dextrose formulation avoid the patent?

Not necessarily. Claims 1 and 19 expressly include 5% dextrose as an alternative to 9 mg/mL sodium chloride. The remaining administration, process, and stability limitations must be evaluated.

Are endotoxin claims separate composition claims?

No. Claims 11-18 and 22-25 are dependent method claims. They narrow the underlying administration claims by adding endotoxin-performance requirements after specified storage conditions.

Does an Orange Book listing prove that a generic infringes?

No. An Orange Book listing can affect the ANDA certification and litigation process, but infringement depends on whether the accused product and conduct satisfy every enforceable claim limitation.

References

United States Patent No. 11,478,436, claims 1-25 (2022). United States Patent and Trademark Office.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.
Patent Act, 35 U.S.C. §§ 154, 156, 271, 282.
United States Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations.
United States Food and Drug Administration. (n.d.). Approved drug product labeling and FDA regulatory requirements for injectable drug products.

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	213407-001	Apr 17, 2020	AP1	RX	Yes	Yes	11,478,436	⤷ Start Trial				USE OF EPHEDRINE SULFATE FOR TREATING HYPOTENSION	⤷ 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	2020276619	⤷ Start Trial
Canada	3140043	⤷ Start Trial
China	113825500	⤷ Start Trial
European Patent Office	3968975	⤷ Start Trial
Israel	288044	⤷ Start Trial
Japan	2022532657	⤷ Start Trial
Japan	2023091072	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,478,436

Which drugs does patent 11,478,436 protect, and when does it expire?

Summary for Patent: 11,478,436