United States Patent 11,471,400: Phenylephrine Injection Claims, Patent Scope and Competitive Landscape

U.S. Patent No. 11,471,400 protects a narrow ready-to-use phenylephrine hydrochloride intravenous formulation rather than phenylephrine as an active ingredient. Its core limitations are low-dose phenylephrine, EDTA stabilization, a defined acidic pH, low impurity formation under accelerated storage, single-use vial packaging, and the absence of bisulfite or other antioxidants. Dependent claims add benzyl alcohol, citrate buffering, pH adjustment, low-oxygen vial headspace, nitrogen sparging, fill volume, and manufacturing steps.

The commercial risk is highest for ready-to-use phenylephrine products that match the claimed 0.1 mg/mL formulation, contain approximately 0.2 mg/mL EDTA, use a single-use vial, and rely on nitrogen-controlled headspace rather than sulfite antioxidants.

What does U.S. Patent 11,471,400 protect?

The patent has four principal claim groups:

Claim group	Claims	Protected subject matter
Core formulation	1, 2, 6-8, 18-21	Phenylephrine HCl, EDTA, sodium chloride, water, defined pH, stability, and antioxidant exclusion
Vial product	9-11, 17	The formulation in a vial with oxygen-controlled headspace and single-use volume
Manufacturing process	12-16	Admixing, filling, nitrogen addition, and single-use vial preparation
Formulation alternatives	2-5, 8, 18, 21	Preservatives, citrate buffer, pH adjusters, and other excipient categories

The independent claims are narrower than a conventional drug-composition claim because they require several limitations simultaneously. A competing product must be assessed against the complete combination, not against phenylephrine concentration or EDTA content alone.

What are the essential limitations of the independent claims?

Claim 1: core preservative-free formulation architecture

Claim 1 requires:

Phenylephrine hydrochloride at approximately 0.05 to 0.15 mg/mL.
Phenylephrine as the only active pharmaceutical ingredient.
EDTA at approximately 0.1 to 0.3 mg/mL.
Sodium chloride and water.
pH between 3 and 6.5.
A sterile, ready-to-use intravenous injection.
Packaging in a single-use vial.
No bisulfites or other antioxidants.
No more than 0.2% phenylephrine impurities after six months at 40°C.

The claim is directed to a low-concentration, ready-to-administer product. It does not cover all phenylephrine injections, concentrated phenylephrine products requiring dilution, or formulations stabilized with sodium metabisulfite if the antioxidant exclusion is met by the accused product.

The phrase "consists essentially of" is important. It permits components that do not materially alter the basic and novel characteristics of the claimed formulation, while potentially excluding excipients that materially affect stability, delivery, or the claimed technical result. Courts typically evaluate the transitional phrase in the context of the specification and prosecution history. [1]

Claim 2: broader excipient framework

Claim 2 includes the same core phenylephrine, EDTA, sodium chloride, water, pH, sterility, vial, stability, and antioxidant limitations. It expressly allows one or more of:

A preservative.
A buffer.
A pH adjuster.

This claim is broader than claim 1 with respect to additional excipients. Claims 3 through 5 narrow those options to specified preservative, citrate-buffer, and pH-adjustment systems.

Claim 9: low-oxygen headspace product

Claim 9 adds a vial headspace containing less than 10% oxygen by volume. The product must otherwise satisfy the core formulation requirements.

Claim 10 narrows the headspace oxygen level to less than 5% and specifies a 0.05 to 20 mL solution fill. Claim 11 requires a quantity allowing only a single use.

These limitations create a packaging-focused infringement pathway. A product may match the formulation but avoid claims 9 through 11 if its vial headspace is not within the recited oxygen range.

Claim 12: formulation manufacturing method

Claim 12 covers admixing:

Phenylephrine hydrochloride.
EDTA.
Sodium chloride.
Water for injection.

Claims 13 through 16 add vial filling, fill volume, single-use quantity, oxygen reduction, and nitrogen addition.

The method claims can reach a manufacturer even where finished-product testing does not establish every product limitation, provided the accused manufacturing process practices the claimed steps.

How strong is the patent estate based on the claim structure?

The patent is technically focused and commercially relevant, but its claim strength depends on proof of several quantitative and functional limitations.

Limitation	Enforcement significance	Design-around potential
Phenylephrine 0.05-0.15 mg/mL	Captures common ready-to-use concentrations, especially 0.1 mg/mL	Use a concentration outside the range, subject to equivalents analysis
EDTA 0.1-0.3 mg/mL	Identifies the stabilization platform	Use another chelator or a materially different EDTA level
pH 3-6.5	Broad acidic range	Use a pH outside the claimed range, if clinically acceptable
0.2% or less impurities after 40°C/6 months	Functional stability limitation	Challenge testing, sampling, assay method, and batch variability become central
No bisulfites or other antioxidants	Excludes sulfite-stabilized products from literal coverage	Use sulfite or another antioxidant, although claim construction may be contested
Single-use vial	Limits the product claims to a defined presentation	Use ampules, cartridges, syringes, bags, or multidose packaging
Oxygen below 10% or 5%	Applies only to the low-oxygen product claims	Use ambient-air headspace or a different package
Nitrogen addition	Narrows process claims	Use vacuum, argon, oxygen displacement, or another process

The strongest commercial claims are likely claims 1, 2, 7, 9, and 12. Claim 7 is particularly important because it recites the commercially intuitive target of approximately 0.1 mg/mL phenylephrine, approximately 0.2 mg EDTA, and pH 5 to 5.3.

The wording in claim 7 states "edetate disodium in an amount of about 0.2 mg" without expressly reciting a volume basis. That wording may generate claim-construction and indefiniteness arguments if the specification does not supply a clear unit or concentration context. The surrounding claims use mg/mL, and the claim may be interpreted in light of the specification. [1]

What formulations are protected by U.S. Patent 11,471,400?

Core formulation

The central formulation is:

Component	Claimed range or requirement
Phenylephrine HCl	Approximately 0.05-0.15 mg/mL
EDTA	Approximately 0.1-0.3 mg/mL
Sodium chloride	Required
Water	Required
pH	3-6.5
Active ingredient	Phenylephrine HCl as the only active pharmaceutical ingredient
Antioxidants	Bisulfites and other antioxidants excluded
Stability	0.2% or less phenylephrine impurities after six months at 40°C
Presentation	Sterile, ready-to-use, single-use vial

Claim 6 narrows the impurity threshold to approximately 0.1% or less. Claim 7 narrows the formulation toward a 0.1 mg/mL commercial product. Claim 8 adds approximately 8 mg/mL benzyl alcohol and optional buffering or pH adjustment.

Preserved and buffered alternatives

Claims 2 through 5 and claim 18 cover formulations that include:

Benzyl alcohol.
Chlorobutanol.
Parabens.
Phenol.
Sorbic acid.
Citrate buffering systems.
Hydrochloric acid.
Sodium hydroxide.

The claims therefore extend beyond a strictly preservative-free formulation. A product containing benzyl alcohol can remain within the claim set if it satisfies the concentration, EDTA, pH, impurity, vial, and antioxidant limitations.

Oxygen-controlled presentations

Claims 9 and 10 cover products with reduced oxygen in the vial headspace. The claims do not require nitrogen in the product claims, but claims 14 and 15 expressly cover nitrogen addition in the manufacturing process.

A manufacturer using nitrogen flushing can therefore face both product and process claim exposure. The product claim focuses on the resulting oxygen content. The process claim focuses on the act of providing oxygen-reduced headspace by adding nitrogen.

When does U.S. Patent 11,471,400 lose exclusivity?

The patent’s enforceable expiration date cannot be derived from the claims alone. The statutory term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other adjustments. [2]

The patent issued in 2022. Its effective exclusivity period therefore extends materially beyond issuance and may reach the late 2030s, depending on the priority chain and term adjustments. The issue date does not establish the expiration date.

Patent expiration must be separated from regulatory exclusivity:

Exclusivity category	Relevance
Patent term	Depends on priority filing date and PTA/PTE
New drug exclusivity	Depends on the applicable FDA approval pathway
Orange Book patent listing	Depends on whether the patent claims an approved drug, formulation, or method of use and satisfies FDA listing requirements
Pediatric exclusivity	Can add six months if granted
180-day generic exclusivity	Applies to qualifying first Paragraph IV applicants, not to the patent holder

A patent may remain unexpired while a generic or competing product enters after a successful invalidity, noninfringement, settlement, or regulatory challenge.

What is the Orange Book status of U.S. Patent 11,471,400?

The claims are formulation, packaging, and manufacturing claims. Those categories can be relevant to Orange Book listing when the patent claims the drug substance, drug product, or an approved method of use associated with an NDA product. FDA listing is not established by the patent claims themselves. [3]

For a phenylephrine injection product, an Orange Book analysis should distinguish:

The NDA product associated with the formulation.
Whether the patent is listed against that NDA.
Whether an approved product label corresponds to the claimed concentration and presentation.
Whether the listed claims are formulation claims or method-of-use claims.
Whether an ANDA applicant must make a Paragraph IV certification.

The claim set contains no disease or clinical-use limitation. It is therefore not a conventional method-of-use patent. Its relevance would arise primarily through formulation or product listing, if accepted by FDA.

Which companies are most exposed to the patent?

The principal competitive exposure is for companies marketing or developing ready-to-use phenylephrine hydrochloride injections in the same concentration and vial format.

Eton Pharmaceuticals and Biorphen

Biorphen is a ready-to-use phenylephrine hydrochloride injection product associated with Eton Pharmaceuticals. FDA labeling identifies phenylephrine hydrochloride injection as an intravenous product used to increase blood pressure in adults with clinically important hypotension resulting primarily from vasodilation. [4]

A Biorphen-like product would warrant comparison against:

0.1 mg/mL phenylephrine concentration.
EDTA concentration.
pH.
Presence or absence of benzyl alcohol.
Single-use vial format.
Headspace oxygen.
Stability data at 40°C.
Any antioxidant or sulfite excipient.

Commercial identity alone does not establish infringement. Product composition, packaging records, manufacturing specifications, and stability data control.

Generic manufacturers

Potentially exposed manufacturers include suppliers of:

Phenylephrine hydrochloride injection, 0.1 mg/mL.
Ready-to-use phenylephrine vials.
Premixed vasopressor products.
Hospital-use injectable products supplied in small-volume single-use containers.

The most important competitors are manufacturers with FDA-approved or pending products that use the same low-dose presentation. A concentrated 10 mg/mL product requiring dilution presents a materially different technical and claim profile.

What Paragraph IV challenges could arise?

An ANDA applicant seeking approval for a product covered by a listed patent generally must certify under Paragraph IV that the patent is invalid, unenforceable, or will not be infringed. A Paragraph IV notice can trigger a 30-month FDA approval stay if statutory conditions are satisfied. [5]

For this patent, likely challenge theories include:

Anticipation

An ANDA applicant could identify prior art disclosing the complete combination of:

Low-dose phenylephrine.
EDTA.
Sodium chloride.
Water.
The claimed pH.
A single-use vial.
The accelerated impurity result.
The absence of antioxidants.

Anticipation is difficult if no single reference discloses every limitation, including the stability result and packaging requirements.

Obviousness

Obviousness arguments would likely combine:

Existing phenylephrine injection formulations.
EDTA as a chelator.
Known oxygen-control or nitrogen-flushing techniques.
Known acidic pH ranges.
Routine sterile vial packaging.
Predictable stability testing.

The patent holder would likely argue that the specific EDTA range, impurity threshold, antioxidant-free formulation, and commercial-ready presentation produce an unexpected stability result.

Indefiniteness

Potential pressure points include:

"About" applied to concentration, impurity, pH, and amount.
The claim 7 reference to approximately 0.2 mg without a stated volume.
"Other antioxidants."
The analytical method used to quantify "phenylephrine impurities."
The meaning of "allows only a single use."
The boundary between "consists essentially of" and permitted excipients.

Written description and enablement

A challenger could examine whether the specification supports the full breadth of:

Multiple preservatives.
Multiple pH adjusters.
Broad pH from 3 to 6.5.
Broad EDTA and phenylephrine ranges.
All oxygen-control methods.
The claimed stability threshold across the full formulation scope.

The strength of these challenges will depend heavily on the examples and stability data in the patent specification.

What generic launch scenarios exist?

Launch pathway	Patent exposure
Same 0.1 mg/mL formulation, same EDTA level, same vial	Highest exposure
Same formulation with sodium metabisulfite	Potentially avoids the antioxidant-free limitation
Same phenylephrine concentration but no EDTA	Avoids the core EDTA limitation, subject to equivalents
Concentrated phenylephrine requiring dilution	May avoid ready-to-use and concentration limitations
Prefilled syringe or infusion bag	May avoid vial limitations, though formulation claims can remain relevant
Multidose vial	May avoid single-use limitations, subject to formulation claim coverage
Different pH outside 3-6.5	Potential design-around
Same formulation with oxygen above the claimed threshold	May avoid claims 9-16, but not necessarily claims 1, 2, or 19

The most credible design-around strategy is a materially different stabilization system, such as a different chelator, antioxidant-containing formulation, or non-vial delivery system. A superficial change in fill volume or label language would not necessarily avoid the formulation claims.

What patent litigation affects the phenylephrine market?

The provided claim text does not identify litigation, settlements, Paragraph IV notices, or a judicial construction involving U.S. Patent 11,471,400. Litigation exposure should be evaluated through:

District court complaints and docket entries.
ANDA Paragraph IV notices.
FDA Orange Book patent listings.
Patent-term data.
Product labels and approved supplements.
Any covenant-not-to-sue or settlement agreement.

The absence of a method-of-use limitation makes the patent more dependent on product identification and formulation evidence than on prescribing behavior. In litigation, discovery would likely focus on batch records, certificates of analysis, formulation development reports, oxygen measurements, EDTA concentration, impurity methodology, and stability protocols.

How does this patent compare with conventional phenylephrine injection patents?

Issue	U.S. Patent 11,471,400	Conventional phenylephrine patent
Active ingredient	Phenylephrine HCl	Often broad drug substance or therapeutic use
Product concentration	Narrow, approximately 0.05-0.15 mg/mL	May cover broader or concentrated ranges
Stabilizer	EDTA required in core claims	May rely on sulfites or other antioxidants
Packaging	Single-use vial required in core claims	May cover ampules, syringes, bags, or multiple formats
Stability	Explicit accelerated impurity threshold	Often absent or less specific
Oxygen control	Central to claims 9-16	May not be claimed
Method of use	Not central	May claim treatment of hypotension or vasodilation
Design-around space	Formulation and packaging changes	May require clinical or therapeutic alternatives

This patent is strongest against a specific commercial product configuration. It is weaker as a barrier to phenylephrine competition generally.

What manufacturing and IP barriers matter most?

The primary manufacturing barrier is achieving low impurity formation without bisulfite or another antioxidant while maintaining sterility, pH, and product performance. EDTA concentration alone does not establish the claimed stability result. The manufacturer must also control:

Raw-material purity.
Dissolved oxygen.
Vial headspace oxygen.
Stopper and container interaction.
Terminal sterilization or aseptic processing.
Filling accuracy.
Stability-indicating analytical methods.
Single-use packaging configuration.

Nitrogen addition is expressly claimed in process claim 15 when used to reduce headspace oxygen below 5%. Alternative gas-handling processes may avoid that specific process claim, but the resulting product can still implicate claims 9 and 10 if the oxygen limitation is met.

Key Takeaways

U.S. Patent 11,471,400 is a formulation, packaging, and manufacturing patent for ready-to-use sterile phenylephrine hydrochloride injection.
The commercial center of gravity is approximately 0.1 mg/mL phenylephrine with approximately 0.2 mg/mL EDTA, acidic pH, single-use vial packaging, and no bisulfite antioxidant.
The claims require both compositional and performance limitations. A product must satisfy the claimed impurity result, not merely match the ingredient list.
Claims 9 through 16 add low-oxygen headspace and nitrogen-controlled manufacturing limitations.
Claim 7 is commercially significant but contains a potentially contestable "about 0.2 mg" drafting issue.
Concentrated phenylephrine products, antioxidant-containing products, non-vial presentations, and formulations without EDTA are the clearest design-around categories.
The patent’s exact expiration date, Orange Book listing status, Paragraph IV activity, litigation history, and settlement status are not established by the claim text.
The patent is a targeted barrier to matching ready-to-use phenylephrine products, not a broad monopoly over phenylephrine hydrochloride.

FAQs About U.S. Patent 11,471,400

Does the patent cover phenylephrine hydrochloride concentrate?

Generally, the claims target a ready-to-use low-dose solution at approximately 0.05 to 0.15 mg/mL. A concentrated product requiring dilution would not ordinarily satisfy those limitations as sold, although the final diluted product and manufacturing pathway require separate analysis.

Can a product avoid the patent by replacing EDTA with another chelator?

Replacing EDTA is a direct strategy against the express EDTA limitation. The patent holder could still assert equivalents, but the technical and legal analysis would depend on the substitute chelator, function, formulation behavior, and prosecution history.

Does adding sodium metabisulfite avoid the patent?

It may avoid claims requiring the solution to be free of bisulfites or other antioxidants. The result depends on the exact claim, the amount and role of the antioxidant, and whether other claims remain applicable.

Does a prefilled syringe avoid the patent?

A prefilled syringe may avoid claims expressly requiring a vial or single-use vial. It may not avoid formulation claims if those claims are construed without a packaging limitation or if the syringe is treated as an equivalent presentation.

Is an FDA-approved phenylephrine product automatically infringing?

No. FDA approval and patent infringement are separate questions. Infringement depends on whether the approved product and its manufacturing process satisfy every limitation of an asserted claim.

Sources:

United States Patent and Trademark Office. (2022). U.S. Patent No. 11,471,400.
United States Code, 35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
U.S. Food and Drug Administration. (2020). Biorphen (phenylephrine hydrochloride injection) prescribing information.
United States Code, 21 U.S.C. § 355(j)(2)(A)(vii)(IV); 21 C.F.R. § 314.107.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Hikma	IMMPHENTIV	phenylephrine hydrochloride	SOLUTION;INTRAVENOUS	203826-004	Mar 9, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Hikma	IMMPHENTIV	phenylephrine hydrochloride	SOLUTION;INTRAVENOUS	203826-005	Mar 9, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ 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

Details for Patent: 11,471,400

Which drugs does patent 11,471,400 protect, and when does it expire?

Summary for Patent: 11,471,400