US Patent 11,213,480: Phenylephrine Injection Claims, Scope, Expiration and Generic-Entry Risk

US Patent 11,213,480 protects a ready-to-use, sterile phenylephrine hydrochloride intravenous injection in a single-use vial. Its central combination is low-dose phenylephrine, sodium chloride, EDTA, water, controlled acidity, and low impurity formation without bisulfite or another antioxidant. The patent also covers reduced-oxygen headspace, specific excipients, manufacturing steps, and single-use packaging.

The broadest commercial risk is concentrated in claims 1, 2 and 9. A competing product could avoid some claims by changing the phenylephrine concentration, omitting EDTA, using a different stabilizer, altering the pH, exceeding the impurity threshold, or adopting a different container and oxygen-control strategy. Those design changes may still face other patents, regulatory barriers or equivalence issues.

What does US Patent 11,213,480 cover?

The patent covers a formulation and container system rather than phenylephrine as an active pharmaceutical ingredient. The independent claims require a defined combination of formulation composition, stability performance and packaging characteristics.

Claim	Principal subject matter	Commercial significance
1	Ready-to-use sterile IV phenylephrine solution in a single-use vial	Core formulation claim
2	Similar formulation with optional preservative, buffer or pH adjustor	Broader excipient architecture
9	Claim 1 formulation with less than 10% oxygen in vial headspace	Formulation plus packaging claim
12	Method of admixing phenylephrine, sodium chloride, EDTA and water	Basic manufacturing claim
13-16	Filling volume, nitrogen or low-oxygen headspace and single-use amount	Process and packaging limitations
17	Product containing the claim 2 solution in an injection container	Product-by-assembly claim
19	Claim 1 formulation with optional preservative, buffer or pH adjustor	Dependent formulation coverage

The patent uses the transitional phrase "consists essentially of." That language generally permits additional ingredients that do not materially alter the basic and novel characteristics of the claimed formulation. The central characteristics appear to be phenylephrine stability, EDTA-associated impurity control, the specified pH and the absence of bisulfites or other antioxidants.

What formulation is protected by the patent?

The principal formulation range is:

Component	Claimed range
Phenylephrine hydrochloride	About 0.05 to 0.15 mg/mL
Sodium chloride	About 3 to 4 mg/mL
Edetate disodium	About 0.1 to 0.3 mg/mL
pH	3.0 to 6.5
Phenylephrine impurities	0.2% or less after 40°C for six months
Antioxidants	Excluded; no bisulfites or other antioxidants
Container	Single-use vial or injection container
Dosage form	Sterile, ready-to-use intravenous solution

Claim 1 is the principal composition claim. It requires phenylephrine hydrochloride to be the only active pharmaceutical ingredient. Sodium chloride and EDTA are mandatory. Water is also mandatory. The claim does not require a preservative, buffer or pH adjustor.

Claim 2 has the same core formulation but expressly permits one or more of a preservative, buffer and pH adjustor. Claims 3, 4 and 5 narrow that coverage to benzyl alcohol, citrate buffer and hydrochloric acid or sodium hydroxide.

The patent therefore targets a ready-to-use injectable product that avoids the conventional use of bisulfite antioxidants in phenylephrine formulations.

How narrow are the concentration and pH limitations?

The concentration ranges are commercially meaningful but not exceptionally narrow.

A product containing 0.1 mg/mL phenylephrine hydrochloride, 3.64 mg/mL sodium chloride and 0.2 mg/mL EDTA falls within claim 1 and the more specific formulation of claim 7. Claim 7 also requires a pH of 5.0 to 5.3. Claim 8 adds optional benzyl alcohol at about 8 mg/mL and permits buffering or pH adjustment.

The word "about" creates potential claim-construction disputes around the numerical boundaries. A product at or near 0.05 mg/mL, 0.15 mg/mL, 3 mg/mL, 4 mg/mL, 0.1 mg/mL or 0.3 mg/mL would require detailed analysis of prosecution history, specification examples and ordinary pharmaceutical measurement tolerances.

The impurity limitation is a substantial constraint. The accused product must exhibit no more than 0.2% phenylephrine impurities after six months at 40°C. That limitation is not merely a manufacturing specification. It is a performance limitation embedded in the composition claim.

What is the strongest claim in US Patent 11,213,480?

Claim 1 is likely the strongest commercial claim because it combines a relatively broad formulation range with the stability result and the single-use vial requirement.

Claim 2 may provide broader practical coverage where a product includes benzyl alcohol, citrate or a pH adjustor. It is compositionally similar to claim 1, but the optional-excipient language could make it more difficult for a competitor to avoid infringement through routine formulation additions.

Claim 9 adds low oxygen in the vial headspace. It is narrower than claim 1 because it requires the headspace to contain less than 10% oxygen. Claim 10 narrows it further to less than 5% oxygen and a fill volume of 0.05 to 20 mL.

Claims 12-16 are less powerful against a finished-product competitor unless the patent owner can establish that the competitor performs the claimed manufacturing steps in the United States. They may be more useful against a domestic contract manufacturer or a party importing a product made by a claimed process.

What are the main design-around options?

A competitor may target several limitations:

Use a phenylephrine concentration outside the claimed 0.05 to 0.15 mg/mL range.
Omit EDTA or use a different chelating agent.
Use sodium chloride outside the 3 to 4 mg/mL range.
Use a pH outside 3 to 6.5.
Use a formulation containing a bisulfite or another antioxidant, although this may create regulatory or safety disadvantages.
Use a multidose container rather than a single-use vial.
Use a prefilled syringe, ampule, bag or cartridge instead of the claimed vial or injection container, subject to the wording of the applicable claim.
Use a formulation that does not meet the 0.2% impurity limit under the specified accelerated-stability test.
Maintain a headspace oxygen concentration at 10% or higher to avoid claim 9, while recognizing that claims 1 and 2 do not require a low-oxygen headspace.
Use a different manufacturing sequence or outsource manufacture outside the United States, subject to importation and process-claim exposure.

The easiest formulation design-arounds are likely to involve EDTA, the pH range or the phenylephrine concentration. Those changes can affect stability, compatibility, injection tolerability and FDA comparability requirements.

What does claim 7 protect?

Claim 7 is a product-specific formulation claim covering approximately:

0.1 mg/mL phenylephrine hydrochloride;
3.64 mg/mL sodium chloride;
0.2 mg/mL EDTA; and
pH 5.0 to 5.3.

Claim 8 adds approximately 8 mg/mL benzyl alcohol or a buffering and pH-adjustment system.

These claims are important because they track a conventional ready-to-use phenylephrine injection strength. A product matching those parameters could face a direct literal-infringement theory if it also satisfies the sterile, vial, single-use, impurity and antioxidant limitations inherited from the parent claims.

Claim 7 contains a drafting issue: the supplied text states "edetate disodium in an amount of about 0.2 mg" without specifying a volume basis. The specification and surrounding concentration claims may clarify that the intended amount is approximately 0.2 mg/mL. The unit error could affect claim construction and enforceability, but the impact depends on the issued patent record and prosecution history.

What does the oxygen headspace coverage add?

Claims 9-11 extend protection from the liquid formulation to the container environment.

Claim 9 requires less than 10% oxygen by volume in the vial headspace. Claim 10 narrows this to less than 5% and specifies a solution volume of 0.05 to 20 mL. Claim 15 identifies nitrogen as the mechanism for reducing headspace oxygen in the manufacturing method.

This limitation is commercially relevant because oxygen exposure can contribute to phenylephrine degradation. A product may use nitrogen purging, vacuum replacement or another inert-gas process. The patent does not appear, based on the supplied claims, to require nitrogen in the product claim itself. Nitrogen is expressly required only in method claim 15.

A competitor using the same formulation but ordinary air in the headspace could avoid claims 9 and 10 while remaining exposed to claims 1, 2, 7, 17 or 19.

What patents protect ready-to-use phenylephrine products?

US Patent 11,213,480 is directed to the formulation and packaging architecture described above. It should be evaluated alongside several separate patent categories:

Patent category	Typical protected subject matter	Relevance to phenylephrine
Active-ingredient patents	New chemical entities or salts	Limited for an old active such as phenylephrine
Formulation patents	Concentration, stabilizer, pH and impurity control	Primary relevance
Container patents	Vials, prefilled syringes, oxygen control and closure systems	Relevant to claims 9-16
Method-of-use patents	Vasopressor use, dosing or clinical settings	May affect a specific indication
Manufacturing patents	Sterile compounding, filling and nitrogen purging	Relevant to claims 12-16
Regulatory exclusivity	New-drug, orphan or pediatric exclusivity	Separate from patent rights

The supplied claims do not include a method-of-treatment claim. They focus on composition, product configuration and manufacturing. A competitor could therefore avoid this patent while still needing to address other patents directed to clinical use, delivery devices or manufacturing technology.

When does US Patent 11,213,480 lose exclusivity?

The patent issued on January 4, 2022. Its term is expected to extend into 2038 based on the underlying application timeline, subject to the official patent-term calculation, any patent-term adjustment, terminal disclaimer or patent-term extension reflected in the USPTO record. The controlling expiration date should be taken from USPTO Patent Center and the FDA Orange Book if the patent is listed for an approved product. [1][2]

The patent term is distinct from FDA regulatory exclusivity. A patent may remain in force after regulatory exclusivity ends, and an ANDA applicant may challenge a listed patent before expiration through a Paragraph IV certification.

What is the Orange Book status?

The Orange Book is the relevant FDA publication for approved small-molecule drug products and listed patents. Phenylephrine hydrochloride is a small molecule, so biosimilar procedures do not apply. A prospective generic sponsor would generally use an abbreviated new drug application, or in some cases a 505(b)(2) application, depending on the product and reliance strategy. [2][3]

The relevant regulatory questions are:

Whether US 11,213,480 is listed against the reference product;
Whether the listing identifies the patent as a formulation, method-of-use or other patent;
Whether the listed patent has an expiration date in the Orange Book;
Whether a generic applicant has submitted a Paragraph IV certification;
Whether the NDA holder has filed a patent-infringement action within the statutory 45-day period; and
Whether any settlement includes a licensed launch date.

The claims provided do not establish an Orange Book listing, a Paragraph IV notice or a current lawsuit. Those matters must be determined from the current FDA and court records rather than inferred from the patent claims.

Which companies are challenging the patent?

The claim text alone does not identify a Paragraph IV challenger, ANDA filer, licensee or litigant. A patent landscape should distinguish among:

an ANDA applicant that has filed a Paragraph IV certification;
a company that has received tentative FDA approval;
a company that has launched an authorized product;
a defendant in a patent case; and
a manufacturer selling a formulation outside the patent claims.

Those categories are not interchangeable. A generic product can enter after a Paragraph IV settlement without invalidating the patent, while a commercial competitor may avoid the patent without ever litigating.

What patent litigation affects the patent?

A complete litigation assessment requires checking PACER, district-court dockets, the Federal Circuit docket and FDA records for cases involving the patent number, the NDA holder and the relevant phenylephrine product.

The principal legal issues likely to arise from the claims are:

Anticipation and obviousness

The formulation combines known injectable ingredients, but the patentee may rely on the claimed impurity result and the absence of bisulfites to distinguish prior art. A challenger would likely examine earlier phenylephrine solutions containing EDTA, sodium chloride, buffers, preservatives or antioxidant systems.

The stability limitation may be difficult to attack if the patent specification contains reproducible examples. It may be vulnerable if the test method is ambiguous, the impurity definition is incomplete or the result is not commensurate with the full concentration range.

Written description and enablement

The broad ranges cover many compositions. A challenger could argue that the specification does not enable the entire range to meet the 0.2% impurity threshold at 40°C for six months, especially where claim 2 permits multiple excipient combinations.

Indefiniteness

Potential issues include the meaning of "about," the definition of "phenylephrine impurities," the scope of "consists essentially of," and the units in claim 7. The stability test must also be sufficiently defined to permit consistent measurement.

Infringement proof

The impurity limitation may require product testing, stability data or discovery of the manufacturer's formulation records. Oxygen headspace claims may require container testing or batch records. Those facts make claims 9-16 more evidence-intensive than a simple concentration claim.

Does the patent create biosimilar risk?

No. Phenylephrine hydrochloride is a chemically synthesized small-molecule drug, not a biologic. The relevant competitive pathways are ANDA approval, 505(b)(2) approval, authorized generic entry and conventional branded competition. The FDA biosimilar pathway under the Public Health Service Act does not govern this product. [3]

How strong is the patent estate?

US Patent 11,213,480 has a focused but commercially relevant estate.

Strength factor	Assessment
Product relevance	High for ready-to-use low-dose phenylephrine vials
Formulation breadth	Moderate to high
Dependence on test results	High
Packaging coverage	Moderate; strongest where low oxygen is used
Process coverage	Moderate
Design-around availability	Meaningful
Biosimilar barrier	Not applicable
Generic litigation exposure	Potentially significant if Orange Book listed
Manufacturing barrier	Moderate, particularly for nitrogen-purged products

The estate is stronger against a product that duplicates the 0.1 mg/mL commercial formulation, uses approximately 0.2 mg/mL EDTA, maintains pH near 5.0-5.3 and uses single-use vials. It is weaker against products that use a different chelator, a different dose, a different container or an antioxidant-based stabilization strategy.

What generic launch scenarios exist?

At-risk launch before patent expiration

A generic applicant could file Paragraph IV, receive approval and launch before patent expiration if the patent is not asserted, is held invalid or is not listed against the relevant reference product. This creates damages and injunction exposure.

Authorized or licensed launch

A settlement or license could permit entry on a negotiated date before the expected patent expiration. The agreement may include restrictions on product formulation, manufacturing source or supply arrangement.

Post-expiration launch

A product that matches the patented formulation could launch after patent expiration without resolving the patent claims, assuming regulatory approval and no other blocking rights.

Design-around launch

A competitor may pursue a different concentration, chelator, pH, preservative system or package. The regulatory burden may be higher if the change prevents a straightforward ANDA showing.

What is the commercial exposure?

Ready-to-use phenylephrine injection products compete on shortage availability, hospital purchasing contracts, dosing convenience, compounding reduction and supply reliability. A formulation patent can protect a product even where the active ingredient itself is long established.

The principal commercial exposure is therefore product-specific rather than molecule-wide. A generic version of concentrated phenylephrine may not practice these claims. A ready-to-use 0.1 mg/mL vial with EDTA and no bisulfite is more likely to fall within the core claim set.

Revenue exposure should be modeled against:

sales of the protected ready-to-use vial strength;
hospital and group-purchasing contracts;
shortage-driven demand;
the ability of competitors to substitute prefilled syringes or compounded solutions;
the cost and timing of a formulation redesign; and
additional patents listed for the reference product.

Key Takeaways

US Patent 11,213,480 primarily protects a ready-to-use sterile phenylephrine hydrochloride IV solution in a single-use vial.
The core combination is 0.05-0.15 mg/mL phenylephrine hydrochloride, 3-4 mg/mL sodium chloride, 0.1-0.3 mg/mL EDTA, pH 3-6.5 and no bisulfite or other antioxidant.
The claims require no more than 0.2% phenylephrine impurities after six months at 40°C.
Claim 7 targets a commercially specific formulation of 0.1 mg/mL phenylephrine, 3.64 mg/mL sodium chloride, 0.2 mg/mL EDTA and pH 5.0-5.3.
Claims 9-16 add low-oxygen headspace and nitrogen-purging coverage.
The patent is expected to remain relevant into 2038, subject to the official USPTO term calculation.
Phenylephrine does not present biosimilar risk; generic competition proceeds through ANDA or, in some cases, 505(b)(2) pathways.
The principal design-around routes are changing EDTA, concentration, pH, antioxidant system, container type or oxygen conditions.
Current Orange Book listing, Paragraph IV activity, litigation and settlement status cannot be established from the claim text alone.

FAQs About US Patent 11,213,480

Does US Patent 11,213,480 cover all phenylephrine injections?

No. It covers a defined ready-to-use formulation and packaging combination. Concentrated phenylephrine products, products without EDTA, products outside the claimed ranges and products using materially different stabilization systems may fall outside the claims.

Can a phenylephrine generic avoid the patent by using sodium metabisulfite?

Potentially, but the answer depends on the full formulation and the scope of "consists essentially of." The claims expressly exclude bisulfites and other antioxidants, so an antioxidant-based product has a strong design-around position against the claims as supplied.

Is a prefilled syringe outside the patent?

Not automatically. Claims 1 and 2 require a vial, while claims 9-16 refer to a container or vial. A prefilled syringe may avoid the vial-specific claims, but the exact wording of the issued claims and any other patent family members must be reviewed.

Does nitrogen purging alone infringe US Patent 11,213,480?

No. Nitrogen purging is relevant to method claim 15, which also requires the claimed formulation, fill and low-oxygen conditions. Nitrogen use by itself is not enough.

Can an ANDA applicant challenge this patent before expiration?

Yes. If the patent is listed in the Orange Book for the relevant reference product, an ANDA applicant may submit a Paragraph IV certification. The NDA holder may then bring an infringement action, potentially triggering the statutory 30-month stay under the Hatch-Waxman framework. [2][4]

References

United States Patent and Trademark Office. (2022). US Patent No. 11,213,480, Stable phenylephrine formulations. USPTO Patent Center.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
U.S. Food and Drug Administration. (2024). Generic drug user fees and abbreviated new drug applications. FDA.
U.S. Food and Drug Administration. (2024). Patent certification and approval requirements under the Hatch-Waxman Amendments. FDA.

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: 11,213,480

Which drugs does patent 11,213,480 protect, and when does it expire?

Summary for Patent: 11,213,480