US Patent 9,486,406: Scope, Claims, Expiration and Patent Landscape for Phenylephrine-Ketorolac Formulations

US Patent 9,486,406 protects specific stable, preservative-free pharmaceutical formulations combining phenylephrine and ketorolac for ophthalmic use, including the concentrated formulation used to prepare an intraocular irrigation solution. The patent is closely associated with Omeros Corporation’s Omidria product, approved by the FDA as phenylephrine and ketorolac intraocular solution.

The strongest commercial coverage is concentrated in claims 6, 12 and 13. These claims reach the pH-adjusted, sodium-citrate-buffered concentrate, the approximately 1% phenylephrine/0.3% ketorolac formulation, and the diluted intraocular irrigation concentrations used during ophthalmic surgery.

What drug and product does US Patent 9,486,406 cover?

US Patent 9,486,406 covers formulations containing phenylephrine and ketorolac in an aqueous carrier. The commercial product most directly associated with the claims is Omidria, an intraocular solution used during cataract surgery and intraocular lens replacement procedures.

Product attribute	Omidria-related specification
Active ingredients	Phenylephrine hydrochloride and ketorolac tromethamine
FDA product	Omidria
FDA application	NDA 205410
Dosage form	Sterile intraocular solution concentrate
Commercial concentration	Approximately 10 mg/mL phenylephrine and 3 mg/mL ketorolac
Molar concentration	Approximately 60.75 mM phenylephrine and 11.25 mM ketorolac
Administration	Added to an ophthalmic irrigation solution
Indication	Maintenance of pupil size and reduction of postoperative ocular pain
Patent owner	Omeros Corporation
Patent	US 9,486,406 B2
Issue date	November 8, 2016
Nominal patent-term endpoint	Approximately June 30, 2032, before any applicable patent-term adjustment

The marketed concentrate is diluted into an irrigation carrier before use. That dilution produces phenylephrine and ketorolac concentrations within the ranges recited in claims 1 and 13.

The FDA label describes Omidria as a sterile solution supplied in a single-dose vial for addition to the irrigation solution used during surgery.[1]

What are the key claim categories in US 9,486,406?

The claims divide into four principal categories:

A diluted intraocular irrigation formulation.
A stable, preservative-free aqueous formulation.
A formulation consisting essentially of the two active ingredients and a buffer system.
Packaging and manufacturing-related limitations, including single-use containers and nitrogen overlay.

Claim 1: Sterile diluted intraocular formulation

Claim 1 requires:

phenylephrine;
ketorolac;
a buffer system;
an aqueous or intraocular irrigation carrier;
injection into that carrier;
final phenylephrine concentration of 30 to 720 micromolar;
final ketorolac concentration of 10 to 270 micromolar; and
stability for at least 24 months under specified storage conditions.

The claim is directed to the formulation after the concentrate has been introduced into the irrigation carrier. Its concentration ranges are broad enough to encompass typical surgical dilution conditions.

The language "that is injected into and an intraocular irrigation carrier" appears grammatically defective in the supplied claim text. The likely technical meaning is a formulation injected into an intraocular irrigation carrier. Claim construction would depend on the issued patent, prosecution history and specification rather than the isolated text.

Claim 2: Preservative-free and antioxidant-free formulation

Claim 2 covers a liquid aqueous formulation containing phenylephrine, ketorolac and a buffer system that remains stable without preservatives or antioxidants for at least six months at refrigerated or room-temperature conditions.

This is a broad composition claim because it does not recite:

a specific pH;
a specific buffer;
specific active-ingredient concentrations;
sterility;
a single-use container; or
nitrogen overlay.

The functional stability requirement is central. A formulation containing the same active ingredients may fall outside the claim if it does not satisfy the stated stability period and storage conditions.

Claims 3 and 4: pH and extended stability

Claim 3 limits claim 2 to a pH of 5.8 to 6.8.

Claim 4 requires at least 24 months of stability rather than six months. The pH range in claim 3 is commercially important because it identifies the operating window in which the formulation is intended to maintain chemical and physical stability without conventional preservatives or antioxidants.

Claim 5: Single-use packaging and nitrogen overlay

Claim 5 adds:

a single-use injection container; and
a nitrogen overlay that displaces air from the container.

The nitrogen limitation addresses oxygen exposure during storage. It is a packaging limitation, not a limitation on the chemical identity of the formulation itself.

A competing product using the same active ingredients and buffer system but a different headspace gas may avoid this dependent claim while potentially remaining within broader claims 2, 4 or 6.

Claim 6: "Consisting essentially of" formulation

Claim 6 is one of the most commercially significant claims. It requires a liquid formulation consisting essentially of:

phenylephrine;
ketorolac;
a buffer system; and
a pH-adjusted aqueous carrier.

The phrase "consisting essentially of" generally permits components that do not materially affect the basic and novel characteristics of the claimed formulation. It is narrower than "comprising" but broader than "consisting of."

The claim does not expressly recite:

sodium citrate;
the 5.8 to 6.8 pH range;
specific concentrations;
sterility;
a single-use container; or
nitrogen overlay.

Those limitations appear in dependent claims 7 through 13.

Claim 7: Sodium citrate buffer

Claim 7 limits claim 6 to a sodium citrate buffer system. This claim creates a direct point of comparison for a generic or follow-on manufacturer using a different buffer, such as phosphate or acetate.

A different buffer may avoid claim 7 but would not necessarily avoid claim 6 if the alternative buffer falls within the broader claim 6 language.

Claims 8 and 9: pH and 24-month stability

Claim 8 adds a pH of 5.8 to 6.8.

Claim 9 requires at least 24 months of stability under the specified temperature conditions.

Together, claims 7 through 9 identify a formulation architecture that is highly aligned with the commercial product: sodium citrate buffering, controlled acidic pH, and long-term stability.

Claims 10 and 11: Single-use container and nitrogen overlay

Claim 10 requires the formulation to be contained in a single-use container.

Claim 11 adds the nitrogen overlay limitation.

These claims are relevant to vial-based products and sterile fill-finish processes. A manufacturer could attempt to design around them through packaging differences, but that strategy would not address the broader formulation claims.

Claim 12: Commercial-strength concentrate

Claim 12 requires approximately:

60.75 mM phenylephrine; and
11.25 mM ketorolac.

These concentrations correspond closely to approximately 10 mg/mL phenylephrine and 3 mg/mL ketorolac, the strength associated with Omidria.[1]

This claim has high product-read-through value. A pharmaceutical formulation matching these molar concentrations, together with the limitations inherited from claim 6, would face a substantial literal-infringement risk.

Claim 13: Diluted irrigation concentrations

Claim 13 depends on claim 6 and requires the formulation to be injected into an irrigation carrier. After injection, it requires:

phenylephrine at 240 to 720 micromolar; and
ketorolac at 10 to 270 micromolar.

The claim is directed to the use-stage concentration rather than only the vial concentrate. It is potentially relevant to the final ophthalmic irrigation solution supplied or prepared for surgical use.

How broad are the claims of US 9,486,406?

The claim breadth varies materially by claim type.

Claim	Principal limitation	Relative breadth
1	Sterile diluted irrigation formulation, concentration ranges, 24-month stability	Moderate
2	Phenylephrine, ketorolac, buffer, preservative-free stability	Broad
3	Claim 2 plus pH 5.8-6.8	Moderate
4	Claim 2 plus 24-month stability	Moderate
5	Claim 2 plus single-use container and nitrogen overlay	Narrow
6	"Consisting essentially of" phenylephrine, ketorolac, buffer and aqueous carrier	Broad-to-moderate
7	Claim 6 plus sodium citrate buffer	Narrower
8	Claim 6 plus pH 5.8-6.8	Narrower
9	Claim 6 plus 24-month stability	Narrower
10	Claim 6 plus single-use container	Narrower
11	Claim 10 plus nitrogen overlay	Narrow
12	Claim 6 plus commercial-strength molar concentrations	Product-specific
13	Claim 6 plus diluted irrigation concentrations	Product-use-specific

Claims 2 and 6 provide the principal platform coverage. Claims 7 through 13 provide narrower fallback positions that are more closely tied to the commercial formulation and its packaging.

The patent does not claim phenylephrine or ketorolac individually. It claims the combination in a specific aqueous, buffered and stable formulation environment. A product containing only phenylephrine or only ketorolac would not infringe these composition claims.

What formulations are protected by US 9,486,406?

The patent’s technical center is a stable combination formulation without preservatives and antioxidants.

Protected formulation attributes

The relevant attributes include:

phenylephrine and ketorolac in the same formulation;
an aqueous carrier;
a buffer system;
pH adjustment;
stability for six months or 24 months;
optional sodium citrate buffering;
optional single-use vial packaging;
optional nitrogen headspace;
concentration of approximately 60.75 mM phenylephrine and 11.25 mM ketorolac; and
dilution into an intraocular irrigation solution.

What is not expressly required by every claim?

Not every claim requires:

sodium citrate;
sterility;
nitrogen overlay;
a single-use vial;
a specific pH;
the commercial concentrations; or
dilution before administration.

This creates a layered estate. A competitor may avoid a narrow dependent claim while remaining exposed under a broader independent claim.

When does US Patent 9,486,406 lose exclusivity?

The patent’s nominal term is expected to end around June 30, 2032, based on the relevant nonprovisional filing timeline and the standard 20-year patent term under 35 U.S.C. §154.[2]

The operative date must be determined from the USPTO patent-term calculation, including:

patent-term adjustment;
any terminal disclaimer;
any patent-term extension under 35 U.S.C. §156; and
the relationship between the patent and the approved NDA.

The patent issued in 2016, but the issue date does not determine expiration. Patent expiration is generally calculated from the earliest effective nonprovisional filing date in the chain, subject to statutory adjustments.

FDA regulatory exclusivity is separate from patent exclusivity. Omidria received FDA approval in 2014. Any five-year new chemical entity exclusivity associated with the NDA would have expired before the patent term, leaving patent protection as the principal barrier to an ANDA launch.[1,3]

What is the Orange Book status of US 9,486,406?

US 9,486,406 is associated with the Omidria NDA and has been listed in FDA Orange Book patent records for the product.[3]

An Orange Book listing allows the NDA holder to provide patent information that an ANDA applicant must address through one of the statutory certifications:

Paragraph I: no patent information has been submitted;
Paragraph II: the patent has expired;
Paragraph III: the applicant will wait until patent expiration; or
Paragraph IV: the patent is invalid, unenforceable or will not be infringed.

For a listed formulation patent covering the marketed product, a generic applicant seeking launch before expiration would ordinarily evaluate a Paragraph IV certification.

The relevant regulatory distinction is important:

the Orange Book listing concerns patents associated with an approved small-molecule drug;
the FDA does not determine patent validity through the Orange Book;
a Paragraph IV certification can trigger patent litigation under the Hatch-Waxman Act;
a successful Paragraph IV challenge can remove or narrow the patent barrier before the listed expiration date.

Which companies are challenging Omidria patent protection?

The principal competitive risk is from ANDA applicants seeking approval for a phenylephrine and ketorolac intraocular solution equivalent to Omidria.

A Paragraph IV litigation determination requires a review of:

FDA Orange Book updates;
ANDA litigation filings;
district court complaints;
case-specific settlements; and
any appellate decisions.

The claim text alone does not establish that a particular manufacturer has filed a Paragraph IV certification. The relevant risk is product-specific: an ANDA applicant may challenge one patent, several listed patents, or the entire listed estate through separate certifications.

A generic applicant could pursue several design-around strategies:

use a different buffer;
alter the pH outside the claimed range;
change the concentration of one or both active ingredients;
use preservatives or antioxidants;
use different container or headspace conditions;
avoid a formulation that satisfies the 24-month stability limitation; or
challenge claim validity based on anticipation, obviousness, written description, enablement or indefiniteness.

The first three strategies may avoid dependent claims but may not avoid claims 2 or 6.

What patent litigation affects US 9,486,406?

A patent litigation analysis must distinguish between:

litigation involving US 9,486,406 itself;
litigation involving other Omidria patents;
ANDA litigation that names Omeros;
contractual disputes involving distribution or commercialization; and
post-grant proceedings before the USPTO.

The relevant causes of action in an ANDA case would ordinarily include infringement under 35 U.S.C. §271(e)(2), declaratory claims concerning validity or enforceability, and counterclaims addressing Orange Book listing or patent scope.

No conclusion about validity follows from the fact that the patent issued or was listed. Issued patents carry a presumption of validity, but the presumption does not prevent an ANDA applicant from asserting invalidity defenses.

The patent’s most likely litigation pressure points are:

whether a generic formulation satisfies the stability limitation;
whether "consisting essentially of" excludes a particular excipient;
whether the accused formulation is within the claimed concentration range;
whether the final irrigation solution, rather than the concentrate, is the relevant article of manufacture;
whether the asserted claims are enabled across their full breadth; and
whether the claims are anticipated or rendered obvious by earlier ophthalmic combination formulations.

How strong is the patent estate for Omidria?

US 9,486,406 has meaningful commercial strength because several claims map directly to the approved product. Its strength is strongest where the accused formulation reproduces the commercial formulation and the specified storage profile.

Strengths

Claim 12 closely tracks the commercial-strength concentrate.
Claim 13 reaches the diluted surgical irrigation concentrations.
Claims 7 through 11 provide multiple fallback positions based on buffer, pH, packaging and nitrogen overlay.
The patent covers both the concentrate and the use-stage diluted formulation.
The claims target formulation stability, which may be difficult to design around while preserving commercial shelf life.

Vulnerabilities

Claims 2 and 6 are functionally broad and may face obviousness or enablement attacks.
Stability limitations can create fact-intensive infringement disputes.
A competitor may use a different buffer or packaging configuration.
"Consisting essentially of" can create uncertainty over permitted excipients.
The claims do not independently cover the active ingredients, manufacturing process or ophthalmic indication in the absence of the specified formulation features.
A generic applicant may challenge concentration, dilution and stability measurements through analytical and scientific evidence.

The estate is stronger as a product-specific barrier than as a broad composition monopoly over all phenylephrine-ketorolac combinations.

Does US 9,486,406 create biosimilar risk?

No conventional biosimilar pathway applies. Omidria is a small-molecule drug regulated under the FDA’s abbreviated new drug application pathway, not a biologic regulated under the Biologics Price Competition and Innovation Act.

The relevant competitive pathway is an ANDA for a generic phenylephrine and ketorolac ophthalmic solution. The main legal tools are Orange Book patent certifications, Paragraph IV litigation and potential 30-month stays under the Hatch-Waxman framework.

What manufacturing and intellectual-property barriers matter?

The formulation claims create barriers beyond the active ingredients themselves.

A competing manufacturer would need to establish:

compatible phenylephrine and ketorolac concentrations;
acceptable pH;
chemical stability of both active ingredients;
absence or controlled use of preservatives and antioxidants;
sterile fill-finish performance;
container-closure compatibility;
acceptable headspace oxygen control;
dilution stability in the irrigation carrier; and
an FDA-equivalent product profile.

The nitrogen-overlay limitation is unlikely to be the principal barrier by itself. The more important constraints are the combination of preservative-free stability, commercial concentration, pH and final irrigation concentration.

How does Omidria compare with competing ophthalmic products?

Omidria differs from conventional intraocular phenylephrine or ketorolac products because it combines both actives in a single formulation intended for addition to the surgical irrigation solution.

Product type	Phenylephrine	Ketorolac	Intraocular irrigation use	Main patent-risk profile
Omidria	Yes	Yes	Yes	Direct exposure to claims 6, 12 and 13
Phenylephrine-only ophthalmic product	Yes	No	Usually no	Outside the combination claims
Ketorolac-only ophthalmic product	No	Yes	Usually no	Outside the combination claims
Separate phenylephrine and ketorolac products	Separate products	Separate products	Depends on use	May avoid composition claims but requires separate regulatory pathway
Combination product with different formulation	Yes	Yes	Possible	Depends on buffer, pH, stability and concentrations

The patent does not prevent all competition in perioperative ophthalmology. It creates a targeted barrier against a stable combined formulation designed for the same intraocular irrigation use.

What generic launch scenarios exist?

Launch after patent expiration

This is the lowest litigation-risk scenario. An ANDA applicant can certify Paragraph III and wait until the listed patent expires, subject to other patents, regulatory exclusivity and manufacturing readiness.

Launch after successful Paragraph IV challenge

A generic applicant may launch before the nominal expiration date if the patent is held invalid, not infringed or unenforceable, or if the patent owner does not obtain effective injunctive relief.

Launch after settlement

A settlement could establish a licensed or otherwise agreed entry date. The commercial effect depends on:

the agreed launch date;
authorized-generic provisions;
supply obligations;
royalty terms;
restrictions on formulation changes; and
treatment of other Omidria patents.

Design-around launch

A competing product may attempt to avoid the claims by changing buffer chemistry, pH, concentrations, packaging or stability profile. This approach carries regulatory and commercial risk because changes may affect equivalence, shelf life and ophthalmic tolerability.

Are there licensing deals or settlement agreements tied to this patent?

Omeros is the principal commercial rights holder associated with Omidria and US 9,486,406. A patent-specific licensing or settlement agreement cannot be inferred from the patent record alone.

Commercial arrangements involving distributors, contract manufacturers or regional partners do not necessarily transfer patent rights or create an authorization to market a competing formulation. Any settlement would need to be evaluated against the Orange Book-listed patents, the relevant ANDA applicant and the effective entry date.

Key Takeaways

US 9,486,406 is a formulation patent centered on phenylephrine-ketorolac ophthalmic solutions.
Claims 2 and 6 provide the broadest platform coverage.
Claim 12 closely tracks the commercial-strength Omidria concentrate.
Claim 13 covers the diluted intraocular irrigation concentrations.
Sodium citrate, pH 5.8 to 6.8, single-use packaging and nitrogen overlay create narrower fallback claims.
The patent is associated with Omeros Corporation’s Omidria NDA 205410.
The nominal patent-term endpoint is approximately June 30, 2032, before applicable adjustments.
Generic competition would proceed through an ANDA and Orange Book certification, with Paragraph IV as the principal early-entry challenge.
Biosimilar competition is not applicable because Omidria is a small-molecule drug.
The estate is strongest against a product that reproduces the commercial formulation, concentrations, stability profile and intraocular irrigation use.
The principal validity and infringement issues are obviousness, enablement, stability testing, concentration ranges, excipient scope and the interpretation of "consisting essentially of."

FAQs

What is the active-ingredient ratio in the formulation covered by claim 12?

Claim 12 recites approximately 60.75 mM phenylephrine and 11.25 mM ketorolac, corresponding approximately to a 10 mg/mL phenylephrine and 3 mg/mL ketorolac concentrate.

Does using a phosphate buffer avoid US 9,486,406?

It may avoid claim 7, which specifically requires sodium citrate, but it would not automatically avoid claims 2 or 6. The full formulation would need to be assessed against every limitation of the asserted claims.

Does a preservative-containing formulation fall outside the patent?

A preservative-containing formulation may avoid claim 2 because that claim expressly requires stability without preservatives and antioxidants. It may still require analysis under other claims, particularly claim 6, depending on the meaning and effect of the added preservative.

Does the patent cover use of the active ingredients in separate vials?

The claims are directed to a formulation containing phenylephrine and ketorolac together. Separate-vial administration generally presents a different claim profile, although the final combined irrigation solution would require separate analysis under claims directed to the diluted formulation.

Can a generic launch before 2032 occur without invalidating the patent?

Yes. Early launch could follow a successful Paragraph IV challenge, a court determination of noninfringement or invalidity, a settlement permitting entry, or a formulation design-around that avoids all enforceable claims.

References

U.S. Food and Drug Administration. (2014). Omidria (phenylephrine and ketorolac injection) prescribing information. FDA.
United States Patent and Trademark Office. (2016). U.S. Patent No. 9,486,406 B2: Pharmaceutical compositions comprising phenylephrine and ketorolac. Washington, DC: U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
United States Congress. (2011). Leahy-Smith America Invents Act and 35 U.S.C. §§ 154, 156 and 271. Washington, DC.
Omeros Corporation. (2023). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Rayner Surgical	OMIDRIA	ketorolac tromethamine; phenylephrine hydrochloride	SOLUTION;IRRIGATION	205388-001	May 30, 2014	AT	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

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	093115	⤷ Start Trial
Australia	2013201465	⤷ Start Trial
Brazil	112015009228	⤷ Start Trial
Canada	2887772	⤷ Start Trial
Chile	2015001078	⤷ Start Trial
China	104822265	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,486,406