US Patent 10,966,990: Midazolam IV Bag Claims, Patent Scope, Expiration Risk, and Competitive Landscape

US Patent 10,966,990 protects a specific ready-to-use midazolam intravenous presentation rather than midazolam generally. The independent claim requires a preservative-free aqueous solution, terminal sterilization, an acidic pH, controlled osmolality, defined midazolam concentration, accelerated-stability performance, and a multilayer laminated plastic bag with an ethylene-vinyl acetate inner layer. The patent’s commercial relevance is concentrated in premixed midazolam injection bags containing approximately 0.5 or 1 mg/mL midazolam in a sodium-chloride vehicle.

The principal infringement risk applies to a product that combines all of those elements. A conventional midazolam vial, a formulation outside the claimed pH or concentration ranges, or a bag lacking the claimed EVA innermost layer would not literally satisfy claim 1.

What does US Patent 10,966,990 protect?

The claims cover a pharmaceutical product defined by both formulation and packaging characteristics.

Claim element	Required limitation
Dosage form	Ready-to-use aqueous intravenous solution
Active ingredient	Midazolam
Midazolam concentration	0.25 to 1.5 mg/mL in claim 1
Preservatives	Preservative-free
Sterilization	Terminally sterilized
Osmolality	260 to 320 mOsm/kg
pH	About 2.5 to 3.5
Acid	Hydrochloric acid
Optional base	Sodium hydroxide
Tonicity agent	Sodium chloride, potassium chloride, or calcium chloride
Stability	More than 97% midazolam remaining after six months at 40°C
Container	Intravenous laminated flexible plastic bag
Bag construction	Three to seven layers
Inner layer	Ethylene-vinyl acetate copolymer

Claim 1 is therefore a combination claim. Each required limitation must be present for literal infringement. The patent does not claim every ready-to-use midazolam injection or every midazolam solution in a flexible bag.

The claim also contains a performance limitation. A competing product must satisfy the stability requirement as claimed, although infringement disputes may focus on the testing protocol, analytical method, batch selection, and whether the limitation is treated as a product characteristic or merely evidence of an intended result.

How do dependent claims narrow the protected midazolam formulations?

Claims 2 through 12 identify commercially practical embodiments of the broad combination in claim 1.

Claim	Narrowed subject matter
2	Sodium chloride as the tonicity agent
3	Sodium chloride at 9 mg/mL
4	Midazolam at approximately 0.5 to 1.25 mg/mL
5	Midazolam at approximately 0.5 mg/mL
6	Midazolam at approximately 1 mg/mL
7	pH of 2.5 to 3.5
8	pH of 2.8 to 3.2
9	pH of approximately 3
10	Approximately 0.5 mg/mL midazolam, pH about 3, sodium chloride, and hydrochloric acid
11	Approximately 1 mg/mL midazolam, pH about 3, sodium chloride, and hydrochloric acid
12	Claim 11 with approximately 9 mg/mL sodium chloride
13	Composition consisting essentially of the identified formulation components

Claims 10 through 12 are the most commercially targeted claims. They cover the likely premixed presentations using 0.9% sodium chloride, which corresponds to approximately 9 mg/mL sodium chloride.

Claim 13 is important because “consisting essentially of” generally permits components that do not materially alter the basic and novel characteristics of the composition. It may exclude preservatives, buffers, antioxidants, or excipients that materially affect the claimed formulation, but the precise scope depends on the patent specification and prosecution history.

What is the core patent scope of claim 1?

Claim 1 has four principal protection layers:

Formulation protection

The solution must contain midazolam in a concentration from 0.25 to 1.5 mg/mL. The formulation must be acidic, with a pH from approximately 2.5 to 3.5, and must use hydrochloric acid. It must also contain one of the listed chloride salts to provide near-isotonic osmolality.

This excludes a formulation that uses a different acid, such as acetic, citric, or sulfuric acid, unless the alternative formulation is found equivalent under the doctrine of equivalents. It also creates a design-around opportunity through a different tonicity agent, although the claim expressly includes potassium chloride and calcium chloride.

Packaging protection

The bag must be a laminated flexible plastic container with three to seven layers and an EVA innermost layer. This limitation distinguishes the patent from a formulation claim that would cover the same solution in a glass vial, polypropylene syringe, or a bag with a different product-contact layer.

The innermost EVA layer is likely directed to compatibility between the acidic midazolam solution and the container. Packaging records, resin specifications, supplier declarations, and multilayer film certificates would be central to an infringement analysis.

Manufacturing and sterility protection

The product must be terminally sterilized. Aseptic filling without terminal sterilization would not literally satisfy this limitation. The distinction is material because terminal sterilization can create degradation, extractables, leachables, or container-integrity issues in an acidic benzodiazepine formulation.

Stability protection

The formulation must retain more than 97% midazolam after accelerated storage at 40°C for six months. This requirement links the claimed formulation and container to a defined stability outcome. It may make infringement fact-intensive because the result must be established through analytical testing rather than inferred solely from the label.

Which patent claims present the greatest generic-entry risk?

Claims 1, 10, 11, and 12 present the greatest risk for a product matching a standard premixed presentation.

Product design	Literal infringement exposure
0.5 mg/mL midazolam in 0.9% sodium chloride, pH about 3, terminally sterilized EVA-lined bag	High, if stability and layer count also match
1 mg/mL midazolam in 0.9% sodium chloride, pH about 3, same bag construction	High, particularly under claims 11 and 12
Same formulation in a glass vial	Lower under the asserted claims because the bag limitation is absent
Same concentration in a non-EVA multilayer bag	Lower on literal infringement
Same bag and concentration using a different acid	Lower on literal infringement
Aseptically filled product without terminal sterilization	Lower on literal infringement
Product with a preservative	Outside the express preservative-free limitation
Midazolam concentration below 0.25 or above 1.5 mg/mL	Outside claim 1’s concentration range
Product with pH above 3.5 or below 2.5	Outside the express pH range

A design-around based only on a minor numerical change may face doctrine-of-equivalents risk. A design-around that changes the dosage form, container-contact polymer, sterilization method, or acid system is structurally stronger.

When does US Patent 10,966,990 lose exclusivity?

The patent’s enforceable term depends on its earliest effective nonprovisional priority date, any terminal disclaimer, patent-term adjustment, patent-term extension, and applicable regulatory history. The issue date, April 6, 2021, does not by itself establish the expiration date. The controlling source is the USPTO patent record and the patent-term calculation associated with the patent. [1]

The patent term for a modern utility patent generally runs 20 years from the earliest effective US nonprovisional filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156. [2] A precise expiration date cannot be determined from the claims alone.

The practical exclusivity timeline is therefore:

Event	Relevance
Earliest effective filing date	Starts the ordinary 20-year term calculation
Patent issue date	Establishes enforceable patent rights after grant
Patent-term adjustment	May extend the ordinary term for USPTO delay
Terminal disclaimer	May limit the term to an earlier-expiring patent
Patent-term extension	May apply only in the statutory circumstances
Expiration	Ends ordinary patent-based exclusion, subject to other patents

A generic applicant should not rely on the absence of an expiration date from the product label. The patent file, continuity data, terminal-disclaimer records, and USPTO Patent Center status control.

What is the Orange Book status of US Patent 10,966,990?

A patent number alone does not establish Orange Book listing status. FDA Orange Book listing requires an NDA sponsor to submit patent information covering the approved drug product, including patents claiming the drug substance, drug product, or an approved method of use. [3]

US Patent 10,966,990 is directed to a combination of formulation, sterilization, stability, and container features. Its Orange Book relevance would depend on whether the NDA holder submitted the patent under the applicable FDA patent-listing categories and whether FDA accepted the submission.

The likely regulatory classification is drug-product patent information, not a drug-substance patent. The patent does not claim midazolam as a chemical compound. It also does not claim a method of treating a disease, sedating a patient, inducing anesthesia, or administering midazolam.

A diligence review should distinguish:

Patent ownership and assignment.
FDA listing in the Orange Book.
The NDA product associated with the listing.
Whether the patent is listed for a specific dosage form or presentation.
Whether the patent has been delisted, expired, or removed.
Whether the patent creates a Paragraph IV certification obligation.

How would a Paragraph IV challenge apply?

A generic applicant seeking approval of a product that references an NDA could address the patent through a Paragraph IV certification if the patent is listed and the applicant asserts that the patent is invalid, unenforceable, or will not be infringed. [4]

The strongest noninfringement arguments would target limitations that are difficult to satisfy accidentally:

No laminated flexible bag.
No EVA inner layer.
No terminal sterilization.
Use of an acid other than hydrochloric acid.
pH outside the claimed range.
Osmolality outside 260 to 320 mOsm/kg.
Inclusion of a preservative.
Different midazolam concentration.
Failure to meet the greater-than-97% stability limitation.

Invalidity arguments would likely focus on anticipation and obviousness based on prior art disclosing:

Ready-to-use midazolam solutions.
Premixed IV benzodiazepine products.
Acidified midazolam formulations.
Isotonic sodium-chloride vehicles.
Terminal sterilization of parenteral bags.
EVA or EVA-containing multilayer pharmaceutical films.
Stability data for midazolam in plastic containers.

The claim’s combined limitations may make anticipation difficult if no single reference discloses the complete formulation, package, sterilization process, and stability result. Obviousness analysis could be stronger if the prior art separately teaches acidic midazolam, isotonic sodium chloride, terminal sterilization, and EVA-lined bags, particularly if the specification identifies predictable compatibility and stability objectives. The Supreme Court’s obviousness framework in KSR v. Teleflex is relevant to that combination analysis. [5]

What method-of-use and formulation patents are relevant?

US Patent 10,966,990 is not principally a method-of-use patent. Its claims are directed to a physical pharmaceutical product. The claims do not require a particular patient population, clinical indication, dose regimen, or administration rate.

The patent estate should be separated into four categories:

Patent category	Relevance to this patent
Drug-substance patents	Not implicated by the supplied claims
Drug-product or formulation patents	Directly implicated
Container or packaging patents	Directly implicated through the EVA bag limitation
Method-of-use patents	Not present in claims 1-13

A generic product could avoid this patent but still face separate patents covering administration methods, premixed parenteral packaging, manufacturing processes, or other midazolam presentations. Conversely, a product may fall within this patent even if it does not infringe any method-of-use patent.

Does biosimilar risk apply to midazolam?

No. Midazolam is a small-molecule active pharmaceutical ingredient, not a biologic subject to the biosimilar pathway under the Public Health Service Act. The relevant competitive pathway is an ANDA or, for certain products, another small-molecule FDA application pathway. [6]

Biosimilar litigation concepts such as the Biologics Price Competition and Innovation Act patent dance do not apply to this product. The relevant patent challenge mechanism is the Hatch-Waxman framework, including Paragraph IV certification and potential 30-month litigation stays. [4]

Which companies could challenge or design around the patent?

The competitive field includes manufacturers of injectable midazolam, premixed IV products, flexible parenteral bags, and contract-manufactured hospital injectables. Potential challengers would generally include:

Generic injectable manufacturers.
Hospital-injectable specialists.
Branded pharmaceutical companies with midazolam NDAs.
Contract manufacturers developing ready-to-use IV products.
Suppliers with alternative multilayer film systems.

A company selling midazolam in vials has a different risk profile from a company selling premixed IV bags. The latter must audit the container film, sterilization cycle, pH adjustment, osmolality, and accelerated-stability data before commercialization.

No litigation, settlement, or license agreement can be inferred from the claims supplied. A reliable litigation conclusion requires the USPTO assignment file, PACER district-court records, PTAB records, FDA Orange Book data, and public company disclosures. [1, 3, 7]

How strong is the patent estate for ready-to-use midazolam bags?

The individual patent is technically narrow but commercially focused.

Its strengths are:

It covers the complete marketed presentation rather than only the active ingredient.
Claims 10 through 12 target common 0.5 and 1 mg/mL embodiments.
The EVA bag limitation may be difficult to assess without manufacturer and supplier records.
The stability limitation ties the formulation to a measurable performance result.
The claim combines multiple independent design choices, which may reduce simple label-based design-around arguments.

Its weaknesses are:

The claim requires a specific bag architecture.
The patent does not cover vials, syringes, or every midazolam formulation.
Alternative acids, sterilization approaches, polymers, and concentrations may avoid literal infringement.
The stability limitation may create proof and reproducibility issues.
Prior art may disclose the individual elements of the combination.

The patent is strongest against a substantially identical premixed product in the same type of EVA-lined laminated bag. It is materially weaker against a product using a different container-contact material or a different manufacturing pathway.

What generic launch scenarios exist?

Scenario 1: Identical premixed bag

A generic launches a 0.5 or 1 mg/mL midazolam product in a 0.9% sodium chloride EVA-lined bag, with pH near 3 and terminal sterilization. This scenario creates the highest infringement exposure and would likely require a Paragraph IV strategy if the patent is Orange Book listed.

Scenario 2: Same formulation in a different container

A generic uses a glass vial, syringe, or non-EVA bag. This approach removes a central claim limitation but may change shipping, administration, extractables, and hospital purchasing economics.

Scenario 3: Different formulation architecture

A generic changes the acid system, pH, tonicity agent, or sterilization method. This can avoid literal infringement but requires new stability, compatibility, sterility, and regulatory data.

Scenario 4: Launch after patent expiry

A manufacturer waits until the patent term ends. This eliminates infringement risk under this patent but does not resolve other formulation, packaging, method-of-use, or regulatory exclusivity issues.

Key Takeaways

US Patent 10,966,990 is a combination patent covering a ready-to-use, terminally sterilized, preservative-free midazolam IV solution in a specific multilayer flexible bag.
The commercial center of gravity is the 0.5 and 1 mg/mL embodiments in approximately 0.9% sodium chloride.
The EVA innermost layer, terminal sterilization, hydrochloric acid, pH, osmolality, and stability limitations are critical claim elements.
The patent does not claim midazolam generally, midazolam vials, or a method of treating patients.
The strongest generic design-arounds change the container-contact polymer, dosage form, acid system, or sterilization process.
Orange Book listing, litigation, settlements, licensing, and the precise expiration date require review of the FDA and USPTO records rather than the claim text alone.
Biosimilar risk does not apply because midazolam is a small-molecule drug.

FAQs

Does a midazolam vial infringe US Patent 10,966,990?

Not literally under the supplied claims because claim 1 requires an intravenous laminated flexible plastic bag with three to seven layers and an EVA innermost layer.

Does 0.9% sodium chloride satisfy the claimed tonicity limitation?

Approximately 9 mg/mL sodium chloride corresponds to 0.9% sodium chloride and is expressly recited in claims 3 and 12, subject to the remaining claim limitations.

Can a product avoid the patent by using polypropylene instead of EVA?

A product using polypropylene as the innermost product-contact layer would not literally satisfy the EVA limitation. Doctrine-of-equivalents exposure would depend on the technical and prosecution history record.

Is terminal sterilization required for infringement?

Yes. Claim 1 expressly requires a terminally sterilized product. An aseptically filled product without terminal sterilization would have a substantial noninfringement position on that limitation.

Does the patent cover midazolam injection in any concentration?

No. Claim 1 is limited to 0.25 to 1.5 mg/mL. The dependent claims narrow the range further, including approximately 0.5 and 1 mg/mL embodiments.

References

United States Patent and Trademark Office. (2021). US Patent No. 10,966,990.
35 U.S.C. §§ 154, 156.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
21 U.S.C. § 355(j).
KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007).
42 U.S.C. § 262.
United States Patent and Trademark Office. (2024). Patent Center and Patent Trial and Appeal Board public records.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Inforlife	MIDAZOLAM IN 0.9% SODIUM CHLORIDE	midazolam	SOLUTION;INTRAVENOUS	211844-001	Mar 22, 2021	AP	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
Inforlife	MIDAZOLAM IN 0.9% SODIUM CHLORIDE	midazolam	SOLUTION;INTRAVENOUS	211844-002	Mar 22, 2021	AP	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: 10,966,990

Which drugs does patent 10,966,990 protect, and when does it expire?

Summary for Patent: 10,966,990