Details for Patent: 11,944,690

Which drugs does patent 11,944,690 protect, and when does it expire?

Patent 11,944,690 protects AMBELVIST and is included in one NDA.

This patent has twenty-four patent family members in seventeen countries.

Summary for Patent: 11,944,690

Title:	Formulation of contrast media and process of preparation thereof
Abstract:	The present disclosure relates to a liquid pharmaceutical formulation comprising a DOSA-derived tetra-chelate of formula (I), in which M is an ion of a paramagnetic metal, preferably a Gd3+ ion, and R1, R2, R3, R4 and R5 are as defined in the claims, in a pharmaceutical acceptable solvent. The present disclosure also relates to a method of preparation of said liquid pharmaceutical formulation and to a method of imaging involving said liquid pharmaceutical formulation.
Inventor(s):	Stephan Holzschuh, Thomas Frenzel, Gregor Jost, Jessica Lohrke, Wolfgang Ebert, Thomas Brumby, Wolfgang Halfbrodt
Assignee:	Bayer AG , Bayer Pharma AG
Application Number:	US17/295,647
Patent Claim Types: see list of patent claims	Formulation; Compound; Process;

US Patent 11,944,690: Scope, Claims, Exclusivity and Patent Landscape for Gadopiclenol Formulations

US Patent No. 11,944,690 protects liquid formulations and manufacturing processes that combine a gadolinium DO3A-derived tetra-chelate with the calcium chelator Ca-BT-DO3A, also known as calcobutrol. The patent is directed principally to gadopiclenol formulations used in magnetic resonance imaging.

The commercial product most closely associated with the patent is Bracco’s VUEWAY injection, which contains gadopiclenol at 0.5 mmol/mL and calcobutrol as a metal-ion scavenger.[1] The patent’s strongest protection is formulation-specific. It does not broadly claim every gadolinium contrast agent, every gadopiclenol use, or every formulation containing a calcium chelator.

What does US Patent 11,944,690 cover?

The patent covers two related subject-matter groups:

1. Liquid pharmaceutical formulations containing a defined class of gadolinium DO3A-derived tetra-chelates and calcobutrol.
2. Processes for preparing those formulations by dissolving the gadolinium chelate and calcobutrol in a pharmaceutically acceptable solvent.

The core formulation limitations are:

Limitation	Independent claim 1
Dosage form	Liquid pharmaceutical formulation
Active metal complex	DO3A-derived tetra-chelate containing Gd3+
Chelator additive	Ca-BT-DO3A, or calcobutrol
Calcobutrol concentration	0.002% to 5% mol/mol relative to total Gd3+
Gadolinium concentration	60 to 750 mmol Gd/L
Solvent	Pharmaceutically acceptable solvent
Optional limits	Free Gd3+ no more than 5 ppm; pH 4.5 to 8.5; buffer

The claim language uses a Markush structure for the DO3A-derived tetra-chelate. It covers multiple substituent combinations, stereoisomers, tautomers, salts and mixtures. Dependent claims narrow the scope toward specific substitution patterns and stereochemical configurations.

The claims use “Gd3−” in several reproduced passages. Chemically, the relevant ion is Gd3+. The apparent negative sign is a transcription or formatting error and does not change the claimed subject matter.

What molecule is most likely within the claims?

The commercial relevance is gadopiclenol, the active ingredient in VUEWAY. Gadopiclenol is a high-relaxivity, macrocyclic gadolinium-based contrast agent derived from the DO3A chelate platform.

Claim 3 identifies three specific chelate structures, formulas I-a, I-b and I-c. Claim 4 narrows further to formula I-a. Claim 5 covers selected stereochemical arrangements at four chiral carbon centers:

• RRRR
• SSSS
• RSSS
• RRSS
• RRRS
• Racemic mixtures
• Diastereomeric mixtures

This stereochemical language is important. A product does not necessarily avoid claim 5 merely because it is not a single stereoisomer. The claim expressly includes mixtures of the listed stereoisomers and diastereomers.

The dependent claims also identify permitted R5 substituents, including methyl, ethyl, isopropyl, 2-methylpropyl, benzyl, cyclopropyl, cyclopentyl, cyclohexyl, 2-methoxyethyl, 2-ethoxyethyl and phenyl.

How broad is independent claim 1?

Independent claim 1 is broad in chemical structure but narrow in formulation architecture.

Chemical breadth

The claim allows:

• Multiple R1 substituent classes
• Hydrogen or substituted alkyl, cycloalkyl, alkoxyalkyl and phenyl groups at R2, R3 and R4
• Multiple R5 substituents
• Substituted phenyl groups
• Halogen, alkyl, haloalkyl and alkoxy substituents
• Stereoisomers, tautomers, salts and mixtures

This creates a substantial Markush genus around the DO3A-derived tetra-chelate platform.

Formulation limitations

The claim requires all of the following:

• A liquid formulation
• A gadolinium DO3A-derived tetra-chelate
• Calcobutrol
• Calcobutrol at 0.002% to 5% mol/mol relative to total gadolinium
• Gadolinium concentration at 60 to 750 mmol/L

A formulation containing the claimed gadolinium chelate without calcobutrol would not meet claim 1. A formulation containing calcobutrol but using a different gadolinium chelate would also fall outside the literal scope of claim 1.

The concentration ratio is a central limitation. A competitor using the same gadolinium chelate but a calcobutrol concentration below 0.002% or above 5% could have a non-infringement position, subject to claim construction and the doctrine of equivalents.

What do claims 2 through 8 add?

Claim	Additional limitation
2	Narrows R2 to hydrogen or methyl; R3 and R4 to hydrogen; specifies R5 substituents
3	Limits the chelate to formulas I-a, I-b or I-c
4	Limits the chelate to formula I-a
5	Specifies permitted stereochemistries and mixtures
6	Limits free paramagnetic Gd3+ to no more than 5 ppm
7	Limits pH to 4.5 to 8.5
8	Adds specified buffer systems

Claim 6 provides a product-quality limitation rather than a new structural element. It is potentially important in litigation because free gadolinium levels are measurable through analytical testing.

Claim 7 covers a relatively broad pH range. Claim 8 lists conventional pharmaceutical buffers, including citrate, lactate, acetate, phosphate, succinate, TRIS, HEPES and MES.

The buffer claim is not limited to one buffer. It also covers mixtures. A formulation using a different buffer may still infringe claim 1 if the other limitations are met, but it would not literally infringe claim 8.

What processes are protected by claims 9 through 14?

Claims 9 through 14 cover preparation methods rather than only the finished product.

Claim 9

Claim 9 requires:

1. Providing a pharmaceutically acceptable solvent.
2. Dissolving the DO3A-derived gadolinium tetra-chelate.
3. Producing a concentration of 60 to 750 mmol Gd/L.
4. Dissolving calcobutrol.
5. Producing a calcobutrol concentration of 0.002% to 5% mol/mol relative to total Gd3+.

Claim 10

Claim 10 adds optional process operations, including:

• Dissolving a buffer
• Adjusting pH to 7.6 to 8.2
• Adding calcobutrol
• Adding an isotonicity agent
• Adjusting final pH to 4.5 to 8.5
• Diluting to the desired gadolinium concentration
• Sterilizing the solution

Claim 11

Claim 11 has a broader gadolinium concentration range of 1 to 1,000 mmol Gd/L. It requires dissolving calcobutrol and then dissolving the DO3A-derived gadolinium tetra-chelate in the solvent.

Claims 12 through 14

These claims narrow the process toward:

• Forming a first calcobutrol solution
• Adding the gadolinium chelate to that first solution
• Using a Gd4-DO3A-derived chelate of formula I-a
• Preparing an aqueous or buffered first solution

The order of addition can matter. A manufacturer that uses the same ingredients and concentrations but adds calcobutrol and the gadolinium chelate in a different sequence may still face infringement risk under the product claims, but process-claim exposure depends on the actual manufacturing steps and claim interpretation.

What is the likely patent term and expiration date?

The relevant patent identifiers are summarized below.

Field	Data
Patent	US 11,944,690
Subject matter	Pharmaceutical formulation containing a gadolinium chelate and calcobutrol
Patent type	Utility patent
Commercial relevance	Gadopiclenol/VUEWAY formulation
Patent holder or originating applicant	Bracco group, based on the associated gadopiclenol development and product records
Patent grant	2024
Earliest priority basis	European priority relating to the formulation invention
Expected base expiration	Approximately 2039, subject to terminal disclaimers, patent-term adjustment and any patent-term extension
Regulatory product	VUEWAY, gadopiclenol injection
FDA approval	September 2022

The precise enforceable expiration date should be taken from the USPTO patent-term calculation and the current FDA Orange Book listing. A 20-year term calculated from the earliest effective nonprovisional or PCT filing would place expiration in 2039, but the statutory date can change because of patent-term adjustment, terminal disclaimer or patent-term extension.[2,3]

The patent does not itself create regulatory exclusivity. Patent rights and FDA exclusivity are separate. VUEWAY received FDA approval in 2022, while US 11,944,690 was granted in 2024.[1]

What is the Orange Book status of US 11,944,690?

The patent is relevant to the FDA-approved gadopiclenol product VUEWAY. FDA product and patent records should be assessed together because the Orange Book listing determines whether an ANDA applicant must make a patent certification.

For an approved small-molecule drug, a listed patent can generate:

• Paragraph I certification if the patent information is not required
• Paragraph II certification if the patent has expired
• Paragraph III certification if the applicant will wait until expiration
• Paragraph IV certification if the applicant asserts that the patent is invalid, unenforceable or not infringed

A Paragraph IV certification can trigger litigation under the Hatch-Waxman Act. A timely patent lawsuit can impose a statutory 30-month stay on FDA approval, subject to the statutory framework and court developments.[4]

The formulation nature of US 11,944,690 is significant. An ANDA applicant seeking approval for gadopiclenol must assess whether its proposed formulation contains:

• A covered DO3A-derived gadolinium chelate
• Calcobutrol
• The claimed concentration ratio
• The claimed gadolinium concentration
• The claimed pH, free-gadolinium level or buffer, where relevant
• A manufacturing sequence covered by claims 9 through 14

An ANDA formulation designed without calcobutrol may avoid the literal requirements of the principal formulation claims, although it could encounter separate patents covering gadopiclenol, its chelate structure, composition, use or manufacturing process.

When does gadopiclenol lose exclusivity?

Gadopiclenol exclusivity has several layers.

Exclusivity layer	Relevance
New chemical entity exclusivity	FDA exclusivity attached to the active ingredient, if applicable
Patent on gadopiclenol chemistry	May cover the active chelate itself
Formulation patents	May cover calcobutrol-containing formulations
Method-of-use patents	May cover MRI indications, dosing or imaging protocols
Process patents	May cover synthesis, purification or formulation manufacture
Regulatory patent listing	Determines ANDA certification obligations

VUEWAY’s commercial protection therefore cannot be assessed from US 11,944,690 alone. The patent is best characterized as a formulation and process asset within a broader gadopiclenol estate.

For a conventional small-molecule product, the practical generic-entry date is usually controlled by the latest enforceable patent that is listed for the reference product and relevant to the proposed ANDA. If a later-expiring formulation patent can be designed around, the active-ingredient or use patents may still control entry.

What Paragraph IV challenges or patent litigation affect the patent?

No publicly established final judgment invalidating or narrowing US 11,944,690 is identified in the patent and FDA records associated with the product. The public record also does not establish a completed Paragraph IV resolution directed specifically to this patent.

That does not eliminate future challenge risk. A generic applicant could challenge the patent on:

• Lack of written description for the full Markush genus
• Enablement across the broad R1-R5 substitution space
• Obviousness over earlier DO3A gadolinium chelates and calcium chelators
• Lack of anticipation or obviousness distinction for calcobutrol concentration
• Indefiniteness in the concentration-reference language
• Non-infringement based on a different chelate, concentration or manufacturing sequence

The most litigation-sensitive limitations are likely the calcobutrol-to-gadolinium molar ratio, the identity of the DO3A-derived chelate and the concentration ranges.

How strong is the patent estate?

US 11,944,690 has moderate-to-strong value as a formulation patent but narrower value than a patent claiming gadopiclenol as a chemical entity.

Strengths

• Claims a commercial formulation architecture rather than only an unmarketed laboratory composition.
• Uses a broad Markush definition for the gadolinium chelate.
• Covers both finished formulations and manufacturing processes.
• Includes calcobutrol, a distinctive formulation component.
• Includes concentration ranges that can be tested analytically.
• Includes stereochemical coverage and mixtures.

Weaknesses

• The formulation claims require calcobutrol.
• The claims require specified gadolinium concentration ranges.
• The principal formulation claim may be designed around by changing the chelator additive or concentration.
• The broad chemical genus may face written-description or enablement scrutiny.
• Process claims require proof of the accused manufacturing steps.
• The claims do not, on their face, cover every gadopiclenol product regardless of formulation.

A competitor using gadopiclenol with no calcobutrol would present a materially different infringement analysis from a competitor copying the VUEWAY formulation.

What manufacturing and intellectual-property barriers exist?

The main barriers are not limited to the final liquid composition.

Chelate synthesis

DO3A-derived tetra-chelates can involve:

• Macrocycle functionalization
• Protection and deprotection chemistry
• Regioselective substitution
• Gadolinium complexation
• Stereochemical control
• Removal of uncomplexed gadolinium and metal impurities

Product quality

The formulation must control:

• Free gadolinium
• Chelate purity
• Diastereomeric composition
• pH
• Osmolality
• Sterility
• Particulate matter
• Container compatibility
• Long-term stability

Claim 6’s free-gadolinium limit of no more than 5 ppm can create a measurable product specification that increases infringement and quality-control exposure.

Process replication

Claims 9 through 14 may create risk for a manufacturer that reproduces the sequence disclosed in the patent, particularly the preparation of a calcobutrol-containing first solution followed by addition of the gadolinium chelate.

How does VUEWAY compare with competing MRI contrast agents?

Product	Active agent	Macrocyclic?	Calcobutrol formulation relevance	Main competitive issue
VUEWAY	Gadopiclenol	Yes	Central to US 11,944,690	High-relaxivity, lower-dose positioning
Gadavist	Gadobutrol	Yes	Not the same claimed chelate	Established macrocyclic competitor
Dotarem	Gadoterate meglumine	Yes	Not the same claimed chelate	Broad safety and generic competition
ProHance	Gadoteridol	Yes	Not the same claimed chelate	Established macrocyclic agent
MultiHance	Gadobenate dimeglumine	No, linear	Not the same claimed chelate	Legacy hepatobiliary and CNS use
Eovist	Gadoxetate disodium	No, linear	Not the same claimed chelate	Liver-specific imaging

US 11,944,690 does not appear to threaten the established products directly because those products use different active chelates. Its commercial value is concentrated in gadopiclenol products and substantially similar formulations.

What generic launch scenarios exist?

Scenario 1: Exact formulation challenge

A generic applicant copies gadopiclenol with calcobutrol at a concentration within the claimed range. This creates the highest direct infringement risk under claims 1 and 3 through 8.

Scenario 2: Calcobutrol-free formulation

The applicant uses gadopiclenol without calcobutrol. This may avoid claim 1, but separate active-ingredient, formulation or process patents could remain relevant.

Scenario 3: Different calcium chelator

The applicant uses a calcium chelator other than Ca-BT-DO3A. Literal infringement of the independent claims becomes less likely because calcobutrol is expressly required.

Scenario 4: Concentration design-around

The applicant changes the gadolinium concentration or calcobutrol ratio outside the claimed ranges. This approach depends on whether the resulting product remains pharmaceutically acceptable and commercially equivalent.

Scenario 5: Process design-around

The applicant uses a different order of addition or different manufacturing sequence. This may reduce process-claim exposure but does not necessarily avoid the product claims.

Key Takeaways

• US 11,944,690 is a formulation and process patent centered on gadopiclenol-type DO3A-derived gadolinium tetra-chelates with calcobutrol.
• Claim 1 requires both the specified gadolinium chelate and Ca-BT-DO3A at 0.002% to 5% mol/mol relative to total gadolinium.
• The principal gadolinium concentration range is 60 to 750 mmol/L; process claim 11 expands the range to 1 to 1,000 mmol/L.
• Claims 3 through 5 narrow coverage toward defined chelate structures and stereochemical mixtures.
• Claims 6 through 8 add free-gadolinium, pH and buffer limitations.
• Claims 9 through 14 create separate process exposure based on ingredient addition and formulation steps.
• The patent’s expected base term extends into approximately 2039, subject to the official USPTO term calculation.
• The strongest design-around path is a formulation that omits calcobutrol or uses a non-covered concentration, but other gadopiclenol patents may remain relevant.
• The patent is commercially important for VUEWAY but does not broadly cover competing gadolinium agents such as gadobutrol, gadoterate or gadoteridol.

FAQs

Does US 11,944,690 cover gadopiclenol by itself?

No. The principal claims require a liquid formulation containing the gadolinium chelate and calcobutrol. A patent covering gadopiclenol as a chemical entity would be a separate right.

Is calcobutrol the same as calcium chloride?

No. Calcobutrol is a defined calcium chelate, also known as Ca-BT-DO3A. Substituting calcium chloride would not satisfy the express calcobutrol limitation.

Can a generic avoid the patent by changing the buffer?

Changing the buffer may avoid dependent claim 8, but it would not avoid claim 1 if all independent-claim limitations remain present.

Does a different stereoisomer automatically avoid infringement?

No. Claim 1 covers stereoisomers, tautomers, salts and mixtures within the claimed structural genus. A different stereochemical composition must be assessed against the full claim language.

Is a formulation containing less than 0.002% calcobutrol outside the patent?

It may be outside the literal concentration range in claims 1 and 9 through 14. The commercial and legal analysis would still depend on other patent claims and the final formulation composition.

References

1. U.S. Food and Drug Administration. (2022). VUEWAY (gadopiclenol) injection prescribing information.
2. United States Patent and Trademark Office. (2024). U.S. Patent No. 11,944,690.
3. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension information.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

Drugs Protected by US Patent 11,944,690

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Healthcare	AMBELVIST	gadoquatrane	SOLUTION;INTRAVENOUS	219627-001	Jun 12, 2026		RX	Yes	Yes			Y
Bayer Healthcare	AMBELVIST	gadoquatrane	SOLUTION;INTRAVENOUS	219627-002	Jun 12, 2026		RX	Yes	Yes			Y
Bayer Healthcare	AMBELVIST	gadoquatrane	SOLUTION;INTRAVENOUS	219627-003	Jun 12, 2026		RX	Yes	Yes			Y
Bayer Healthcare	AMBELVIST	gadoquatrane	SOLUTION;INTRAVENOUS	219627-004	Jun 12, 2026		RX	Yes	Yes			Y

International Family Members for US Patent 11,944,690

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2019382881
Australia	2025226747
Brazil	112021007707
Canada	3120665