United States Patent 10,722,601: Claim Scope, Exclusivity and Patent Landscape for Tetragadolinium MRI Contrast Agents
US Patent 10,722,601 protects stereochemically defined tetragadolinium complexes, their corresponding gadolinium-free ligands, stereoisomeric mixtures, and use in magnetic resonance imaging. The patent is most closely associated with Bayer’s gadoquatrane program, an investigational high-relaxivity macrocyclic MRI contrast agent containing four gadolinium chelates.
The composition claims are the principal barrier. They cover defined stereochemical configurations, racemic and diastereomeric mixtures, salts, hydrates, solvates, tautomers, and related chemical forms. The method claims add MRI administration and a seven-day patient-retention limitation. Based on the apparent 2015 nonprovisional or PCT filing date, the nominal US patent term likely runs into November 2035, subject to patent-term adjustment or extension.
What does US Patent 10,722,601 protect?
US 10,722,601 has two central composition families:
| Claim group |
Protected subject matter |
Commercial relevance |
| Claims 1-8 |
Formula I tetragadolinium complexes and stereoisomeric mixtures |
Directly covers the gadolinium-containing MRI contrast agent |
| Claims 9-14 |
Formula II gadolinium-free ligands and stereoisomers |
Covers key intermediates, precursors, or ligand forms |
| Claim 15 |
MRI imaging method using Formula I compounds |
Use protection for administration and imaging |
| Claim 16 |
Claim 15 method in which less than 0.5% remains in the patient after seven days |
Pharmacokinetic and clearance limitation |
The independent composition claims use "comprising," which generally permits additional chemical components or formulation ingredients unless the claim construction or specification indicates otherwise. Claims 1 and 9 are therefore broader than the individually named stereoisomers in dependent claims 2-6 and 10-14.
The patent does not merely claim a generic gadolinium chelate. It claims a large, covalently linked structure containing four macrocyclic gadolinium-binding units joined through a peptide-like or amide-containing central scaffold.
How broad are claims 1-8 for tetragadolinium complexes?
Claim 1 covers Formula I compounds in which the four alanine-derived chiral centers have selected configurations:
It also covers racemic mixtures and diastereomeric mixtures of those configurations. The claim extends to:
- Tautomers
- Hydrates
- Solvates
- Salts
- Mixtures of those forms
The five listed configurations appear to represent stereochemical classes after accounting for molecular symmetry. Configurations that might be written as SRRR or other permutations can be chemically equivalent to a listed configuration depending on how the symmetrical molecule is numbered. That symmetry issue is material to infringement analysis and claim construction.
What do claims 2-6 add?
Claims 2-6 identify specific tetragadolinium stereoisomers by full systematic chemical name. They correspond to defined configurations at the central chiral centers and alanine-derived positions.
| Claim |
General stereochemical subject |
| 2 |
R/R-type tetragadolinium stereoisomer |
| 3 |
S/S-type tetragadolinium stereoisomer |
| 4 |
R/S-type stereoisomer |
| 5 |
R/S configuration with the opposite alanine-derived relationship |
| 6 |
S/R-type stereoisomer |
These claims narrow the scope from the Formula I genus to specific molecular entities. They may be more resilient against prior-art attacks directed at the full genus, provided the named stereoisomers are adequately disclosed and enabled.
What do claims 7 and 8 cover?
Claim 7 covers racemic mixtures of:
- RRRR and SSSS; and
- RSSS and SRRR.
Claim 8 covers diastereomeric mixtures containing two or more of the listed stereoisomers.
Claim 8 is commercially important because a manufacturing process may produce a mixture rather than a single stereoisomer. A product would not necessarily avoid the patent merely because it contains multiple stereoisomers. The claim does not state a minimum percentage for each stereoisomer, which creates potential breadth but also raises claim-construction and enablement questions.
What do claims 9-14 protect?
Claims 9-14 cover Formula II compounds corresponding to the gadolinium-free ligand. Unlike claims 1-8, the named compounds in claims 10-14 are described as acids, with coverage extending to tautomers, N-oxides, hydrates, solvates, salts, and mixtures.
The Formula II claims matter for manufacturing because the ligand is a likely precursor to the final tetragadolinium complex. A competitor could face infringement risk before the final chelation step if it makes, imports, sells, or uses a claimed ligand.
Why are the Formula II claims commercially significant?
The ligand claims can create several enforcement points:
- Manufacture of the protected ligand
- Importation of the ligand into the United States
- Sale to a contrast-agent manufacturer
- Use of the ligand to prepare the tetragadolinium product
- Contract manufacturing involving the protected intermediate
- Possession of a claimed salt, hydrate, solvate, or N-oxide
The claims are not limited to the final injectable formulation. They reach chemical entities used during development and production.
How does claim 15 cover MRI imaging?
Claim 15 requires:
- Administering an effective amount of one or more Formula I compounds;
- Using a pharmaceutically acceptable carrier; and
- Subjecting the patient to an MRI procedure.
The claim is directed to a method of imaging body tissue. It does not expressly limit the claim to a particular organ, imaging sequence, dose, injection rate, gadolinium concentration, or disease state.
A competing MRI agent would not infringe claim 15 solely because it is used for MRI. The administered compound must fall within Formula I claim 1, either literally or under a potentially applicable doctrine of equivalents.
What does claim 16 add?
Claim 16 requires that less than 0.5% of the administered compound remain in the patient seven days after administration.
This limitation creates a narrower method claim with a pharmacokinetic endpoint. It may be relevant to a high-clearance, macrocyclic agent designed to reduce long-term gadolinium retention.
The limitation creates evidentiary issues:
- The parties must define "less than 0.5%."
- The relevant denominator must be established, likely administered dose or systemic exposure.
- The assay must distinguish intact complex from dissociated or metabolized species.
- The claim may require patient-level or population-level analysis.
- Renal function, dose, sampling method, and assay sensitivity may affect the result.
Claim 16 may be more difficult to enforce than the composition claims because infringement requires pharmacokinetic evidence. It may also be vulnerable if the specification does not adequately support the claimed threshold across the full scope of Formula I compounds and patient populations.
When does US Patent 10,722,601 expire?
The patent issued on July 28, 2020. Its apparent international or nonprovisional filing date is in November 2015. On that basis, the estimated ordinary US expiration date is in November 2035.
| Event |
Date or status |
| Earliest apparent priority period |
2014 |
| Apparent PCT or nonprovisional filing |
November 2015 |
| US patent grant |
July 28, 2020 |
| Estimated ordinary patent expiration |
November 2035 |
| Patent-term adjustment |
Must be confirmed from the USPTO patent-term calculation |
| Patent-term extension |
No confirmed extension identified |
| Pediatric exclusivity |
Not established |
| Current FDA approval of covered gadoquatrane product |
None identified |
The final expiration date should be taken from the USPTO patent-term information rather than calculated solely from priority dates. A provisional application does not start the 20-year patent term, while a PCT filing can affect the term depending on the relevant US national-stage filing framework.
What is the FDA and Orange Book status?
The patent appears to cover an investigational MRI contrast agent rather than an FDA-approved product. Gadoquatrane has been associated with Bayer’s clinical development program, but it does not have an established FDA-approved brand or Orange Book-listed reference product based on the available record.
| Regulatory issue |
Status |
| FDA-approved product under the patent |
No confirmed approval |
| Orange Book reference-listed drug |
None confirmed |
| Approved US NDA |
None confirmed |
| ANDA Paragraph IV challenges |
None identified |
| FDA therapeutic equivalence rating |
Not applicable |
| Biosimilar pathway |
Not applicable |
| Likely future pathway |
NDA for a new chemical entity or comparable drug application |
The absence of an approved reference product means that current generic-entry litigation under the Hatch-Waxman framework is not expected. If the product is later approved, the sponsor could seek Orange Book listing for eligible composition, formulation, and method-of-use patents. A future ANDA applicant could then submit Paragraph IV certifications against listed patents.
Which companies are challenging US 10,722,601?
No publicly established Paragraph IV litigation or ANDA challenge against US 10,722,601 is identified.
That result is consistent with the apparent development status of the covered product. A generic company ordinarily has limited commercial incentive to file an ANDA against an unapproved contrast agent because there is no FDA reference-listed drug against which the ANDA can be evaluated.
Potential future challengers would include:
- Generic radiology-contrast manufacturers
- Specialty injectable-drug companies
- Contract manufacturers seeking a US launch
- Developers of alternative high-relaxivity gadolinium agents
- Companies pursuing a 505(b)(2) route rather than a conventional ANDA
A 505(b)(2) applicant would not necessarily eliminate patent risk. It could still encounter listed patents, patent-certification requirements, or infringement litigation if it relies on the reference product’s clinical or regulatory information.
What patent landscape surrounds gadoquatrane and tetragadolinium MRI agents?
The patent landscape is likely divided into six layers.
Core composition patents
US 10,722,601 is a core composition patent because it covers the molecular architecture and stereochemistry of the tetragadolinium complex. A valid claim to the exact active ingredient is generally stronger than a claim limited to a formulation or imaging protocol.
Ligand and intermediate patents
Claims 9-14 cover the gadolinium-free Formula II ligand. Related patents or applications may cover:
- Protected ligand intermediates
- Coupling sequences
- Macrocycle synthesis
- Stereochemical resolution
- Metalation and transmetalation
- Purification and removal of free gadolinium
- Specific salt forms
These rights can make design-around manufacturing difficult even when a competitor avoids the final product claims.
Formulation patents
The provided claims do not expressly recite:
- A particular pH
- Buffer system
- Excipient
- Concentration
- Container
- Syringe
- Vial
- Premixed infusion system
- Stabilizer
- Chelation-control additive
A separate formulation patent could therefore provide additional protection for the commercial injectable product. No specific formulation patent number can be attributed to this record without a verified family search.
Method-of-use patents
Claim 15 is a broad MRI-use claim, and claim 16 adds the seven-day clearance limitation. Separate method patents could target:
- Brain MRI
- Cardiac MRI
- Liver imaging
- Vascular imaging
- Dynamic contrast-enhanced MRI
- Reduced-dose imaging
- Imaging in patients with renal impairment
- Use for specific signal-to-noise or relaxivity outcomes
Manufacturing patents
The product’s manufacturing barriers are substantial. The molecule contains four gadolinium-chelate units and multiple stereogenic centers. Commercial manufacture must control:
- Stereochemical composition
- Regioselective coupling
- Macrocycle integrity
- Metal loading
- Free gadolinium
- Residual solvents
- Endotoxin
- Particulate matter
- Batch-to-batch composition
- Long-term solution stability
A process that produces a different stereoisomeric distribution may still fall within claims 1 or 8.
Regulatory and clinical barriers
A competing product must establish safety, efficacy, stability, dosing, and gadolinium-retention characteristics. The patent estate is only one part of the entry barrier. Clinical development, injectable manufacturing, pharmacovigilance, and regulatory approval may delay entry even if a patent design-around is available.
How strong is the patent estate?
Strengths
- Claims 1 and 9 reach broad structural classes.
- Claims 2-6 and 10-14 identify specific stereoisomers.
- Claims cover salts, hydrates, solvates, tautomers, and mixtures.
- The Formula II claims may reach important manufacturing intermediates.
- The claims cover both active gadolinium complexes and precursor ligands.
- The structure is chemically complex and difficult to reproduce through a simple substitution.
Vulnerabilities
- Formula I and Formula II are not reproduced in the supplied claim text, limiting independent assessment of their exact structural boundaries.
- Broad stereochemical mixture claims may face written-description or enablement challenges if the specification does not support every claimed mixture.
- The claim language may invite disputes over symmetry-equivalent stereoisomers.
- Claim 16 depends on a pharmacokinetic threshold that may be difficult to measure consistently.
- Prior-art risk depends on earlier disclosures of multimeric gadolinium chelates, peptide-linked chelators, and stereochemically mixed complexes.
- The ultimate commercial value depends on FDA approval of the covered product.
Overall, the composition claims appear materially stronger than the method claim. A competitor with the same tetragadolinium active ingredient would face substantial literal infringement risk. A competitor using a different central scaffold, a different number of gadolinium units, or a non-covered chelator may have a stronger design-around position.
How does this patent compare with competing MRI contrast-agent estates?
| Product or program |
Developer |
General structure |
Regulatory position |
Relationship to US 10,722,601 |
| Gadoquatrane |
Bayer |
Multimeric, four-gadolinium investigational agent |
Clinical development |
Directly associated subject matter |
| Gadopiclenol, Vueway |
Guerbet |
High-relaxivity macrocyclic gadolinium agent |
FDA approved |
Different active structure and patent estate |
| Gadobutrol, Gadavist |
Bayer |
Macrocyclic monogadolinium agent |
FDA approved |
Different composition |
| Gadoterate meglumine, Dotarem |
Guerbet |
Macrocyclic monogadolinium agent |
FDA approved |
Different composition |
| Gadoteridol, ProHance |
Bracco |
Macrocyclic monogadolinium agent |
FDA approved |
Different composition |
The principal competitive risk is not that existing monogadolinium agents literally infringe the tetragadolinium claims. It is that established MRI contrast companies may develop competing high-relaxivity or lower-retention agents with separate composition and formulation patents.
What generic launch scenarios exist?
Launch after patent expiry
The clearest pathway is entry after the expected 2035 patent expiration, assuming no patent-term adjustment, patent-term extension, or additional unexpired family patents.
Design-around launch
A competitor could attempt to avoid the patent by changing:
- The number of gadolinium chelates
- The central linker
- The macrocycle
- The alanine stereochemistry
- The connectivity between ligand units
- The use of non-gadolinium paramagnetic metals
- The final ligand architecture
The design must avoid both literal infringement and a substantial-equivalence argument.
Regulatory challenge
After approval, an applicant could pursue an ANDA or 505(b)(2) application, depending on the FDA’s determination of pharmaceutical equivalence and regulatory reliance. A Paragraph IV certification could trigger litigation and a potential 30-month stay if the statutory conditions are met.
Manufacturing challenge
Even a non-infringing final product may encounter process patents covering ligand synthesis, stereochemical resolution, metal loading, or purification. A freedom-to-operate review must therefore extend beyond the product claims.
Is there a public licensing deal for this patent?
No publicly confirmed licensing transaction for US 10,722,601 is established in the information provided. The patent appears aligned with Bayer’s own gadoquatrane development program rather than a publicly disclosed third-party licensing platform.
A licensing review should distinguish:
- Ownership of the patent
- Clinical development rights
- Manufacturing rights
- Regional commercialization rights
- Patent prosecution control
- Rights to related continuation applications
- Rights to regulatory data
An apparent absence of a public license does not establish that no private agreement exists.
Key Takeaways
- US 10,722,601 is a core composition patent for tetragadolinium MRI contrast agents associated with gadoquatrane.
- Claims 1-8 cover Formula I complexes across selected stereoisomers and mixtures.
- Claims 9-14 cover the corresponding gadolinium-free Formula II ligands.
- Claim 15 covers MRI imaging with the Formula I compounds.
- Claim 16 adds a less-than-0.5% seven-day patient-retention requirement.
- The estimated ordinary expiration is in November 2035, subject to USPTO term adjustments or extensions.
- No confirmed FDA approval, Orange Book listing, Paragraph IV challenge, or biosimilar pathway applies at present.
- The composition claims are the strongest commercial barriers.
- The largest legal vulnerabilities involve claim breadth, stereochemical symmetry, enablement of mixtures, prior art, and the evidentiary burden for claim 16.
- A complete freedom-to-operate review must include continuations, divisionals, foreign counterparts, formulation patents, process patents, and later applications directed to gadoquatrane.
FAQs
Is US 10,722,601 an Orange Book patent?
No Orange Book listing is confirmed because the covered tetragadolinium product does not have an identified FDA-approved reference product.
Does the patent cover gadopiclenol?
No. Gadopiclenol is a structurally different high-relaxivity gadolinium agent with a separate patent estate.
Can a company sell a mixture of tetragadolinium stereoisomers without infringing?
Not necessarily. Claim 8 expressly covers diastereomeric mixtures containing two or more specified stereoisomers, and claim 1 also covers racemic and diastereomeric mixtures.
Does the patent cover the gadolinium-free ligand?
Yes. Claims 9-14 cover Formula II ligand compounds, including specified stereoisomers and certain salts, hydrates, solvates, tautomers, N-oxides, and mixtures.
Is a biosimilar required for a competing gadoquatrane product?
No. Gadoquatrane is a small-molecule chemical contrast agent, not a biologic. A competing product would more likely use an NDA, ANDA, or 505(b)(2) pathway depending on FDA determinations.
References
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United States Patent and Trademark Office. (2020). US Patent No. 10,722,601, Gadolinium complexes. U.S. Department of Commerce.
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U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
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U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
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United States Code. (2023). 35 U.S.C. §§ 154, 156. U.S. Government Publishing Office.
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Bayer AG. (n.d.). Gadoquatrane clinical development information. Bayer Pharmaceuticals.
