Scope and Claims Analysis of US Patent 5,980,864: 1,4,7,10-Tetraazacyclododecane “butyltriol” Contrast Agents for NMR Imaging (Gd(III), Compositions, and Methods)
US 5,980,864 protects a defined class of chelated tetraazacyclododecane derivatives carrying a “butyltriol” type substituent (as claim language frames it) and, critically, ties the compounds to NMR imaging via pharmaceutical compositions and administration-based method claims. The estate is claim-broad on (i) the metal, (ii) the salt form, and (iii) the substitution pattern, while the tightest technical core is anchored by the specific scaffold substitution in claim 1 (and in the dependent claim set) and by the explicit gadolinium complex in claim 10.
How broad is the compound scope under Claim 1 of US 5,980,864?
Core rule: Claim 1 is a Markush-style genus claim to compounds of a specific macrocyclic cage: 1,4,7,10-tetraazacyclododecane bearing (a) the “butyltriol” substituent expressed as R2 = 1-hydroxymethyl-2,3-dihydroxypropyl and (b) three “R1” positions defined as hydrogen or “metal ion equivalent” (coordination equivalents), independent of one another.
Claim 1 structure captured in plain claim terms
- Base scaffold: 1,4,7,10-tetraazacyclododecane
- Substituents:
- R1 at defined positions: each is H or a metal ion equivalent (independent choice per R1)
- R2: fixed as 1-hydroxymethyl-2,3-dihydroxypropyl, or a salt of that R2 form “with an organic or inorganic base or an amino acid”
- Overall protected subject matter: the genus of compounds meeting the formula IA with those substitutions.
What the “metal ion equivalent” language does
The claim uses “metal ion equivalent” rather than naming metal ions directly. That typically expands literal coverage to:
- chelated metal complexes of the macrocycle; and
- possibly coordination or salt-like stoichiometry embodiments that satisfy the “equivalent” concept.
This is especially important because dependent claim 3 narrows which metals/radionuclides fall within the genus (with atomic-number lists), but claim 1 sets the mechanism as a general chelation framework.
Which specific compounds are explicitly covered by dependent claims?
The dependent claims narrow the genus in two ways: (i) substitution pattern (all R1 hydrogen vs multiple metal equivalents) and (ii) explicit metal categories. A third narrowing is the “fully substituted” R2 scaffold form in claim 4.
Claim 2: all R1 are hydrogen
- Protected subset: the “all R1 = H” form of the claim 1 compound.
- Meaning: this covers the non-chelated or non-metal-loaded version of the same scaffold bearing the R2 group.
Claim 3: at least two R1 are metal ion equivalents from defined element/radionuclide sets
- Metal categories covered (by atomic number):
- elements: atomic numbers 21–29; 42; 44; 57–83
- radionuclides: atomic numbers 27, 29, 31, 32, 37–39, 43, 49, 62, 64, 70, 77
- Functional effect: the claim captures mixed loading patterns as long as at least two metal-equivalent R1 positions are occupied by ions in those sets.
Claim 5: further narrowing of metal list
- This re-anchors to a smaller element set:
- atomic numbers 21–29, 42, 44, 58–70
- Scope compression vs claim 3: claim 5 is a subset of claim 3 because it covers fewer elements/ranges.
Claim 4: a specific named compound
10-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane
- This is the most concrete “product form” in the claim set.
- It hardens the chemical identity beyond the Markush abstraction.
Claim 10: explicit gadolinium(III) complex
- “The gadolinium (III) complex of 10-(1-hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane.”
- This is a direct target for NMR/MRI contrast market entry because gadolinium(III) is the canonical paramagnetic MRI contrast ion.
What does the patent protect beyond the molecule: compositions and NMR imaging methods?
The later claims shift from chemical identity to use and formulation.
Claim 6 and Claim 8: pharmaceutical compositions
- Claim 6: a pharmaceutical composition comprising claim 1 compound + pharmaceutically acceptable carrier.
- Claim 8: same concept but limited to claim 3 compound + carrier.
This is typical contrast-agent claim architecture: you get compound coverage plus dosing form coverage to support commercial formulations.
Claim 7 and Claim 9: methods of NMR imaging by administration
- Claim 7: method conducting NMR imaging comprising administering a composition of claim 6.
- Claim 9: method conducting NMR imaging comprising administering a composition of claim 8.
These are “use-by-administration” claims. In practice, such claims are enforceable against parties that both (i) make/supply the composition covered and (ii) carry out the administration for imaging.
Claim 12: method of NMR imaging using the gadolinium complex formulation
- Claim 11: composition comprising claim 10 compound + carrier
- Claim 12: method conducting NMR imaging comprising administering claim 11 composition
This ties the explicit Gd(III) agent to the clinical workflow.
How does the claim language map to MRI/NMR contrast-agent commercial design?
US 5,980,864 is structured to cover:
- Chelator identity: macrocyclic 1,4,7,10-tetraazacyclododecane derivatives with the specified “butyltriol” type substituent (R2).
- Metal loading flexibility: R1 positions can be hydrogen or metal equivalents (claim 1), and at least two can be selected from large atomic-number sets (claim 3), with another narrowed set in claim 5.
- Clinical use: NMR imaging by administration (claims 7, 9, 12).
- Commercial packaging/formulation: “pharmaceutical composition” carriers (claims 6, 8, 11).
Practical effect for freedom-to-operate (FTO)
- A competitor using the same scaffold with the same R2 but different metals may still fall within claim 1 and/or claim 3 depending on metal identity and substitution pattern.
- A competitor using a Gd(III) complex of the explicit claim 4 named compound lands directly in claim 10 and related method/composition claims.
- A competitor using a different R2 substituent likely avoids literal claim 1/4 because R2 is explicitly defined.
What is the “design-around” surface area implied by the claims?
From the face of the claim set, the primary non-infringement levers are:
- changing R2 away from 1-hydroxymethyl-2,3-dihydroxypropyl (since claim 1 fixes R2), and/or
- changing the core substitution pattern so that the compound no longer matches the formula IA with R1 behaving as claimed, and/or
- avoiding administration of a covered composition for NMR imaging (harder in practice because clinical use is integral to contrast agents).
Changing the metal alone is less reliable because:
- claim 1 already covers “metal ion equivalents,” and
- claim 3 and claim 5 include broad atomic-number ranges.
How does US 5,980,864 likely sit in the broader patent landscape?
Based on the claim architecture, the patent targets a contrast-agent family for MRI/NMR:
- macrocyclic chelator (1,4,7,10-tetraazacyclododecane),
- with a polyol/trihydroxy side chain (R2 = 1-hydroxymethyl-2,3-dihydroxypropyl),
- and carboxymethyl functionality implied by claim 4’s explicit “triscarboxymethyl” framing,
- including Gd(III and also other metals/radionuclides.
In a typical MRI agent landscape, overlapping protection commonly appears in three places:
- Chelator chemistry patents (synthetic intermediates, chelator scaffolds, complexation to specific metals).
- Formulation and stability patents (pH, buffers, osmolality, viscosity, sterilization).
- Use patents (imaging methods, dose ranges, indications).
US 5,980,864’s set spans (1) and (2)/(3) at least in composition/use form through claims 6, 7, 8, 9, 11, 12.
What are the key claim-strength positions?
Strongest claim targets (highest litigation “hit rate”)
- Claim 10 (Gd(III) complex of the named compound) plus claims 11-12.
- If a commercial product matches the gadolinium complex identity, these are the most direct “product-claims.”
- Claim 4 named compound (even independent of the metal).
- If a competitor sells or uses that exact chelator form (and then complexes it to cover R1 as required), claim 4 supports chemical identity enforcement.
Broadest platform coverage
- Claim 1 is a wide genus because it covers:
- R1 hydrogen vs metal equivalents per position,
- and any pharmaceutically acceptable salts for the R2 substituent with organic/inorganic base or amino acid.
- Claim 3 extends to a long list of metal elements and radionuclides.
Potential vulnerability in enforcement
The biggest enforcement hinge is whether accused compounds satisfy the formula IA and the specific R2 definition and substitution positions. On chemical patents, infringement often turns on exact structural match, tautomer/salt identity, and complex composition.
How to interpret “formula IA” impact on scope (practical claim construction)
Because the claim excerpt references “formula IA” and shows R1 and R2 definitions, the operational scope depends on:
- the exact structural diagram of formula IA (not provided here),
- how many R1 positions exist in the formula,
- and where R2 is attached.
Even without the diagram, dependent claims strongly imply a specific architecture tied to the named compound in claim 4 and to the gadolinium complex in claim 10. That means the genus in claim 1 is not abstractly unlimited; it is anchored to the same core scaffold chemistry.
Does this patent likely cover a specific commercial MRI agent family?
The explicit “gadolinium (III) complex” plus the tetraazacyclododecane with a triol-containing pendant side chain and triscarboxymethyl motif points to a known pattern seen in certain generations of macrocyclic gadolinium contrast agents. Claim 10 and dependent claims are written to capture the commercial product molecule rather than only intermediates or experimental variants.
Timeline: when would US 5,980,864 expire?
US utility patents filed in the modern era generally expire 20 years from the earliest effective non-provisional filing date, subject to any patent term adjustment or PTA. The claim text provided does not include the filing date, so an exact expiration date cannot be stated from the information available here.
Key takeaways on the claims and landscape posture
- US 5,980,864 protects a macrocyclic tetraazacyclododecane contrast-agent class with a fixed R2 = 1-hydroxymethyl-2,3-dihydroxypropyl substituent.
- The patent is wide on metal loading through “metal ion equivalents” (claim 1) and explicit atomic-number/radionuclide lists (claim 3 and claim 5).
- The patent is tight on the commercially relevant target by explicitly claiming:
- the named chelator in claim 4, and
- the Gd(III) complex of that chelator in claim 10.
- It also covers pharmaceutical compositions and NMR imaging methods by administration, creating enforceable coverage for both product supply and clinical use.
Key Takeaways
- Most enforceable hook: claim 10 (Gd(III) complex) and the corresponding composition/use claims (11-12).
- Broad platform hook: claim 1 (fixed R2 + variable R1 H/metal equivalents) and claim 3 (broad metal/radionuclide eligibility).
- Design-around likelihood: primarily hinges on changing R2 away from 1-hydroxymethyl-2,3-dihydroxypropyl or structurally departing from formula IA’s scaffold/substitution arrangement.
FAQs
- How many R1 positions does claim 1 cover and how does that affect infringement risk?
- Does “metal ion equivalent” capture mixed-metal complexes or only true chelated metal complexes?
- Are salt forms of the R2 substituent explicitly covered, and does that expand generic formulation risk?
- Do the imaging method claims require diagnosis/indication language, or are generic MRI administrations sufficient for coverage?
- How does claim 4’s “triscarboxymethyl” identity narrow the protected universe relative to the Markush genus in claim 1?
References
No references are included because only the claim text was provided, and no patent bibliographic data (filing date, assignees, prosecution history, citations, maintenance status) or related-family document set was supplied.
