Details for Patent: 6,056,941

Summary for Patent: 6,056,941

Title:	Kit for the preparation of technetium TC 99m teboroxime myocardial perfusion agent
Abstract:	A kit containing a solution of boronic acid adducts of technetium-99 m dioxime complexes; and hydroxypropyl gamma cyclodextrin to maintain the solution free of particulate matter originating from the formulation.
Inventor(s):	Ernest Schramm, Margaret Newborn, Julius P. Zodda, Thomas Katona, Jo Anna Monteferrante
Assignee:	Bracco Diagnostics Inc , Clear Image Concepts LLC
Application Number:	US09/363,132
Patent Claim Types: see list of patent claims	Compound; Device;

US Patent 6,056,941 Landscape: Scope, Claim Boundaries, and Infringement Risk for Myocardial Imaging Kits Using Tc-99m Boron/Dioxime Complexes

US 6,056,941 claims an “improved kit” for myocardial diagnosis (rest and stress) that combines (i) lyophilized precursor reagents in a first container and (ii) Tc-99m in a second container, where the Tc-99m is complexed in situ with a defined boronic acid derivative and a defined dioxime (dioxime family and named examples), with explicit quantitative ranges and a cyclodextrin additive (hydroxypropyl gamma cyclodextrin). The add-on that differentiates the improvement is the cyclodextrin amount (30 to 50 mg) included in the lyophilized first container.

Below is a claim-by-claim scope map and a landscape view geared for freedom-to-operate (FTO), licensing, and litigation posture.

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What does US Patent 6,056,941 claim for Tc-99m myocardial imaging kits?

Core claim concept (independent claim 1): A two-container, lyophilized imaging kit for myocardial diagnosis using rest/stress techniques, where the kit’s first container contains defined salts/acids plus (i) a boronic acid derivative (or a precursor that forms such a derivative in situ) and (ii) a dioxime (or salt), plus (iii) stannous chloride, pentetic acid, citric acid, and defined sodium chloride or sodium bromide; then a second container supplies Tc-99m in physiological saline at a defined activity and volume; and the claimed improvement is 30–50 mg hydroxypropyl gamma cyclodextrin in the first container.

Claim 1 elements and numerical boundaries (literal scope)

Independent claim 1 requires all of the following structural and compositional features in combination:

Kit format

• Two containers
  • First container: lyophilized ingredients
  • Second container: Tc-99m solution in physiological saline

Second container parameters

• 1–3 mL of Tc-99m in physiological saline containing 10–100 mCi
  • Volume and activity ranges are explicit.

First container composition ranges

The lyophilized first container includes, in the claimed ranges:

• 5–15 mg sodium chloride or sodium bromide
• 1–3 mg boronic acid derivative (or precursor that forms it in situ)
  • Boronic acid derivative is defined by a claimed general formula (the claim includes variable substitutions for R3, R4, R5, R7; and also allows nitrogen heterocycles from R4/R5 taken together)
• 1–3 mg dioxime
  • Dioxime is defined by a formula (R1 and R2 variable definitions, plus a specific combined option where R2 and R3 are tethered through an alkyl chain)
• 0.03–0.06 mg stannous chloride
• 1–3 mg pentetic acid
• 8–10 mg citric acid
• Improvement: 30–50 mg hydroxypropyl gamma cyclodextrin added to the first container

In situ complexing requirement

Claim 1 requires the kit design such that when Tc-99m is added, complex formation occurs from the contents, but claim 1 itself does not enumerate particular complex stoichiometries or ligands in the way dependent claim 4 does. The claim architecture nonetheless fixes the necessary ligand classes and ranges.

Claim 1 ligand scope: boronic acids and dioximes

Claim 1 broadly covers a set of boronic acid derivatives (or in situ-forming precursors) described by the claim’s formula variables (including multiple substituent categories such as hydroxy, alkyl, aryl, carboxyalkyl, alkoxyalkyl, haloalkyl, heterocycles, and nitrogen heterocycles formed by R4/R5).

For dioximes, claim 1 broadly defines a dioxime family by its formula variables for R1 and R2 (including halogen/alkyl/aryl/amino/heterocycles), plus an option where tethering between groups occurs via a substituted alkylene chain.

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Which boronic acid derivatives are explicitly covered (and how broad is the functional formula)?

Claim 3: named boronic acid substituent classes

Claim 3 narrows but still stays broad at the class level:

• Boronic acid derivative selected from:
  • B-alkyl
  • B-alkoxy
  • B-benzyl
  • B-cycloalkyl

This is a helpful “at least that” scope limiter for invalidity and infringement analysis:

• A product using boronic acids outside these B-substitution motifs may still fall under claim 1’s broader formula set, but claim 3 offers explicit coverage for these B-classes.

Claim 1 boronic acid formula: likely practical breadth

Because claim 1 includes an extensive list of substitution types for R3 and allows nitrogen-heterocycle formation from R4/R5, the independent claim’s boronic acid scope is materially broader than claim 3. For FTO, claim 3 is not needed to catch common alkyl/alkoxy variants if they already meet claim 1’s formula constraints.

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Which dioximes are explicitly covered?

Claim 2: named dioxime species

Claim 2 limits dioxime selection to specific named examples:

• Dimethyl glyoxime
• 1,2-cyclohexanedione dioxime
• 1,2-ethanedione dioxime
• α-furyldioxime
• 1,2-cyclopentanedione dioxime
• 3-methyl-1,2-cyclopentanedione dioxime

These species map to common dioxime chemistries used in Tc-99m chelation patterns. For infringement, a product using one of these exact dioximes will have a straightforward pathway to matching claim 2 (and also claim 1).

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What Tc-99m complexes are enumerated in claim 4, and what does that mean for infringement?

Claim 4: listed complex identities

Claim 4 enumerates specific Tc-99m complex names combining:

• oxidation/coordination notation “99m Tc (chlorine) …”
• dioxime identity (predominantly dimethyl glyoxime)
• boron substitution identity

Examples listed include (non-exhaustive from the claim text):

• 99m Tc (chlorine) (dimethyl glyoxime)3 methoxy boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 hydroxy boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 ethoxy boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 propyloxy boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 hexyloxy boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 1-methylpropyl boron
• 99m Tc (bromine) (dimethyl glyoxime)3 butyl boron
• 99m Tc (iodine) (dimethyl glyoxime)3 butyl boron
• 99m Tc (fluorine) (dimethyl glyoxime)3 butyl boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 3-(4-morpholinyl)propyl boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 2-phenylethyl boron
• 99m Tc (chlorine) (1,2-cyclohexanedione dioxime)3 methyl boron
• 99m Tc (chlorine) (dimethyl glyoxime)3 4-formylphenyl boron

Infringement significance of claim 4

• Claim 4 is a dependent claim that ties the complex identity to “when Tc-99m is added to the first container forms a complex” selected from its list.
• For a competitor product to infringe claim 4, it must be able to establish that the in situ complex formed is one of the enumerated complexes.
• Claim 4’s listing is also a litigation lever for parties: it gives concrete chemical targets rather than leaving it entirely to broad formula matching.

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What is claim 5, and how does it narrow the composition compared to claim 1?

Claim 5: tighter exemplified kit composition

Claim 5 is another independent improvement kit claim with narrower, explicitly recited ingredients/ranges:

• First container lyophilized ingredients:
  • 1–3 mg cyclohexanedione dioxime
  • 1–3 mg methyl boronic acid
  • 8–10 mg citric acid
  • 5–10 mg sodium chloride
  • 0.030–0.060 mg stannous chloride (SnCl2)
• Second container:
  • 1–3 mL Tc-99m in physiological saline
• Improvement:
  • 30–50 mg hydroxypropyl gamma cyclodextrin added to the first container

Key difference vs claim 1: claim 5 locks the boron and dioxime to specific exemplars (methyl boronic acid and cyclohexanedione dioxime) and drops pentetic acid from the explicitly recited list in the provided claim text. In practice, claim 5 may still be satisfied if pentetic acid is present but it is not expressly required by the recited portion in the user-supplied text.

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What is the practical “core infringement hook” in US 6,056,941?

Across the provided claims, the most consistent, high-value claim hook is:

1. Two-container rest/stress myocardial imaging kit
2. In situ formation of Tc-99m complexes using:
   • defined boronic acid derivative class and amounts
   • defined dioxime class and amounts
3. Defined excipient/kit chemistry including
   • stannous chloride at 0.03–0.06 mg
   • acids/salts including citric acid (8–10 mg) and pentetic acid (in claim 1)
4. Improvement requirement
   • 30–50 mg hydroxypropyl gamma cyclodextrin in the first lyophilized container

From an FTO and design-around standpoint, that cyclodextrin addition is the most “single-variable” differentiation embedded in the improvement language. A design that changes the cyclodextrin amount outside 30–50 mg or uses a different cyclodextrin chemistry may reduce literal risk, but validity and doctrine-of-equivalents analysis would still be relevant in litigation contexts.

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How does the patent claim structure affect enforcement strategy (independent vs dependent claims)?

Independent claim 1

• Best for broad enforcement where products broadly follow the quantitative and ligand classes.
• Strongest coverage where a manufacturer uses lyophilized kit formulations matching the ranges and provides Tc-99m in the stated activity/volume.

Independent claim 5

• Narrower but powerful when products intentionally adopt the specific exemplified chemistry (methyl boronic acid + cyclohexanedione dioxime) with the cyclodextrin improvement.

Dependent claims 2–4

• Useful for pinning infringement to specific ligand selections (claim 2) and specific complexes (claim 4).
• Useful as “backstop” arguments: if a challenger disputes whether their ligand structures match claim 1 formula scope, the patentee can still seek coverage under claim 2 or claim 4 if the same species are used.

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What is the estimated patent landscape around this claim set (kit chemistry and Tc-99m complexing)?

The provided text indicates a kit platform centered on Tc-99m coordination to dioxime ligands and boron-containing substituents, producing enumerated complexes. In the US myocardial imaging market, infringement and licensing risks often come from three overlapping patent clusters:

1) Tc-99m dioxime complexation kits

• Patents typically claim:
  • ligand classes (dioximes)
  • stabilizers/reductants (including stannous salts)
  • acids/chelators to control radiochemistry and stability
  • kit formats (two-vial lyophilized systems)

2) Boron-derived targeting chemistry using boronic acid derivatives

• Boronic acids are used as affinity moieties; patents frequently claim:
  • specific boronic acid substitution patterns
  • in situ formation precursors
  • resulting Tc-99m complexes that preserve binding and biodistribution

3) Formulation improvements to radiopharmaceutical kits

• Cyclodextrin additives are commonly claimed to improve:
  • solubilization
  • radiochemical yield
  • stability and reconstitution performance
• The improvement clause here is specifically hydroxypropyl gamma cyclodextrin at 30–50 mg.

Business implication: Even if a competitor diverges from the boronic substituent chosen, the cyclodextrin addition and kit parameter ranges can still create a “partial overlap” infringement narrative depending on how strictly they stay within the numerical windows.

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How strong is the claim estate for knock-out validity or straightforward infringement?

Based solely on the claim text provided, the patent has litigation-relevant strength in two dimensions:

1. Claim specificity via quantitative ranges

   • Sodium salt (5–15 mg or 5–10 mg), stannous chloride (0.030–0.060 mg), citric acid (8–10 mg), pentetic acid (1–3 mg in claim 1), Tc-99m activity and volume (10–100 mCi; 1–3 mL), and the cyclodextrin improvement (30–50 mg).
   • These are not just “ingredient categories”; they are dose-specific.

2. Chemical specificity in ligands and (in claim 4) complex identities

   • Claim 2 enumerates exact dioximes.
   • Claim 4 enumerates exact complex compositions by ligand substitution identity.

Where a product matches those numerics and uses one of the named species, infringement is more direct than with patents that rely only on broad functional language.

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What generic entry risks exist if a competitor attempts a kit “work-alike”?

Risk is highest when “work-alike” still matches the improvement formulation

A kit that uses:

• dioxime + boronic acid derivative complexation in situ
• Tc-99m addition to lyophilized precursors
• the same or tightly overlapping excipient package
• hydroxypropyl gamma cyclodextrin at 30–50 mg

faces the most direct literal risk for independent claim 1 and/or claim 5.

Lower-risk avenues for design-around (litigation posture dependent)

• Changing cyclodextrin type or amount (outside 30–50 mg).
• Changing ligand class or substituent set so that claim formula constraints are avoided.
• Adjusting kit chemistry so that the in situ formed complex is not one of the enumerated claim 4 identities.

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Key takeaways

• US 6,056,941 covers a two-container Tc-99m myocardial imaging kit where Tc-99m forms in situ complexes with boronic acid derivatives and dioximes.
• The formulation is anchored to explicit quantitative ranges for salts/acids and Tc-99m activity/volume.
• The enforcement “center of gravity” is the hydroxypropyl gamma cyclodextrin improvement at 30–50 mg in the first lyophilized container.
• Dependent claims lock in particular ligand species (claim 2) and particular complex identities (claim 4), strengthening infringement narratives for products using those exact chemicals/complexes.

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FAQs

Which element is most important to avoid literal infringement: boronic acid choice or hydroxypropyl gamma cyclodextrin amount?

The cyclodextrin amount is a repeated improvement term at 30–50 mg across the independent claims provided, making it the most conspicuous formulation boundary.

Can a product that uses a different dioxime still infringe US 6,056,941?

Yes. Claim 1 covers dioximes by formula-defined categories; claim 2 is a narrower dependent limitation listing specific dioximes.

Do claim 4 complex identities control infringement if a product forms a different Tc-99m complex?

They control claim 4 specifically. Independent claim 1 does not require one of the enumerated complexes in the text provided, so infringement can still occur without matching claim 4’s listed complexes if claim 1’s chemistry and ranges are met.

What are the key Tc-99m preparation parameters the kit must satisfy?

Claim 1 requires 1–3 mL Tc-99m in physiological saline with 10–100 mCi; claim 5 also requires 1–3 mL Tc-99m in physiological saline.

Is the kit limited to specific rest/stress clinical workflows?

The claims state “myocardial diagnosis… using rest and stress techniques,” framing the kit for that clinical use, while the chemical/formulation limitations drive technical infringement.

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References

1. United States Patent 6,056,941. “Improved kit for myocardial diagnosis using rest and stress techniques” (claims as provided in the prompt).

Drugs Protected by US Patent 6,056,941

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,056,941

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	5838400
Australia	763988
Canada	2378096