United States Patent 7,589,106: Scope, Claims, and US Patent Landscape for Argatroban + Methionine + Lactobionic Acid Aqueous Formulations
US Patent 7,589,106 is a US-focused formulation-and-method estate built around a specific aqueous argatroban composition that uses methionine plus lactobionic acid (and optionally carbonic/acetate-based pH system components) to achieve a basic pH (>8.5) while being substantially free of ethanol and sugar alcohols. Independent protection is tight: the claims require a multi-component matrix and multiple functional constraints (pH, excipient identity, and exclusions). Dependent claims then narrow via concentration windows, weight ratios, packaging formats, and reconstitutable vs ready-to-administer embodiments.
What does US Patent 7,589,106 claim for argatroban formulations in the US?
Bottom line: The patent claims pharmaceutically acceptable aqueous formulations of argatroban (or its salts) with a required combination of:
- Methionine (or salt)
- One pH-adjusting component selected from non-amino-acid acids/bases (or salts)
- Lactobionic acid (or salts)
- A functional regime: substantially ethanol-free, substantially sugar-alcohol-free, and pH > 8.5
- Additional dependent limits on amounts and weight ratios, plus packaging and ready-to-administer vs concentrate embodiments.
Independent claim structure (Claims 1 and 22)
Two independent formulation claims appear (your text includes both in parallel form):
- Claim 1: formulation with (a) argatroban formula I or salt; (b) methionine; (c) non-amino-acid pH adjusting organic acids/bases or salts; (d) lactobionic acid or salts; and the exclusion/pH requirements.
- Claim 22: materially similar independent formulation, with the (c) group expressed as “non-amino acid pH adjusting organic acids or organic base or salts” (no explicit mention of “in excess of 8.5” remains in claim 22’s independent text provided, but it does include pH in excess of 8.5).
Key scope drivers
- Excipients are not optional. Removing methionine, replacing lactobionic acid with another polyhydroxy acid, or changing the pH system category can land outside the claim.
- Functional constraints are central:
- pH > 8.5
- substantially free of ethanol
- substantially free of sugar alcohol
- pH-adjuster identity is categorical, not just functional: (c) must be within the listed classes (non-amino-acid pH adjusting organic acids/bases or salts).
What is “formula I” in the claims?
The claim is limited to argatroban “of formula I” or its pharmaceutically acceptable salts. Because your text uses argatroban as the designated active, the practical claim scope is to argatroban itself and its salts, not other thrombin inhibitors.
What does “substantially free” mean for claim scope?
The claims use “substantially free of ethanol” and “substantially free of a sugar alcohol.” This creates a factual assay boundary: an accused formulation must be demonstrably low (relative to some practical tolerance) in ethanol and sugar alcohol. For infringement analysis, this tends to be litigated on composition/assay data and formulation specs.
How narrow are the formulation concentration and ratio limits within US 7,589,106?
The estate uses layered narrowing.
Concentration window claims
- Claim 2: argatroban concentration “equivalent to” about 1 / 1.25 / 2 / 2.5 / 5 mg/mL based on the argatroban moiety.
- Claim 5: methionine amount about 1 mg/mL to about 50 mg/mL.
- Claim 8: ready-to-administer solution has:
- argatroban ≥ 0.75 mg/mL
- lactobionic acid (or salt) and/or carbonic salts based on CO3 ≥ 1.5x and/or ≥ 1.4x weight relative to argatroban moiety
- methionine ≥ 1.5x weight relative to argatroban moiety
- Claims 9–11 then add upper bounds:
- Claim 9: argatroban ~0.75 to ~1.25 mg/mL
- Claim 10: lactobionic acid ≤ 2.5x (and/or carbonic CO3 salts ≤ 5.2x) vs argatroban moiety
- Claim 11: methionine ≤ 2.5x vs argatroban moiety
Weight-ratio claims
- Claim 14: multiple ratio bands including:
- argatroban : lactobionic acid : methionine ~0.75–1.25 : ~1.50–2.50 : ~1.50–2.50
- or argatroban : carbonic salt (CO3) : methionine ~0.75–1.25 : ~1.4–5.2 : ~1.50–2.50
- Claim 15: alternative specific ratio targets:
- argatroban : lactobionic acid : methionine ~1 : ~2 : ~2
- or argatroban : carbonic salt (CO3) : methionine ~1 : ~4.1–4.2 (with methionine salt and argatroban salt basis language)
Infringement implication: Even if an accused product contains methionine and lactobionic acid, it must also land in the claimed pH regime and, for claim coverage via dependents, in the argatroban concentration and/or ratio windows. If the product uses different stoichiometry, it may evade dependent claims while still potentially touching the independent claim if all components and pH/exclusion constraints are satisfied.
What pH system is protected by US 7,589,106 and how is it defined?
The patent forces use of lactobionic acid plus a non-amino acid pH adjuster category
Claim 1’s (c) is selected from:
- non-amino acid pH adjusting organic acids/bases or inorganic acids/bases (or salts)
Claim 3 adds examples and expands category:
- carboxylic acids and hydroxy carboxylic acids
- dicarboxylic acids with pKa(s) > 3.0
- salts of those
- plus specific inorganic/alkali systems:
- alkali metal/ammonium carbonate
- alkali metal/ammonium bicarbonate
Specific anion embodiments
- Claim 4: (c) comprises an acetate anion or a carbonate or bicarbonate anion.
- Claim 6: (c) includes acetate and also carbonate/bicarbonate derived from alkali metal/ammonium carbonate/bicarbonate or carbonic acid, and acetate from an acetic acid salt/acetic acid.
pH thresholds and discrete values
- Claim 12: pH > 8.6
- Claim 13: pH about 8.7 / 8.8 / 8.9 / 9.0 / 9.1 / 9.2
- Claim 23 adds a pH adjuster limitation in the dependent context.
Design-around sensitivity: Many aqueous argatroban formulations rely on buffering systems; swapping away from the claimed anion family (acetate/carbonate/bicarbonate) and/or shifting outside the basic pH window creates a direct path to noninfringement.
What packaging and dosage-form variants are covered (vials vs infusion bags, ready-to-administer vs reconstitutable)?
Packaging-dependent claim coverage
- Claim 7: packaging in:
- a vial selected from 5 mg/vial to 500 mg/vial, or
- an IV infusion bag 25 mL/bag to 500 mL/bag
This ties protection partly to distribution/labeling configuration.
Ready-to-administer
- Claim 8 explicitly recites ready-to-administer aqueous solution meeting minimum concentration and ratio/weight constraints.
- Claims 12–15 further constrain pH and ratios for formulations in the ready-to-administer context.
Concentrate and reconstitution
- Claim 16: a reconstitutable formulation with argatroban + methionine + pH adjuster (non-amino acid organic acids/bases) + lactobionic acid, with:
- substantially free of mono-, di-, or oligosaccharide
- substantially free of a sugar alcohol
- Claim 19: method claims cover concentrate diluted with an injectably suitable aqueous diluent to a concentration for injection.
Substance-specific angle: Claim 16 adds sugar constraints beyond ethanol/sugar alcohol:
- excludes mono-, di-, oligosaccharides (this is an additional potential design-around trigger if another formulation uses carbohydrate excipients).
What method-of-use claims exist, and what do they practically cover?
- Claim 17: method of treating thrombosis by administering the composition of claim 1.
- Claim 18: composition is ready-to-administer.
- Claim 19: composition is a concentrate diluted prior to injection.
Practical scope: These are relatively direct and often follow product infringement. If a generic or licensed product practices the claim-1 formulation in a thrombosis treatment regimen, the method claim is typically co-extensive with product infringement risk.
What are the key “what if I change X?” design-around levers?
The claim set is excipient-and-parameter heavy; the main leverage points are:
- Remove or substitute methionine
- Claims require methionine (or salts) as component (b). Substitution with another amino acid (e.g., histidine) is outside the explicit wording unless “methionine” equivalence is pursued under doctrine of equivalents, which is fact-specific.
- Replace lactobionic acid
- Lactobionic acid (or salts) is an explicit component (d). Using a different polyhydroxy carboxylic acid (e.g., gluconate) avoids literal coverage.
- Shift pH outside >8.5
- The independent claims require pH > 8.5; dependents narrow further to >8.6 and discrete basic values.
- Add ethanol or sugar alcohol above “substantially free”
- Increased ethanol content or inclusion of sugar alcohols (e.g., mannitol, sorbitol) can be used to exit “substantially free” limitations.
- Use a different pH system class
- The (c) component is constrained to non-amino-acid organic acids/bases or inorganic acids/bases and specific subgroups (carbonate, bicarbonate, acetate). Using a buffer outside these categories can narrow away from the claim.
- Avoid the stoichiometric/ratio windows (for dependent claims)
- Even if independent claim elements are met, ratio/concentration dependents can be avoided by altering composition to fall outside those bands.
How does US 7,589,106 relate to other argatroban formulation patents in the US patent landscape?
With only the provided claim text, the landscape can be mapped structurally, not by named citations: US 7,589,106 is best categorized as a formulation-specific and process-adjacent aqueous solution patent. It does not appear to claim argatroban synthesis, nor broad method-of-use across all thrombin inhibitors. Instead, it claims:
- the active/excipient combination
- a basic pH target
- specific buffer/excipient identities
- and a low-excipient profile for ethanol and sugar alcohols.
In the broader argatroban landscape, formulation estates typically cluster around:
- stabilization (pH, ionic strength, solubilizers)
- excipient selection and exclusion lists
- delivery format (vials vs bags; ready-to-use vs reconstitutable; concentrate/reconstitution)
- salt selection for the active and sometimes for buffering components.
US 7,589,106 sits in the cluster where the defining excipient markers are methionine and lactobionic acid and where the discriminant technical feature is high pH in the presence of those markers.
When does exclusivity and patent expiration matter for US 7,589,106?
The prompt provides no filing date, priority date, or issue date beyond the patent number itself. As a result, exact expiration calculations for this specific patent cannot be derived from the provided information alone.
What is the expected competitive and generic entry risk if a product practices similar components?
Risk concentrates on “near-match” aqueous argatroban formulations:
- that use methionine and lactobionic acid (or salts),
- buffer into the basic pH regime (>8.5),
- and avoid ethanol and sugar alcohols.
A generic manufacturer that keeps argatroban as the active and converges on the same excipient system will likely face claim 1 coverage, with further narrowing attacks available through ratio and pH limits (claims 2, 8–15, 12–13, 14–15, and packaging claim 7).
If a candidate formulation differs in at least one of the independent claim pillars (methionine absent, lactobionic acid absent, pH not basic enough, ethanol/sugar alcohol not “substantially free”), the risk drops for claim 1 and claim 22, though dependents and doctrine-of-equivalents arguments remain fact-specific.
Patent strength analysis: which claims are likely to be the infringement “center of gravity”?
Claims 1 and 22 are the center of gravity:
- They contain all essential excipients and functional limits.
- They are broad within their excipient categories (especially for the (c) pH adjuster group).
Claims 8–15 are the likely “product fingerprint” dependents:
- They impose numeric minimums and ratio windows tied to ready-to-administer solutions.
- They are often easier to prove or disprove with formulation lab data.
Claims 12–13 are strong for pH-based differentiation:
- Basic pH values are measurable and can be validated on batches.
Claims 16 and 19 matter for concentrate/reconstitution competitors:
- sugar exclusion (mono-, di-, oligosaccharides) plus sugar alcohol exclusions reduce the space of compliant substitutes.
Key claim-by-claim scope map (US 7,589,106)
| Claim |
Coverage type |
What is required (core limitation) |
Practical “do/don’t” for an accused formulation |
| 1 |
Independent formulation |
Argatroban + methionine + non-amino acid pH adjuster + lactobionic acid; aqueous; ethanol-free; sugar-alcohol-free; pH > 8.5 |
Remove lactobionic acid, remove methionine, change pH down, or add ethanol/sugar alcohol |
| 2 |
Dependent |
Argatroban concentration ~1, 1.25, 2, 2.5, or 5 mg/mL |
Move concentration outside recited “about” points |
| 3 |
Dependent (pH adjuster) |
Specific classes including carboxylic/hydroxycarboxylic/dicarboxylic (pKa>3), carbonate/bicarbonate systems |
Use buffer outside these categories |
| 4 |
Dependent |
pH adjuster comprises acetate or carbonate/bicarbonate anion |
Replace acetate/carbonate/bicarbonate with other buffer families |
| 5 |
Dependent |
Methionine 1–50 mg/mL |
Use methionine outside this range |
| 6 |
Dependent |
Composition details of acetate and carbonate/bicarbonate sourcing |
Alter ionic source or remove acetate/alter anion system |
| 7 |
Dependent packaging |
Vial 5–500 mg or bag 25–500 mL |
Different pack size may avoid claim 7 (but not claim 1) |
| 8 |
Dependent formulation form |
Ready-to-administer; argatroban ≥0.75 mg/mL; lactobionic or carbonic CO3 ratios ≥ stated; methionine ≥1.5x |
Change stoichiometry or make reconstitutable instead |
| 9 |
Dependent |
Argatroban ~0.75–1.25 mg/mL |
Move concentration outside this window |
| 10 |
Dependent |
Lactobionic ≤2.5x and/or CO3 salts ≤5.2x |
Adjust anion equivalent ratios |
| 11 |
Dependent |
Methionine ≤2.5x |
Adjust methionine equivalents |
| 12 |
Dependent |
pH > 8.6 |
Set pH at or below 8.6 |
| 13 |
Dependent |
pH about 8.7–9.2 |
Set pH outside listed points |
| 14 |
Dependent ratios |
Specific argatroban:lactobionic:methionine or argatroban:CO3:methionine ratio bands |
Alter ratios |
| 15 |
Dependent ratios |
Specific ratio targets (including 1:2:2 and CO3 window) |
Alter ratios away from targets |
| 16 |
Dependent reconstitutable |
No mono-/di-/oligosaccharides; no sugar alcohol; lactobionic acid present |
Use sugar excipients if they are not excluded (or avoid the lactobionic/methionine system) |
| 17 |
Independent method |
Administer claim 1 composition to treat thrombosis |
Product design avoids claim 1; method claims track product |
| 18 |
Dependent method |
Claim 1 composition is ready-to-administer |
Switch to concentrate-only format |
| 19 |
Dependent method |
Claim 1 composition is a concentrate diluted with aqueous diluent |
Use a different reconstitution approach/format outside the claim |
| 20–21 |
Dependent excipient |
Adds osmolality adjuster and/or pH adjuster beyond core (as stated) |
Adjust excipient set |
| 22 |
Independent formulation |
Parallel independent formulation limited to argatroban + methionine + pH adjuster + lactobionic acid; ethanol-free; sugar-alcohol-free; pH > 8.5 |
Same levers: lactobionic, methionine, pH, ethanol/sugar alcohol |
| 23 |
Dependent |
Adds additional pH adjuster beyond defined elements |
Vary buffering/excipient selection |
Key Takeaways
- US 7,589,106 protects a specific aqueous argatroban formulation defined by required excipients (methionine + lactobionic acid) and a basic pH constraint (>8.5) plus exclusion limits (substantially ethanol-free, substantially sugar-alcohol-free).
- Dependent claims narrow the coverage to specific argatroban concentrations, methionine amounts, lactobionic/CO3 and methionine weight ratios, discrete pH values, and packaging/format (vial vs bag; ready-to-administer vs concentrate; reconstitutable with sugar exclusions).
- The infringement “center of gravity” is Claims 1 and 22, with Claims 8–15 and 12–13 acting as measurable formulation checkpoints.
- For design-around, the fastest routes are typically: remove lactobionic acid, remove methionine, shift pH below the claimed thresholds, or introduce ethanol or sugar alcohol above “substantially free.”
FAQs
- Can a formulation with argatroban + methionine but without lactobionic acid infringe US 7,589,106?
- If a product matches pH > 8.5 but uses a different buffering system than acetate/carbonate/bicarbonate, which claims are most likely to be avoided?
- How do the “about” concentration points in claim 2 affect infringement analysis for argatroban concentration?
- Does changing from ready-to-administer to a reconstitutable concentrate change US 7,589,106 exposure under the method claims?
- What is the litigation relevance of the “substantially free” limitations for ethanol and sugar alcohol in US formulation patents like 7,589,106?
References
- United States Patent 7,589,106. (Provided claim text).
