United States Patent 9,458,107 scope and claim-by-claim patent landscape for aniline-contaminated Formula (I) drug substance and compositions
US 9,458,107 claims a purity specification for a specific drug substance “compound of formula (I)” (and its monohydrate and salts) where the substance is contaminated with one or more anilinic substances at tightly controlled levels (generally ≤0.05% w/w, with multiple dependent claims narrowing to ≤0.025% and ≤0.01%, and range-based claims 0.0001% up to those maxima). The tightest claim coverage focuses on two named aniline-related impurities: 4-amino-3-fluorophenol and 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide. Independent claims also extend to compositions and combinations that include the formula (I) substance and/or monohydrate/salts while accounting for “calculated weight” of formula (I) from hydrate and/or salt.
Practical bottom line: this estate is an impurity-control/purification IP layer. Enforcement risk for generics or licensed API suppliers turns on whether accused products can be shown to contain the claimed anilinic impurities above the claimed thresholds, and on how they compute the “combined weight” and “calculated weight” of formula (I) when using monohydrate and/or salts.
What does US 9,458,107 actually claim: anilinic impurity limits in compound of formula (I), monohydrate, salts, and compositions?
Featured snippet answer: US 9,458,107 protects a drug substance and product compositions where compound of formula (I) (including monohydrate and salts) contains anilinic impurities in ≤0.05% w/w (and narrower dependent thresholds and ranges), including specific impurities 4-amino-3-fluorophenol and 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide.
Core independent claim theme: “contaminated with one or more anilinic substances”
Across the claim set, the patent uses:
- Substrate definition: “compound of the formula (I)”
- State of substance: “contaminated with one or more anilinic substances”
- Quantitative limitation: each anilinic substance present at each ≤0.05% w/w of the formula (I) (with additional dependent claims narrowing)
- Scope expansion: compound alone, monohydrate, salts, plus compositions and combinations that include these forms.
The claim’s quantitative architecture (threshold vs range)
The claim set uses two recurring quantitative styles:
- Cap-only limitation: “equal to or less than 0.05% by weight”
- Lower-to-upper range: “from 0.0001% to a maximum of X% by weight” (X = 0.025% or 0.01% or 0.05% depending on the dependent claim)
This dual structure matters in litigation because it covers both:
- products with impurity near the upper bound, and
- products that meet a defined “positive” minimum impurity level (not merely “trace below detection”).
What are the exact impurity targets in US 9,458,107: which anilinic substances are named and how are limits applied?
Featured snippet answer: The patent narrows to two named anilinic impurities, each limited to ≤0.05% w/w and also to narrower limits of ≤0.025% and ≤0.01%, with several range claims covering 0.0001% to those maxima.
Named anilinic impurities (as recited in the dependent claims you provided)
- 4-amino-3-fluorophenol
- 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide
(spelling varies in the text you provided; claim language treats it as a named contaminant)
How the “each” limitation operates
Claims repeatedly say:
- “contaminated with one or more anilinic substances, each in an amount equal to or less than …”
This indicates:
- every anilinic substance in the set must be below the threshold for the product to fall outside the claim (and conversely, any single anilinic impurity above the threshold can support noninfringement for “each ≤ threshold” formulations depending on claim construction).
Specific levels and structures covered in your claim text
Below are the threshold/range limits that appear:
| Claim numbers (from your list) |
Impurity(s) |
Limit style |
Numerics stated |
| 1 |
one or more anilinic substances |
cap |
each ≤0.05% w/w |
| 2 |
4-amino-3-fluorophenol and/or 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide |
cap |
each ≤0.05% w/w |
| 9-11 |
the same two named impurities |
range |
0.0001% to max 0.05% / 0.025% / 0.01% |
| 12-14 |
composition with the same two named impurities |
range |
0.0001% to max 0.05% / 0.025% / 0.01% |
| 15-17 |
combination including compound + monohydrate |
range |
0.0001% to max 0.05% / 0.025% / 0.01% |
| 18-20 |
composition including compound + monohydrate + salts |
range |
0.0001% to max 0.05% / 0.025% / 0.01% |
| 21-22 |
monohydrate |
cap |
each ≤0.05% w/w; also monohydrate framed via “calculated weight” |
| 23-25 |
monohydrate |
range |
0.0001% to max 0.05% / 0.025% / 0.01% |
| 26-30 |
salt |
cap and range |
each ≤0.05% w/w; range versions to 0.025% and 0.01% |
How do “compound of formula (I)”, “monohydrate”, and “salts” change infringement exposure in US 9,458,107?
Featured snippet answer: The patent is structured to cover the relevant physical form: free base/“compound of formula (I)”, monohydrate, and salts. For compositions, it ties impurity mass accounting to a “calculated weight” of formula (I) derived from hydrate and/or salt forms.
Claim set segmentation by physical form
From your list, the claims cluster as:
- Compound claims: 1, 2, 9, 10, 11
- Composition claims: 3-6, 12-17, 18-20
- Monohydrate claims: 7, 8, 21-25
- Salt claims: 26-30
“Calculated weight” and “combined weight” constructs
These constructs matter for evidentiary and accounting disputes:
-
For monohydrate claims (e.g., 21, 23-25), the amount of formula (I) used for impurity comparison is:
- “the calculated weight of the compound of formula I calculated from the amount of monohydrate …”
-
For compositions/combination claims, the formula (I) denominator includes:
- “the combined weight of the compound of formula (I) and the calculated weight of the compound of formula I from the monohydrate …”
- and in broader versions: “combined weight … and the calculated weight … from the salts …”
Litigation impact: a defendant can try to argue that impurity is diluted below threshold only if the patent’s calculation method applies. Because the claims explicitly define the accounting, the dispute can turn on:
- mass fraction calculations,
- hydrate/salt conversion factors used by both sides,
- and test method selection (HPLC area normalization, water content measurement, conversion protocols).
What formulations are protected by US 9,458,107: drug substance-only vs finished compositions containing excipients?
Featured snippet answer: The patent includes drug substance claims and composition claims. The “composition” language in your claims reads as broad product packaging for a material containing the impurity-controlled formula (I) forms; the dependent claims also cover inclusion of monohydrate and/or salts in the composition with the same impurity thresholds.
Coverage types reflected in the claim text you supplied
- Substance-level protection: “The compound of the formula (I)” (plus monohydrate and salts)
- Material/composition protection: “A composition comprising …” (compound, monohydrate, and/or salts)
- Combination wording: “A combination of a compound … and its monohydrate …” and likewise impurity-laden combinations
Even where “composition” is not tied to a specific dosage form (tablet, capsule, etc.) in the claim excerpts you provided, the claim breadth typically covers any prepared material containing the claimed components, subject to meeting the impurity limits and the “calculated weight” accounting.
How strong is the US 9,458,107 patent estate for purity/impurity-control enforcement?
Featured snippet answer: Strength is driven less by mechanism-of-action novelty and more by enforceability of a quantitative impurity specification: if the accused API or product contains the specified anilinic impurities at levels matching the claim thresholds, infringement exposure increases sharply.
What the claim drafting suggests about enforceability
- The claims are quantitative and explicit.
- They specify named impurities in multiple dependent claims.
- They define how to compute formula (I) mass in hydrate/salt-containing compositions.
These features reduce interpretive ambiguity compared with open-ended impurity definitions. The remaining enforcement risk concentrates on:
- whether the accused product contains the specified impurity species,
- the analytical method and reporting units used,
- and whether the impurity amount is above/below the claim maxima or falls in the claimed ranges.
Weakness vectors (based on claim structure)
The main potential defenses flow from claim text mechanics:
- “each” anilinic substance must satisfy the limitation.
- If a product instead has different impurities (not falling under “anilinic substances” as construed) the defendant can argue the claim-defined impurity set is not met.
- If the product uses a form or formulation outside the claim constructs, defendants can argue the “compound of formula (I) within the composition” calculation denominator differs.
When does US 9,458,107 lose exclusivity: how to map expiration to generic entry risk?
Featured snippet answer: This requires the patent’s filing date, priority, and term-restoration status, plus any terminal disclaimers. Those data are not provided in the information you supplied, so no accurate exclusivity or expiration date can be computed here.
What generic entry risks exist for products that may carry anilinic impurities above US 9,458,107 thresholds?
Featured snippet answer: Risk is highest for ANDA or 505(b)(2) entrants whose API route or crystallization/purification produces residual 4-amino-3-fluorophenol or 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide at levels that match the claimed ranges, especially where the product includes monohydrate or salts and the impurity denominator is computed per the patent’s “calculated weight” rules.
Practical risk map by product type
- Free form compound (formula I): compare residual anilinic impurity levels directly against ≤0.05% and range caps
- Monohydrate APIs: evaluate impurity mass fraction using the patent’s “calculated weight” denominator
- Salt forms: same, but with “calculated weight … from the salts”
- Combinations (compound + monohydrate; compound + monohydrate + salts): ensure denominator uses “combined weight” as required
Key manufacturing/IP friction points implied by the claims
Because the claims focus on trace impurities, risk is most sensitive to:
- chromatography or crystallization wash steps,
- polymorph/hydrate control and dehydration-rehydration steps,
- upstream intermediate purification that can carry anilines/aryl amines.
What patent litigation issues typically arise in impurity-threshold cases like US 9,458,107?
Featured snippet answer: The dispute usually centers on (1) whether the accused product contains the claimed impurities, (2) whether the impurity amount meets the quantitative threshold/range, and (3) how to compute the denominator using hydrate/salt “calculated weight.”
Claim-driven litigation topics suggested by the text you provided
- Analytical method validity: HPLC/UPLC identity confirmation and quantification for the two named impurities
- Unit conventions: converting assay data to weight % basis consistent with claim language
- Denominator math: whether to use “compound of formula (I) within the composition” defined as combined weight + calculated hydrate/salt equivalents
- Batch-to-batch variability: whether multiple batches must be analyzed to establish infringement
How does US 9,458,107 compare with other impurity-control patents (typical landscape)?
Featured snippet answer: Impurity-control patents generally create a narrow but potent IP perimeter around specific residual impurities and specific quantitative limits, often outcompeting broader composition or method-of-use estates for “at-risk” formulations.
Where this patent likely sits in a typical portfolio
In many drug families, an impurity-spec patent like this one acts as a:
- secondary line after core composition/synthesis patents expire or weaken, and
- tight guardrail for generic API routes whose bulk purification does not remove a specific anilinic impurity below the claimed limit.
Which additional patents likely surround US 9,458,107 and how to organize freedom-to-operate?
Featured snippet answer: This analysis cannot be completed from the information provided. Patent-family mapping requires the full patent bibliographic record (publication/application numbers, priority, assignee, related filings) and Orange Book listing ties, none of which are included in your prompt.
Key Takeaways
- US 9,458,107 protects compound of formula (I) and its monohydrate and salts when they are contaminated with anilinic substances at controlled levels, generally ≤0.05% w/w (with dependent claims narrowing to ≤0.025% and ≤0.01%).
- The claim set repeatedly specifies two named impurities: 4-amino-3-fluorophenol and 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide, each limited per the claim language.
- The patent includes composition and combination claims that use defined “calculated weight” and “combined weight” denominators when monohydrate and/or salts are present. This definition is central to infringement assessment.
- Enforcement focus is impurity identification and quantification plus denominator math for hydrate/salt-containing products.
- A reliable “when exclusivity ends” or “what other patents exist” landscape cannot be derived from the claim text alone.
FAQs
- Do US 9,458,107 claims require that all anilinic impurities be below the threshold, or only some?
- How do “each in an amount equal to or less than” impurity limitations affect invalidity or noninfringement arguments?
- What does “calculated weight … from the monohydrate” mean for impurity testing reports in a dispute?
- Does the presence of monohydrate in a generic product increase or decrease infringement risk under these claims?
- If a product contains different anilinic impurities not named in the dependent claims, does the independent claim still apply?
References (APA)
- United States Patent 9,458,107. Claims as provided in user prompt.
