United States Patent 9,333,201: Scope, Claim-Set Structure, and US Landscape
US Patent 9,333,201 is directed to oral, hydrocodone-only analgesic dosing methods with an extended-release (ER) hydrocodone release profile constrained by quantitative exposure targets (AUC0-inf and Cmax) under hepatic impairment. The claims are built to narrow both drug input (hydrocodone as the sole active) and pharmacokinetic behavior (exposure ranges and tolerable increases vs non-impairment populations), plus dissolution-based release performance at USP pH 6.8 buffered conditions.
What do the claims actually cover? (Independent claim spine)
Claim 1 (broadest method frame, exposure-defined)
Claim 1 is a method of treating pain using:
- Oral dosage unit
- Hydrocodone or pharmaceutically acceptable salt as the only active ingredient
- Extended-release formulation of hydrocodone (or salt)
- Release profile constrained by AUC0-inf bands in three patient groups:
1) No renal or hepatic impairment (labeled “not suffering from renal or hepatic impairment”)
- AUC0-inf per dosage equivalent to 20 mg hydrocodone bitartrate: *300 to 500 ngh/mL
2) Mild hepatic impairment**
- AUC0-inf: *300 to 570 ngh/mL
3) Moderate hepatic impairment**
- AUC0-inf: *300 to 700 ngh/mL**
This creates a PK gate: even if the formulation is ER hydrocodone, it does not land in the claim unless exposure stays inside those numeric windows for each impairment category.
Claims 2-3 (salt and dose quantum)
- Claim 2: dosage unit comprises hydrocodone bitartrate
- Claim 3: dosage contains 15, 20, 30, or 40 mg hydrocodone bitartrate
These narrow the candidate formulations to bitartrate and specific labeled strengths.
Claims 4, 5-6 (dual release and hepatic impairment patient selection)
- Claim 4: dosage unit further comprises an immediate-release (IR) formulation (in addition to ER)
- Claims 5-6: explicit patient conditions:
- mild hepatic impairment
- moderate hepatic impairment
Claims 7-8 (incremental exposure caps vs non-impairment)
These add relative constraints beyond the absolute AUC/Cmax bands:
- Claim 7 (AUC increase limits)
- Mild hepatic impairment: AUC0-inf increase not more than 30%
- Moderate hepatic impairment: AUC0-inf increase not more than 50%
- Claim 8 (Cmax increase limits)
- Mild hepatic impairment: Cmax increase not more than 25%
- Moderate hepatic impairment: Cmax increase not more than 30%
This is important for landscape mapping: a formulation can satisfy absolute AUC windows but still fail if it violates the allowed relative escalation in hepatic impairment.
Claims 9-14 (alternative/optional tighter numeric sub-ranges)
The claim set also includes narrower AUC/Cmax ranges, effectively offering multiple “acceptable” bands:
- Claim 9: AUC0-inf (normal) *317 to 465 ngh/mL**
- Claim 10: AUC0-inf (mild) *316 to 564 ngh/mL**
- Claim 11: AUC0-inf (moderate) *352 to 666 ngh/mL**
- Claim 12: Cmax (normal) 17 to 27 ng/mL
- Claim 13: Cmax (mild) 19 to 29 ng/mL
- Claim 14: Cmax (moderate) 20 to 30 ng/mL
Taken as a set, these “ranges within ranges” support multiple formulation/clinical scenario outcomes that still fall inside infringement.
Claim 15 (dissolution performance at USP pH 6.8)
Claim 15 adds a mechanistic release constraint linked to dissolution:
- 10% to 30% of hydrocodone released in first hour
- 60% to 98% released during first 12 hours
- Measurement in USP dissolution apparatus buffered at pH 6.8
This turns the claim from purely “PK-defined” into a release-behavior-defined patent, with a standard dissolution test condition.
How is Claim 16 different? (Beads architecture + fixed two-population ER/IR release)
Claim 16 (hydrocodone bitartrate-only; beads; explicit ER/IR blend release pattern)
Claim 16 is a second independent claim that is more structure-anchored:
- Hydrocodone bitartrate as the only active ingredient
- Dosage unit includes:
- First population of beads: immediate release hydrocodone bitartrate
- Second population of beads: extended release hydrocodone bitartrate
- Formulated to achieve:
- ~10% to ~30% release in first hour
- More than 60% and less than 98% release during first 12 hours (USP dissolution apparatus buffered at pH 6.8)
- Keeps the same three AUC0-inf bands per 20 mg bitartrate equivalent as Claim 1:
- Normal: *300 to 500 ngh/mL**
- Mild hepatic impairment: *300 to 570 ngh/mL**
- Moderate hepatic impairment: *300 to 700 ngh/mL**
Claim 16 thus targets ER hydrocodone products that use a two-bead population strategy (IR beads + ER beads) and that land in the hepatic-impaired exposure corridors.
Claims 17-20 (architecture and coating definitions)
- Claim 17: dosage contains 15, 20, 30, or 40 mg bitartrate
- Claim 18: weight split:
- ER beads: 75% to 85% by weight
- IR beads: 15% to 25% by weight
- Claim 19: ER bead polymer coating (non-exhaustive list of polymers), including:
- cellulose acetate phthalate
- cellulose acetate trimaletate
- hydroxy propyl methylcellulose phthalate
- polyvinyl acetate phthalate
- ammonio methacrylate copolymers
- polyacrylic acid and polyacrylate/methacrylate copolymers
- polyvinyl acetaldiethylamino acetate
- hydroxypropyl methylcellulose acetate succinate
- shellac
- Claim 20: tighter dissolution release slices:
- 15% to 25% released in first hour
- 65% to 95% released during first 12 hours (USP pH 6.8)
What is the enforceable claim “center of gravity”?
The enforceable core is not “hydrocodone ER for pain.” It is hydrocodone-only ER (often with IR fraction) where both:
1) Exposure outcomes under hepatic impairment are within specified bands (AUC0-inf and Cmax), and
2) Dissolution release behavior at USP pH 6.8 matches the claimed early/12-hour release percentages.
This combination creates a high bar for design-around: altering polymer, bead structure, or blending ratio can shift dissolution and thereby PK, risking exit from the AUC/Cmax windows or the allowed percentage increase caps.
Claim map (coverage matrix for infringement screening)
| Claim element |
What it requires |
Where it appears |
| Indication and method |
Treat pain |
Claims 1, 16 |
| Drug actives |
Hydrocodone or salt; Claim 16 is bitartrate-only; no other actives |
Claims 1, 16 |
| Formulation type |
ER hydrocodone; Claim 16 uses two bead populations (IR + ER) |
Claims 1, 4, 16 |
| Strengths |
15/20/30/40 mg bitartrate |
Claims 3, 17 |
| Dissolution at pH 6.8 |
10%-30% first hour and 60%-98% through 12 hours |
Claims 15, 16 |
| Tighter dissolution slice |
15%-25% first hour and 65%-95% through 12 hours |
Claim 20 |
| Hepatic PK exposure (absolute AUC0-inf) |
Normal: 300-500; Mild: 300-570; Moderate: 300-700 ng*h/mL (per 20 mg equivalent) |
Claims 1, 16 |
| PK escalation limits (relative) |
Mild AUC +<=30%; Moderate AUC +<=50% |
Claim 7 |
| Peak exposure limits (Cmax escalation) |
Mild Cmax +<=25%; Moderate Cmax +<=30% |
Claim 8 |
| Narrower AUC windows |
Alternative bands (Claims 9-11) |
Claims 9-11 |
| Narrower Cmax windows |
Alternative bands (Claims 12-14) |
Claims 12-14 |
| Bead weight fraction |
ER 75%-85%; IR 15%-25% by weight |
Claim 18 |
| ER bead coating polymer families |
Specific listed polymer coatings |
Claim 19 |
What’s the patent landscape implication? (How similar products get pulled in)
Likely “read-across” product attributes
Products most likely to test for claim overlap are ER hydrocodone bitartrate products that:
- Use IR/ER layering (IR fraction blended with ER fraction)
- Use bead-based systems or other architecture that yields a dissolution curve matching:
- early-hour release between 10%-30%
- 12-hour release between 60%-98%
(or tighter slices for Claim 20)
- Generate systemic exposure that meets the hepatic impairment AUC0-inf and Cmax criteria
Key risk for generic or follow-on ER hydrocodone
If a competitor’s product:
- uses hydrocodone ER for pain but shows higher AUC/Cmax in mild or moderate hepatic impairment, or
- shifts dissolution release outside the pH 6.8 early and 12-hour bands,
it likely exits the claim.
For design-around, changing dissolution curve timing and polymer choice can be insufficient by itself because the claims include measured PK outcomes in hepatic impairment groups, which are harder to “guess” without running the referenced clinical PK.
Potential claim-scope vulnerabilities (what can fall outside)
The claims are constraining in multiple dimensions. A product can be outside infringement if any required dimension fails, for example:
- No hepatic impairment PK exposure within all three AUC windows (normal, mild, moderate), or
- Violation of the relative increase caps (AUC and Cmax escalation limits), or
- Dissolution mismatch at USP pH 6.8 (first hour and 12-hour release percentages), or
- Missing the two-population beads architecture where Claim 16 is asserted (while still possibly implicated by Claim 1/other method claims).
Key Takeaways
- US 9,333,201 targets hydrocodone-only oral ER pain treatment with quantified PK endpoints in hepatic impairment (AUC0-inf and Cmax) plus USP pH 6.8 dissolution release constraints.
- Claim 1 is the broadest method frame: ER hydrocodone (or salt) with exposure windows for normal, mild, and moderate hepatic impairment.
- Claim 16 adds bead architecture (IR bead population + ER bead population) and keeps the same hepatic PK AUC corridor while tightening dissolution and adding polymer and weight-fraction constraints.
- Landscape screening should focus on products that match (i) drug specificity, (ii) dissolution timing at pH 6.8, and (iii) hepatic-impaired PK exposure corridors.
FAQs
1) Does US 9,333,201 require a specific formulation architecture?
No for Claim 1 (it requires ER hydrocodone with exposure and dissolution constraints), but yes for Claim 16, which requires two bead populations (IR + ER).
2) Are the hepatic impairment limits absolute (range) or relative (percentage increase)?
Both. It has absolute AUC0-inf ranges (normal, mild, moderate) and also relative escalation caps for AUC0-inf and Cmax vs non-impairment.
3) What dissolution test condition ties into the claims?
Release is measured using USP dissolution apparatus buffered at pH 6.8, with first-hour and 12-hour percentage release bands.
4) Does the patent cover hydrocodone salts other than bitartrate?
Claim 1 covers hydrocodone or a pharmaceutically acceptable salt as the only active ingredient, while Claim 16 is explicitly hydrocodone bitartrate as the only active ingredient, and Claims 2-3 and 17 constrain to bitartrate and specified strengths.
5) How do Claim 9-14 and Claim 20 function in infringement screening?
They add additional acceptable numeric sub-ranges for AUC0-inf and Cmax and tightened dissolution bands, broadening the set of formulations that can still fall within the claim.
References
- US Patent 9,333,201 (claims provided in prompt).
