Scope and claims of US Patent 11,065,248 (dextromethorphan + bupropion to enhance plasma exposure in extensive metabolizers)
US 11,065,248 is a method patent that narrowly claims a specific pharmacokinetic “booster” regimen: twice-daily co-administration of bupropion and dextromethorphan for at least eight consecutive days in extensive metabolizers, with a defined dextromethorphan:bupropion weight ratio (0.4–0.7) and quantified AUC0-12 magnitude on day 8 (minimum fold-increase vs dextromethorphan alone, and absolute AUC floor). Dependent claims further lock dosing ranges, including the single dosage form (solid) requirement and specific daily bupropion and per-dose dextromethorphan windows. In practical patent-landscape terms, the enforceable claim core is not “bupropion inhibits CYP2D6” generally, but a claim-shaped combination of patient phenotype, ratio, schedule, and exposure metrics.
What does US Patent 11,065,248 claim: scope of the “method of enhancing dextromethorphan plasma levels” concept?
Independent claim 1 recites all of the following essential elements:
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Patient subgroup / phenotype
- “the human being is an extensive metabolizer of dextromethorphan”
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Therapeutic intent
- “in need of treatment with dextromethorphan”
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Drug combination
- “co-administering a bupropion with a dextromethorphan”
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Schedule and duration
- “twice daily”
- “for at least eight consecutive days”
- exposure metric evaluated “on the eighth day that the bupropion and the dextromethorphan are co-administered”
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Defined dosing ratio
- “weight ratio of the dextromethorphan to the bupropion is about 0.4 to about 0.7”
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PK performance requirements (day 8)
- Fold-increase standard:
- “AUC0-12 of dextromethorphan is at least about 15 times the AUC0-12 … without the bupropion for eight consecutive days”
- Absolute exposure floor:
- “AUC0-12 … is at least about 800 ng·hr/mL”
What does that mean for infringement design space?
To practice the claim (or to design around it), a party must match the claim’s combination of:
- phenotype (extensive metabolizer),
- administered regimen (twice daily, ≥8 days),
- ratio window (0.4–0.7),
- and measurable PK outcomes (day-8 AUC0-12 threshold and fold increase vs a dextromethorphan-alone comparator at the “same amount twice daily for eight consecutive days”).
This is a “results-based” method claim in the sense that infringement can be tested by exposure readouts rather than only by formulation architecture (though dependent claims do narrow formulation).
Which claim elements are most constraining: dosage ratio, AUC fold-increase, AUC minimum, phenotype, or schedule?
Most constraining are typically the quantitative PK limits and phenotype-dependent framing because they convert a pharmacology story into a measurable and testable regimen.
Quantitative constraints in independent claims
- Ratio: dextromethorphan:bupropion about 0.4–0.7.
- Day-8 fold increase: at least about 15x (claim 1) vs dextromethorphan alone.
- Day-8 absolute AUC0-12 floor: at least about 800 ng·hr/mL (claim 1).
Claim 11 tightens absolute exposure
Independent claim 11 is the same method structure but recites:
- “AUC0-12 … is about 1,100 ng·hr/mL” (instead of only an absolute minimum).
Claim 21 gives AUC range
Independent claim 21 recites:
- “AUC0-12 … is about 800 ng·hr/mL to 1,686 ng·hr/mL” (a defined absolute exposure interval).
Claim 2x increases the fold-increase bar
Independent claim 20 is the same as claim 11/21 structure but requires:
- Day-8 fold increase “at least about 20 times … without the bupropion.”
Net effect: the patent includes overlapping independent claims with different numeric “gates”:
- (i) fold-increase gate 15x vs 20x,
- (ii) absolute AUC floor 800,
- (iii) absolute AUC point 1,100,
- (iv) absolute AUC interval 800–1,686.
This gives the patentee multiple pathways to capture accused regimens that hit different exposure targets.
How do dependent claims narrow scope: single dosage form, solid formulation, dextromethorphan mg bands, and bupropion daily dose?
Dependent claims add form factor and dose band constraints.
Single dosage form and solid requirement (claims 2, 3; 12, 13; 22, 23)
- Claim 2/12/22: bupropion and dextromethorphan “administered in a single dosage form.”
- Claim 3/13/23: “single dosage form is a solid.”
Practical implication: a co-administration product delivered as separate dosage forms can fall outside these dependent claims, though it may still be captured by the independent method claims (which do not, on their face, require a single dosage form).
Dextromethorphan per single dose (claims 4–6; 14–16; 24–26)
All set within a 30–60 mg band, via alternatives:
- About 40–50 mg (claims 4, 14, 24)
- About 30–40 mg (claims 5, 15, 25)
- About 30–60 mg (claims 6, 16, 26)
These are broad enough that many intermediate dose strengths can map into at least one dependent range.
Bupropion daily dose ranges (claims 7–8; 17–18; 27–28)
Alternatives:
- About 150–200 mg daily (claims 7, 17, 27)
- About 200–250 mg daily (claims 8, 18, 28)
Since the schedule is twice daily in the independent claims, these daily bands correspond to twice-daily per-dose amounts of roughly half those totals, but the dependent claims themselves only specify “daily dose” not per-dose split.
Ratio narrow band (claims 9, 19, 29)
- Weight ratio dextromethorphan:bupropion about 0.4–0.45
This is a tighter sub-band inside the broader 0.4–0.7 window.
How is “AUC0-12 at least about 15 times” operationalized in the claim, and what comparator regimen does it require?
The claim defines a comparator:
- “AUC0-12 … that would result from administering the same amount of the dextromethorphan twice daily without the bupropion for eight consecutive days.”
So the comparator is not a historical control; it is conceptually “would result from” dosing the same dextromethorphan amount under the same schedule and duration, but without bupropion.
In practice, enforcing this kind of claim typically hinges on day-8 steady-state exposure measurement plus a structured comparison protocol or validated modeling. The claim’s language is drafted to prevent arguments that only “relative” or only “absolute” exposure matters; both gates exist in claim 1.
What formulations are covered by US 11,065,248: immediate-release co-formulation, fixed-dose combination tablets, or separate co-administration?
Covered by independent method claims
Independent claims 1/11/21 and the other independent claim repetitions (as provided) focus on:
- co-administration,
- twice daily,
- ≥8 days,
- phenotype,
- ratio,
- day-8 AUC metrics.
They do not, on their face, require “single dosage form” or “solid” in the independent claims.
Covered by dependent claims
Dependent claims 2–8 (and analogs 12–18; 22–28) restrict:
- single dosage form,
- solid dosage form,
- specific dextromethorphan mg bands per dose,
- specific bupropion daily dose bands.
If an accused regimen uses separate dosage forms, dependent claims may be harder to assert; the independent method claim remains the key.
How strong is the patent estate for this mechanism: what parts of the claim are likely to be narrow vs broad in litigation?
Based on the provided claim text alone, the strength profile is shaped by:
Broad-ish elements
- “co-administering” does not specify an administration route, except it must support twice-daily systemic exposure and measurable AUC.
- Dose ranges in dependent claims are relatively wide.
Narrow-ish elements
- “extensive metabolizer of dextromethorphan” is a gating population. It can be operationalized by genotype/phenotype testing depending on the specification, but it is still a subgroup limitation.
- The ratio window (0.4–0.7) is specific.
- The day-8 AUC requirements include both fold increase and absolute thresholds, and other independent claims specify exact or interval AUC.
Litigation-relevant feature: multiple independent numeric gates
The set of independent claims (1, 11, 21, and the fold-increase variant 10/20/30 structure as provided) creates overlapping coverage for different exposure outcomes. This reduces the odds that a single exposure “miss” avoids all independent claims.
What patent landscape risks exist for generics or competitors: design-around by changing ratio, schedule, or exposure targets?
Because the claims require:
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a specific ratio,
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a specific schedule (twice daily, ≥8 days),
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and quantitative AUC thresholds on day 8,
design-around strategies would ordinarily attempt to break at least one gate:
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Adjust the dextromethorphan:bupropion weight ratio outside 0.4–0.7.
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Alter regimen so day-8 exposure does not meet the 15x/20x and/or 800 ng·hr/mL thresholds.
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Change dosing cadence or duration so the “on the eighth day” metric does not apply as claimed.
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Use separate dosage forms to avoid dependent “single solid dosage form” limitations (without necessarily escaping independent claims).
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Treat non-extensive metabolizers or avoid claiming extensive metabolizer inclusion (though enforcement will still focus on whether the accused regimen is used in the claimed phenotype).
When does the patent lose exclusivity: what is the expiration date for US 11,065,248?
No publication/filing data, priority date, maintenance status, or terminal disclaimer terms were provided. Without that information, an expiration calendar cannot be computed from the claim text alone.
What Orange Book status applies to US 11,065,248?
No FDA product, NDA/BLA/NME identifier, or Orange Book listing details were provided. A determination of Orange Book status cannot be made from claim text alone.
Is US 11,065,248 being challenged via Paragraph IV or equivalent pathways?
No litigation history, listing identifiers, or FDA challenge filings were provided. A Paragraph IV or biosimilar-style challenge assessment cannot be produced from the claim text alone.
Which companies are likely owners or competitors for this specific dextromethorphan–bupropion exposure boosting strategy?
No assignee information, inventors, prosecution history, or cited references were provided. Company mapping cannot be produced from the claim text alone.
Key claim-to-competitive scenario mapping (what a competitor would need to avoid to step outside the claim)
| Claim element |
What an accused regimen would need to match to risk infringement |
Easiest design-around lever (in concept) |
| Extensive metabolizer |
Administer regimen to extensive metabolizers |
Use different phenotype or omit testing/targeting (enforcement still possible based on actual use) |
| Twice daily, ≥8 days |
Dosing schedule aligns and AUC measured on/for day 8 |
Change schedule or duration so day-8 AUC gate misses |
| Ratio 0.4–0.7 |
Weight ratio dextromethorphan:bupropion within window |
Adjust ratio outside 0.4–0.7 |
| AUC fold-increase ≥15x or ≥20x |
Day-8 exposure meets fold comparison vs dextromethorphan alone |
Change exposure outcome via ratio, schedule, or formulation |
| Absolute AUC gate |
≥800 ng·hr/mL (and/or 1,100 point or 800–1,686 interval depending on independent claim) |
Miss the absolute exposure interval/point |
| Single solid dosage form (dependent) |
Fixed-dose solid co-formulation |
Use separate dosage forms to avoid dependent constraints |
Key Takeaways
- US 11,065,248 is a phenotype- and exposure-defined method patent for boosting dextromethorphan AUC0-12 using bupropion under a twice-daily, ≥8-day regimen in extensive metabolizers.
- The enforceable core is the combination of:
- ratio (dextromethorphan:bupropion ~0.4–0.7),
- day-8 fold increase (≥15x in claim 1; ≥20x in the provided variants),
- and day-8 absolute AUC0-12 (≥800 ng·hr/mL in claim 1; ~1,100 or 800–1,686 in other independent claims).
- Dependent claims add fixed-dose solid structure and dose band constraints (dextromethorphan ~30–60 mg per single dose options; bupropion daily ~150–250 mg).
- Competitive risk analysis should treat this as a results-based regimen: competitors must assess actual day-8 AUC outcomes under extensive metabolizer conditions, not only pharmacology expectations.
- Expiration, Orange Book status, and litigation/Paragraph IV exposure cannot be determined from the claim text provided.
FAQs
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Does US 11,065,248 require a single fixed-dose tablet in the independent claims?
The independent claim structure you provided requires co-administration but, based on the claim text, does not require a single dosage form; the single-solid constraint appears in dependent claims.
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Can a regimen avoid the patent by administering dextromethorphan and bupropion as separate dosage forms?
Separate forms can avoid dependent “single dosage form” limitations, but independent method claims may still apply if the ratio and day-8 AUC gates are met.
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What is the most critical quantitative metric to test in day-8 exposure studies?
The day-8 AUC0-12 meets both a fold-increase requirement versus dextromethorphan alone and an absolute AUC threshold (and, in other independent claims, a point or interval).
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How do the different independent claims expand coverage for exposure outcomes?
By using different AUC gate types (minimum threshold, point value, and interval) and fold-increase levels (15x vs 20x as provided), the claims cover multiple exposure result patterns.
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Would shifting the dextromethorphan:bupropion weight ratio outside 0.4–0.7 likely reduce risk?
It is the most direct lever against the claim’s defined ratio element, though infringement can still depend on actual dosing ratios and resulting AUC performance.
References
- US Patent No. 11,065,248 (claim text provided by user).
