US Patent 12,582,625 (DFMO) for Preventing Relapse in High-Risk Neuroblastoma: Scope, Claim Boundaries, and Landscape
United States Drug Patent 12,582,625 is a method-of-treatment patent that claims oral DFMO (α-difluoromethylornithine) hydrochloride monohydrate dosing regimens to reduce the risk of relapse in high-risk neuroblastoma patients whose disease is in remission after prior therapy, specifically including anti-GD2 immunotherapy. Claim scope centers on (i) relapse-risk reduction as the therapeutic endpoint, (ii) patient selection (partial or complete response, remission status, prior anti-GD2), and (iii) dose specification expressed as grams per m² body surface area, plus multiple dependent claims that narrow to tablet strength (250 mg) and twice-daily administration independent of food.
What the independent claim set actually covers
Across claims 1 and 11, the patent covers the same core invention expressed with different dose-format boundaries:
- Claim 1 (twice daily): oral DFMO administered 2x/day, with:
- food independence (independent of food intake)
- total daily dose = 0.05 to 5 g/m² (DFMO hydrochloride monohydrate), expressed as g/m²
- patient has high-risk neuroblastoma in remission and has at least partial response to prior therapy that includes anti-GD2 immunotherapy
- Claim 11 (total daily dose only): oral DFMO administered as a total daily dose = 0.05 to 5 g/m², with the same patient-condition and prior-therapy inclusion (anti-GD2)
Dependent claims then tighten the field with dose bands (1 to 2 g/m², 1 to 3 g/m², 1 to 2 g/m² repeated), tablet presentation, and dose-to-tablet mapping (250 mg tablets).
What is claimed: therapeutic method and patient population
Who is treated (and what condition must exist)?
The claimed methods require all of the following patient and disease elements:
- Diagnosis: “patient diagnosed with high-risk neuroblastoma”
- Post-therapy disease state: “high-risk neuroblastoma is in remission”
- Prior response: the patient has demonstrated at least a partial response (or, in claim 7, complete response)
- Prior therapy composition: “prior therapy comprises anti-GD2 immunotherapy”
- Optional add-on: “prior therapy further comprises chemotherapy” (dependent claims)
How “partial response” is defined
Claim 6 fixes the definitional mechanism for partial response:
- (i) no evidence of neuroblastoma by anatomical imaging and pathological assessment of bone marrow, or
- (ii) neuroblastoma detected on anatomical imaging but metabolically inactive by functional imaging, plus no evidence in bone marrow on pathology.
This language is important because it makes the claim boundary anchored to imaging + marrow pathology criteria, not only clinical judgment or generic “remission.”
What therapeutic endpoint is promised
Every independent method claim is framed as:
- “reducing the risk of relapse of neuroblastoma”
So the patent’s treatment claim is not limited to tumor shrinkage; it is built around relapse-risk reduction post-remission.
How dosing is scoped: DFMO hydrochloride monohydrate and m² normalization
Core dose range
The patent sets an explicit dose envelope for DFMO hydrochloride monohydrate:
- 0.05 g/m² to 5 g/m² total daily dose
- Appears in claim 1 (total daily dose, twice daily regimen)
- Appears in claim 11 (total daily dose, general regimen)
Tightened bands
Dependent claims constrain the dose for narrower protection:
- 1 to 3 g/m² per day (claim 8)
- 1 to 2 g/m² per day (claim 9)
- 1 to 2 g/m² per day (explicit in claim 12)
The independent claims preserve broad coverage (0.05 to 5 g/m²), but the narrower dependents are where practical barriers for design-arounds concentrate.
Twice-daily structure
Claim 1 also locks down:
- oral administration twice a day
- food independence: “twice a day, independent of the patient’s food intake”
Claim 16 similarly requires:
- “total daily dose … administered … in two doses … equal to each other,”
- each being 0.5 to 1 g/m² (per dose)
So, within claim architecture, there are two different constraints:
- claim 1: twice daily and food independence
- claim 16: equal split dosing and per-dose band
Tablet strength and dose-to-tablet mapping
Presentation form
The patent narrows in dependent claims to solid oral forms:
- “pharmaceutical composition is a powder” (claim 2)
- “pharmaceutical composition is one or more tablets” (claim 3)
Tablet strength
Multiple dependents specify 250 mg DFMO hydrochloride monohydrate per tablet:
- claim 4: each tablet comprises 250 mg
- claim 14: each tablet comprises 250 mg
- claim 18: each tablet provides 250 mg
- claim 23: one or more tablets each provide 250 mg
- claim 27: one or more tablets each provide 250 mg
Body surface area (BSA) stepwise dosing (claim 10)
Claim 10 builds a BSA-based dosing schedule tied to 250 mg tablet increments:
- If BSA 0.25 to <0.5 m²: 250 mg twice/day
- If BSA 0.5 to <0.75 m²: 500 mg twice/day
- If BSA 0.75 to ≤1.5 m²: 750 mg twice/day
- If BSA >1.5 m²: 1 gram twice/day
This claim is a high-friction embodiment because it converts an m² dose concept into a discrete tablet dosing ladder.
Explicit daily totals (claims 24 to 29)
The patent also includes method embodiments that use absolute daily totals rather than only g/m²:
- claim 24: total per day is 250 mg, 500 mg, 1,000 mg, 1,500 mg, or 2,000 mg
- claim 26: per day 500, 1,000, 1,500, or 2,000 mg, administered twice/day in tablets, each tablet 250 mg
- claim 28: per day 500, 1,000, 1,500, or 2,000 mg, with a twice/day schedule using 250, 500, 750, or 1,000 mg per dose
- claim 29: for up to two years, administer per day in a 250/500/750/1,000 mg twice-daily pattern
So the landscape risk for DFMO product designers is not limited to a single dosage representation. The patent covers both BSA-normalized and fixed-mg regimes, with emphasis on tablet formulations.
Food-effect and formulation handling boundaries
Food independence (claim 1)
Claim 1 specifies DFMO administration twice daily independent of food intake.
Mixing with liquid/food (claims 15, 20, 22, 30)
Dependent claims also cover situations where DFMO is mixed:
- claim 15: mixed with liquid or food prior to oral administration
- claim 20: mixed with liquid or food prior to said oral administration
- claim 22: dosage amounts are specified with chemotherapy add-on; it does not explicitly mention mixing in claim text you provided, but claim 20 does.
- claim 30: prior therapy comprises anti-GD2 immunotherapy and chemotherapy
Net effect: the patent does not confine infringement to a strict “take on empty stomach” behavior. It spans both a “food independent” regimen and a “mixed with liquid or food” handling pathway.
Prior therapy requirement: anti-GD2 immunotherapy is a gating element
Mandatory inclusion
Every independent method claim you provided includes:
- “prior therapy comprises anti-GD2 immunotherapy”
This is a central boundary. A relapse-prevention DFMO regimen in a population treated without anti-GD2 is outside the literal requirement as drafted.
Chemotherapy is optional but claimed
Chemotherapy inclusion appears in multiple dependents:
- claim 5: prior therapy further comprises chemotherapy
- claim 19: prior therapy further comprises chemotherapy
- claim 21: prior therapy further comprises chemotherapy
- claim 30: prior therapy comprises anti-GD2 immunotherapy and chemotherapy
So, if the clinical protocol used by a competitor uses anti-GD2 plus chemo, the patent becomes easier to map onto actual practice.
Claim set mapping: coverage matrix by feature
Feature-by-feature scope
| Feature |
Broad coverage |
Narrow dependents |
| Indication |
High-risk neuroblastoma relapse-risk reduction |
N/A |
| Disease state |
In remission; partial or complete response required |
Claim 7 adds complete response; claim 6 fixes partial response criteria |
| Prior therapy |
Includes anti-GD2 immunotherapy |
Chemotherapy add-on in claims 5, 19, 21, 30 |
| DFMO form |
Oral DFMO hydrochloride monohydrate |
Powder (claim 2); tablets (claims 3, 13, 17) |
| Dose normalization |
Total daily dose 0.05 to 5 g/m² |
1 to 3 g/m² (claim 8); 1 to 2 g/m² (claims 9, 12) |
| Dosing frequency |
Twice daily in claim 1 |
Equal split two doses (claim 16); also fixed mg twice-daily schedules (claims 26-29) |
| Food handling |
Food-independent dosing in claim 1 |
Mixing with liquid/food in claims 15 and 20 |
| Tablet strength |
Not limited in independent claims |
250 mg/tablet in claims 4, 14, 18, 23, 27 |
| BSA-based schedule |
0.05 to 5 g/m² total daily dose |
Discrete mg ladder tied to BSA ranges (claim 10) |
| Time horizon |
Not in independent claims |
Up to 2 years in claim 29 |
Patent landscape implications for DFMO programs
1) How this claim set can block oral DFMO relapse-prevention dosing
If a developer runs a DFMO trial or commercial protocol that matches:
- high-risk neuroblastoma
- in remission post anti-GD2-based therapy
- dosing within 0.05 to 5 g/m²/day (or narrower dependents like 1 to 2 g/m²/day)
- oral twice-daily regimen and/or equal split dosing
- tablet dosing around 250 mg per tablet or the BSA ladder
then infringement risk is direct on the face of the claims you provided.
2) Design-around levers that are still constrained by dependents
The patent contains multiple overlapping embodiments, so single-parameter workarounds are less likely to eliminate risk. For example:
- Changing food instruction does not fully avoid coverage because claim 1 requires “independent of food intake,” but other dependents allow mixing with liquid/food.
- Switching to fixed mg dosing does not avoid coverage because claims 24-29 recast dosing in discrete daily totals and twice-daily tablets.
- Avoiding tablets by using a non-tablet oral form might evade dependents focused on tablets, but claim 1 still covers a “pharmaceutical composition comprising DFMO hydrochloride monohydrate” and is not limited to tablets.
3) The anti-GD2 linkage is a strategic gate
A competitor pathway that treats patients without anti-GD2 immunotherapy would miss a required prior-therapy element. In practice, however, many post-induction consolidation strategies for high-risk neuroblastoma include anti-GD2. That makes the anti-GD2 requirement a meaningful but not easily circumvented boundary depending on standard-of-care adoption.
Key Takeaways
- US 12,582,625 claims oral DFMO hydrochloride monohydrate methods to reduce relapse risk in high-risk neuroblastoma patients in remission with partial response (or complete response) after anti-GD2 immunotherapy.
- The core dose scope spans 0.05 to 5 g/m² total daily DFMO and is narrowed in multiple dependents to 1 to 2 g/m²/day and 1 to 3 g/m²/day.
- The claim set is reinforced by multiple dosing embodiments: BSA-based mg ladders, twice-daily equal-dose structures, and fixed daily mg totals up to 2,000 mg/day, with repeated anchoring to 250 mg tablet strength.
- Food-handling is not a simple workaround: coverage includes both food-independent twice-daily dosing and mixing with liquid/food.
- The anti-GD2 prior therapy requirement is a gating element for literal coverage, while chemotherapy is optional via dependents.
FAQs
1) Is the patent limited to tablets?
No. Tablet formulations appear in dependent claims, but the independent method claims require only oral administration of a pharmaceutical composition comprising DFMO hydrochloride monohydrate.
2) Does the patent require twice-daily dosing?
Claim 1 requires twice-daily dosing and food independence. Claim 11 is framed as total daily dose without the twice-daily structure in the independent claim text you provided, while other dependents (for example claim 16) require equal split two-dose regimens.
3) What dose formats are covered?
Both m²-normalized dose ranges (0.05 to 5 g/m²/day; narrower dependents) and absolute daily mg totals (claims 24-29) are covered, plus a BSA-to-mg ladder (claim 10).
4) Is anti-GD2 immunotherapy mandatory?
Yes. The independent methods you provided require that prior therapy comprises anti-GD2 immunotherapy.
5) What evidence standards define “partial response”?
Claim 6 defines partial response using specific criteria combining anatomical imaging, functional imaging metabolically inactive determination, and bone marrow pathology.
References
[1] United States Patent Application/Patent claims text provided in the user prompt for US Drug Patent 12,582,625 (DFMO hydrochloride monohydrate oral methods in high-risk neuroblastoma post anti-GD2 therapy).
