United States Patent 8,492,406: Scope, Claim Map, and Follicular Lymphoma Treatment Landscape
What does US 8,492,406 claim, in practical terms?
US 8,492,406 claims a method of treating follicular lymphoma by administering a specific compound (identified in the patent as a compound of “the formula” and/or its salts/solvates/stereoisomers) in a daily dosing window of about 5 to about 50 mg/day.
The claim set is built to cover:
- Disease state: low grade, refractory, relapsed, and resistant to conventional therapy.
- Compound form: parent compound plus pharmaceutically acceptable salts, solvates, and stereoisomers.
- Stereochemistry: explicitly covers enantiomerically pure R and S isomers.
- Combination therapy: allows adding a second active agent (including a broad list and rituximab by name).
- Other modalities: allows radiation, hormonal, biological, or immunotherapy.
- Administration route and formulation: oral administration; capsule or tablet; specific excipient composition in at least one dependent claim.
- Dosing refinements: multiple dependent claims lock in discrete daily amounts and cycle regimens, including a 21-days-on/7-days-off pattern.
The net effect is a claim architecture that targets both monotherapy and combination use, and that narrows enforceable subject matter through multiple dependent claims tied to dose, schedule, and stereochemical purity.
What is the base independent claim (Claim 1) claiming?
Claim 1 is the anchor:
- Indication: treating follicular lymphoma.
- Administration: administer “about 5 to about 50 mg per day” of “a compound of the formula” (including pharmaceutically acceptable salt, solvate, stereoisomer).
Enforcement “center of gravity” is therefore:
- daily exposure in the 5 to 50 mg/day range, and
- treatment of follicular lymphoma using the patent-defined chemical entity class.
Because the independent claim is written as “about 5 to about 50 mg per day,” it typically captures a range of patient-level variability, formulation differences, and dosing adjustments, as long as the delivered daily dose remains within the “about” range.
Which dependent claims narrow disease, compound identity, and stereochemistry?
US 8,492,406 then layers multiple dependent claims:
Disease state narrowing
- Claim 2: low grade, refractory, or relapsed follicular lymphoma.
- Claim 16: relapsed, refractory, or resistant to conventional therapy.
These dependent claims matter because they:
- reduce ambiguity in product labeling and clinical positioning,
- support infringement theories based on patient subgroup inclusion criteria.
Compound form and stereochemistry narrowing
- Claims 4 to 6: pharmaceutically acceptable salt, solvate, or stereoisomer.
- Claims 7 and 8: enantiomerically pure R or S isomer.
This is a key scope lever. If the patent compound class includes stereoisomers, the R and S dependent claims can become infringement hooks even if the accused product uses only one enantiomeric form.
What combination-use scope does the patent cover?
The patent covers add-on combination therapy via:
General combination claim
- Claim 9: administer a therapeutically effective amount of a second active agent in addition to the compound of Claim 1.
Second-agent categories
- Claim 10: second agent is hematopoietic growth factor, a cytokine, or an anti-cancer agent.
Second-agent list (specific named drugs)
- Claim 11: rituximab, vinblastine, fludarabine, cyclophosphamide, vincristine, doxorubicin, prednisone, or combinations.
- Claims 12 to 14: explicitly name rituximab, vinblastine, and fludarabine.
This structure creates two practical infringement pathways for challengers:
- products that add any of the listed agents fall within the dependent claim scope, and
- products that are positioned for use with rituximab, vinblastine, or fludarabine can be specifically mapped to Claims 12-14.
Other modalities
- Claim 15: further comprises radiation therapy, hormonal therapy, biological therapy, or immunotherapy.
This extends the combinations beyond drug-on-drug pairing into broader multimodal treatment regimens.
How does the patent constrain dose and dosing schedule?
Dose and schedule are heavily over-specified across dependent claims, building multiple “landmarks” for infringement analysis.
Discrete daily dosing amounts
- Claim 19: about 10 to about 25 mg/day
- Claim 20: about 5, 10, 20, 25, 30, or 50 mg/day
- Claim 21: about 5 to about 25 mg/day
- Claims 22 and 30 to 32: about 25 mg/day, and about 5 mg/day, 10 mg/day, 15 mg/day
- Claim 29: about 5 mg/day
- Claim 32: capsule doses of 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg
These dependent claims support infringement theories based on marketed strengths and dosing instructions, particularly if a product’s label is written in these exact ranges.
Oral administration and dosage form
- Claim 17: oral administration.
- Claim 18: capsule or tablet.
These claims reduce work for enforcement by targeting route and common dosage forms.
Cyclic regimen scope
The patent explicitly claims cyclic dosing:
- Claim 23: compound administered cyclically.
- Claim 24: one cycle is four to six weeks.
- Claim 25: one cycle = 21 days of dosing followed by 7 days rest.
- Claim 26: one cycle comprises one to twenty-four cycles.
- Claim 27: 5 to 25 mg/day for days 1-21 every 28 days.
- Claim 28: 25 mg/day for 21 days followed by 7 days rest in a 28 day cycle.
These claims are important because they cover:
- the classic 21/7 schedule,
- the monthly cycle definition (28 days),
- both general cyclic use and specific dosing levels during the on-treatment window.
What formulation/excipient scope is claimed?
- Claim 33: capsule comprises the compound plus:
- lactose anhydrous
- microcrystalline cellulose
- croscarmellose sodium
- magnesium stearate
This creates a direct infringement check if a product capsule uses an overlapping excipient system. For enforcement, excipient specificity can be powerful, but it is narrower than the broader route and dose claims.
Claim landscape map (what to test for infringement)
The following table converts the claim text into “product attributes” that can be used in freedom-to-operate (FTO) screening.
| Claim element |
Scope captured in the patent |
Practical “test” for an accused product |
| Indication |
Follicular lymphoma |
Product is used for follicular lymphoma in clinical practice or labeling |
| Core daily dose |
About 5 to about 50 mg/day |
Actual prescribed daily dose (accounting for “about”) |
| Salt/solvate/stereoisomer |
Pharmaceutically acceptable salt/solvate/stereoisomer |
Product uses a covered form (including pure enantiomer) |
| Enantiomers |
Enantiomerically pure R or S |
Product provides only R or S and the compound matches the formula entity |
| Oral dosing form |
Oral administration; capsule or tablet |
Form factor and route in label or clinical protocol |
| Dose landmarks |
5/10/15/20/25/30/50 mg/day; 10-25 mg/day; 5-25 mg/day |
Dose instructions in label and real-world regimens |
| Cycle |
Cyclic dosing; 4-6 week cycles |
Protocol uses 28-day cycles or similar cycle lengths |
| 21/7 schedule |
21 days on, 7 days off |
Regimen matches 21/7 structure |
| Number of cycles |
1 to 24 cycles |
Treatment duration typical to relapsed/refractory protocols |
| Combination therapy |
Second active agent categories and named agents |
Concomitant use with rituximab/vinblastine/fludarabine etc. |
| Named combination |
Rituximab explicitly; plus chemotherapy and prednisone |
Label/indication includes these combinations |
| Modality add-ons |
Radiation/hormonal/biological/immunotherapy |
Multimodal regimen components |
| Capsule composition (narrow) |
Specific excipient list |
Formulation matches excipient inclusion (lactose MCC CCS magnesium stearate) |
How broad is the claim scope versus typical competitors?
Even without reproducing the patent’s chemical formula, the claim scope breadth is clear from dosing, indication, and regimen claims.
Broad coverage
- Any follicular lymphoma patient subset encompassed by dependent claims.
- Any administration method outside Claim 17? Claim 17 narrows to oral; Claim 1 does not explicitly say oral. But Claim 17 creates a strong narrowing for oral products.
- Combination therapy is broad under Claims 9-10 and then narrowed/enabled by a named list under Claim 11.
Targeted coverage
- Stereochemistry is specifically called out (R and S).
- Dose schedules are explicitly called out (21/7 in a 28-day cycle and specific mg/day values).
This structure typically makes the patent most enforceable against products that are marketed with these regimen details and stereospecific positioning.
US patent landscape: what can be inferred from the claim structure
Landscape signals from claim architecture
From the claim set alone, US 8,492,406 aligns with a common small-molecule oncology patent pattern:
- Core method claim with a mg/day band.
- Dependent claims that lock in regimen and combination use.
- Salt/solvate/stereoisomer coverage to prevent design-around by using different crystalline form or stereoisomer.
Common design-around pressure points this patent anticipates
- Switching from racemate to single enantiomer: the patent covers R and S explicitly.
- Switching to salt/solvate/crystal form: the patent covers salt and solvate.
- Changing route to non-oral: oral is claimed; non-oral could be argued outside dependent Claim 17, but Claim 1 is not explicitly limited to oral in the text provided.
- Avoiding specific dose landmarks: the patent contains multiple overlapping dose-dependent claims. The base Claim 1 still sets the 5-50 mg/day range.
What the landscape means for R&D and investment decisions
For formulation and clinical protocol teams
Priority screening should focus on whether the candidate regimen:
- places patients on 5-50 mg/day daily dosing,
- uses an oral capsule/tablet format,
- and matches the 21/7 schedule or one-cycle framing (28 days, 4-6 weeks).
For combination strategy teams
If a candidate therapy is paired with agents listed in Claim 11 (especially rituximab), the patent’s combination claims create direct mapping opportunities:
- clinical protocols that include rituximab in follicular lymphoma can intersect with Claim 12 via Claim 9.
Key Takeaways
- US 8,492,406 claims a follicular lymphoma treatment method using a compound of a formula in the range about 5 to about 50 mg/day.
- The patent’s strongest enforceability hinges on overlapping dependent claims that lock in:
- dose landmarks (5/10/15/20/25/30/50 mg/day and 5-25/10-25 bands),
- a 21-days-on/7-days-off 28-day cycle schedule (and up to 24 cycles),
- stereochemical purity (R or S),
- and combination use with named agents, including rituximab.
- The patent also includes salt/solvate/stereoisomer coverage and a narrow capsule excipient claim.
- The claim architecture is designed to capture both monotherapy and common multimodal regimens for relapsed/refractory follicular lymphoma.
FAQs
1) Does US 8,492,406 cover both monotherapy and combination therapy?
Yes. Claim 1 is method-of-treatment monotherapy. Claims 9-15 broaden scope to combinations with a second active agent and to additional modalities.
2) What daily dose range is the core claim targeting?
Claim 1 targets about 5 to about 50 mg per day.
3) Is the dosing schedule limited to a 21/7 pattern?
The patent includes cyclic dosing generally (Claim 23) and specifies 21 days on and 7 days rest in a 28-day cycle (Claims 25, 27, 28). The cyclic structure also covers 4 to 6 week cycles (Claim 24).
4) Does the patent explicitly cover rituximab combinations?
Yes. Claim 11 lists rituximab, and Claim 12 specifically depends on rituximab.
5) Is stereochemistry included as a limitation?
Yes. Claims 7 and 8 cover enantiomerically pure R and S isomers.
References
[1] US Patent No. 8,492,406. (n.d.). Method of treating follicular lymphoma.
