Executive summary
US Patent 10,450,379 centers on a rituximab retreatment regimen in rheumatoid arthritis (RA) patients with prior inadequate response to one or more anti-TNF biologics, specifically: an initial two-dose 1000 mg IV rituximab course (days 1 and 15), then retreatment with the same dosing at weeks 24 to 40 in patients with active disease (DAS28-ESR ≥ 2.6), with radiographic evidence (at least about 52 weeks) that structural joint damage progression is slowed or halted. The claim set is tightly anchored to (1) patient selection (anti-TNF inadequate responders; DAS28-ESR threshold), (2) dosing schedule (2 × 1000 mg IV on days 1 and 15; retreat window weeks 24–40), (3) outcome timeframe (about 52 weeks), and (4) optional co-therapies (MTX and corticosteroid, including a specified methylprednisolone premed dose) and optional radiographic metrics (TSS/no progression). This combination narrows generic “at-risk” designs largely to rituximab retreatment strategies that replicate the schedule and disease-activity trigger, not to rituximab use in general. The enforceability risk is highest where prior art already taught rituximab retreatment at ~24-week intervals in anti-TNF inadequate responders with DAS28 gating and where radiographic endpoints (TSS/Sharp scores) were already used to demonstrate structural protection.

US Patent 10,450,379: What claims protect rituximab retreatment for rheumatoid arthritis anti-TNF inadequate responders?

US 10,450,379 claims methods of treating RA joint damage by administering rituximab using a defined initial course and a retreatment course, with a defined disease-activity criterion and a structural outcome lasting at least about 52 weeks.

What is the core independent claim scope (Claim 1)?

Claim 1 (method) requires all of the following elements:

Patient population: subject with RA who showed inadequate response to one or more anti-TNF inhibitors.
Prior response: subject previously received rituximab as two 1000 mg IV doses 14 days apart and responded to that course.
Retreatment regimen: administer a further course of two 1000 mg IV rituximab doses given 14 days apart, administered at weeks 24 to 40.
Disease-activity gate for retreatment: at retreatment, subject has active disease based on DAS28-ESR ≥ 2.6.
Structural outcome/time-at-risk: the method slows or halts progression of structural joint damage for at least about 52 weeks.

This claim is not just “rituximab in RA”; it is rituximab retreatment at a specified time window with a specified clinical disease-activity threshold and a structural endpoint over ~52 weeks.

How do dependent claims narrow Claim 1?

Claims 2–4 add specific timing and add-on therapy:

Claim 2: retreatment course at about week 24 (tightens weeks 24–40).
Claim 3: further includes methotrexate (MTX).
Claim 4: adds corticosteroid prior to each rituximab administration.

Claims 5–13 broaden the description style but keep the same regimen logic; they emphasize:

initial course details: 1000 mg IV on days 1 and 15
retreat details: 1000 mg IV on days 1 and 15 at weeks 24–40
disease gate: DAS28-ESR ≥ 2.6
structural test: radiographic measurement comparing to baseline prior to initial administration, with effectiveness demonstrated
optional MTX (Claims 6–7), corticosteroid (Claims 8–9), and radiographic test specifics (TSS in Claims 10–11).
timing at about week 24 (Claims 12–13).

Claims 14–18 similarly restate the overarching “slowing/halting structural progression for at least 52 weeks” concept with gating.

What radiographic element matters (Claims 10–11)?

Claim 10: radiographic test measures total modified Sharp score (TSS).
Claim 11: includes no progression vs baseline by TSS.

This creates a potentially strong evidence hook: defendants cannot easily avoid infringement by using different endpoints unless the claim language is not satisfied.

What regimen premedication is claimed (Claim 9)?

Claim 9: corticosteroid includes 100 mg IV methylprednisolone prior to each rituximab administration.

This is a dosing/route-specific limitation; if a competing regimen uses different premed dosing, it may avoid dependent-claim infringement (but could still fall under independent claims if those do not require the 100 mg dose).

How broad are the “weeks 24 to 40” and “DAS28-ESR ≥ 2.6” limitations for infringement risk?

The two most strategically important claim limitations for design-around are:

Retreatment window: weeks 24 to 40 (and “about week 24” in narrower dependents).
Disease activity threshold: DAS28-ESR ≥ 2.6.

What retreat timing latitude exists?

Claim 1 permits retreatment within weeks 24–40; therefore, an administration at, for example, week 30 is within the window and still potentially infringes if other requirements are met. Dependent Claim 2/12/13/18 narrows to “about week 24,” which is easier to avoid by shifting retreatment timing away from that narrower point, but Claim 1 still covers retreatment across most of the 24–40 span.

What disease-activity gate restricts eligibility?

Claim language requires retreatment occurs when the subject has active disease based on DAS28-ESR ≥ 2.6. That threshold likely maps to how retreatment was defined in clinical protocols. A competitor regimen that waits until DAS28-ESR dips below 2.6 or uses a different scoring cut-off may avoid the gate, but only if the clinician can document that the subject did not meet the threshold at retreatment.

How do these limitations affect “generic rituximab” strategies?

Even if biosimilar versions of rituximab are used, infringement concerns do not disappear because the claims are method-of-treatment claims. Any biosimilar retreatment that mirrors the schedule, prior response history, and disease-activity criterion remains vulnerable.

What prior art is most likely to challenge US 10,450,379’s novelty or obviousness?

US 10,450,379’s claim framing strongly resembles standard-of-care clinical trial logic: retreatment at around six months with a disease activity threshold, plus radiographic structural endpoints.

What “most likely” prior art categories attack the claims?

Without asserting specific references not provided in the prompt, the most likely invalidity themes in this fact pattern are:

Rituximab retreatment protocols in RA already teaching:
- anti-TNF inadequate responders
- initial two-dose 1000 mg course 14 days apart
- retreatment at ~24-week or “every 24 weeks” intervals
- disease activity gating using DAS28 (including DAS28-ESR cut-offs)
Radiographic structural progression endpoints already used in RA to show slowed progression:
- total modified Sharp score (TSS)
- comparison to baseline and “no progression” conclusions over ~52 weeks
Combination background therapy:
- MTX co-administration as standard
- corticosteroid premedication prior to rituximab infusions with specified methylpred dosing

Where the claims are most defensible

The combination of:

anti-TNF inadequate responders + prior response to initial rituximab course
retreatment window weeks 24–40
DAS28-ESR ≥ 2.6 at retreatment
and structural slowing/halting for at least about 52 weeks

creates a narrower intersection than “rituximab in RA” or “retreating RA with rituximab.” The defense usually relies on a specific synergy of limitations and a non-obvious clinical finding that the retreatment strategy slows/halts radiographic damage over the stated period.

Where the claims are most vulnerable

A challenge succeeds if earlier studies or publications already disclosed the same or a closely overlapping retreatment protocol with radiographic endpoints. The vulnerability increases if:

retreatment timing is already within weeks 24–40 (or effectively disclosed as “around six months”), and
DAS28-ESR gating at or near 2.6 (or a clearly equivalent threshold) is disclosed, and
TSS/modified Sharp scoring over about 52 weeks is already part of the evidence plan.

Does US 10,450,379 function like a scheduling patent, a patient-selection patent, or an outcome patent?

It is best characterized as a hybrid:

Scheduling and patient-selection core

The regimen structure is scheduling + selection:

initial course: 2 × 1000 mg IV rituximab on days 1 and 15
retreat course timing: weeks 24–40
selection at retreat: DAS28-ESR ≥ 2.6
prior response: responded to initial rituximab course

Outcome anchor

The method requires slowing or halting structural joint damage progression for at least about 52 weeks. That is an outcome/time claim element, not just a dosing parameter.

Litigation implication

Outcome language can complicate enforcement because proving that the accused method “slows or halts” progression for at least about 52 weeks may require evidence (radiographs, TSS change) linked to the accused regimen. However, if the method is practiced under the same clinical evidence base, plaintiffs typically use trial-like evidence and prescribing documentation.

What method variations could plausibly avoid infringement of US 10,450,379?

Design-around analysis focuses on breaking at least one limitation of the independent claim (Claim 1), then selectively targeting dependent claims.

Timing around the retreat window

Avoid retreatment within the weeks 24–40 window by using significantly earlier (<24) or later (>40) retreatment.

A narrow “about week 24” strategy is insufficient for avoiding Claim 1 infringement because Claim 1 covers weeks 24–40 broadly.

Disease-activity gate manipulation

Ensure retreatment is not given when the patient has DAS28-ESR ≥ 2.6 at the time of retreatment.
Use an alternative disease-activity threshold not meeting that criterion at dosing time.

This is harder in practice than timing because clinical decisions rely on measured DAS28-ESR.

Remove the “prior response” element from the claim path

Claim 1 requires the subject had responded to the initial course. Avoiding “responded to prior course” can reduce infringement risk by selecting retreatments only for non-responders. That is a different clinical strategy, but it matters legally because it breaks an express limitation.

Limitations in dependent claims

Avoid corticosteroid “prior to each administration,” or alter steroid regimen to avoid the specific 100 mg IV methylprednisolone limitation (dependent Claim 9).
Avoid MTX co-administration if clinically appropriate. Dependent claims require MTX explicitly (Claims 3, 6, 15).

These changes do not necessarily avoid Claim 1, since Claim 1 does not require MTX or a specified steroid dose.

What Orange Book status or FDA exclusivity affects enforcement strategy?

US 10,450,379 is a method-of-use patent tied to rituximab. The legal relevance is that FDA listings (Orange Book for small molecules; biologics pathway uses BLA patent listings rather than Orange Book) can trigger litigation frameworks for biosimilars.

Because the prompt does not provide:

the specific BLA reference product,
the biologics patent listing identifiers,
or any FDA patent listing numbers for this patent,

no reliable “Orange Book status” or biosimilar litigation posture can be stated from the information provided.

(Under the task constraints, no further status claims are included.)

How strong is the patent estate for this rituximab retreatment concept beyond US 10,450,379?

A robust estate analysis requires:

other related US applications and family members,
continuations/divisionals,
co-pending amendments,
and other jurisdictions.

The prompt provides only US 10,450,379 and the asserted claims. No claim-family set, priority date, or continuations are provided, so an estate-strength analysis is not supportable from the available data.

Claim-by-claim risk matrix (practical infringement sensitivity)

Below is a structured view of how claims behave in real-world practice. “High sensitivity” means small protocol changes can remove the element; “Medium” means it is harder to change without changing clinical practice.

Claim	Key additional limitation(s) beyond the independent concept	Practical sensitivity	Primary design-around lever
1	anti-TNF inadequate responder; responded to initial 2 × 1000 mg (days 1 & 15); retreat weeks 24–40; DAS28-ESR ≥ 2.6 at retreat; slows/halts structural progression ≥ ~52 weeks	High	change retreat window, change disease-gate threshold, treat only non-responders, or fail the structural endpoint
2	retreat at about week 24	Medium	retreat outside “about week 24” but still could fall under Claim 1 if within 24–40
3	adds MTX	Medium	omit MTX (if clinically/label-allowed)
4	adds corticosteroid prior to each rituximab	High	omit steroid premed (if allowed) or change practice to remove “prior to each”
5	recites same regimen plus radiographic test after at least about 52 weeks; baseline comparison	Medium-High	change radiographic protocol or endpoint measure (but could still meet core “slow/halting” limitation)
6	adds MTX	Medium	omit MTX
7	MTX dose 10–25 mg/week	Medium	use outside range
8	adds corticosteroid	High	omit or change steroid requirement
9	100 mg IV methylprednisolone prior to each	High	change steroid dose/regimen
10	radiographic test measures TSS	Medium	use non-TSS scoring (may still meet “structural joint damage” depending on proof)
11	no progression vs baseline by TSS	High	aim for progression or use alternative radiographic evidence to avoid “no progression”
12	further course at about week 24	Medium	retreat outside “about week 24”
13	Claim 11 + about week 24	High	retreat outside “about week 24” or ensure “progression” per measured endpoint
14	restates “slowing/halting structural damage ≥ 52 weeks” with anti-TNF inadequate response and retreat course	High	same levers as Claim 1
15	adds MTX	Medium	omit MTX
16	adds corticosteroid prior to each	High	omit or alter premed
17	halts progression for at least 52 weeks	High	ensure progression (hard commercially)
18	further course about week 24	Medium	retreat outside “about week 24”

Litigation, settlements, and Paragraph IV biosimilar challenges: what patent assertions are implicated?

No litigation docket, asserted claim numbers, or biosimilar competitors are included in the prompt. Without those identifiers, a credible litigation-map cannot be produced.

Key Takeaways

US 10,450,379 is a method patent focused on rituximab retreatment in RA anti-TNF inadequate responders who responded to the initial rituximab course, with retreat at weeks 24–40 and DAS28-ESR ≥ 2.6 gating.
The enforceability hinge is the intersection of regimen timing, disease-activity threshold, prior response history, and a radiographic/structural outcome over ~52 weeks.
Design-around risk is highest for competitors replicating the same retreatment schedule and DAS28-ESR gating; lower for those treating outside the window, gating retreatment differently, or avoiding the prior-response population framing.
Dependent claims add operational specificity (MTX, steroid timing/dose, TSS/no progression), offering additional “escape hatches” through protocol variation, though they do not eliminate exposure under Claim 1.

FAQs

1) What exact rituximab dosing schedule does US 10,450,379 require for initial and retreatment courses?
Two 1000 mg IV doses given 14 days apart for the initial course (days 1 and 15), and the same two-dose course for retreatment given 14 days apart during weeks 24 to 40.

2) What disease activity measure gates whether retreatment is given?
DAS28-ESR with a threshold of ≥ 2.6 at the time of retreatment.

3) Is MTX required to infringe US 10,450,379?
No. MTX is required only for dependent claims (for example Claims 3, 6, and 15). Independent Claim 1 does not require MTX.

4) Does the patent depend on using TSS to prove infringement?
TSS is specified in dependent Claim 10. Independent claim language focuses on slowing/halting structural joint damage progression for at least about 52 weeks, with Claim 5 adding a radiographic test concept.

5) What time period must be shown to protect the method under the claim language?
The method requires slowing or halting progression of structural joint damage for at least about 52 weeks.

References (APA)

No sources were cited because the prompt does not include bibliographic details, FDA/BLA listing data, prosecution history, related family members, or external documents needed to support specific citations.

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	November 26, 1997	10,450,379	2039-04-15
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	February 19, 2002	10,450,379	2039-04-15
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	June 22, 2017	10,450,379	2039-04-15
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
Argentina	058838	⤷ Start Trial
Australia	2006315498	⤷ Start Trial
Brazil	PI0618577	⤷ Start Trial
Canada	2627886	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 10,450,379

Summary for Patent: 10,450,379