US Patent 11,938,132 Landscape: Scope, Claim Boundaries, and US Exclusivity/Design-Around Paths for a 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide Oral Solid

The US patent 11,938,132 is drafted as a narrow process-and-formulation performance claim set: it protects an oral pharmaceutical manufacturing method (fluidized-bed granulation using an aqueous additive solution) and resulting compositions defined by (i) a crystal-proportion window and (ii) a stringent stability limit for a specific oxidative decomposition product measured by an LC method with a defined column/gradient method, after storage under opened conditions (40°C, 75% RH) for 1 month. Dependent claims then narrow to specific excipients, tablet form factors, hemifumarate crystal proportions (NIR-determined), additive loss on drying, and quantitative ingredient ratios.

What does US 11,938,132 claim protect: method-of-manufacturing and performance-limited oral solid composition?

Core answer: US 11,938,132 claims protect a method of manufacturing an oral pharmaceutical composition comprising the specific active (or salt) 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide (and salts), combined with specified excipients, granulated in a fluidized bed using an aqueous pharmaceutical additive solution, where the resulting composition has (a) >=62% crystals of the defined active/salt relative to total active/salt and (b) no more than 0.11% of an oxidative decomposition product at a defined LC retention time, after 1 month at 40°C/75% RH opened.

Claim 1 is the infringement “spine”

Claim 1 is structured as a manufacturing method that includes a composition-recited performance requirement, which typically gives the patentee two leverage points:

Process path: fluidized bed granulation; granulation medium includes an aqueous pharmaceutical additive solution; starting material is the specified active/salt plus selected additives.
Material state + analytical spec: crystal proportion threshold and an oxidative decomposition limit measured under tightly defined LC conditions.

Key protected combination elements in Claim 1:

Active/salt identity: the exact chemical name is recited; Claim 1 also covers pharmaceutically acceptable salts.
At least one additive from a defined list: lactose, D-mannitol, anhydrous dibasic calcium phosphate, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, hydroxypropyl cellulose, hypromellose, corn starch, low-substituted hydroxypropyl cellulose, croscarmellose sodium.
Crystal proportion: >=62% crystals of the active (or salt) relative to total active.
Granulation: fluidized bed granulation using an aqueous pharmaceutical additive solution.
Stability performance:
- oxidative decomposition product with relative retention time 1.06 vs the active.
- limit: increase of <=0.11% of that oxidative decomposition product after storage (40°C, 75% RH, opened) for 1 month.
- measured by HPLC using:
  - Kinetex XB-C18, 2.6 μm, 4.6 mm × 75 mm
  - column temp 40°C
  - mobile phase A: perchlorate solution (pH 2.2)
  - mobile phase B: acetonitrile
  - sample concentration 0.8 mg/mL; standard 0.008 mg/mL; detector UV 220 nm
  - explicit gradient schedule from 0–30 minutes.

Why Claim 1 is difficult to work around

Most generic/formulation process changes fail because Claim 1 mixes:

structural limits (defined excipient list; defined process equipment/operation),
state limits (crystal proportion >=62%), and
functional limits (oxidative decomposition spec tied to a specific analytical method).

A design-around must usually break at least one leg without reintroducing an equivalent performance profile that still meets the “no more than 0.11%” spec under the claimed test conditions.

How broad are the Claim 1 “additive” and “crystal” ranges, and what do they mean for formulation design?

Excipients are open-ended within a closed list

Claim 1 requires at least one additive from the enumerated group. Dependent claims then specify common combinations (lactose/D-mannitol), but Claim 1’s additive scope is broad across the list.

Practical boundary: a manufacturer can’t use a substitute excipient outside the list and still rely on Claim 1’s “selected from the group consisting of…” language (for claims where that phrase appears). Claim 1 itself uses the list but with “at least one” additive, so a change to a different excipient not on the list likely avoids that literal element.

Crystal proportion threshold is a hard numerical limit

Claim 1: >=62% crystals of the active or salt (relative to total active).

Dependent Claim 3 refines hemifumarate crystal proportion by NIR to a broader window of 62% to 98%.

Design implications:

If a generic applicant manages an active solid form distribution below 62%, it potentially exits literal scope for that leg.
If the applicant is above 62%, it must then clear the decomposition limit (and the exact LC test) to avoid infringement under Claim 1.

What do dependent claims add: hemifumarate, NIR crystal control, tablet embodiments, and excipient drying stability?

Claims 2, 11, 12, 15: dosage form downstream steps

Claim 2 adds optional downstream operations:

drying granules to dried product,
optional magnesium stearate blending,
optional compression molding to tablet,
optional film coating to coated tablet.

Claims 11, 12, 15, 19, 23 directly tie the protected method to tablet compositions and method-produced oral pharmaceutical compositions.

Claims 3 and 4: hemifumarate-specific crystal window and NIR determination

Claim 3 specifies:

active as hemifumarate (a specific salt),
crystal proportion 62% to 98% determined by near-infrared spectroscopy (NIR).

Claim 4 parallels Claim 1’s method with the same hemifumarate and adds the drying/tableting/film-coating dependencies.

Boundary effect: if an applicant uses a different salt form (or different solid form distribution) or uses a method inconsistent with NIR-determined crystallinity windows, it may avoid those dependent claim elements (while still facing Claim 1 if the active is still within Claim 1’s “pharmaceutically acceptable salt” framing and crystalline fraction remains >=62%).

Claims 5: excipient loss-on-drying limit

Claim 5 limits an additive’s loss on drying to <=1.0% after storage under opened conditions (40°C, 75% RH) for 1 week.

This is a moisture-handling constraint on the additive material quality.

Claims 6–9: active and excipient weight fraction windows

Claim 6: active content 10% to 40% by weight of total composition.
Claim 7: additive weight content 1.5× to 4.5× the active weight content.
Claim 8: additive content 50% to 70% by weight.
Claim 9: additive content 50% to 60% by weight.

These interact with Claim 6 to define typical tablet solids composition bands.

Claims 10, 13, 14: lactose or D-mannitol and additive ratio

Claim 10: additive is lactose or D-mannitol (narrow).
Claim 13: composition additive list is limited to the same group and includes weight content via dependent Claim 14 (1.5× to 4.5× active, hemifumarate variant).
Claim 15: tablet embodiment.

Claims 16, 17, 18, 19: method-to-composition for Claim 2-dependent route

Claim 16: method-produced composition corresponding to Claim 2. Claims 17–19 then constrain excipient selection, additive weight content (1.5× to 4.5×), and tablet form.

Claims 20–23: method-to-composition for Claim 4-dependent route

Claim 20: composition produced by Claim 4 route. Claims 21–23 constrain excipient selection, additive weight ratio (for the hemifumarate salt example), and tablet form.

What is the practical scope of infringement: does the claim require meeting the oxidative decomposition test?

Answer: yes for Claim 1 literal scope, because Claim 1 includes a performance clause on oxidative decomposition product increase after the specified storage condition, quantified by the specified HPLC method with defined operational parameters.

That makes Claim 11/12/15/19/23 “composition” embodiments particularly tethered to Claim 1’s performance specification, since they are “produced by the method” that includes the oxidative decomposition constraint.

In practice for litigation: to prove infringement, a patentee typically will attempt to show:

the product is made by (or necessarily results from) the claimed fluidized-bed aqueous granulation process and
the product meets the crystallinity threshold and the oxidative decomposition increase threshold under the specific analytical method.

For defendants, this pushes disputes toward:

process evidence (granulation method, equipment, binder/additive solution being aqueous),
solid-state evidence (crystal proportion and measurement method), and
analytical evidence (whether the oxidative decomposition product peak at relative retention time 1.06 is <= the limit after the claimed stress storage).

How much of the formulation space is covered by the claims: excipient class, additive loading, and tablet form?

Coverage map (US 11,938,132):

Claim element	Scope	Hard boundaries
Active identity	Exact chemical name + pharmaceutically acceptable salts	Other APIs not covered; different salt may still be “acceptable” but dependent hemifumarate claims require hemifumarate
Additive selection	At least one from enumerated list	Excludes excipients outside enumerated set when “selected from the group consisting of” appears
Granulation method	Fluidized bed granulation	Excludes non-fluid-bed granulation for Claim 1 literal process element
Granulation medium	Aqueous pharmaceutical additive solution	Excludes non-aqueous granulation mediums
Crystal proportion	>=62% crystals (Claim 1)	Below 62% likely avoids Claim 1’s crystal threshold
Oxidative decomposition	<=0.11% increase; relative retention time 1.06	Requires meeting LC method-defined measurement result
Dosage forms	Tablet and coated tablet via optional steps	Oral solid; claims explicitly include tablet embodiments

What patents typically cluster around this kind of claim set, and where does US 11,938,132 likely sit in the estate?

The claim is highly “process analytics” heavy: a specific active oxidative degradation product with an LC retention time reference and explicit chromatographic conditions. Estates with this structure commonly include neighboring patents on:

solid form control (crystal polymorph or hydrates, salt selection like hemifumarate),
manufacturing processes (granulation, drying, binder solutions, moisture control),
stability-indicating analytical methods or acceptance criteria, and
formulation composition ranges for tablet or coated tablets.

Given Claim 3 explicitly uses hemifumarate and NIR for crystal proportion, the broader estate likely contains earlier foundational coverage on:

hemifumarate formation and/or its solid-state properties, and/or
analytical methods for crystallinity measurement.

But without the patent’s bibliographic data and the full family record, the overall estate map cannot be enumerated here.

What is the likely patent expiration and exclusivity timeline for US 11,938,132?

No timeline can be calculated from the claim text alone. Expiration depends on filing date, earliest priority, patent term adjustments, and whether the application is subject to 35 USC 154(b) adjustments. Those data are not included in the prompt; a precise exclusivity window is not derivable here.

What generic entry risks exist for an ANDA Paragraph IV strategy against products that use this active?

Key risk posture: this patent is not just about the API. It is about:

the solid-state distribution (>=62% crystals),
the exact fluidized-bed aqueous granulation process, and
a defined oxidative decomposition increase spec.

A generic company risks infringement if its product is manufactured to land within all those boundaries and if its stability profile under forced storage meets the claimed oxidative decomposition limit in the same LC window.

Most common risk points to anticipate:

If the ANDA product uses the same (or equivalent) fluidized-bed granulation with aqueous additive solution and produces a composition with >=62% crystals, it will likely be tested against the oxidative decomposition spec.
If the applicant’s stress samples, tested under the specified HPLC conditions, generate an oxidative decomposition increase above the 0.11% cap, the composition may fall outside literal scope but would still need evaluation for doctrine-of-equivalents arguments and related dependent claim fallbacks.

What are the main design-around strategies implied by the claim language?

1) Break the process leg

Switch manufacturing away from fluidized bed granulation or away from aqueous additive solution. Since Claim 1’s method requires both, changing either can avoid literal infringement.

2) Break the solid-state leg

Ensure crystal proportion is below 62% (Claim 1) or outside 62%–98% (Claim 3 hemifumarate NIR window). This requires stable control across manufacturing batches.

3) Break the analytical/spec leg

Target higher oxidative decomposition increase above the claimed <=0.11% cap, measured with the specified HPLC conditions after opened storage. This is generally not an attractive product goal, but it is a literal boundary.

4) Use excipients outside the enumerated list

When dependent composition claims use “selected from the group consisting of,” swapping to excipients outside that list is a direct escape from that dependent scope. Claim 1 still requires “at least one” from the list; using only outside excipients would miss that element.

Key Takeaways

US 11,938,132 is centered on a specific oral solid manufacturing route: fluidized-bed granulation using an aqueous pharmaceutical additive solution.
Claim 1 couples process and product performance via a defined crystallinity threshold (>=62%) and a narrowly defined LC-based oxidative decomposition limit (relative retention time 1.06; <=0.11% increase after 40°C/75% RH opened for 1 month).
Dependent claims expand specificity into hemifumarate and NIR-measured crystal windows (62%–98%), excipient moisture performance (LOD <=1.0% after 1 week), and tablet composition ranges (active 10%–40% and additive loadings 50%–70% with ratio-based constraints).
Design-arounds are most plausible by changing at least one of three critical legs: fluidized-bed aqueous granulation method, crystal proportion, or the oxidative decomposition spec under the claimed HPLC conditions.

FAQs

1) Does US 11,938,132 cover capsules or only tablets?
The claims explicitly cover oral compositions including tablets, with tablet formation and optional film coating recited; capsule-specific embodiments are not stated in the provided claim set.

2) What oxidative degradation product is referenced in Claim 1?
A specific oxidative decomposition product identified by LC relative retention time 1.06 versus the active, with an explicit <=0.11% increase limit after opened storage (40°C/75% RH, 1 month) under a defined Kinetex XB-C18 HPLC method.

3) Can a generic avoid Claim 1 by changing granulation equipment but keeping excipients the same?
Changing away from fluidized bed granulation can remove the literal process element, even if excipients match the listed group and the stability/crystallinity targets are otherwise met.

4) Is hemifumarate required for infringement?
No. Hemifumarate is required for the dependent hemifumarate-specific crystal/NIR claims (Claim 3 and derivatives). Claim 1 covers the active and pharmaceutically acceptable salts generally.

5) Does the claim require near-infrared spectroscopy for all products?
No. NIR is explicitly required for Claim 3’s hemifumarate crystal proportion determination; Claim 1 uses a crystallinity “>=62% crystals” element without mandating NIR in the provided text.

References

US Patent 11,938,132 (claim text provided in prompt).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astellas	XOSPATA	gilteritinib fumarate	TABLET;ORAL	211349-001	Nov 28, 2018		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2989534	⤷ Start Trial
China	107847500	⤷ Start Trial
Denmark	3318259	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,938,132

Which drugs does patent 11,938,132 protect, and when does it expire?

Summary for Patent: 11,938,132