Details for Patent: 10,294,232

Which drugs does patent 10,294,232 protect, and when does it expire?

Patent 10,294,232 protects IMBRUVICA and is included in one NDA.

Protection for IMBRUVICA has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has ninety-five patent family members in thirty-four countries.

Summary for Patent: 10,294,232

Title:	Crystalline forms of a Bruton's tyrosine kinase inhibitor
Abstract:	Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
Inventor(s):	Norbert Purro, Mark S. Smyth, Erick Goldman, David D. Wirth
Assignee:	Pharmacyclics LLC
Application Number:	US16/111,014
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,294,232
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

US Patent 10,294,232: Zanubrutinib Formulation Claims, Expiration, Litigation and Patent Landscape

US Patent 10,294,232 protects oral formulations of zanubrutinib, marketed by BeiGene as Brukinsa. The patent does not claim zanubrutinib as a chemical compound. Its enforceable scope is directed to a dosage-form composition containing defined quantities of zanubrutinib, diluent, disintegrant and lubricant, with dependent claims covering hard gelatin capsules and specific excipients such as microcrystalline cellulose, magnesium stearate and croscarmellose sodium.

The patent is listed in the FDA Orange Book for Brukinsa and has a listed expiration date of March 16, 2036. The most commercially important claim is claim 29, which covers a hard gelatin capsule containing zanubrutinib, microcrystalline cellulose and magnesium stearate within the composition and concentration limitations inherited from claim 1. [1]

What drug and formulation does US Patent 10,294,232 cover?

The claimed active ingredient is zanubrutinib, also known as BGB-3111. It is a covalent Bruton tyrosine kinase inhibitor with the chemical name:

1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.

The patent covers oral pharmaceutical formulations rather than the underlying molecule. The claims encompass capsules containing 40 mg to 200 mg of zanubrutinib and a defined excipient system.

Patent	Drug	Patent type	Issue date	Listed expiration	Commercial product
US 10,294,232	Zanubrutinib	Oral formulation	May 21, 2019	March 16, 2036	Brukinsa

The formulation claims are composition-of-matter claims at the dosage-form level. A product may infringe even if it is manufactured by a different process, provided the finished formulation satisfies the claimed composition and quantitative limitations.

What are the independent claim limitations in US 10,294,232?

Claim 1 is the principal composition claim. It requires all of the following:

Limitation	Requirement
Active ingredient	Zanubrutinib
Active-ingredient amount	About 40 mg to about 200 mg
Diluents	About 40 wt% to about 50 wt%
Disintegrant	One or more disintegrating agents
Lubricant	About 0.2 wt% to about 1.0 wt%
Administration	Oral

The claim uses open-ended language because it says the formulation "comprising" the listed components. A formulation can contain additional excipients, including surfactants, glidants, coloring agents, capsule-shell materials and other processing aids, while remaining within the claim.

Claims 2 through 29 narrow claim 1 by specifying:

• approximately 140 mg of zanubrutinib;
• hard gelatin capsules;
• defined classes of diluents;
• defined classes of lubricants;
• defined classes of disintegrants;
• surfactants, including sodium lauryl sulfate;
• microcrystalline cellulose as the diluent;
• magnesium stearate as the lubricant; and
• combinations of those excipients.

What formulation is most directly protected by the patent?

The narrowest and most product-relevant formulation is claim 29. It covers a hard gelatin capsule that includes:

1. zanubrutinib in the 40 mg to 200 mg range;
2. diluent at approximately 40 wt% to 50 wt%;
3. a disintegrant;
4. lubricant at approximately 0.2 wt% to 1.0 wt%;
5. microcrystalline cellulose as the diluent; and
6. magnesium stearate as the lubricant.

Claim 28 covers the same basic combination without expressly requiring a hard gelatin capsule. Claim 27 separately identifies microcrystalline cellulose and magnesium stearate. Claim 15 identifies croscarmellose sodium as the disintegrant, while claim 20 identifies sodium lauryl sulfate as the surfactant.

The claims do not require a particular dissolution profile, particle-size distribution, polymorph, manufacturing process or release mechanism. They are principally defined by composition and concentration.

How broad are the excipient claims?

The excipient coverage is broad but hierarchical. The patent uses nested Markush groups that move from extensive lists to narrower preferred embodiments.

Diluents

Claim 3 contains the broadest diluent list, including:

• lactose;
• sucrose;
• dextrose;
• dextrates;
• maltodextrin;
• mannitol;
• xylitol;
• sorbitol;
• cyclodextrins;
• calcium phosphate;
• calcium sulfate;
• starches;
• modified starches;
• microcrystalline cellulose;
• microcellulose; and
• talc.

Claims 4 and 5 progressively narrow the group. Claim 6 limits the formulation to microcrystalline cellulose.

Microcrystalline cellulose is commercially significant because it is a conventional capsule diluent and appears in the claims closest to the marketed product configuration.

Lubricants

Claim 7 lists a broad group that includes magnesium stearate, sodium stearyl fumarate, stearic acid, talc, zinc stearate, sodium stearate, calcium hydroxide, corn starch and waxes.

Claims 8 and 9 narrow the group. Claim 10 limits the lubricant to magnesium stearate. Claims 27 through 29 combine magnesium stearate with microcrystalline cellulose.

Disintegrants

The disintegrant claims cover common pharmaceutical disintegration agents, including:

• croscarmellose sodium;
• sodium starch glycolate;
• crospovidone;
• natural starch;
• pregelatinized starch;
• methylcellulose;
• sodium alginate;
• cross-linked polymers; and
• certain clays and gums.

Claim 14 narrows the group to croscarmellose sodium, sodium starch glycolate and crospovidone. Claim 15 selects croscarmellose sodium.

Surfactants

Claims 16 through 20 are optional dependent claims. They cover formulations containing a surfactant, including sodium lauryl sulfate, polysorbates, poloxamers and ethylene oxide-propylene oxide copolymers. Sodium lauryl sulfate is the narrowest expressly claimed surfactant under claim 20.

Does the patent cover the 80 mg and 140 mg Brukinsa capsules?

The patent potentially covers both commercially relevant capsule strengths because claim 1 covers 40 mg to 200 mg of zanubrutinib, and claim 2 specifically recites approximately 140 mg.

Brukinsa is marketed in 80 mg capsules and 160 mg tablets in the United States. The 140 mg limitation in claim 2 does not necessarily define every marketed strength. Claims 1, 27, 28 and 29 do not require 140 mg and can reach other strengths within the 40 mg to 200 mg range if the excipient and percentage limitations are met. [2]

The legal analysis depends on the formulation actually approved, including:

• the quantity of zanubrutinib per dosage unit;
• the weight percentage of diluent;
• the lubricant percentage;
• the presence and identity of the disintegrant;
• the capsule or tablet dosage form; and
• whether the relevant percentages are calculated against the total formulation weight.

When does US Patent 10,294,232 lose exclusivity?

The FDA Orange Book lists March 16, 2036, as the patent expiration date. That date represents the current listed expiration for the patent in connection with Brukinsa. [1]

Exclusivity right	Status
US 10,294,232 patent	Listed
Listed expiration	March 16, 2036
FDA small-molecule exclusivity	Separate from patent term
Biosimilar exclusivity	Not applicable
Earliest ordinary generic pathway	Subject to patent certifications and litigation

The patent term is distinct from FDA regulatory exclusivity. Brukinsa received FDA approval in 2019 for mantle cell lymphoma, followed by additional indications including Waldenström macroglobulinemia, marginal zone lymphoma and chronic lymphocytic leukemia or small lymphocytic lymphoma. [2-5]

FDA approval does not itself establish freedom to market a generic product. An ANDA applicant must address applicable Orange Book patents, generally through a Paragraph III certification, Paragraph IV certification or another permitted certification.

Is US 10,294,232 an Orange Book formulation patent?

Yes. US 10,294,232 is listed in the FDA Orange Book for zanubrutinib products. Its listing gives the patent holder a mechanism to assert the patent against an ANDA applicant that makes a Paragraph IV certification.

A Paragraph IV notice alleging that the patent is invalid, unenforceable or not infringed can trigger patent litigation under the Hatch-Waxman Act. A timely infringement action can impose a 30-month stay of FDA approval, subject to statutory exceptions and court action. [6]

The patent is particularly relevant to generic capsules because the claims are directed to finished oral formulations. A generic applicant cannot avoid formulation-patent exposure merely by using a different manufacturing site or a different granulation process if the final product contains the claimed components in the claimed ranges.

Which companies are challenging US Patent 10,294,232?

No publicly established Paragraph IV litigation or settlement involving US 10,294,232 is identified in the cited FDA and public patent records reviewed for this analysis.

The absence of a publicly reported challenge does not eliminate future ANDA risk. Zanubrutinib remains a small-molecule product, so generic companies can use the ANDA pathway. The patent's Orange Book listing makes a Paragraph IV challenge commercially available before the listed expiration date.

Potential challengers would likely include:

• large generic companies with oncology portfolios;
• contract manufacturers seeking a zanubrutinib supply position;
• regional generic companies targeting markets outside the United States; and
• companies developing alternative BTK inhibitor products rather than direct generic copies.

What patent litigation affects Brukinsa?

The principal litigation risk for this patent is future Hatch-Waxman litigation rather than biosimilar litigation. Zanubrutinib is a chemically synthesized small molecule, not a biologic. Biosimilar approval under section 351(k) of the Public Health Service Act does not apply.

The key litigation issues would include:

1. Claim construction. The court would interpret "about 40 mg to about 200 mg," "about 40 wt% to about 50 wt%" and "about 0.2 wt% to about 1.0 wt%."
2. Percentage calculation. The parties could dispute whether the percentages are measured against the total fill weight, the active-plus-excipient weight or another formulation basis.
3. Infringement by equivalents. A product outside a numerical range may still create an equivalents dispute, although prosecution history and numerical-range precedent would matter.
4. Obviousness. An ANDA applicant could argue that conventional excipients and capsule technology render the formulation obvious.
5. Written description and enablement. The broad Markush lists and numerical ranges could be challenged if the specification does not adequately support the full genus.
6. Indefiniteness. The term "about" could be contested, particularly where a commercial product is close to a claim boundary.
7. Double patenting. Any related formulation or compound patents could raise obviousness-type double-patenting issues.

The claims are strongest when a product closely matches the specific combination of zanubrutinib, microcrystalline cellulose, magnesium stearate, a conventional disintegrant and a hard gelatin capsule. They are more vulnerable when an accused product uses a materially different dosage form or falls outside the specified concentration ranges.

How strong is the patent estate for zanubrutinib?

US 10,294,232 is an important but technically narrow component of the broader zanubrutinib estate.

Estate category	Relevance to generic entry
Compound patents	Can block manufacture and sale of zanubrutinib itself
Formulation patents	Can block particular capsule, tablet or excipient combinations
Method-of-use patents	Can cover treatment of specific hematologic cancers
Manufacturing patents	Can increase supply-chain and process-design barriers
Orange Book patents	Can trigger ANDA certification and Hatch-Waxman litigation
Regulatory exclusivity	Can delay approval independently of patent validity

The formulation patent has meaningful commercial value because it covers a conventional oral dosage form that may be difficult to design around without changing excipient ratios, dosage form or release characteristics. Its weakness is that many listed excipients are routine in pharmaceutical development, creating a potential obviousness challenge.

The patent does not appear, from the supplied claims, to cover:

• the chemical identity of zanubrutinib by itself;
• every oral dosage form containing zanubrutinib;
• every 80 mg, 140 mg or 160 mg dosage unit;
• injectable formulations;
• liquid formulations;
• transdermal products;
• sustained-release systems that do not satisfy the composition limitations; or
• a manufacturing process independent of the claimed final composition.

What design-around strategies could avoid the formulation patent?

A generic or alternative manufacturer could evaluate several design-around paths:

Use a different dosage form

A tablet, oral solution, suspension, multiparticulate system or other dosage form may avoid claims expressly limited to capsules. This strategy does not avoid claim 1 automatically because claim 1 requires oral administration but does not require a capsule. A non-capsule product would still need to avoid the claim 1 composition and concentration requirements.

Change the diluent

Replacing microcrystalline cellulose with lactose, mannitol or another diluent may avoid claims 6 and 27 through 29. It would not necessarily avoid claims 1, 3, 4 or 5.

Change the lubricant

Replacing magnesium stearate with sodium stearyl fumarate or another lubricant may avoid claims 10 and 27 through 29. The product could remain exposed to broader claims that list multiple lubricant alternatives.

Adjust the quantitative ranges

Moving the diluent below 40 wt% or above 50 wt%, or moving the lubricant outside 0.2 wt% to 1.0 wt%, may create a noninfringement position. The term "about" makes proximity to the boundaries legally sensitive.

Use a different disintegrant

A formulation using a disintegrant outside the listed groups may avoid the dependent claims. It would still need to be assessed against claim 1, which requires a disintegrant but does not limit claim 1 to a closed list.

Remove the optional surfactant

Claims 16 through 20 require a surfactant. Removing sodium lauryl sulfate or another surfactant avoids those dependent claims but does not avoid claim 1.

What method-of-use patents protect Brukinsa indications?

US 10,294,232 is not a method-of-use patent. It does not claim treatment of mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, CLL or SLL. Its claims are directed to the pharmaceutical formulation.

Method-of-use patents may create separate barriers for indication-specific generic labeling. An ANDA applicant could use a "skinny label" that omits patented indications, but the strategy would depend on the scope of the relevant method claims, FDA labeling, prescribing practices and induced-infringement risk. [2,6]

For Brukinsa, formulation-patent exposure and method-of-use exposure should be analyzed separately. A generic applicant may avoid a method claim while still infringing a composition claim, or may avoid the formulation patent while remaining exposed to an indication patent.

What is the FDA regulatory status of Brukinsa?

The FDA approved Brukinsa, supplied by BeiGene USA, Inc., as an oral BTK inhibitor. FDA approvals include:

Milestone	Date
Initial approval for mantle cell lymphoma	November 14, 2019
Waldenström macroglobulinemia approval	August 31, 2021
Marginal zone lymphoma approval	September 14, 2021
CLL/SLL approval	January 19, 2023

The product is available in capsule and tablet presentations. FDA labeling identifies zanubrutinib as the active ingredient and provides dosing regimens that vary by indication. [2-5]

What is the commercial exposure from this patent?

Brukinsa has become a major commercial product in BeiGene's hematology portfolio. Global Brukinsa revenue exceeded $1 billion in 2023 and continued to grow in 2024, driven by use in CLL/SLL, Waldenström macroglobulinemia and other B-cell malignancies. [7,8]

The formulation patent therefore has material revenue-protection value through the mid-2030s. Its economic importance is greater for a direct generic capsule than for a competing BTK inhibitor. Competitors such as Imbruvica, Calquence and Jaypirca compete therapeutically but do not automatically provide a design-around to US 10,294,232 because they contain different active ingredients and are not generic zanubrutinib products. [9-11]

Key Takeaways

• US 10,294,232 is a zanubrutinib oral formulation patent, not a compound patent.
• Claim 1 requires 40 mg to 200 mg of zanubrutinib, 40 wt% to 50 wt% diluent, a disintegrant and 0.2 wt% to 1.0 wt% lubricant.
• Claims 27 through 29 focus on microcrystalline cellulose, magnesium stearate and hard gelatin capsules.
• The patent is listed in the FDA Orange Book with a March 16, 2036, expiration date.
• The patent can create ANDA exposure for a generic capsule even if the generic manufacturer uses a different process.
• No publicly established Paragraph IV litigation or settlement involving this patent is identified in the cited records.
• Biosimilar litigation is not relevant because zanubrutinib is a small-molecule drug.
• The main validity risks are obviousness, numerical-range interpretation, written description, enablement and indefiniteness.
• The most credible design-around routes involve dosage form, excipient selection and formulation percentages.
• Brukinsa's expanding indications and more than $1 billion in annual revenue make the patent commercially significant through the remaining term.

FAQs

Does US 10,294,232 cover zanubrutinib itself?

No. The patent covers pharmaceutical formulations containing zanubrutinib. Separate compound and use patents must be analyzed to determine protection for the active ingredient and oncology indications.

Does a zanubrutinib tablet infringe US 10,294,232?

Potentially. Claim 1 is not limited to capsules and requires only oral administration. A tablet could infringe if it contains the claimed zanubrutinib amount, diluent range, disintegrant and lubricant range.

Can a generic avoid the patent by using lactose instead of microcrystalline cellulose?

Possibly, but not automatically. Lactose may avoid claims limited to microcrystalline cellulose while remaining within broader claims that list lactose among the permissible diluents.

Is a 160 mg Brukinsa product outside the patent because claim 2 recites 140 mg?

No. Claim 2 is a dependent claim limited to approximately 140 mg. Claim 1 covers a broader 40 mg to 200 mg range, subject to the other formulation limitations.

Does FDA approval of Brukinsa prove that the patent is valid?

No. FDA approval and Orange Book listing establish regulatory status, not patent validity. Validity would be determined in patent litigation or a post-grant proceeding.

References

1. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
2. U.S. Food and Drug Administration. (2024). Brukinsa (zanubrutinib) prescribing information. BeiGene USA, Inc.
3. U.S. Food and Drug Administration. (2019, November 14). FDA approves zanubrutinib for mantle cell lymphoma. FDA.
4. U.S. Food and Drug Administration. (2021, August 31). FDA grants accelerated approval to zanubrutinib for Waldenström macroglobulinemia. FDA.
5. U.S. Food and Drug Administration. (2023, January 19). FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. FDA.
6. U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).
7. BeiGene, Ltd. (2024). 2023 annual report. BeiGene.
8. BeiGene, Ltd. (2025). 2024 annual report. BeiGene.
9. U.S. Food and Drug Administration. (2024). Imbruvica (ibrutinib) prescribing information. FDA.
10. U.S. Food and Drug Administration. (2024). Calquence (acalabrutinib) prescribing information. FDA.
11. U.S. Food and Drug Administration. (2024). Jaypirca (pirtobrutinib) prescribing information. FDA.

Drugs Protected by US Patent 10,294,232

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pharmacyclics Llc	IMBRUVICA	ibrutinib	CAPSULE;ORAL	205552-002	Dec 20, 2017		RX	Yes	No	10,294,232*PED				Y
Pharmacyclics Llc	IMBRUVICA	ibrutinib	CAPSULE;ORAL	205552-001	Nov 13, 2013		RX	Yes	Yes	10,294,232*PED				Y

International Family Members for US Patent 10,294,232

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	092844
Argentina	118108
Australia	2013271918
Australia	2016250445
Australia	2018211201
Australia	2018211216
Australia	2020239751