US Patent 10,239,883: Acalabrutinib Claims, Patent Scope, Expiry and Generic Risk
US Patent No. 10,239,883 protects methods of treating chronic lymphocytic leukemia (CLL) with acalabrutinib, marketed by AstraZeneca as Calquence. The patent claims the active compound, its pharmaceutically acceptable salts, pharmaceutical compositions, oral administration, tablets, capsules, suspensions, and a broad weight-based dose range. The patent is a method-of-treatment patent rather than a basic compound patent.
The claims do not require a particular CLL stage, biomarker, prior therapy, treatment line, response level, combination partner, or dosing schedule. That breadth gives the patent potential relevance against generic acalabrutinib products labeled for CLL, although infringement depends on the approved label, product instructions, and the scope of any enforceable patent term.
What drug does US Patent 10,239,883 protect?
The claimed compound is acalabrutinib, also known as ACP-196.
| Attribute |
Detail |
| Generic name |
Acalabrutinib |
| Brand |
Calquence |
| Drug class |
Covalent Bruton's tyrosine kinase inhibitor |
| Molecular target |
Bruton's tyrosine kinase, or BTK |
| Chemical class |
Imidazo[1,5-a]pyrazine derivative |
| Warhead |
But-2-ynoyl, or butynamide, group |
| Primary patent holder and marketer |
AstraZeneca, following acquisition of Acerta Pharma |
| FDA dosage forms |
Tablets and capsules |
| FDA CLL indication |
Adult patients with CLL or small lymphocytic lymphoma |
| FDA approval for CLL |
November 21, 2019 |
| Original FDA approval |
October 31, 2017, for mantle cell lymphoma |
The chemical structure in claim 1 is the covalent BTK inhibitor acalabrutinib. Its but-2-ynoyl group reacts irreversibly with cysteine 481 in BTK. The imidazopyrazine and substituted benzamide regions provide target-binding interactions, while the chiral pyrrolidine substituent is part of the claimed stereochemical configuration. [1, 2]
What are the legal elements of claim 1?
Claim 1 requires four core elements:
- A human subject.
- Chronic lymphocytic leukemia.
- Administration of acalabrutinib or a pharmaceutically acceptable salt.
- Treatment of the disease.
The claim is an affirmative method-of-treatment claim. It does not claim acalabrutinib as a chemical substance in the abstract, a manufacturing process, or a particular pharmaceutical composition.
The compound limitation is structurally specific. The claim uses the full chemical name and covers the stated stereoisomer. It also covers pharmaceutically acceptable salts. It does not expressly claim every possible stereoisomer, regioisomer, metabolite, prodrug, analog, or polymorph unless those forms fall within the claimed compound or salt language under applicable claim construction.
What does “pharmaceutically acceptable salt” cover?
The salt language expands claim 1 beyond the neutral form of acalabrutinib. A salt generally must retain the active compound’s relevant pharmaceutical identity and be suitable for administration. The claim can therefore reach a generic product supplied as a qualifying salt rather than as the free compound.
The claim does not automatically cover every formulation containing an acalabrutinib-related impurity, metabolite, prodrug, or different chemical derivative. Those products would require a separate infringement analysis.
How do claims 2 through 11 expand patent coverage?
Claims 2 through 11 add composition and administration limitations.
| Claims |
Added limitation |
Commercial relevance |
| 2 |
Compound is present in a pharmaceutical composition |
Reaches a finished dosage product |
| 3 |
Composition includes one or more pharmaceutically acceptable auxiliaries |
Covers excipients and other formulation ingredients |
| 4-5 |
Oral administration |
Aligns with Calquence’s oral route |
| 6-7 |
Tablet |
Reaches acalabrutinib tablet products |
| 8-9 |
Capsule |
Reaches acalabrutinib capsule products |
| 10-11 |
Suspension |
Covers oral suspension presentations if marketed |
“Pharmaceutically acceptable auxiliaries” is broad formulation language. It may include excipients, carriers, binders, lubricants, disintegrants, stabilizers, coatings, suspending agents, and related pharmaceutical ingredients.
The tablet, capsule, and suspension claims are narrower than claim 1 but commercially important. A generic applicant seeking approval for an oral acalabrutinib tablet or capsule would face a direct product-label and method-of-use analysis. A suspension claim matters only if a covered suspension is made, sold, or induced for CLL treatment.
What dose range does US 10,239,883 cover?
Claim 12 covers administration of acalabrutinib in an amount of 0.0001 to 25 mg per kilogram of body weight.
| Item |
Claimed range |
| Lower limit |
0.0001 mg/kg |
| Upper limit |
25 mg/kg |
| FDA-approved adult tablet dose for CLL |
100 mg twice daily |
| FDA-approved adult capsule dose for CLL |
100 mg twice daily |
For a 70-kg adult, the claimed range corresponds to approximately 0.007 to 1,750 mg per administration if the claim is read as a per-administration amount. The claim does not state whether the range is per dose, per day, or another dosing interval. That issue can affect claim construction.
The FDA-approved 100-mg dose is approximately 1.43 mg/kg for a 70-kg adult and falls within the literal numerical range. The approved Calquence regimen therefore aligns with the dose limitation in claim 12. [2]
Why are claims 13 and 14 included?
Claims 13 and 14 restate the active-substance alternatives:
- Claim 13 covers administration of acalabrutinib itself.
- Claim 14 covers administration of a pharmaceutically acceptable salt.
These claims create separately numbered fallbacks for the free compound and salt form. They do not add a disease, route, dose, formulation, or patient-selection limitation beyond claim 1.
What is the patent type and scope?
US 10,239,883 is principally a method-of-treatment patent covering CLL use of acalabrutinib. Its scope can be summarized as follows:
| Scope category |
Covered by US 10,239,883? |
| Acalabrutinib treatment of CLL |
Yes |
| Acalabrutinib salts for CLL |
Yes |
| Oral CLL treatment |
Yes, under claims 4-11 |
| Tablets |
Yes, under claims 6-7 |
| Capsules |
Yes, under claims 8-9 |
| Suspensions |
Yes, under claims 10-11 |
| Claimed dose range |
Yes, under claim 12 |
| Combination with obinutuzumab or venetoclax |
Not expressly required |
| Specific CLL genetic subgroup |
Not required |
| Relapsed or refractory CLL |
Not required |
| Manufacturing process |
No express process claim |
| Active pharmaceutical ingredient per se |
Not as a standalone composition claim |
| Non-CLL indications |
Not covered by the claims provided |
The absence of a combination limitation is commercially significant. A CLL treatment using acalabrutinib alone or with another agent can potentially satisfy claim 1 if the other limitations are met. The claim also does not require first-line treatment, relapsed disease, a defined treatment duration, or a particular clinical response.
When does US Patent 10,239,883 expire?
The patent’s enforceable term is determined by its earliest effective nonprovisional priority date, any patent-term adjustment, terminal disclaimer, patent-term extension, and applicable USPTO term records. The nominal patent term is generally 20 years from the relevant U.S. nonprovisional filing date under 35 U.S.C. §154.
US 10,239,883 issued on March 26, 2019. Its term should be assessed together with the continuation and divisional members in the acalabrutinib patent family. The patent number alone does not establish a separate 20-year term beginning on its issue date. [1, 3]
For commercial planning, the relevant date is not only the expiration date of US 10,239,883. A generic applicant must also clear the Orange Book-listed acalabrutinib compound, formulation, method-of-use, and other patent barriers. Later-expiring patents can prevent practical market entry after this patent expires.
What is the Orange Book status of acalabrutinib?
Calquence is listed in the FDA Orange Book. AstraZeneca’s listed patent estate includes patents directed to the active ingredient, formulations, methods of treatment, and related pharmaceutical protections. The exact list and expiration dates can change as FDA listings are updated. [3]
The Orange Book creates the statutory framework for patent certifications by abbreviated new drug application applicants:
- Paragraph I: no patent information is listed.
- Paragraph II: the listed patent has expired.
- Paragraph III: the applicant will wait until expiration.
- Paragraph IV: the listed patent is invalid, unenforceable, or will not be infringed.
A Paragraph IV notice for an Orange Book-listed Calquence patent can trigger patent litigation under 21 U.S.C. §355(j)(5)(B)(iii) and 35 U.S.C. §271(e)(2). A timely infringement action can impose a 30-month stay on FDA approval, subject to statutory exceptions and court developments. [4, 5]
Which patents are most relevant to acalabrutinib generic entry?
The relevant patent estate has several layers.
Compound patents
Compound patents protect acalabrutinib and related imidazopyrazine BTK inhibitors. These patents are generally the strongest barrier because they can apply to the active ingredient regardless of tablet or capsule design.
Method-of-use patents
US 10,239,883 is in this category. It targets the use of acalabrutinib to treat CLL. Method claims can create an induced-infringement risk when a generic label instructs physicians to use the product for the patented indication.
Formulation patents
Formulation patents can cover particle size, solid forms, excipient combinations, release characteristics, stability, dissolution, or specific dosage forms. A generic applicant may attempt to design around a formulation claim while still selling the same active ingredient.
The claims provided for US 10,239,883 are broad enough to cover ordinary tablets and capsules but do not require a specific excipient, dissolution profile, coating, crystalline form, or release mechanism.
Manufacturing and process patents
Process patents may cover synthesis steps, intermediates, purification, chiral resolution, crystallization, or production of a particular solid form. They can remain relevant even when a compound or method patent expires, especially if the generic manufacturing route practices a protected process.
How strong is the patent estate for acalabrutinib?
The estate is strongest where three conditions overlap:
- The generic product contains acalabrutinib.
- The label includes CLL or another patented indication.
- The product uses a listed tablet, capsule, salt, or formulation configuration.
US 10,239,883 has several strengths:
- It identifies the approved active compound precisely.
- It covers pharmaceutically acceptable salts.
- It covers oral administration.
- It reaches tablets, capsules, and suspensions.
- It does not depend on a narrow biomarker or treatment line.
- Its dose range encompasses the FDA-approved CLL dose.
- It may apply to monotherapy and combination therapy because no combination limitation appears in the claim.
Its principal limitation is that it is not a standalone composition-of-matter claim. A product containing acalabrutinib may face this patent through its labeled CLL use, but a generic applicant may seek a skinny label excluding the patented indication. The success of that strategy depends on the remaining approved indications, label language, promotional conduct, physician use, and the scope of other listed patents.
What generic launch scenarios exist for Calquence?
| Scenario |
Entry risk |
| Launch after all Orange Book patents expire |
Lowest litigation risk |
| Paragraph III certification |
Delayed entry until the specified patent expires |
| Paragraph IV challenge with settlement |
Entry date depends on settlement terms |
| Skinny-label CLL exclusion |
Potentially viable only if the label and market conduct avoid the patented use |
| Formulation design-around |
May avoid narrow formulation claims but not compound or method claims |
| At-risk launch after litigation |
High damages and injunction exposure |
| Launch after invalidity judgment |
Depends on final judgment and surviving family patents |
A skinny label would be difficult if CLL is the principal commercial indication or if non-CLL prescribing predictably results in substantial use for CLL. The FDA label and physician prescribing practices therefore matter as much as the text of claim 1.
What FDA exclusivity applies to acalabrutinib?
FDA regulatory exclusivity is separate from patent protection.
Acalabrutinib received new chemical entity exclusivity associated with its first approval in 2017. The initial approval also involved orphan-drug treatment for mantle cell lymphoma. The later CLL approval generated additional regulatory protection for the clinical investigation supporting that indication, subject to FDA’s exclusivity determinations. Pediatric exclusivity, if granted and attached to the product, can add six months to applicable exclusivity or patent periods. [2, 6]
Regulatory exclusivity does not extend the claims of US 10,239,883. It can, however, prevent FDA approval of an ANDA or 505(b)(2) application during the relevant statutory period.
Does acalabrutinib face biosimilar risk?
No conventional biosimilar pathway applies to acalabrutinib because it is a chemically synthesized small-molecule drug. Generic applicants would normally use the ANDA pathway under section 505(j), not the biosimilar pathway under section 351(k).
The principal risks are therefore:
- Orange Book patent challenges.
- Paragraph IV litigation.
- Formulation and solid-state patents.
- Label-based induced infringement.
- Manufacturing-process patents.
- Regulatory exclusivity timing.
What litigation and settlement issues affect US 10,239,883?
A complete litigation assessment requires review of PACER, district-court dockets, Federal Circuit decisions, FDA patent certifications, and any confidential or publicly reported settlement terms. The legal questions most relevant to this patent are:
- Whether a generic label induces CLL treatment.
- Whether the claims are anticipated or obvious in view of earlier BTK inhibitor disclosures.
- Whether the claimed dose range has written-description and enablement support.
- Whether “pharmaceutically acceptable salt” is adequately supported.
- Whether the patent is subject to a terminal disclaimer or overlapping patent-family term.
- Whether later Orange Book patents independently block launch.
The patent’s method claims would generally be asserted against a generic applicant through the ANDA litigation mechanism if the applicant files a Paragraph IV certification. A settlement could provide a licensed entry date before patent expiration, but the date and commercial terms would control the economic value of the settlement.
How does acalabrutinib compare with competing BTK inhibitors?
| Drug |
Manufacturer |
BTK binding |
Patent-risk profile |
| Acalabrutinib |
AstraZeneca |
Covalent, irreversible |
Compound, formulation, and method estate |
| Ibrutinib |
AbbVie/Janssen |
Covalent, irreversible |
Mature estate with extensive formulation and method patents |
| Zanubrutinib |
BeiGene |
Covalent, irreversible |
Separate compound and use estate |
| Pirtobrutinib |
Eli Lilly |
Reversible, noncovalent |
Different chemical and patent landscape |
| Nemtabrutinib |
Merck |
Reversible or noncovalent development program |
Development-stage and indication-dependent risk |
Acalabrutinib competes most directly with ibrutinib and zanubrutinib in CLL and related B-cell malignancies. Its patent strategy relies on the specific acalabrutinib molecule and clinically defined treatment uses rather than on a broad platform claim covering all BTK inhibitors.
Key Takeaways
- US 10,239,883 is a CLL method-of-treatment patent for acalabrutinib.
- Claim 1 covers administering acalabrutinib or a pharmaceutically acceptable salt to a human with CLL.
- Claims 2 through 11 extend coverage to oral pharmaceutical compositions, tablets, capsules, and suspensions.
- Claim 12 covers a broad dose range that includes the FDA-approved 100-mg twice-daily regimen for a typical adult.
- Claims 13 and 14 separately recite the free compound and salt form.
- The patent does not require a specific CLL treatment line, biomarker, combination, or response.
- The patent is not a standalone composition-of-matter claim and must be analyzed with the broader Orange Book estate.
- Generic entry risk depends on compound patents, method-of-use listings, formulation patents, regulatory exclusivity, and any Paragraph IV settlement.
- Acalabrutinib is a small molecule, so biosimilar risk is not the relevant pathway.
- The FDA Orange Book and USPTO patent-term records control the current commercial exclusivity analysis.
FAQs
What is the active ingredient in US Patent 10,239,883?
The active ingredient is acalabrutinib, also known as ACP-196, a covalent Bruton's tyrosine kinase inhibitor.
Does US 10,239,883 cover acalabrutinib for mantle cell lymphoma?
The claims provided are limited to treating chronic lymphocytic leukemia. They do not expressly claim mantle cell lymphoma.
Can a generic sell acalabrutinib before US 10,239,883 expires?
Potentially, but only after addressing the patent through a Paragraph III certification, Paragraph IV challenge, litigation outcome, settlement license, or a legally effective label and product design that avoids infringement.
Does the patent cover acalabrutinib tablets sold under the Calquence brand?
Yes. Claims 6 and 7 expressly cover oral tablet administration when the tablet contains acalabrutinib and is used to treat CLL.
Is acalabrutinib eligible for a biosimilar application?
No. Acalabrutinib is a chemically synthesized small molecule. The expected abbreviated pathway is an ANDA, not a biosimilar application.
References
-
United States Patent No. 10,239,883. (2019). Methods of treating chronic lymphocytic leukemia using an imidazopyrazine BTK inhibitor. United States Patent and Trademark Office.
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U.S. Food and Drug Administration. (2024). Calquence (acalabrutinib) prescribing information. AstraZeneca Pharmaceuticals LP.
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U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
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21 U.S.C. §355(j). Abbreviated new drug applications.
-
35 U.S.C. §271(e)(2). Infringement based on submission of an abbreviated new drug application.
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U.S. Food and Drug Administration. (2025). Small business and industry assistance: Drug patent and exclusivity information. FDA.
