United States Patent 9,758,524: Acalabrutinib MCL Claims, Patent Scope, Expiration and Generic Risk
US Patent No. 9,758,524 protects the use of acalabrutinib, marketed as Calquence, for treating mantle cell lymphoma (MCL). The patent does not claim the molecule broadly, its synthesis, or every acalabrutinib indication. Its principal protection is a method-of-treatment claim directed to administering acalabrutinib, or a pharmaceutically acceptable salt, to a human with MCL.
The patent is particularly important because the claimed compound is the active pharmaceutical ingredient in Calquence. The core patent term is expected to run through February 12, 2034, subject to any applicable patent-term adjustment. The claims cover oral tablets, capsules and suspensions, but do not require a particular dose, treatment line, biomarker, combination regimen or formulation technology.
What drug does US Patent 9,758,524 cover?
US 9,758,524 covers acalabrutinib, also known by the development code ACP-196.
The compound identified in claim 1 is:
(S)-4-(8-amino-3-(1-but-2-ynoylpyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide
Acalabrutinib is a covalent Bruton's tyrosine kinase inhibitor. It binds to BTK and is used in B-cell malignancies, including MCL, chronic lymphocytic leukemia and small lymphocytic lymphoma.
| Item |
Data |
| Patent |
US 9,758,524 B2 |
| Title |
Methods of treating mantle cell lymphoma |
| Active ingredient |
Acalabrutinib |
| Applicant/assignee lineage |
Acerta Pharma B.V.; subsequently associated with AstraZeneca |
| Patent type |
Method of treatment |
| Primary disease |
Mantle cell lymphoma |
| U.S. issue date |
September 19, 2017 |
| Earliest priority date |
February 12, 2014 |
| Expected basic expiration |
February 12, 2034 |
| Commercial product |
Calquence |
| FDA sponsor |
AstraZeneca Pharmaceuticals LP |
| Relevant FDA pathway |
New Drug Application, 21 U.S.C. § 355 |
The chemical identity in the patent corresponds to the active ingredient in Calquence capsules and tablets. The patent therefore has direct product relevance even though its claims are framed as treatment methods rather than product claims.
What does claim 1 of US 9,758,524 protect?
Claim 1 protects a method comprising administering acalabrutinib, or a pharmaceutically acceptable salt, to a human subject in an amount effective to treat MCL.
The claim has four central elements:
- A human subject.
- A diagnosis or treatment target involving MCL.
- Administration of the specified acalabrutinib compound or an acceptable salt.
- An amount effective to treat the MCL.
The claim is not limited to patients who previously received another therapy. It does not require relapsed or refractory disease, a particular disease stage, a specific BTK mutation or a particular response endpoint.
That breadth gives claim 1 substantial commercial relevance. A product administered for the patented MCL indication can potentially fall within the claim regardless of whether the treatment occurs in first-line, second-line or later-line care, provided the use is within the claim's treatment language.
What limitations are absent from claim 1?
Claim 1 does not expressly require:
- A particular dose or dosing schedule.
- Twice-daily administration.
- A tablet, capsule or suspension.
- Combination with an anti-CD20 antibody, chemotherapy or another targeted agent.
- Relapsed MCL.
- Prior exposure to a BTK inhibitor.
- A specific formulation excipient.
- A particular level of BTK inhibition.
- A particular duration of therapy.
The absence of these limitations makes claim 1 broader than the dependent claims. A competing product does not avoid claim 1 merely by changing the dosage form or administration schedule.
How do claims 2 through 11 expand formulation and administration coverage?
Claims 2 through 11 add pharmaceutical composition and administration limitations.
| Claims |
Added limitation |
| 2 |
The compound is present in a pharmaceutical composition |
| 3 |
The composition includes one or more pharmaceutically acceptable auxiliaries |
| 4 |
Oral administration |
| 5 |
Oral administration with pharmaceutically acceptable auxiliaries |
| 6 |
Oral tablet |
| 7 |
Oral tablet with auxiliaries |
| 8 |
Oral capsule |
| 9 |
Oral capsule with auxiliaries |
| 10 |
Oral suspension |
| 11 |
Oral suspension with auxiliaries |
These claims create fallback positions if a court construes claim 1 narrowly or if a method is practiced through a specific dosage form.
The formulation claims are not conventional formulation patents in the strongest sense. They do not recite a defined excipient system, particle-size distribution, dissolution profile, release mechanism, coating, polymorph or manufacturing process. Their protection is tied to the use of acalabrutinib in a composition and, for later claims, in an oral tablet, capsule or suspension.
What formulations are protected by US 9,758,524?
The patent covers methods using acalabrutinib in:
- Tablets.
- Capsules.
- Suspensions.
- Other pharmaceutical compositions under broader dependent claims.
The claims do not appear limited to immediate-release or modified-release products. They also do not identify a required tablet strength or excipient. A generic oral capsule or tablet designed to administer acalabrutinib for MCL could present method-of-use risk even if its inactive ingredients differ from Calquence.
What does claim 12 protect?
Claim 12 limits the administered amount to 0.0001 to 25 mg per kilogram of body weight.
This is a broad numerical range. For a 70-kilogram patient, the range corresponds approximately to:
| Dose per kg |
Approximate total dose for 70 kg patient |
| 0.0001 mg/kg |
0.007 mg |
| 0.01 mg/kg |
0.7 mg |
| 0.1 mg/kg |
7 mg |
| 1 mg/kg |
70 mg |
| 25 mg/kg |
1,750 mg |
The marketed Calquence regimen is generally expressed as a fixed dose rather than a weight-based dose. A 100 mg twice-daily regimen corresponds to approximately 2.86 mg/kg/day for a 70-kilogram patient, or approximately 1.43 mg/kg per administration. That falls within the numerical range in claim 12 if the relevant calculation is based on each administered dose or the claimed method's applicable dosing unit.
Claim 12 does not require the marketed 100 mg strength. It reaches materially lower and higher doses, subject to the claim's other requirements.
How do claims 13 and 14 differ from claim 1?
Claim 13 recites administration of the unmodified acalabrutinib compound. Claim 14 recites administration of a pharmaceutically acceptable salt.
Claim 1 already covers the compound and its pharmaceutically acceptable salts. Claims 13 and 14 therefore operate as narrower claim formats that separately identify the free compound and salt forms.
| Claim |
Practical scope |
| 1 |
Acalabrutinib or a pharmaceutically acceptable salt for MCL |
| 13 |
The specified acalabrutinib compound itself |
| 14 |
A pharmaceutically acceptable salt of that compound |
A salt claim does not automatically cover every salt of every acalabrutinib-related molecule. The salt must be a pharmaceutically acceptable salt of the claimed compound.
What is the patent expiration date for US 9,758,524?
The basic patent term is expected to expire on February 12, 2034, based on the earliest claimed priority date of February 12, 2014 and the standard 20-year term applicable to the relevant U.S. patent filing framework.
The precise enforceable expiration date can be affected by patent-term adjustment. A patent-term extension under 35 U.S.C. § 156 is a separate issue and depends on the regulatory product and the specific extension record. The Orange Book-listed expiration date should control for FDA patent-listing analysis.
The patent was issued on September 19, 2017. Its remaining term is therefore commercially meaningful for generic applicants seeking MCL labeling before 2034.
What is the Orange Book status of US 9,758,524?
US 9,758,524 has been associated with Calquence and is relevant to the Orange Book patent landscape for acalabrutinib products. Orange Book listing determines whether an ANDA applicant must address the patent through a certification.
For a listed method-of-use patent, an ANDA applicant may use a section viii statement to omit the patented indication if the proposed labeling excludes MCL. If the applicant seeks approval for MCL treatment, it generally must provide a Paragraph III or Paragraph IV certification, depending on the proposed timing and patent status.
A section viii strategy can materially reduce infringement exposure because the patent claims are directed to MCL treatment, not every use of acalabrutinib. A generic seeking only non-MCL indications may attempt to carve out MCL from its labeling.
When does acalabrutinib lose exclusivity?
Acalabrutinib has several different exclusivity concepts:
| Exclusivity category |
Commercial effect |
| New chemical entity exclusivity |
Blocks ANDA approval for the statutory NCE period |
| Orphan-drug exclusivity |
May protect a designated MCL indication for seven years from approval |
| Patent exclusivity |
US 9,758,524 is expected to extend to February 12, 2034 |
| Other listed patents |
May protect formulations, additional indications or other product characteristics |
Calquence received FDA accelerated approval for MCL in October 2017 for adults who had received at least one prior therapy. FDA later granted additional approvals for CLL and SLL. The MCL patent claim is broader in treatment-line language than the initial MCL label because claim 1 does not require prior therapy.
Regulatory exclusivity and patent exclusivity are distinct. Expiration of an FDA exclusivity period does not remove a valid patent. Conversely, a patent challenge can affect launch timing even after regulatory exclusivity has ended.
What generic entry risks exist for acalabrutinib?
The main generic-entry risk depends on the proposed label.
MCL-labeled generic
A generic seeking an MCL indication would face direct method-of-use exposure under claim 1. The risk is highest where the product label expressly identifies MCL treatment and the product contains acalabrutinib.
Potential defenses could focus on patent validity, claim construction, noninfringement or the scope of an approved label. The molecule-specific language reduces the ability to distinguish the product based on chemical structure.
Carved-out generic
A generic applicant may seek to omit MCL from its labeling and rely on CLL or SLL indications, assuming the remaining label can be approved without the patented use. This approach does not eliminate all commercial or regulatory risk, but it can reduce the direct relevance of a method-of-use patent directed solely to MCL.
Alternative BTK inhibitor
A competitor using a different BTK inhibitor does not practice the claimed acalabrutinib method. The patent therefore does not directly block ibrutinib, zanubrutinib or pirtobrutinib products, although those products compete commercially with Calquence.
Are there Paragraph IV challenges to US 9,758,524?
A Paragraph IV certification would assert that the patent is invalid, unenforceable or will not be infringed. A public Paragraph IV challenge involving US 9,758,524 would ordinarily generate an FDA notice and potentially Hatch-Waxman litigation.
No widely reported final judgment invalidating US 9,758,524 appears in the principal public patent and regulatory records associated with Calquence. The absence of a reported invalidity judgment does not establish that the patent is immune from challenge. It indicates that the patent remains a relevant barrier in the U.S. approval and launch analysis.
For an ANDA applicant, the commercial options are:
- File with a Paragraph III certification and defer approval until patent expiration.
- File with a Paragraph IV certification and pursue an early launch strategy.
- Submit a section viii statement and omit the MCL indication.
- Seek a settlement or license from the patent holder.
What litigation and settlement issues affect Calquence?
A patent dispute involving this patent would likely center on:
- Whether the proposed generic label induces MCL treatment.
- Whether the product is acalabrutinib or a covered salt.
- Whether the claimed “effective” amount is met.
- Whether the patent adequately describes and enables MCL treatment.
- Whether prior art disclosed acalabrutinib use in MCL.
- Whether the listed patent is properly tied to the approved product and indication.
A settlement could allow an agreed generic entry date before February 2034, subject to antitrust review and the agreement's terms. No publicly established settlement date should be assumed without an identified court filing, FDA notice or company disclosure.
How strong is the patent estate for acalabrutinib?
US 9,758,524 is strong against an identical acalabrutinib product labeled for MCL because:
- The claim names the active compound structurally.
- The claim covers a human treatment method.
- The claim is not limited to a narrow MCL subtype.
- The claim does not require a specific formulation.
- The marketed product is administered orally in forms expressly addressed by dependent claims.
Its weaknesses are equally defined:
- It is not a composition-of-matter claim.
- It does not cover every acalabrutinib indication.
- It may be avoided through an effective section viii carve-out.
- Its validity depends on the patent's written-description, enablement and prior-art record.
- Competing BTK inhibitors remain outside its literal compound scope.
The strongest practical protection is therefore indication-specific rather than platform-wide.
How does US 9,758,524 compare with competing BTK inhibitor patents?
| Product |
Active ingredient |
Main commercial use |
Relationship to US 9,758,524 |
| Calquence |
Acalabrutinib |
MCL, CLL, SLL |
Directly covered for MCL |
| Imbruvica |
Ibrutinib |
MCL and other B-cell malignancies |
Different molecule; outside literal compound scope |
| Brukinsa |
Zanubrutinib |
MCL and other B-cell malignancies |
Different molecule; outside literal compound scope |
| Jaypirca |
Pirtobrutinib |
Previously treated B-cell malignancies |
Different molecule; outside literal compound scope |
The patent does not prevent competitive treatment of MCL with another BTK inhibitor. Its commercial value depends on the degree to which physicians, payers and treatment guidelines continue to use acalabrutinib for MCL.
What licensing transaction transferred acalabrutinib rights?
AstraZeneca obtained control of acalabrutinib through its transactions with Acerta Pharma. AstraZeneca initially acquired a majority interest in Acerta and later acquired the remaining interest. Acerta had developed acalabrutinib before the transaction.
The transaction made AstraZeneca the principal commercial and patent-rights holder for Calquence. Patent ownership, FDA sponsorship, Orange Book maintenance and generic litigation strategy are therefore aligned under the AstraZeneca group.
Key Takeaways
- US 9,758,524 is a method-of-treatment patent for acalabrutinib in human MCL patients.
- Claim 1 is the central claim and covers acalabrutinib or a pharmaceutically acceptable salt.
- Claims 2 through 11 cover pharmaceutical compositions, oral administration, tablets, capsules and suspensions.
- Claim 12 covers a broad administered-dose range of 0.0001 to 25 mg/kg.
- Claims 13 and 14 separately recite the free compound and its pharmaceutically acceptable salts.
- The expected basic patent expiration is February 12, 2034.
- The patent does not block competing BTK inhibitors with different active ingredients.
- A generic MCL label creates the highest infringement risk.
- A section viii carve-out excluding MCL may offer a path for a generic seeking approval for other acalabrutinib indications.
- The patent is commercially strong for the approved acalabrutinib MCL use but does not provide composition-of-matter protection.
FAQs About US Patent 9,758,524 and Acalabrutinib
Does US 9,758,524 cover Calquence for chronic lymphocytic leukemia?
No. The claims provided are directed to treating MCL. They do not expressly claim treatment of CLL or SLL.
Can a generic acalabrutinib product launch before 2034?
Potentially, but the path depends on the proposed labeling, Orange Book certifications, patent challenges, litigation outcomes and any settlement. An MCL-labeled product faces the most direct risk under US 9,758,524.
Does the patent cover intravenous acalabrutinib?
Claim 1 is not limited to oral administration. Claims 4 through 11 add oral forms. A nonoral product could still be analyzed under claim 1 if it otherwise satisfies the claimed compound, patient, MCL and effective-treatment elements.
Does changing the capsule excipients avoid US 9,758,524?
Not necessarily. Claim 1 does not require a particular formulation, and claims 2 through 11 do not identify a narrow excipient recipe. Changing inactive ingredients alone may not avoid the broader method claim.
Is US 9,758,524 a composition-of-matter patent?
No. It is principally a method-of-treatment patent. It identifies acalabrutinib as the administered compound and claims its use for treating MCL, but it does not broadly claim the compound as a chemical composition.
References
-
AstraZeneca. (2015). AstraZeneca and Acerta Pharma announce agreement for majority ownership of Acerta Pharma and global rights to acalabrutinib. AstraZeneca press release.
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AstraZeneca. (2021). AstraZeneca completes acquisition of remaining interest in Acerta Pharma. AstraZeneca press release.
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U.S. Food and Drug Administration. (2017). FDA approves Calquence for mantle cell lymphoma. FDA Drug Safety and Availability.
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U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. FDA.
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U.S. Patent No. 9,758,524. (2017). Methods of treating mantle cell lymphoma. United States Patent and Trademark Office.
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U.S. Food and Drug Administration. (2024). Calquence (acalabrutinib) prescribing information. AstraZeneca Pharmaceuticals LP.
