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Patent landscape, scope, and claims: |
United States Patent 11,723,898 (Apalutamide)
What the patent claims cover
US Drug Patent 11,723,898 is directed to methods for treating non-metastatic castration-resistant prostate cancer (nmCRPC) in male humans with severe hepatic impairment, using apalutamide at specified dosing ranges and within a constrained clinical monitoring and comedication framework. The claims are primarily patient-phenotype and dosing/regimen based (hepatic impairment state, concomitant therapy boundaries, cardiac/vitals qualifiers, renal function qualifier) rather than new chemical entities.
Core claimed construct
- Disease: nmCRPC (including “high-risk nmCRPC”)
- Patient subgroup: severe hepatic impairment (with “stable hepatic impairment” and also dosing adjustment language)
- Drug: apalutamide
- Dose band: about 30 mg/day to about 480 mg/day
- Clinical constraints in dependent claims: cardiac rhythm/rate/QTc, blood pressure ranges, creatinine clearance threshold, comedication classes, and CYP2C8/CYP3A4 interaction exclusions/limits
- Outcome/performance assertions in dependent claims: increased metastasis-free survival; relative risk of adverse events; PSADT threshold; prior therapy inclusion
What are the independent claims and how broad are they?
Claim 1
A method for treating nmCRPC in a male human comprising:
- Administer apalutamide at about 30 mg/day to about 480 mg/day
- to a male human in need of such treatment who has severe hepatic impairment
Scope implications
- Claim 1 is broad across:
- apalutamide within a wide dose range (30 to 480 mg/day)
- nmCRPC risk stratification (only later dependent claims specify “high-risk nmCRPC”)
- concomitant therapy (only later claims define classes)
- Claim 1 does not, by itself, confine:
- cardiac measures (QTc, heart rate)
- renal function (creatinine clearance)
- prior therapy status or treatment naïve
- ADT/orchiectomy co-administration (these appear in dependent claims)
Claim 30
A method comprising:
- determining whether the male human has severe hepatic impairment
- if severe hepatic impairment is present, administer apalutamide at about 30 mg/day to about 480 mg/day to treat nmCRPC
Scope implications
- Claim 30 is a decision-and-treat pathway claim that can cover:
- physician decision workflow
- clinical protocols that include “if severe hepatic impairment then apalutamide dose range”
- It still hinges on the same severity condition + apalutamide dosing band.
What dependent claim layers narrow the scope (and how)?
Cardiac and QTc-based qualifier (Claims 2–3, 31)
- Claim 2: normal cardiac condition and function
- Claim 3: sinus rhythm; HR 50–100 bpm; QTc ≤ 480 ms
Effect
- This narrows to a cardiac “permission set”. It is not explicit that a provider must measure QTc, but claim language makes it a required condition of the treated patient in the method.
Renal qualifier (Claim 4, 32)
- Creatinine clearance ≤ 45 mL/min/17.3 m²
Effect
- The method becomes a combined hepatic-severe + renal-function-defined subset.
Hepatic impairment stabilization (Claim 5, 33)
- Stable hepatic impairment
Effect
- Narrows from “severe hepatic impairment” generally to “stable” severe impairment.
Blood pressure constraints (Claims 6–7, 34–35)
- Systolic 90–170 mmHg
- Diastolic < 100 mmHg
Effect
- Narrows the patient population and potentially implicates trial/label-like eligibility criteria for cardiovascular safety.
Concomitant therapy for hepatic impairment (Claims 8–9, 36–37)
- Concomitant therapy exists for the severe hepatic impairment
- Therapy can comprise:
- antihypertensive agents
- calcium channel blockers
- ACE inhibitors
- angiotensin II receptor antagonists
- diuretics
- cholesterol-lowering drugs
- oral antidiabetics
- electrolyte substitution
Effect
- This claim layer creates method coverage for treated patients receiving typical comedications for comorbid conditions tied to hepatic impairment management.
- It also reduces “design-around” value of leaving patients untreated with those common classes because the patent can cover those who receive them.
CYP interaction restriction (Claims 10, 38)
- Male human is not administered a strong inhibitor or inducer of CYP2C8 or CYP3A4
Effect
- This narrows to a drug-drug interaction-managed population.
- It can also be used as a protocol constraint: methods that avoid certain strong CYP2C8/CYP3A4 modulators are within the claims.
Risk and efficacy assertions (Claims 11, 13)
- Claim 11: apalutamide administration is associated with increased risk of adverse events relative to nmCRPC not receiving apalutamide
- Claim 13: apalutamide provides increase in metastasis-free survival relative to untreated population
Effect
- These are comparative performance statements. While they do not specify a measurement endpoint in the provided excerpt, they anchor the claimed method in clinical-effect expectations for nmCRPC treatment.
High-risk nmCRPC (Claim 12)
- nmCRPC is “high-risk nmCRPC”
Effect
- Narrows to a disease-risk subgroup.
PSADT threshold (Claim 14)
Effect
- Another eligibility/narrowing criterion.
Prior therapy inclusion (Claims 15–16)
- At least one prior cancer therapy
- Prior therapy is bicalutamide, flutamide, or nilutamide
Effect
- Narrows to post-antiandrogen exposure settings.
Treatment-naïve inclusion (Claim 17)
Effect
- This is alternative positioning within the dependent set. The claim family includes both:
- “has received at least one prior therapy” (claims 15–16)
- “is treatment naïve” (claim 17)
- That reduces the practical ability to argue the population is exclusively previously treated.
Dose form and administration (Claims 18–26)
- Daily dosing (Claim 18)
- Oral administration (Claims 19–20)
- Continuous daily dosing schedule (Claim 20)
- Dose band examples:
- 180–480 mg/day (Claim 21)
- 240 mg/day (Claim 22)
- 60 mg four times per day (Claim 23)
- 120 mg/day (Claim 24)
- Formulation constraints:
- solid dosage form (Claim 25)
- tablet (Claim 26)
Effect
- The invention is not confined to one dose or schedule; it includes specific examples and supports protocol flexibility while still maintaining a claimed hinge on the severe hepatic impairment condition.
Combination with ADT or other androgen suppression (Claims 27–29)
- With androgen deprivation therapy (ADT) (Claim 27)
- With GnRH agonist/antagonist (Claim 28)
- With bilateral orchiectomy (Claim 29)
Effect
- Covers nmCRPC standard-of-care alignment across multiple forms of castration-level androgen suppression.
What does Claim 39 add?
Dose adjustment language (Claim 39)
- “The therapeutically effective amount of apalutamide is adjusted if the male human has severe hepatic impairment.”
Effect
- This strengthens the argument that the patent anticipates hepatically adjusted dosing, even though the general dose range remains “about 30 mg/day to about 480 mg/day.”
- Practically, this can capture regimens where the clinician does not select a single fixed dose but instead modifies dosing to achieve a therapeutic effect under severe hepatic impairment.
How does this claim structure affect freedom-to-operate and design-around?
1) The central hook is the severity phenotype (severe hepatic impairment)
Most dependent claim limitations (cardiac measures, QTc, BP, creatinine clearance, comedication classes, CYP interaction avoidance) layer onto an already defined anchor: nmCRPC + severe hepatic impairment + apalutamide dose range.
2) Dose range is wide, so many “lower-dose” strategies remain within coverage
Claim 1 and claim 30 cover 30 to 480 mg/day. A defendant cannot simply claim they used a “low” dose unless it is below the about 30 mg/day boundary or otherwise removed from the “severe hepatic impairment” condition.
3) Protocol constraints are common in clinical practice
The comedication list (antihypertensives, CCBs, ACEi/ARBs, diuretics, statins, oral antidiabetics, electrolyte substitution) and CYP restriction (no strong CYP2C8/CYP3A4 inhibitors/inducers) are consistent with safety management. That reduces the effectiveness of changing concomitant medication patterns as a design-around without changing the treated indication and severity category.
4) Patient qualifiers broaden relevance across multiple patient archetypes
The patent simultaneously includes:
- treatment naïve (Claim 17)
- prior therapy including bicalutamide/flutamide/nilutamide (Claims 15–16)
- high-risk nmCRPC (Claim 12)
- PSADT ≤ 10 months (Claim 14)
That means a competitor’s “we treated a different risk population” argument may not avoid coverage if the severe hepatic impairment + apalutamide dose band conditions are met.
Patent landscape: what this patent likely occupies in the broader apalutamide and nmCRPC space
Where it fits
This US patent sits in the aputamide second-order use/patient-phenotype space, not in:
- chemical entity (apalutamide itself)
- first-line nmCRPC efficacy claims in the overall population
- generic composition/formulation claims without the hepatic impairment-specific method framing
The key legal distinction is that the claims are method-of-treatment with subpopulation criteria, a pattern typically used to capture label expansions and protocol refinements where an existing drug already has market authorization.
Claim-to-landscape mapping
- Existing drug: apalutamide (known active)
- Clinical area: nmCRPC
- Refinement driver: severe hepatic impairment and related safe-use constraints (CYP interaction restrictions, cardiac/QTc and BP constraints, renal threshold, stable impairment)
- Operational coverage: determination step (Claim 30) plus administration regimen (Claim 1)
Implication for competitor strategies
- Any clinical protocol that includes apalutamide administration to nmCRPC patients with severe hepatic impairment in the claimed dose range can face infringement risk if it aligns with additional dependent criteria, even if the protocol is otherwise “label-like.”
- Strategies that reduce risk would need to move outside at least one hard claim element:
- remove “severe hepatic impairment” condition from inclusion
- reduce dose outside “about 30 mg/day to about 480 mg/day”
- avoid the dosing adjustment paradigm (Claim 39) if interpreted as a condition of the method
- remove matching dependent prerequisites if those are asserted in the asserted claim set
Because this dataset only provides claims (not prosecution history, claim construction record, or asserted claims in litigation), the landscape inference is constrained to the claim language.
Claim coverage matrix (what is covered by which claim layer)
| Claim |
Treats nmCRPC? |
Severe hepatic impairment required? |
Apalutamide dose range required |
Extra patient constraints |
| 1 |
Yes |
Yes |
Yes (30–480 mg/day) |
None in independent claim |
| 2–3 |
Yes |
Yes |
Yes |
Normal cardiac; HR 50–100; QTc ≤ 480 ms |
| 4 |
Yes |
Yes |
Yes |
Creatinine clearance ≤ 45 mL/min/17.3 m² |
| 5 |
Yes |
Yes |
Yes |
Stable hepatic impairment |
| 6–7 |
Yes |
Yes |
Yes |
BP systolic 90–170; diastolic < 100 |
| 8–9 |
Yes |
Yes |
Yes |
Concomitant therapy classes listed |
| 10 |
Yes |
Yes |
Yes |
No strong CYP2C8/CYP3A4 inhibitor/inducer |
| 11 |
Yes |
Yes |
Yes |
Comparative adverse event risk statement |
| 12 |
Yes |
Yes |
Yes |
High-risk nmCRPC |
| 13 |
Yes |
Yes |
Yes |
Metastasis-free survival comparative statement |
| 14 |
Yes |
Yes |
Yes |
PSADT ≤ 10 months |
| 15–16 |
Yes |
Yes |
Yes |
Prior therapy; bicalutamide/flutamide/nilutamide |
| 17 |
Yes |
Yes |
Yes |
Treatment naïve |
| 18–20 |
Yes |
Yes |
Yes |
Daily, oral, continuous dosing |
| 21–24 |
Yes |
Yes |
Yes |
Specific dose embodiments |
| 25–26 |
Yes |
Yes |
Yes |
Solid dosage form; tablet |
| 27–29 |
Yes |
Yes |
Yes |
ADT / GnRH agonist/antagonist / orchiectomy |
| 30 |
Yes |
Yes (conditional) |
Yes (30–480 mg/day) |
Determination step |
| 31–38 |
Yes |
Yes (conditional) |
Yes |
Cardiac, renal, stable hepatic, BP, concomitant classes, CYP restriction |
| 39 |
Yes |
Yes |
Yes |
Therapeutically effective amount adjusted if severe hepatic impairment |
Key Takeaways
- US Drug Patent 11,723,898 claims apalutamide dosing methods for nmCRPC specifically in male humans with severe hepatic impairment, using a dose band of about 30 mg/day to about 480 mg/day (Claims 1 and 30).
- The broadest protection is anchored to severity phenotype and dose range; dependent claims add cardiac/QTc, blood pressure, renal function, concomitant medication classes, and CYP2C8/CYP3A4 interaction avoidance.
- The claim set covers both treatment-naïve and previously treated populations, and it includes multiple standard androgen suppression approaches (ADT, GnRH agonist/antagonist, bilateral orchiectomy).
- Practical design-around pressure is high because the claims combine (1) severe hepatic impairment + (2) apalutamide within a wide dose range + (3) common clinical protocol constraints.
FAQs
-
Is the patent limited to a specific apalutamide schedule?
No. It includes daily/oral continuous dosing language and also specific embodiments (e.g., 60 mg four times per day) while keeping the core dose band of about 30–480 mg/day.
-
Does the patent require ADT or castration-level androgen suppression?
Not in the independent claims provided. ADT, GnRH agonist/antagonist, or orchiectomy appear in dependent claims (Claims 27–29).
-
What does “severe hepatic impairment” do to the scope?
It is the defining patient subgroup for independent claim coverage (Claims 1 and 30), with additional narrowing to “stable hepatic impairment” in dependent claims (Claims 5 and 33).
-
Can use of strong CYP2C8 or CYP3A4 modulators avoid infringement?
If asserted claims include the CYP interaction limitation, then the method requires the male human is not administered strong CYP2C8/CYP3A4 inhibitors or inducers (Claims 10 and 38).
-
Does the patent cover diagnostic decision workflows?
Yes. Claim 30 includes a determining step for severe hepatic impairment followed by apalutamide administration.
References
[1] United States Patent 11,723,898. Claims as provided in user prompt.
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