United States Patent 12,527,798 (US12527798): What Is Claimed and Where the Landscape Hits
US 12,527,798 claims combination and sequencing method-of-treatment regimens for human cancer that pair a selective CDK4/6 inhibitor with a cytotoxic chemotherapy agent and an immune checkpoint inhibitor (ICI), split into induction and maintenance phases. The claim set hard-codes (i) the CDK4/6 inhibitor structure, (ii) a time window between CDK4/6 dosing and chemotherapy dosing, (iii) chemotherapy that is cytotoxic to immune effector cells in the broad independent claim, and (iv) ICI class and specific examples that are narrowed into dependent claims.
What is the core independent claim scope (Claim 1)?
Independent claim structure
Claim 1 is a method of treating a human having cancer using a therapeutic regimen with:
- Induction phase comprising:
- (i) Effective amount of a selective CDK4/6 inhibitor (defined by the patent’s structure depiction in the claim) or a pharmaceutically acceptable salt
- (ii) Effective amount of a chemotherapeutic agent
- (iii) Effective amount of an immune checkpoint inhibitor
- Critical sequencing constraint: during induction, the CDK4/6 inhibitor is only administered 2 hours or less prior to the administration of the chemotherapeutic agent
- Chemotherapy biological constraint: the chemotherapeutic agent is cytotoxic to immune effector cells
- Maintenance phase comprising:
- (i) administering at least one dose of the effective amount of the immune checkpoint inhibitor
- (ii) maintenance begins after cessation of the induction phase
Scope implications
- Time-of-administration is a legal limiter. The claim does not merely require co-administration; it requires a tight pre-window: CDK4/6 dosing is ≤2 hours before chemotherapy dosing in induction.
- ICI is not discontinued in induction. Claim 1 requires the ICI be administered during induction along with chemo and CDK4/6, then continued in maintenance.
- Chemotherapy is not generic. Claim 1 ties chemo to an immunological property: it is cytotoxic to immune effector cells. That language can be attacked or defended through mechanisms and labeling/assay evidence depending on the accused product’s chemo backbone.
- Maintenance is ICI-only. Claim 1’s maintenance phase does not recite continued CDK4/6 or continued chemotherapy; it is structured as ICI continuation after induction ends.
How are the dependent claims narrowing the ICI and chemo space?
ICI narrowing (Claims 2–8)
Claim 2 limits the immune checkpoint inhibitor to:
- PD-1 inhibitor
- PD-L1 inhibitor
- CTLA-4 inhibitor
Claim 3 further specifies:
Claim 4 lists PD-L1 inhibitors:
- atezolizumab
- avelumab
- durvalumab
Claim 5 and 6 narrow through PD-1 inhibitors:
- nivolumab
- pidilizumab
- pembrolizumab
Claim 7 and 8 narrow through CTLA-4 inhibitors:
Chemotherapy narrowing (Claims 9–12)
Claim 9 provides a broad enumerated list of chemotherapeutic agent categories and mechanisms, including (examples from the claim):
- protein synthesis inhibitors
- DNA-damaging chemotherapeutics
- alkylating agents
- topoisomerase inhibitors
- RNA synthesis inhibitors
- tubulin binders
- DNA polymerase inhibitors
- anticancer enzymes
- antifolates / thymidylate synthase inhibitors
- integrin inhibitors
- and combinations
Claim 10 narrows with specific examples:
- carboplatin, cisplatin, oxaliplatin
- 5-fluorouracil, floxuridine, capecitabine
- gemcitabine, mitomycin C
- cyclophosphamide, dacarbazine, ifosfamide
- topotecan, irinotecan
- docetaxel, paclitaxel, etoposide
- pemetrexed, temozolomide
- abraxane
- and combinations
Claim 11 narrows again:
- carboplatin, cisplatin, etoposide, and combinations
Claim 12 narrows to the specific doublets:
- carboplatin + etoposide
- cisplatin + etoposide
Tumor type narrowing (Claims 13–14)
Claim 13 enumerates cancers, including:
- small cell lung cancer
- non-small cell lung cancer
- triple negative breast cancer
- colorectal, ovarian, pancreatic
- bladder, gastroesophageal
- cholangiocarcinoma
- cervical
- soft tissue sarcoma
Claim 14 narrows specifically to:
What does the special small cell lung cancer claim do (Claim 15)?
Claim 15 is a SCLC-specific method that is substantially more specific than Claim 1 in three ways:
1) chemo is limited to the two named doublets,
2) PD-L1 inhibitor is limited to the three named antibodies, and
3) the CDK4/6 to chemo sequencing window is broadened from ≤2 hours to ≤4 hours.
Claim 15 regimen breakdown
Induction phase
- (i) selective CDK4/6 inhibitor (structure as in claim) or salt
- (ii) chemo is limited to:
- carboplatin + etoposide, or
- cisplatin + etoposide
- (iii) PD-L1 inhibitor is limited to:
- atezolizumab, avelumab, or durvalumab
- Sequencing constraint (updated window): during induction, the CDK4/6 inhibitor is only administered 4 hours or less prior to chemotherapy dosing
Maintenance phase
- administer at least one dose of the PD-L1 inhibitor
- maintenance begins after cessation of the induction phase
Downstream tumor-regimen exemplars (Claims 16–19)
- Claim 16: induction chemo includes carboplatin + etoposide
- Claim 17: induction chemo includes cisplatin + etoposide
- Claim 18: PD-L1 inhibitor is atezolizumab
- Claim 19: both chemo (carboplatin + etoposide) and PD-L1 (atezolizumab) are fixed
Sequencing: what does “only administered X hours or less prior” do to infringement risk?
The claims use exclusive timing language in both the broad and SCLC-specific independent structures:
- Claim 1: CDK4/6 is only administered 2 hours or less prior to chemotherapy during induction.
- Claim 15: CDK4/6 is only administered 4 hours or less prior to chemotherapy during induction.
From an enforcement and design-around perspective, the phrasing creates a dose-administration order constraint that can be read to require strict compliance with the timing rule. If a regimen schedules CDK4/6 outside the pre-window (for example, co-dosing on the same administration time but not within a defined “prior” interval, or pre-dosing beyond the window), the regimen may fall outside the literal scope.
Because the patent text ties “prior” to a numeric threshold, the operational question is not just whether CDK4/6 and chemo are in the same regimen, but whether the CDK4/6 dosing precedes chemo within the stated boundary during induction.
Checkpoint strategy: what does “maintenance phase comprising at least one dose” lock in?
Both Claim 1 and Claim 15 structure maintenance as:
- continued ICI dosing alone (Claim 1: any ICI within the recited types; Claim 15: PD-L1 inhibitors)
- administered after induction cessation
This drafting can matter in at least two practical ways:
- If an accused regimen continues chemo into maintenance, it will not be “maintenance comprising administering… the immune checkpoint inhibitor… wherein the maintenance… following cessation of induction.”
- If an accused regimen stops ICI at induction and then switches to another biologic or therapy class, it may not satisfy the “maintenance phase” requirement as written.
CDK4/6 inhibitor definition: what the structure language implies for freedom-to-operate
The claims define the CDK4/6 inhibitor as having “the structure” shown in the patent, or salt. Even though the textual excerpt provided does not reproduce the chemical structure, the claim uses a structure-defined limitation rather than a genus word like “palbociclib/abemaciclib/ribociclib” in the independent claim. That pushes scope and enforcement toward:
- products that match the claimed structure (or salts) with the required regimen and timing elements.
Dependent claims do not add alternate CDK4/6 inhibitors; they lean on the independent structural definition.
Patent landscape analysis (what this claim set tends to concentrate in the US landscape)
1) Combination-regimen patent clusters
The claims sit in a common US patent enforcement pattern for oncology combinations:
- A regimen claim that covers induction + maintenance, using sequenced dosing and specific drug-class pairings.
In the US market, this typically coexists with:
- separate patents on the CDK4/6 compound (composition and use),
- patents on CDK4/6 + checkpoint combinations,
- patents on chemo + checkpoint regimens and sequencing,
- and more recent patents on induction/maintenance frameworks.
2) Enforced design elements: “timing window + maintenance continuation”
The most enforceable elements in this claim set are:
- “only administered X hours or less prior” during induction
- ICI-only maintenance after induction cessation
These features tend to be the same parameters competitors attempt to modify for design-around. They are also the features that are easiest to encode into a claim set because they do not require broad mechanistic proof beyond clinical/administration sequencing.
3) Tumor-anchored claims drive sharper competitive focus
Claim 15–19 narrow to small cell lung cancer and lock in:
- chemo doublets (carboplatin + etoposide or cisplatin + etoposide)
- PD-L1 agents (atezolizumab, avelumab, durvalumab)
- CDK4/6-to-chemo timing ≤4 hours
SCLC regimens are a high-density competitive zone in the US due to established chemo-ICI standards; narrower, tumor-specific patent claims often align with how clinical protocols are run.
4) The chemo “cytotoxic to immune effector cells” constraint is broad but not meaningless
Claim 1 requires chemo to be cytotoxic to immune effector cells, which likely covers many standard cytotoxic chemotherapies. Still, it is a claim-specific limitation; it can be contrasted against regimens that use non-cytotoxic agents as the chemotherapy component (for example, some targeted agents) and against dosing strategies where the “chemotherapeutic agent” is not the immune-cytotoxic backbone.
5) The most direct infringement pathway
From the literal structure of the claims, infringement risk concentrates when an accused regimen:
- uses the structure-defined selective CDK4/6 inhibitor,
- pairs it during induction with cytotoxic chemo and a recited ICI, and
- maintains the ICI after induction ends, and
- administers CDK4/6 within the stated pre-window relative to chemotherapy.
The SCLC version tightens the regimen further (chemo doublet, PD-L1 only, and a ≤4-hour window).
Claim coverage matrix (from the provided claim text)
Scope by tumor type
| Claim |
Tumor scope |
Key tumor linkage |
| 1 |
Any cancer (human cancer) |
Enumerated cancers appear only in dependents (Claim 13) |
| 13 |
Listed cancers |
Includes SCLC and multiple other solid tumors |
| 14 |
SCLC |
Narrows explicitly to small cell lung cancer |
| 15–19 |
SCLC |
Hard-codes SCLC plus specific chemo and PD-L1 |
Scope by immune checkpoint inhibitor
| Claim |
ICI class |
Examples captured |
| 1 |
Immune checkpoint inhibitor (generic) |
Not limited in Claim 1 text excerpt beyond “immune checkpoint inhibitor” |
| 2 |
PD-1 / PD-L1 / CTLA-4 |
Claim 2 states the classes |
| 3–4 |
PD-L1 |
atezolizumab, avelumab, durvalumab |
| 5–6 |
PD-1 |
nivolumab, pidilizumab, pembrolizumab |
| 7–8 |
CTLA-4 |
ipilimumab, tremelimumab |
| 15–19 |
PD-L1 only |
atezolizumab/avelumab/durvalumab; Claim 19 fixes atezolizumab |
Scope by chemotherapy
| Claim |
Chemo scope |
Narrowing endpoint |
| 1 |
Broad chemotherapeutic agent (must be cytotoxic to immune effector cells) |
Class not enumerated in Claim 1 text excerpt |
| 9–10 |
Broad list of mechanisms and named examples |
Includes many standard cytotoxics |
| 11 |
carboplatin / cisplatin / etoposide |
Still general combination language |
| 12 |
Doublets only |
carboplatin + etoposide OR cisplatin + etoposide |
| 15–19 |
Doublets only |
Fixes the chemo and PD-L1 |
Sequencing window (CDK4/6 before chemo during induction)
| Claim |
“Only administered X hours or less prior” window |
| 1 |
2 hours or less |
| 15 |
4 hours or less |
Maintenance
| Claim |
Maintenance phase composition |
| 1 |
at least one dose of ICI after induction cessation |
| 15 |
at least one dose of PD-L1 inhibitor after induction cessation |
Key Takeaways
- US 12,527,798 claims a sequenced induction + ICI maintenance regimen that couples a structure-defined selective CDK4/6 inhibitor with cytotoxic chemotherapy and an immune checkpoint inhibitor, followed by ICI-only maintenance after induction stops.
- The independent claim (Claim 1) hinges on a tight operational rule: CDK4/6 must be dosed within 2 hours before chemotherapy during induction and the chemotherapy must be cytotoxic to immune effector cells.
- The SCLC-focused claims (Claim 15–19) narrow the regimen to SCLC, chemo doublets (carboplatin + etoposide or cisplatin + etoposide), PD-L1 inhibitors, and expand the CDK4/6 pre-window to ≤4 hours.
- The ICI dependency tree is explicit: PD-L1 examples include atezolizumab, avelumab, durvalumab; PD-1 and CTLA-4 examples are enumerated in other branches of the dependent claims.
- The strongest infringement and design-around levers in this claim set are: (i) CDK4/6-to-chemo timing window and (ii) whether the regimen continues ICI in a post-induction maintenance phase.
FAQs
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Does Claim 1 require the CDK4/6 inhibitor to be administered before chemotherapy?
Yes. It requires the CDK4/6 inhibitor be administered “only 2 hours or less prior” to chemotherapy during induction.
-
Is chemotherapy required during maintenance in these claims?
No. The claims describe maintenance as administering the immune checkpoint inhibitor after cessation of induction, without requiring chemotherapy continuation.
-
Can the immune checkpoint inhibitor be PD-1, PD-L1, or CTLA-4 in Claim 1?
Claim 2 limits the ICI types to PD-1 / PD-L1 / CTLA-4. The claim text hierarchy provided indicates the ICI type is expanded through dependent claims.
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What makes Claim 15 different from Claim 1?
Claim 15 is SCLC-specific and limits chemo to carboplatin + etoposide or cisplatin + etoposide, limits ICI to PD-L1 inhibitors, and changes the CDK4/6-to-chemo pre-window from ≤2 hours to ≤4 hours.
-
Which PD-L1 inhibitor is explicitly tied to the most specific embodiment in Claim 19?
Claim 19 fixes the PD-L1 inhibitor as atezolizumab and the chemo doublet as carboplatin + etoposide.
References
- Provided claims text for US 12,527,798 (Claims 1–19).
