US Patent 8,377,921: What Do the Claims Actually Cover?
US Drug Patent 8,377,921 is a method-of-treatment patent built around ALK (anaplastic lymphoma kinase) inhibition using pyrimidine-2,4-diamine scaffold compounds defined by broad Formula (1) and Formula (2) claim sets, with optional combination therapy. The claim language targets multiple ALK-mediated malignancies and expressly includes non-small cell lung cancer (NSCLC) and neuroblastoma, plus other ALK-pathway conditions.
The scope is driven less by the medical use language and more by the chemical genus breadth in the definition of substituents, heterocycles, and sulfonyl/heteroatom-containing moieties.
What conditions are in-scope under the method claims?
Across the independent method claims you provided, the in-scope conditions are:
- anaplastic large cell lymphoma
- ALK+ non-Hodgkin’s lymphoma
- inflammatory myofibrolastic tumor
- neuroblastoma
- a neoplastic disease, where the neoplastic disease is non-small cell lung cancer
This condition set appears repeatedly in both:
- the Formula (2) method claims (claims 1, 2, 3, 10–13), and
- the Formula (1) method claims (claims 5, 6–10, 16–18).
Dependent claim narrowing you listed
- Claim 2: NSCLC
- Claim 3: neuroblastoma
- Claim 11: NSCLC
- Claim 12: neuroblastoma
Optional combination therapy
Multiple claims allow an “optionally in combination with a second therapeutic agent” and, in at least one dependent claim, specify the second agent as a chemotherapeutic agent (claim 4, and claim 13 for the Formula (1) branch).
Practical implication: the patent covers monotherapy and combination regimens where the second agent is “therapeutic” (and optionally “chemotherapeutic” if you look to the narrower dependent claim).
What chemical breadth do Formulas (1) and (2) create in the claims?
The independent method claims are not limited to a single molecule. They cover a genus defined by R-group substituent rules. Your claim text shows the same overall architecture:
- pyrimidine-2,4-diamine core (implied by the explicit named examples and Formula description)
- substituted aryl system(s)
- sulfonyl / sulfone-containing segment(s)
- a distinct ring system for Y attached via carbon to the phenyl ring
Shared genus features (as written in your claims)
For the Formula (2) branch (claim 1 and claim 10):
- R1: halo or C1–6 alkyl
- R2: H
- R3: (CR2)0–2SO2R12
- R4: C1–6 alkyl or C2–6 alkenyl or C2–6 alkynyl (or H in certain alternatives)
- R6: isopropoxy or methoxy
- One of R8/R9: (CR2)qY; the other is selected from a set including C1–6 alkyl and additional functional options
- X: is either (CR2)qY or other listed groups (cyano, ester-like, amide-like, sulfonamide-like, etc.)
- Y: pyrrolidinyl, piperidinyl, or azetidinyl, attached to the phenyl ring via a carbon
- R12/R13: either small carbocycles (3–7 membered, saturated or partially unsaturated), or 5–7 membered heterocycles containing N/O/S, or aryl/heteroaryl (with limited alternatives allowing H or C1–6 alkyl)
- n = 0–1
- p = 0–4
- q = 0
For the Formula (1) branch (claim 5 and claim 16):
- Similar R1/R2/R3/R4 themes with a structured set of constraints
- R6: C1–6 alkyl or C2–6 alkenyl or C2–6 alkynyl (as written in your claim text)
- Y: a 5–12 membered heterocyclic ring containing N/O/S, optionally substituted with defined lower alkyl and alkoxy/alkyl-hydroxyl patterns
- q = 0; n = 0
- Y attaches via carbon to A2 or A3 depending on the “when q in (CR2)qY is 0” language
Practical implication: Formula (1) reads like a broader heterocycle substitution allowance for Y (5–12 membered heterocycle with N/O/S), while Formula (2) narrows Y to specific azacyclic saturated amines (pyrrolidinyl, piperidinyl, azetidinyl). Both still constrain q to 0, which removes variable polymeric insertion described by (CR2)qY and keeps the attachment pattern fixed.
What do “X” and the functional options for R8/R9 imply for infringement risk?
In the Formula (2) claim language you provided:
Practical implication: once a competitor product lands in the defined scaffold and uses an ALK-responsive indication, the remaining infringement fight becomes mapping substituent identity (especially the presence/absence of Y-bound phenyl substitution and the exact X functional class). The breadth of X and the amide/ester/sulfur options increases coverage for designer analogs that swap functional groups at that locus.
Which compounds are explicitly called out in the claims you provided?
Your text lists specific members that act as anchor points for the genus and typically reflect commercially relevant or exemplified molecules.
Explicit examples listed
Claim 7 (Formula (2) branch):
- 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine
- or pharmaceutically acceptable salts.
Claim 9 (Formula (1) branch):
- N2-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5-methylpyrimidine-2,4-diamine
These examples also act as useful “claim construction anchors” during validity and infringement analysis because they show which moieties are considered within the intended scope of Formula (1)/(2).
What does the independent method claim “composition-to-treatment” structure mean for enforcement?
Your independent claims are drafted as:
- a method for treating a condition mediated by ALK, comprising:
- administering to a subject:
- a therapeutically effective amount of:
- a compound of Formula (1) or Formula (2),
- or a pharmaceutically acceptable salt,
- optionally with a second therapeutic agent.
So the claim is:
- indication-bound (ALK-mediated disease types),
- mechanism-bound (“condition mediated by anaplastic lymphoma kinase” / “responds to inhibition of ALK”),
- compound-genus-bound.
This is classic for ALK inhibitors where the clinical response is mechanism-linked.
Enforcement posture: liability attaches to the act of administering the defined compound for the defined ALK-responsive diseases, not to manufacturing per se, unless manufacturing induces direct performance of treatment steps (and unless there are separate product claims in the patent family).
How do claim 1 and claim 10 differ in practical scope?
Based on your text:
- Claim 1: method for treating ALK-mediated condition using compound of Formula (2), with additional detailed substituent definitions including:
- R6 is isopropoxy or methoxy
- Y is pyrrolidinyl/piperidinyl/azetidinyl
- R8/R9 includes explicit functional categories
- q is 0
- Claim 10: method for treating a condition “which responds to inhibition of ALK” using compound of Formula (2), repeating essentially the same R-group logic, but written in a slightly different structure.
Functionally, both cover the same chemical genus, but claim 10 emphasizes responsiveness to ALK inhibition rather than “mediated by ALK.” In litigation, that can matter only if an accused regimen disputes that ALK is causally implicated versus merely inhibited.
The dependent claims (NSCLC and neuroblastoma) sit under both branches.
How do Formula (1) method claims expand or contract relative to Formula (2)?
Comparing the two independent branches as provided:
Practical implication: Formula (1) likely creates broader coverage for alternative heterocycle “Y” rings and different R6 substituent classes. Formula (2) likely aligns closer to exemplified “piperidine/pyrrolidine/azetidine” patterns and can be easier to map for competitor scaffolds.
What does this imply for patent landscape and competitive freedom-to-operate?
Scope footprint in one line
US 8,377,921 covers ALK-mediated disease treatment in multiple indications by administering a pyrimidine-2,4-diamine ALK inhibitor chemical genus defined by complex substituent rules, including specific piperidinyl-based members.
Landscape effects (business impact)
- Indication lock-in risk: competitors developing ALK inhibitors for the listed diseases must check whether their molecule falls inside the Formula (1)/(2) substituent space. If it does, treatment of NSCLC or neuroblastoma can directly implicate the claim set as drafted.
- Salt and combination regimen coverage: “pharmaceutically acceptable salts” expand product coverage. “Optionally in combination with a second therapeutic agent” expands operational risk for standard-of-care combinations (chemotherapy + ALK inhibitor).
- Design-around complexity: because X and the functional options for other positions include amide/ester/cyano and sulfonyl-related patterns, simple functional group swaps at a single position may not remove coverage. The key design-around levers are more likely structural class changes that eliminate:
- the required phenyl-linked Y carbon attachment pattern (as constrained by q = 0 and the Y rule),
- the pyrimidine-2,4-diamine core mapping,
- or the sulfonyl-containing R3 / R12-defined moiety alignment.
What you can read from the claim language (not from missing data)
This patent is a method-of-treatment grant tied to a chemical genus. In practice, FTO risk can remain high even where competitors change dose, schedule, or specific second agent, as long as they administer the defined genus compound for the enumerated ALK-mediated diseases.
Key Takeaways
- US 8,377,921 is an ALK inhibitor method-of-treatment patent using broad Formula (1) and Formula (2) chemical genus claims plus optional combination therapy.
- The claims cover multiple ALK-mediated conditions, with explicit dependent narrowing to NSCLC and neuroblastoma.
- Formula (2) constrains Y to pyrrolidinyl/piperidinyl/azetidinyl and limits R6 to isopropoxy or methoxy.
- Formula (1) expands Y to a 5–12 membered N/O/S heterocycle and broadens R6 to alkyl/alkenyl/alkynyl as written.
- Functional position X and related substituent options include multiple amide/ester/cyano and sulfur-containing classes, reducing the effectiveness of minor functional group edits as a design-around.
FAQs
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Is this patent limited to ALK+ cancers only?
Yes for the listed ALK-mediated conditions, and it also includes neoplastic disease where the neoplastic disease is NSCLC.
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Does the patent require monotherapy?
No. It explicitly allows optional combination therapy with a second therapeutic agent, including chemotherapeutic agents in dependent claims.
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Does the patent cover salts of the compounds?
Yes. Each relevant method claim includes pharmaceutically acceptable salts.
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Are specific drug candidates named in the claims?
Yes. Your provided claims explicitly name at least two specific pyrimidine-2,4-diamine members (claim 7 for the Formula (2) branch and claim 9 for the Formula (1) branch).
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What is the key structural hook for infringement risk?
The requirement to administer a compound that fits Formula (1) or Formula (2), especially the pyrrolidinyl/piperidinyl/azetidinyl or N/O/S heterocycle Y linkage pattern (with q = 0) and the sulfonyl-containing and diamine core mapping.
References
- United States Patent and Trademark Office. US Patent 8,377,921. (Claims text as provided in the prompt).
