|
Patent landscape, scope, and claims: |
United States Patent 9,416,136: Scope, Claim Boundaries, and US Patent Landscape for CDK4 Inhibition in Cancer
What does US 9,416,136 claim, in plain functional terms?
US 9,416,136 claims methods of treating cancer by inhibiting cyclin-dependent kinase 4 (CDK4) through administration of a compound “of formula I” (and dependent narrower formulas/definitions) or pharmaceutically acceptable salts. The inventive hinge is structural variation inside a broad Markush-style scaffold that constrains the core heteroaromatic system and the ring-linker/amine substituent patterns, while allowing wide latitude in substituent identity.
The independent claim set provided contains two independent method pathways:
- Claim 1: method by administering “compound of formula I” with extensive substituent variables (X, R1-R6, R2, L, Y, R3, R9, m, n, R8, R14-R15).
- Claim 5: method by administering a “compound of formula I(a)” with a narrower, enumerated variable set (R50-R57, Z, V) and fixed sub-substituent values (notably R54 and R55 both methyl; several others set to H).
A third independent-style scope comes from Claim 6, which enumerates specific drug candidates (named chemical structures) and treats their administration as falling within the claimed CDK4-inhibiting method.
What is the claim 1 structural “machine”: which variables matter most?
Claim 1 recites a Markush formula I where the variable definitions effectively define:
1) the heteroatom identity at X (X is CR9)
2) the amide substituent at R1 (R1 is CONR5R6 and R5-R6 are C1-8 alkyl)
3) the cycloalkyl ring at R2
4) the linker L joining to the Y/W-containing segment
5) the Y/W unit (H/OH or an N-containing moiety)
6) the R3 aryl/alkyl envelope for additional substitution on the core
7) the terminal substitution at R9 (H or halogen)
8) spacing/degree parameters m and n (each 0-2)
9) where allowed, R8 substituents on the Y part (C1-8 alkyl, oxo, or bridged alkyl)
10) the R14/R15 amine substituent envelope.
Claim 1 variable map (as provided)
| Variable |
Claim 1 limitation (key bounds) |
Practical meaning for scope |
| X |
CR9 |
X is carbon bearing R9 (H or halogen). Locks that position as non-hetero. |
| R9 |
H or halogen |
Halogen at that carbon is permitted; no other substituents. |
| R1 |
CONR5R6 |
Adds an amide at this position. |
| R5, R6 |
C1-8 alkyl |
Amide is N,N-dialkyl (or dialkyl amide), no aryl/hetero on N in this claim. |
| R2 |
C3-14 cycloalkyl |
Broad cycloalkyl substitution. Dependent claim 3 narrows to cyclopentane. |
| L |
bond, C1-8 alkylene, C(O), or C(O)NH (optionally substituted/unsubstituted) |
Linker chemistry is flexible (alkylene vs carbonyl types vs direct bond). Substitution allowed on L. |
| Y |
H, OH, or Y is part of a group where Y is N and W is CR9, or N and 0-2 R8 may be present |
Y is either simple H/OH or part of a defined N-containing fused/linked unit with W and possible R8 patterning. |
| R8 |
C1-8 alkyl, oxo, or bridged alkyl group |
Permits substitution richness in the Y-domain. |
| R3 |
enumerated set of alkyl/cycloalkyl/amine-carbonyl/alcohol/cyano substituents, with optional substitution OH, CN, F, NH2 |
This is one of the most expansive degrees of freedom in Claim 1. |
| R14/R15 |
each independently H, C1-8 alkyl, C3-14 cycloalkyl, alkoxy, C(O)C1-3 alkyl, C1-8 alkylNH2, or C1-6 alkylOH |
Defines terminal substituents on the R3-associated N atoms (where present). |
| m,n |
independently 0-2 |
Controls length or substitution count on the Y/W segment per the formula definition. |
What is claim 2-4 doing: tightening the scaffold along a narrower corridor?
- Claim 2: narrows R3 to H, C1-8 alkyl, or C1-8 alkylOH (or salts). This excludes many enumerated R3 forms from Claim 1.
- Claim 3: narrows R2 to cyclopentane (or salts).
- Claim 4: narrows Y to the case where m=1 and n=1 and Y and W are N (or salts). This selects a specific topology for the Y/W unit.
These dependent claims operate as fences inside the already broad Markush.
How does Claim 5 narrow the scope versus Claim 1?
Claim 5 claims the method via formula I(a), with a defined variable pattern:
- R50 = CONR54R55
- R51 = C3-14 cycloalkyl optionally substituted by C1-3 alkyl or OH
- Z = CH or N
- V = NR56 or CHR57
- R54 and R55 both methyl
- R52, R53, R56, R57 all H
This is a material reduction of degrees of freedom relative to Claim 1:
- Amide nitrogens are fixed as dimethyl (R54=R55=methyl).
- Several other variables are fixed to H.
- The remaining flexibility clusters in:
- cycloalkyl identity at R51
- whether Z is CH or N
- V being an N-substitution vs CH.
Claim 6: enumerated “product” compounds inside a method claim
Claim 6 lists a large set of specific chemical entities as options for administration (with stereochemical variants). In practice, this converts parts of the Markush space into explicit coverage for particular analogs.
Representative structure classes appearing in Claim 6 (from the enumerated list)
All listed examples share the same broad core scaffold flavor, with variations concentrated in:
- substitution at the pyridine-2-ylamino region
- the amine substituent side chain (often piperazine with ethyl/methyl/hydroxyethyl/hydroxypropyl/various substituted piperazines, plus other saturated bicyclic amines)
- optional stereochemistry (R/S configurations on chiral side chains)
- optional carbonyl substituents (carbamoylmethyl, piperazine-1-carbonyl, and related acylated amines).
This claim is important for the landscape because it creates clear, checkable infringement targets: if a competitor compound is one of the enumerated structures, the method claim directly tracks.
Dependent claims 7-12: further internal restriction on R3, m/n, R8, and L/Y cases
- Claim 7: R3 limited to H, methyl, ethyl, propyl, isopropyl, CH2OH, CH2CH2OH (or salts).
- Claim 8: m=2 and n=1.
- Claim 9: R8 = methyl, ethyl, propyl, butyl, oxo or two R8 form a bridged group.
- Claim 10: L is bond and Y is not H.
- Claim 11: L is bond, with Y is where m and n are 1 or 2 and Y and W are N.
- Claim 12: dependent on Claim 11, sets R3 again to the limited small aliphatic set (H, methyl/ethyl/propyl/isopropyl/CH2OH/CH2CH2OH).
These dependent claims carve out a subset that is far less likely to read on remote analogs.
What cancer indications are expressly named in the claims?
Claim 13-23 list tumor types as dependent embodiments under the umbrella “cancer” in Claim 1. They include:
| Dependent claim |
Cancer type specified |
| 13 |
breast carcinoma |
| 14 |
colon carcinoma |
| 15 |
lung carcinoma |
| 16 |
acute lymphoblastic leukemia |
| 17 |
chronic myelogenous leukemia |
| 18 |
melanoma |
| 19 |
tumor of mesenchymal origin |
| 20 |
pancreatic cancer |
| 21 |
prostate cancer |
| 22 |
non-small-cell lung cancer |
| 23 |
mantle cell lymphoma |
From a landscape angle, this indication list is a use-based claim scope. If a competitor runs CDK4 inhibitors in any of these settings, a method claim reading on the compound can become enforceable by indication.
Where are the “most probable design-around” pressure points?
Even without prosecution history, the claim language identifies key constraint axes that designers typically target:
1) The amide N,N-dialkyl feature at R1 / R50
- Claim 1: R1 is CONR5R6 with R5 and R6 C1-8 alkyl.
- Claim 5: R54 and R55 both methyl (dimethylamide).
If a competitor changes the amide identity away from dialkyl amide (for example, swaps to non-amide linkage or changes N substitution beyond C1-8 alkyl), they may avoid reading the formula variables.
2) The cycloalkyl range at R2
- Claim 1: C3-14 cycloalkyl.
- Claim 3: cyclopentane.
A competitor with non-cycloalkyl or a constrained ring outside the allowed band may reduce overlap.
3) Linker L options
- Allowed: bond, C1-8 alkylene, C(O), C(O)NH (substituted/unsubstituted).
Changing the linker chemistry outside those enumerations is a likely design-around lever.
4) Y/W N-containing topology
Claim 4/10/11 heavily condition Y and W on m,n and N assignments. Avoiding that topology is a direct way to evade the dependent claim subsets, though Claim 1 still has broad “Y is H or OH” and an N-defined alternative.
5) R3 substitution envelope
- Claim 1 enumerates R3 categories including several carbonyl-bound amine motifs, alcohols, cyano, halogenable patterns, and related groups.
- Claim 2/7/12 narrow R3 to only small groups.
Competitors can try to use R3 substitutions outside the enumerated categories.
What does this imply for claim coverage versus a competitor’s pipeline?
Given the claim construction:
- If the competitor compound is within the enumerated Claim 6 list, the method claim is strong because it is not dependent on Markush interpretation for that subset.
- For compounds not literally listed, enforcement depends on Markush mapping:
- Whether the compound can be mapped to formula I under Claim 1 (broad) or formula I(a) under Claim 5 (narrower).
- Whether the competitor’s specific R2, L, Y/W, and R3 substitutions fit the variable definitions.
- Whether the competitor is treating any of the dependent indications listed in Claims 13-23.
Patent landscape: how to position US 9,416,136 against likely related CDK4 inhibitor IP
The provided text contains no assignee, filing history, priority dates, prosecution details, or references. Without those bibliographic facts, the landscape cannot be accurately populated with:
- family members
- related US continuations
- co-owned method vs composition claims
- citation sets (prior art patents/non-patent literature)
- expiration, PTA, or terminal disclaimer information
Per constraints, the landscape below is limited to claim-logic-based positioning rather than specific patent-by-patent mapping.
Landscape buckets determined by claim architecture (actionable for freedom-to-operate triage)
| Landscape bucket |
What to check in the patent record |
Why it matters to US 9,416,136 |
| Composition-of-matter claims on the same scaffold |
Look for companion US patents claiming the compounds themselves (not just methods) |
If a strong composition claim exists, method-only defenses are insufficient. |
| Method-of-use continuations |
Look for continuations/divisionals that keep Markush expansion but change indication or linker/amide variables |
Dependent indication claims suggest use-specific amendment paths. |
| Second-gen analog families |
Look for later filings that alter R3/R8/L/Y topology |
Claim 1 is broad, but Claim 5 and Claim 6 enumerate specific analog patterns that may anchor later families. |
| Regulatory exclusivity overlap |
Check whether any listed analog ties to approved products |
A method claim can still be relevant, but enforcement often aligns with clinical development. |
How strong is the US claim set structurally, for coverage breadth?
Based on what is visible in the claims text:
- Claim 1 is very broad structurally due to:
- wide R3 enumerations
- multiple linker options for L
- optional substitution patterns via R8 and m/n
- Y can be H/OH or N-defined unit
- Claim 5 is tighter structurally:
- dimethylamide is fixed
- multiple variables fixed to H
- V and Z each limited
- Claim 6 hard-codes a large set of compounds that likely sit near the marketed/lead chemical series.
The overall coverage pattern is typical of a portfolio approach:
- one broad Markush method claim
- one narrower Markush method claim
- one enumerated list to reduce claim construction risk for key analogs.
Key Takeaways
- US 9,416,136 claims CDK4-inhibiting cancer treatment by administering formula-based compounds, with Claim 1 providing broad Markush coverage and Claim 5 narrowing to formula I(a) with fixed dimethylamide (R54=R55=methyl).
- Claim 6 enumerates dozens of specific compounds, turning parts of the Markush space into directly identifiable administration options.
- Design-around pressure points are the amide N,N-dialkyl feature, the allowed linker L, the Y/W N-containing topology, and the enumerated R3 envelope.
- Indication language is explicit for breast, colon, lung (including non-small-cell lung), leukemia subtypes, melanoma, pancreatic cancer, prostate cancer, mesenchymal-origin tumors, and mantle cell lymphoma.
FAQs
1) Does US 9,416,136 claim a treatment method for any cancer or only specified cancers?
It claims a general cancer treatment method in Claim 1, with dependent claims expressly listing specific cancer types (Claims 13-23).
2) Is Claim 6 tied to formula interpretation or literal compound identity?
Claim 6 lists specific chemical names/structures for administration, so coverage for those embodiments depends on whether the administered compound matches one of the listed candidates.
3) Which claim is broader: Claim 1 or Claim 5?
Claim 1 is broader because it allows wide variation across many variables; Claim 5 fixes several variables (notably R54 and R55 to methyl and others to H).
4) What is the most constrained chemical feature across the independent claims?
The amide is constrained in both: Claim 1 requires CONR5R6 with C1-8 alkyl N-substituents, while Claim 5 fixes the amide N-substituents as methyl (dimethylamide).
5) How do the dependent R3 and Y-linked claims affect risk assessment?
Dependent claims 2, 4, 7, 8, 10-12 narrow variable ranges and topology. They reduce breadth for those subsets, but Claim 1 can still cover broader embodiments if the competitor compound fits the general formula variables.
References
[1] US Patent 9,416,136 (claims text as provided by user).
More… ↓
⤷ Start Trial
|
