Scope, Claims, and US Patent Landscape for US Drug Patent 9,314,464
What does US 9,314,464 claim?
US Patent 9,314,464 is a method-of-treatment patent for cancers driven by B-Raf protein kinase signaling, using a compound of Formula (Ia) (or a tautomer, stereoisomer, or pharmaceutically acceptable salt). The claim set is built around (i) a broad oncology target and indication basket, (ii) a large Markush chemical space for Formula (Ia)/(Ib), and (iii) combination therapy that includes MEK inhibitors (with ARRY-438162 called out multiple times).
Core treatment method (Claim 1)
Claim 1 covers:
- Target / mechanism: “a B-Raf protein kinase mediated cancer”
- Indications (basket): lung, pancreatic, bladder, colon; prostate; thyroid; melanoma; myeloid disorders; and adenomas and carcinomas of ovary, eye, liver, biliary tract, and nervous system
- Therapeutic intervention: administering “an effective amount” of Formula (Ia) compound, including
- tautomers
- stereoisomers
- pharmaceutically acceptable salts
Chemical scope construct: Formula (Ia) is defined through variables including:
- Y is N or CR6
- R2, R3, R5, R6 each independently from H, halo, cyano, C1-4alkyl, halo-C1-4alkyl, C1-4alkoxy, halo-C1-4alkoxy
- a specific proviso: “when R5 is fluoro, R3 and R6 are not both hydrogen”
- R4 is —R9 or —NR10R11
- R9 is a C1-6 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, aryl, or heteroaryl, optionally substituted with 1 to 3 radicals selected from halo, cyano, C1-4alkyl, halo-C1-4alkyl, C1-4alkoxy, halo-C1-4alkoxy
- R10 and R11 are independently H or R9
- R7 is H, C1-4alkyl, C3-5 cycloalkyl, or C3-5 heterocycloalkyl, optionally substituted with 1 to 3 radicals from halo, cyano, hydroxyl, C1-4alkyl, halo-C1-4alkyl, C1-4alkoxy, halo-C1-4alkoxy
Narrowing dependent claims (Claims 2–3)
- Claim 2: restricts R4 to —R9 and limits R9 to C1-3 alkyl and C3-8 cycloalkyl, with optional substitution limited to halo / halo-substituted C1-4alkyl.
- Claim 3: selects specific halogen and alkyl patterns:
- R2 is H or fluoro
- R3 is chloro, fluoro, or methyl
- R5 is H, chloro, or fluoro
- Y is N or CR6
- R6 is H or fluoro
Enumerated compounds list (Claim 4)
Claim 4 selects Formula (Ia) compounds from a named list of specific methyl carbamate derivatives with defined pyrazole/pyrimidine cores and substituted sulfonamides and fluoro/chloro patterns. This list includes (examples from the claim):
- “methyl N-[(2S)-1-({4-[3-(3-chloro-5-methanesulfonamidophenyl)-1-(propan-2-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
- “methyl N-[(2S)-1-({4-[3-(5-chloro-2-fluoro-3-methanesulfonamidophenyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
- “methyl N-[(2R)-1-({4-[3-(5-chloro-2-fluoro-3-methanesulfonamidophenyl)-1-(propan-2-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
- “methyl N-[(2S)-1-[(4-{3-[5-chloro-2-fluoro-3-(propane-1-sulfonamido)phenyl]-1-(propan-2-yl)-1H-pyrazol-4-yl}pyrimidin-2-yl)amino]propan-2-yl]carbamate”
This matters for enforcement strategy: even if a generic competitor stays within Claim 1’s Markush ranges, Claim 4’s explicit “selected from the group consisting of …” list creates a set of high-confidence infringements where mapping is direct.
What is Formula (Ib) and how does it change the scope? (Claims 5–6)
Claims 5 and 6 shift from Formula (Ia) to a narrower Formula (Ib) defined by functional variable selection:
Claim 5: Formula (Ia) equals Formula (Ib)
For Claim 5:
- R3 is chloro, fluoro, or methyl
- R5 is fluoro or chloro
- R7 is ethyl or isopropyl
Claim 6: enumerated Formula (Ib) compounds
Claim 6 lists additional specific methyl carbamate derivatives meeting the Formula (Ib) constraint. The list includes compounds such as:
- “methyl N-[(2S)-1-({4-[3-(5-chloro-2-fluoro-3-methanesulfonamidophenyl)-1-(propan-2-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
- “methyl N-[(2S)-1-({4-[3-(2,5-difluoro-3-methanesulfonamidophenyl)-1-(propan-2-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
- “methyl N-[(2S)-1-({4-[3-(5-chloro-2-fluoro-3-methanesulfonamidophenyl)-1-ethyl-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
- “methyl N-[(2R)-1-({4-[3-(5-chloro-2-fluoro-3-methanesulfonamidophenyl)-1-(propan-2-yl)-1H-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate”
These enumerations are the enforcement pivot points for the narrower sub-portfolio.
How broad is the combination therapy coverage?
US 9,314,464 includes combination claims layered onto the method-of-treatment concept. This expands infringement risk to regimens, not only to chemical structure.
Additional therapeutic agent basket (Claims 7–8 and 14–16 and 21–23)
Claim 7 adds:
- “an additional therapeutic agent selected from”
- anticancer drug
- pain medication
- antiemetic
- antidepressant
- anti-inflammatory agent
Claim 8 ties administration logistics:
- additional agent may be simultaneously, concurrently or sequentially with Formula (Ia).
Switch to targeted partner class (Claims 9–13)
Claim 9 narrows the additional agent class to:
- “a Raf kinase inhibitor or an inhibitor of MEK, mTOR, HSP90, AKT, PI3K, CDK9, PAK, Protein Kinase C, a MAP kinase, a MAPK Kinase, or ERK.”
Claim 10 narrows further:
- “an inhibitor of MEK or PI3K”
Claim 11 enumerates MEK inhibitors:
- AS703026
- MSC1936369B
- GSK1120212
- AZD6244
- PD-0325901
- ARRY-438162
- RDEA119
- GDC0941
- GDC0973
- TAK-733
- RO5126766
- XL-518
Claim 12 selects ARRY-438162.
Claims 13 (and the corresponding chain for Formula (Ib)) specify sequencing:
- ARRY-438162 administered sequentially with Formula (Ia).
Formula (Ib) combination chain (Claims 14–20 and 21–27)
Claims 14–20 mirror the above but reference Formula (Ib).
Claims 21–27 mirror again and include the same MEK inhibitor enumeration and the ARRY-438162 sequential administration concept.
Practical scope map: what the claims cover and how it infringes
The patent can be read as three concentric coverage layers.
Layer 1: Indication and target
- Any subject with a qualifying cancer
- Defined by “B-Raf protein kinase mediated cancer”
- Broad tissue basket list
Layer 2: Drug definition by Markush
- Formula (Ia) Markush space in Claim 1
- Specific sub-ranges in Claims 2–3
- Named “selected from” compounds in Claim 4 (high signal for infringement mapping)
Layer 3: Regimen coverage
- Combination with broad categories in Claim 7
- Combination with pathway inhibitors in Claim 9
- Combination with MEK/PI3K inhibitors in Claim 10
- Specific MEK inhibitor list in Claim 11
- ARRY-438162 explicitly called out in Claims 12–13 and 19–20 (and corresponding (Ib) counterparts)
Patent landscape implications in the US (what this claim structure signals)
Without the rest of the patent record (publication history, assignee, file lineage, priority chain, prosecution events, expiration), a complete landscape cannot be built. What can be concluded from the claim architecture alone is how the patent functions in a US freedom-to-operate (FTO) exercise:
1) The infringement risk is driven by “method of treating” rather than composition claims
This pushes FTO analysis toward:
- whether a clinician/prescriber regimen maps to the claims
- whether any label-like or study-like dosing protocol includes the Formula (Ia)/(Ib) compound with MEK inhibitors
2) Combination claims enlarge the addressable product-use scenarios
If a sponsor markets or studies a B-Raf directed agent that overlaps Formula (Ia)/(Ib) chemistry and pairs it with:
- MEK inhibitors from the enumerated list (especially ARRY-438162)
then the combination claims create a direct infringement vector even when the chemical core mapping is narrow.
3) Enumerated compounds function as “anchor points”
Claim 4 and Claim 6 enumerate specific methyl carbamate stereochemical variants. In enforcement and FTO, enumerated anchors reduce interpretive leeway and support straightforward element-by-element mapping.
Claim coverage checklist (for counsel or BD diligence)
A regime or competitor product is within the claimed method if all of the following line up:
- Cancer type matches the listed basket in Claim 1 (lung, pancreatic, bladder, colon, prostate, thyroid, melanoma, myeloid disorders, and adenomas/carcinomas in ovary/eye/liver/biliary tract/nervous system).
- The treatment is B-Raf protein kinase mediated.
- The administered compound is Formula (Ia) or a tautomer/stereoisomer/salt, with variable constraints satisfied (Claims 1–3) or with one of the enumerated list compounds (Claim 4).
- If combinations are involved:
- additional agent falls in the Claim 7 basket, or
- is a Raf/MEK/PI3K pathway inhibitor class (Claims 9–10),
- and if MEK inhibitors are used, the agent must match the Claim 11 list, with ARRY-438162 creating the tightest mapping (Claims 12–13; 19–20; and equivalents for Formula (Ib)).
Key Takeaways
- US 9,314,464 is a method-of-treatment patent for B-Raf mediated cancers with a broad tissue basket and a Markush-defined chemical core (Formula Ia).
- Claims 4 and 6 enumerate specific methyl carbamate stereochemical compounds, creating high-confidence infringement anchors.
- The claims expand beyond monotherapy: combination therapy is covered across broad supportive-care and oncology combination categories, with a focused pathway inhibitor subset.
- The most actionable commercial infringement risk is tied to MEK/PI3K combinations, especially where the MEK inhibitor is ARRY-438162 and is given in sequence.
FAQs
1) Are the claims limited to a single cancer indication?
No. Claim 1 lists a broad basket spanning multiple carcinomas and myeloid disorders plus adenomas and carcinomas across several organ sites.
2) Does infringement require exact matching to Formula (Ia) or (Ib) enumerated compounds?
Not necessarily for Claim 1. The Markush definition in Claim 1 can capture unenumerated structures, while Claims 4 and 6 create explicit “selected from” sets.
3) Do the claims cover both salts and stereoisomers?
Yes. Claim 1 includes tautomers, stereoisomers, and pharmaceutically acceptable salts of the Formula (Ia) compound.
4) Is combination therapy required for all claims?
No. Claims 1–3 can cover monotherapy by administering Formula (Ia). Combination claims start at Claim 7 (and their dependent chains).
5) Which co-therapy agents are most critical for risk mapping?
MEK inhibitors in Claim 11, with ARRY-438162 expressly selected in multiple dependent claims, including sequential administration language.
References
[1] US Patent 9,314,464 (claims provided in prompt).
