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Patent landscape, scope, and claims: |
United States Patent 9,273,047: what glucocorticoid receptor modulation method claims cover and how wide the claim set is
Scope of US 9,273,047 claims: what does Claim 1 actually cover?
Executive summary: US 9,273,047 Claim 1 is a broad Markush method-of-use claim covering any glucocorticoid receptor modulation achieved by contacting the receptor with a compound of Formula I, where Formula I is defined by a large, combinatorial set of ring systems and substituent options (heteroaryl R1, ring J, substituted R2, and substituted R3), plus salts. Dependent claims narrow mainly by fixing R1 classes, specific ring J choices, and listing many specific stereochemical compound exemplars within the claimed Formula I space.
Claim type and exerted right
- Method of modulating glucocorticoid receptor by contacting the receptor with a Formula I compound.
- The claim is not limited to a route, dosing regimen, patient population, indication, disease state, or clinical endpoint.
- “Modulating” includes agonism, antagonism, partial agonism, or functional modulation as long as the receptor response is altered (scope depends on construction and prosecution history, not provided here).
Core structural architecture of Formula I (claim 1)
The claim’s Formula I definition is modular and can be mapped to four substitution “axes” that control infringement risk:
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Heteroaryl ring R1 (5–6 ring members; 1–4 heteroatoms from N/O/S)
- Optionally substituted with 1–4 groups R1a.
- R1a allowed: hydrogen; C1–6 alkyl; halogen; C1–6 haloalkyl; C1–6 alkoxy; C1–6 haloalkoxy; —CN; N-oxide; C3–8 cycloalkyl; C3–8 heterocycloalkyl.
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Ring J (linked to the remainder of the scaffold)
- Allowed: cycloalkyl, heterocycloalkyl, aryl, heteroaryl.
- Heterocycloalkyl/heteroaryl must be 5–6 ring members with 1–4 heteroatoms (N/O/S).
-
R2 (substituent set on the scaffold)
- Broadly defined hetero/hydrocarbyl groups and functional groups including: H, alkyl, halogen, haloalkyl, alkoxy, haloalkoxy, alkyl-alkoxy, —CN, —OH, —NR2aR2b, carbonyl/esters/amides, thio/ sulfone (including —S(O)R2a, —S(O)2R2a), cycloalkyl/heterocycloalkyl.
- Special structural alternatives:
- Two R2 groups on the same carbon may combine to make oxo (═O).
- Two R2 groups may combine to form a heterocycloalkyl ring (5–6 members; 1–3 N/O/S) optionally substituted by R2d (1–3 groups).
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R3 (phenyl or pyridyl, optionally substituted with 1–4 R3a)
- R3a allowed: hydrogen, halogen, and C1 haloalkyl.
-
n is 0–3
- The definition includes an integer subscript that likely corresponds to repeated substituents on an allowed position.
What dependent Claim 2/3/4/5 do
- Claim 2 lists a large set of heteroaryl choices for R1.
- Claim 3 further enumerates a large number of positional isomers and specific ring-member substitutions for R1 (e.g., 2/3/4/5-pyridine, pyrazole regioisomers, imidazole/triazole/tetrazole positional variants, oxazole/isoxazole positional variants, etc.).
- Claims 4 and 5 provide additional narrower sets (but still wide) for R1 in Claim 1’s Markush.
Net effect: dependent claims do not remove much coverage. They mainly demonstrate that the specification supports many R1 variants already encompassed by Claim 1’s generic R1 definition.
What dependent Claim 6/7 do
- Claim 6: restricts R1a to a smaller set (H, C1–6 alkyl, C1–6 haloalkyl, C1–6 alkoxy, C3–8 heterocycloalkyl).
- Claim 7: further restricts R1a to five exemplars: H, methyl, ethyl, trifluoromethyl, methoxy.
Net effect: these claims narrow substitution on R1, but remain operationally broad for product design because R1 substitution is only one axis among several.
What dependent Claim 8/9/10/11/12 do
- Claim 8: limits ring J to heterocycloalkyl, aryl, heteroaryl.
- Claim 9: limits ring J to aryl or heteroaryl.
- Claim 10: gives specific ring J examples: phenyl, pyridyl, imidazole, pyrazole, triazole, tetrazole, thiadiazole, isothiazole, cyclohexyl, tetrahydrofuran, tetrahydro-2H-pyran.
- Claims 11–12: fix ring J to phenyl and pyridyl respectively.
Net effect: ring J is another major infringement determinant. These claims show that the patent’s “commercially relevant” scaffold variants likely use aromatic and heteroaromatic J rings plus select saturated heterocycles.
What dependent Claim 13/14 do (R2 narrowing)
- Claim 13: restricts each R2 to a broad but somewhat constrained set and imposes that heterocycloalkyl group has 5–6 members and 1–2 heteroatoms.
- Claim 14: gives an even narrower set of R2 exemplars: H, methyl, ethyl, F, Cl, —CF3, OMe, OCHF2, —CN, —NMe2, —S(O)2Me, pyrrolidine, piperidine, morpholine.
Net effect: Claim 14 identifies the types of R2 functionalities that frequently appear in the enumerated compounds in Claim 16–18.
What dependent Claim 15 does (R3 narrowing)
- Claim 15: fixes R3 to “4-F-phenyl”.
- This indicates the patent’s examples include a 4-fluorophenyl R3 substituent.
Claims 16–18: enumerated compounds as “anchor” infringement bullets
Claims 16, 17, 18 recite selections from the compound universe under Claim 1. They are not independent structural formulas; they are hard lists of specific stereo-defined compounds (many include “(R)-” stereochemistry) that fall within Formula I.
Key point: Claim 1 already covers them if they match Formula I parameters; Claim 16–18 provide additional narrowing dependent claims and can help enforceability where Claim 1’s construction might be disputed.
- Claim 16 lists a very large set of compounds spanning:
- Sulfonyl-containing linkers (many “-sulfonyl” groups)
- Various heteroaryl/triazole/tetrazole/oxazole/thiazole substituents
- Various pyridyl variants (pyridin-2-yl, pyridin-3-yl, methyl-substituted pyridyl, trifluoromethyl-pyridyl)
- Multiple substituent regimes on the scaffold
- Multiple stereochemical states with “(R)-” at least, and at least one listing that includes “((4aR)-...)”
- Claim 17 trims to three specific compounds: two sulfonyl-linked variants and one pyridin-2-yl methanone variant with a specified trifluoromethyl phenyl sulfonyl group and thiazole variant.
- Claim 18 narrows to six specific compounds: a blend of trifluoromethyl-phenyl sulfonyl with pyridin-2-yl or thiazol-2-yl, plus two dichlorophenyl sulfonyl plus pyridin-2-yl variants, plus two additional exemplars with methyl-substituted pyrazole or thiazole heterocycles.
Infringement takeaway: Even if a challenger argues that Claim 1’s Markush coverage is overly broad, these listed compounds create an enforcement path for “near hits” that match at least one enumerated dependent claim.
Claim breadth quantification: how wide is the combinatorial space?
Executive summary: Coverage is defined by multiple Markush dimensions. While exact numeric combinations are constrained by the exact Claim 1 formula placement, the inclusion of:
- R1 heteroaryl (numerous ring types and positional isomers),
- ring J (aryl/heteroaryl/cycloalkyl/heterocycloalkyl),
- R2 with many functional group options plus cyclic/oxo alternatives,
- R3 as phenyl/pyridyl with halogen/C1 haloalkyl substitution,
- salts,
creates a highly heterogeneous chemical genus.
High-impact scope levers
- R1 ring system and substitution: broad inclusion of N/O/S heteroaryl rings and typical medicinal chemistry substitutions (alkyl, halogens, haloalkyl, alkoxy, CN, N-oxide).
- R2 substituents: includes classic polar and electrophile-friendly groups (amide/ester/carbonyl, sulfone/sulfoxide-like functions, amines, thioethers, —CN, —OH) which increase the number of plausible “design around” candidates while still likely falling in the Markush.
- R2 “merge” options: the oxo (═O) and heterocycloalkyl ring-formation alternatives materially affect infringement because they allow structural variation without changing the Markush endpoints.
- ring J: aromatic and heteroaromatic options mean that scaffold modifications can still land inside the claim if they keep J within the enumerated families.
What does the claim say about “glucocorticoid receptor modulation” and patient use?
Executive summary: The patent is framed as a target engagement method (contacting glucocorticoid receptor with Formula I compound) and does not limit to a disease indication.
What is included (by claim construction logic)
- Any experimental setup where a glucocorticoid receptor is contacted with a Formula I compound and the receptor is modulated.
- Cellular assays, in vitro binding/functional assays, ex vivo systems, or in vivo administration can all potentially meet the “contacting” language if receptor modulation is demonstrated.
What is not stated in the provided claims
- No explicit therapeutic indication (inflammatory disease, asthma, COPD, autoimmune conditions, dermatologic conditions, etc.).
- No route-of-administration limitation.
- No dosing schedule or patient subgroup limitation.
- No “effective amount” language appears in the excerpted claims; even so, enforcement may rely on statutory method-of-use construction and specification support, but the excerpt alone does not supply that.
Practical implication: For licensing or litigation strategy, the enforceability focus becomes the chemical match (Formula I coverage) rather than the clinical claims.
Which parts of the claim are most vulnerable to design-around?
Executive summary: For a generic, licensee, or competitor, the main design-around levers are to exit the Formula I parameter space or to remove “contacting glucocorticoid receptor” from the literal method-of-use frame (e.g., by changing the mechanism so it does not modulate the receptor).
Design-around strategies aligned to the claim language
- Change R1 class outside the allowed heteroaryl space
- Example: use heterocycles not covered by the Claim 1 R1 definition (or add atom types outside N/O/S counts, depending on how “from 1 to 4 heteroatoms each independently selected from N, O and S” is construed).
- Change ring J outside allowed J families
- Claim 10 and others narrow J, but Claim 1 allows broad J families; still, a competitor could use a J substituent outside allowed types (for example, if a scaffold uses different ring composition outside the “cycloalkyl/heterocycloalkyl/aryl/heteroaryl with N/O/S heteroatoms in 5–6 membered rings” constraints).
- Change R2 substituent type outside listed substituent classes
- Claim 1 includes many functional group classes; the vulnerability is to use a functional group family not in the allowed “including” list and not captured by the Markush generalities.
- Exploit R2 merge alternatives as a trap
- Because Claim 1 includes oxo and heterocyclo merge alternatives, design-around should avoid a structural configuration that could be argued to fall under a “combined R2” alternative.
Patent landscape analysis for US 9,273,047: what else likely exists in the estate?
Executive summary: The excerpt provides claim text only, not bibliographic data (assignee, filing date, application number, priority, family members). Without that, an accurate landscape across continuation family members, counterpart jurisdictions, and citation map cannot be produced from the provided record.
Result: No complete, citation-grade landscape can be generated under the constraint that only sufficient information can be used.
Key infringement mapping: the “enumerated compounds” in Claims 16–18
Executive summary: Claims 16–18 list multiple (R)-stereochemical variants anchored to a pyrazolo-fused bicyclic scaffold and a sulfonyl-linked aromatic/heteroaryl system, each tied to a pyridinyl or thiazolyl carboxamide/methanone moiety.
Below is the most decision-relevant structure-to-claim linkage:
Claim 17 (3 anchor compounds)
- (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-...)(pyridin-2-yl)methanone
- (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-...)(thiazol-2-yl)methanone
- (R)-(1-(4-fluorophenyl)-6-((3-(trifluoromethyl)phenyl)sulfonyl)-...)(pyridin-2-yl)methanone
Claim 18 (6 anchor compounds)
- Includes the same core trio above plus:
- (6-((3,4-difluorophenyl)sulfonyl)-...)(pyridin-2-yl)methanone
- (6-((3,4-dichlorophenyl)sulfonyl)-...)(pyridin-2-yl)methanone
- (1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-...)(4-(trifluoromethyl)pyridin-2-yl)methanone
- (6-((3,4-dichlorophenyl)sulfonyl)-...)(thiazol-2-yl)methanone
- (6-((3,4-dichlorophenyl)sulfonyl)-...)(5-methylthiazol-2-yl)methanone
Enforcement logic: Any competitor product, research tool, or intermediate that matches one of these exemplars will likely meet Claim 1 as well, assuming it fits the Formula I parameterization.
Key Takeaways
- US 9,273,047 Claim 1 is a broad method-of-modulating glucocorticoid receptor claim tied to a large Markush Formula I compound genus.
- Dependent claims narrow by fixing R1, ring J, and R2/R3 sets, but these are still wide medicinal-chemistry families.
- Claims 16–18 are enforceable “anchor” lists of specific stereodefined compounds centered on a sulfonyl-linked aromatic/heteroaryl motif and a fused bicyclic scaffold, each aimed at modulation of the glucocorticoid receptor.
- Design-around must focus on structural axes that drive Formula I boundaries: R1 heteroaryl family/substitution; ring J ring class; R2 functional group class and merge alternatives; and R3 phenyl/pyridyl substitution limits.
- A full US patent landscape (expiration, continuation claims, Orange Book, litigation, generic/biosimilar risks, family members) cannot be generated from the provided excerpt alone.
FAQs
- Does US 9,273,047 require a specific therapeutic indication to infringe?
- How do the Markush definitions in Claim 1 affect “design-around” compared with a single-spec structure claim?
- If a compound matches one enumerated example in Claim 17 or 18, does it automatically fall under Claim 1?
- Which substituent axis (R1, J, R2, or R3) is the most likely to be targeted in a chemical redesign to avoid Formula I?
- Can in vitro receptor assays satisfy the “contacting a glucocorticoid receptor” method language?
References
- United States Patent 9,273,047, claims 1–18 (text provided in prompt).
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