Details for Patent: 8,859,774

Which drugs does patent 8,859,774 protect, and when does it expire?

Patent 8,859,774 protects LIFYORLI (COPACKAGED) and is included in one NDA.

This patent has sixty-nine patent family members in twenty-five countries.

Summary for Patent: 8,859,774

Title:	Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
Abstract:	The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.
Inventor(s):	Hazel Hunt, Tony Johnson, Nicholas Ray, Iain Walters
Assignee:	Corcept Therapeutics Inc
Application Number:	US13/901,946
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,859,774
Patent Claim Types: see list of patent claims	Composition; Compound;

Scope and claims dissection of US Patent 8,859,774: what chemical space is covered, what is narrow, and where generic or follow-on entry risk concentrates

What is US Patent 8,859,774 claiming in plain claim-scope terms?

US 8,859,774 is an all-purpose Markush-style small-molecule composition-of-matter patent covering a large substituted pyrazolo[3,4-g]isoquinoline core scaffold with variable three-region substitution patterns and optional salts/isomers.

The independent claim (claim 1) is structured as:

• A core scaffold containing a bicyclic system explicitly present in the claim’s enumerated examples (pyrazolo[3,4-g]isoquinoline / hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl).
• Three substitution “handles” expressed as:
  • R1: a heteroaryl ring (5–6 members; 1–4 atoms N/O/S) optionally substituted by 1–4 groups from R1a.
  • ring J: a second ring (cycloalkyl, heterocycloalkyl, aryl, heteroaryl) with its own N/O/S limits when heterocyclic.
  • R2: a wide menu of substituents or linked-substituent alternatives (including conversion of two substituents into an oxo group, or into a heterocycloalkyl ring).
  • R3: phenyl or pyridyl, optionally substituted by 1–4 groups from R3a.
• Integer n = 0–3.
• Optional salts and isomers.

Claim 1 is therefore not a method-of-use or formulation-only claim. Claims 22–23 add a composition-of matter for a pharmaceutical composition.

How broad is the Markush space in claim 1?

Claim 1’s breadth is driven by three features: (i) R1 heteroaryl variability, (ii) ring J flexibility, (iii) R2’s “either-or” architecture that permits substituent linking into rings or oxo.

R1 heteroaryl scope (5–6 ring members; 1–4 N/O/S)

• R1 must be a heteroaryl with:
  • 5–6 ring members
  • 1–4 heteroatoms selected from N/O/S
• R1 is optionally substituted with 1–4 groups chosen from R1a.

R1’s own diversity is later narrowed and enumerated across dependent claims (5–8 and 6/7/8 in particular) into specific ring systems.

Implication: claim 1 covers any heteroaryl meeting the ring/member/heteroatom constraints, not just the examples. Dependent claims then “pin” subsets.

R1a substituent scope (optional 1–4 substituents on R1)

In claim 1, each R1a can be:

• hydrogen
• C1-6 alkyl
• halogen
• C1-6 haloalkyl
• C1-6 alkoxy
• C1-6 haloalkoxy
• CN
• N-oxide
• C3-8 cycloalkyl
• C3-8 heterocycloalkyl

Dependent claim 9 narrows R1a to:

• hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-8 heterocycloalkyl

Dependent claim 10 narrows further to:

• hydrogen, methyl, ethyl, trifluoromethyl, methoxy

Implication: the top claim is extremely permissive about substituents on the R1 heteroaryl. The dependent chain creates fallback positions for narrower compositions that may map better to actual lead compounds.

ring J scope

In claim 1:

• ring J can be:
  • cycloalkyl ring
  • heterocycloalkyl ring
  • aryl ring
  • heteroaryl ring
• if heterocycloalkyl or heteroaryl:
  • 5–6 ring members
  • 1–4 N/O/S atoms

Dependent claims narrow ring J to specific exemplars:

• Claim 3 includes ring J selected from tetrahydrofuran, phenyl, pyridyl.
• Claim 13 enumerates: phenyl, pyridyl, imidazole, pyrazole, triazole, tetrazole, thiadiazole, isothiazole, cyclohexyl, tetrahydrofuran, tetrahydro-2H-pyran.
• Claims 14–15 pick phenyl or pyridyl.

Implication: “ring J” is a key off-target risk for generics that attempt scaffold swaps or ring substitutions.

R2 scope: substituent menu plus “two R2 linked” alternatives

In claim 1, each R2 can be one of:

• hydrogen
• C1-6 alkyl
• halogen
• C1-6 haloalkyl
• C1-6 alkoxy
• C1-6 haloalkoxy
• C1-6 alkyl-C1-6 alkoxy
• CN
• OH
• —NR2aR2b
• —C(O)R2a
• —C(O)OR2a
• —C(O)NR2aR2b
• —SR2a
• —S(O)R2a
• —S(O)2R2a
• C3-8 cycloalkyl
• C3-8 heterocycloalkyl (optionally substituted)

Claim 1 also provides two architecture transformations:

1. two R2 groups linked to the same carbon → oxo group (═O)
2. two R2 groups → heterocycloalkyl ring (5–6 members; 1–3 N/O/S), optionally substituted with 1–3 R2d

And it further defines:

• R2a and R2b = hydrogen or C1-6 alkyl (for amine fragments)
• R2c = hydrogen, halogen, hydroxy, C1-6 alkoxy, C1-6 haloalkoxy, CN, —NR2aR2b
• R2d = hydrogen or C1-6 alkyl, or two R2d on same ring atom form oxo.

Dependent claims show R2 is also concretized:

• Claim 16 restricts R2 to hydrogen, C1-6 alkyl, halogen, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, and specific heterocycloalkyl (5–6 members; 1–2 heteroatoms).
• Claim 17 restricts R2 to a defined set: hydrogen, methyl, ethyl, F, Cl, —CF3, OMe, OCHF2, CN, NMe2, S(O)2Me, pyrrolidine, piperidine, morpholine.

Implication: the independent claim protects not only a broad substituent list, but also structural “collapse” options where substituent pairing can change functional group identity (e.g., oxo) or cyclize into a heterocycle. That blocks many straightforward design-around tactics that would otherwise swap two substituents for a ring or oxygen.

R3 scope

In claim 1:

• R3 is phenyl or pyridyl, optionally substituted with 1–4 groups from R3a.
• R3a = hydrogen, halogen, or C1-6 haloalkyl.

Dependent claims pin:

• Claim 18: R3 is “4-F-phenyl.”
• Other dependent claims keep phenyl/pyridyl options and/or narrow R3a.
• Claim 4 (very narrow) limits R2 and fixes R3a = F.

Implication: R3 appears to be a “signature” aromatic ring substituent position; its dependent claim ladder suggests litigation focus likely tracks specific R3 substitutions from the example list.

n = 0–3

Claim 1 has n as 0–3. Dependent claims include:

• claim 3: n = 0 or 1
• claim 2: n = 0–3 (no additional restriction beyond others)

Implication: n adds another axis of structural degrees of freedom and can preserve coverage even if a competitor shifts substitution pattern count.

Which dependent claims narrow the scope and how?

The dependent claims create fallback claim strata with narrower ring families and substituents.

R1 fixed lists (claims 5–8)

These enumerate heteroaryl ring identities for R1, including:

• Claim 5: broad set of 26 ring systems (pyrrole/pyrazole/imidzole/triazole/tetrazole/furan/oxazole/isoxazole/oxadiazole/thiophene/thiazole/isothiazole/thiadiazole plus pyridine derivatives).
• Claim 6: expanded positional variants and additional specific ring substitutions (e.g., “1,2,4-triazol-5-yl”, “2-furan”, “3-isoxazole”, “1,2,4-oxadiazol-3-yl”, etc.).
• Claim 7: narrower set (pyrazole, imidazole, triazole, furan, oxazole, oxadiazole, thiophene, thiazole, pyridine, pyrazine, pyrimidine).
• Claim 8: further narrower positional set including “1-pyrazole…5-pyrazole”, multiple imidazole/triazole positions, furan/oxazole/isoxazole positions, and pyridine/pyrimidine positions.

Implication: if actual commercial or accused compounds use a specific R1 positional isomer, dependent claims provide narrower infringement anchors.

R1a narrowed substituents (claims 9–10)

• Claim 9 restricts R1a to hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-8 heterocycloalkyl.
• Claim 10 restricts R1a to hydrogen, methyl, ethyl, trifluoromethyl, methoxy.

Implication: these are litigation-relevant because many practical medicinal chemistry series use limited R1a motifs.

ring J narrower enumerations (claims 3, 4, 11–15)

• Claim 3: ring J = tetrahydrofuran, phenyl, pyridyl.
• Claim 4: ring J = phenyl or pyridyl.
• Claim 11: ring J = heterocycloalkyl, aryl, or heteroaryl.
• Claim 12: ring J = aryl or heteroaryl.
• Claim 13: long enumerated list including phenyl, pyridine, imidazole, pyrazole, triazole, tetrazole, thiadiazole, isothiazole, cyclohexyl, tetrahydrofuran, tetrahydro-2H-pyran.
• Claim 14: ring J = phenyl.
• Claim 15: ring J = pyridyl.

Implication: ring J restrictions can make claim 1’s full breadth harder to prove if competitor design shifts ring J away from the example scaffolds.

R2 narrowed lists (claims 16–17)

• Claim 16: R2 constrained including heterocycloalkyl with 5–6 members and 1–2 heteroatoms.
• Claim 17: R2 in a concrete set including methyl/ethyl/F/Cl/CF3/OMe/OCHF2/CN/NMe2/S(O)2Me and cyclic amines (pyrrolidine/piperidine/morpholine).

Implication: claim 17 likely aligns with actual substitution patterns used in the enumerated compounds in claim 19–21.

R3 fixed to 4-F-phenyl (claim 18)

• Claim 18 sets R3 = 4-F-phenyl.

Implication: if the core marketed lead uses that R3 motif, claim 18 is a direct infringement position.

How do claims 19–21 function: do they “cover named compounds” or “ratchet the Markush”?

Claims 19–21 appear to list a very large set of specific stereochemically defined compounds and closely related examples, each described as:

• (R)-(…)(pyridin-2-yl)methanone, or similar methanone motifs
• salts and isomers.

Claim 19 includes extremely many enumerated compounds, including variants with:

• sulfonyl groups (e.g., aryl sulfonyl motifs with CF3, F, Cl, OMe, etc.)
• different heteroaryl acyl fragments (pyridinyl, thiazolyl, oxazolyl, furan-yl, thiophene-yl, pyrazinyl, etc.)
• stereochemistry on the hexahydro scaffold (e.g., “(R)-” at the substituted center).

Claim 20 is a very small subset: three specific compounds. Claim 21 is a middle subset: five specific compounds.

Interpretive effect for enforcement strategy (scope mechanics):

• Claim 1 already covers these examples by Markush ranges.
• Claims 19–21 create explicit “named species” anchors that can be used to streamline claim construction arguments around whether the accused compound falls squarely within the Markush parameters.
• They also reduce ambiguity in proving that the applicant contemplated those exact structures, which matters when arguing written description and enablement in litigation.

What about claim 22 and claim 23: are they composition-of-matter or formulation-only?

• Claim 22: a pharmaceutical composition comprising the claim 1 compound and a pharmaceutically acceptable excipient.
• Claim 23: claim 22 further comprising an anti-inflammatory glucocorticosteroid.

Implication:

• Claim 22 is standard and typically broad enough to cover finished dosage forms containing the API plus excipients.
• Claim 23 introduces a combination claim with a glucocorticosteroid, which can be used to block combination generics or label-proposed combination products, even if monotherapy formulations face separate design-around constraints.

What patent landscape questions matter most for this patent’s enforcement risk?

Even without external Orange Book and litigation data provided here, the claim architecture implies the following high-intent landscape issues:

1) Are competitors likely to be blocked by the R1/ring J/R2 Markush permutations?

• Because claim 1 is broad across R1 heteroaryls (5–6 members; N/O/S), ring J classes, R2 substituent families, and optional formation of oxo or heterocyclic ring via linked R2 groups, a large fraction of “follow-on analogs” still fall inside the claimed genus.

2) How do design-arounds typically fail against this claim?

Common generic or new-chemical-entity moves that may still be within scope:

• Changing aromatic substitution patterns but staying within R1a, R3a limits.
• Swapping among halogen/alkyl/alkoxy/haloalkoxy/CN families.
• Pairing substituents into oxo or heterocyclic constructs that match the “two R2 linked” alternatives.

3) Where is narrowing likely to be most consequential?

If an accused compound uses:

• a ring J outside the defined heteroatom count (for heterocyclic forms),
• an R2 outside the listed families or incompatible with the two-substituent-to-oxo or ring conversion,
• R1 heteroaryls outside the 5–6 member plus 1–4 N/O/S constraint, then claim 1 may not read. The dependent claims then become essential as “belt and suspenders” rather than the primary enforcement hook.

Scope map: claim elements to example compound motifs

From the enumerated species in claim 19, the repeated structural motifs are consistent with:

• sulfonyl aryl group attached to the hexahydro pyrazolo[3,4-g]isoquinoline nitrogen framework
• aryl/heteroaryl acyl fragment described as (…)(pyridin-2-yl)methanone or (…)(thiazol-2-yl)methanone etc.
• R3 appears to correspond to a phenyl or pyridyl substituted ring, including “4-fluorophenyl” and pyridyl variants.
• R1 likely corresponds to heteroaryls such as thiazole/oxazole/isoxazole/furan/pyrazole/triazole/tetrazole or pyridine/pyrimidine family rings, with substituent patterns matching halogen or CF3 motifs found in examples.
• stereochemistry: many examples are explicitly “(R)-” at a specific stereocenter.

This tight correspondence between Markush parameters and the listed species suggests the Markush is not hypothetical; it is built around a real lead series.

Business impact: what this means for generic entry or licensing

• If the marketed product API is one of the enumerated species or a close Markush variant, US 8,859,774 offers strong genus coverage, with explicit species listings for litigation convenience.
• If a generic attempts a scaffold shift, it must escape not only the core scaffold but also ring J class, R1 heteroatom constraints, and R2 permissible substituents including linked-substituent transformations.
• Combination risk: if the competitor targets glucocorticosteroid combination products, claim 23 adds a direct barrier.

Key Takeaways

• US 8,859,774 is a broad genus composition-of-matter patent driven by Markush variables R1, ring J, R2, R3, and n, with explicit stereochemical species lists in claims 19–21.
• The breadth is reinforced by structural “escape routes” being explicitly closed: R2 can convert into oxo or into a heterocycloalkyl ring through linked substituent alternatives.
• Dependent claims (5–10, 3–4, 13–18, 16–17) create a tiered narrowing ladder that can match specific stereochemical and substitution patterns used in the example compounds.
• Claims 22–23 expand protection into pharmaceutical compositions and a combination with anti-inflammatory glucocorticosteroids, relevant for formulation and label-level competition.

FAQs

1) Does US 8,859,774 protect only specific named compounds?
No. Claim 1 protects a broad Markush genus; claims 19–21 list specific species inside that genus.

2) What structural element is most likely to determine whether an analog still infringes claim 1?
ring J and the permitted R2 classes, including the linked two-R2 oxo/heterocycle transformations.

3) Are stereoisomers covered?
Yes. Claim 1 states “salts and isomers thereof,” and many examples are explicitly (R)-.

4) Can a company avoid infringement by changing R1 substitution patterns but keeping the ring type?
Claim 1 allows many R1a substituents; avoiding infringement likely requires exiting the defined heteroaryl constraints (5–6 members, 1–4 N/O/S) or leaving the R1a menu.

5) How does the glucocorticosteroid combination claim affect development strategy?
Claim 23 extends protection to compositions that pair the claimed compound with an anti-inflammatory glucocorticosteroid, raising combination-label and combination-product barriers.

References

(No external sources were cited in the provided content.)

Drugs Protected by US Patent 8,859,774

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Corcept Therap	LIFYORLI (COPACKAGED)	relacorilant	CAPSULE;ORAL	220641-001	Mar 25, 2026		RX	Yes	Yes			Y	Y

International Family Members for US Patent 8,859,774

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013266110
Brazil	112014028857
Brazil	112015022109
Brazil	112015022112
Canada	2872260
Chile	2014003173