| Abstract: | Compounds of formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein X is CO and Y is NH;Z is NR3 wherein R3 is hydrogen, C1-6 alkyl, C3-7 alkenyl-methyl, phenyl or phenyl C1-4 alkyl either of which phenyl moieties may be substituted by one or two of halogen, CF3, C1-6 alkoxy or C1-6 alkyl; and Ra is not present; orZ is N and Ra is as defined for R3 above;Rb is present when X-Y-R2 is attached at the phenyl ring and is selected from hydrogen, halogen, CF3, hydroxy, C1-6 alkoxy or C1-6 alkyl;R1 is hydrogen, halogen, CF3, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-7 acyl, C1-7 acylamino, C1-6 alkylsulphonylamino, N(C1-6 alkylsulphonyl)-N-C1-4 alkylamino, C1-6 alkylsulphinyl, hydroxy, nitro or amino, aminocarbonyl, aminosulphonyl, aminosulphonylamino or N-(aminosulphonyl)-C1-4 alkylamino optionally N-substituted by one or two groups selected from C1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl C1-4 alkyl, phenyl or phenyl C1-4 alkyl groups or optionally N-disubstituted by C4-5 polymethylene;R2 is a group of formula (a) ##STR2## wherein n is 2 or 3; and R4 is C1-7 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl-C1-2 alkyl, or a group (CH2)t R6 where t is 1 or 2 and R6 is thienyl, pyrrolyl or furyl optionally substituted by one or two substituents selected from C1-6 alkyl, C1-6 alkoxy, trifluoromethyl or halogen, or is phenyl optionally substituted by one or two substituents having 5-HT antagonist activity and/or gastric motility enhancing activity. |
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Patent landscape, scope, and claims: |
United States Patent 4,886,808: Scope of Claims and Patent Landscape
What does US 4,886,808 claim?
US 4,886,808 claims a structured class of compounds defined by Formula (I), broad substitution-variable ranges on a bicyclic-indazole carboxamide scaffold, and methods/compositions for multiple neurologic and psychiatric indications.
At the top level, Claim 1 covers:
- A compound of Formula (I) (or pharmaceutically acceptable salt).
- Substitution constraints on:
- The bicyclic linkage via X, Y, Z.
- The indazole carboxamide substitution via R1.
- The side-chain via R2 (Formula (a), with n = 2 or 3).
- The terminal substituent via R4 (alkyl/cycloalkyl/alkylated cycloalkyl/heteroaryl via (CH2)t R6).
Claims 2-10 and 11-20 narrow or specify variants and use cases.
How is the chemical scope defined in Claim 1 (core genus)
Claim 1 is a genus with a large Markush structure. The binding logic is expressed through the variables and allowed substituent sets.
Key structural variables
- X = CO
- Y = NH
- Z = NR3, where R3 can be:
- H
- C1-6 alkyl
- C3-7 alkenyl-methyl
- Phenyl or phenyl C1-4 alkyl, with phenyl optionally substituted by 1-2 of:
- halogen
- CF3
- C1-6 alkoxy
- C1-6 alkyl
- Rb appears when X–Y–R2 attaches at the phenyl ring, and is selected from:
- hydrogen
- halogen
- CF3
- hydroxy
- C1-6 alkoxy
- C1-6 alkyl
- R1 is an extensive indazole-carboxamide substitution set:
- hydrogen
- halogen
- CF3
- C1-6 alkyl
- C1-6 alkoxy
- C1-6 alkylthio
- C1-7 acyl
- C1-7 acylamino
- C1-6 alkylsulphonylamino
- N-(C1-6 alkylsulphonyl)-N-C1-4 alkylamino
- C1-6 alkylsulphinyl
- hydroxy
- nitro
- amino
- aminocarbonyl
- aminosulphonyl
- aminosulphonylamino
- N-(aminosulphonyl)-C1-4 alkylamino
- with N optionally substituted by 1-2 groups selected from:
- C1-6 alkyl
- C3-8 cycloalkyl
- C3-8 cycloalkyl C1-4 alkyl
- phenyl
- phenyl C1-4 alkyl
- with additional optional N substitution:
- C4-5 polymethylene
- R2 is defined by Formula (a):
- R4 is defined as one of:
- C1-7 alkyl
- C3-8 cycloalkyl
- C3-8 cycloalkyl C1-2 alkyl
- or (CH2)t R6, where:
- t = 1 or 2
- R6 = thienyl, pyrrolyl, or furyl
- R6 optionally substituted by 1-2 of:
- C1-6 alkyl
- C1-6 alkoxy
- CF3
- halogen
- or phenyl optionally substituted by 1-2 of:
- C1-4 alkoxy
- CF3
- halogen
- nitro
- carboxy
- esterified carboxy
- C1-4 alkyl optionally substituted by hydroxy, C1-4 alkoxy, carboxy, esterified carboxy, or in vivo hydrolysable acyloxy
What this means for freedom-to-operate (FTO)
Claim 1 is not limited to a few structures. It sweeps:
- Multiple N-substituted variants (R3 wide).
- Multiple indazole N-carboxamide ring substituents (R1 broad).
- Two possible linker lengths or analog definitions via n = 2 or 3 in R2.
- A large set of terminal R4 groups, including heteroaryl-(CH2)t substituents and substituted phenyl.
The net effect is a broad chemical genus where a large portion of “medchem neighbor” space can still fall inside the literal terms.
Where the claim narrows (Claims 2-10, 6-7, 8-10)
Parameter narrowing
- Claim 2: n = 3 (from Claim 1’s n = 2 or 3).
- Claim 3: R3 = H or methyl.
- Claim 4: side chain attached at position 3 (relative to the depicted Formula (I) attachment point).
- Claim 5: R1 = H or 5-halo.
- Claim 6: R4 = C1-7 alkyl.
- Claim 7: R4 = methyl.
- Claim 9: Y–R2 in endo configuration.
- Claim 10: a specific salt:
- N-(Endo-9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methylindazole-3-carboxamide monohydrochloride
Hard-coded examples (Claim 8)
Claim 8 includes a list of specific compounds captured in the patent text, covering multiple core variants of:
- azabicyclo skeleton substitution (9-methyl with bicyclic framework)
- indazole core substitution (3-carboxamide; N-substitution and halogenated variants)
- multiple ring systems (bicyclo[3.3.1]non and bicyclo[3.3.2]non)
- and salt forms.
Claim 8 compounds:
- N-(endo-9-methyl-9-azabicyclo[3.3.1]non-3-yl)-indazole-3-carboxamide
- N-(endo-9-methyl-9-azabicyclo[3.3.1]non-3-yl)-5-fluoroindazole-3-carboxamide
- N-(endo-9-methyl-9-azabicyclo[3.3.1]non-3-yl)-5-chloroindazole-3-carboxamide
- N-(endo-9-methyl-9-azabicyclo[3.3.2]non-3-yl)-1-methylindazole-3-carboxamide
- N-(endo-9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-ethylindazole-3-carboxamide
Plus pharmaceutically acceptable salts of any.
These explicit examples matter because they can be used to interpret the genus (what the patentee intended as practicing embodiments), and because “listed compounds” can constrain prosecution history estoppel arguments depending on how claim interpretation is later contested.
How Claim 1 translates into indication coverage (Claims 11-20)
US 4,886,808 also claims medical uses and pharmaceutical compositions built around the same compound genus.
Compositions
- Claim 11: migraine or cluster headache
- Claim 12: trigeminal neuralgia
- Claim 13: emesis
- Claim 19: anxiety
- Claim 20: psychosis
All require:
- effective amount of a compound of Claim 1 or salt
- and a pharmaceutically acceptable carrier
Methods
- Claim 14: migraine or cluster headache (mammals)
- Claim 15: trigeminal neuralgia (mammals)
- Claim 16: emesis (mammals)
- Claim 17: anxiety (mammals)
- Claim 18: psychosis (mammals)
All require:
- administering an effective amount of Claim 1 compound (or salt) to mammals
What this means legally
Even if a competitor designs around Claim 1’s chemical scope, there can still be exposure through:
- literal coverage under the genus if they land inside the Markush ranges, or
- dependent-claim narrowing that matches specific known analogs,
- and the method claims remain tethered to “a compound according to Claim 1.”
Because all method/composition claims are tied to Claim 1, the chemical-genus boundary is the central risk point.
Practical scope map: where design modifications likely fall
Below is a “claim-mapping” view of what typically drives inclusion vs exclusion under this patent language.
Inclusion drivers (literal)
A compound is more likely to fall within Claim 1 if it matches:
- the X-Y-Z pattern: X = CO; Y = NH; Z = NR3
- R3 within the broad set (H, C1-6 alkyl, C3-7 alkenyl-methyl, or substituted phenyl/phenyl C1-4 alkyl with specified substitutions)
- R2 defined by Formula (a) with n = 2 or 3
- R4 being one of the enumerated groups: alkyl/cycloalkyl/alkylated cycloalkyl/heteroaryl-(CH2)t or substituted phenyl with enumerated substituent types
- the correct positional attachment and endo configuration where required by dependent claims
Exclusion drivers (typical)
Common routes to avoid literal infringement based on claim wording alone (without asserting legal validity issues):
- change X away from CO
- change Y away from NH
- change Z away from NR3 or move to an oxygen substitution
- change R2 away from Formula (a) (or change n outside 2 or 3, if Formula (a) structure still needs to be followed)
- change R4 to a group outside the enumerated classes and substitution constraints
This is not an infringement opinion. It is a direct reading of the claim variables and enumerated sets.
Patent landscape: what can be inferred from this claim set (and what cannot)
A complete US “landscape” normally requires:
- bibliographic data (publication, filing dates),
- prosecution history (continuations, divisionals),
- expiration dates,
- citation graph (family members),
- related patents on the same scaffold and indications.
That dataset is not present in the prompt. Without it, any “landscape” beyond the internal structure and dependency relationships would be speculative.
What can be grounded strictly from the claim text you provided is the internal landscape of what this patent covers:
- a single chemical genus (Formula I) spanning a large variable space,
- multiple therapeutic areas (migraine/cluster headache, trigeminal neuralgia, emesis, anxiety, psychosis),
- both composition and method claim forms.
Internal claim dependency and coverage breadth
| Claim type |
Claims |
Key tether |
| Chemical genus |
1 |
Formula (I) variable ranges |
| Chemical narrowing |
2-10 |
tighter ranges and stereochemistry/position/salt |
| Specific listed embodiments |
8, 10 |
enumerated compounds and monohydrochloride |
| Composition claims |
11-13, 19-20 |
“compound of Claim 1 (or salt)” + carrier |
| Method claims |
14-18 |
“compound of Claim 1 (or salt)” to mammals |
Key takeaways
- US 4,886,808 is built around a broad Markush genus in Claim 1 with wide substitution latitude on R1, R3, R4, and defined R2 with n = 2 or 3.
- All downstream use and composition claims (11-20) are tethered to Claim 1, so chemical scope controls overall exposure.
- Dependent claims narrow into specific subspaces (n = 3; R3 = H/methyl; R4 = methyl; endo configuration; particular attachment position; specific salt), which can guide both product design targets and diligence focus.
- The patent’s therapeutic coverage spans five indication clusters: migraine/cluster headache, trigeminal neuralgia, emesis, anxiety, and psychosis, with both methods and pharmaceutical compositions.
FAQs
-
Is the patent limited to a single molecule?
No. Claim 1 covers a broad class of Formula (I) compounds with multiple variable substitution ranges.
-
Do the method-of-treatment claims cover all compounds in Claim 1?
Yes. Claims 14-18 cover methods using “a compound according to claim 1 or a pharmaceutically acceptable salt thereof.”
-
What parameter most directly controls the size of the chemical space?
The combined variable sets in Claim 1 for R1, R3, R2 (n = 2 or 3), and R4, especially R4 and R1, which are heavily enumerated.
-
Does the patent include both free bases and salts?
Yes. Claim 1 and the dependent claims repeatedly include “pharmaceutically acceptable salts,” and Claim 10 specifically claims a monohydrochloride.
-
Are migraine and anxiety both covered by the same patent?
Yes. The patent includes both indication categories through composition and method claims (Claims 11-18 and 19-20).
References
- United States Patent 4,886,808. “Compounds and methods for treatment of…” (claims as provided in prompt).
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