Details for Patent: 8,314,117

Which drugs does patent 8,314,117 protect, and when does it expire?

Patent 8,314,117 protects NURTEC ODT and is included in one NDA.

This patent has fifty-one patent family members in thirty-five countries.

Summary for Patent: 8,314,117

Title:	CGRP receptor antagonists
Abstract:	The disclosure generally relates to the novel compounds of formula I, including pharmaceutically acceptable salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).
Inventor(s):	Guanglin Luo, Gene M. Dubowchik, John E. Macor
Assignee:	Bristol Myers Squibb Co
Application Number:	US12/902,714
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,314,117
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 8,314,117: Scope of Claims and Patent-Landscape Readout

What does US 8,314,117 claim, in plain claim-structure terms?

US 8,314,117 is an organic small-molecule patent that claims “a compound of Formula I” with broad structural variability across multiple substituent positions, plus downstream claims to stereoisomers, selected embodiments, pharmaceutically acceptable salts, a pharmaceutical composition, and a migraine-treatment method.

The independent claim is claim 1, with dependent claims tightening substituent sets and then specifying particular stereochemical and positional variants and specific named molecules (claim 13 and claim 14). Claim 15 adds formulation, and claims 17-18 add therapeutic use for migraine.

What is the core structural scope in Claim 1 (Formula I)?

Claim 1 defines a Markush-style Formula I with multiple variable sites:

Variable group coverage (Claim 1)

• R1: hydrogen, cyano, halo, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, azetidinyl, pyrrolidinyl, piperidinyl
• R2: piperidinyl substituted with 1 substituent selected from:
  • R3: hydrogen, halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy
• R4: hydrogen, halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy
• R5 to R11: each independently selected from:
  • hydrogen, hydroxy, alkoxy, haloalkoxy, azido, amino, alkylamino, dialkylamino
  • plus R11 also allows: alkoxycarbonyl or benzyloxycarbonyl
  • and a special linkage option: “or R10 and R11 taken together is O or N-OH”
• Non-triviality requirement: at least one of R5-R11 is not hydrogen
• Ar1: phenyl substituted with 0-3 substituents selected from:
  • cyano, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylSO2
• X: O, CH2, or NH
• Y: bond, O, CH2, or NH

What is the claimed “functional” endpoint?

The claims cover:

• Free-base compounds and pharmaceutically acceptable salts (explicitly stated in claim 1)
• Stereochemistry-defined compounds (claim 3)
• A pharmaceutical composition containing the claimed compound (claim 15)
• Migraine treatment by administration (claim 17)

What does “design space” look like across the claim set?

The claim set is structured as a broad Markush scaffold plus progressively narrower dependent claims and then explicit enumerated structures.

Claim hierarchy (high level)

Claim	Coverage type	Tightening axis
1	Broad scaffold (Formula I)	Multi-site Markush substitutions with non-hydrogen requirement
2	Similar scaffold with R10/R11 locked to “oxo”	Limits the R10-R11 linkage category
3	Stereochemistry designation	Adds chiral specificity
4-5	Further reduced substituent options and specific linkage rules	Restricts R1-R11 to smaller sets
6	R1 coverage subset	Keeps Markush but excludes some groups
7-8	R2 subset: N-piperidinyl, 4-substituted	Narrows a key ring attachment point
9-12	“Pinpoint” functional patterns on R5-R11 and Ar1/X	Locks certain positions to hydrogen/hydroxy/azido/amino
10-11	Ar1 narrowed to 2-halo and then 2,3-difluoro	Narrows aromatic substitution
12	X locked to O	Narrows heteroatom connectivity
13	Specific named compounds list	Enumerates concrete structures including stereoisomers
14	Specific stereoisomer (single)	Locks to one named compound
15	Composition	Adds carrier + salt/compound
16	Composition for one named compound	Locks to claim 1 compound # from claim 14
17	Method of treating migraine	Adds clinical use
18	Method with specific compound	Locks to claim 14 compound

What do dependent claims do to narrow the scaffold?

Claim 2: R10 and R11 “taken together is oxo”

Claim 2 keeps the overall Formula I but replaces the broader R11 linkage options. It states “or R10 and R11 taken together is oxo.” It also maintains the constraint that at least one of R5-R11 is not hydrogen.

Impact: this eliminates many hydroxylated or N-OH linkage configurations while preserving the broader substituent vocabulary for the remaining positions.

Claims 4 and 5: squeeze specific positions to small subsets

Claim 4 reduces the permissible substituent sets substantially. Representative constraints:

• R1 limited to hydrogen, halo, cyano, amino, alkylamino, dialkylamino
• R2 piperidinyl substituted with R3 = hydrogen or halo
• R4 = hydrogen or halo
• R5, R6, R7, R8 mostly hydrogen
• R9 = hydrogen or hydroxy
• R10 includes hydrogen, hydroxy, azido, amino, alkylamino, dialkylamino
• R11 = hydrogen (or linkage option where “R10 and R11 taken together is oxo”)

Claim 5 narrows further:

• R1 = hydrogen
• Ar1 = phenyl or difluorophenyl
• R5 and R9 tied to hydrogen or hydroxy
• R10 = hydroxy, azido, or amino
• R11 = hydrogen (or oxo linkage with R10)

Impact: these claims are positioned as intermediate “lock-in” steps between broad Formula I and the enumerated stereochemical examples.

Claims 6-12: additional position-based narrowing

• Claim 6 is a subset that keeps R1 broad but effectively asserts the Formula I definition where R1 is in that listed set.
• Claim 7-8 narrow R2 to N-piperidinyl and assert “4-substituted” (claim 7) for R2.
• Claim 9 enumerates multiple allowed patterns for the R5-R11 arrangement, including:
  • one case with R10 = hydroxy/azido/amino and R11 = hydrogen
  • multiple cases where R10 and R11 are taken together as oxo
  • a third where R5 = hydroxy and all others are hydrogen in the specified positions
• Claim 10-11 narrows Ar1 to 2,3-difluorophenyl in claim 11.
• Claim 12 locks X = O.

What is claimed by specific enumerated structures (Claim 13)?

Claim 13 lists a long set of named compounds. These are concrete instances of the Formula I scaffold with explicit stereochemistry and substitution patterns.

The enumerated list includes these distinct chemical “classes” (as written)

1. Core cycloheptapyridine + imidazopyridinyl piperidine-1-carboxylate motif with 2,3-difluorophenyl and specific stereocenters, for example:
   • (6R,9R)-…-6-(2,3-Difluorophenyl)-6-hydroxy-…-piperidine-1-carboxylate
   • (9R)-…-6-(2,3-difluorophenyl)-5-oxo-…-piperidine-1-carboxylate
   • multiple (5S,6R/6S,9R) variants with 5-hydroxy and/or 5-oxo and 5-azido and 5-amino
2. Carbamate variants, including:
   • “spiro[indene...pyrrolo...]” carbamate expression
   • “tert-butyl ... carbamate” examples (two entries shown in claim 13 list)
3. A specific “acetyl” tether example:
   • “1-(1-(2-((5S,6S,9R)-5-amino-…-yl)acetyl)piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one”

Impact on scope: Claim 13 provides direct claim coverage without needing to prove Markush boundaries, because each entry is specified as a complete structure. Claim 14 then selects one entry from that set.

What is the single most commercially relevant claim narrowing (Claim 14)?

Claim 14 identifies one specific stereoisomer:

• (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate
• plus pharmaceutically acceptable salt

Claim 16 then ties that compound to a pharmaceutical composition, and claims 17-18 tie it to migraine treatment.

How far does the patent reach into therapy claims?

Claim 17: Method of treating migraine

Claim 17 claims a method that administers:

• “a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof” to a patient for migraine.

Claim 18: Method locked to the single compound

Claim 18 restricts the method to the compound specified in claim 14.

Scope character: This is a classic “use claim” anchored to the compound claims, so the method claim’s enforceability depends on whether the accused product falls within claim 1 (or its dependents) or the explicit claim 14 compound.

Where does this sit in the broader patent landscape (what can be inferred from the claim content)?

The claim content itself points to a structured family strategy typical of CNS small-molecule portfolios:

• Broad scaffold claim (Formula I)
• Multiple dependent claims locking substitution positions and linkage states (R10/R11 as oxo vs O vs N-OH)
• Stereochemistry-dependent claims
• A dense set of enumerated example structures, suggesting the patent is meant to cover multiple stereoisomeric drug candidates and salts
• A migraine indication, which is consistent with downstream clinical-stage optimization around a single mechanism series

Practical landscape implications for freedom-to-operate (FTO) and R&D

1. Design-around pressure concentrates on core scaffold invariants
   • The claims repeatedly constrain the structure to the same multi-ring system plus piperidine-1-carboxylate and imidazopyridinyl components, while changing peripheral substitutions (R groups) and certain linkage options (X, Y, R10/R11).
2. Stereochemistry is monetized
   • Claim 3 and especially claim 13 and claim 14 show the portfolio expects enantiomer-specific or stereochemical-specific market value.
3. A single “commercial” compound is singled out
   • Claim 14 is the most direct hook for enforcement against a lead candidate or clinical compound.

Litigation-style claim pressure points (what is most likely to matter in claim construction)

Even without external procedural data, the claim language highlights where disputes typically concentrate:

Markush boundaries and “at least one not hydrogen”

• Claim 1 requires: “provided that at least one of R5, R6, R7, R8, R9, R10, or R11 is not hydrogen.”
• That can matter if an accused compound tries to map to the scaffold while setting many positions to hydrogen.

The R10/R11 “taken together” linkage switch

• Claim 1 allows “R10 and R11 taken together is O or N-OH”
• Claim 2 restricts to “oxo”
• Dependent claims (4-5) also include versions with oxo as the linkage mode

This creates distinct chemical subspaces within Formula I, useful both for asserting infringement and for designing around.

X and Y heteroatom/connection constraints

• Claim 1: X = O, CH2, or NH
• Claim 12: X = O
• Claim 1: Y = bond, O, CH2, or NH

If an accused compound changes these connection types, it can exit dependent claims without necessarily leaving claim 1, depending on the exact mapping.

Patent landscape summary by claim type (enforcement leverage)

Patent element	What it covers	Enforcement leverage
Formula I (claim 1)	Broad structural family	High leverage if accused compound maps to Formula I
Stereochemical claim (claim 3)	Stereospecific variants	Medium to high, depending on marketed stereochemistry
Enumerated examples (claim 13)	Literal structures	Very high for those exact examples
Single key compound (claim 14)	One locked stereoisomer	Very high for lead/clinical candidate
Composition (claim 15-16)	Formulations with carrier	Adds leverage on finished dose forms
Migraine method (claim 17-18)	Therapeutic use	Adds leverage tied to indication and administration

Key Takeaways

• US 8,314,117 is scaffold-to-usage coverage: Formula I compounds, stereoisomers, enumerated structures, compositions, and a migraine-treatment method.
• The enforceable “center of gravity” is Claim 14: one specifically named stereoisomer that anchors claim 16 (composition) and claim 18 (method).
• The claim set is designed to resist easy substitution: major structural features are preserved while peripheral substitutions vary, with strong constraints on heteroatom/linkage states (X, Y; R10/R11 “taken together”).
• Freedom-to-operate risk concentrates on the single lead structure and its immediate stereochemical and salt forms, and on whether any competitor product maps to Claim 1’s Markush boundaries.

FAQs

1. Is US 8,314,117 limited to the enumerated examples in claim 13?
   No. Claim 1 provides broad coverage via Formula I; claim 13 enumerates additional specific embodiments.

2. Which claim is the most direct infringement target for a lead compound?
   Claim 14, because it isolates one stereochemically defined compound that drives claims 16 and 18.

3. Does the patent protect formulations as well as the active compound?
   Yes. Claims 15 and 16 cover a pharmaceutical composition with a pharmaceutically acceptable carrier.

4. What medical use is claimed?
   Migraine treatment (claims 17-18).

5. What structural features are most likely to be crucial in mapping an accused compound to the claims?
   The scaffold boundaries in Formula I plus the substituent set constraints, especially X/Y and the R10/R11 linkage category (“oxo” vs O vs N-OH).

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References (APA)

1. United States Patent No. 8,314,117 (claims text provided in the prompt).

Drugs Protected by US Patent 8,314,117

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pfizer	NURTEC ODT	rimegepant sulfate	TABLET, ORALLY DISINTEGRATING;ORAL	212728-001	Feb 27, 2020		RX	Yes	Yes			Y	Y		ACUTE TREATMENT OF MIGRAINE WITH OR WITHOUT AURA IN ADULTS
Pfizer	NURTEC ODT	rimegepant sulfate	TABLET, ORALLY DISINTEGRATING;ORAL	212728-001	Feb 27, 2020		RX	Yes	Yes			Y	Y		PREVENTIVE TREATMENT OF EPISODIC MIGRAINE IN ADULTS

International Family Members for US Patent 8,314,117

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2488512		301187	Netherlands
European Patent Office	2488512		LUC00272	Luxembourg
European Patent Office	2488512		PA2022516	Lithuania
European Patent Office	2488512		122022000048	Germany