IP Library › Granted Patent US 9,469,632

Granted Patent B2

US 9,469,632 · App. 14/718,129 · Granted Oct 18, 2016

6-substituted-3

Inventors: Kevin Matthew Gardinier (Fishers, IN); Douglas Linn Gernert (Indianapolis, IN); Patric James Hahn (Indianapolis, IN); Sean Patrick Hollinshead (Indianapolis, IN); Albert Khilevich (Westfield, IN); Daniel Ray Mayhugh (Carmel, IN); Paul Leslie Ornstein (Northbrook, IL); Warren Jaye Porter (Indianapolis, IN); Jon Kevin Reel (Carmel, IN); Jeffrey Michael Schkeryantz (Fishers, IN); Patrick Gianpietro Spinazze (Avon, IN); Freddie Craig Stevens (Indianapolis, IN); Jeffrey Michael Witkin (Carmel, IN)

Assignee: Eli Lilly and Company

C07D417/14 A61K31/41

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Quick Facts

Patent No.: US 9,469,632
App. No.: 14/718,129
Granted: Oct 18, 2016
Kind: B2

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Abstract

A TARP γ8 dependant AMPA receptor antagonist of the formula: wherein X is CH or N; A is and R 1 is as defined herein; its pharmaceutically acceptable salts, uses, and methods for its preparation are described.

Claims (329)

1. A compound of the formula

or a pharmaceutically acceptable salt thereof,

wherein X is CH or N;

A is

and

R 1 is selected from the group consisting of

hydrogen,

deuterium,

fluoro,

methyl,

HO—(C 1 -C 4 )-alkyl, optionally substituted with with one or two methyl or deuterium groups,

HO—(C 1 -C 3 )-alkoxy, optionally substituted with one or two methyl or deuterium groups,

fluoro-(C 1 -C 3 )-alkyl,

HO—(C 1 -C 3 )-alkoxy-methyl, optionally substituted with with one or two methyl groups,

cyano-(C 1 -C 3 )-alkoxy,

HO—(C 1 -C 3 )-alkylthio, optionally substituted with with one or two methyl groups,

HO—(C 1 -C 3 )-alkyl-NH—,

HO—(C 1 -C 3 )-alkyl-N(CH 3 )—,

methylsulfinyl,

acyl,

aminocarbonyl,

methylcarbonylmethoxymethyl,

aminomethylcarbonyloxyethoxy,

triazolylmethyl,

1-methyl-imidizol-2-ylthio,

5-hydroxymethyl-tetrahydrofuran-2-yl,

3-hydroxy-3-methylazetidin-1-yl,

3-methoxy-azetidin-1-yl

3-methoxy-3-methylazetidin-1-yl

4-hydroxypiperidin-1-yl,

4-hydroxy-4-methyl-piperidin-1-yl,

4-hydroxy-4-vinyl-piperidin-1-yl,

4-hydroxymethyl-piperidin-1-yl,

4-(2-hydroxyethyl)-piperindin-1-yl,

morpholin-4-yl,

2-hydroxymethyl-morpholin-4-yl,

morpholin-4-yl-ethoxy, and

tetrahydropyran-4-yl,

provided that when A is

then R 1 is not unsubstituted HO—(C 1 -C 3 )-alkoxy, deuterium substituted HO—(C 1 -C 3 )-alkoxy, or HO—(C 1 -C 3 )-alkythio.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, having the following stereochemistry:

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof,

wherein

X is CH;

A is

and

R 1 is selected from the group consisting of

deuterium,

fluoro,

2-hydroxyethyl,

1-hydroxyethyl,

2-hydroxy-2,2-dideutero-ethyl,

1-hydroxy-1-methylethyl,

2-hydroxy-propyl,

2-hydroxy-2-methylpropyl,

3-hydroxy-3-methylbutyl,

2-hydroxy-2-methyl-propoxy,

3-hydroxy-2,2-dimethyl-propoxy,

2-fluoroethyl,

2-hydroxyethoxymethyl,

2-hydroxy-2-methylpropoxymethyl,

2-hydroxypropoxymethyl,

1-(2-hydroxyethoxy)-ethyl,

1-(2-hydroxypropoxy)-ethyl,

cyanomethoxy,

2-hydroxy-1-methyl-ethylthio,

2-hydroxyethylamino,

N-(2-hydroxyethyl)-N-(methyl)amino,

methylsulfinyl,

methylcarbonylmethoxymethyl,

aminomethylcarbonyloxyethoxy,

1,2,3-triazol-1-ylmethyl,

1-methyl-imidizol-2-ylthio,

5-hydroxymethyl-tetrahydrofuran-2-yl,

3-hydroxy-3-methylazetidin-1-yl,

3-methoxy-azetidin-1-yl

3-methoxy-3-methylazetidin-1-yl

4-hydroxypiperidin-1-yl,

4-hydroxy-4-methyl-piperidin-1-yl,

4-hydroxy-4-vinyl-piperidin-1-yl,

4-(2-hydroxyethyl)-piperindin-1-yl,

morpholin-4-yl,

2-hydroxymethyl-morpholin-4-yl,

morpholin-4-yl-ethoxy, and

tetrahydropyran-4-yl.

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof,

wherein X is N;

A is

and

R 1 is selected from the group consisting of

hydrogen,

methyl,

hydroxymethyl, and

aminocarbonyl.

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof

wherein X is CH;

A is

and

R 1 is selected from the group consisting of

hydrogen,

2-hydroxyethyl,

3-hydroxy-3-methylbutyl,

2-hydroxyethoxy, and

acyl.

6. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof,

wherein

X is CH;

A is

and

R 1 is selected from the group consisting of

deuterium,

fluoro,

2-hydroxyethyl,

1-hydroxyethyl,

2-hydroxy-2,2-dideutero-ethyl,

1-hydroxy-1-methylethyl,

2-hydroxy-propyl,

2-hydroxy-2-methylpropyl,

3-hydroxy-3-methylbutyl,

2-hydroxy-2-methyl-propoxy,

3-hydroxy-2,2-dimethyl-propoxy,

2-fluoroethyl,

2-hydroxyethoxymethyl,

2-hydroxy-2-methylpropoxymethyl,

2-hydroxypropoxymethyl,

1-(2-hydroxyethoxy)-ethyl,

1-(2-hydroxypropoxy)-ethyl,

cyanomethoxy,

2-hydroxy-1-methyl-ethylthio,

2-hydroxyethylamino,

N-(2-hydroxyethyl)-N-(methyl)amino,

methylsulfinyl,

methylcarbonylmethoxymethyl,

aminomethylcarbonyloxyethoxy,

1,2,3-triazol-1-ylmethyl,

1-methyl-imidizol-2-ylthio,

5-hydroxymethyl-tetrahydrofuran-2-yl,

3-hydroxy-3-methylazetidin-1-yl,

3-methoxy-azetidin-1-yl

3-methoxy-3-methylazetidin-1-yl

4-hydroxypiperidin-1-yl,

4-hydroxy-4-methyl-piperidin-1-yl,

4-hydroxy-4-vinyl-piperidin-1-yl,

4-(2-hydroxyethyl)-piperindin-1-yl,

morpholin-4-yl,

2-hydroxymethyl-morpholin-4-yl,

morpholin-4-yl-ethoxy, and

tetrahydropyran-4-yl.

7. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof,

wherein X is N;

A is

and

R 1 is selected from the group consisting of

hydrogen,

methyl,

hydroxymethyl, and

aminocarbonyl.

8. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof

wherein X is CH;

A is

and

R 1 is selected from the group consisting of

hydrogen,

2-hydroxyethyl,

3-hydroxy-3-methylbutyl,

2-hydroxyethoxy, and

acyl.

9. The compound according to claim 1 which is selected from:

6-[1-[1-[5-(2-hydroxyethoxymethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 2;

6-[1-[1-[5-(acetonyloxymethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-(1-(1-(5-(4-hydroxypiperidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 1;

6-{1-[1-(5-Methanesulfinyl-pyridin-2-yl)-1H-pyrazol-3-yl]-ethyl}-3H-benzothiazol-2-one, isomer 4;

6-[1-[1-[5-[2-(hydroxymethyl)morpholin-4-yl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-[5-(1-hydroxyethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-(1-hydroxyethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-(5-fluoro-2-pyridyl)pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-(2,2-dideuterio-2-hydroxy-ethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-(5-morpholino-2-pyridyl)pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 1;

6-[1-[1-[5-(2-hydroxy-2-methyl-propoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-(2-Hydroxyethylamino)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-[5-[2-Hydroxyethyl(methyl)amino]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-[5-[(2-hydroxy-2-methyl-propoxy)methyl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1; and

6-(1-(1-(5-((1-hydroxypropan-2-yl)thio)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 1; or

a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 which is selected from:

6-(1-(1-(5-((1-hydroxypropan-2-yl)thio)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 2;

6-(1-(1-(5-(4-hydroxy-4-vinylpiperidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 1;

6-(1-(1-(5-(3-hydroxy-3-methylazetidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 1;

6-(1-(1-(5-(3-methoxyazetidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 2;

6-(1-(1-(5-(3-methoxy-3-methylazetidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one isomer 2;

6-((S)-1-{1-[5-(2-Hydroxy-propyl)-pyridin-2-yl]-1H-pyrazol-3-yl}-ethyl)-3H-benzothiazol-2-one, isomer 2;

6-[1-[1-(5-tetrahydropyran-4-yl-2-pyridyl)pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[(S)-1-[1-[5-(2-hydroxyethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer;

6-[1-[1-(5-deuterio-2-pyridyl)pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-[5-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[(1S)-1-[1-[5-(3-hydroxy-3-methyl-butyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-(3-hydroxy-2,2-dimethyl-propoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-(2-hydroxy-2-methyl-propyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-(1-methylimidazol-2-yl)sulfanyl-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one hydrochloride, isomer 1;

6-[1-[1-[5-(Triazol-1-ylmethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one hydrochloride, isomer 1; or

a pharmaceutically acceptable salt thereof.

11. A compound according to claim 1 which is:

2-[[6-[3-[1-(2-Oxo-3H-1,3-benzothiazol-6-yl)ethyl]pyrazol-1-yl]-3-pyridyl]oxy]acetonitrile, isomer 2;

2-[[6-[3-[(1S)-1-(2-oxo-3H-1,3-benzothiazol-6-yl)ethyl]pyrazol-1-yl]-3-pyridyl]oxy]ethyl 2-aminoacetate;

6-[(1S)-1-[1-[5-(2-morpholinoethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one;

6-[1-[1-[5-[1-(2-hydroxyethoxyl)ethyl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-[1-[5-[1-(2-hydroxyethoxyl)ethyl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-[5-[1-(2-hydroxypropoxyl)ethyl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-(1-(1-(5-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 1;

6-(1-(1-(5-(4-(2-hydroxyethyl)piperidin-1-yl)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 1;

6-(1-(1-(5-((2-hydroxypropyl)thio)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 3;

6-(1-(1-(5-((2-hydroxypropyl)thio)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one, isomer 4;

6-[1-[1-[5-(2-hydroxypropoxymethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 3;

6-[1-[1-[5-(2-hydroxypropoxymethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 4; and

6-[1-[1-[5-(2-fluoroethyl)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2; or

a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 which is selected from:

6-[1-[1-(6-methylpyridazin-3-yl)pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[1-[6-(hydroxymethyl)pyridazin-3-yl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-(1-{1-[6-(2-Hydroxy-ethylsulfanyl)-pyridazin-3-yl]-1H-pyrazol-3-yl}-ethyl)-3H-benzothiazol-2-one, isomer 2;

6-[1-(1-Pyridazin-3-yl-1H-pyrazol-3-yl)-ethyl]-3H-benzothiazol-2-one, isomer 2; and

6-[3-[1-(2-oxo-3H-1,3-benzothiazol-6-yl)ethyl]pyrazol-1-yl]pyridazine-3-carboxamide, isomer 1; or

a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 which is selected from:

6-[1-[1-[5-[5-(Hydroxymethyl)tetrahydrofuran-2-yl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 1 Cis;

6-[1-[1-[5-[5-(Hydroxymethyl)tetrahydrofuran-2-yl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 2 Cis;

6-[1-[1-[5-[5-(hydroxymethyl)tetrahydrofuran-2-yl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 3 Trans; and

6-[1-[1-[5-[5-(hydroxymethyl)tetrahydrofuran-2-yl]-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one, Isomer 4 Trans; or

a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 which is selected from:

6-[1-[4-[5-(2-hydroxyethoxy)-2-pyridyl]thiazol-2-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[4-[5-(2-hydroxyethyl)-2-pyridyl]thiazol-2-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2;

6-[1-[4-[5-(3-hydroxy-3-methyl-butyl)-2-pyridyl]thiazol-2-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 1;

6-[1-(4-pyridazin-3-ylthiazol-2-yl)ethyl]-3H-1,3-benzothiazol-2-one, isomer 2; and

6-[1-[4-(5-acetyl-2-pyridyl)thiazol-2-yl]ethyl]-3H-1,3-benzothiazol-2-one, isomer 2; or

a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 which is selected from:

6-(1-{2-[5-(2-hydroxy-ethyl)-pyridin-2-yl]-thiazol-4-yl}-ethyl)-3H-benzothiazol-2-one, isomer 2; and

6-[1-(2-pyridin-2-yl-thiazol-4-yl)-ethyl]-3H-benzothiazol-2-one, isomer 2; or

a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients.

17. A method of treating seizures in a mammal with epilepsy comprising administering to a mammal in need of such treatment an effective amount of a compound of the formula

or a pharmaceutically acceptable salt thereof,

wherein X is CH or N;

A is

and

R 1 is selected from the group consisting of

hydrogen,

deuterium,

fluoro,

methyl,

HO—(C 1 -C 4 )-alkyl, optionally substituted with with one or two methyl or deuterium groups,

HO—(C 1 -C 3 )-alkoxy, optionally substituted with one or two methyl or deuterium groups,

fluoro-(C 1 -C 3 )-alkyl,

HO—(C 1 -C 3 )-alkoxy-methyl, optionally substituted with with one or two methyl groups,

cyano-(C 1 -C 3 )-alkoxy,

HO—(C 1 -C 3 )-alkylthio, optionally substituted with with one or two methyl groups,

HO—(C 1 -C 3 )-alkyl-NH—,

HO—(C 1 -C 3 )-alkyl-N(CH 3 )—,

methylsulfinyl,

acyl,

aminocarbonyl,

methylcarbonylmethoxymethyl,

aminomethylcarbonyloxyethoxy,

triazolylmethyl,

1-methyl-imidizol-2-ylthio,

5-hydroxymethyl-tetrahydrofuran-2-yl,

3-hydroxy-3-methylazetidin-1-yl,

3-methoxy-azetidin-1-yl

3-methoxy-3-methylazetidin-1-yl

4-hydroxypiperidin-1-yl,

4-hydroxy-4-methyl-piperidin-1-yl,

4-hydroxy-4-vinyl-piperidin-1-yl,

4-hydroxymethyl-piperidin-1-yl,

4-(2-hydroxyethyl)-piperindin-1-yl,

morpholin-4-yl,

2-hydroxymethyl-morpholin-4-yl,

morpholin-4-yl-ethoxy, and

tetrahydropyran-4-yl,

provided that when A is

then R 1 is not unsubstituted HO—(C 1 -C 3 )-alkoxy, deuterium substituted HO—(C 1 -C 3 )-alkoxy, or HO—(C 1 -C 3 )-alkythio.

18. The method according to claim 17 wherein the mammal is a human.

19. The method according to claim 17 wherein the seizures are simple or complex partial onset seizures.

20. The method according to claim 19 wherein the mammal is a human.

21. The method according to claim 17 wherein the seizures are primary or secondary generalized seizures.

22. The method according to claim 21 wherein the mammal is a human.

23. A method of treating pain in a mammal comprising administering to a mammal in need of such treatment an effective amount of a compound of the formula

or a pharmaceutically acceptable salt thereof,

wherein X is CH or N;

A is

and

R 1 is selected from the group consisting of

hydrogen,

deuterium,

fluoro,

methyl,

HO—(C 1 -C 4 )-alkyl, optionally substituted with with one or two methyl or deuterium groups,

HO—(C 1 -C 3 )-alkoxy, optionally substituted with one or two methyl or deuterium groups,

fluoro-(C 1 -C 3 )-alkyl,

HO—(C 1 -C 3 )-alkoxy-methyl, optionally substituted with with one or two methyl groups,

cyano-(C 1 -C 3 )-alkoxy,

HO—(C 1 -C 3 )-alkylthio, optionally substituted with with one or two methyl groups,

HO—(C 1 -C 3 )-alkyl-NH—,

HO—(C 1 -C 3 )-alkyl-N(CH 3 )—,

methylsulfinyl,

acyl,

aminocarbonyl,

methylcarbonylmethoxymethyl,

aminomethylcarbonyloxyethoxy,

triazolylmethyl,

1-methyl-imidizol-2-ylthio,

5-hydroxymethyl-tetrahydrofuran-2-yl,

3-hydroxy-3-methylazetidin-1-yl,

3-methoxy-azetidin-1-yl

3-methoxy-3-methylazetidin-1-yl

4-hydroxypiperidin-1-yl,

4-hydroxy-4-methyl-piperidin-1-yl,

4-hydroxy-4-vinyl-piperidin-1-yl,

4-hydroxymethyl-piperidin-1-yl,

4-(2-hydroxyethyl)-piperindin-1-yl,

morpholin-4-yl,

2-hydroxymethyl-morpholin-4-yl,

morpholin-4-yl-ethoxy, and

tetrahydropyran-4-yl,

provided that when A is

then R 1 is not unsubstituted HO—(C 1 -C 3 )-alkoxy, deuterium substituted HO—(C 1 -C 3 )-alkoxy, or HO—(C 1 -C 3 )-alkythio.

24. The method according to claim 23 where the mammal is a human.

25. The method according to claim 23 where the pain is nociceptive pain.

26. The method according to claim 25 where the mammal is a human.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 28, 2015

From: GARDINIER, KEVIN MATTHEW; GERNERT, DOUGLAS LINN; HAHN, PATRIC JAMES; HOLLINSHEAD, SEAN PATRICK; KHILEVICH, ALBERT; MAYHUGH, DANIEL RAY; ORNSTEIN, PAUL LESLIE; PORTER, WARREN JAYE; REEL, JON KEVIN; SCHKERYANTZ, JEFFREY MICHAEL; SPINAZZE, PATRICK GIANPIETRO; STEVENS, FREDDIE CRAIG; WITKIN, JEFFREY MICHAEL

To: ELI LILLY AND COMPANY

Reel/Frame 035773/0591 →

Continuity (2)

Provisional Application 62004005 · May 28, 2014

Related Publication 20150344468A1 · Dec 3, 2015