US2013324467A1PendingUtilityA1

Neuropeptide analogs, compositions, and methods for treating pain

30
Assignee: WHITE H STEVEPriority: Dec 15, 2010Filed: Dec 14, 2011Published: Dec 5, 2013
Est. expiryDec 15, 2030(~4.4 yrs left)· nominal 20-yr term from priority
Inventors:H. Steve WhiteBrian D. KleinCameron Spencer MetcalfDaniel Ryan McdougleErika Adkins SchollMisty Danielle SmithGrzegorz BulajLiuyin Zhang
A61P 25/04A61K 47/60C07K 7/083A61K 38/31C07K 14/57545A61K 38/2271A61P 25/00A61K 38/10C07K 14/655
30
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Neuropeptide analogs and compositions including neuropeptide analogs are described herein. Also provided are methods of producing and using the neuropeptide analogs and compositions including one or more neuropeptide analogs.

Claims

exact text as granted — not AI-modified
1 . A composition with increased metabolic stability, the composition comprising:
 a neuropeptide analog wherein at least one amino acid is covalently attached to a monodisperse oligoethylene glycol unit;   wherein the monodisperse oligoethylene glycol unit attached to the amino acid of the neuropeptide analog increases the metabolic stability of the composition compared to the metabolic stability of the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit.   
     
     
         2 . The composition of  claim 1 , wherein the neuropeptide analog comprises at least one of a galanin analog, a neuropeptide Y analog, a neurotensin analog, and a somatostatin analog. 
     
     
         3 . The composition of  claim 1 , wherein the monodisperse oligoethylene glycol unit attached to the amino acid of the neuropeptide analog increases the metabolic stability of the composition by increasing the half-life of the composition compared to the half-life of a composition comprising the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit. 
     
     
         4 . The composition of  claim 1 , wherein the monodisperse oligoethylene glycol unit comprises at least 2 ethylene glycol repeats. 
     
     
         5 . The composition of  claim 1 , wherein the monodisperse oligoethylene glycol unit comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, and 48 ethylene glycol repeats. 
     
     
         6 . The composition of  claim 1 , wherein the neuropeptide analog is a truncated neuropeptide. 
     
     
         7 . The composition of  claim 1 , wherein the neuropeptide analog comprises at least one terminal lysine. 
     
     
         8 . The composition of  claim 1 , wherein the monodisperse oligoethylene glycol unit is covalently linked to a lysine amino acid. 
     
     
         9 . The composition of  claim 1 , wherein the neuropeptide analog is a truncated neuropeptide analog comprising at least 1, 2, 3, 4, or 5 terminal lysine residues. 
     
     
         10 . The composition of  claim 9 , wherein the neuropeptide analog comprises 4 terminal lysine residues and wherein the monodisperse oligoethylene glycol unit is covalently attached to at least one of the 4 terminal lysine residues. 
     
     
         11 . The composition of  claim 9 , wherein the neuropeptide analog comprises 5 terminal lysine residues and wherein the monodisperse oligoethylene glycol unit is covalently attached to at least one of the 5 terminal lysine residues. 
     
     
         12 . A composition according to  claim 7 , wherein the monodisperse oligoethylene glycol unit is covalently attached to the final terminal lysine residue. 
     
     
         13 . A composition according to  claim 7 , wherein the monodisperse oligoethylene glycol unit is covalently attached to the penultimate terminal lysine residue. 
     
     
         14 . The composition of  claim 1 , wherein the neuropeptide analog is selected from at least one of SEQ ID NO: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. 
     
     
         15 . The composition of  claim 1 , wherein the neuropeptide analog has at least 95% homology with at least one of SEQ ID NO: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. 
     
     
         16 . The composition of  claim 1 , wherein the composition has an increased metabolic stability of at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to a composition comprising the wild-type neuropeptide. 
     
     
         17 . The composition of  claim 1 , wherein the composition is administered to a subject for the treatment of pain. 
     
     
         18 . The composition of  claim 1 , wherein the composition does not cross the blood brain barrier of a subject. 
     
     
         19 . The composition of  claim 1 , wherein the monodisperse oligoethylene glycol unit is a monodisperse polyethylene glycol unit. 
     
     
         20 . The composition of  claim 1 , wherein the neuropeptide analog is N-methylated. 
     
     
         21 . A method of making a neuropeptide analog with increased metabolic stability, the method comprising:
 providing a neuropeptide;   covalently attaching at least one monodisperse oligoethylene glycol unit to at least one amino acid of the neuropeptide, thereby making a neuropeptide analog;   wherein the covalently attached monodisperse oligoethylene glycol unit increases the metabolic stability of the neuropeptide analog in comparison to the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit; and   thereby making a neuropeptide analog with increased metabolic stability.   
     
     
         22 . The method of  claim 21 , wherein the neuropeptide analog comprises at least one of a galanin analog, a neuropeptide Y analog, a neurotensin analog, and a somatostatin analog. 
     
     
         23 . The method of  claim 21 , wherein the neuropeptide analog comprises at least one of a truncated galanin analog, a truncated neuropeptide Y analog, a truncated neurotensin analog, and a truncated somatostatin analog. 
     
     
         24 . The method of  claim 21 , wherein the monodisperse oligoethylene glycol unit covalently attached to the amino acid of the neuropeptide analog increases the metabolic stability of the composition by increasing the half-life of the composition compared to the half-life of a composition comprising the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit 
     
     
         25 . The method of  claim 21 , wherein the neuropeptide analog is a truncated neuropeptide analog comprising at least one terminal lysine. 
     
     
         26 . The method of  claim 21 , wherein the neuropeptide analog is selected from at least one of SEQ ID NO: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. 
     
     
         27 . The method of  claim 21 , wherein the monodisperse oligoethylene glycol unit comprises at least 2 ethylene glycol repeats. 
     
     
         28 . The method of  claim 21 , wherein the monodisperse oligoethylene glycol unit is covalently linked to a lysine amino acid. 
     
     
         29 . The method of  claim 21 , wherein the neuropeptide analog has an increased metabolic stability of at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit. 
     
     
         30 . The method of  claim 21 , wherein the neuropeptide analog is administered to a subject for the treatment of pain. 
     
     
         31 . The method of  claim 21 , wherein the neuropeptide analog does not cross the blood brain barrier of a subject. 
     
     
         32 . The method of  claim 21 , wherein the monodisperse oligoethylene glycol unit is a monodisperse polyethylene glycol unit. 
     
     
         33 . A method of making a neuropeptide analog that does not cross the blood brain barrier, the method comprising:
 providing a neuropeptide;   covalently attaching at least one monodisperse oligoethylene glycol unit to at least one amino acid of the neuropeptide, thereby making a galanin analog;   wherein the covalently attached monodisperse oligoethylene glycol unit prevents the galanin analog from crossing the blood brain barrier.   
     
     
         34 . The method of  claim 33 , wherein covalently attaching at least one monodisperse oligoethylene glycol unit to the at least one amino acid of the neuropeptide analog comprises replacing a lipoamino acid with the monodisperse oligoethylene glycol unit. 
     
     
         35 . The method of  claim 33 , wherein the neuropeptide is at least one of galanin, neuropeptide Y, somatostatin, and neurotensin. 
     
     
         36 . A method of treating pain in a subject, the method comprising:
 administering to the subject a pharmaceutically effective amount of a compound comprising a neuropeptide analog, wherein the neuropeptide analog comprises at least one amino acid covalently attached to a monodisperse oligoethylene glycol unit.   
     
     
         37 . The method of  claim 36 , wherein the neuropeptide analog does not cross the blood brain barrier. 
     
     
         38 . The method of  claim 36 , wherein the neuropeptide analog is selected from at least one of SEQ ID NO: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. 
     
     
         39 . The method of  claim 36 , wherein the neuropeptide analog has at least 95% homology to at least one of SEQ ID NO: 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. 
     
     
         40 . The method of  claim 36 , wherein the neuropeptide analog has an increased metabolic stability of at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit. 
     
     
         41 . The method of  claim 36 , wherein the neuropeptide analog comprises at least one of a galanin analog, a neuropeptide Y analog, a neurotensin analog, and a somatostatin analog. 
     
     
         42 . The method according to  claim 36 , wherein the monodisperse oligoethylene glycol unit attached to the amino acid of the neuropeptide analog increases the metabolic stability of the composition by increasing the half-life of the composition by at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% compared to the half-life of a composition comprising the neuropeptide without the covalently attached monodisperse oligoethylene glycol unit. 
     
     
         43 . The method of  claim 36 , wherein the neuropeptide analog is a truncated neuropeptide analog comprising at least one terminal lysine residue. 
     
     
         44 . The method of  claim 43 , wherein the neuropeptide analog is a truncated neuropeptide analog comprising at least 1, 2, 3, 4, or 5 terminal lysine residues. 
     
     
         45 . The method of  claim 44 , wherein the neuropeptide analog comprises 4 terminal lysine residues and wherein the monodisperse oligoethylene glycol unit is covalently attached to at least one of the 4 terminal lysine residues. 
     
     
         46 . The method of  claim 44 , wherein the neuropeptide analog comprises 5 terminal lysine residues and wherein the monodisperse oligoethylene glycol unit is covalently attached to at least one of the 5 terminal lysine residues. 
     
     
         47 . The method of  claim 43 , wherein the monodisperse oligoethylene glycol unit is covalently attached to the final terminal lysine residue. 
     
     
         48 . The method of  claim 43 , wherein the monodisperse oligoethylene glycol unit is covalently attached to the penultimate terminal lysine residue. 
     
     
         49 . The method of  claim 36 , wherein the monodisperse oligoethylene glycol unit comprises at least 2 ethylene glycol repeats. 
     
     
         50 . The method of  claim 49 , wherein the monodisperse oligoethylene glycol unit comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, and 48 ethylene glycol repeats. 
     
     
         51 . The method of  claim 36 , wherein the monodisperse oligoethylene glycol unit is a monodisperse polyethylene glycol unit.

Join the waitlist — get patent alerts

Track US2013324467A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.