US2014127260A1PendingUtilityA1

Hpv vaccine formulations comprising aluminum adjuvant and methods of producing same

39
Individually held — no corporate assignee on recordPriority: Jun 24, 2011Filed: Jun 22, 2012Published: May 8, 2014
Est. expiryJun 24, 2031(~4.9 yrs left)· nominal 20-yr term from priority
Inventors:Ramesh V. ChintalaAkhilesh Bhambhani
A61P 31/20A61P 37/04A61P 31/12A61K 9/19A61K 47/02C12N 2710/20034A61K 39/39A61K 47/26A61K 47/183C12N 7/00A61K 2039/70A61K 2039/55505A61K 39/12C12N 2710/20023A61K 2039/5258A61K 9/0019
39
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Claims

Abstract

The invention provides human papillomavirus (HPV) antigen formulations which show increased antigen stability. More specifically, the invention provides stable HPV formulations comprising HPV virus-like particles (VLPs) bound to an aluminum salt adjuvant and further comprise a combination of sucrose and mannitol. The vaccine formulations of the invention are stable following freeze-thaw and freeze-drying. Also provided are lyophilized and frozen HPV vaccine formulations comprising HPV VLPs of at least one HPV type adsorbed onto an aluminum salt adjuvant, sucrose, and mannitol. Methods of making the stable vaccine formulations of the invention are also provided.

Claims

exact text as granted — not AI-modified
1 . A human papillomavirus vaccine formulation comprising:
 a) a therapeutically effective amount of HPV virus-like particles (VLPs) which are adsorbed onto an aluminum adjuvant;   b) mannitol and sucrose; and   c) optionally a salt.   
     
     
         2 . The HPV formulation of  claim 1 , wherein the formulation comprises:
 a) HPV VLPs of at least one HPV type adsorbed on an aluminum adjuvant, wherein the VLPs of each HPV type are present in a concentration of 10-200 mcg/ml and wherein the VLPs are selected from the group consisting of: HPV6, HPV11, HPV16, HPV18, HPV26, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV53, HPV55, HPV56, HPV58, HPV59, HPV66, HPV68, HPV73, and HPV82; and   b) about 1% to about 10% w/v mannitol; and about 0.5% to about 10% sucrose.   
     
     
         3 . The formulation of  claim 2 , further comprising about 0.15 M to about 0.32M NaCl. 
     
     
         4 . The formulation of  claim 3 , further comprising about 5 mM to about 20 mM histidine. 
     
     
         5 . The formulation of  claim 4 , further comprising about 0.01% to about 0.03% weight to volume concentration of a surfactant selected from the group consisting of Polysorbate 20 and Polysorbate 80. 
     
     
         6 . The formulation of  claim 5 , wherein the surfactant is Polysorbate 80 which is present in a weight to volume concentration of about 0.01%. 
     
     
         7 . The formulation of  claim 3 , wherein mannitol is present in a weight to volume concentration of about 4% to about 7% and sucrose is present in a weight to volume concentration of about 1% to about 5%. 
     
     
         8 . The formulation of  claim 7 , wherein the aluminum adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate, and aluminum hydroxyphosphate. 
     
     
         9 . The formulation of  claim 8 , wherein the HPV VLPs are from HPV types 6, 11, 16 and 18. 
     
     
         10 . The formulation of  claim 9 , further comprising HPV VLPs of at least one additional HPV type selected from the group consisting of: 31, 33, 45, 52 and 58. 
     
     
         11 . The formulation of  claim 7 , wherein the formulation is freeze-dried. 
     
     
         12 . The formulation of  claim 7 , wherein the formulation is frozen. 
     
     
         13 . The formulation of  claim 7  wherein the formulation is stable for 1 month at 25° C. following lyophilization or freeze-thaw process stress. 
     
     
         14 . The formulation  claim 13 , wherein the formulation is stable for 3 months at 25° C. following lyophilization or freeze-thaw process stress. 
     
     
         15 . The formulation of  claim 14 , wherein the formulation is stable for 6 months at 25° C. or 30 days at 37° C. following lyophilization or freeze-thaw process stress. 
     
     
         16 . The formulation of  claim 7 , wherein the formulation is stable for 3 months at 37° C. following lyophilization or freeze-thaw process stress. 
     
     
         17 . The formulation of  claim 7 , wherein the formulation is stable for over 6 months at 2-8° C. following lyophilization or freeze-thaw process stress. 
     
     
         18 . A method for producing a stable lyophilized HPV vaccine formulation comprising:
 (a) formulating a liquid HPV vaccine formulation comprising (i) HPV VLPs of at least one HPV type adsorbed onto an aluminum salt adjuvant, wherein the VLPs of at least one HPV type are present in a concentration of 10-200 mcg/ml and wherein the VLPs are selected from the group consisting of: HPV6, HPV11, HPV16, HPV18, HPV26, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV53, HPV55, HPV56, HPV58, HPV59, HPV66, HPV68, HPV73, and HPV82; (ii) about 1% to about 10% w/v mannitol; and (iii) about 0.5% to about 10% sucrose;   (b) freezing the liquid formulation to produce a frozen formulation and   (c) drying the frozen formulation to provide a lyophilized HPV vaccine formulation.   
     
     
         19 . The method of  claim 18 , wherein the liquid formulation further comprises about 5 mM to about 20 mM histidine. 
     
     
         20 . The method of  claim 19 , wherein the liquid formulation further comprises about 50 mM to about 350 mM NaCl. 
     
     
         21 . The method of  claim 20 , wherein the liquid formulation further comprises Polysorbate 80 which is present in a weight to volume concentration of from about 0.005% to about 0.03%. 
     
     
         22 . The method of  claim 21 , wherein the liquid formulation comprises HPV VLPs of HPV types 16 and 18. 
     
     
         23 . The method of  claim 22 , wherein the liquid formulation further comprises HPV VLPs of HPV types 6 and 11. 
     
     
         24 . A method for producing a stable frozen HPV vaccine formulation comprising:
 (a) formulating a liquid HPV vaccine formulation comprising (i) HPV VLPs of at least one HPV type adsorbed onto an aluminum salt adjuvant, wherein the VLPs of at least one HPV type are present in a concentration of 10-200 mcg/ml and wherein the VLPs are selected from the group consisting of: HPV6, HPV11, HPV16, HPV18, HPV26, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV53, HPV55, HPV56, HPV58, HPV59, HPV66, HPV68, HPV73, and HPV82; (ii) about 1% to about 10% w/v mannitol; and (iii) about 0.5% to about 10% sucrose; and   (b) freezing the liquid formulation to produce a frozen vaccine formulation.

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