US 12,268,738 B2
Liquid six combined vaccine composition
Shun Yamashita, Kikuchi (JP); Tatsuya Shirai, Kikuchi (JP); Kazuhiro Daimon, Kikuchi (JP); Tomohiro Minoda, Kikuchi (JP); Shinji Akasaki, Kikuchi (JP); Kanae Ishikawa, Kikuchi (JP); and Haruna Iwata, Kikuchi (JP)
Assigned to KM BIOLOGICS CO., LTD., Kumamoto (JP)
Appl. No. 18/287,248
Filed by KM Biologics Co., Ltd., Kumamoto (JP)
PCT Filed Apr. 19, 2022, PCT No. PCT/JP2022/018211
§ 371(c)(1), (2) Date Oct. 17, 2023,
PCT Pub. No. WO2022/224966, PCT Pub. Date Oct. 27, 2022.
Claims priority of application No. 2021-070897 (JP), filed on Apr. 20, 2021.
Prior Publication US 2024/0197863 A1, Jun. 20, 2024
Int. Cl. A61K 39/39 (2006.01); A61K 39/00 (2006.01); A61K 39/02 (2006.01); A61K 39/05 (2006.01); A61K 39/08 (2006.01); A61K 39/13 (2006.01); A61K 39/145 (2006.01); A61K 39/29 (2006.01)
CPC A61K 39/292 (2013.01) [A61K 39/05 (2013.01); A61K 39/08 (2013.01); A61K 39/099 (2013.01); A61K 39/13 (2013.01); A61K 39/145 (2013.01); A61K 2039/5252 (2013.01); A61K 2039/55505 (2013.01); A61K 2039/55516 (2013.01); A61K 2039/55544 (2013.01); A61K 2039/70 (2013.01)] 8 Claims
OG exemplary drawing
 
1. A method for producing a stable liquid formulation of a six combined vaccine against diphtheria, pertussis, tetanus, polio, Haemophilus influenzae type b (Hib), and hepatitis B (HepB), the method comprising the following steps of:
(1) mixing diphtheria toxoid (D) and tetanus toxoid (T) with an aluminum adjuvant to produce a DT adjuvant;
(2) mixing a hepatitis B surface (HBs) antigen with the DT adjuvant obtained in step (1) to produce a DT-HBs adjuvant;
(3) mixing a pertussis antigen (P) with the DT-HBs adjuvant obtained in step (2) to produce a DPT-HBs adjuvant;
(4) mixing inactivated poliovirus (IPV) with the DPT-HBs adjuvant obtained in step (3) to produce a DPT-IPV-HBs adjuvant;
(5) adding a succinate phosphate buffer to the DPT-IPV-HBs adjuvant obtained in step (4), and then adding Polyribosyl-Ribitol-Phosphate (PRP) (Polyribosyl-Ribitol-Phosphate conjugated to tetanus toxoid (PRP-T conjugate) as a Hib antigen to produce a mixture of DPT-IPV-Hib-HBs adjuvant and PRP-T conjugate; and
(6) adjusting pH of the mixture of DPT-IPV-Hib-HBs adjuvant and PRP-T conjugate obtained in step (5) to 5.4 to 5.9,
wherein the aluminum adjuvant is an aluminum phosphate gel.