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Publication Number
US-12239697-B2
Publication Date
2025-03-04
Expiration Date
Abstract
This invention is directed to immunogenic composition, conjugates, virus-like particles (VLP) compositions, vaccines and methods directed to the treatment and/or prevent of infection by Human Papillomavirus.
Core Innovation
The invention relates to HPV VLP conjugate immunogenic compositions and vaccines in which HPV L1 and/or L2 proteins are linked to carrier proteins using spacer arms. The spacer arms are heterobifunctional, homobifunctional, or multifunctional spacer arms that form coupled HPV L1 or L2 proteins and enable coupling to the carrier protein to form the immunogenic composition.
The immunogenic composition is manufactured by coupling a first set of HPV L1 or L2 proteins to a first set of heterobifunctional, homobifunctional, or multifunctional spacer arms to form a first set of coupled L1 or L2 proteins. A second set of HPV L1 or L2 proteins is coupled to a second set of spacer arms to form a second set of coupled L1 or L2 proteins, and each of the first and second sets of coupled proteins is coupled to a carrier protein.
In related formats, carrier proteins are coupled to spacer arms forming carrier proteins containing multiple spacer arms, and HPV L1 or L2 proteins are coupled to the multiple spacer arms. The resulting immunogenic composition comprises multi-spacer-linked constructs in which L1 or L2 protein coupled to a spacer arm is coupled to a carrier protein, which is coupled to another spacer arm coupled to another L1 or L2 protein. Spacer arm chemistries described include PEG-based functionalized reagents and hydrazide/modified hydrazide variants, and the carrier protein is exemplified by CRM197 and toxoid antigens.
Claims Coverage
The independent claims (four total) cover multiple manufacturing schemes for producing HPV-based immunogenic compositions by coupling HPV L1 and/or L2 proteins to heterobifunctional, homobifunctional, or multifunctional spacer arms and coupling the resulting conjugates to carrier proteins. Across the independent claims, the inventive features center on how the spacer-linked conjugation stages are performed, whether spacer arms are attached to HPV first or to the carrier first, and how the final multi-spacer-linked construct is arranged with one or more L1/L2 proteins on shared or multiple carriers.
Coupling first and second HPV L1/L2 sets to spacer arms and coupling both to a carrier
Coupling a first set of L1 or L2 proteins of Human papilloma virus (HPV) to a first set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming a first set of coupled L1 or L2 proteins; coupling a second set of L1 or L2 proteins of HPV to a second set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming a second set of coupled L1 or L2 proteins; and coupling each of the first and second sets of coupled L1 or L2 proteins to a carrier protein forming the immunogenic composition.
Coupling HPV L1/L2 to spacer-arm-coupled carrier proteins
Coupling a first set of L1 or L2 proteins of Human papilloma virus (HPV) to a first set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming a first set of coupled L1 or L2 proteins; coupling carrier proteins to a second set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming coupled carrier proteins; and coupling the first set of coupled L1 or L2 proteins and a second set of L1 or L2 proteins to the coupled carrier proteins forming the immunogenic composition.
Forming carrier proteins with multiple spacer arms and coupling HPV L1/L2 to the multiple spacers
Coupling carrier proteins to a first and a second set of heterobifunctional, homobifunctional, or multifunctional spacer arms forming carrier proteins containing multiple spacers arms; and coupling L1 or L2 proteins of Human papilloma virus (HPV) to the multiple spacer arms of the carrier proteins forming the immunogenic composition.
Multi-spacer-linked construct where carrier is coupled via spacer arms to multiple HPV L1/L2 proteins
Providing L1 or L2 proteins of Human papilloma virus (HPV) and carrier proteins; and coupling the L1 or L2 proteins and carrier proteins to heterobifunctional, homobifunctional, or multifunctional spacer arms forming the immunogenic composition which comprises the L1 or L2 protein coupled to a spacer arm which is coupled to a carrier protein which is coupled to another spacer arm which is coupled to another L1 or L2 protein.
Across the independent claims, the claim coverage is directed to manufacturing HPV L1/L2 conjugate immunogenic compositions using heterobifunctional, homobifunctional, or multifunctional spacer arms and carrier proteins. The claims distinguish whether HPV L1/L2 are coupled to spacer arms before attaching to the carrier, whether carrier proteins are first coupled to spacer arms before attaching HPV L1/L2 conjugates, whether spacer arms are formed on the carrier as multiple spacers prior to coupling HPV L1/L2, and whether the final construct is a multi-spacer-linked arrangement with carrier-mediated linkage between spacer-linked L1/L2 proteins.
Stated Advantages
Reduced antigen dose and/or number of doses compared to commercial HPV VLP vaccines (e.g., 8–10 µg/dose vs 20–40 µg).
Provides immunogenic composition and vaccine formulations using various adjuvants, especially aluminum salts and MPLA/QS-21/TLR agonists.
Documented Applications
Immunogenic compositions and vaccine candidates based on HPV VLP conjugates (including multivalent vaccine candidates such as 9- and 10-valent constructs with L1/L2).
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