Abstract: Through a combination of in vitro and in vivo approaches, the inventors show that human lgG2 (h2) delivers unique Fc?R-independent agonistic activity to anti-CD40 antibodies and to antibodies specific to other immunostimulatory receptors, including 4-1BB and CD28. Investigation of an anti-human CD40 mAb, LOB7.4, revealed that the unique activity of h2 was dependent upon the precise arrangement of hinge and CH1 disulfide bonds. Chemical ‘shuffling’ or mutagenesis to ‘lock’ LOB7.4 into either a more flexible ‘h2A’ or more compact ‘h2B’ conformation endowed antagonistic and agonistic properties, respectively. Engineering of h2 in this way allows development of reagents with either immunostimulatory or immunosuppressive characteristics, with direct implication for the design of therapeutic mAb agents and fusion proteins.

Abstract: Through a combination of in vitro and in vivo approaches, the inventors show that human IgG2 (h2) delivers unique Fc?R-independent agonistic activity to anti-CD40 antibodies and to antibodies specific to other immunostimulatory receptors, including 4-1BB and CD28. Investigation of an anti-human CD40 mAb, LOB7.4, revealed that the unique activity of h2 was dependent upon the precise arrangement of hinge and CH1 disulfide bonds. Chemical ‘shuffling’ or mutagenesis to ‘lock’ LOB7.4 into either a more flexible ‘h2A’ or more compact ‘h2B’ conformation endowed antagonistic and agonistic properties, respectively. Engineering of h2 in this way allows development of reagents with either immunostimulatory or immunosuppressive characteristics, with direct implication for the design of therapeutic mAb agents and fusion proteins.

Abstract: Through a combination of in vitro and in vivo approaches, the inventors show that human IgG2 (h2) delivers unique Fc?R-independent agonistic activity to anti-CD40 antibodies and to antibodies specific to other immunostimulatory receptors, including 4-1BB and CD28. Investigation of an anti-human CD40 mAb, LOB7.4, revealed that the unique activity of h2 was dependent upon the precise arrangement of hinge and CH1 disulfide bonds. Chemical ‘shuffling’ or mutagenesis to ‘lock’ LOB7.4 into either a more flexible ‘h2A’ or more compact ‘h2B’ conformation endowed antagonistic and agonistic properties, respectively. Engineering of h2 in this way allows development of reagents with either immunostimulatory or immunosuppressive characteristics, with direct implication for the design of therapeutic mAb agents and fusion proteins.

Abstract: An exercise apparatus for fully figured individuals includes a low profile frame having a first support member, a second support member, a front base, a rear base, and stem support member, a seat bar pivotally attached to said frame, an oversized seat rotatably connected to said seat bar, first and second stems pivotally attached to said stem support member, first and second rocking bars, wherein the first rocking bar is pivotally attached to said first stem and said second rocking bar is pivotally attached to said second stem, and wherein said rocking bars are pivotally attachable to said seat bar, first and second handlebars connected to said first and second stems, first and second oversized foot pedals connected to said first and second stems, and a piston having two ends, wherein one end is connected to said frame, and the second end is connected to said bar. An exercise apparatus for fully figured individuals configured to provide at least 432 square inches of surface seating area.