Anti-ANGPTL8 antibodies and uses thereof
An antibody and antigen technology, applied in the direction of antibodies, antibody medical components, anti-hormonal immunoglobulin, etc., can solve problems such as elevated
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Embodiment 1
[0233] Example 1. Generation of anti-ANGPTL8 antibodies
[0234] by immunization with an immunogen comprising recombinant human ANGPTL8 (see SEQ ID NO: 340) expressing a C-terminal mouse IgG2a tag Mice (ie, engineered mice comprising DNA encoding human immunoglobulin heavy and kappa light chain variable regions) obtained anti-ANGPTL8 antibodies. Antibody immune responses were monitored by an ANGPTL8 specific immunoassay. When the desired immune response was obtained, several fully human anti-ANGPTL8 antibodies were generated from antigen-positive B cells as described in US 2007 / 0280945A1, which is incorporated herein by reference in its entirety.
[0235] Certain biological properties of exemplary anti-ANGPTL8 antibodies produced according to the methods of this Example are described in detail in the Examples set forth below.
Embodiment 2
[0236] Example 2. Heavy and light chain variable region amino acid and nucleic acid sequences
[0237] Table 1 lists the amino acid sequence identifiers of the heavy and light chain variable regions and CDRs of the selected anti-ANGPTL8 antibodies of the present invention. Table 2 lists the corresponding nucleic acid sequence identifiers.
[0238] Table 1: Amino acid sequence identifiers
[0239]
[0240] Table 2: Nucleic Acid Sequence Identification
[0241]
[0242] Antibodies are generally referred to herein according to the following nomenclature: Fc prefix (eg "H1H", "H1M", "H2M", "H4H" etc.) followed by a numerical designation (eg "15321", "15341", "15350" etc.), followed by a "P" or "N" suffix, as shown in Tables 1 and 2. Thus, according to this nomenclature, the antibody may be referred to herein as, eg, "H4H15321P" or the like. The H4H prefix on antibody names as used herein indicates the specific Fc region isotype of the antibody. For example, "H4H" antibo...
Embodiment 3
[0243] Example 3: Surface Plasmon Resonance (SPR) Determination of Dissociation Rate Constants (k) of ANGPTL8 Antibody Binding to ANGPTL8, ANGPTL3 and ANGPTL4 Peptides d )
[0244] It has been previously shown that the N-terminal coiled-coil of ANGPTL3 [WO 2012 / 174178 A1; Lee et al. (2009) JBC, 284:13735-13745] and ANGPTL4 [Desai et al. (2007) PNAS, 104:11766-11771] Region-bound antibodies block the LPL inhibitory activity of the ANGPTL protein. In this experiment, antibodies against ANGPTL8 were tested for binding to peptides from the N-terminal region of ANGPTL8.
[0245] The dissociation rate constant of ANGPTL8 antibody binding to human ANGPTL8 peptide (hANGPTL8 peptide, SEQ ID NO: 337) was determined using the real-time surface plasmon resonance based MASS-1 biosensor platform. The assay used a format in which the ANGPTL8 antibody was captured on the sensor surface and the peptide was injected onto the antibody surface. Also included as controls were a peptide from the...
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