Antigen-binding molecules that bind cd38 and/or cd28, and uses thereof

An isolated bispecific antigen-binding molecule, comprising:

• (a) a first antigen-binding domain that comprises an HCDR1 amino acid sequence of SEQ ID NO:
• 4, an HCDR2 amino acid sequence of SEQ ID NO:
• 6, and an HCDR3 amino acid sequence of SEQ ID NO:
• 8;
• and
• (b) a second antigen binding domain that comprises an HCDR1 amino acid sequence of SEQ ID NO:
• 12, an HCDR2 amino acid sequence of SEQ ID NO:
• 14, and an HCDR3 amino acid sequence of SEQ ID NO:
• 16.

An isolated bispecific antigen-binding molecule, comprising:

• (a) a first antigen-binding domain that comprises an HCDR1 amino acid sequence of SEQ ID NO:
• 34, an HCDR2 amino acid sequence of SEQ ID NO:
• 36, and an HCDR3 amino acid sequence of SEQ ID NO:
• 38;
• and
• (b) a second antigen binding domain that comprises an HCDR1 amino acid sequence of SEQ ID NO:
• 42, an HCDR2 amino acid sequence of SEQ ID NO:
• 44, and an HCDR3 amino acid sequence of SEQ ID NO:
• 46.

An isolated recombinant antibody or antigen-binding fragment thereof that specifically binds to human CD38, wherein the antibody comprises sequences selected from the group consisting of:

• (i) three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3) contained within a heavy chain variable region (HCVR) amino acid sequence having at least about 90% sequence identity to SEQ ID NOs:
• 2 or 32;
• and three light chain CDRs (LCDR1, LCDR2, and LCDR3) contained within a light chain variable region (LCVR) amino acid sequence having at least about 90% sequence identity to SEQ ID NO:
• 18 or 48;
• (ii) three HCDRs contained within an HCVR amino acid sequence of SEQ ID NO:
• 2 and three LCDRs contained within an LCVR amino acid sequence of SEQ ID NO:
• 18;
• (iii) three HCDRs contained within an HCVR amino acid sequence of SEQ ID NO:
• 32 and three LCDRs contained within an LCVR amino acid sequence of SEQ ID NO:
• 48;
• (iv) an HCDR/LCDR amino acid sequence combination of SEQ ID NOs:
• 4-6-8-20-22-24;
• (v) an HCDR/LCDR amino acid sequence combination of SEQ ID NOs:
• 34-36-38-50-52-54;
• (vi) an HCVR amino acid sequence comprising SEQ ID NO:
• 2 or 32;
• and an LCVR amino acid sequence comprising SEQ ID NO:
• 18 or 48;
• (vii) an HCVR amino acid sequence comprising SEQ ID NO:
• 2 and an LCVR amino acid sequence comprising SEQ ID NO:
• 18;
• and
• (viii) an HCVR amino acid sequence comprising SEQ ID NO:
• 32 and an LCVR amino acid sequence comprising SEQ ID NO:
• 48.

An isolated recombinant antibody or antigen-binding fragment thereof that specifically binds to human CD28, wherein the antibody comprises sequences selected from the group consisting of:

• (i) three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3) contained within a heavy chain variable region (HCVR) amino acid sequence having at least about 90% sequence identity to SEQ ID NOs:
• 10 or 40;
• and three light chain CDRs (LCDR1, LCDR2, and LCDR3) contained within a light chain variable region (LCVR) amino acid sequence having at least about 90% sequence identity to SEQ ID NO:
• 18 or 48;
• (ii) three HCDRs contained within an HCVR amino acid sequence of SEQ ID NO:
• 10 and three LCDRs contained within an LCVR amino acid sequence of SEQ ID NO:
• 18;
• (iii) three HCDRs contained within an HCVR amino acid sequence of SEQ ID NO:
• 40 and three LCDRs contained within an LCVR amino acid sequence of SEQ ID NO:
• 48;
• (iv) an HCDR/LCDR amino acid sequence combination of SEQ ID NOs:12-14-16-20-22-24;
• (v) an HCDR/LCDR amino acid sequence combination of SEQ ID NOs:42-44-46-50-52-54;
• (vi) an HCVR amino acid sequence comprising SEQ ID NO:
• 10 or 40;
• and an LCVR amino acid sequence comprising SEQ ID NO:
• 18 or 48;
• (vii) an HCVR amino acid sequence comprising SEQ ID NO:
• 10 and an LCVR amino acid sequence comprising SEQ ID NO:
• 18;
• and
• (viii) an HCVR amino acid sequence comprising SEQ ID NO:
• 40 and an LCVR amino acid sequence comprising SEQ ID NO:
• 48.