Use of anti-cd40 antibodies for treatment of inflammatory conditions

A method of treating or preventing an autoimmune or inflammatory disease in a subject in need thereof, the method comprising administering to the subject a composition comprising an anti-CD40 (anti-cluster of differentiation 40) antibody,

• wherein the anti-CD40 antibody comprises a heavy chain and a light chain, wherein the heavy chain sequence and light chain sequence are selected from the group consisting of:
• a) a heavy chain CDR1 sequence selected from the group consisting of SEQ ID NO:
• 9 through SEQ ID NO:11, a heavy chain CDR2 sequence selected from the group consisting of SEQ ID NO:12 through SEQ ID NO:15, and a heavy chain CDR3 sequence selected from the group consisting of SEQ ID NO:16 through SEQ ID NO:17;
• and b) the light chain CDR1 sequence has a sequence selected from the group consisting of SEQ ID NO:18 through SEQ ID NO:21, a light chain CDR2 sequence of SEQ ID NO:22 through SEQ ID NO:23, and a light chain CDR3 sequence selected from the group consisting of SEQ ID NO:24 through SEQ ID NO:25;
• or
• wherein the anti-CD40 antibody comprises a variable heavy chain domain comprising any of SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:53, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73;
• and a variable light chain domain comprising any of SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:74, SEQ ID NO:75, or SEQ ID NO:76;
• or
• wherein the anti-CD40 antibody comprises a heavy chain sequence and a light chain sequence comprising the amino acid sequences of SEQ ID NO:27 and SEQ ID NO:26, respectively;
• SEQ ID NO:28 and SEQ ID NO:26, respectively;
• SEQ ID NO:29 and SEQ ID NO:26, respectively;
• SEQ ID NO:30 and SEQ ID NO:26, respectively;
• SEQ ID NO:32 and SEQ ID NO:31, respectively;
• SEQ ID NO:33 and SEQ ID NO:31, respectively;
• SEQ ID NO:34 and 2 of 9 SEQ ID NO:31, respectively;
• SEQ ID NO:35 and SEQ ID NO:31, respectively;
• SEQ ID NO:37 and SEQ ID NO:36, respectively;
• SEQ ID NO:38 and SEQ ID NO:36, respectively;
• SEQ ID NO:39 and SEQ ID NO:36, respectively;
• or SEQ ID NO:40 and SEQ ID NO:
• 36, respectively;
• wherein the composition comprises 80 mg, 120 mg, 180 mg or 240 mg of the anti-CD40 antibody;
• wherein a single-dose administration of the composition comprising 80 mg of the anti-CD40 antibody results in Cmax (ng mL−1) of about 888 to about 1550, AUC0-tz (μg·h mL−1) of about 126 to about 365, or AUC0-inf (μg·h mL−1) of about 330 to about 464;
• or
• wherein a single-dose administration of the composition comprising 120 mg of the anti-CD40 antibody results in Cmax (ng mL−1) of about 5160 to about 7210, AUC0-tz (μg·h mL−1) of about 1110 to about 2010, or AUC0-inf (μg·h mL−1) of about 1120 to about 2020;
• or
• wherein a single-dose administration of the composition comprising 180 mg of the anti-CD40 antibody results in Cmax (ng mL−1) of about 8650 to about 16300, AUC0-tz (μg·h mL−1) of about 2900 to about 6380, or AUC0-inf (μg·h mL−1) of about 2020 to about 2910;
• or
• wherein a single-dose administration of the composition comprising 240 mg of the anti-CD40 antibody results in Cmax (ng mL−1) of about 15700 to about 21300, AUC0-tz (μg·h mL−1) of about 5680 to about 7750, or AUC0-inf (μg·h mL−1) of about 5610 to about 7780;
• or
• wherein a multiple-dose administration (q1w or once every week) of the composition comprising 240 mg of the anti-CD40 antibody results in Cmax,1 (μg mL−1) of about 23 after the first dose or AUCT, 1 (μg·h mL−1) of about 2600 after the first dose;
• or
• wherein a multiple-dose administration (q1w or once every week) of the composition comprising 240 mg of the anti-CD40 antibody results in Cmax,4 (μg mL−1) of about 74 after the frouth dose, or Cmin, 4 (μg mL−1) of about 49 after the fourth dose, or AUCτ, 4 (μg·h mL−1) of about 10900 after the fourth dose.