Human antibodies that bind human TNF.alpha.

An isolated human antibody, or antigen-binding portion thereof, with the following characteristics:

• a) dissociates from human TNF.alpha. with a K.sub.off rate constant of 1.times.10.sup.-3 s.sup.-1 or less, as determined by surface plasmon resonance;
• b) has a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO:
• 3, or modified from SEQ ID NO:
• 3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9;
• c) has a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO:
• 4, or modified from SEQ ID NO:
• 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12.

An isolated human antibody, or an antigen-binding portion thereof, with a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:

• 3, or modified from SEQ ID NO:
• 3 by a single alanine substitution at position 1, 4, 5, 7 or 8, and with a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:
• 4, or modified from SEQ ID NO:
• 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11.

An isolated human antibody, or an antigen-binding portions thereof, with a light chain variable region (LCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

• 3, SEQ ID NO:
• 11, SEQ ID NO:
• 12, SEQ ID NO:
• 13, SEQ ID NO:
• 14, SEQ ID NO:
• 15, SEQ ID NO:
• 16, SEQ ID NO:
• 17, SEQ ID NO:
• 18, SEQ ID NO:
• 19, SEQ ID NO:
• 20, SEQ ID NO:
• 21, SEQ ID NO:
• 22, SEQ ID NO:
• 23, SEQ ID NO:
• 24, SEQ ID NO:
• 25, SEQ ID NO:
• 26 or with a heavy chain variable region (HCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
• 4, SEQ ID NO:
• 27, SEQ ID NO:
• 28, SEQ ID NO:
• 29, SEQ ID NO:
• 30, SEQ ID NO:
• 31, SEQ ID NO:
• 32, SEQ ID NO:
• 33 and SEQ ID NO:
• 34.

An isolated human antibody, or antigen-binding portion thereof, that binds to human TNF.alpha. and comprises a light chain CDR3 domain comprising

• the amino acid sequence of SEQ ID NO:
• 3, or modified from SEQ ID NO:
• 3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9, and
• a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO;
• 4, or modified from SEQ ID NO:
• 4 by a single alanine substitutions at position 2, 3, 4, 5, 6, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 11 and/or 12.

An isolated human antibody, or an antigen-binding portion thereof, that binds human TNF.alpha. and comprises a light chain variable region (LCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:

• 3, SEQ ID NO:
• 11, SEQ ID NO:
• 12, SEQ ID NO:
• 13, SEQ ID NO:
• 14, SEQ ID NO:
• 15, SEQ ID NO:
• 16, SEQ ID NO:
• 17, SEQ ID NO:
• 18, SEQ ID NO:
• 19, SEQ ID NO:
• 20, SEQ ID NO:
• 21, SEQ ID NO:
• 22, SEQ ID NO:
• 23, SEQ ID NO:
• 24, SEQ ID NO:
• 25, SEQ ID NO:
• 26 or a heavy chain variable region (HCVR) having a CDR3 domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
• 4, SEQ ID NO:
• 27, SEQ ID NO:
• 28, SEQ ID NO:
• 29, SEQ ID NO:
• 30, SEQ ID NO:
• 31, SEQ ID NO:
• 32, SEQ ID NO:
• 33 and SEQ ID NO:
• 34.