ANTIBODIES TO IL-6 AND USE THEREOF

• US 20090297513A1
• Filed: 02/24/2009
• Published: 12/03/2009
• Est. Priority Date: 05/21/2007
• Status: Active Grant

• Current Assignee: Vitaeris Inc. (CSL Limited)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Latham, John, Jensen, Anne Elisabeth Carvalho, Garcia-Martinez, Leon, Kovacevich, Brian, Dutzar, Ben, Olson, Katie, Ojala, Ethan, Smith, Jeffrey T.L.
• Granted Patent: US 8,178,101 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention is directed to antibodies and fragments thereof and humanized versions thereof having binding specificity for IL-6. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V_H, V_L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-IL-6 antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-IL-6 antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-IL-6 antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with IL-6. These antibodies may bind at least one of soluble IL-6, cell surface expressed IL-6, IL-6/IL-6R and/or prevent the association of IL-6 and IL-6R, the association of IL-6/IL-6R and gp130 and or the formation of IL-6/IL-6R/gp130 multimers and thereby inhibit a biological effect associated with any of the foregoing.

Claims

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134. A humanized anti-IL-6 antibody or IL-6 binding fragment containing a humanized variable light region contained in SEQ ID NO:

709 and a humanized heavy chain region contained in SEQ ID NO;

656 or 657.

135. A composition containing a diagnostically or therapeutically effective amount of an humanized anti-IL-6 antibody according to claim 134.

136. A therapy for a condition treatable with an anti-IL-6 antibody comprising administration of an antibody or composition according to claim 134 or 135.

137. The therapy of claim 136 wherein the condition is selected from cancer, an inflammatory disease, arthritis, fatigue, viral disorder or cachexia.

138. A chimeric or humanized antibody, comprising one or more of the polypeptide sequences of SEQ ID NO:

4;

SEQ ID NO;

5; and

SEQ ID NO;

6 which correspond to the complementarity-determining regions (CDRs, or hypervariable regions) of the variable light chain sequence of SEQ ID NO;

2, and/or one or more of the polypeptide sequences of SEQ ID NO;

7 (CDR1);

SEQ ID NO;

8 (CDR2);

SEQ ID NO;

120 (CDR2) or SEQ ID NO;

659 (CDR2); and

SEQ ID NO;

9 (CDR3) which correspond to the complementarity-determining regions (CDRs, or hypervariable regions) of the variable heavy chain sequence of SEQ ID NO;

3 or SEQ ID NO;

19, or combinations of these polypeptide sequences.

139. An anti-IL-6 antibody comprising at least one CDR or variable heavy or variable light chain sequence as set forth in FIG. 15.

140. An anti-IL-6 antibody or antibody fragment which comprises the variable heavy chain polypeptide sequence of SEQ ID NO:

3, 18, 19, 652, 653, 654, 655, 656, 657, 661, 664, 665, 657, 658, 704, or 708.

144. The anti-IL-6 antibody or antibody fragment of claim 140 which has binding specificity to IL-6 comprising.

141. An anti-IL-6 antibody or antibody fragment which comprises the variable light chain polypeptide sequence of SEQ ID NO:

2, 20, 647, 648, 649, 650, 651, 660, 666, 699, 702, 706, or 709.

142. The anti-IL-6 antibody or antibody fragment of claim 141 which further comprises a variable heavy chain polypeptide sequence selected from SEQ ID NO:

3, 18, 19, 652, 653, 654, 655, 656, 657, 661, 664, 665, 657, 658, 704, or 708.

145. The antibody or antibody fragment of claim 142 which has specificity to IL-6 comprising.

143. An antibody or antibody fragments having binding specificity to IL-6 comprising a light chain CDR1 as in SEQ ID NO:

4, a light chain CDR2 as in SEQ ID NO;

5 an light chain CDR3 as in SEQ ID NO;

6, a heavy chain CDR1 as in SEQ ID NO;

7, a heavy chain CDR2 as in SEQ ID NO;

8 or 120 and a heavy chain CDR3 as in SEQ ID NO;

9.

146. A nucleic acid sequence encoding a CDR or variable heavy or light chain polypeptide of an anti-IL-6 antibody selected from the following:

the light chain CDR1 in SEQ ID NO;

12 or SEQ ID NO;

694;

the light chain CDR2 in SEQ ID NO;

13;

the light chain CDR3 encoded by the sequence in SEQ ID NO;

14 or SEQ ID NO;

695;

a heavy chain CDR1 in SEQ ID NO;

15, a heavy chain CDR2 in SEQ ID NO;

16 or SEQ ID NO;

696 and a heavy chain CDR3 in SEQ ID NO;

17 or SEQ ID NO;

697.

147. A vector containing at least one nucleic acid sequence according to claim 146.

148. The nucleic acid sequence of claim 146 which encodes an anti-IL-6 antibody or fragment and comprises least one of SEQ ID NO:

10, 662, 698, 701, or 705 and/or at least one of SEQ ID NO;

11, 663, 700, 703, or 707.

149. The nucleic acid sequence of claim 146 which encodes a portion of an anti-IL-6 antibody and comprises at least one sequence selected from SEQ ID NO:

12, 694, 13, 14, 695, 15, 16, 696, 697, 17, 698, 10, 662, 11, 663, 700, 701, 703, 705 and 707.

150. The nucleic acid sequence of claim 149 which further comprises at least one nucleic acid sequence encoding a human or rabbit framework region or humanized variant.

151. A variable light chain encoded by SEQ ID NO:

10, 662, 698, 701, or 705.

152. A variable heavy chain polypeptide encoded by SEQ ID NO:

11, 663, 700, 703, or 707.

153. An anti-IL-6 antibody or fragment containing variable heavy and light chains encoded by SEQ ID NO:

10 and 11, or SEQ ID NO;

698 and SEQ ID NO;

700, or SEQ ID NO;

701 and SEQ ID NO;

703 or SEQ ID NO;

705 and SEQ ID NO;

707 or SEQ ID NO;

662 and SEQ ID NO;

663.