Interleukin-10 antibodies
AssigneeSchering Corporation
InventorLeonard Presta
Life of this patent
Estimating the term…
Abstract
The methods and compositions provided herein relate generally to IL-10 specific antibodies and uses thereof. More specifically, compositions of humanized IL-10 specific antibodies and methods to use such antibodies in modulating the biological activity of IL-10, particularly in autoimmune disorders and pathogen-mediated immunopathology.
Claims57
A humanized recombinant antibody molecule that binds IL-10 or binding fragment thereof, comprising:
- at least one antibody light chain variable region, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence selected from the group consisting of SEQ ID NO:1 at CDR1, SEQ ID NO:2 at CDR2, and SEQ ID NO:3 at CDR3;
- and a framework region, wherein the amino acid sequence of framework region is all or substantially all of a human immunoglobin amino acid sequence;
- and
- at least one antibody heavy chain variable region, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence selected from the group consisting of SEQ ID NO:6 at CDR1, SEQ ID NO:7 at CDR2, and SEQ ID NO:8 at CDR3;
- and a framework region, wherein the amino acid sequence of framework region is all or substantially all of a human immunoglobin amino acid sequence.
A chimeric recombinant antibody molecule that binds IL-10 or binding fragment thereof, comprising:
- at least one antibody light chain variable region, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence selected from the group of SEQ ID NO:1 at CDR1, SEQ ID NO:2 at CDR2, and SEQ ID NO:3 at CDR3;
- and
- at least one antibody heavy chain variable region, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence selected from the group of SEQ ID NO:6 at CDR1, SEQ ID NO:7 at CDR2, and SEQ ID NO:8 at CDR3.
A humanized recombinant antibody molecule that binds IL-10, or binding fragment thereof, comprising:
- at least one antibody light chain, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence selected from the group consisting of SEQ ID NO:11 at CDR1, SEQ ID NO:12 at CDR2, and SEQ ID NO:13 at CDR3;
- and a framework region, wherein the amino acid sequence of framework region is all or substantially all of a human immunoglobin amino acid sequence;
- and
- at least one antibody heavy chain, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence selected of SEQ ID NO:15 at CDR1, SEQ ID NO:16 at CDR2, and SEQ ID NO:17 at CDR3;
- and a framework region, wherein the amino acid sequence of framework region is all or substantially all of a human immunoglobin amino acid sequence.
A chimeric recombinant antibody molecule that binds IL-10, or binding fragment thereof, comprising:
- at least one antibody light chain, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence of SEQ ID NO:11 at CDR1, SEQ ID NO:12 at CDR2, and SEQ ID NO:13 at CDR3;
- and
- at least one antibody heavy chain, or binding fragment thereof, comprising a polypeptide having at least one amino acid sequence of SEQ ID NO:15 at CDR1, SEQ IDf NO:16 at CDR2, and SEQ ID NO:17 at CDR3.
An isolated nucleic acid sequence encoding an antibody specific for IL-10 comprising a light chain having the nucleic acid sequence of SEQ ID NO:21 and a heavy chain having the nucleic acid sequence of SEQ ID NO:22.
An isolated nucleic acid sequence encoding an antibody specific for IL-10 comprising a light chain having the nucleic acid sequence of SEQ ID NO:23 and a heavy chain having the nucleic acid sequence of SEQ ID NO:24.
A method to identify an acceptor germline sequence for a humanized antibody, which method comprises the steps of:
- a) identifying a non-human antibody that has the desired biological activity;
- b) determining the amino acid sequence of a non-human antibody VH and VL domains;
- and
- c) comparing the nonhuman antibody sequence to a group of human germline sequences, wherein the comparison comprises the substeps of:
- 1) assigning the sequence of non-human VH and VL domain sequences residue numbers;
- 2) delineating the CDR and FR regions in the sequence;
- 3) assigning a predetermined numerical score at each residue position for which the non-human and human germline sequences are identical;
- and
- 4) totaling all of the residue scores to generate a total score for each human germline sequence;
- and
- d) identifying the human germline sequence with the highest total residue score as the acceptor germline sequence.
Dependencies are inferred from the claim text.