Human anti-B7RP1 Neutralizing Antibodies
AssigneeAmgen Inc.
InventorsGerald Siu, Wenyan Shen, Steven Kiyoshi Yoshinaga, Haichun Huang
Life of this patent
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Abstract
This invention provides antibodies that interact with or bind to human B7 related protein-1 (B7RP1) and antibodies that bind to and neutralize the function of B7RP1 thereby The invention also provides pharmaceutical compositions of said antibodies and methods for neutralizing B7RP1 function, and particularly for treating immune disorders (e.g., inappropriate immune response) by administering a pharmaceutically effective amount of anti-B7RP1 antibodies Methods of detecting the amount of B7RP1 in a sample using anti-B7RP1 antibodies are also provided.
Claims87
An isolated antibody that binds specifically to B7RP1, wherein the antibody comprises a heavy chain having a heavy chain variable region and a light chain wherein the heavy chain variable region comprises an amino acid sequence that has at least 80% sequence identity to the amino acid sequence set forth in any of SEQ ID NO:
- 7-14, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
An isolated antibody that binds specifically to B7RP1 comprising:
- a) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 7, an antigen-binding or an immunologically functional immunoglobulin fragment thereof, and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 1, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof;
- b) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 8, an antigen-binding or an immunologically functional immunoglobulin fragment thereof, and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 1, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof;
- c) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 9, an antigen-binding or an immunologically functional immunoglobulin fragment thereof, and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 2, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof;
- d) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 10, an antigen-binding or an immunologically functional immunoglobulin fragment thereof, and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 3, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof;
- e) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 11, an antigen-binding or an immunologically functional immunoglobulin fragment thereof, and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 3, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
- f) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 12, an antigen-binding or an immunologically functional immunoglobulin fragment thereof and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 4, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof;
- g) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 13, an antigen-binding or an immunologically functional immunoglobulin fragment thereof and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 5, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof;
- or
- h) a heavy chain having a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 14, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof and a light chain having a light chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:
- 6, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
An isolated antibody that binds specifically to B7RP1, wherein the antibody comprises a heavy chain and a light chain having a light chain variable region, wherein the light chain variable region comprises an amino acid sequence that has at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:
- 1-6, or an antigen-binding or immunogenic fragment thereof.
An isolated antibody that binds specifically to B7RP1, comprising:
- a) the heavy chain CDR1 has an amino acid sequence as set forth in SEQ ID NO:
- 27, the heavy chain CDR2 has an amino acid sequence as set forth in SEQ ID NO:
- 28, and the heavy chain CDR 3 has an amino acid sequence as set forth in SEQ ID NO:
- 29;
- b) the heavy chain CDR1 has an amino acid sequence as set forth in SEQ NO:
- 30, the heavy chain CDR2 has an amino acid sequence as set forth in SEQ ID NO:
- 31, and the heavy chain CDR 3 has an amino acid sequence as set forth in SEQ ID NO:
- 32;
- c) the heavy chain CDR1 has an amino acid sequence as set forth in SEQ ID NO:
- 27, the heavy chain CDR has an amino acid sequence as set forth in SEQ ID NO:
- 33, and the heavy chain CDR 3 has an amino acid sequence as set forth in SEQ ID NO:
- 34;
- d) the heavy chain CDR1 has an amino acid sequence as set forth in SEQ ID NO:
- 35, the heavy chain CDR2 has an amino acid sequence as set forth in SEQ ID NO:
- 36, and the heavy chain CDR 3 has an amino acid sequence as set forth in SEQ ID NO:
- 37;
- e) the heavy chain CDR1 has an amino acid sequence as set forth in SEQ ID NO:
- 27, the heavy chain CDR2 has an amino acid sequence as set forth in SEQ ID NO:
- 33, and the heavy chain CDR 3 has an amino acid sequence as set forth in SEQ ID NO:
- 38;
- or
- f) the heavy chain CDR1 has an amino acid sequence as set forth in SEQ ID NO:
- 35, the heavy chain CDR2 has an amino acid sequence as set forth in SEQ ID NO:
- 39, and the heavy chain CDR 3 has an amino acid sequence as set forth in SEQ ID NO:
- 40.
A method of treating an autoimmune disease or inflammatory response in a patient, comprising administering to a patient a pharmaceutically effective amount of an isolated antibody that binds specifically to B7RP1, wherein the antibody comprises an amino acid sequence as set forth in any of SEQ ID NO:
- 1-40, 44-58, or 70-76, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
A method of inhibiting co-stimulatory signal T-cell activation in a patient comprising administering to a patient a pharmaceutically effective amount of an isolated human antibody that binds specifically to B7RP1, wherein the antibody comprises an amino acid sequence as set forth in any of SEQ ID NO:
- 1-40, 44-58, or 70-76, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
A method of treating a patient having asthma, rheumatoid arthritis, or systemic Lupus erythematosus, the method comprising administering to a patient a pharmaceutically effective amount of an isolated human antibody that binds specifically to B7RP1, wherein the antibody comprises an amino acid sequence as set forth in any of SEQ ID NO:
- 1-40, 44-58, or 70-76, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an isolated antibody that binds specifically to B7RP1, wherein the antibody comprises an amino acid sequence as set forth in any of SEQ ID NO:
- 1-40, 44-58, or 70-76, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
A B7RP1 specific binding agent comprising at least one amino acid sequence selected from SEQ ID NO:
- 15-40, and wherein the specific binding agent can bind to B7RP1.
An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a peptide having an amino acid as set forth in any of SEQ ID NO:
- 1-39.
An isolated antibody that binds specifically to:
- a) the D region of B7RP1, or an antigen-binding or an immunologically functional immnunoglobulin fragment thereof;
- or
- b) the H region of B7RP1, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
An isolated antibody that is competitive with binding of an antibody that comprises any of SEQ ID NO:
- 1-40.
An isolated human antibody that binds specifically to B7RP1, wherein the antibody comprises an amino acid sequence as set forth in any of SEQ ID NO:
- 44-58 or 70-76, or an antigen-binding or an immunologically functional immunoglobulin fragment thereof.
An isolated nucleic acid molecule that encodes a polypeptide having an amino acid sequence as set forth in any of SEQ ID NO. 1-40, 44-58 or 70-76.
Dependencies are inferred from the claim text.