Anti-ctla4 monoclonal antibody or its antigen binding fragments, pharmaceutical compositions and uses
AssigneeAkeso Biopharma, Inc.
InventorsBaiyong LI, Yu XIA, Zhongmin WANG, Peng ZHANG, Xinghua PANG
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Abstract
The present invention belongs to the fields of tumor therapy and molecular immunology, and provides an anti-CTLA4 monoclonal antibody or antigen binding fragment thereof, a pharmaceutical composition thereof and use thereof. The monoclonal antibody of the present invention can block the binding of CLTA4 to B7, relieve the immunosuppression on the body by CTLA4, and activate T lymphocytes.
Claims37
A monoclonal antibody or antigen binding fragment thereof, wherein
- the monoclonal antibody or antigen binding fragment thereof binds to human CTLA4 and comprises a heavy chain variable region and a light chain variable region,
- wherein the heavy chain variable region comprises:
- a. an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 27,
- b. an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 28, and
- c. an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 29;
- and the light chain variable region comprises:
- d. an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 30,
- e. an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 31, and
- f. an LCDR3 comprising an amino acid sequence selected from SEQ ID NO:
- 32, SEQ ID NO:
- 33, and SEQ ID NO:
- 34, wherein the monoclonal antibody or antigen binding fragment thereof has an activity selected from the group consisting of:
- blocks the binding of human CTLA4 to human B7, decreases or inhibits CTLA4 activity, increases IL-2 expression by T-lymphocytes when administered to a host, and reduces immunosuppression in a subject when administered to the subject.
An isolated nucleic acid molecule comprising a nucleic acid sequence capable of encoding a heavy chain variable region of an antibody, wherein the heavy chain variable region of the antibody comprises:
- CDRs with the amino acid sequences of SEQ ID NOs:
- 27-29.
An isolated nucleic acid molecule comprising a nucleic acid sequence capable of encoding a light chain variable region of an antibody, wherein the light chain variable region of the antibody comprises:
- CDRs with the amino acid sequences of SEQ ID NOs:
- 30-32.
13-17. (canceled)
A method of diagnosing a tumor, comprising the step of administrating an effective amount of a monoclonal antibody or antigen binding fragment thereof to a sample obtained from a patient and assessing whether the sample binds the monoclonal antibody or antigen binding fragment thereof, wherein the sample is a biopsy of the patient wherein the tumor is selected from a melanoma, a kidney tumor, a prostate cancer, a bladder cancer, a colorectal cancer, a cancer of gastrointestinal tract, and a liver cancer, and wherein the monoclonal antibody or antigen binding fragment thereof comprises the complementary determining regions (CDR's) selected from the following:
- a. a HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 27,
- b. a HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 28, and
- c. a HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 29;
- and/or
- d. a LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 30,
- e. a LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 31, and
- f. a LCDR3 comprising an amino acid sequence selected from SEQ ID NO:
- 32, SEQ ID NO:
- 33, and SEQ ID NO:
- 34, and optionally wherein the monoclonal antibody or antigen binding fragment thereof is linked to a detectable compound.
20-21. (canceled)
Dependencies are inferred from the claim text.