Anti-4-1bb nanobodies
US-2024383993-A1 · Nov 21, 2024 · US
US9683046B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9683046-B2 |
| Application number | US-201514790144-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jul 2, 2015 |
| Priority date | Mar 15, 2012 |
| Publication date | Jun 20, 2017 |
| Grant date | Jun 20, 2017 |
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Human antibodies immunospecific for human CD27 are capable of blocking CD27 binding to its ligand CD70 and neutralizing bioactivity of CD27 including, but not limited to, CD27 intracellular signaling, T-cell proliferation and activation, B-cell proliferation and differentiation, plasmablast formation and alleviation of antibody responses, stimulation of tumor cells by CD70, and the production of soluble mediators from T and B-cells. The antibodies are useful in diagnosing or treating CD27 activity associated diseases and conditions.
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What is claimed: 1. An isolated nucleic acid molecule, selected from the group consisting of (i) the light chain nucleotide sequence of SEQ ID NO: 163 and/or the heavy chain nucleotide sequence of SEQ ID NO: 164; (ii) a nucleotide sequence encoding the light chain variable region amino acid sequence of SEQ ID NO: 143 and/or a nucleotide sequence encoding the heavy chain variable region amino acid sequence of SEQ ID NO: 133; (iii) a nucleotide sequence encoding the light chain variable region amino acid sequence of SEQ ID NO: 127 and/or a nucleotide sequence encoding the heavy chain variable region amino acid sequence of SEQ ID NO: 126; (iv) a nucleotide sequence encoding the light chain variable region amino acid sequence selected from the group consisting of SEQ ID NOs: 137-144 and 148 and/or a nucleotide sequence encoding the heavy chain variable region amino acid sequence selected from the group consisting of SEQ ID NOs: 128-136 and 145-147; and (v) a nucleotide sequence encoding the light chain variable region amino acid sequence of SEQ ID NO: 143, a nucleotide sequence encoding the heavy chain variable region amino acid sequence of SEQ ID NO: 133, a nucleotide sequence encoding the IgG4 heavy chain constant region amino acid sequence of SEQ ID NO: 159, and a nucleotide sequence encoding the IgG4 light chain constant region amino acid sequence of SEQ ID NO: 160. 2. An isolated nucleic acid vector or vectors comprising the isolated nucleic acid molecule of claim 1 . 3. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid vector or vectors of claim 2 . 4. The host cell according to claim 3 , wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof. 5. A method for producing an anti-CD27 antibody, comprising incorporating the nucleic acid molecule of claim 1 into a vector, transforming a host cell, transgenic animal or transgenic plant to express an antibody and recovering the expressed antibody. 6. An isolated nucleic acid molecule, comprising a nucleotide or nucleotides encoding an light chain variable region and an antibody heavy chain variable region, said light chain variable region comprising a complementarity determining region light chain 1 (CDRL1) amino acid sequence selected from the group consisting of SEQ ID NOs: 59-66 and 158, a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NOs: 67-74, a CDRL3 amino acid sequence of SEQ ID NO: 75, said heavy chain variable region comprising a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOs: 42-45 and 161, a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOs: 46-57, 156, and 157; and a CDRH3 amino acid sequence of SEQ ID NO: 58. 7. An isolated nucleic acid vector or vectors comprising the isolated nucleic acid molecule of claim 6 . 8. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid vector or vectors of claim 7 . 9. The host cell according to claim 8 , wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof. 10. A method for producing an anti-CD27 antibody, comprising incorporating the nucleic acid molecule of claim 6 into a vector, transforming a host cell, transgenic animal or transgenic plant to express an antibody and recovering the expressed antibody. 11. An isolated nucleic acid molecule, comprising a nucleotide or nucleotides encoding an light chain variable region and an antibody heavy chain variable region, said light chain variable region comprising a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO: 62, a CDRL2 amino acid sequence of SEQ ID NO: 68, a CDRL3 amino acid sequence of SEQ ID NO: 75, said heavy chain variable region comprising a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOs: 44 and 161, a CDRH2 amino acid sequence of SEQ ID NO: 47; and a CDRH3 amino acid sequence of SEQ ID NO: 58. 12. An isolated nucleic acid vector or vectors comprising the isolated nucleic acid molecule of claim 11 . 13. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid vector or vectors of claim 12 . 14. The host cell according to claim 13 , wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof. 15. A method for producing an anti-CD27 antibody, comprising incorporating the nucleic acid molecule of claim 11 into a vector, transforming a host cell, transgenic animal or transgenic plant to express an antibody and recovering the expressed antibody. 16. An isolated nucleic acid molecule, comprising a nucleotide or nucleotides encoding an light chain variable region and an antibody heavy chain variable region, said light chain variable region comprising a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO: 59, a CDRL2 amino acid sequence of SEQ ID NO: 67, a CDRL3 amino acid sequence of SEQ ID NO: 75, said heavy chain variable region comprising a CDRH1 amino acid sequence of SEQ ID NO: 42, a CDRH2 amino acid sequence of SEQ ID NO: 46; and a CDRH3 amino acid sequence of SEQ ID NO: 58. 17. An isolated nucleic acid vector or vectors comprising the isolated nucleic acid molecule of claim 16 . 18. A prokaryotic or eukaryotic host cell comprising the isolated nucleic acid vector or vectors of claim 17 . 19. The host cell according to claim 18 , wherein said host cell is at least one selected from COS-1, COS-7, HEK293, BHK21, CHO, BSC-1, Hep G2, 653, SP2/0, 293, HeLa, myeloma, or lymphoma cells, or any derivative, immortalized or transformed cell thereof. 20. A method for producing an anti-CD27 antibody, comprising incorporating the nucleic acid molecule of claim 16 into a vector, transforming a host cell, transgenic animal or transgenic plant to express an antibody and recovering the expressed antibody.
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