CA2376485A1 - Recombinant anti-cd40 antibody and uses thereof - Google Patents
Recombinant anti-cd40 antibody and uses thereof Download PDFInfo
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Abstract
The present invention relates to methods and compositions for the prevention and treatment of cancer, inflammatory diseases and disorders or deficiencies of the immune system. The methods of the invention comprise administering a CD40 binding protein that potentiates the binding of CD40 to CD40 ligand.</S DOAB>
Claims (47)
1. A molecule comprising SEQ ID NO:3, SEQ ID NO:4, SEQ
ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (a) immunospecifically binds CD40, and (b) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110.
ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (a) immunospecifically binds CD40, and (b) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110.
2. A molecule comprising SEQ ID NO:3, SEQ ID NO:4, SEQ
ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (a) immunospecifically binds CD40, and (b) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin.
ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (a) immunospecifically binds CD40, and (b) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin.
3. The molecule of claim 1 or 2 comprising the amino acid sequence of SEQ ID NO:2 or the amino acid sequence of SEQ ID NO:7 or the amino acid sequences of both SEQ ID NO:2 and NO:7.
4. The molecule of claim 1 or 2 which is an antibody.
5. The molecule of claim 1 or 2 which is a fusion protein comprising the amino acid sequence of a second molecule that is not an antibody.
6. The molecule of claim 5 that comprises an amino acid sequence of bryodin (BD1) fused to SEQ ID NO:7 fused to SEQ ID NO:2.
7. The molecule of claim 1 or 2 which is an antibody comprising a variable domain of monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and a human constant region.
8. The molecule of any one of claims 1-4 which is purified.
9. A purified protein comprising an amino acid sequence that has at least 95% identity to SEQ ID NO:2 or SEQ ID NO:7, which protein (a) immunospecifically binds CD40;
and (b) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110.
and (b) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110.
10. A purified protein, which protein (a) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (b) increases the binding of CD40 ligand to CD40 by at least 45%, and (c) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110.
11. A purified protein, which protein (a) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (b) increases the binding of CD40 ligand to CD40 by at least 45%, and (c) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin.
12. An isolated nucleic acid comprising SEQ ID NO:1, SEQ ID NO:6, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID
NO:14, or SEQ ID NO:15.
NO:14, or SEQ ID NO:15.
13. An isolated nucleic acid comprising a nucleotide sequence encoding a protein comprising SEQ ID NO:3, SEQ ID
NO:4, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10.
NO:4, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10.
14. The isolated nucleic acid of claim 13 comprising a nucleotide sequence encoding a protein comprising (a) a heavy chain variable domain of monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and (b) a human constant region.
15. An isolated nucleic acid comprising a nucleotide sequence encoding a protein comprising an amino acid sequence that has at least 95% identity to SEQ ID NO:2 or SEQ ID NO:7.
16. An isolated nucleic acid comprising a nucleotide sequence encoding a protein, which protein competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and which protein increases the binding of CD40 ligand to CD40 by at least 45%.
17. An isolated nucleic acid comprising a nucleotide sequence encoding a fusion protein, said fusion protein comprising an amino acid sequence of bryodin 1 (BD1) fused to SEQ ID NO:7 fused to SEQ ID NO:2.
18. An isolated nucleic acid which hybridizes to the reverse complement of a DNA consisting of a coding DNA
sequence encoding a protein consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:7, under highly stringent conditions, which isolated nucleic acid encodes a protein that immunospecifically binds CD40.
sequence encoding a protein consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:7, under highly stringent conditions, which isolated nucleic acid encodes a protein that immunospecifically binds CD40.
19. A recombinant cell containing a recombinant nucleic acid vector comprising a nucleotide sequence encoding a protein, which protein competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and which protein increases the binding of CD40 ligand to CD40 by at least 450.
20. A recombinant cell containing a recombinant nucleic acid vector comprising SEQ ID NO:1, SEQ ID NO:6, SEQ ID
NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID
NO:15.
NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, or SEQ ID
NO:15.
21. A method of producing a protein comprising:
(a) growing a cell containing a recombinant nucleotide sequence encoding a protein, which protein competes for binding to CD40 with monoclonal antibody S2C6 as deposited with the ATCC and assigned accession number PTA-110, and which protein increases the binding of CD40 ligand to CD40 by at least 45%, such that the protein is expressed by the cell; and (b) recovering the expressed protein.
(a) growing a cell containing a recombinant nucleotide sequence encoding a protein, which protein competes for binding to CD40 with monoclonal antibody S2C6 as deposited with the ATCC and assigned accession number PTA-110, and which protein increases the binding of CD40 ligand to CD40 by at least 45%, such that the protein is expressed by the cell; and (b) recovering the expressed protein.
22. A method of producing a protein comprising:
(a) growing a cell containing a recombinant nucleotide sequence encoding a protein comprising SEQ ID NO:2, SEQ ID NO:3, SEQ ID
NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, such that a protein encoded by said nucleotide sequence is expressed by the cell; and (b) recovering the expressed protein.
(a) growing a cell containing a recombinant nucleotide sequence encoding a protein comprising SEQ ID NO:2, SEQ ID NO:3, SEQ ID
NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, such that a protein encoded by said nucleotide sequence is expressed by the cell; and (b) recovering the expressed protein.
23. A pharmaceutical composition comprising:
(a) a molecule comprising SEQ ID NO:2, SEQ ID
NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 450, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for the treatment or prevention of cancer; and (b) a pharmaceutically acceptable carrier.
(a) a molecule comprising SEQ ID NO:2, SEQ ID
NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 450, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for the treatment or prevention of cancer; and (b) a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising:
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for the treatment or prevention of cancer; and (b) a pharmaceutically acceptable carrier.
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for the treatment or prevention of cancer; and (b) a pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising:
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 450, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, in an amount effective for the treatment or prevention of cancer; and (b) a pharmaceutically acceptable carrier.
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 450, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, in an amount effective for the treatment or prevention of cancer; and (b) a pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising:
(a) a molecule comprising SEQ ID NO:2, SEQ ID
NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for activating or augmenting an immune response; and (b) a pharmaceutically acceptable carrier.
(a) a molecule comprising SEQ ID NO:2, SEQ ID
NO:3, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for activating or augmenting an immune response; and (b) a pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising:
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for activating or augmenting an immune response; and (b) a pharmaceutically acceptable carrier.
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, in an amount effective for activating or augmenting an immune response; and (b) a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising:
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, in an amount effective for activating or augmenting an immune response;
and (b) a pharmaceutically acceptable carrier.
(a) a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, in an amount effective for activating or augmenting an immune response;
and (b) a pharmaceutically acceptable carrier.
29. The pharmaceutical composition of any one of claims 23-28 further comprising CD40 ligand.
30. A method for the treatment or prevention of cancer in a subject comprising:
administering to the subject an amount of a molecule comprising SEQ ID NO:2, SEQ ID NO:3, SEQ
ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of cancer.
administering to the subject an amount of a molecule comprising SEQ ID NO:2, SEQ ID NO:3, SEQ
ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of cancer.
31. A method for the treatment or prevention of cancer in a subject comprising:
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of cancer.
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of cancer.
32. A method for the treatment or prevention of cancer in a subject comprising:
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, which amount is effective for the treatment or prevention of cancer.
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, which amount is effective for the treatment or prevention of cancer.
33. A method for activating or augmenting the immune response of a subject comprising:
administering to the subject an amount of a molecule comprising SEQ ID NO:2, SEQ ID NO:3, SEQ
ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is such that the immune response of the subject is activated or augmented.
administering to the subject an amount of a molecule comprising SEQ ID NO:2, SEQ ID NO:3, SEQ
ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is such that the immune response of the subject is activated or augmented.
34. A method for activating or augmenting the immune response of a subject comprising:
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is such that the immune response of the subject is activated or augmented.
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is such that the immune response of the subject is activated or augmented.
35. A method for activating or augmenting the immune response of a subject comprising:
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, which amount is such that the immune response of the subject is activated or augmented.
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110, (ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, which amount is such that the immune response of the subject is activated or augmented.
36. A method for the treatment or prevention of an immune disorder in a subject comprising:
administering to the subject an amount of a molecule comprising SEQ ID NO:2, SEQ ID NO:3, SEQ
ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of an immune disorder.
administering to the subject an amount of a molecule comprising SEQ ID NO:2, SEQ ID NO:3, SEQ
ID NO:4, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, which molecule (i) immunospecifically binds CD40,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of an immune disorder.
37. A method for the treatment or prevention of an immune disorder in a subject comprising:
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of an immune disorder.
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) comprises one or more substitutions or insertions in primary amino acid sequence relative to native monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, which amount is effective for the treatment or prevention of an immune disorder.
38. A method for the treatment or prevention of an immune disorder in a subject comprising:
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, which amount is effective for the treatment or prevention of an immune disorder.
administering to the subject an amount of a purified protein, which protein (i) competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC
and assigned accession number PTA-110,(ii) increases the binding of CD40 ligand to CD40 by at least 45%, and (iii) is not monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and does not result from cleavage of S2C6 with papain or pepsin, which amount is effective for the treatment or prevention of an immune disorder.
39. The method of any one of claims 30-38 further comprising administering CD40 ligand to the subject.
40. The method of any one of claims 30-38 in which the subject is a human.
41. The antibody of claim 4 which is not isotype IgG1.
42. A transgenic non-human animal, plant, or an isolated cell containing one or more transgenes encoding a protein, which protein competes for binding to CD40 with monoclonal antibody S2C6 as secreted by the hybridoma deposited with the ATCC and assigned accession number PTA-110, and which protein increases the binding of CD40 ligand to CD40 by at least 45%.
43. A pharmaceutical composition comprising in an amount effective for the treatment or prevention of cancer or an immune disorder, or for activating or augmenting an immune response: (a) a molecule that immunospecifically binds CD40, which molecule increases the binding of CD40 ligand to CD40;
(b) CD40 ligand; and (c) a pharmaceutically acceptable carrier.
(b) CD40 ligand; and (c) a pharmaceutically acceptable carrier.
44. A method for the treatment or prevention of cancer or an immune disorder in a subject comprising administering to the subject, in an amount effective for said treatment or prevention: (a) a molecule that immunospecifically binds CD40, which molecule increases the binding of CD40 ligand to CD40; and (b) CD40 ligand.
45. The method of claim 44, wherein the method is for the treatment of cancer.
46. The method of any one of claims 30-32 and 45, wherein the cancer is a solid tumor.
47. The method of any one of claims 36-38, wherein the immune disorder is rheumatoid arthritis.
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PCT/US2000/015749 WO2000075348A1 (en) | 1999-06-08 | 2000-06-08 | Recombinant anti-cd40 antibody and uses thereof |
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