Humanised anti-CD52 antibodies
View Patent ↗The present invention relates to novel humanised antibodies against human CD52 and their use in methods of treating or preventing human diseases.
1. An anti-CD52 antibody or antigen-bending portion thereof comprising at least three CDR sequences:
(i) CDRH1 comprising sequence RYGMS (SEQ ID NO: 5),
(ii) CDRH2 comprising sequence MMKTKGGRTYYPDSVKG (SEQ ID NO: 6), and
(iii) CDRH3 comprising sequence DGYY (SEQ ID NO: 7); or
(iv) CDRL1 comprising sequence KSSQSLLHSDGKTYLN (SEQ ID NO: 8),
(v) CDRL2 comprising sequence LVSKLDS (SEQ ID NO: 9), and
(vi) CDRL3 comprising sequence WQGTHLWT (SEQ ID NO: 10).
2. An anti-CD52 antibody or antigen-binding portion thereof comprising one or more variable region sequences selected from the group consisting of SEQ ID NOS: 20-24 for the heavy chain variable region in combination with one or more sequences selected from the group consisting of SEQ ID NOS: 25-28 for the light chain variable region.
3. An anti-CD52 antibody or antigen-binding portion thereof comprising SEQ ID NO: 22 for the heavy chain variable region in combination with SEQ ID NO: 28 for the light chain variable region.
4. The anti-CD52 antibody or antigen-binding portion thereof of claim 1 which, when tested in vitro for induction of CD4+helper T cell responses in 50 human blood samples with a distribution of HLA-DR allotypes from the human population, gives rise to <=4% of T cell responses.
5. The antibody or antigen-binding portion thereof of claim 1 where variable region sequences are entirely derived from sequences in human antibody variable regions.
6. The antibody of claim 5 which is comprised of variable regions together with human constant regions.
7. The antibody of claim 6 where the human heavy chain constant region is either isotype IgG1, IgG2, IgG3 or IgG4, or a mutated IgG constant region, and the human light chain human constant region is isotype kappa.
8. The antibody of claim 6 where the human constant regions are isotypes IgG1 and kappa, or isotypes IgG4 and kappa.
9. The antibody or antigen-binding portion thereof of of claim 1 where the antigen-binding portion is a scFv or Fab.
10. A polynucleotide encoding the antibody or antigen-binding portion thereof of claim 1 .
11. A vector comprising the polynucleotide of claim 10 .
12. A host cell comprising a vector of claim 11 .
13. A composition comprising the anti-CD52 antibody or antigen-binding portion thereof of claim 1 , a polynucleotide encoding the antibody, or antigen-binding portion thereof, or a vector comprising the polynucleotide.
14. A method for treating a disease selected from the group consisting of chronic lymphocytic leukemia (CLL), other leukemias, multiple sclerosis, rheumatoid arthritis, vasculitis, myositis, diabetes, other autoimmune diseases, organ transplant rejection, and graft-vs-host disease; said method comprising administering an effective amount of (i) the antibody or antigen-binding portion thereof of claim 1 , (ii) a polynucleotide encoding the antibody or antigen-binding portion thereof, or (iii) a composition comprising the antibody or antigen-binding portion thereof, the polynucleotide, or a vector comprising the polynucleotide to a subject in need of such treatment.
15. The method of claim 14 which further comprises co-administering an effective amount of a chemotherapeutic agent.
16. The method of claim 14 which further comprises co-administering a pharmaceutical carrier.
17. A method using the antibody or antigen-binding portion thereof of claim 1 , said method comprising;
(a) contacting a test sample with the antibody or antigen-binding portion thereof under conditions that allow for formation of a complex between human CD52 antigen and the antibody or antigen-binding portion thereof, and
(b) detecting the presence of the complex.
18. An anti-CD52 antibody or antigen-binding portion thereof comprising at least six CDR sequences:
(i) CDRH1 comprising sequence RYGMS (SEQ ID NO: 5),
(ii) CDRH2 comprising sequence MMKTKGGRTYYPDSVSKG (SEQ ID NO: 6),
(iii) CDRH3 comprising sequence DGYY(SEQ ID NO: 7),
(iv) CDRL1 comprising sequence KSSQSLLHSDGKTYLN (SEQ ID NO: 8),
(v) CDRL2 comprising sequence LVSKLDS (SEQ ID NO: 9), and
(vi) CDRL3 comprising sequence WQGTHLWT (SEQ ID NO: 10).
19. A polynucleotide encoding the antibody or antigen-binding portion thereof of claim 18 .
20. A vector comprising the polynucleotide of claim 19 .
21. A host cell comprising a vector of claim 20 .