Nova Patents
IL273918A

Trispecific proteins and methods of use

Abstract

This record has no abstract on file.

Term

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52 claims: 23 independent, 29 dependent

  1. 1
    CLAIMS What is claimed is:1. AB cell maturation agent (BCMA) binding trispecific protein that comprises: (a) a first domain (A) which specifically binds to human CD3;(b) a second domain (B) which is a half-life extension domain;and (c) a third domain (C) which specifically binds to BCMA, wherein the domains are linked in the order H2N-(A)-(C)-(B)-COOH, H2N-(B)(A)-(C)-COOH, H2N-(C)-(B)-(A)-COOH, H2N-(C)-(A)-(B)-COOH, H2N-(A)(B)-(C)-COOH, or H2N-(B)-(C)-(A)-COOH, wherein the domains are linked by linkers LI and L2.
  2. 24
    The BCMA binding trispecific protein of any one of claims 1-23, wherein the third domain is a human VHH domain, a humanized VHH domain, an affinity matured VHH domain, or a combination thereof.
  3. 25
    The BCMA binding trispecific protein of any one of claims 1-24, wherein said protein has an elimination half-time of at least 12 hours, at least 20 hours, at least 25 hours, at least 30 hours, at least 35 hours, at least 40 hours, at least 45 hours, at least 50 hours, or at least 100 hours.
  4. 28
    The BCMA binding trispecific protein of any one of claims 1-27, wherein the third domain binds to a human BCMA protein comprising the sequence set forth as SEQ ID NO:468.
  5. 29
    The BCMA binding trispecific protein of any one of claims 1-27, wherein the third domain binds to an extracellular domain of BCMA.
  6. 30
    The BCMA binding trispecific protein of any one of claims 1-29, wherein linkers LI and L2 are each independently selected from (GS)n (SEQ ID NO:472), (GGS)n (SEQ ID NO: 473), (GGGS)n (SEQ ID NO: 474), (GGSG)n (SEQ ID NO: 475), (GGSGG)n (SEQ ID NO: 476), (GGGGS)n (SEQ ID NO: 477), (GGGGG)n (SEQ ID NO: 478) or (GGG)n (SEQ ID NO: 479) wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
  7. 31
    The BCMA binding trispecific protein of any one of claims 1-30, wherein linkers LI and L2 are each independently (GGGGS)4 (SEQ ID NO:480) or (GGGGS)3 (SEQ ID NO: 481).
  8. 32
    The BCMA binding trispecific protein of any one of claims 1-31, wherein the domains are linked in the order H2N-(C)-(B)-(A)-COOH.
  9. 33
    The BCMA binding trispecific protein of any one of claims 1-32, wherein the protein is less than about 80 kDa.
  10. 34
    The BCMA binding trispecific protein of any one of claims 1-32, wherein the protein is about 50 to about 75 kDa.
  11. 35
    The BCMA binding trispecific protein of any one of claims 1-32, wherein the protein is less than about 60 kDa.
  12. 36
    The BCMA binding trispecific protein of any one of claims 1-35, wherein the protein has an elimination half-time of at least about 50 hours.
  13. 37
    The BCMA binding trispecific protein of any one of claims 1-36, wherein the protein has an elimination half-time of at least about 100 hours.
  14. 38
    The BCMA binding trispecific protein of any one of claims 1-37, wherein the protein has increased tissue penetration as compared to an IgG to the same BCMA.
  15. 39
    The BCMA binding trispecific protein of any one of claims 1-38, wherein the protein comprises a sequence selected from the group consisting of SEQ ID NOs:483-597.
  16. 40
    The BCMA binding trispecific protein of any one of claims 1-39, wherein the protein comprises a sequence as set forth in SEQ ID NO:520.
  17. 41
    A pharmaceutical composition comprising a BCMA binding trispecific protein according to any one of claims 1-40 and a pharmaceutically acceptable carrier.
  18. 42
    A process for the production of a BCMA binding trispecific protein according to any one of claims 1-40, said process comprising culturing a host transformed or transfected with a vector comprising a nucleic acid sequence encoding a BCMA binding trispecific protein according to any one of claims 1-40 under conditions allowing the expression of the BCMA binding trispecific protein and recovering and purifying the produced protein from the culture.
  19. 46
    The method of any one of claims 43-45, comprising treatment or amelioration of a tumorous disease, wherein the BCMA binding trispecific protein selectively binds to tumor cells expressing BCMA.
  20. 47
    The method of any one of claims 43-46, comprising treatment or amelioration of a tumorous disease, wherein the tumorous disease comprises a primary cancer or a metastasis thereof.
  21. 50
    A B cell maturation agent (BCMA) binding trispecific protein comprising:(a) a first domain (A) which specifically binds to human CD3;(b) a second domain (B) which is a half-life extension domain;and (c) a third domain (C) which specifically binds to BCMA, wherein the third domain comprises an amino sequence set forth as any one of SEQ ID NOS: 346-460.
  22. 51
    AB cell maturation agent (BCMA) binding trispecific protein comprising:(a) a first domain (A) which specifically binds to human CD3;(b) a second domain (B) which is a half-life extension domain;and (c) a third domain (C) which specifically binds to BCMA, wherein the third domain comprises complementarity determining regions CDR1, CDR2, and CDR3, wherein CDR1 comprises an amino acid sequence set forth as any one of SEQ ID NOS: 4-117, CDR2 comprises an amino acid sequence set forth as any one of SEQ ID NOS: 118-231, and CDR3 comprises an amino acid sequence set forth as any one of SEQ ID NOS: 232-345.
  23. 52
    A method for the treatment or amelioration of a tumorous disease, an autoimmune disease or an infection disease associated with BCMA in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a BCMA binding trispecific protein, wherein the BCMA binding protein comprises (a) a first domain (A) which specifically binds to human CD3;(b) a second domain (B) which is a half-life extension domain;and (c) a third domain (C) which specifically binds to BCMA, wherein the domains are linked in the order H2N-(A)-(C)-(B)-COOH, H2N-(B)-(A)-(C)-COOH, H2N-(C)-(B)-(A)-COOH, H2N-(C)-(A)-(B)-COOH, H2N-(A)-(B)-(C)-COOH, H2N-(B)-(C)(A)-COOH, wherein the domains are linked by linkers LI and L2. -
Independent claims23