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WO-2026096885-A1 - COMPOSITIONS THAT TARGET CD47 AND CD138 AND METHODS OF MAKING AND USING THE SAME

WO2026096885A1WO 2026096885 A1WO2026096885 A1WO 2026096885A1WO-2026096885-A1

Abstract

Disclosed are bispecific single-chain constructs comprising an anti-CD47 domain and an anti-CD138 domain, pharmaceutical compositions comprising the constructs, methods of treatment using the pharmaceutical compositions, polynucleotides encoding the constructs, methods of making the constructs, and kits. In some embodiments, the anti-CD47 domain comprises a first heavy chain and a first light chain and the anti-CD138 domain comprises a second heavy chain and a second light chain.

Inventors

  • VENNIYIL RADHAKRISHNAN, Sabarinath
  • GALEANA FIGUEROA, Maday

Assignees

  • THE MEDICAL COLLEGE OF WISCONSIN, INC.

Dates

Publication Date
20260507
Application Date
20251031
Priority Date
20241101

Claims (20)

  1. 1. A bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain.
  2. 2. The construct of claim 1, wherein the anti-CD47 domain comprises a first heavy chain and a first light chain and the anti-CD138 domain comprises a second heavy chain and a second light chain.
  3. 3. The construct of claim 1 or 2, wherein the anti-CD47 domain comprises SEQ ID NO: 1.
  4. 4. The construct of claim 1. wherein the anti-CD138 domain comprises SEQ ID NO: 4.
  5. 5. The construct of claim 1, wherein the first heavy chain comprises SEQ ID NO: 2.
  6. 6. The construct of claim 1. wherein the first light chain comprises SEQ ID NO: 3.
  7. 7. The construct of claim 1, wherein the second heavy chain comprises SEQ ID NO: 5.
  8. 8. The construct of claim 1. wherein the second light chain comprises SEQ ID NO: 6.
  9. 9. The construct of claim 1, wherein the construct does not induce antibody dependent cellular cytotoxicity in a cell comprising an Fc receptor.
  10. 10. The construct of claim 1, wherein the construct does not comprise an Fc domain.
  11. 11. The construct of claim 1, wherein the construct does not have antibody dependent cellular cytotoxicity (ADCC) activity.
  12. 12. The construct of claim 1, wherein the construct has a sequence with at least 85% identity to one of SEQ ID NOs: 7-9.
  13. 13. The construct of claim 1, wherein the construct comprises a linker between the anti- CD138 domain and the anti-CD47 domain.
  14. 14. The construct of claim 13, wherein the linker comprises SEQ ID NO: 14.
  15. 15. A polynucleotide comprising a sequence encoding the construct of claim 1. Atty. Dkt. No. 650053.01238
  16. 16. The polynucleotide of claim 15, wherein the polynucleotide further comprises a chimeric antigen receptor (CAR) sequence.
  17. 17. A cell comprising the polynucleotide of claim 15 or 16.
  18. 18. The cell of claim 17, wherein the cell is a human cell.
  19. 19. The cell of claim 18, wherein the cell is a human embry onic kidney (HEK) cell.
  20. 20. The cell of claim 18. wherein the human cell is a chimeric antigen receptor (CAR) T cell.

Description

Atty. Dkt. No. 650053.01238 COMPOSITIONS THAT TARGET CD47 AND CD138 AND METHODS OF MAKING AND USING THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present application claims priority to U.S. Provisional Patent Application No. 63/715,1 15 that was filed November 1 , 2024, the entire contents of which are hereby incorporated by reference. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] Not applicable. SEQUENCE LISTING [0003] A Sequence Listing accompanies this application and is submitted as an xml file of the sequence listing named “650053_01238.xml” which is 72,792 bytes in size and was created on October 30. 2025. The sequence listing is electronically submitted via Patent Center and is incorporated by reference herein in its entirety. BACKGROUND [0004] CD47 is a “do not eat me signal” that is overexpressed on malignant tumors including multiple myeloma (MM). CD47 on tumor cells interacts with SIRP-a on macrophages and inhibits its phagocytosis enabling tumor progression. Clinical studies with antibodies blocking CD47-SIRP-a interaction to promote tumor phagocytosis have shown varying success. CD47 is widely expressed on normal tissue and their binding to these monoclonal antibodies can lead to loss of treatment efficacy due to “sink effect” and to off-tumor on-target toxicity . In addition, when used as an adjuvant, CD47 antibody had a deleterious effect on CAR T cell survival and efficacy (Y amada-Hunter et al., Nature 2024). Accordingly, improved agents that target CD47 are needed in the art and are needed for the treatment of cancer, e.g., multiple myeloma. SUMMARY [0005] In an aspect of the current disclosure, bispecific single-chain polypeptide constructs are provided. In some embodiments, the anti-CD47 domain comprises a first heavy chain and a first light chain and the anti-CD138 domain comprises a second heavy chain and a second light chain. Atty. Dkt. No. 650053.01238 [0006] In an aspect of the current disclosure, polynucleotides are provided. In some embodiments, the polynucleotides comprise a sequence encoding a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain. [0007] In an aspect of the current disclosure, cells comprising a polynucleotide comprising a sequence encoding a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain. [0008] In an aspect of the current disclosure, pharmaceutical compositions are provided. In some embodiments, the pharmaceutical compositions comprise a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain, optionally, further comprising a suitable excipient. [0009] In some embodiments, the pharmaceutical compositions comprise a cell comprising a polynucleotide comprising a sequence encoding a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain. [0010] In an aspect of the current disclosure, methods are provided. In some embodiments, the methods comprise contacting a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain to a cell. [0011] In some embodiments, the methods comprise administering a pharmaceutical composition comprising a cell comprising a polynucleotide comprising a sequence encoding a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an antiCD 138 domain to a subject. [0012] In some embodiments, the methods are methods of treating a disease or disorder associated with CD47 expression in a subject in need thereof and the methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an antiCD 138 domain to the subject to treat the disease or disorder associated with CD47 expression in the subject. [0013] In an aspect of the current disclosure, methods of treating a cell proliferative disease or disorder in a subject in need thereof are provided. In some embodiments, the methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a bispecific single-chain polypeptide construct comprising an anti-CD47 domain and an anti-CD138 domain to the subject to treat the cell proliferative disease or disorder. [0014] In an aspect of the current disclosure, further methods of treating a cell proliferative disease or disorder in a subject in need thereof are provided. In some embodiments, the methods comprise administering a therapeutically effective amount of a pharmaceutical Atty. Dkt. No. 650053.01238 composition comprising a bispecific single-chain polypeptide construct comprising an anti- CD47 domain and an anti-CD138 domain and a chimeric antigen receptor (CAR) T cell therapy to the subject to treat the cell proliferative disease or disorder in the subject. [0015] In an aspect o