Fully humanized anti-platelet factor 4 antibodies that treat heparin-induced thrombocytopenia

Patent metadata

Field	Value
Publication number	US-12304948-B2
Application number	US-202218071057-A
Country	US
Kind code	B2
Filing date	Nov 29, 2022
Priority date	May 12, 2017
Publication date	May 20, 2025
Grant date	May 20, 2025

Abstract

Provided herein are isolated antibodies or antibody fragments thereof that immunospecifically bind to platelet factor 4 (PF4). In some embodiments the isolated antibodies or antigen-binding fragments thereof comprise a light chain CDR and framework region comprising SEQ ID NO: 4 and a heavy chain CDR and framework region comprising SEQ ID NO: 10. Also provided herein are methods for treating heparin-induced thrombocytopenia (HIT) and methods for reducing the likelihood that subject will become afflicted with HIT. Further disclosed are uses of the isolated antibodies or antibody fragments in the treatment of HIT or the manufacture of compositions for the treatment of HIT.

First claim

What is claimed:

1. A polynucleotide encoding a light chain of an antibody, or antigen-binding fragment thereof, that immunospecifically binds to platelet factor 4 (PF4), wherein the light chain or antigen-binding fragment thereof comprises a light chain CDR and framework region comprising the amino acid sequence of SEQ ID NO: 4.

2. The polynucleotide of claim 1 , wherein the light chain or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 6.

3. An expression vector comprising the polynucleotide of claim 2 .

4. The polynucleotide of claim 1 , wherein the light chain or antigen-binding fragment thereof comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 5.

5. An expression vector comprising the polynucleotide of claim 4 .

6. A host cell comprising the expression vector of claim 5 .

7. The host cell of claim 6 , wherein the host cell is a eukaryotic cell, a yeast cell, a plant cell or a bacterium.

8. The host cell of claim 7 , wherein the eukaryotic cell is a 293T cell or a Chinese Hamster Ovary (CHO) cell.

9. An expression vector comprising the polynucleotide of claim 1 .

10. A polynucleotide encoding a heavy chain of an antibody, or antigen-binding fragment thereof, that immunospecifically binds to platelet factor 4 (PF4), wherein the heavy chain or antigen-binding fragment thereof comprises a heavy chain CDR and framework region comprising the amino acid sequence of SEQ ID NO: 10.

11. The polynucleotide of claim 10 , wherein the heavy chain or antigen-binding fragment thereof comprises the amino acid sequence of SEQ ID NO: 12.

12. An expression vector comprising the polynucleotide of claim 11 .

13. The polynucleotide of claim 10 , wherein the heavy chain or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

14. An expression vector comprising the polynucleotide of claim 13 .

15. A host cell comprising the expression vector of claim 14 .

16. The host cell of claim 15 , wherein the host cell is a eukaryotic cell, a yeast cell, a plant cell or a bacterium.

17. The host cell of claim 16 , wherein the eukaryotic cell is a 293T cell or a Chinese Hamster ovary (CHO) cell.

18. An expression vector comprising the polynucleotide of claim 10 .

Assignees

• Univ Pennsylvania

Inventors

• Greene Mark I
• Cai Zheng
• Zhu Zhiqiang
• Cines Douglas B

Classifications

• A61K39/39533

  against materials from animals · CPC title

• C12N15/85

  for animal cells · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title