Antibody agents specific for human CD19 and uses thereof

• US 10,301,388 B2
• Filed: 12/13/2017
• Issued: 05/28/2019
• Est. Priority Date: 10/13/2015
• Status: Active Grant

• Current Assignee: Eureka Therapeutics Incorporated
• Original Assignee: Eureka Therapeutics Incorporated
• Inventors: Liu, Hong, Lu, Jingwei, Yang, Zhiyuan, Long, Li, Cheng, Neal
• Primary Examiner(s): Wehbe, Anne Marie S
• Application Number:
  US15/840,870
• Publication Number:
  US 20180134787A1
• Time in Patent Office: 531 Days
• Field of Search: 5303871, 5303873, 435325, 424 9321
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/522 CH1 domain
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/02 : containing a signal sequence
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• CPC Class Codes: C12N 2501/599 : with CD designations not provided for elsewhere
• CPC Class Codes: C12N 2510/00 : Genetically modified cells
• CPC Class Codes: C12N 5/0638 : Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]

Abstract

Described herein are human antibody agents and multi-specific binding agents that specifically bind human CD 19, in particular, native human CD 19. Also provided herein are methods of using the same or compositions thereof for the detection, prevention and/or therapeutic treatment of diseases characterized by CD 19 expression, in particular, B cell lymphomas and leukemias.

Claims

1. An antibody agent that specifically binds human cluster of differentiation 19 (CD19), wherein the antibody agent comprises heavy chain variable region (HCVR) of 131-260 segment of SEQ ID NO:

42 and light chain variable region (LCVR) of 1-109 segment of SEQ ID NO;

42.

2. The antibody agent of claim 1, wherein the antibody agent comprises a sequence comprising a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the sequence comprises the sequence of SEQ ID NO:

42.

3. The antibody agent of claim 1, wherein the antibody agent is or comprises an immunoglobulin, Fab, F(ab′

)₂, Fd, Fv, single chain Fv (scFv), or a dAb.

4. The antibody agent of claim 1, wherein the antibody agent is conjugated to a therapeutic agent, a detection agent, a cytotoxic agent or moiety, or a radio-isotope.

5. The antibody agent of claim 1, wherein the antibody agent is a human antibody agent.

6. A bi-specific antibody comprising a first antigen-binding site and a second antigen-binding site, wherein the first antigen-binding site is from an antibody agent of claim 1.

7. The bi-specific antibody of claim 6, wherein the second antigen-binding site binds an immune cell selected from the group consisting of a T cell, NK cell, B cell, dendritic cell, monocyte, macrophage, neutrophil, mesenchymal stem cell and neural stem cell.

8. A chimeric antigen receptor comprising an antigen-binding site of an antibody agent of claim 1.

9. The chimeric antigen receptor of claim 8, further comprising a transmembrane domain and an intracellular signaling domain, wherein the intracellular signaling domain comprises a CD3 intracellular signaling sequence and a CD28 intracellular signaling sequence.

10. A nucleic acid molecule encoding, in whole, the antibody agent of claim 1.

11. A vector comprising the nucleic acid molecule of claim 10.

12. A cell comprising the nucleic acid molecule of claim 10.

13. An effector cell expressing the antibody agent of claim 1.

14. The effector cell of claim 13, wherein the effector cell is a T cell.

15. A composition comprising the effector cell of claim 14, and a carrier or diluent.

16. A method of treating a CD19-expressing B cell malignancy in a subject, comprising a step of administering to the subject (1) a bi-specific antibody having a first antigen-binding site that is from the antibody agent of claim 1 and a second antigen-binding site that binds a T cell;

or (2) T cells expressing a chimeric antigen receptor comprising (a) the antigen-binding site that is from the antibody agent of claim 1, (b) a transmembrane domain, and (c) an intracelluar signaling domain.

17. The method of claim 16, wherein the CD19-expressing B cell malignancy is B cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, non-Hodgkin'"'"'s lymphoma, or acute myeloid leukemia.

18. The method of claim 16, wherein the second antigen-binding site binds CD3.

19. The method of claim 16, wherein the intracellular signaling domain comprises a CD3ζ

intracellular signaling sequence.