ANTIBODY AGENTS SPECIFIC FOR HUMAN CD19 AND USES THEREOF

• US 20180134787A1
• Filed: 12/13/2017
• Published: 05/17/2018
• 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
• Granted Patent: US 10,301,388 B2
• Time in Patent Office: Days
• 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

1-41. -41. (canceled)

42. An antibody agent that specifically binds human cluster of differentiation 19 (CD19), wherein the antibody agent comprises heavy chain-complementarity determining regions (HC-CDRs) of SEQ ID NO:

151, SEQ ID NO;

152, and SEQ ID NO;

153, and light chain-complementarity determining regions (LC-CDRs) of SEQ ID NO;

259, SEQ ID NO;

260, and SEQ ID NO;

261.

43. The antibody agent of claim 42, 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.

44. The antibody agent of claim 42, wherein the antibody agent is or comprises an immunoglobulin, Fab, F(ab′

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

45. The antibody agent of claim 42, wherein the antibody agent is conjugated to a therapeutic agent, a detection agent, a cytotoxic agent or moiety, or a radio-isotope.

46. The antibody agent of claim 42, wherein the antibody agent is a human antibody agent.

47. A bi-specific antibody comprising a first antigen-binding site and a second antigen-binding site, wherein the first antigen-binding site is from or based on an antibody agent of claim 42.

48. The bi-specific antibody of claim 47, 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.

49. A chimeric antigen receptor comprising an antigen-binding site of an antibody agent of claim 42.

50. The chimeric antigen receptor of claim 49, further comprising a transmembrane domain and an intracellular signaling domain, wherein the intracellular signaling domain comprises a CD3ζ

intracellular signaling sequence and a CD28 intracellular signaling sequence.

51. A nucleic acid molecule encoding, in whole, the antibody agent of claim 42.

52. A vector comprising the nucleic acid molecule of claim 51.

53. A cell comprising the nucleic acid molecule of claim 51.

54. An effector cell expressing the antibody agent of claim 42.

55. The effector cell of claim 54, wherein the effector cell is a T cell.

56. A pharmaceutical composition comprising the effector cell of claim 55, and a pharmaceutically acceptable carrier or diluent.

57. A method of treating a medical condition characterized by CD19 expression in a subject, comprising a step of administering the pharmaceutical composition of claim 56.

58. The method of claim 57, wherein the medical condition characterized by CD19 expression is B cell lymphoma, acute lymphoblastic leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, non-Hodgkin'"'"'s lymphoma, or acute myeloid leukemia.

59. A method of treating cancer, the method comprising a step of administering to a subject the pharmaceutical composition of claim 56.

60. A method of inhibiting tumor growth or killing tumor cells, the method comprising a step of contacting tumor cells with the pharmaceutical composition of claim 56, wherein the contacting is being performed under conditions and for a time sufficient so that inhibition of tumor growth or tumor cell killing is observed.