Patent application EP19180008A (EP), filed 2019-06-13
Publication number: EP3750547A1
Title: MODIFIED NK-92 CELLS, AND THERAPEUTIC AND DIAGNOSTIC USES THEREOF
Abstract: The present invention relates to modified natural killer 92 (NK-92) cells and their use in cancer therapy, in particular for the prevention or treatment of solid tumours such as sarcomas, carcinomas, melanoma and lymphoma, and non-solid tumours such as leukaemia and related disorders. The invention further relates to the use of the modified NK-92 cells for in vitro diagnosis, diagnostics and/or screening. Finally, the invention also relates to methods for the preparation of a modified NK-92 cell that is specific for a target antigen of a target cell in a subject. The invention also relates to an expression vector, comprising the nucleic acid sequences of an antigen-specific functional T cell receptor (TCR), CD3, CD4 and/or CD8.
IPC codes: A61K  35/    17            A I
C07K  14/   725            A I
C12N  15/    63            A I
C12N   5/  0783            A I
Claims: number: 1
text: A modified natural killer 92 (NK-92) cell expressing:
number: 2
text: The modified NK-92 cell according to claim 1, wherein said TCR has the ability of specifically binding to an antigen MHC complex on the surface of a target cell.
number: 3
text: The modified NK-92 according to claim 1 or claim 2, wherein the target cell is a cancer cell.
number: 4
text: The modified NK-92 cell according to any one of claims 1 to 3, wherein the TCR originates from 5B2, 25F2 or 5H11 cells.
number: 5
text: The modified NK-92 cell according to claim 4, wherein the 5B2 TCR is composed of an alpha chain encoded by a nucleic acid sequence as defined in SEQ ID NO: 1 and a beta chain encoded by a nucleic acid sequence as defined in SEQ ID NO: 2, or degenerate variants thereof.
number: 6
text: The modified NK-92 cell according to claim 4, wherein the 25F2 TCR is composed of an alpha chain encoded by a nucleic acid sequence as defined in SEQ ID NO: 3 and a beta chain encoded by a nucleic acid sequence as defined in SEQ ID NO: 4, or degenerate variants thereof.
number: 7
text: The modified NK-92 cell according to claim 4, wherein the 5H11 TCR is composed of an alpha chain encoded by a nucleic acid sequence as defined in SEQ ID NO: 5 and a beta chain encoded by a nucleic acid sequence as defined in SEQ ID NO: 6, or degenerate variants thereof.
number: 8
text: The modified NK-92 cell according to any one of claims 1 to 7, wherein the TCR is expressed by the NK-92 cell as a fusion protein together with CD3 in conjunction with CD8 and/or CD4.
number: 9
text: A modified natural killer 92 (NK-92) cell according to any one of claims 1 to 8 for use as a medicament.
number: 10
text: A modified natural killer 92 (NK-92) cell according to any one of claims 1 to 8 for use in cancer therapy.
number: 11
text: The modified NK-92 cell according to claim 10, wherein the cancer is a solid tumour, preferably selected from sarcomas, carcinomas, melanoma and lymphoma.
number: 12
text: A modified natural killer 92 (NK-92) cell according to any one of claims 1 to 8 for use in the prevention or treatment of leukaemia and related disorders.
number: 13
text: The modified NK-92 cell according to claim 12, wherein the leukaemia is selected from acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic myelomonocytic leukaemia (CMML), eosinophilic leukaemia, hairy cell leukaemia, Hodgkin's lymphoma (HL), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), myeloproliferative disorders or myelodysplastic syndrome (MDS).
number: 14
text: Use of a modified natural killer 92 (NK-92) cell according to any one of claims 1 to 8 for in vitro diagnosis, diagnostics and/or screening.
number: 15
text: A pharmaceutical composition, comprising a modified natural killer 92 (NK-92) cell according to any one of claims 1 to 8, and at least one pharmaceutically acceptable carrier or excipient.
number: 16
text: An in vitro method for the preparation of a modified natural killer 92 (NK-92) cell that is specific for a target antigen of a target cell in a subject,
number: 17
text: The method according to claim 16, wherein the CD3 consists of a CD3 γ chain, a δ chain, two ε chains and two ζ chains.
number: 18
text: An expression vector, comprising the nucleic acid sequences of an antigen-specific functional T cell receptor (TCR), CD3, CD4 and/or CD8.
number: 19
text: The expression vector of claim 18, wherein the vector comprises nucleic acid sequences derived from any one of the nucleic acid sequences defined in SEQ ID NO: 1 to 12 for expressing TCR-CD3-CD4 and/or -CD8.
Office action: search_report, dated 2020-12-16
Rejection reasons: novelty_epc_54
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Final disposition: pending (2020-12-16)