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Last Updated: March 28, 2024

Claims for Patent: 10,456,420


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Summary for Patent: 10,456,420
Title:Genetically modified NK-92 cells and monoclonal antibodies for the treatment of cancer
Abstract: This invention is directed to treatment of a subject having or suspected of having a cancer comprising administering to the subject a monoclonal antibody and NK-92 expressing Fc receptor.
Inventor(s): Lee; Tien (Culver City, CA), Klingemann; Hans G. (Culver City, CA), Simon; Barry J. (Culver City, CA), Boissel; Laurent (Culver City, CA)
Assignee: NantKwest, Inc. (San Diego, CA)
Application Number:15/529,848
Patent Claims:1. A method for treating cancer in a subject in need thereof comprising administering to the subject a monoclonal antibody having a cytotoxic effect and genetically modified NK-92 cells, wherein the genetically modified NK-92 cells are genetically modified using a plasmid expression vector to generate stable NK-92 cells that express a CD16 polypeptide having a valine at position 158 of the mature form of the CD16 polypeptide; and express interleukin-2 (IL-2) targeted to the endoplasmic reticulum (ER); and further, wherein the expression vector comprises a transgene encoding the CD16 polypeptide and the IL-2 targeted to the ER comprising, in the 5' to 3' direction: a polynucleotide encoding the CD16 polypeptide, an IRES, and a polynucleotide encoding the IL-2 targeted to the ER.

2. The method of claim 1, wherein the CD16 polypeptide comprises a polynucleotide sequence encoding a polypeptide having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2 and comprises valine at position 158.

3. The method of claim 1, wherein the CD16 polypeptide comprises the amino acid sequence of SEQ ID NO:2.

4. The method of claim 1, wherein the genetically modified NK-92 cells are further modified to express a suicide gene.

5. The method of claim 4, wherein the suicide gene is inducible caspase 9.

6. The method of claim 1, wherein the cancer is multiple myeloma, leukemia, non-Hodgkin's lymphoma, metastatic breast cancer or gastric carcinoma.

7. The method of claim 1, wherein the monoclonal antibody is a naked monoclonal antibody of an IgG subtype that induces ADCC.

8. The method of claim 7, wherein the monoclonal antibody is alemtuzumab, rituximab, trastuzumab, avelumab, daratumumab or elotuzumab.

9. The method of claim 1, wherein the monoclonal antibody and the genetically modified NK-92 cells are administered simultaneously to the subject; or the subject is administered the monoclonal antibody and subsequently treated with the genetically modified NK-92 cells.

10. The method of claim 9, wherein the monoclonal antibody is injected intravenously into the subject.

11. The method of claim 9, wherein the genetically modified NK-92 cells are injected into the bone marrow.

Details for Patent 10,456,420

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Genentech, Inc. RITUXAN rituximab Injection 103705 11/26/1997 ⤷  Try a Trial 2035-03-27
Genentech, Inc. HERCEPTIN trastuzumab For Injection 103792 09/25/1998 ⤷  Try a Trial 2035-03-27
Genentech, Inc. HERCEPTIN trastuzumab For Injection 103792 02/10/2017 ⤷  Try a Trial 2035-03-27
Genzyme Corporation CAMPATH alemtuzumab Injection 103948 05/07/2001 ⤷  Try a Trial 2035-03-27
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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