You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 28, 2024

Claims for Patent: 10,059,765


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 10,059,765
Title:Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds
Abstract: The present invention relates, generally, to methods and compositions for increasing the efficiency of therapeutic antibodies. Their efficiency is enhanced through the increase of the ADCC mechanism. More particularly, the invention relates to the use of a therapeutic antibody in combination with compounds that block an inhibitory receptor or stimulate an activating receptor of an NK cell in order to enhance the efficiency of the treatment with therapeutic antibodies in human subjects.
Inventor(s): Velardi; Andrea (Perugia, IT), Romagne; Francois (La Ciotat, FR)
Assignee: INNATE PHARMA S.A. (Marseilles, FR)
Application Number:14/789,548
Patent Claims:1. A method of treating a disease in a human subject comprising administering to a human subject in need thereof: (a) a therapeutically effective amount of a therapeutic antibody or antigen-binding fragment thereof that specifically binds to an antigen that is expressed on target cells but not on NK. cells, wherein the therapeutic antibody or antigen-binding fragment thereof binds via its Fe region to CD16 and is capable of mediating depletion of the target cells by antibody-dependent cell-mediated cytotoxicity (ADCC); and (b) at least one NK cell-potentiating antibody or antigen-binding fragment thereof that specifically binds to and blocks an NK cell inhibitory receptor expressed on the surface of an NK cell, wherein the at least one NK cell-potentiating anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof is present in an amount sufficient to enhance the efficacy of the therapeutic antibody or antigen-binding fragment thereof by enhancing the depletion of the target cells by ADCC, wherein the disease is mediated at least in part by the target cells expressing the antigen specifically bound by the therapeutic antibody or antigen-binding fragment thereof.

2. The method of claim 1, wherein the therapeutic antibody or antigen-binding fragment thereof comprises a human or non-human primate IgG1 or IgG3 Fc portion.

3. The method of claim 1, wherein the at least one anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof comprises (i) a monoclonal antibody or an antigen-binding fragment thereof; or (ii) a human, humanized or chimeric antibody or an antigen-binding fragment thereof.

4. The method of claim 1, wherein the therapeutic antibody is a monoclonal antibody or comprises an antigen-binding fragment thereof.

5. The method of claim 4, wherein the monoclonal antibody is a human, humanized or chimeric antibody or comprises an antigen-binding fragment thereof.

6. The method of claim 4, wherein the therapeutic antibody or antigen-binding fragment thereof is not conjugated with a radioactive or toxic moiety.

7. The method of claim 1, wherein the therapeutic antibody is rituximab or alemtuzumab.

8. The method of claim 1, wherein (i) the NK cell inhibitory receptor is selected from the group consisting of KIR2DL1, KIR2DL2/3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR3DL1, KIR3DL2, KIR3DL3, LILRB1, and LILRBS; or (ii) the at least one anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof binds to a common determinant of KIR2DL human receptors and inhibits KIR2DL-mediated inhibition of NK cell cytotoxicity.

9. The method of claim 8, wherein the NK cell inhibitory receptor is KIR2DL1 or KIR2DL2/3.

10. The method of claim 1, wherein the at least one anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof (i) binds to a common determinant of KIR2DL human receptors and inhibits KIR2DL-mediated inhibition of NK cell cytotoxicity; (ii) binds to a common determinant of KIR2DL1 and KIR2DL2/3 human receptors and inhibits KIR2DL1- and KIR2DL2/3-mediated inhibition of NK cell cytotoxicity; or (iii) inhibits the binding of an HLA-C polypeptide having a Lys residue at position 80 to a human KIR2DL1 receptor, and the binding of an HLA-C polypeptide having an Asn residue at position 80 to a human KIR2DL2/3 receptor.

11. The method of claim 1, wherein the at least one anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof (i) binds to the same epitope on a KIR receptor expressed on the surface of a human NK cell as does monoclonal antibody DE200 produced by hybridoma DF200 (deposited as CNCM 1-3224), or as does monoclonal antibody EB6; (ii) competes with monoclonal antibody DF200 produced by hybridoma DF200 (deposited as CNCM 1-3224), or monoclonal antibody EB6, for binding to a KIR. receptor expressed on the surface of a human NK cell; or (iii) comprises monoclonal antibody DF200 produced by hybridoma DF200 (deposited as CNCM 1-3224) or a fragment or derivative thereof, or monoclonal antibody EB6 or a fragment or derivative thereof.

12. The method of claim 1, wherein the therapeutic antibody or antigen-binding fragment thereof specifically binds to an antigen expressed on cells selected from tumor cells, virus-infected cells, allogeneic cells, non-tumorigenic pathological cells, pathological immunocompetent cells, and endothelial cells.

13. The method of claim 1, wherein the at least one anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof enhances the ability of the therapeutic antibody or antigen-binding fragment thereof to deplete said target cells by at least 30% or by at least 50%.

14. The method of claim 1, wherein the therapeutic antibody or antigen-binding fragment thereof elicits essentially no ADCC in the absence of the at least one anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof.

15. The method of claim 1, wherein the therapeutic antibody or antigen-binding fragment thereof binds to an antigen selected from CD20, CD52, CD33, HLA-DR, CD22, HER2, erbB2, CA125, MUC1, PEM antigen, CD44, gp72, EpCAM, VEGFR, CD18, nuC242 EGFR, HER-1, CEA, aVf33, KDR (VEGFR2), VRS, CMV, HBs, CD25, TNF-a, CD80, IgE, CD1 1 a (LFA-1), CD4, CD3, CD64, CD147, a4 131-a4 (37, integrin 137, a4 137, HLA-DR10 13, GD2, SK-1, IL-8, VLA-4, CD4OL, E-selectin, CD11/CD18, ICAM-3, CBL, CD147, CD23, T1-ACY, TTs, CA19.9, PSA, HMFG1, hCH, collagen, CD46, 17A-1, HM1.24, CD38, IL-15R, 11-6, TRAIL-R1, VEGF2, BlyS, SCLS, Lewis Y antigen, VE cadherin, CD56, mertansine/mucine, AFP, CSap, CD30, PS:MA, Cd15, CD19/CD3, mesothelin, DNA, histone, a5B1 integrin, p97, and CDS.

16. The method of claim 1, wherein the target cells are tumor cells or virus-infected cells.

17. The method of claim 12, wherein the pathological immunocompetent cells are B lymphocytes, T lymphocytes, or antigen-presenting cells.

18. The method of claim 12, wherein the endothelial cells are to be targeted in an anti-angiogenic therapeutic strategy.

19. The method of claim 1, wherein the NK cell inhibitory receptor expressed on the surface of an NK cell is KIR2DL1 or KIR2DL2/3.

20. The method of claim 1, wherein the NK cell inhibitory. receptor expressed on the surface of an NK cell is selected from the group consisting of KIR2DL1, KIR2DL2/3, KIR2DLSA, KIR2DLSB, KIR3DL1, KIR3DL2, KIR3DL3, LILRB1, and LILRBS.

21. The method of claim 1, wherein said anti-NK cell inhibitory receptor antibody or antigen-binding fragment thereof enhances the ability of said therapeutic antibody to deplete said target cells by ADCC by at least 100%, by at least 200%, or by at least 300%.

22. A method of treating a disease in a human subject comprising administering to a human subject in need thereof: (a) a therapeutically effective amount of a therapeutic antibody or an antigen-binding fragment thereof that specifically binds to an antigen that is expressed on target cells but not on NK cells, wherein the therapeutic antibody or antigen-binding fragment thereof binds via its Fe region to CD16 and is capable of mediating depletion of the target cells by antibody-dependent cell-mediated cytotoxicity (ADCC); and (b) at least one NK cell-potentiating antibody or antigen-binding fragment thereof that specifically binds to and stimulates an activating receptor expressed on the surface of an NK cell, wherein the at least one NK cell-potentiating antibody or antigen-binding fragment thereof is present in an amount sufficient to enhance the efficacy of the therapeutic antibody or antigen-binding fragment thereof by enhancing the depletion of the target cells by ADCC, wherein the disease is mediated at least in part by the target cells expressing the antigen specifically hound by the therapeutic antibody or antigen-binding fragment thereof.

23. The method of claim 22, wherein the activating receptor expressed on the surface of an NK cell is selected from the group consisting of NKp30, NKp44, NKp46, NKG2C, NKG2E, NKG2D, and KIR2DS44.

Details for Patent 10,059,765

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Genentech, Inc. RITUXAN rituximab Injection 103705 11/26/1997 ⤷  Try a Trial 2023-07-24
Genzyme Corporation CAMPATH alemtuzumab Injection 103948 05/07/2001 ⤷  Try a Trial 2023-07-24
Genzyme Corporation LEMTRADA alemtuzumab Injection 103948 11/14/2014 ⤷  Try a Trial 2023-07-24
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.