COMPOUNDS BINDING TO JMJD6 WITH ANTIFIBROTIC ACTIVITY

• US 20180044433A1
• Filed: 02/26/2016
• Published: 02/15/2018
• Est. Priority Date: 02/27/2015
• Status: Active Grant

• Current Assignee: Fondazione Irccs Istituto Nazionale Dei Tumori
• Original Assignee: Fondazione Irccs Istituto Nazionale Dei Tumori
• Inventors: Colombo, Mario Paolo, Miotti, Silvia, Tagliabue, Elda, Sangaletti, Sabina
• Granted Patent: US 10,457,746 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12Y 114/11004 Procollagen-lysine 5-dioxygenase (1.14.11.4), i.e. lysine-hydroxylase

Abstract

The present invention relates to the interaction between JMJD6 protein and collagen and to the possibility of inhibiting this interaction for the prevention and treatment of fibrosis and of tumor metastases. The invention further relates to a compound that is able to block the interaction between collagen and JMJD6 protein, in particular the invention relates to a new monoclonal antibody that recognizes JMJD6 and is able to block this interaction.

Claims

1. A compound which binds to one or more portions of at least 5 consecutive amino acids of at least 2 of the following amino acid sequences of JMJD6 protein:

2. A compound according to claim 1, wherein said at least 2 sequences of JMJD6 protein comprise a sequence selected from KMKYYIE (SEQ ID NO:

35) and KRWCLFP (SEQ ID NO;

38).

3. A compound according to claim 1 wherein said at least 2 sequences comprise the sequences KMKYYIE (SEQ ID NO:

35) and KRWCLFP (SEQ ID NO;

38).

4. A compound according to claim 2, wherein said compound also binds to one or more portions of 5 amino acids of the sequence RSARPEL (SEQ ID NO:

10).

5. A compound according to claim 1, wherein the compound is selected from polyclonal antibodies and/or fragments thereof, monoclonal antibodies and/or fragments thereof, peptidomimetics, and low molecular weight molecules.

6. A compound according to claim 5, consisting of a monoclonal antibody and/or a fragment thereof.

7. A compound according to claim 6, wherein the variable regions of the light chains (VkCk) of said monoclonal antibody, or a fragment thereof, comprise the following sequence:

8. A compound according to claim 6, produced from the hybridoma deposited with the Autorità

Internazionale di Deposito (AID) Centro di Biotecnologie Avanzate (CBA)—

Interlab Cell Line Collection (ICLC) of Genoa (Italy), access number PD 15001.

9. A method of using the compound of claim 1, as a medicament.

10. A method of using the compound of claim 1, in the prevention and/or treatment of fibrosis, in the prevention and/or treatment of tumor metastases, or in the treatment of a tumor.

11. A pharmaceutical composition comprising a compound according to claim 1, and at least one pharmaceutically acceptable carrier and/or excipient.

12. A combination of a compound according to claim 1, with at least one chemotherapeutic drug.

16. The method of claim 10, wherein the fibrosis comprises pulmonary, peritoneal, medullary, or tumor tissue fibrosis.

17. The method of claim 10, wherein the treatment of a tumor comprises prevention and/or treatment of metastases of mammary or ovarian cancer.

18. The method of claim 10, wherein the method further comprises radiotherapy and/or chemotherapy.

13. A combination according to claim 13, wherein said chemotherapeutic drug is selected from bleomycin, fludarabine and methotrexate.

14. A combination according to claim 13, for use in the treatment of a tumor.

15. A hybridoma deposited with the Autorità

Internazionale di Deposito (AID) Centro di Biotecnologie Avanzate (CBA)—

Interlab Cell Line Collection (ICLC) of Genoa (Italy), access number PD 15001.