Compounds binding to JMJD6 with antifibrotic activity

• US 10,457,746 B2
• Filed: 02/26/2016
• Issued: 10/29/2019
• 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
• Primary Examiner(s): Haddad, Maher M
• Application Number:
  US15/553,642
• Publication Number:
  US 20180044433A1
• Time in Patent Office: 1,341 Days
• Field of Search: None
• 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 monoclonal antibody or a fragment thereof,

wherein the monoclonal antibody or a fragment thereof binds to JMJD6,

wherein the monoclonal antibody or a fragment thereof comprises a light chain variable region and a heavy chain variable region,

wherein the light chain variable region comprises the following CDRs:

QSILYSSNHKN (SEQ ID NO;

42), WASTRESGVP (SEQ ID NO;

43), and HQYLSS (SEQ ID NO;

44); and

wherein the heavy chain variable region comprises the following CDRs;

GFSLSSYG (SEQ ID NO;

45), IWRSGNT (SEQ ID NO;

46), and AKNFRYDVGSWFAY (SEQ ID NO;

47).

2. The monoclonal antibody or a fragment thereof according to claim 1, wherein the variable region of the light chain (VkCk) or a fragment thereof comprises the following sequence:

3. The monoclonal antibody or a gragment thereof according to claim 1, produced from the hybridoma deposited with the Autorita Internazionale di Deposito (AID) Centro di Biotecnologie Avanzate (CBA)—

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

4. A method of treating fibrosis, treating a tumor, or treating tumor metastases in a subject, the method comprising administering a pharmaceutically effective amount of the monoclonal antibody or a fragment thereof of claim 1 to the subject.

5. A pharmaceutical composition comprising a monoclonal antibody or a fragment thereof according to claim 1 and at least one pharmaceutically acceptable carrier and/or excipient.

6. The method according to claim 4, the method further comprising administering at least one chemotherapeutic drug.

7. The method according to claim 4, wherein said chemotherapeutic drug is selected from bleomycin, fludarabine and methotrexate.

9. The method of claim 4, wherein the fibrosis comprises pulmonary, peritoneal, medullary, or tumor tissue fibrosis.

10. The method of claim 4, wherein the tumor metastases comprise metastases of mammary or ovarian cancer.

11. The method of claim 4, wherein the method further comprises treating the subject with radiotherapy and/or chemotherapy.

8. 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.