Anti-alpha-v integrin antibody for the treatment of fibrosis and/or fibrotic disorders

Patent metadata

Field	Value
Publication number	US-12054549-B2
Application number	US-202218050817-A
Country	US
Kind code	B2
Filing date	Oct 28, 2022
Priority date	Nov 23, 2015
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

A method can treat a patient suffering from at least one of fibrosis and a fibrotic disorder. The method includes administering a therapeutically effective amount of an anti-αv integrin antibody DI17E6, or a biologically active variant or modification thereof, to the patient.

First claim

The invention claimed is:

1. A method of treating fibrosis and/or a fibrotic disorder, said method comprising:
determining that a patient suffering from the fibrosis and/or the fibrotic disorder is likely to respond to treatment with anti-av integrin antibody DI17E6;
administering an effective dose of said anti-av integrin antibody DI17E6 to the patient; wherein said anti-av integrin antibody DI17E6 is abituzumab and comprises
a light chain variable region (VL) complementarity determining region (CDR)1 comprising the sequence of amino acids 24 to 34 of SEQ ID NO: 1, VL CDR2 comprising the sequence of amino acids 50 to 56 of SEQ ID NO: 1, and VL CDR3 comprising the sequence of amino acids 89 to 97 of SEQ ID NO: 1; and
a heavy chain variable region (VH) CDR1 comprising the sequence of amino acids 31 to 35 of SEQ ID NO: 2, VH CDR2 comprising the sequence of amino acids 50 to 53 of SEQ ID NO: 2, and VH CDR3 comprising the sequence of amino acids 99 to 107 of SEQ ID NO: 2,

wherein the organs affected by said fibrosis and/or fibrotic disorder are selected from the group consisting of liver, kidney or both;
wherein the determining is based upon a TGF-β-up/abituzumab-down signature (“TUAD”) for the patient suffering from the fibrosis and/or the fibrotic disorder, wherein genes in the TUAD signature are upregulated by TGF-β and down modulated by abituzumab, the genes of the TUAD signature are selected from the group consisting of two or more of COL15A1, COL1A1, COMP, RGS5, COL10A1, COL5A1, IGFBP2, NM_005576, MOXD1, ADRA2A, COL5A2, MMP10, TNFRSF21, ITGA7, TGF-133, MMP11, SPP1, CCL2, and TNC;
wherein a difference in expression of the genes in the TUAD signature is induced by the presence of abituzumab when only abituzumab is administered.

2. The method according to claim 1 , wherein the organ affected by said fibrosis and/or fibrotic disorder is the liver.

3. The method according to claim 1 , wherein the fibrosis and/or a fibrotic disorder comprises systemic sclerosis of the liver, kidney or both.

4. The method according to claim 1 , wherein the fibrosis and/or a fibrotic disorder comprises one or more indications selected from the group consisting of non-alcoholic steatohepatitis (NASH), primary focal glomerulosclerosis, primary segmental glomerulosclerosis and diabetic nephropathy.

5. The method according to claim 1 , comprising administering the effective dose of said antibody in an amount of 500 mg-3000 mg per month.

6. The method according to claim 1 , comprising administering the effective dose of said antibody in an amount of 1000 mg-2000 mg per month.

7. The method according to claim 1 , comprising administering said antibody, in an amount of about 500 mg per month, about 1000 mg per month, about 1500 mg per month, about 2000 mg per month or about 2500 mg per month.

8. The method according to claim 1 , wherein the genes of the TUAD signature are selected from the group consisting of COL15A1, COL1A1, COMP, COL10A1, COL5A1, COL5A2, ITGA7, MMP11, and TNC.

9. The method according to claim 1 , wherein the effective dose is administered in a single dose as monotherapy.

Assignees

• Merck Patent Gmbh

Inventors

• Celik Ilhan
• Staub Eike
• Urban Miriam
• Raab-Westphal Sabine
• Samy Eileen
• Bender Andrew
• Varrone Georgianna
• Wu Yin
• Xu Daigen

Classifications

• G01N33/54366

  Apparatus specially adapted for solid-phase testing · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C12Q3/00

  Condition responsive control processes (apparatus therefor C12M1/36; controlling or regulating in general G05) · CPC title