Biomarkers for anti-IL4-IL13 bispecific antibodies

Patent metadata

Field	Value
Publication number	US-11136388-B2
Application number	US-201916297419-A
Country	US
Kind code	B2
Filing date	Mar 8, 2019
Priority date	Jun 27, 2014
Publication date	Oct 5, 2021
Grant date	Oct 5, 2021

Abstract

Disclosed herein are safe doses of dual-V-region antibody-like binding proteins or fragments thereof, as well as methods for assessing binding of dual-V-region antibody-like proteins or fragments thereof to their targets, and methods of treating idiopathic pulmonary fibrosis (IPF) by administering safe doses of dual-V-region antibody-like binding proteins or fragments thereof. In some embodiments, the dual-V-region antibody-like binding proteins or fragments thereof bind both IL-4 and IL-13.

First claim

The invention claimed is:

1. A method of determining whether a dose comprising a dual-V-region bispecific antibody or a fragment thereof administered to a human subject specifically binds to IL-4 and IL-13 within the human subject, the method comprising:
(a) administering the dose to the human subject;
(b) measuring the amount of TARC/CCL17 protein in a blood, plasma, or serum sample drawn from the human subject, wherein a decrease in the amount of TARC/CCL17 in the blood sample relative to an amount of TARC/CCL17 in the subject measured before the dose was administered signifies binding of the dual-V-region bispecific antibody protein or fragment thereof to IL-4 or IL-13; and
(c) increasing the dose if the decrease in TARC/CCL17 measured in step (b) is below a threshold value or decreasing the dose if the decrease in TARC/CCL17 measured in step (b) is above a threshold value, wherein the threshold value is a 20% to 60% decrease in the amount of TARC/CCL17 relative to the amount of TARC/CCL17 in the subject measured before the dose was administered;
wherein said dual-V-region bispecific antibody comprises a variable light chain domain and a variable heavy chain domain,
wherein said variable light chain domain comprises amino acid sequences SEQ ID NO: 1 and SEQ ID NO: 3,
wherein said variable heavy chain domain comprises amino acid sequences SEQ ID NO: 2 and SEQ ID NO: 4; and
wherein the human subject has an IL-4 and/or IL-13 mediated disease.

2. The method of claim 1 , wherein the threshold value is a 43% decrease in the amount of TARC/CCL17 relative to the amount of TARC/CCL17 in the subject measured before the dose was administered.

3. The method of claim 1 , wherein the dose is administered subcutaneously.

4. The method of claim 1 , wherein the amount of TARC/CCL17 is detected by enzyme-linked immunosorbent assay (ELISA).

5. The method of claim 1 , wherein the human subject has idiopathic pulmonary fibrosis (IPF).

6. The method of claim 1 , wherein the threshold value is a 40% to 50% decrease in the amount of TARC/CCL17 relative to the amount of TARC/CCL17 in the subject measured before the dose was administered.

Assignees

• Sanofi Sa

Inventors

• Esperet Corinne
• Jagerschmidt Alexandre
• Soubrane Christina
• Subramaniam Arun

Classifications

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2333/521

  Chemokines · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title