IGF-1R ANTIBODY AND ITS USE FOR THE DIAGNOSIS OF CANCER

• US 20180094060A1
• Filed: 04/27/2016
• Published: 04/05/2018
• Est. Priority Date: 04/27/2015
• Status: Active Grant

• Current Assignee: Pierre Fabre Medicament (Fondation Pierre Fabre)
• Original Assignee: Pierre Fabre Medicament (Fondation Pierre Fabre)
• Inventors: JOUHANNEAUD, Alexandra
• Granted Patent: US 10,457,734 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

The present disclosure relates to a novel antibody, in particular a monoclonal antibody, capable of binding to IGF-1R, as well as the amino and nucleic acid sequences coding for said antibody.

Claims

1. An IGF-1R antibody, or an antigen-binding fragment thereof, characterized in that it comprises:

i) a heavy chain with CDR-H1 of sequence SEQ ID No. 1, CDR-H2 of sequence SEQ ID No. 2 and CDR-H3 of sequence SEQ ID No. 3; and

ii) a light chain with CDR-L1 of sequence SEQ ID No. 4, CDR-L2 of sequence SEQ ID No. 5 and CDR-L3 of sequence SEQ ID No. 6.

2. The IGF-1R antibody according to claim 1, characterized in that it comprises a heavy chain variable domain of sequence SEQ ID No. 7, or any sequence with at least 90% of homology with the sequence SEQ ID No. 7;

and/or a light chain variable domain of sequence SEQ ID No. 8, or any sequence with at least 90% of homology with the sequence SEQ ID No. 8.

4. The IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3 for use as an agent for the detection of IGF-1R expressing tumoral cells or for determining the expression level of IGF-1R expressing tumoral cells.

5. The IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3, for use in the in vitro or ex vivo diagnosing or prognosing of an oncogenic disorder associated with expression of IGF-1R.

6. The IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3, for use in determining whether a patient with an oncogenic disorder is likely to benefit from treatment with an inhibitor targeting the IGF-1R pathway, preferentially an IGF-1R antibody alone, combined or conjugated.

7. A method for detecting in vitro or ex vivo the presence and/or the location of IGF-1R expressing tumoral cells in a subject, said method comprising the steps of:

(a) contacting a biological sample from the said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3; and

(b) detecting the binding of the said IGF-1R antibody, or an antigen-binding fragment thereof, with the said biological sample.

8. A method for detecting in vitro or ex vivo the percentage of tumoral cells expressing IGF-1R in a subject, said method comprising the steps of:

(a) contacting a biological sample from the said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3; and

(b) quantifying the percentage of cells expressing IGF-1R in the biological sample.

9. A method for determining in vitro or ex vivo the expression level of IGF-1R in tumoral cells in a subject, said method comprising the steps of:

(a) contacting a biological sample from the said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3; and

(b) quantifying the level of binding of the said IGF-1R antibody, or an antigen-binding fragment thereof, to IGF-1R in the said biological sample.

10. A method for determining in vitro or ex vivo the IGF-1R scoring of tumoral cells or of a tumor in a subject, said method comprising the steps of:

(a) contacting a biological sample from the said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3;

(b) quantifying by Fluorescence Activated Cell Sorting (FACS) or immunohistochemistry (IHC) the level of binding of the said IGF-1R antibody, or an antigen-binding fragment thereof, to IGF-1R in the said biological sample; and

(c) scoring the tumoral cells or the tumor by comparing the quantified level obtained in step (b) to an appropriate scale based on two parameters which are the intensity of the staining and the percentage of positive cells.

11. A method for determining whether an oncogenic disorder is susceptible to treatment with an antibody drug targeting the IGF-1R pathway, said method comprising the steps of:

(a) determining in vitro or ex vivo the IGF-1R status of tumoral cells or of a tumor of a subject according to the method of claim 10, and

(b) determining that, if the IGF-1R status of tumoral cells or the tumor is IGF-1R(+), the oncogenic disorder is susceptible to treatment with an antibody drug targeting the IGF-1R pathway.

12. A method for determining in vitro or ex vivo the efficacy of a therapeutic regimen designed to alleviate an oncogenic disorder associated with IGF-1R in a subject suffering from said disorder, said method comprising the steps of:

(a) determining a first expression level of IGF-1R according to claim 9 in a first biological sample, said first biological sample corresponding to first time point of the said treatment;

(b) determining a second expression level of IGF-1R according to claim 9 in a second biological sample, said second biological sample corresponding to a second, later time point of the said treatment;

(c) calculating the ratio of the said first expression level obtained in step (a) to the said second expression level obtained in step (b); and

(d) determining that the efficacy of said therapeutic regime is high when the ratio of step (c) is greater than 1;

or determining that the efficacy of said therapeutic regime is low when the ratio of step (c) is inferior or equal to 1.

13. A method for selecting a cancer patient predicted to benefit or not from the administration of a therapeutic amount of an antibody drug targeting the IGF-1R pathway, said method comprising the steps of:

(a) determining the expression level of IGF-1R according to the method of claim 9;

(b) comparing the expression level of the previous step (a) with a reference expression level; and

(c) selecting the patient as being predicted to benefit from a treatment with an antibody drug targeting the IGF-1R pathway, if the ratio of the expression level obtained in (a) to the reference expression level is greater than 1;

or

(d) selecting the patient as being not predicted to benefit from a treatment with an antibody drug targeting the IGF-1R pathway, if the ratio of the expression level obtained in (a) to the reference expression level is inferior or equal to 1.

14. A kit for the detection of IGF-1R expressing tumoral cells in a patient, characterized in that said kit comprises at least the IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3.

15. A kit for determining whether a patient with an oncogenic disorder is likely to benefit from treatment with an antibody drug targeting the IGF-1R pathway, characterized in that said kit comprises at least the IGF-1R antibody, or an antigen-binding fragment thereof, according to anyone of claims 1 to 3.

3. An IGF-1R antibody, or an antigen-binding fragment thereof, characterized in that it is secreted by the hybridoma filed at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number 1-4893.