IGF-1R antibody and its use for the diagnosis of cancer

• US 10,457,734 B2
• Filed: 04/27/2016
• Issued: 10/29/2019
• 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
• Primary Examiner(s): Li, Ruixiang
• Application Number:
  US15/569,550
• Publication Number:
  US 20180094060A1
• Time in Patent Office: 1,280 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, said antibody comprising:

i) a heavy chain comprising the following three CDRs, respectively 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 comprising the following three CDRs, respectively 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, said antibody comprising 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. 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 said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, of claim 1; and

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

5. 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 said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, of claim 1; and

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

6. 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 said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, of claim 1; and

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

7. 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 said subject with the IGF-1R antibody, or an antigen-binding fragment thereof, of claim 1;

(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 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 the intensity of the staining and the percentage of positive cells.

8. A method for determining whether an oncogenic disorder is susceptible to treatment with an inhibitor 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 6, 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.

9. The method of claim 8 wherein said inhibitor is an IGF-1R antibody.

10. The method of claim 9 wherein said IGF-1R antibody is alone, combined or conjugated.

11. 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) measuring a first expression level of IGF-1R according to the method of claim 6 in a first biological sample, said first biological sample corresponding to first time point of the said treatment;

(b) measuring a second expression level of IGF-1R according to the method of claim 6 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 said first expression level of step (a) to said second expression level of step (b); and

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

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

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

(a) measuring the expression level of IGF-1R according to the method of claim 6 in a biological sample of said patient;

(b) comparing the expression level of (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 of (a) to said 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 of (a) to said reference expression level is inferior or equal to 1.

13. The method of claim 12 wherein said inhibitor is an IGF-1R antibody.

14. The method of claim 13 wherein said IGF-1R antibody is alone, combined or conjugated.

15. The method of claim 13 wherein said reference expression level is the expression level of IGF-1R in a biological sample from a healthy subject.

16. A kit for the detection of IGF-1R expressing tumoral cells in a patient, said kit comprising the IGF-1R antibody, or an antigen-binding fragment thereof, of claim 1.

17. The kit of claim 16, wherein said antibody or antigen-binding thereof is labelled.

18. The kit of claim 16, further comprising positive and negative control samples for the scoring of IGF-1R expression level.

20. An isolated polynucleotide comprising a sequence coding for an antibody, according to claim 1.

21. The isolated polynucleotide of claim 20, said polynucleotide comprising a sequence selected from the group consisting of:

SEQ ID NO. 9 and SEQ ID NO. 10.

22. A vector comprising the polynucleotide of claim 20.

23. A host cell transformed by the vector of claim 22.

24. A method for producing an IGF-1R antibody, said method comprising the steps of:

a) growing the host cell of claim 23 in a culture medium and under suitable culture conditions; and

b) recovering said antibody produced from the culture medium or from said cultured cells.

3. An IGF-1R antibody secreted by the hybridoma deposited at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number 1-4893.

19. A murine hybridoma capable of secreting an IGF-1R antibody or an antigen-binding fragment thereof, said murine hybridoma being deposited at the CNCM, Institut Pasteur, Paris, on Sep. 17, 2014, under number I-4893.