US20190202901A1 – July 4, 2019 – COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER

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Inventors :

Alexandra JOUHANNEAUD; Liliane GOETSCH; Matthieu BROUSSAS; Charlotte BEAU-LARVOR; Thierry CHAMPION; Robert ALAIN; Jean-François HAEUW; Ian RILATT; Michel PEREZ

Owner :

PIERRE FABRE MEDICAMENT

Application Number :

US15771082

Document Number :

US20190202901A1

Priority Date :

October 26, 2015

Filing Date :

October 26, 2016

Date of Grant/ Publication :

July 4, 2019

Class :

C07K16 / 22; A61K47 / 68; A61P35 / 00; A61K47 / 65

Abstract

The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention relates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.

Claim(s)

16 . A method of treating cancer in a subject in need thereof, said method comprising the steps of a) determining whether the subject is IGF-1R(+), wherein said determining comprises contacting a biological sample of the subject with a first anti-IGF-1R antibody, said first anti-IGF-1R antibody being selected from the group consisting of: i) an antibody, or an antigen-binding fragment thereof, said antibody comprising: a heavy chain with CDR-H1 of SEQ ID No. 1, CDR-H2 of SEQ ID No. 2, and CDR-H3 of SEQ ID No. 3; and a light chain with CDR-L1 of SEQ ID No. 4, CDR-L2 of SEQ ID No. 5, and CDR-L3 of SEQ ID No. 6; and ii) an antibody, or an antigen-binding fragment thereof, said antibody comprising: a heavy chain with CDR-H1 of SEQ ID No. 11, CDR-H2 of sequence SEQ ID No. 12 and CDR-H3 of sequence SEQ ID No. 13; and a light chain with CDR-L1 of sequence SEQ ID No. 14, CDR-L2 of sequence SEQ ID No. 15, and CDR-L3 of sequence SEQ ID No. 16; and b) if said subject is IGF-1R(+), administering a composition to said subject, said composition comprising an antibody-drug-conjugate of formula (I): Ab-(L-D) n ??(I) or a pharmaceutically acceptable salt thereof, wherein Ab is a second anti-IGF-1R antibody, or an antigen binding fragment thereof, which binds to the human IGF-1R and which is internalized following its binding to IGF-1R; L is a linker; D is a drug moiety; and n is an integer from 1 to 12;;
30 . A kit comprising: a) a first anti-IGF-1R antibody selected from the group consisting of: i) an antibody, or an antigen-binding fragment thereof, said antibody comprising: a heavy chain with CDR-H1 of SEQ ID No. 1, CDR-H2 of SEQ ID No. 2, and CDR-H3 of SEQ ID No. 3; and a light chain with CDR-L1 of SEQ ID No. 4, CDR-L2 of SEQ ID No. 5, and CDR-L3 of SEQ ID No. 6; and ii) an antibody, or an antigen-binding fragment thereof, said antibody comprising: a heavy chain with CDR-H1 of SEQ ID No. 11, CDR-H2 of sequence SEQ ID No. 12 and CDR-H3 of sequence SEQ ID No. 13; and a light chain with CDR-L1 of sequence SEQ ID No. 14, CDR-L2 of sequence SEQ ID No. 15, and CDR-L3 of sequence SEQ ID No. 16; and b) an antibody-drug-conjugate of formula (I): Ab-(L-D) n ??(I) or a pharmaceutically acceptable salt thereof, wherein Ab is a second anti-IGF-1R antibody, or an antigen binding fragment thereof, capable of binding to the human IGF-1R selected from the group consisting of: i) an antibody comprising: three heavy chain CDRs of sequence SEQ ID Nos. 21, 22 and 23 and three light chain CDRs of sequence SEQ ID Nos. 24, 25 and 26; ii) an antibody capable of competing for binding to IGF-1R with the antibody of i); and iii) an antibody capable of binding to the same IGF-1R epitope as the antibody of i); L is a linker; and D is a drug moiety of formula (II): wherein: R 2 is COOH, COOCH 3 or thiazolyl; R 3 is H or (C 1 -C 6 )alkyl; R 9 is H or (C 1 -C 6 )alkyl; m is an integer from 1 to 8; the wavy line indicates the point of attachment to L; and n is an integer from 1 to 12.

Summary

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