Antibodies having specificity to Nectin-4 and uses thereof

Patent metadata

Field	Value
Publication number	US-11274160-B2
Application number	US-201816490388-A
Country	US
Kind code	B2
Filing date	Mar 1, 2018
Priority date	Mar 2, 2017
Publication date	Mar 15, 2022
Grant date	Mar 15, 2022

Abstract

The present invention relates to a new antibody anti-nectin-4. Nectin-4 is a tumor-associated antigen overexpressed in several cancers and notably in 30%, 49% and 86% of breast, ovarian and lung carcinomas, respectively, which are tumors of bad prognosis. Treatments remain still elusive. That's why the inventors developed a new targeted therapy based on an antibody having specificity to nectin-4 (called 14A5.2 mab). Indeed, the inventors selected this antibody for its intrinsic prophylactic anti-metastatic properties and also for the treatment of localized primary and metastatic cancer. More, the 14A5.2 mab could be indicated for the treatment of cancer resistant to ASG-22ME (from Astellas company). Thus, the invention relates to the 14A5.2 mab and its uses thereof.

First claim

The invention claimed is:

1. An antibody having a heavy chain comprising i) the H-CDR1 of 14A5.2 mab, ii) the H-CDR2 of 14A5.2 mab and iii) the H-CDR3 of 14A5.2 mab and a light chain comprising i) the L-CDR1 of 14A5.2 mab, ii) the L-CDR2 of 14A5.2 mab and iii) the L-CDR3 of 14A5.2 mab
wherein
the H-CDR1 of 14A5.2 mab is defined by the sequence ranging from the amino acid residue at position 31 to the amino acid residue at position 35 in SEQ ID NO:1;
the H-CDR2 of 14A5.2 mab is defined by the sequence ranging from the amino acid residue at position 50 to the amino acid residue at position 66 in SEQ ID NO:1;
the H-CDR3 of 14A5.2 mab is defined by the sequence ranging from the amino acid residue at position 99 to the amino acid residue at position 104 in SEQ ID NO:1;
the L-CDR1 of 14A5.2 mab is defined by the sequence ranging from the amino acid residue at position 24 to the amino acid residue at position 38 in SEQ ID NO:2;
the L-CDR2 of 14A5.2 mab is defined by the sequence ranging from the amino acid residue at position 54 to the amino acid residue at position 60 in SEQ ID NO:2 and
the L-CDR3 of 14A5.2 mab is defined by the sequence ranging from the amino acid residue at position 93 to the amino acid residue at position 101 in SEQ ID NO:2.

2. An antibody according to claim 1 wherein the heavy chain has at least 70% of identity with SEQ ID NO:1 and the light chain has at least 70% of identity with SEQ ID NO:2.

3. An antibody according to claim 2 wherein the heavy chain is identical to SEQ ID NO:1 and the light chain is identical to SEQ ID NO:2.

4. The antibody of claim 1 wherein the antibody is a chimeric antibody.

5. The antibody of claim 1 wherein the antibody is a humanized antibody which comprises the CDRs of the 14A5.2 mab antibody.

6. A nucleic acid molecule encoding the antibody of claim 1 .

7. The antibody of claim 1 wherein the antibody is conjugated to a cytotoxic moiety.

8. The antibody of claim 7 wherein the cytotoxic moiety is selected from the group consisting of taxol; cytochalasin B; gramicidin D; ethidium bromide; emetine; mitomycin; etoposide; tenoposide; vincristine; vinblastine; colchicin; doxorubicin; daunorubicin; dihydroxy anthracin dione; a tubulin-inhibitor; an antimitotic agent; dolastatin 10 or 15 or an analogue thereof; irinotecan or an analogue thereof; mitoxantrone; mithramycin; actinomycin D; 1-dehydrotestosterone; a glucocorticoid; procaine; tetracaine; lidocaine; propranolol; puromycin; calicheamicin or an analog or derivative thereof; an antimetabolite; an alkylating agent; a platinum derivative; duocarmycin A, duocarmycin SA, rachelmycin (CC-1065), or an analog or derivative thereof; an antibiotic; pyrrolo[2,1-c][1,4] benzodiazepine (PDB); a toxin; ribonuclease (RNase); DNase I; and pokeweed antiviral protein.

9. A pharmaceutical composition comprising the antibody of claim 1 .

10. The antibody of claim 8 , wherein
the tubulin-inhibitor is maytansine or an analog or derivative thereof;
the antimitotic agent is monomethyl auristatin E or F or an analog or derivative thereof;
the antimetabolite is methotrexate, 6 mercaptopurine, 6 thioguanine, cytarabine, fludarabin, 5 fluorouracil, decarbazine, hydroxyurea, asparaginase, gemcitabine, or cladribine;
the alkylating agent is mechlorethamine, thioepa, chlorambucil, melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, dacarbazine (DTIC), procarbazine or mitomycin C;
the platinum derivative is cisplatin or carboplatin;
the antibiotic is dactinomycin, bleomycin, daunorubicin, doxorubicin, idarubicin, mithramycin, mitomycin, mitoxantrone, plicamycin or anthramycin (AMC);
the toxin is a diphtheria toxin, a ricin toxin, a cholera toxin, a Shiga-like toxin, LT toxin, C3 toxin, Shiga toxin, pertussis toxin, tetanus toxin, soybean Bowman-Birk protease inhibitor, Pseudomonas exotoxin, Pseudomonas endotoxin, alorin, saporin, modeccin, gelanin, abrin A chain, modeccin A chain, alpha-sarcin, an Aleurites fordii protein, a dianthin protein, a Phytolacca americana protein, Momordica charantia inhibitor, curcin, crotin, Sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, neomycin or Staphylococcal enterotoxin A.

Assignees

• Inst Nat Sante Rech Med
• Inst Jean Paoli & Irene Calmettes
• Centre Nat Rech Scient
• Univ Aix Marseille
• Inst Jean Paoli & Irene Calettes
• Centre Nationale De La Recherche Scient

Inventors

• Lopez Marc

Classifications

• A61K47/68031

  the drug being an auristatin · CPC title

• C07K16/30 Primary

  from tumour cells · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• C07K2317/14

  Specific host cells or culture conditions, e.g. components, pH or temperature · CPC title

• A61K2039/505

  comprising antibodies · CPC title