Antibodies having specificity to nectin-4 and uses thereof

Patent metadata

Field	Value
Publication number	US-10675357-B2
Application number	US-201615754047-A
Country	US
Kind code	B2
Filing date	Sep 7, 2016
Priority date	Sep 9, 2015
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

The present invention relates to antibodies having specificity to nectin-4 and uses thereof.

First claim

The invention claimed is:

1. An antibody having specificity to nectin-4 and having
a heavy chain comprising i) the H-CDR1 of N41mab, ii) the H-CDR2 of N41mab and iii) the H-CDR3 of N41mab and
a light chain comprising i) the L-CDR1 of N41mab, ii) the L-CDR2 of N41mab and iii) the L-CDR3 of N41mab

wherein
the H-CDR1 of N41mab 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 N41mab is defined by the sequence ranging from the amino acid residue at position 50 to the amino acid residue at position 65 in SEQ ID NO:1,
the H-CDR3 of N41mab is defined by the sequence ranging from the amino acid residue at position 98 to the amino acid residue at position 105 in SEQ ID NO:1,
the L-CDR1 of N41mab is defined by the sequence ranging from the amino acid residue at position 24 to the amino acid residue at position 34 in SEQ ID NO:2,
the L-CDR2 of N41mab is defined by the sequence ranging from the amino acid residue at position 50 to the amino acid residue at position 56 in SEQ ID NO:2, and
the L-CDR3 of N41mab is defined by the sequence ranging from the amino acid residue at position 89 to the amino acid residue at position 96 in SEQ ID NO:2.

2. The antibody of claim 1 having a heavy chain identical to SEQ ID NO: 1 and a light chain identical to SEQ ID NO:2.

3. The antibody of claim 1 which is a chimeric antibody.

4. The antibody of claim 1 which is a humanized antibody which comprises the CDRs of the N41mab antibody.

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

6. The antibody of claim 1 which is conjugated to a cytotoxic moiety.

7. The antibody of claim 6 which is conjugated to a cytotoxic moiety 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; Mertansine or a peptide analog, derivative or prodrug thereof; 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]-benzodiazepines (PDB); diphtheria toxin or derivative thereof, ricin toxin or derivative thereof, cholera toxin, Shiga toxin or a Shiga like toxin, pertussis toxin, tetanus toxin, soybean Bowman-Birk protease inhibitor, Pseudomonas exotoxin, alorin, saporin, modeccin, gelanin, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, a Phytolacca americana protein, Momordica charantia inhibitor, curcin, crotin, Sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin toxins; ribonuclease (RNase); DNase I, Staphylococcal enterotoxin A; pokeweed antiviral protein; and Pseudomonas endotoxin.

8. The antibody of claim 6 which is conjugated to an auristatin or a peptide analog, derivative or prodrug thereof.

9. A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the antibody of claim 1 .

10. The method of claim 9 wherein the cancer is a breast cancer, an ovarian cancer or a lung cancer.

11. The method of claim 9 wherein the cancer is a metastatic cancer.

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

13. A chimeric antigen receptor which comprises at least one VH and/or VL sequence of the antibody of claim 1 .

14. The antibody of claim 7 , wherein
a. the tubulin-inhibitor is maytansine or an analog or derivative thereof;
b. the antimitotic agent is monomethyl auristatin E or F or an analog or derivative thereof;
c. the antimetabolite is methotrexate, 6 mercaptopurine, 6 thioguanine, cytarabine, fludarabin, 5 fluorouracil, decarbazine, hydroxyurea, asparaginase, gemcitabine, or cladribine;
d. the alkylating agent is mechlorethamine, thioepa, chlorambucil, melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, dacarbazine (DTIC), procarbazine or mitomycin C;
e. the platinum derivative is cisplatin or carboplatin;
f. the antibiotic is dactinomycin, bleomycin, daunorubicin, doxorubicin, idarubicin, mithramycin, mitomycin, mitoxantrone, plicamycin or anthramycin (AMC);
g. the diphtheria toxin or derivative thereof is diphtheria A chain, an active fragment of diphtheria toxin or a hybrid molecule of diphtheria toxin or diphtheria A chain;
h. the ricin toxin or derivative thereof is ricin A or a deglycosylated ricin A chain toxin;
i. the Shiga-like toxin is SLT I, SLT II, SLT IIV, LT toxin or C3 toxin; and/or
j. the Phytolacca americana protein is PAPI, PAPII or PAP-S.

Assignees

• Inst Nat Sante Rech Med
• Univ Aix Marseille
• Centre Nat Rech Scient
• Inst Jean Paoli & Irene Calmettes

Inventors

• Lopez Marc
• Olive Daniel

Classifications

• A61K39/395 Primary

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• A61K47/6899

  Antibody-Directed Enzyme Prodrug Therapy [ADEPT] · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title