Cd48 antibodies and conjugates thereof

Patent metadata

Field	Value
Publication number	US-2018092984-A1
Application number	US-201615557910-A
Country	US
Kind code	A1
Filing date	Mar 17, 2016
Priority date	Mar 18, 2015
Publication date	Apr 5, 2018
Grant date	—

Abstract

The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD48 and conjugates thereof.

First claim

1 . A chimeric or humanized antibody that specifically binds to the human CD48 protein, wherein the antibody comprises heavy chain CDR sequences of SEQ ID NOs:3-5 and light chain CDR sequences of SEQ ID NOs:6-8, and wherein the antibody exhibits higher binding affinity to the human CD48 protein, as compared to a murine antibody that specifically binds to the human CD48 protein and comprises heavy chain CDR sequences of SEQ ID NOs:3-5 and light chain CDR sequences of SEQ ID NOs:6-8.

2 . The antibody of claim 1 , wherein the chimeric or humanized antibody exhibits at least 2-fold higher binding affinity for the human CD48 protein, as compared to the murine antibody.

3 . The antibody of claim 1 , wherein the antibody is a humanized antibody.

4 . The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region of SEQ ID NO:1.

5 . The antibody of claim 1 , wherein the antibody comprises a light chain variable region of SEQ ID NO:2.

6 . (canceled)

7 . The antibody of claim 1 , wherein the antibody is conjugated to a drug-linker wherein a cytotoxic drug is attached to a linker.

8 . The antibody of claim 7 wherein the drug-linker has the formula:

or a pharmaceutically acceptable salt thereof wherein Z represents an organic moiety having a reactive site capable of reacting with a functional group on the antibody to form a covalent attachment thereto, n ranges from 8 to 36, R 21 is a capping unit for the polyethylene glycol moiety.

9 . A humanized antibody that specifically binds to the human CD48 protein, wherein the antibody comprises a heavy chain variable region of SEQ ID NO:1 and a light chain variable region of SEQ ID NO:2.

10 . The antibody of claim 9 , wherein the antibody is conjugated to a drug-linker wherein a cytotoxic drug is attached to a linker.

11 . The antibody of claim 10 wherein the drug-linker has the formula:

or a pharmaceutically acceptable salt thereof wherein Z represents an organic moiety having a reactive site capable of reacting with a functional group on the antibody to form a covalent attachment thereto, n ranges from 8 to 36, R 21 is a capping unit for the polyethylene glycol moiety.

12 . (canceled)

13 . The antibody of claim 11 wherein drug-linker has the formula

or a pharmaceutically acceptable salt thereof wherein, n ranges from 8 to 36, R PR is hydrogen or a protecting group, R 21 is a capping unit for the polyethylene glycol moiety.

14 . The antibody of claim 11 wherein drug-linker has the formula

or a pharmaceutically acceptable salt thereof wherein, n ranges from 8 to 36, R 21 is a capping unit for the polyethylene glycol moiety.

15 . The antibody of claim 11 wherein n ranges from 8 to 14.

16 - 17 . (canceled)

18 . The antibody of claim 15 wherein R 21 is —CH 3 or —CH 2 CH 2 CO 2 H.

19 . The antibody of claim 11 , having the formula

or a pharmaceutically acceptable salt thereof wherein Ab represents the antibody, and p represents the number of the drug-link attached to the antibody and is from 1 to 16.

20 - 29 . (canceled)

30 . The antibody of claim 11 wherein attachment of the drug-linker to the antibody is via the cysteine residues of the interchain disulfide bonds of the antibody.

31 . A composition comprising a population of the antibody of claim 19 wherein the average drug load of the antibodies in the composition is 8 and the predominant drug load of the antibodies in the composition is 8.

32 . (canceled)

33 . A method of treating a patient with a CD48 expressing cancer, the method comprising the step of administering the composition of claim 31 to the patient.

34 . (canceled)

35 . The method of claim 33 , wherein the CD48 expressing cancer is selected from the group consisting of multiple myeloma, B cell malignancies and acute myelogenous leukemia.

36 . An isolated nucleic acid comprising a sequence encoding a heavy chain variable region comprising CDRs having the amino acid sequences of SEQ ID NOs: 3-5 and a light chain variable region comprising CDRs having the amino acid sequences of SEQ ID NOs: 6-8 of an antibody that specifically binds to the human CD48 protein.

37 - 43 . (canceled)

44 . The isolated nucleic acid of claim 36 comprising a sequence encoding a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 2.

45 - 51 . (canceled)

Assignees

• Seattle Genetics Inc

Inventors

• Lewis Timothy
• Gordon Kristine
• Westendorf Lori

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• A61K47/6883

  Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy · CPC title

• A61K47/6807

  the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense · CPC title

• C07K5/0205

  containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title