Anti-CD98 antibody processes

Patent metadata

Field	Value
Publication number	US-9688770-B2
Application number	US-201514703354-A
Country	US
Kind code	B2
Filing date	May 4, 2015
Priority date	Apr 6, 2006
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

A human antibody or a functional fragment thereof having specific binding ability to CD98 which is derived from the cell membrane of cancer cells and is in the form of a complex with a protein having an amino acid transporter activity (for example, LAT1) is disclosed. This antibody binds to CD98 in the form of a dimer with LAT1 on the surface of cancer cells, specifically attacks cancer cells expressing CD98 via the immune system by ADCC or CDC, and further inhibits amino acid uptake of the cancer cells via LAT1, to suppress growth of the cancer cells. Accordingly, a preventive and therapeutic agent for cancer comprising this antibody or a fragment thereof, which acts on various cancers, is specific to cancer, and causes no side effect, is provided.

First claim

The invention claimed is:

1. An isolated monoclonal antibody or fragment thereof which specifically binds to a CD98 epitope bound by an antibody or fragment thereof that:
(i) has the amino acid sequence of complementarity determining region (CDR)s comprised in (a) SEQ ID NOs: 41 and 47, (b) SEQ ID NOs: 43 and 47, (c) SEQ ID NOs: 43 and 77, (d) SEQ ID NOs: 43 and 79, (e) SEQ ID NOs: 43 and 81, (f) SEQ ID NOs: 43 and 83; and (g) SEQ ID NOs: 29 and 31,
(ii) has the amino acid sequence of CDRs of the antibody produced by the cell line having a plasmid deposited under Accession Number FERM BP-10551 or a plasmid deposited under Accession Number FERM BP-10552, or
(iii) has the amino acid sequence of CDRs encoded by a BglII-BsiWI fragment and a SalI-NheI fragment obtained from a plasmid vector K3/pCR4 deposited under Accession Number FERM BP-10552.

2. The isolated monoclonal antibody or fragment thereof according to claim 1 , wherein said antibody or said fragment has anti-tumor activity.

3. The isolated monoclonal antibody or fragment thereof according to claim 1 , wherein said antibody inhibits amino acid transport into a cell expressing CD98.

4. The isolated monoclonal antibody or fragment thereof according to claim 3 , wherein a protein having said amino acid transporter activity is LAT1.

5. The isolated monoclonal antibody or fragment thereof according to claim 1 , wherein a subclass of the antibody heavy chain constant region is an IgG.

6. The isolated monoclonal antibody or fragment thereof according to claim 1 , which binds to an epitope comprising at least 8 consecutive or non-consecutive amino acid residues of amino acid 1 to amino acid 529 of a CD98, a human CD98 or SEQ ID NO: 66.

7. The isolated monoclonal antibody or fragment thereof according to claim 6 , which binds to an epitope comprising a consecutive or non-consecutive amino acid residue of amino acid 371 to amino acid 529 of a CD98, a human CD98 or SEQ ID NO: 66.

8. The isolated monoclonal antibody or fragment thereof according to claim 1 , wherein the fragment specifically binds a CD98, and wherein said fragment comprises a fragment selected from the group consisting of a heavy chain variable region and a light chain variable region (VH and VL), a Fab, a Fab′, a (Fab′) 2 , a Fv, a Fd, a scFv, and a sdFv.

9. The isolated monoclonal antibody or fragment thereof according to claim 1 , wherein the antibody has:
(i) the amino acid sequence of complementarity determining region (CDR)s comprised in (a) SEQ ID NOs; 41 and 47, (b) SEQ ID NOs; 43 and 47, (c) SEQ ID NOs: 43 and 77, (d) SEQ ID NOs: 43 and 79, (e) SEQ ID NOs: 43 and 81, (f) SEQ ID NOs: 43 and 83; and (g) SEQ ID NOs: 29 and 31,
(ii) the amino acid sequence of CDRs of the antibody produced by the cell line having a plasmid deposited under Accession Number FERM BP-10551 or a plasmid deposited under Accession Number FERM BP-10552, or
(iii) the amino acid sequence of CDRs encoded by a BglII-BsiWI fragment and a SalI-NheI fragment obtained from a plasmid vector K3/pCR4 deposited under Accession Number FERM BP-10552.

10. The isolated monoclonal antibody or fragment thereof according to claim 1 , wherein the antibody has:
(i) the amino acid sequence of variable regions comprised in (a) SEQ ID NOs: 41 and 47, (b) SEQ ID NOs: 43 and 47, (c) SEQ ID NOs: 43 and 77, (d) SEQ ID NOs: 43 and 79, (e) SEQ ID NOs: 43 and 81, (f) SEQ ID NOs: 43 and 83; and (g) SEQ ID NOs: 29 and 31,
(ii) the amino acid sequence of variable regions of the antibody produced by the cell line having a plasmid deposited under Accession Number FERM BP-10551 or a plasmid deposited under Accession Number FERM BP-10552, or
(iii) the amino acid sequence of variable regions encoded by a BglII-BsiWI fragment and a SalI-NheI fragment obtained from a plasmid vector K3/pCR4 deposited under Accession Number FERM BP-10552.

11. A conjugate comprising: the isolated antibody or fragment thereof according to claim 1 and an agent selected from the group consisting of a binding protein, an enzyme, a drug, a toxin, a radionuclide, an immunomodulator, a detectable moiety and a tag.

12. A pharmaceutical composition comprising the isolated monoclonal antibody or fragment thereof according to claim 1 as an active ingredient.

13. An isolated monoclonal antibody or fragment thereof which has:
(i) the amino acid sequence of complementarity determining region (CDR)s comprised in (a) SEQ ID NOs: 41 and 47, (b) SEQ ID NOs: 43 and 47, (c) SEQ ID NOs: 43 and 77, (d) SEQ ID NOs: 43 and 79, (e) SEQ ID NOs: 43 and 81, (f) SEQ ID NOs: 43 and 83; and (g) SEQ ID NOs: 29 and 31,
(ii) the amino acid sequence of CDRs of the antibody produced by the cell line having a plasmid deposited under Accession Number FERM BP-10551 or a plasmid deposited under Accession Number FERM BP-10552, or
(iii) the amino acid sequence of CDRs encoded by a BglII-BsiWI fragment and a SalI-NheI fragment obtained from a plasmid vector K3/pCR4 deposited under Accession Number FERM BP-10552.

14. An isolated monoclonal antibody or fragment thereof which has:
(i) the amino acid sequence of variable regions comprised in (a) SEQ ID NOs: 41 and 47, (b) SEQ ID NOs: 43 and 47, (c) SEQ ID NOs: 43 and 77, (d) SEQ ID NOs: 43 and 79, (e) SEQ ID NOs: 43 and 81, (f) SEQ ID NOs: 43 and 83; and (g) SEQ ID NOs: 29 and 31,
(ii) the amino acid sequence of variable regions of the antibody produced by the cell line having a plasmid deposited under Accession Number FERM BP-10551 or a plasmid deposited under Accession Number FERM BP-10552, or
(iii) the amino acid sequence of variable regions encoded by a BglII-BsiWI fragment and a SalI-NheI fragment obtained from a plasmid vector K3/pCR4 deposited under Accession Number FERM BP-10552.

Assignees

• Kyowa Hakko Kirin Co Ltd

Inventors

• Tahara Tomoyuki
• Kanai Yoshikatsu
• Endou Hitoshi
• Kataoka Shiro
• Hasegawa Kazumasa
• Yoshino Tetsuya

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2896 Primary

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title