Anti-MFI2 antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10428156-B2
Application number	US-201515508836-A
Country	US
Kind code	B2
Filing date	Sep 4, 2015
Priority date	Sep 5, 2014
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

Provided are novel anti-MFI2 antibodies and antibody drug conjugates, and methods of using such anti-MFI2 antibodies and antibody drug conjugates to treat cancer.

First claim

The invention claimed is:

1. A humanized antibody that binds to a human MFI2 protein and comprises a light chain variable region and a heavy chain variable region, wherein the antibody comprises:
(a) three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 99 and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 101;
(b) three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 105 and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 107;
(c) three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 93 and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 95; or
(d) three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 93 and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 97.

2. The humanized antibody of claim 1 , wherein the antibody comprises three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 99 and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 101.

3. The humanized antibody of claim 2 , wherein the antibody comprises:
(a) residues 24-34 of SEQ ID NO: 99 for CDR-L1, residues 50-56 of SEQ ID NO: 99 for CDR-L2, residues 89-97 of SEQ ID NO: 99 for CDR-L3, residues 31-35 of SEQ ID NO: 101 for CDR-H1, residues 50-65 of SEQ ID NO: 101 for CDR-H2 and residues 95-102 of SEQ ID NO: 101 for CDR-H3, wherein the CDR residues are numbered according to Kabat;
(b) residues 24-34 of SEQ ID NO: 99 for CDR-L1, residues 50-56 of SEQ ID NO: 99 for CDR-L2, residues 89-97 of SEQ ID NO: 99 for CDR-L3, residues 26-32 of SEQ ID NO: 101 for CDR-H1, residues 52-56 of SEQ ID NO: 101 for CDR-H2 and residues 95-102 of SEQ ID NO: 101 for CDR-H3, wherein the CDR residues are numbered according to Chothia; or
(c) residues 30-36 of SEQ ID NO: 99 for CDR-L1, residues 46-55 of SEQ ID NO: 99 for CDR-L2, residues 89-96 of SEQ ID NO: 99 for CDR-L3, residues 30-35 of SEQ ID NO: 101 for CDR-H1, residues 47-58 of SEQ ID NO: 101 for CDR-H2 and residues 93-101 of SEQ ID NO: 101 for CDR-H3, wherein the CDR residues are numbered according to MacCallum.

4. The humanized antibody of claim 1 , wherein the antibody comprises three complementarity determining regions of a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 105 and three complementarity determining regions of a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 107.

5. The humanized antibody of claim 4 , wherein the antibody comprises:
(a) residues 24-34 of SEQ ID NO: 105 for CDR-L1, residues 50-56 of SEQ ID NO: 105 for CDR-L2, residues 89-97 of SEQ ID NO: 105 for CDR-L3, residues 31-35 of SEQ ID NO: 107 for CDR-H1, residues 50-65 of SEQ ID NO: 107 for CDR-H2 and residues 95-102 of SEQ ID NO: 107 for CDR-H3, wherein the CDR residues are numbered according to Kabat;
(b) residues 24-34 of SEQ ID NO: 105 for CDR-L1, residues 50-56 of SEQ ID NO: 105 for CDR-L2, residues 89-97 of SEQ ID NO: 105 for CDR-L3, residues 26-32 of SEQ ID NO: 107 for CDR-H1, residues 52-56 of SEQ ID NO: 107 for CDR-H2 and residues 95-102 of SEQ ID NO: 107 for CDR-H3, wherein the CDR residues are numbered according to Chothia; or
(c) residues 30-36 of SEQ ID NO: 105 for CDR-L1, residues 46-55 of SEQ ID NO: 105 for CDR-L2, residues 89-96 of SEQ ID NO: 105 for CDR-L3, residues 30-35 of SEQ ID NO: 107 for CDR-H1, residues 47-58 of SEQ ID NO: 107 for CDR-H2 and residues 93-101 of SEQ ID NO: 107 for CDR-H3, wherein the CDR residues are numbered according to MacCallum.

6. The humanized antibody of claim 1 , wherein the antibody comprises
(a) a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 99 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 101;
(b) a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 93 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 95;
(c) a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 93 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 97;
(d) a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 99 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 103; or
(e) a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 105 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 107.

7. The humanized antibody of claim 1 , wherein the antibody comprises a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 99 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 101.

8. The humanized antibody of claim 1 , wherein the antibody comprises a light chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 105 and a heavy chain variable region comprising an amino acid sequence set forth as SEQ ID NO: 107.

9. The humanized antibody of claim 1 , wherein the antibody comprises:
(a) a light chain comprising an amino acid sequence set forth as SEQ ID NO: 112 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 114;
(b) a light chain comprising an amino acid sequence set forth as SEQ ID NO: 112 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 113;
(c) a light chain comprising an amino acid sequence set forth as SEQ ID NO: 112 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 115;
(d) a light chain comprising an amino acid sequence set forth as SEQ ID NO: 116 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 117; or
(e) a light chain set comprising an amino acid sequence forth as SEQ ID NO: 116 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 118.

10. The humanized antibody of claim 1 , wherein the antibody comprises a light chain comprising an amino acid sequence set forth as SEQ ID NO: 112 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 114.

11. The humanized antibody of claim 1 , wherein the antibody comprises a light chain comprising an amino acid sequence set forth as SEQ ID NO: 116 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 118.

12. The humanized antibody of claim 1 , wherein the antibody is conjugated to a cytotoxic agent.

13. The humanized antibody of claim 12 , wherein the cytotoxic agent is a dolastatin, a duocarmycin, a pyrrolobenzodiazepine (PBD), an auristatin, an aminitin, a maytansinoid, a calichearmicin, or a radioisotope.

14. An antibody drug conjugate comprising a humanized antibody conjugated to a cytotoxic agent, wherein the humanized antibody is the antibody of claim 1 .

15. The antibody drug conjugate of claim 14 , wherein the antibody comprises three complementarity determin

Assignees

• Abbvie Stemcentrx Llc

Inventors

• Williams Samuel
• Saunders Laura
• Karsunky Holger
• Boontanrart Mandy

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• G01N33/57535

  of the large intestine, e.g. colon, rectum or anus · CPC title