IP Library › Granted Patent US 10,428,156
Granted Patent B2
US 10,428,156 · App. 15/508,836 · Granted Oct 1, 2019

Anti-MFI2 antibodies and methods of use

Inventors: Samuel Williams (San Mateo, CA); Laura Saunders (San Francisco, CA); Holger Karsunky (Redwood City, CA); Mandy Boontanrart (San Francisco, CA)
Assignee: Abbvie Stemcentrx LLC
C07K16/2896A61K39/3955A61K45/06A61K47/6803A61K47/6809A61K47/6849A61K49/0004C07K16/30C12Q1/6886G01N33/57492A61K2039/505C07K2317/24C07K2317/33C07K2317/34C07K2317/53C07K2317/56C07K2317/565C07K2317/73C07K2317/77C07K2317/92C12Q2600/158G01N33/5743G01N33/57415G01N33/57419G01N33/57423G01N2333/70596
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,428,156
App. No.
15/508,836
Granted
Oct 1, 2019
Kind
B2
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.

Claims (78)

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 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.

16. The antibody drug conjugate of claim 15 , 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.

17. The antibody drug conjugate of claim 16 , 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.

18. The antibody drug conjugate of claim 17 , 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.

19. The antibody drug conjugate of claim 14 , 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.

20. The antibody drug conjugate of claim 14 , 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.

21. The antibody drug conjugate of claim 14 , 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.

22. The antibody drug conjugate of claim 14 , 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.

23. The antibody drug conjugate of claim 14 , 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.

24. The antibody drug conjugate of claim 14 , wherein the antibody comprises 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.

25. The antibody drug conjugate of claim 14 , wherein the cytotoxic agent is a dolastatin, a duocarmycin, a pyrrolobenzodiazepine (PBD), an auristatin, an aminitin, a maytansinoid, a calicheamicin, or a radioisotope.

26. A pharmaceutical composition comprising (a) the antibody drug conjugate of claim 14 and (b) a pharmaceutically acceptable carrier.

27. The pharmaceutical composition of claim 26 , 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.

28. The pharmaceutical composition of claim 26 , 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.

29. The pharmaceutical composition of claim 26 , 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.

30. The pharmaceutical composition of claim 26 , 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.

31. The pharmaceutical composition of claim 26 , 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.

32. The pharmaceutical composition of claim 26 , wherein the cytotoxic agent is a dolastatin, a duocarmycin, a pyrrolobenzodiazepine (PBD), an auristatin, an aminitin, a maytansinoid, a calicheamicin, or a radioisotope.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2017
From: WILLIAMS, SAMUEL; SAUNDERS, LAURA; KARSUNKY, HOLGER; BOONTANRART, MANDY
To: STEMCENTRX, INC.
Reel/Frame 044040/0915 →
MERGER Recorded Nov 6, 2017
From: STEMCENTRX, INC.
To: ABBVIE STEMCENTRX LLC
Reel/Frame 044040/0944 →
Continuity (3)
Provisional Application 62203836 · Aug 11, 2015
Provisional Application 62046610 · Sep 5, 2014
Related Publication 20170320960A1 · Nov 9, 2017