Anti-CD22 antibody-maytansine conjugates and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12102689-B2
Application number	US-201615774384-A
Country	US
Kind code	B2
Filing date	Nov 8, 2016
Priority date	Nov 9, 2015
Publication date	Oct 1, 2024
Grant date	Oct 1, 2024

Abstract

The present disclosure provides anti-CD22 antibody-maytansine conjugate structures. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same.

First claim

What is claimed is:

1. A conjugate that includes at least one modified amino acid residue with a side chain of formula (I):

wherein
W 2 is an anti-CD22 antibody.

2. The conjugate of claim 1 , wherein the anti-CD22 antibody constant region comprises a sequence of the formula (II):
X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein
FG1y′ is the modified amino acid residue of formula (I);
Z 20 is either a proline or alanine residue;
Z 30 is a basic amino acid or an aliphatic amino acid;
X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and
X 2 and X 3 are each independently any amino acid.

3. The conjugate of claim 2 , wherein the sequence is L(FG1y′)TPSR (SEQ ID NO: 11).

4. The conjugate of claim 2 , wherein
Z 30 is selected from R, K, H, A, G, L, V, I, and P;
X 1 is selected from L, M, S, and V; and
X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

5. The conjugate of claim 1 , wherein the modified amino acid residue is positioned at a C-terminus of a heavy chain constant region of the anti-CD22 antibody.

6. The conjugate of claim 5 , wherein the heavy chain constant region comprises a sequence of the formula (II):
X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein
FG1y′ is the modified amino acid residue of formula (I);
Z 20 is either a proline or alanine residue;
Z 30 is a basic amino acid or an aliphatic amino acid;
X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and
X 2 and X 3 are each independently any amino acid, and
wherein the sequence is C-terminal to the amino acid sequence SLSLSPG (SEQ ID NO: 12).

7. The conjugate of claim 6 , wherein the heavy chain constant region comprises the sequence SPGSL(FG1y′)TPSRGS (SEQ ID NO: 13).

8. The conjugate of claim 6 , wherein
Z 30 is selected from R, K, H, A, G, L, V, I, and P;
X 1 is selected from L, M, S, and V; and
X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

9. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a light chain constant region of the anti-CD22 antibody.

10. The conjugate of claim 9 , wherein the light chain constant region comprises a sequence of the formula (II):
X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein
FG1y′ is the modified amino acid residue of formula (I);
Z 20 is either a proline or alanine residue;
Z 30 is a basic amino acid or an aliphatic amino acid;
X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and
X 2 and X 3 are each independently any amino acid, and
wherein the sequence is C-terminal to the sequence KVDNAL (SEQ ID NO: 14), and/or is N-terminal to the sequence QSGNSQ (SEQ ID NO: 15).

11. The conjugate of claim 10 , wherein the light chain constant region comprises the sequence KVDNAL(FG1y′)TPSRQSGNSQ (SEQ ID NO: 16).

12. The conjugate of claim 10 , wherein
Z 30 is selected from R, K, H, A, G, L, V, I, and P;
X 1 is selected from L, M, S, and V; and
X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

13. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a heavy chain CH 1 region of the anti-CD22 antibody.

14. The conjugate of claim 13 , wherein the heavy chain CH 1 region comprises a sequence of the formula (II):
X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein
FG1y′ is the modified amino acid residue of formula (I);
Z 20 is either a proline or alanine residue;
Z 30 is a basic amino acid or an aliphatic amino acid;
X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and
X 2 and X 3 are each independently any amino acid, and
wherein the sequence is C-terminal to the amino acid sequence SWNSGA (SEQ ID NO: 17) and/or is N-terminal to the amino acid sequence GVHTFP (SEQ ID NO: 18).

15. The conjugate of claim 14 , wherein the heavy chain CH 1 region comprises the sequence SWNSGAL(FG1y′)TPSRGVHTFP (SEQ ID NO: 19).

16. The conjugate of claim 14 , wherein
Z 30 is selected from R, K, H, A, G, L, V, I, and P;
X 1 is selected from L, M, S, and V; and
X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

17. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a heavy chain CH2 region of the anti-CD22 antibody.

18. The conjugate of claim 1 , wherein the modified amino acid residue is positioned in a heavy chain CH3 region of the anti-CD22 antibody.

19. A pharmaceutical composition comprising:
a conjugate of claim 1 ; and
a pharmaceutically acceptable excipient.

20. A method comprising:
administering to a subject an effective amount of a conjugate of claim 1 .

21. A method of treating a leukemia or a lymphoma in a subject, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a conjugate of claim 1 , wherein the administering is effective to treat the leukemia or the lymphoma in the subject.

22. A method of delivering a drug to a target site in a subject, the method comprising:
administering to the subject a pharmaceutical composition comprising a conjugate of claim 1 , wherein the administering is effective to release a therapeutically effective amount of the drug from the conjugate at the target site in the subject.

23. The conjugate of claim 1 , wherein the modified amino acid residue is positioned at a C-terminus of a heavy chain CH3 region of the anti-CD22 antibody.

24. The conjugate of claim 5 , wherein the heavy chain constant region comprises a sequence of the formula (II):
X 1 ( FG 1 y ′) X 2 Z 20 X 3 Z 30 ( SEQ ID NO: 10)  (II)

wherein
FG1y′ is the modified amino acid residue of formula (I);
Z 20 is either a proline or alanine residue;
Z 30 is a basic amino acid or an aliphatic amino acid;
X 1 may be present or absent and, when present, can be any amino acid, with the proviso that when the sequence is at the N-terminus of the conjugate, X 1 is present; and
X 2 and X 3 are each independently any amino acid, and
wherein the sequence is C-terminal to the amino acid sequence SLSLSPG (SEQ ID NO: 12).

25. The conjugate of claim 6 , wherein the heavy chain CH3 region comprises the sequence SPGSL(FG1y′)TPSRGS (SEQ ID NO: 13).

26. The conjugate of claim 6 , wherein
Z 30 is selected from R, K, H, A, G, L, V, I, and P;
X 1 is selected from L, M, S, and V; and
X 2 and X 3 are each independently selected from S, T, A, V, G, and C.

27. The method of claim 21 , comprising treating the leukemia.

28. The method of claim 27 , wherein the leukemia is a B-cell derived leukemia.

29. The method

Assignees

• Scherer Technologies Llc R P

Inventors

• Rabuka David
• Mcfarland Jesse M
• Drake Penelope M
• Barfield Robyn M

Classifications

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• C07D498/18 Primary

  Bridged systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6809

  Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin · CPC title

• A61P35/02

  specific for leukemia · CPC title