Pyrrolobenzodiazepine-anti-CD22 antibody conjugates

Patent metadata

Field	Value
Publication number	US-10722594-B2
Application number	US-201815884665-A
Country	US
Kind code	B2
Filing date	Jan 31, 2018
Priority date	Oct 12, 2012
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

Conjugates of an isolated humanized, anti-CD22 antibody with PBD dimers.

First claim

The invention claimed is:

1. A conjugate of formula ConjA:

wherein Ab is an antibody that binds to CD22, the antibody comprising a VH domain having the amino acid sequence according to SEQ ID NO. 1 and a VL domain having the amino acid sequence of SEQ ID NO. 2; and wherein the drug loading (p) of drugs (D) to antibody (Ab) is an integer from 1 to about 8.

2. The conjugate according to claim 1 , wherein the antibody is an intact antibody.

3. The conjugate according to claim 2 , wherein the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO. 3 paired with a light chain having the amino acid sequence of SEQ ID NO. 4.

4. The conjugate according to claim 3 , wherein the antibody comprises two heavy chains having the amino acid sequence of SEQ ID NO. 3, each paired with a light chain having the amino acid sequence of SEQ ID NO. 4.

5. The conjugate according to claim 1 , wherein the antibody is humanised, deimmunised, or resurfaced.

6. The conjugate according to claim 1 , wherein p is 1, 2, 3, or 4.

7. The conjugate according to claim 6 , comprising a mixture of the antibody-drug conjugate compounds, wherein the average drug loading per antibody in the mixture of antibody-drug conjugate compounds is about 2 to about 5.

8. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable diluent, carrier, or excipient.

9. The pharmaceutical composition of claim 8 , further comprising a therapeutically effective amount of a chemotherapeutic agent.

10. A method of treating a cancer expressing CD22 comprising administering to a patient the pharmaceutical composition of claim 8 .

11. The method of claim 10 , wherein the patient is administered a chemotherapeutic agent in combination with the conjugate.

Assignees

• Howard Philip Wilson
• Van Berkel Patricius Hendrikus Cornelis
• Adc Therapeutics S A
• Medimmune Ltd

Inventors

• Howard Philip Wilson
• Van Berkel Patricius Hendrikus Cornelis

Classifications

• C07K16/1145

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · CPC title

• A61K39/001113

  CD22, BL-CAM, siglec-2 or sialic acid- binding Ig-related lectin 2 · CPC title

• A61K47/68035

  the drug being a pyrrolobenzodiazepine · CPC title

• A61K31/551 Primary

  having two nitrogen atoms, e.g. dilazep · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title