Anti-CLL-1 antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-11466087-B2
Application number	US-201916658706-A
Country	US
Kind code	B2
Filing date	Oct 21, 2019
Priority date	Jun 16, 2015
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

The present invention relates to anti-CLL-1 antibodies including anti-CLL-1 antibodies comprising a CLL-1 binding domain and a CD3 binding domain (e.g., anti-CLL-1/CD3 T cell dependent bispecific (TDB) antibody) and methods of using the same.

First claim

What is claimed is:

1. A method of treating or delaying the progression of a cell proliferative disorder in a subject in need thereof, the method comprising administering to the subject an anti-CLL-1 antibody, wherein the antibody comprises:
(a) a CLL-1 binding domain, wherein the CLL-1 binding domain comprises six hypervariable regions (HVRs) as follows:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 5, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 45 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; or
(ii) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 13, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 14, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 16 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 17; or
(iii) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 18, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 19, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 20, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 21, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 22 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 23; or
(iv) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 25, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 27, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 28 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 29; and

(b) a CD3 binding domain, wherein the CD3 binding domain comprises six HVRs as follows:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 74, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 75, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 76, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 72 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73; or
(ii) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 74, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 80, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 76, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 77, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 78 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 79; or
(iii) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 74, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 80, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 81, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 77, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 78 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 79.

2. The method of claim 1 , wherein the cell proliferative disorder is a cancer.

3. The method of claim 2 , wherein the cell proliferative disorder is AML, CML, and/or MDS.

4. The method of claim 1 , further comprising administering to the subject daunorubicin and/or cytarabine.

5. The method of claim 1 , further comprising administering to the subject a glucocorticoid.

6. The method of claim 5 , wherein the glucocorticoid is dexamethasone.

7. The method of claim 1 , further comprising administering to the subject a PD-1 axis binding antagonist.

8. The method of claim 7 , wherein the PD-1 axis binding antagonist is an anti-PD-L1 antibody.

9. The method of claim 1 , wherein the antibody comprises:
(a) a CLL-1 binding domain, wherein the CLL-1 binding domain comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 31 and a light chain comprising the amino acid sequence of SEQ ID NO: 30; or
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 33 and a light chain comprising the amino acid sequence of SEQ ID NO: 32; or
(iii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 34 and a light chain comprising the amino acid sequence of SEQ ID NO: 32; or
(iv) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 36 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 35; or
(v) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 37; or
(vi) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 40 and a light chain comprising the amino acid sequence of SEQ ID NO: 39; or
(vii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 41; or
(viii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 46 and a light chain comprising the amino acid sequence of SEQ ID NO: 32;

and
(b) a CD3 binding domain comprising:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 82 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 83; or
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 84 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 93; or
(iii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 84 and the light chain variable region comprising the amino acid sequence of SEQ ID NO: 85.

10. The method of claim 1 , wherein the CLL-1 binding domain comprises the following six hypervariable regions (HVRs): (a) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:5; (b) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:6; (c) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:7; (d) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:8; (e) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:45; and (f) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:10.

11. The method of claim 10 , wherein the CLL-1 binding domain comprises HVR-H2 comprising the amino acid sequence of SEQ ID NO:11.

12. The method of claim 1 , wherein the CD3 binding domain comprises an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 71, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 72, an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 73, an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 74, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 75, and an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 76.

13. A method of enhancing immune function in a subject having a cell proliferative disorder, the method comprising administering to the subject an effective amount of an anti-CLL-1 antibody, wherein the antibody comprises:
(a) a CLL-1 binding domain, wherein the CLL-1 binding domain comprises six hypervariable regions (HVRs) as follows:
(i) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 5, an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 6, an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 7, an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 8, an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 45 and an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; or
(ii)

Assignees

• Genentech Inc

Inventors

• Kelley Robert F
• Leong Steven R
• Liang Wei-Ching
• Mathieu Mary
• Polson Andrew G
• Zheng Bing
• Chen Xiaocheng
• Chiu Cecilia Pui Chi
• Dennis Mark S
• Ebens Allen
• Wu Yan

Classifications

• C07K16/2803

  against the immunoglobulin superfamily · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C07K2317/55

  Fab or Fab' · CPC title