Compositions comprising anti-CEACAM1 and anti-PD antibodies for cancer therapy

• US 10,081,679 B2
• Filed: 11/25/2014
• Issued: 09/25/2018
• Est. Priority Date: 11/25/2013
• Status: Active Grant

• Current Assignee: FameWave Ltd. (Purple Biotech Ltd.)
• Original Assignee: Ccam Biotherapeutics Ltd. (Merck & Co., Inc.)
• Inventors: Ben-Moshe, Tehila, Sapir, Yair, Mandel, Ilana, Meilin, Edna
• Primary Examiner(s): Goddard, Laura B
• Assistant Examiner(s): Natarajan, Meera
• Application Number:
  US15/039,022
• Publication Number:
  US 20170166637A1
• Time in Patent Office: 1,400 Days
• Field of Search: None
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/464411 Immunoglobulin superfamily
• CPC Class Codes: A61K 39/464413 CD22, BL-CAM, siglec-2 or sialic acid binding Ig-related lectin 2
• CPC Class Codes: A61K 39/464482 Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention provides compositions comprising anti-CEACAM1 antibodies, compositions comprising antibodies capable of inhibiting or blocking the interaction between PD-1 and its ligands, and methods for their combined use in treating cancer.

Claims

1. A composition comprising:

a pharmaceutical composition comprising a monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof having a heavy-chain CDR1 comprising a sequence set forth in SEQ ID NO;

1, a heavy-chain CDR2 comprising a sequence set forth in SEQ ID NO;

2, a heavy-chain CDR3 comprising a sequence set forth in SEQ ID NO;

3, a light-chain CDR1 comprising a sequence set forth in SEQ ID NO;

4, a light-chain CDR2 comprising a sequence set forth in SEQ ID NO;

5 and a light-chain CDR3 comprising a sequence set forth in SEQ ID NO;

6; and

a pharmaceutical composition comprising a monoclonal antibody to at least one of human PD-1, PD-L1 and PD-L2 or an antigen-binding fragment thereof, capable of disrupting the binding of PD-1 to its ligands;

wherein said pharmaceutical compositions are in separate containers.

2. The composition of claim 1, comprising a monoclonal antibody to human CEACAM1 and a monoclonal antibody to human PD-1.

3. The composition of claim 1, wherein said monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof is capable of binding with an affinity of at least about 10⁻

8M to human CEACAM1.

4. The composition of claim 1, wherein said monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof is capable of binding with an affinity of at least about 5×

10<sup>−

7</sup>M to at least one of human CEACAM3 and human CEACAM5.

5. The composition of claim 1, wherein said monoclonal antibody to human CEACAM1 is CM-24 or an antigen-binding fragment thereof.

6. The composition of claim 2, wherein said monoclonal antibody to human PD-1 is selected from the group consisting of MK-3475, AMP514, BMS-936558, CT-011, antigen-binding fragments thereof, and any combination thereof.

7. The composition of claim 1, wherein said monoclonal antibodies are human or humanized monoclonal antibodies.

8. The composition of claim 1, further comprising a human lymphocyte cell.

18. The composition of claim 1, wherein said monoclonal antibody to human PD-L1 is selected from the group consisting of MEDI-4736, BMS-936559, MSB0010718C, MPDL3280A, antigen-binding fragments thereof, and any combination thereof.

9. A method for treating a patient having cancer, comprising the steps of separately administering to said patient:

(i) a pharmaceutical composition comprising a monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof, capable of blocking CEACAM1 ligand having a heavy-chain CDR1 comprising a sequence set forth in SEQ ID NO;

1, a heavy-chain CDR2 comprising a sequence set forth in SEQ ID NO;

2, a heavy-chain CDR3 comprising a sequence set forth in SEQ ID NO;

3, a light-chain CDR1 comprising a sequence set forth in SEQ ID NO;

4, a light-chain CDR2 comprising a sequence set forth in SEQ ID NO;

5 and a light-chain CDR3 comprising a sequence set forth in SEQ ID NO;

6; and

(ii) a pharmaceutical composition comprising a monoclonal antibody to at least one of human PD-1, PD-L1 and PD-L2 or an antigen-binding fragment thereof, capable of disrupting the binding of PD-1 to its ligands;

thereby treating said cancer.

10. The method of claim 9, comprising separately administering to said patient:

(i) a pharmaceutical composition comprising said monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof; and

(ii) a pharmaceutical composition comprising said monoclonal antibody to human PD-1 or an antigen-binding fragment thereof.

11. The method of claim 9, wherein said monoclonal antibody to human PD-1, PD-L1 and PD-L2 is administered to said patient before said monoclonal antibody to human CEACAM1.

12. The method of claim 9, wherein said monoclonal antibody to human PD-1, PD-L1 and PD-L2 is administered to said patient simultaneously with said monoclonal antibody to human CEACAM1.

13. The method of claim 9, wherein said monoclonal antibody to human PD-1, PD-L1 and PD-L2 is administered to said patient after said monoclonal antibody to human CEACAM1.

14. The method of claim 9, further comprising administering to said patient a pharmaceutical composition comprising a lymphocyte cell.

15. The method of claim 9, wherein said cancer expresses CEACAM1, PD-1, PD-L1, PD-L2, or any combination thereof.

16. The method of claim 9, wherein said cancer is selected from the group consisting of a melanoma, lymphoma, lung, thyroid, breast, colon, prostate, hepatic, bladder, renal, cervical, pancreatic, leukemia, myeloid, ovarian, uterus, sarcoma, biliary, and endometrial cells cancers.

17. A kit comprising:

(i) a pharmaceutical composition comprising a monoclonal antibody to human CEACAM1 or an antigen-binding fragment thereof, having a heavy-chain CDR1 comprising a sequence set forth in SEQ ID NO;

1, a heavy-chain CDR2 comprising a sequence set forth in SEQ ID NO;

2, a heavy-chain CDR3 comprising a sequence set forth in SEQ ID NO;

3, a light-chain CDR1 comprising a sequence set forth in SEQ ID NO;

4, a light-chain CDR2 comprising a sequence set forth in SEQ ID NO;

5 and a light-chain CDR3 comprising a sequence set forth in SEQ ID NO;

6; and

(ii) a pharmaceutical composition comprising a monoclonal antibody to at least one of human PD-1, PD-L1 and PD-L2 or an antigen-binding fragment thereof, capable of disrupting the binding of PD-1 to its ligands.