Checkpoint Inhibitor Bispecific Antibodies

Patent metadata

Field	Value
Publication number	US-2019010232-A1
Application number	US-201816029979-A
Country	US
Kind code	A1
Filing date	Jul 9, 2018
Priority date	Jul 10, 2017
Publication date	Jan 10, 2019
Grant date	—

Abstract

The present invention relates to antibodies that are heterodimeric and bind human PD-L1 and human PD-1, and may be useful for treating cancer alone and in combination with chemotherapy and other cancer therapeutics.

First claim

We claim:

1 . An antibody that binds human PD-L1 (SEQ ID NO: 1) and human PD-1 (SEQ ID NO: 2) comprising:
a) a first heavy chain (HC1) comprising, in order from the N-terminus to the C-terminus, a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 3, the amino acid sequence of SEQ ID NO: 9 in the CH1 domain, the amino acid sequence of SEQ ID NO: 10 in the CH2 domain, and the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO: 12 in the CH3 domain; b) a first light chain (LC1) comprising, in order from the N-terminus to the C-terminus, a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 4 and the amino acid sequence of SEQ ID NO: 14 in the constant region; c) a second heavy chain (HC2) comprising, in order from the N-terminus to the C-terminus, a HCVR comprising the amino acid sequence of SEQ ID NO: 5, the amino acid sequence of SEQ ID NO: 13 in the CH1 domain, the amino acid sequence of SEQ ID NO: 10 in the CH2 domain, and the amino acid sequence of SEQ ID NO: 12 or the amino acid sequence of SEQ ID NO: 11 in the CH3 domain; and d) a second light chain (LC2) comprising, in order from N-terminus, a LCVR comprising the amino acid sequence of SEQ ID NO: 8 and the amino acid sequence of SEQ ID NO: 15 in the constant region, provided that when the amino acid sequence of SEQ ID NO: 11 is present in the CH3 domain of said HC1, the amino acid sequence of SEQ ID NO: 12 is present in the CH3 domain of said HC2; or when the amino acid sequence of SEQ ID NO: 12 is present in the CH3 domain of said HC1, the amino acid sequence of SEQ ID NO: 11 is present in the CH3 domain of said HC2.

2 . The antibody of claim 1 , wherein said HC1 comprises the amino acid sequence of SEQ ID NO: 11 in the CH3 domain, and wherein said HC2 comprises the HCVR comprising the amino acid sequence of SEQ ID NO: 6 and said HC2 comprises the amino acid sequence of SEQ ID NO: 12 in the CH3 domain.

3 . The antibody of claim 1 , wherein said HC1, LC1, HC2, and LC2 comprises the amino acid sequences of SEQ ID NO: 49, SEQ ID NO: 30, SEQ ID NO 31, and SEQ ID NO: 34, respectively.

4 . The antibody of claim 1 , wherein said HC1, LC1, HC2, and LC2 comprises the amino acid sequences of SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 33, and SEQ ID NO: 34, respectively.

5 . A mammalian cell comprising a DNA molecule comprising a polynucleotide sequence encoding polypeptides having the amino acid sequences of SEQ ID NO: 49, SEQ ID NO: 30, SEQ ID NO: 31, and SEQ ID NO: 34, wherein the cell is capable of expressing the antibody of claim 3 .

6 . A mammalian cell comprising a DNA molecule comprising a polynucleotide sequence encoding polypeptides having the amino acid sequences of SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 33, and SEQ ID NO: 34, wherein the cell is capable of expressing the antibody of claim 4 .

7 . A process for producing an antibody comprising cultivating the mammalian cell of claim 5 under conditions such that the antibody is expressed, and recovering the expressed antibody.

8 . A process for producing an antibody comprising cultivating the mammalian cell of claim 6 under conditions such that the antibody is expressed, and recovering the expressed antibody.

9 . A pharmaceutical composition, comprising the antibody of claim 3 and an acceptable carrier, diluent, or excipient.

10 . A method of treating cancer, comprising administering to a patient in need thereof, an effective amount of the antibody of claim 3 .

11 . The method of claim 10 , wherein the cancer is Hodgkin's or non-Hodgkin's lymphomas, melanoma, renal cell cancer, kidney cancer, lung cancer, bladder cancer, gastric and esophageal cancer, colorectal cancer, liver cancer, hepatocellular cancer, cholangiocarcinoma, pancreatic cancer, breast cancer, triple-negative breast cancer, ovarian cancer, endometrial cancer, prostate cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), mesothelioma, squamous cancer of head neck cancer (SCCHN), soft tissue sarcoma, or glioblastoma multiforme.

12 . The method of claim 11 , wherein the lung cancer is NSCLC, small cell lung cancer, or mesothelioma.

13 . The method of claim 11 , further comprising administering simultaneously, separately, or sequentially one or more antitumor agents selected from the group consisting of cisplatin, carboplatin, dacarbazine, liposomal doxorubicin, docetaxel, cyclophosphamide and doxorubicin, navelbine, eribulin, paclitaxel, paclitaxel protein-bound particles for injectable suspension, ixabepilone, capecitabine, FOLFOX (leucovorin, fluorouracil, and oxaliplatin), FOLFIRI (leucovorin, fluorouracil, and irinotecan), gemcitabine, topotecan, liposomal irinotecan, pemetrexed, cetuximab, nivolumab, ipilimumab, pidilizumab, pembrolizumab, tremelimumab, urelumab, lirilumab, atezolizumab, epacadostat, and durvalumab.

Assignees

• Lilly Co Eli
• Zymeworks Inc

Inventors

• Kalos Michael Dewain
• Li Yiwen
• Ludwig Dale Lincoln
• Shen Yang
• D'Angelo Igor Edmondo Paolo
• Plowman Gregory D

Classifications

• C07K16/468

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title

• C07K2317/64

  comprising a combination of variable region and constant region components · CPC title

• C07K2317/524

  CH2 domain · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K2039/505

  comprising antibodies · CPC title