IP Library › Granted Patent US 12,637,515
Granted Patent B2
US 12,637,515 · App. 17/172,700 · Granted May 26, 2026

Binding agents binding to PD-L1 and CD137 and use thereof

Inventors: Isil Altintas (Utrecht, NL); David Satijn (Utrecht, NL); Rik Rademaker (Utrecht, NL); Paul Parren (Odijk, NL); Ugur Sahin (Mainz, DE); Friederike Gieseke (Mainz, DE); Alexander Muik (Mainz, DE); Christian Grunwitz (Mainz, DE); Edward Van Den Brink (Utrecht, NL); Dennis Verzijl (Utrecht, NL)
Assignee: GENMAB A/S
C07K16/2878C07K16/2827C07K2317/24C07K2317/31C07K2317/33C07K2317/565C07K2317/76
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Quick Facts
Patent No.
US 12,637,515
App. No.
17/172,700
Granted
May 26, 2026
Kind
B2
Abstract

The present invention relates to novel binding agents and their use in medicine. In particular, the invention relates to binding agents such as bispecific antibodies binding human PD-L1 and binding human CD137. The invention furthermore relates to uses of the antibodies of the invention and to methods, nucleic acid constructs and host cells for producing antibodies of the invention.

Claims (26)

1 . A method of treating cancer in a subject in need thereof, the method comprising administering a multispecific antibody to the subject, wherein the multispecific antibody comprises a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, wherein

(i) the first antigen-binding region comprises a first heavy chain variable region (VH) and a first light chain variable region (VL), wherein the first VH comprises a first HCDR1 sequence, a first HCDR2 sequence, and a first HCDR3 sequence, wherein the first HCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 9, the first HCDR2 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 10, and the first HCDR3 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 11, and wherein the first VL comprises a first LCDR1 sequence, a first LCDR2 sequence, and a first LCDR3 sequence, wherein the first LCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 13, the first LCDR2 sequence comprises the amino acid sequence GAS, and the first LCDR3 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 14; and

(ii) the second antigen-binding region comprises a second heavy chain variable region (VH) and a second light chain variable region (VL), wherein the second VH comprises a second HCDR1 sequence, a second HCDR2 sequence, and a second HCDR3 sequence, wherein the second HCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 18, the second HCDR2 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 19, and the second HCDR3 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 20, and wherein the second VL comprises a second LCDR1 sequence, a second LCDR2 sequence, and a second LCDR3 sequence, wherein the second LCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 22, the second LCDR2 sequence comprises the amino acid sequence DDN, and wherein the LCDR3 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 23, thereby treating cancer in the subject.

2 . The method according to claim 1 , wherein

(i) the first VH comprises the amino acid sequence as set forth in SEQ ID NO: 15; and

(ii) the second VH comprises the amino acid sequence as set forth in SEQ ID NO: 17.

3 . The method according to claim 1 , wherein

(i) the first VH comprises the amino acid sequence as set forth in SEQ ID NO: 15 and the first VL comprises the amino acid sequence as set forth in SEQ ID NO: 16; and

(ii) the second VH comprises the amino sequence as set forth in SEQ ID NO: 17 and the second VL comprises the amino acid sequence as set forth in SEQ ID NO:21.

4 . The method according to claim 1 , wherein the cancer is characterized by the presence of solid tumors or is selected from the group consisting of: melanoma, ovarian cancer, lung cancer, colon cancer and head and neck cancer.

5 . The method according to claim 4 , wherein the cancer is non-small cell lung cancer (NSCLC).

6 . A method of treating cancer in a subject in need thereof, the method comprising administering a multispecific antibody to the subject, wherein the multispecific antibody comprises:

(i) a first antigen-binding region capable of binding to human CD137, wherein the first antigen binding region comprises a first heavy chain variable region (VH) comprising a first HCDR1 sequence, a first HCDR2 sequence, and a first HCDR3 sequence, wherein the first HCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 9, the first HCDR2 comprises the amino acid sequence as set forth in SEQ ID NO: 10, and the first HCDR3 comprises the amino acid sequence as set forth in SEQ ID NO: 11, and wherein said first antigen-binding region further comprises a light chain variable region (VL) comprising a first LCDR1 sequence, a first LCDR2 sequence, and a first LCDR3 sequence, wherein the first LCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 13, the first LCDR2 sequence comprises the amino acid sequence GAS, and the first LCDR3 sequence comprises the amino acid sequence set forth in SEQ ID NO:14; wherein the first antigen binding region further comprises a first heavy chain constant region (CH), wherein in said first CH at least one of the amino acids in a position corresponding to a position selected from the group consisting of T366, L368, K370, D399, F405, Y407, and K409 in a human IgG1 heavy chain according to EU numbering has been substituted, and

(ii) a second antigen-binding region capable of binding to human PD-L1, wherein said second antigen-binding region comprises a second VH comprising a second HCDR1 sequence, a second HCDR2 sequence, and a second HCDR3 sequence, wherein the second HCDR1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 18, the second HCDR2 comprises the amino acid sequence as set forth in SEQ ID NO: 19, and the second HCDR3 comprises the amino acid sequence as set forth in SEQ ID NO: 20, and wherein said second antigen-binding region further comprises a second VL comprising a second LCDR1 sequence, a second LCDR2 sequence, and a second LCDR3 sequence, wherein the second LCDR 1 sequence comprises the amino acid sequence as set forth in SEQ ID NO: 22, the second LCDR2 sequence comprises the amino acid sequence DDN, and the second LCDR3 sequence comprises the amino acid sequence set forth in SEQ ID NO:23; and wherein the second antigen binding region further comprises a second CH, wherein in said second CH at least one of the amino acids in a position corresponding to a position selected from the group consisting of T366, L368, K370, D399, F405, Y407, and K409 in a human IgG1 heavy chain according to EU numbering has been substituted, and wherein said first and said second heavy chains are not substituted in the same positions, thereby treating cancer in the subject.

7 . The method of claim 6 , wherein (i) the amino acid in the position corresponding to F405 in a human IgG1 heavy chain according to EU numbering is L in said first CH, and the amino acid in the position corresponding to K409 in a human IgG1 heavy chain according to EU numbering is R in said second CH, or (ii) the amino acid in the position corresponding to K409 in a human IgG1 heavy chain according to EU numbering is R in said first CH, and the amino acid in the position corresponding to F405 in a human IgG1 heavy chain according to EU numbering is L in said second CH.

8 . The method of claim 6 , wherein in at least one of said first and second CH one or more amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain according to EU numbering, are not L, L, D, N, and P, respectively.

9 . The method according to claim 8 , wherein the positions corresponding to positions L234, L235, and D265 in a human IgG1 heavy chain according to EU numbering are F, E, and A, respectively, in said first and second CH.

10 . The method according to claim 6 , wherein the position corresponding to positions L234, L235 and D265 in a human IgG1 heavy chain according to EU numbering are F, E, and A, respectively, in said first and second CH, and wherein (i) the amino acid in the position corresponding to F405 in a human IgG1 heavy chain according to EU numbering is L in said first CH, and the amino acid in the position corresponding to K409 in a human IgG1 heavy chain according to EU numbering is R in said second CH, or (ii) the amino acid in the position corresponding to K409 in a human IgG1 heavy chain according to EU numbering is R in said first CH and the amino acid in the position corresponding to F405 in a human IgG1 heavy chain according to EU numbering is L in said second CH.

11 . The method according to claim 6 , wherein the VH of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:15.

12 . The method according to claim 11 , wherein the VL of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:16.

13 . The method according to claim 6 , wherein VH of the second antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:17.

14 . The method according to claim 13 , wherein the VL of the second antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:21.

15 . The method according to claim 6 , wherein the VH of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:15, wherein the VL of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO: 16, wherein the VH of the second antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:17, wherein the VL of the second antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:21, and wherein (i) the first CH comprises amino acid sequence at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 24 and the second CH comprises amino acid sequence at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 25, or (ii) the first CH comprises amino acid sequence at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 25 and the second CH comprises amino acid sequence at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 24.

16 . The method according to claim 15 , wherein (i) the first CH comprises the amino acid sequence set forth in SEQ ID NO: 24 and the second CH comprises the amino acid sequence set forth in SEQ ID NO: 25, or (ii) the first CH comprises the amino acid sequence set forth in SEQ ID NO: 25 and the second CH comprises the amino acid sequence set forth in SEQ ID NO: 24.

17 . The method according to claim 6 , wherein the cancer is characterized by the presence of solid tumors or is selected from the group consisting of: melanoma, ovarian cancer, lung cancer, colon cancer and head and neck cancer.

18 . The method according to claim 17 , wherein the cancer is non-small cell lung cancer (NSCLC).

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2026
From: BIONTECH SE
To: GENMAB A/S
Reel/Frame 074463/0678 →
CHANGE OF ADDRESS Recorded Feb 13, 2024
From: GENMAB A/S
To: GENMAB A/S
Reel/Frame 066570/0587 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2022
From: ALTINTAS, ISIL; SATIJN, DAVID; RADEMAKER, RIK; PARREN, PAUL
To: GENMAB A/S
Reel/Frame 060892/0605 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2022
From: SAHIN, UGUR; GIESEKE, FRIEDERIKE; MUIK, ALEXANDER; GRUNWITZ, CHRISTIAN
To: BIONTECH AG
Reel/Frame 060892/0614 →
CHANGE OF NAME Recorded Aug 24, 2022
From: BIONTECH AG
To: BIONTECH SE
Reel/Frame 061314/0036 →
Continuity (3)
Division 16779011 · Jan 31, 2020
Continuation PCTEP2018071002 · Aug 2, 2018
Related Publication 20210277133A1 · Sep 9, 2021
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