Granted Patent B2

US 12,674,002 · App. 17/783,506 · Granted Jul 7, 2026

Inventors: Bert Vogelstein (Baltimore, MD); Kenneth W. Kinzler (Frankford, DE); Emily Han-Chung Hsiue (Baltimore, MD); Jacqueline Douglass (Baltimore, MD); Michael S. Hwang (Seattle, WA); Alexander H. Pearlman (Baltimore, MD); Nickolas Papadopoulos (Towson, MD); Shibin Zhou (Owings Mills, MD); Brian J. Mog (Baltimore, MD); Katharine M. Wright (Baltimore, MD); Sandra B. Gabelli (Ellicott City, MD)

Assignee: The Johns Hopkins University

C07K16/30A61P35/00C07K16/2809A61K39/395A61K2039/505C07K2317/24C07K2317/622

Abstract

Claims (20)

1 . A molecule comprising an antigen-binding domain comprising a variable heavy chain and a variable light chain that can bind to a peptide-HLA complex, wherein said peptide is a modified p53 peptide comprising the amino acid sequence set forth in SEQ ID NO:1, wherein the antigen-binding domain comprises a CDR-VL1, a CDR-VL2, a CDR-VL3, a CDR-VH1, a CDR-VH2, and a CDR-VH3 as set forth in one of the groups below:

(i) the CDR-VL1 set forth in SEQ ID NO:5, the CDR-VL2 having the amino acid sequence SAY or SAS, the CDR-VL3 set forth in SEQ ID NO:6, the CDR-VH1 set forth in SEQ ID NO: 11, the CDR-VH2 set forth in SEQ ID NO:16, and the CDR-VH3 set forth in SEQ ID NO: 21;

(ii) the CDR-VL 1 set forth in SEQ ID NO:5, the CDR-VL2 having the amino acid sequence SAY or SAS, the CDR-VL3 set forth in SEQ ID NO:7, the CDR-VH1 set forth in SEQ ID NO: 12, the CDR-VH2 set forth in SEQ ID NO: 17, and the CDR-VH3 set forth in SEQ ID NO: 22;

(iii) the CDR-VL 1 set forth in SEQ ID NO:5, the CDR-VL2 having the amino acid sequence SAY or SAS, the CDR-VL3 set forth in SEQ ID NO:8, the CDR-VH1 set forth in SEQ ID NO: 13, the CDR-VH2 set forth in SEQ ID NO: 18, and the CDR-VH3 set forth in SEQ ID NO: 23;

(iv) the CDR-VL1 set forth in SEQ ID NO:5, the CDR-VL2 having the amino acid sequence SAY or SAS, the CDR-VL3 set forth in SEQ ID NO:9, the CDR-VH1 set forth in SEQ ID NO: 14, the CDR-VH2 set forth in SEQ ID NO: 19, and the CDR-VH3 set forth in SEQ ID NO: 24; and

(v) the CDR-VL 1 set forth in SEQ ID NO:5, the CDR-VL2 having the amino acid sequence SAY or SAS, the CDR-VL3 set forth in SEQ ID NO:10, the CDR-VH1 set forth in SEQ ID NO:15, the CDR-VH2 set forth in SEQ ID NO:20, and the CDR-VH3 set forth in SEQ ID NO: 25.

2 . The molecule of claim 1 , wherein said antigen binding domain comprises an amino acid sequence having at least 90% identity to the amino acid sequence set forth in SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, or SEQ ID NO:141.

3 . The molecule of claim 1 , wherein said molecule is selected from the group consisting of an antibody, a single chain variable fragment (scFv), a chimeric antigen receptor (CAR), a tandem scFv, a bispecific T cell engager, a diabody, a single-chain diabody (scDb), an scFv-Fc, a bispecific antibody, and a dual-affinity re-targeting antibody.

4 . The molecule of claim 1 , wherein said molecule further comprises a second antigen-binding domain comprising a variable heavy chain and a variable light chain that binds to an effector cell receptor selected from the group consisting of CD3, CD28, CD4, CD8, CD16a, NKG2D, PD-1, CTLA-4, 4-1BB, OX40, ICOS, and CD27.

5 . The molecule of claim 4 , wherein said second antigen-binding domain binds to CD3, and wherein said second antigen-binding domain comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO:176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO:181, SEQ ID NO:182, and SEQ ID NO:183.

6 . The molecule of claim 4 , wherein the second antigen-binding domain binds CD3 and comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, and SEQ ID NO: 175.

7 . The molecule of claim 4 , wherein said second antigen-binding domain binds CD16a and wherein said second antigen-binding domain comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO:188, and SEQ ID NO: 189.

8 . The molecule of claim 1 , wherein said antigen binding domain comprises an amino acid sequence having at least 95% identity to the amino acid sequence set forth in SEQ ID NO: 137, SEQ ID NO:138, SEQ ID NO: 139, SEQ ID NO: 140, or SEQ ID NO: 141.

9 . The molecule of claim 1 , wherein said antigen binding domain comprises a VL having at least 95% identity to SEQ ID NO:729 and/or a VH having at least 95% identity to SEQ ID NO:730.

10 . The molecule of claim 1 , wherein said antigen binding domain comprises a VL comprising the amino acid sequence set forth in SEQ ID NO:729 and a VH comprising the amino acid sequence set forth in SEQ ID NO:730.

11 . The molecule of claim 1 , wherein the HLA of the peptide-HLA complex is HLA-A*02:01.

12 . The molecule of claim 1 , wherein the HLA of the peptide/HLA complex comprises an HLA allele alpha chain and a beta-2 microglobulin.

13 . A method for treating a human having a cancer, said method comprising:

administering to said human the molecule of claim 1 , wherein said cancer comprises cancer cells expressing a modified p53 peptide comprising the amino acid sequence of SEQ ID NO: 1 .

14 . The method of claim 13 , wherein said cancer is selected from the group consisting of Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, lung cancer, pancreatic cancer, gastric cancer, colorectal cancer, ovarian cancer, endometrial cancer, biliary tract cancer, liver cancer, breast cancer, prostate cancer, esophageal cancer, stomach cancer, kidney cancer, bone cancer, soft tissue cancer, head and neck cancer, glioblastoma multiforme, astrocytoma, thyroid cancer, germ cell tumor, and melanoma.

Assignments (1)

Continuity (3)

References Cited (304)