Granted Patent B2

US 12,528,859 · App. 17/933,336 · Granted Jan 20, 2026

Inventors: Robert B. Dubridge (Belmont, CA); Bryan D. Lemon (Mountain View, CA); Richard J. Austin (San Francisco, CA); Luke Evnin (San Francisco, CA); Jeanmarie Guenot (San Francisco, CA)

Assignee: Harpoon Therapeutics, Inc.

C07K16/18C07K16/005C07K16/2809C07K16/2887A61K2039/505C07K2317/31C07K2317/33C07K2317/565C07K2317/567C07K2317/569C07K2317/92C07K2317/94

Abstract

Claims (26)

1 . A method for the treatment or amelioration of a proliferative disease, a tumorous disease, an inflammatory disease, an immunological disorder, an autoimmune disease, an infectious disease, a viral disease, an allergic reaction, a parasitic reaction, a graft-versus-host disease or a host-versus-graft disease in a subject in need thereof, the method comprising administering to the subject a multispecific protein, wherein the multispecific protein comprises a serum albumin binding domain, a target antigen binding domain, and a domain that binds to a protein within a T cell receptor complex (TCR),

wherein the serum albumin binding domain comprises complementarity determining regions CDR1, CDR2, and CDR3, wherein

(a) the amino acid sequence of CDR1 is as set forth in SEQ ID NO. 14, SEQ ID NO. 15 or SEQ ID NO. 16;

(b) the amino acid sequence of CDR2 is as set forth in SISGSGX 5 X 6 TLYAX 7 SX 8 K (SEQ ID NO. 2), wherein X 5 is serine, arginine, threonine, or alanine, X 6 is aspartic acid, histidine, valine, or threonine, X 7 is aspartic acid, histidine, arginine, or serine, and X 8 is valine or leucine; and

(c) the amino acid sequence of CDR3 is as set forth in GGSLX 9 X 10 (SEQ ID NO. 3), wherein X 9 is serine, arginine, threonine, or lysine, and X 10 is arginine, lysine, valine, proline, or asparagine,

wherein X 5 , X 6 , X 7 , X 8 , X 9 , and X 10 are not simultaneously serine, aspartic acid, aspartic acid, valine, serine, and arginine, respectively.

2 . The method of claim 1 , wherein the serum albumin binding domain is at least eighty percent identical to the amino acid sequence set forth in SEQ ID NO. 10.

3 . The method of claim 1 , wherein the CDR2 has an amino acid sequence as set forth in SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, or SEQ ID NO. 22.

4 . The method of claim 1 , wherein the CDR3 has an amino acid sequence as set forth in SEQ ID NO. 23 or SEQ ID NO. 24.

5 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 14.

6 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 15, the CDR2 has an amino acid sequence as set forth in SEQ ID NO. 17, and the CDR3 has an amino acid sequence as set forth in SEQ ID NO. 23.

7 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 16, and the CDR3 has an amino acid sequence as set forth in SEQ ID NO. 23.

8 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 15 and the CDR2 has an amino acid sequence as set forth in SEQ ID NO. 18.

9 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 14 and the CDR3 has an amino acid sequence as set forth in SEQ ID NO. 23.

10 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 15, the CDR2 comprises SEQ ID NO. 19 and the CDR3 comprises SEQ ID NO. 24.

11 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 14 and the CDR2 has an amino acid sequence as set forth in SEQ ID NO. 20.

12 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 15, and the CDR2 has an amino acid sequence as set forth in SEQ ID NO. 21.

13 . The method of claim 1 , wherein the CDR1 has an amino acid sequence as set forth in SEQ ID NO. 15, the CDR2 has an amino acid sequence as set forth in SEQ ID NO. 22 and the CDR3 has an amino acid sequence as set forth in SEQ ID NO. 24.

14 . The method of claim 1 , wherein the target antigen binding domain binds to a target antigen expressed on a tumor cell.

15 . The method of claim 1 , wherein the protein within the T cell receptor complex (TCR) is CD3.

16 . The method of claim 1 , wherein the serum albumin binding domain has an amino acid sequence selected from SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 25, SEQ ID NO. 26, and SEQ ID NO. 27.

17 . The method of claim 1 , wherein the subject is human.

18 . The method of claim 1 , wherein the method further comprises administering to the subject an additional agent in combination with the multispecific protein.

19 . The method of claim 1 , wherein the serum albumin binding domain has the amino acid sequence of SEQ ID NO. 9.

20 . The method of claim 1 , wherein the serum albumin binding domain comprises a single domain antibody, the target antigen binding domain comprises a single domain antibody, and the domain that binds to a protein within a TCR is an scFv.

21 . The method of claim 1 , wherein the proliferative disease or the tumorous disease is a cancer.

Assignments (1)

Continuity (4)

References Cited (400)