Granted Patent B2

US 12,492,238 · App. 17/985,012 · Granted Dec 9, 2025

Inventors: Dasa Lipovsek (Pepperell, MA); Joseph Toth (Waltham, MA); Ginger C. Rakestraw (Somerville, MA); Irvith M. Carvajal (Brighton, MA); Stanley Richard Krystek, Jr. (Ringoes, NJ); Steven R. O'Neil (Wayland, MA); Guodong Chen (East Brunswick, NJ); Richard Y. Huang (Bridgewater, NJ); Bryan C. Barnhart (Vancouver, CA); John Thomas Loffredo (Yardley, PA); Christina Terragni (Wilmington, MA)

Assignee: Bristol-Myers Squibb Company

C07K14/78A61K47/60A61K47/64A61K47/6435G01N33/6872A61K38/00

Abstract

Claims (23)

1 . A method of producing a polypeptide comprising a tenth fibronectin type III ( 10 Fn3) domain comprising BC, DE and FG loops, wherein the polypeptide binds specifically to human glypican-3 (GPC3), and wherein

(a) the BC, DE and FG loops comprise SEQ ID NOs: 6, 7 and 8, respectively;

(b) the BC, DE and FG loops comprise SEQ ID NOs: 19, 20 and 21, respectively;

(c) the BC, DE and FG loops comprise SEQ ID NOs: 32, 33 and 34, respectively;

(d) the BC, DE and FG loops comprise SEQ ID NOs: 45, 46 and 47, respectively;

(e) the BC, DE and FG loops comprise SEQ ID NOs: 58, 59 and 60, respectively;

(f) the BC, DE and FG loops comprise SEQ ID NOs: 71, 72 and 73, respectively;

(g) the BC, DE and FG loops comprise SEQ ID NOs: 84, 85 and 86, respectively;

(h) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 101, respectively;

(i) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 129, respectively;

(j) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 156, respectively;

(k) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 183, respectively;

(l) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 210, respectively;

(m) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 237, respectively;

(n) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 264, respectively;

(o) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 291, respectively; or

(p) the BC, DE and FG loops comprise SEQ ID NOs: 99, 100 and 318, respectively, and

the method comprising culturing a cell expressing a nucleic acid encoding the polypeptide under conditions suitable for expressing the polypeptide, and purifying the polypeptide.

2 . The method of claim 1 , wherein the nucleic acid encodes a polypeptide comprising an amino acid sequence at least 90% identical to the amino acid sequence of any one of SEQ ID NOs: 5, 9-18, 22-31, 35-44, 48-57, 61-70, 74-83, 87-98, 102-128, 130-155, 157-182, 184-209, 211-236, 238-263, 265-290, 292-317 or 319-343.

3 . The method of claim 1 , wherein the nucleic acid encodes a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 5, 9-18, 22-31, 35-44, 48-57, 61-70, 74-83, 87-98, 102-128, 130-155, 157-182, 184-209, 211-236, 238-263, 265-290, 292-317 and 319-343.

4 . The method of claim 1 , wherein the nucleic acid encodes a polypeptide further comprising a heterologous protein.

5 . The method of claim 4 , wherein the heterologous protein comprises a polypeptide selected from the group consisting of a 10 Fn3 domain, an Fc, Fc fragment, transferrin, serum albumin, a serum albumin binding protein, and a serum immunoglobulin binding protein.

6 . The method of claim 1 , wherein the C-terminus of the 10 Fn3 domain comprises a moiety consisting of the amino acid sequence P m X n , wherein P is proline, each X is independently any amino acid, m is an integer that is at least 1 and n is 0 or an integer that is at least 1.

Assignments (2)

Continuity (4)

References Cited (30)