Granted Patent B2

US 12,194,110 · App. 17/483,393 · Granted Jan 14, 2025

Inventors: Paul E. Morin (Pennington, NJ); David Donnelly (Doylestown, PA); Dasa Lipovsek (Pepperell, MA); Jochem Gokemeijer (Wayland, MA); Maria N. Jure-Kunkel (Plainsboro, NJ); David Fabrizio (South Hamilton, MA); Martin C. Wright (Belmont, MA); Douglas Dischino (Middlefield, CT); Samuel J. Bonacorsi, Jr. (Flemington, NJ); Ralph Adam Smith (Yardley, PA); Virginie Lafont (Lawrence Township, NJ); Daniel Cohen (New York, NY)

Assignee: Bristol-Myers Squibb Company

A61K51/08A61K51/088C07K14/78C12N5/00C12N15/09G01N33/57492G01N33/60G01N33/6872C07K2319/60C12N2330/50G01N2333/70532G01N2333/78

Abstract

Claims (74)

1. A method of detecting PD-L1 in a sample comprising

(a) contacting the sample with a polypeptide comprising a modified human fibronectin type III tenth domain ( 10 Fn3) comprising AB, BC, CD, DE, EF, and FG loops, wherein the polypeptide specifically binds to PD-L1; and

(b) detecting PD-L1,

wherein the BC, DE, and FG loops of the modified human 10 Fn3 domain comprise the amino acid sequences of:

(a) SEQ ID NOs: 6, 7 and 8, respectively;

(b) SEQ ID NOs: 21, 22 and 23, respectively;

(c) SEQ ID NOs: 36, 37 and 38, respectively;

(d) SEQ ID NOs: 51, 52 and 53, respectively;

(e) SEQ ID NOs: 66, 67 and 68, respectively;

(f) SEQ ID NOs: 81, 82 and 83, respectively;

(g) SEQ ID NOs: 97, 98 and 99, respectively;

(h) SEQ ID NOs: 113, 114 and 115, respectively;

(i) SEQ ID NOs: 124, 125 and 126, respectively;

(j) SEQ ID NOs: 135, 136 and 137, respectively;

(k) SEQ ID NOs: 146, 147 and 148, respectively;

(l) SEQ ID NOs: 157, 158 and 159, respectively;

(m) SEQ ID NOs: 168, 169 and 170, respectively;

(n) SEQ ID NOs: 179, 180 and 181, respectively;

(o) SEQ ID NOs: 190, 191 and 192, respectively;

(p) SEQ ID NOs: 201, 202 and 203, respectively;

(q) SEQ ID NOs: 212, 213 and 214, respectively;

(r) SEQ ID NOs: 223, 224 and 225, respectively;

(s) SEQ ID NOs: 234, 235 and 236, respectively;

(t) SEQ ID NOs: 245, 246 and 247, respectively;

(u) SEQ ID NOs: 256, 257 and 258, respectively;

(v) SEQ ID NOs: 267, 268 and 269, respectively;

(w) SEQ ID NOs: 278, 279 and 280, respectively;

(x) SEQ ID NOs: 289, 290 and 291, respectively;

(y) SEQ ID NOs: 300, 301 and 302, respectively;

(z) SEQ ID NOs: 311, 312 and 313, respectively;

(aa) SEQ ID NOs: 322, 323 and 324, respectively;

(bb) SEQ ID NOs: 333, 334 and 335, respectively;

(cc) SEQ ID NOs: 344, 345 and 346, respectively;

(dd) SEQ ID NOs: 355, 356 and 357, respectively;

(ee) SEQ ID NOs: 366, 367 and 368, respectively;

(ff) SEQ ID NOs: 377, 378 and 379, respectively;

(gg) SEQ ID NOs: 388, 389 and 390, respectively;

(hh) SEQ ID NOs: 399, 400 and 401, respectively;

(ii) SEQ ID NOs: 410, 411 and 412, respectively;

(jj) SEQ ID NOs: 421, 422 and 423, respectively;

(kk) SEQ ID NOs: 432, 433 and 434, respectively;

(ll) SEQ ID NOs: 443, 444 and 445, respectively;

(mm) SEQ ID NOs: 454, 455 and 456, respectively;

(nn) SEQ ID NOs: 465, 466 and 467, respectively;

(oo) SEQ ID NOs: 476, 477 and 478, respectively;

(pp) SEQ ID NOs: 487, 488 and 489, respectively;

(qq) SEQ ID NOs: 498, 499 and 500, respectively;

(rr) SEQ ID NOs: 509, 510 and 511, respectively;

(ss) SEQ ID NOs: 520, 521 and 522, respectively;

(tt) SEQ ID NOs: 531, 532 and 533, respectively;

(uu) SEQ ID NOs: 542, 543 and 544, respectively;

(vv) SEQ ID NOs: 553, 554 and 555, respectively; or

SEQ ID NOs: 564, 565 and 566, respectively.

2. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in any one of SEQ ID NOs: 5, 20, 35, 50, 65, 80, 96, 112, 123, 134, 145, 156, 167, 178, 189, 200, 211, 222, 233, 244, 255, 266, 277, 288, 299, 310, 321, 332, 343, 354, 365, 376, 387, 398, 409, 420, 431, 442, 453, 464, 475, 486, 497, 508, 519, 530, 541, 552 and 563.

3. The method of claim 1 , wherein the polypeptide comprises a detectable label.

4. The method of claim 3 , wherein the detectable label is a radionuclide.

5. The method of claim 4 , wherein the detectable label is an 18 F-radiolabeled prosthetic group.

6. The method of claim 1 , wherein the BC, DE and FG loops of the modified human 10 Fn3 domain comprise the amino acid sequences set forth in:

(a) SEQ ID NOs: 6, 7 and 8, respectively;

(b) SEQ ID NOs: 21, 22 and 23, respectively;

(c) SEQ ID NOs: 36, 37 and 38, respectively;

(d) SEQ ID NOs: 51, 52 and 53, respectively;

(e) SEQ ID NOs: 66, 67 and 68, respectively;

(f) SEQ ID NOs: 81, 82 and 83, respectively; or

(g) SEQ ID NOs: 97, 98 and 99, respectively.

7. The method of claim 6 , wherein the modified human 10 Fn3 domain comprises the amino acid sequence set forth in any one of SEQ ID NOs: 5, 20, 35, 65, 80 and 96.

8. The method of claim 1 , wherein the BC, DE and FG loops of the modified human 10 Fn3 domain comprise the amino acid sequences set forth in SEQ ID NOs: 81, 82 and 83, respectively.

9. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 80.

10. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 84.

11. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 88.

12. The method of claim 1 , wherein the BC, DE and FG loops of the modified human 10 Fn3 domain comprise the amino acid sequences set forth in SEQ ID NOs: 97, 98 and 99, respectively.

13. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 96.

14. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 100.

15. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 104.

Assignments (2)

Continuity (4)

References Cited (160)