IP Library › Granted Patent US 11,173,219
Granted Patent B2
US 11,173,219 · App. 16/520,965 · Granted Nov 16, 2021

PD-L1 binding polypeptides for imaging

Inventors: Paul E. Morin (Pennington, NJ); David Donnelly (Doylestown, PA); Dasa Lipovsek (Pepperell, MA); Jochem Gokemeijer (Wayland, MA); Maria 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
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Quick Facts
Patent No.
US 11,173,219
App. No.
16/520,965
Granted
Nov 16, 2021
Kind
B2
Abstract

Provided herein are novel 10 Fn3 domains which specifically bind to PD-L1, as well as imaging agents based on the same for diagnostics.

Claims (77)

1. A nucleic acid encoding a polypeptide comprising a modified fibronectin type III tenth domain ( 10 Fn3), wherein the 10 Fn3 domain comprises AB, BC, CD, DE, EF, and FG loops and the polypeptide specifically binds to human Programmed Death Ligand-1 (PD-L1), and wherein the BC, DE, and FG loops of the modified 10 Fn3 domain comprise the amino acid sequences set forth in:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

(49) SEQ ID NOs: 564, 565 and 566, respectively.

2. The nucleic acid of claim 1 , wherein the nucleic acid encodes a polypeptide comprising 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. A vector comprising the nucleic acid of claim 1 .

4. A cell comprising the nucleic acid of claim 1 .

5. The nucleic acid of claim 1 , wherein the nucleic acid encodes a polypeptide comprising a modified human 10 Fn3 domain 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.

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

7. The nucleic acid of claim 5 , wherein the nucleic acid comprises the nucleotide sequence set forth in any of SEQ ID NOs: 16-19, 31-34, 46-49, 61-64, 76-79-92-95, and 108-111.

8. The nucleic acid of claim 1 , wherein the nucleic acid encodes a polypeptide comprising a modified human 10 Fn3 domain 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 nucleic acid of claim 8 , wherein the nucleic acid encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 80.

10. The nucleic acid of claim 8 , wherein the nucleic acid encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 84.

11. The nucleic acid of claim 8 , wherein the nucleic acid encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 88.

12. The nucleic acid of claim 8 , wherein the nucleic acid comprises the nucleotide sequence set forth in any of SEQ ID NOs: 92-95.

13. The nucleic acid of claim 12 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 92.

14. The nucleic acid of claim 12 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 94.

15. The nucleic acid of claim 1 , wherein the nucleic acid encodes a polypeptide comprising a modified human 10 Fn3 domain 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.

16. The nucleic acid of claim 15 , wherein the nucleic acid encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 96.

17. The nucleic acid of claim 15 , wherein the nucleic acid encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 100.

18. The nucleic acid of claim 15 , wherein the nucleic acid encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 104.

19. The nucleic acid of claim 15 , wherein the nucleic acid comprises the nucleotide sequence set forth in any one of SEQ ID NOs: 108-111.

20. The nucleic acid of claim 15 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 108.

21. The nucleic acid of claim 15 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 110.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2020
From: COHEN, DANIEL
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 053086/0773 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2020
From: MORIN, PAUL E.; DONNELLY, DAVID; LIPOVSEK, DASA; GOKEMEIJER, JOCHEM; JURE-KUNKEL, MARIA N.; FABRIZIO, DAVID; WRIGHT, MARTIN C.; DISCHINO, DOUGLAS; BONACORSI, SAMUEL J., JR.; LAFONT, VIRGINIE; SMITH, RALPH ADAM
To: BRISTOL-MYERS SQUIBB COMPANY
Reel/Frame 053086/0817 →
Continuity (3)
Division 15529260
Provisional Application 62084298 · Nov 25, 2014
Related Publication 20190343972A1 · Nov 14, 2019
Cited By (2)
US 12,194,110 US 12,529,165