IP Library › Granted Patent US 10,208,125

Granted Patent B2

US 10,208,125 · App. 14/904,575 · Granted Feb 19, 2019

Anti-mucin 1 binding agents and uses thereof

Inventors: Robert E. Schoen (Pittsburgh, PA); Olivera J. Finn (Pittsburgh, PA); Shuji Sato (Somerville, MA); Wan Cheung Cheung (Lexington, MA); Roberto D. Polakiewicz (Lexington, MA)

Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education; Bluefin BioMedicine, Inc.

C07K16/2896 C07K14/7051 C07K14/70521 C07K16/30 C07K16/3092 G01N33/57492 C07K2317/14 C07K2317/21 C07K2317/33 C07K2317/34 C07K2317/51 C07K2317/515 C07K2317/56 C07K2317/565 C07K2317/622 C07K2317/77 G01N2333/70596

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 10,208,125
App. No.: 14/904,575
Granted: Feb 19, 2019
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

This disclosure provides anti-MUC1 binding agents (e.g., antibodies and chimeric antigen receptors) and methods of treatment, prophylaxis, detection, and diagnosis using the same.

Claims (335)

1. A purified anti-MUC1 binding agent comprising:

(a) a heavy chain variable region having complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences of DYYMS (SEQ ID NO: 59), YISSSG(S/T)T(I/K)YYADSVKG (SEQ ID NO: 357), and E(R/N)(I/L)GYC(S/T)GG(S/N) C(Y/F)YYYYMDV (SEQ ID NO: 360), respectively; and a light chain variable region having CDRs 1, 2, 3, comprising the amino acid sequences of RSSQSL(V/L)(H/R)S(D/N)G(N/Y)TYL(S/H) (SEQ ID NO: 366), (K/R)(I/V)SN(R/H)(F/L)S (SEQ ID NO: 367), and (M/L)Q(A/G)(T/S)QFP(L/I/F/V)T (SEQ ID NO: 368), respectively;

(b) a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively; and a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 150, 152, and 154, respectively;

(ii) SEQ ID NOs: 159, 152, and 154, respectively; or

(iii) SEQ ID NOs: 150, 152, and 163, respectively;

(i) SEQ ID NOs: 16, 17, and 19, respectively;

(ii) SEQ ID NOs: 16, 24, and 19, respectively;

(iii) SEQ ID NOs: 29, 24, and 19, respectively;

(iv) SEQ ID NOs: 34, 17, and 36, respectively;

(v) SEQ ID NOs: 16, 17, and 36, respectively; or

(vi) SEQ ID NOs: 16, 43, and 36, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 176, 178, and 180, respectively;

(ii) SEQ ID NOs: 185, 187, and 180, respectively; or

(iii) SEQ ID NOs: 185, 138, and 180, respectively;

(d) a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 49, 51, and 53, respectively; and a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 195, 197, and 199, respectively;

(ii) SEQ ID NOs: 204, 205, and 199, respectively;

(iii) SEQ ID NOs: 195, 205, and 199, respectively;

(iv) SEQ ID NOs: 216, 217, and 199, respectively;

(v) SEQ ID NOs: 195, 205, and 221, respectively;

(vi) SEQ ID NOs: 195, 205, and 226, respectively;

(vii) SEQ ID NOs: 230, 205, and 226, respectively;

(viii) SEQ ID NOs: 236, 238, and 226, respectively;

(ix) SEQ ID NOs: 247, 205, and 226, respectively;

(x) SEQ ID NOs: 251, 205, and 226, respectively; or

(xi) SEQ ID NOs: 257, 238, and 226, respectively;

(e) a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 59, 61, and 63, respectively;

(ii) SEQ ID NOs: 59, 67, and 63, respectively;

(iii) SEQ ID NOs: 59, 61, and 72, respectively;

(iv) SEQ ID NOs: 59, 76, and 77, respectively;

(v) SEQ ID NOs: 59, 61, and 77, respectively;

(vi) SEQ ID NOs: 59, 67, and 116, respectively;

(vii) SEQ ID NOs: 59, 61, and 120, respectively;

(viii) SEQ ID NOs: 59, 61, and 84, respectively;

(ix) SEQ ID NOs: 59, 61, and 124, respectively;

(x) SEQ ID NOs: 59, 67, and 129, respectively; or

(xi) SEQ ID NOs: 59, 61, and 89, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 267, respectively;

(ii) SEQ ID NOs: 310, 311, and 267, respectively;

(iii) SEQ ID NOs: 263, 265, and 316, respectively;

(iv) SEQ ID NOs: 263, 265, and 320, respectively;

(v) SEQ ID NOs: 263, 265, and 325, respectively;

(vi) SEQ ID NOs: 263, 265, and 329, respectively;

(vii) SEQ ID NOs: 335, 265, and 337, respectively;

(viii) SEQ ID NOs: 263, 265, and 342, respectively;

(ix) SEQ ID NOs: 263, 265, and 271, respectively; or

(x) SEQ ID NOs: 263, 265, and 276, respectively;

(f) a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 94, 96, and 98, respectively;

(ii) SEQ ID NOs: 49, 51, and 103, respectively; or

(iii) SEQ ID NOs: 49, 110, and 112, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 267, respectively;

(ii) SEQ ID NOs: 310, 311, and 267, respectively;

(iii) SEQ ID NOs: 263, 265, and 271, respectively; or

(iv) SEQ ID NOs: 263, 265, and 276, respectively;

(g) a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively; and a light chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 150, 152, and 163, respectively;

(h) a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 59, 61, and 63, respectively;

(ii) SEQ ID NOs: 59, 67, and 63, respectively;

(iii) SEQ ID NOs: 59, 61, and 72, respectively;

(iv) SEQ ID NOs: 59, 76, and 77, respectively;

(v) SEQ ID NOs: 59, 61, and 77, respectively;

(vi) SEQ ID NOs: 59, 67, and 116, respectively;

(vii) SEQ ID NOs: 59, 61, and 120, respectively;

(viii) SEQ ID NOs: 59, 61, and 84, respectively;

(ix) SEQ ID NOs: 59, 61, and 124, respectively;

(x) SEQ ID NOs: 59, 67, and 129, respectively; or

(xi) SEQ ID NOs: 59, 61, and 89, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 267, respectively;

(ii) SEQ ID NOs: 310, 311, and 267, respectively;

(iii) SEQ ID NOs: 263, 265, and 316, respectively;

(iv) SEQ ID NOs: 263, 265, and 320, respectively;

(v) SEQ ID NOs: 263, 265, and 325, respectively;

(vi) SEQ ID NOs: 263, 265, and 329, respectively;

(vii) SEQ ID NOs: 335, 265, and 337, respectively; or

(viii) SEQ ID NOs: 263, 265, and 342, respectively;

(i) a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively; and a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NO: 150 and SEQ ID NO: 159;

(ii) CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 152; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NO: 154 and SEQ ID NO: 163;

(j) a heavy chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 16, 29, and 34;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 17, 24, and 43; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NO: 19 and SEQ ID NO: 36; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NO: 176 and SEQ ID NO: 185;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 138, 178, and 187; and

(iii) CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 180;

(k) a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 49, 51, and 53, respectively; and a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 195, 204, 216, 230, 236, 247, 251, and 257;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 197, 205, 217, and 238; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 199, 221, and 226;

(l) a heavy chain variable region having

(i) CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 59;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 61, 67, and 76; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 63, 72, 77, 84, 116, 120, 124, and 129; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 195, 204, 216, 230, 236, 247, 251, and 257;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NO: 265 and SEQ ID NO: 311; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 267, 271, 276, 316, 320, 325, 329, 337, and 342;

(m) a heavy chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NO: 49 and SEQ ID NO: 94;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 51, 96, and 110; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 98, 103, and 112; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 285, 292, and 299;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 205, 287, 293, and 304; and

(iii) CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 288;

(n) a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 59, 357, and 358, respectively;

(ii) SEQ ID NOs: 59, 357, and 359, respectively;

(iii) SEQ ID NOs: 59, 357, and 360, respectively;

(iv) SEQ ID NOs: 59, 357, and 361, respectively; or

(v) SEQ ID NOs: 59, 357, and 362, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 363, respectively;

(ii) SEQ ID NOs: 364, 265, and 365, respectively; or

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

(o) a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively; and a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 369, 152, and 154, respectively; or

(ii) SEQ ID NOs: 369, 152, and 370, respectively.

2. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

(a) a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 16, 17, and 19, respectively;

(ii) SEQ ID NOs: 16, 24, and 19, respectively;

(iii) SEQ ID NOs: 29, 24, and 19, respectively;

(iv) SEQ ID NOs: 34, 17, and 36, respectively;

(v) SEQ ID NOs: 16, 17, and 36, respectively; or

(vi) SEQ ID NOs: 16, 43, and 36, respectively; and

(b) a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 176, 178, and 180, respectively;

(ii) SEQ ID NOs: 185, 187, and 180, respectively; or

(iii) SEQ ID NOs: 185, 138, and 180, respectively.

3. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 49, 51, and 53, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 195, 197, and 199, respectively;

(ii) SEQ ID NOs: 204, 205, and 199, respectively;

(iii) SEQ ID NOs: 195, 205, and 199, respectively;

(iv) SEQ ID NOs: 216, 217, and 199, respectively;

(v) SEQ ID NOs: 195, 205, and 221, respectively;

(vi) SEQ ID NOs: 195, 205, and 226, respectively;

(vii) SEQ ID NOs: 230, 205, and 226, respectively;

(viii) SEQ ID NOs: 236, 238, and 226, respectively;

(ix) SEQ ID NOs: 247, 205, and 226, respectively;

(x) SEQ ID NOs: 251, 205, and 226, respectively; or

(xi) SEQ ID NOs: 257, 238, and 226, respectively.

4. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 59, 61, and 63, respectively;

(ii) SEQ ID NOs: 59, 67, and 63, respectively;

(iii) SEQ ID NOs: 59, 61, and 72, respectively;

(iv) SEQ ID NOs: 59, 76, and 77, respectively;

(v) SEQ ID NOs: 59, 61, and 77, respectively;

(vi) SEQ ID NOs: 59, 67, and 116, respectively;

(vii) SEQ ID NOs: 59, 61, and 120, respectively;

(viii) SEQ ID NOs: 59, 61, and 84, respectively;

(ix) SEQ ID NOs: 59, 61, and 124, respectively;

(x) SEQ ID NOs: 59, 67, and 129, respectively; or

(xi) SEQ ID NOs: 59, 61, and 89, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 267, respectively;

(ii) SEQ ID NOs: 310, 311, and 267, respectively;

(iii) SEQ ID NOs: 263, 265, and 316, respectively;

(iv) SEQ ID NOs: 263, 265, and 320, respectively;

(v) SEQ ID NOs: 263, 265, and 325, respectively;

(vi) SEQ ID NOs: 263, 265, and 329, respectively;

(vii) SEQ ID NOs: 335, 265, and 337, respectively;

(viii) SEQ ID NOs: 263, 265, and 342, respectively;

(ix) SEQ ID NOs: 263, 265, and 271, respectively; or

(x) SEQ ID NOs: 263, 265, and 276, respectively.

5. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 94, 96, and 98, respectively;

(ii) SEQ ID NOs: 49, 51, and 103, respectively; or

(iii) SEQ ID NOs: 49, 110, and 112, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 267, respectively;

(ii) SEQ ID NOs: 310, 311, and 267, respectively;

(iii) SEQ ID NOs: 263, 265, and 271, respectively; or

(iv) SEQ ID NOs: 263, 265, and 276, respectively.

6. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively, and

a light chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 150, 152, and 163, respectively.

7. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 59, 61, and 63, respectively;

(ii) SEQ ID NOs: 59, 67, and 63, respectively;

(iii) SEQ ID NOs: 59, 61, and 72, respectively;

(iv) SEQ ID NOs: 59, 76, and 77, respectively;

(v) SEQ ID NOs: 59, 61, and 77, respectively;

(vi) SEQ ID NOs: 59, 67, and 116, respectively;

(vii) SEQ ID NOs: 59, 61, and 120, respectively;

(viii) SEQ ID NOs: 59, 61, and 84, respectively;

(ix) SEQ ID NOs: 59, 61, and 124, respectively;

(x) SEQ ID NOs: 59, 67, and 129, respectively; or

(xi) SEQ ID NOs: 59, 61, and 89, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 267, respectively;

(ii) SEQ ID NOs: 310, 311, and 267, respectively;

(iii) SEQ ID NOs: 263, 265, and 316, respectively;

(iv) SEQ ID NOs: 263, 265, and 320, respectively;

(v) SEQ ID NOs: 263, 265, and 325, respectively;

(vi) SEQ ID NOs: 263, 265, and 329, respectively;

(vii) SEQ ID NOs: 335, 265, and 337, respectively; or

(viii) SEQ ID NOs: 263, 265, and 342, respectively.

8. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NO: 150 and SEQ ID NO: 159;

(ii) CDR2 comprising an amino acid sequence set forth in SEQ ID NO: 152; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NO: 154 and SEQ ID NO: 163.

9. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 16, 29, and 34;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 17, 24, and 43; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NO: 19 and SEQ ID NO: 36; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NO: 176 and SEQ ID NO: 185;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 138, 178, and 187; and

(iii) CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 180.

10. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 49, 51, and 53, respectively; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 195, 204, 216, 230, 236, 247, 251, and 257;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 197, 205, 217, and 238; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 199, 221, and 226.

11. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having

(i) CDR1 comprising an amino acid sequence set forth in SEQ ID NO: 59;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 61, 67, and 76; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 63, 72, 77, 84, 116, 120, 124, and 129; and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 195, 204, 216, 230, 236, 247, 251, and 257;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NO: 265 and SEQ ID NO: 311; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 267, 271, 276, 316, 320, 325, 329, 337, and 342.

12. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NO: 49 and SEQ ID NO: 94;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 51, 96, and 110; and

(iii) CDR3 comprising an amino acid sequence selected from SEQ ID NOs: 98, 103, and 112, and

a light chain variable region having

(i) CDR1 comprising an amino acid sequence selected from SEQ ID NOs: 285, 292, and 299;

(ii) CDR2 comprising an amino acid sequence selected from SEQ ID NOs: 205, 287, 293, and 304; and

(iii) CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 288.

13. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 59, 357, and 358, respectively;

(ii) SEQ ID NOs: 59, 357, and 359, respectively;

(iii) SEQ ID NOs: 59, 357, and 360, respectively;

(iv) SEQ ID NOs: 59, 357, and 361, respectively; or

(v) SEQ ID NOs: 59, 357, and 362, respectively, and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 263, 265, and 363, respectively;

(ii) SEQ ID NOs: 364, 265, and 365, respectively; or

(iii) SEQ ID NOs: 366, 367, and 368, respectively.

14. The purified anti-MUC1 binding agent of claim 1 , wherein the binding agent comprises:

a heavy chain variable region having CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 9, and 11, respectively; and

a light chain variable region having CDRs 1, 2, and 3 comprising a set of amino acid sequences set forth in

(i) SEQ ID NOs: 369, 152, and 154, respectively; or

(ii) SEQ ID NOs: 369, 152, and 370, respectively.

15. A purified anti-MUC1 binding agent comprising

(a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 148, 158, 162, 167, or 170;

(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 15, 23, 28, 33, 39, or 42; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 174, 184, or 190;

(c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 47; and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 193, 203, 208, 211, 215, 220, 225, 229, 234, 242, 246, 250, or 255;

(d) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 57, 66, 70, 75, 80, 83, 87, 115, 119, 123, 127, 132, 141, or 145; and a light chain variable region comprising an amino acid sequence the amino acid sequence of SEQ ID NO: 261, 270, 275, 279, 308, 315, 319, 323, 328, 333, or 340; or

(e) a heavy chain variable region comprising an amino acid sequence the amino acid sequence of SEQ ID NO: 92, 101, 106, or 109; and a the amino acid sequence of SEQ ID NO: 283, 291, 297, or 303.

16. The purified anti-MUC1 binding agent of claim 1 , comprising:

(a) a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 5; and a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 148, 158, 162, 167, or 170;

(b) a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 15, 23, 28, 33, 39, or 42; and a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 174, 184, or 190;

(c) a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 47; and a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 193, 203, 208, 211, 215, 220, 225, 229, 234, 242, 246, 250, or 255;

(d) a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 57, 66, 70, 75, 80, 83, 87, 115, 119, 123, 127, 132, 141, or 145; and a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 261, 270, 275, 279, 308, 315, 319, 323, 328, 333, or 340; or

(e) a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 92, 101, 106, or 109; and a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 283, 291, 297, or 303.

17. The purified anti-MUC1 binding agent of claim 16 , wherein the binding agent comprises:

a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 15, 23, 28, 33, 39, or 42; and

a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 174, 184, or 190.

18. The purified anti-MUC1 binding agent of claim 16 , wherein the binding agent comprises:

a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 47; and

a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 193, 203, 208, 211, 215, 220, 225, 229, 234, 242, 246, 250, or 255.

19. The purified anti-MUC1 binding agent of claim 16 , wherein the binding agent comprises:

a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 57, 66, 70, 75, 80, 83, 87, 115, 119, 123, 127, 132, 141, or 145; and

a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 261, 270, 275, 279, 308, 315, 319, 323, 328, 333, or 340.

20. The purified anti-MUC1 binding agent of claim 16 , wherein the binding agent comprises:

a heavy chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 92, 101, 106, or 109; and

a light chain variable region comprising an amino acid sequence at least 80% identical to SEQ ID NO: 283, 291, 297, or 303.

21. The purified anti-MUC1 binding agent of claim 1 , comprising:

(a) a heavy chain comprising an amino acid sequence at least 80% to SEQ ID NO: 3; and a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 146, 156, 160, 165, or 168;

(b) a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 13, 21, 26, 31, 37, or 40; and a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 172, 182, or 188;

(c) a heavy chain comprising an amino acid sequence at least 80% identical SEQ ID NO: 45; and a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 191, 201, 206, 209, 213, 218, 223, 227, 232, 240, 244, 248, or 253;

(d) a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 55, 64, 68, 73, 78, 81, 85, 113, 117, 121, 125, 130, 139, or 143; and a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 259, 268, 273, 277, 306, 313, 317, 321, 326, 331, or 338; or

(e) a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 90, 99, 104, or 107; and a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 281, 289, 295, or 301.

22. The purified anti-MUC1 binding agent of claim 21 , wherein the binding agent comprises:

a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 13, 21, 26, 31, 37, or 40; and

a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 172, 182, or 188.

23. The purified anti-MUC1 binding agent of claim 21 , wherein the binding agent comprises:

a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 45; and

a light chain comprising an amino acid sequence at least 80% identical SEQ ID NO: 191, 201, 206, 209, 213, 218, 223, 227, 232, 240, 244, 248, or 253.

24. The purified anti-MUC1 binding agent of claim 21 , wherein the binding agent comprises:

a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 55, 64, 68, 73, 78, 81, 85, 113, 117, 121, 125, 130, 139, or 143; and

a light chain comprising an amino acid sequence at least 80% to SEQ ID NO: 259, 268, 273, 277, 306, 313, 317, 321, 326, 331, or 338.

25. The purified anti-MUC1 binding agent of claim 21 , wherein the binding agent comprises:

a heavy chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 90, 99, 104, or 107; and

a light chain comprising an amino acid sequence at least 80% identical to SEQ ID NO: 281, 289, 295, or 301.

26. The binding agent of claim 1 , wherein the binding agent is a human antibody.

27. A method of detecting a MUC1 polypeptide in a sample, the method comprising:

contacting a sample with the binding agent of claim 1 ; and

detecting binding of the binding agent to the sample, thereby detecting a MUC1 polypeptide in the sample.

28. A composition comprising the binding agent of claim 1 conjugated to a cytotoxic drug.

29. A method for treatment of a cancer comprising administering a therapeutically effective amount of the binding agent of claim 1 to a subject with the cancer, thereby treating the cancer, wherein cells in the cancer express MUC-1, and wherein:

a) the binding agent is an antibody or a chimeric antigen receptor, or

b) the binding agent is conjugated to a therapeutic agent.

30. The method of claim 29 , wherein the subject is a human.

31. A method of inhibiting proliferation of a cell comprising contacting the cell with the binding agent of claim 1 , thereby inhibiting proliferation of the cell, wherein the cell expresses MUC-1, and wherein:

a) the binding agent is an antibody or a chimeric antigen receptor, or

b) the binding agent is conjugated to a therapeutic agent.

32. A polynucleotide that encodes a chimeric antigen receptor comprising a sequence of an anti-MUC1 binding agent of claim 1 .

33. A vector comprising the polynucleotide of claim 32 .

34. The vector of claim 33 , wherein the vector is a lentiviral or retroviral vector.

35. An isolated recombinant cell that expresses a chimeric antigen receptor comprising a sequence of an anti-MUC1 binding agent of claim 1 .

36. The recombinant isolated cell of claim 35 , wherein the cell is a T cell.

37. The purified anti-MUC-1 binding agent of claim 13 , wherein the anti-MUC1 binding agent is a monoclonal antibody or antigen binding fragment thereof.

38. The purified anti-MUC-1 binding agent of claim 37 , wherein the antigen binding fragment is a scFV fragment.

39. The purified anti-MUC-1 binding agent of claim 13 , wherein the anti-MUC1 binding agent is a chimeric antigen receptor.

40. The purified anti-MUC-1 binding agent of claim 1 , wherein the anti-MUC1 binding agent is a chimeric antigen receptor.

41. A polynucleotide comprising a sequence that encodes the scFV of claim 38 .

42. A recombinant vector comprising the polynucleotide of claim 41 .

43. An isolated cell comprising the vector of claim 42 .

44. A method of producing an anti-MUC1 binding agent, the method comprising culturing the cell of claim 43 under conditions where the binding agent is expressed and collecting the binding agent.

Assignments (5)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 11, 2016

From: FINN, OLIVERA J.; SCHOEN, ROBERT E.

To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Reel/Frame 039404/0819 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2016

From: SATO, SHUJI; CHEUNG, WAN CHEUNG; POLAKIEWICZ, ROBERTO D.

To: CELL SIGNALING TECHNOLOGY, INC.

Reel/Frame 038993/0681 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 23, 2016

From: CELL SIGNALING TECHNOLOGY, INC.

To: BLUE FIN THERAPEUTICS HOLDINGS, LLC