IP Library › Granted Patent US 10,906,978
Granted Patent B2
US 10,906,978 · App. 15/943,685 · Granted Feb 2, 2021

Anti-CD3 antibodies, anti-CD123 antibodies and bispecific antibodies specifically binding to CD3 and/or CD123

Inventors: Jana Albrecht (Frankfurt, DE); Cédric Barriere (Paris, FR); Christian Beil (Frankfurt, DE); Jochen Beninga (Eltville, DE); Chantal Carrez (Thiais, FR); Stéphane Guerif (Paris, FR); Katja Kroll (Frankfurt, DE); Christian Lange (Holler, DE); Cendrine Lemoine (Massy, FR); Wulf-Dirk Leuschner (Niedernhausen, DE); Ercole Rao (Moerfelden-Walldorf, DE); Marion Schneider (Hofheim, DE); Marie-Cécile Wetzel (Paris, FR); Peter Wonerow (Frankfurt, DE)
Assignee: SANOFI
C07K16/2866C07K16/2809C07K16/30G01N33/57492A61K2039/505C07K2317/21C07K2317/24C07K2317/31C07K2317/33C07K2317/52C07K2317/55C07K2317/56C07K2317/565C07K2317/92C07K2318/00G01N2333/7155
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Quick Facts
Patent No.
US 10,906,978
App. No.
15/943,685
Granted
Feb 2, 2021
Kind
B2
Abstract

The present invention concerns antibody-like binding protein specifically binding to CD3 and binding specifically to at least one further antigen, for example CD123. The present invention also concerns antibody-like binding protein specifically binding to CD123 and binding specifically to at least one further antigen. The invention further concerns anti-CD3 antibodies and anti-CD123 antibodies. The invention also relates to pharmaceutical compositions comprising the antibody-like binding protein, anti-CD3 antibodies or anti-CD123 antibodies of the invention, and their use to treat cancer. The invention further relates to isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibody-like binding protein, anti-CD3 or anti-CD123 antibody and the use of said anti-CD123 antibody as a diagnostic tool.

Claims (134)

1. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 388; and a second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 390.

2. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 391; and a second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 393.

3. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein the first polypeptide chain comprises a structure represented by the formula [I]:

V D1 -L 1 -V D2 -L 2 -C L   [I]

and the second polypeptide chain comprises a structure represented by the formula [II]:

V D3 -L 3 -V D4 -L 4 -C H1   [II]

wherein:

V D1 is a light chain variable domain of a first immunoglobulin;

V D2 is a light chain variable domain of a second immunoglobulin;

V D3 is a heavy chain variable domain of the second immunoglobulin;

V D4 is a heavy chain variable domain of the first immunoglobulin;

C L is a light chain constant domain of an immunoglobulin;

C H1 is a C H1 heavy chain constant domain of an immunoglobulin; and

L 1 , L 2 , L 3 , and L 4 are amino acid linkers;

wherein the first polypeptide chain and the second polypeptide chain form a cross-over light chain-heavy chain pair; and

wherein V D1 comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence of WAS, and a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379;

V D2 comprises a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11;

V D3 comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, and a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8; and

V D4 comprises a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

4. The antibody-like binding protein of claim 3 , wherein:

L 1 comprises an amino acid sequence as set forth in SEQ ID NO: 389;

L 2 comprises an amino acid sequence as set forth in SEQ ID NO: 389; and

L 3 and L 4 are 0 amino acids in length.

5. The antibody-like binding protein of claim 3 , wherein:

V D1 comprises an amino acid sequence as set forth in SEQ ID NO: 385;

V D2 comprises an amino acid sequence as set forth in SEQ ID NO: 141;

V D3 comprises an amino acid sequence as set forth in SEQ ID NO: 138;

V D4 comprises an amino acid sequence as set forth in SEQ ID NO: 383;

C L comprises an amino acid sequence as set forth in SEQ ID NO: 310; and

C H1 comprises an amino acid sequence as set forth in SEQ ID NO: 313.

6. The antibody-like binding protein of claim 3 , wherein:

(a) the first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 388, or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 388, which comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence WAS, a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379, a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11; and

(b) the second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 390, or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 390, which comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8, a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

7. The antibody-like binding protein of claim 3 , wherein the second polypeptide chain further comprises a Fc domain (“Fc”).

8. The antibody-like binding protein of claim 3 , wherein the first polypeptide chain further comprises a Fc domain (“Fc”).

9. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein the first polypeptide chain comprises a structure represented by the formula [IV]:

V D1 -L 1 -V D2 -L 2 -C L -L 5 -Fc 2   [IV]

and the second polypeptide chain comprises a structure represented by the formula [III]:

V D3 -L 3 -V D4 -L 4 -C H1 -Fc  [III]

wherein:

V D1 is a light chain variable domain of a first immunoglobulin;

V D2 is a light chain variable domain of a second immunoglobulin;

V D3 is a heavy chain variable domain of the second immunoglobulin;

V D4 is a heavy chain variable domain of the first immunoglobulin;

C L is a light chain constant domain of an immunoglobulin;

C H1 is a C H1 heavy chain constant domain of an immunoglobulin;

Fc is the immunoglobulin hinge region and CH 2 , CH 3 immunoglobulin heavy chain constant domains of a first immunoglobulin;

Fc 2 is the immunoglobulin hinge region and CH 2 , CH 3 immunoglobulin heavy chain constant domains of a second immunoglobulin; and

L 1 , L 2 , L 3 , L 4 , and L 5 are amino acid linkers;

wherein the first polypeptide chain of formula [IV] and the second polypeptide chain of formula [III] form a cross-over light chain-heavy chain pair; and

wherein V D1 comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence of WAS, and a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379;

V D2 comprises a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11;

V D3 comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, and a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8; and

V D4 comprises a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

10. The antibody-like binding protein of claim 9 , wherein:

L 1 comprises an amino acid sequence as set forth in SEQ ID NO: 389;

L 2 comprises an amino acid sequence as set forth in SEQ ID NO: 389; and

L 3 , L 4 , and L 5 are 0 amino acids in length.

11. The antibody-like binding protein of claim 9 , wherein:

Fc comprises an amino acid sequence as set forth in SEQ ID NO: 394; and

Fc 2 comprises an amino acid sequence as set forth in SEQ ID NO: 392.

12. The antibody-like binding protein of claim 9 , wherein:

V D1 comprises an amino acid sequence as set forth in SEQ ID NO: 385;

V D2 comprises an amino acid sequence as set forth in SEQ ID NO: 141;

V D3 comprises an amino acid sequence as set forth in SEQ ID NO: 138;

V D4 comprises an amino acid sequence as set forth in SEQ ID NO: 383;

C L comprises an amino acid sequence as set forth in SEQ ID NO: 310; and

C H1 comprises an amino acid sequence as set forth in SEQ ID NO: 313.

13. The antibody-like binding protein of claim 9 , wherein:

(a) the first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 391, or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 391, which comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence WAS, a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379, a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11; and

(b) the second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 393, or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 393, which comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8, a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

14. An antibody-like binding protein that binds specifically to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide has a structure represented by the formula [I]:

V D1 -L 1 -V D2 -L 2 -C L   [I]

and a second polypeptide has a structure represented by the formula [II]:

V D3 -L 3 -V D4 -L 4 -C H1   [II]

wherein:

V D1 is a light chain variable domain of a first immunoglobulin;

V D2 is a light chain variable domain of a second immunoglobulin;

V D3 is a heavy chain variable domain of the second immunoglobulin;

V D4 is a heavy chain variable domain of the first immunoglobulin;

C L is a light chain constant domain of an immunoglobulin;

C H1 is a C H1 heavy chain constant domain of an immunoglobulin;

L 1 , L 2 , L 3 , and L 4 are amino acid linkers; and

wherein the first polypeptide and the second polypeptide form a cross-over light chain-heavy chain pair; and

wherein V D1 consists of the amino acid sequence as set forth in SEQ ID NO: 385, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 385, which comprises a CDR1-L of sequence SEQ ID NO: 378, a CDR2-L of sequence WAS, and a CDR3-L of sequence SEQ ID NO: 379;

V D2 consists of the amino acid sequence as set forth in SEQ ID NO: 141, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 141, which comprises a CDR1-L of sequence SEQ ID NO: 142, a CDR2-L of sequence KVS, and a CDR3-L of sequence SEQ ID NO: 11;

V D3 consists of the amino acid sequence as set forth in SEQ ID NO: 138, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 138, which comprises a CDR1-H of sequence SEQ ID NO: 6, a CDR2-H of sequence SEQ ID NO: 7, and a CDR3-H of sequence SEQ ID NO: 8; and

V D4 consists of the amino acid sequence as set forth in SEQ ID NO: 383, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 383, which comprises a CDR1-H of sequence SEQ ID NO: 381, a CDR2-H of sequence SEQ ID NO: 384, and a CDR3-H of sequence SEQ ID NO: 382.

15. The antibody-like binding protein of claim 14 , wherein:

(a) the first polypeptide consists of the amino acid sequence as set forth in SEQ ID NO: 388, which comprises V D1 of amino acid sequence SEQ ID NO: 385, L 1 of amino acid sequence SEQ ID NO: 389, V D2 of amino acid sequence SEQ ID NO: 141, L 2 of amino acid sequence SEQ ID NO: 389, and C L of amino acid sequence SEQ ID NO: 310; or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 388, wherein the three CDRs of amino acid sequences SEQ ID NO: 378, WAS, and SEQ ID NO: 379 of V D1 , and the three CDRs of amino acid sequences SEQ ID NO: 142, KVS, and SEQ ID NO: 11 of V D2 are unaltered; and

(b) the second polypeptide consists of the amino acid sequence as set forth in SEQ ID NO: 390, which comprises V D3 of amino acid sequence SEQ ID NO: 138, L 3 is 0 amino acids, V D4 of amino acid sequence SEQ ID NO: 383, L 4 is 0 amino acids, and C H1 of amino acid sequence SEQ ID NO: 313, or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 390, wherein the three CDRs of amino acid sequences SEQ ID NO: 381, SEQ ID NO: 384, and SEQ ID NO: 382 of V D4 , and the three CDRs of amino acid sequences SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8 of V D3 are unaltered.

16. The antibody-like binding protein according to claim 14 , wherein the polypeptide of formula [II] further comprises a Fc domain and has a structure represented by formula [III]:

V D3 -L 3 -V D4 -L 4 -C H1 -Fc  [III]

wherein the polypeptide of formula [I] further comprises a Fc domain (Fc 2 ) and has a structure represented by formula [IV]:

V D1 -L 1 -V D2 -L 2 -C L -L 5 -Fc 2   [IV]

wherein:

Fc is the immunoglobulin hinge region and CH 2 , CH 3 immunoglobulin heavy chain constant domains of an immunoglobulin,

Fc 2 is the immunoglobulin hinge region and CH 2 , CH 3 immunoglobulin heavy chain constant domains of an immunoglobulin, and

L 5 is an amino acid linker; and

wherein:

(a) the polypeptide according to formula [IV] consists of the amino acid sequence as set forth in SEQ ID NO: 391, which comprises V D1 of amino acid sequence SEQ ID NO: 385, L 1 of amino acid sequence SEQ ID NO: 389, V D2 of amino acid sequence SEQ ID NO: 141, L 2 of amino acid sequence SEQ ID NO: 389, C L of amino acid sequence SEQ ID NO: 310, L 5 which is 0 amino acids, and Fc 2 of amino acid sequence SEQ ID NO: 392; or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 391, wherein the three CDRs of amino acid sequences SEQ ID NO: 378, WAS, and SEQ ID NO: 379 of V D1 , and the three CDRs of amino acid sequences SEQ ID NO: 142, KVS, and SEQ ID NO: 11 of V D2 are unaltered; and

(b) the polypeptide according to formula [III] consists of the amino acid sequence as set forth in SEQ ID NO: 393, which comprises V D3 of amino acid sequence SEQ ID NO: 138, L 3 is 0 amino acids, V D4 of amino acid sequence SEQ ID NO: 383, L 4 is 0 amino acids, C H1 of amino acid sequence SEQ ID NO: 313, and Fc of amino acid sequence SEQ ID NO: 394; or

an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 393, wherein the three CDRs of amino acid sequences SEQ ID NO: 381, SEQ ID NO: 384, and SEQ ID NO: 382 of V D4 , and the three CDRs of amino acid sequences SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8 of V D3 are unaltered; and

wherein the polypeptide of formula [IV] and the polypeptide of formula [III] form a cross-over light chain-heavy chain pair.

17. An antibody-like binding protein comprising two polypeptide chains that form two antigen-binding sites, wherein:

a first polypeptide chain comprises:

a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378;

a CDR2-L comprising an amino acid sequence WAS;

a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379;

a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142;

a CDR5-L comprising an amino acid sequence of KVS; and

a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11;

and

wherein a second polypeptide chain comprises:

a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6;

a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7;

a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8;

a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381;

a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384; and

a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

18. A pharmaceutical composition comprising:

(a) the antibody-like binding protein of any one of claim 1 , 2 , 3 , 9 , 14 , or 17 ; and

(b) a pharmaceutically acceptable carrier.

19. A method of treating a hematological cancer comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 18 .

20. An isolated nucleic acid comprising a nucleotide sequence encoding the antibody-like binding protein of any one of claim 1 , 2 , 3 , 9 , 14 , or 17 .

21. A host cell which has been transformed by the nucleic acid of claim 20 .

22. A kit comprising at least one antibody-like binding protein of any one of claim 1 , 2 , 3 , 9 , 14 , or 17 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 18, 2019
From: ALBRECHT, JANA; BARRIERE, CEDRIC; BEIL, CHRISTIAN; BENINGA, JOCHEN; CARREZ, CHANTAL; GUERIF, STEPHANE; KROLL, KATJA; LANGE, CHRISTIAN; LEMOINE, CENDRINE; LEUSCHNER, WULF-DIRK; RAO, ERCOLE; SCHNEIDER, MARION; WETZEL, MARIE-CECILE; WONEROW, PETER
To: SANOFI
Reel/Frame 049505/0189 →
Priority Claims (1)
EP 15305077 · Jan 23, 2015 · regional
Continuity (3)
Continuation 15654857 · Jul 20, 2017
Continuation PCTEP2016051386 · Jan 22, 2016
Related Publication 20180222987A1 · Aug 9, 2018