IP Library › Granted Patent US 12,252,534
Granted Patent B2
US 12,252,534 · App. 16/074,600 · Granted Mar 18, 2025

Humanized anti-CD3 antibodies, conjugates and uses thereof

Inventors: Chanhyuk Kim (Daejeon, KR); Travis Young (La Jolla, CA); Minsoo Kim (San Diego, CA); Jennifer Ma (Los Angeles, CA); Leonard Presta (San Francisco, CA); Peter G. Schultz (La Jolla, CA)
Assignee: THE SCRIPPS RESEARCH INSTITUTE
C07K16/2803A61P35/00C07K2317/24C07K2317/522C07K2317/565C07K2317/92
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Quick Facts
Patent No.
US 12,252,534
App. No.
16/074,600
Granted
Mar 18, 2025
Kind
B2
Abstract

The present invention provides for humanized anti-CD3 antibodies and conjugates thereof. These conjugates may be useful in the treatment of conditions such as prostate cancer.

Claims (37)

1. An antibody or antigen-binding fragment thereof that binds to cluster of differentiation 3 (CD3), comprising (a) a heavy chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 27, and (b) a light chain variable region comprising an amino acid sequence at least 96% identical to SEQ ID NO: 32; wherein (i) the light chain variable region comprises the light chain complementarity determining region 1 (CDR1), the light chain CDR2, and the light chain CDR3 of SEQ ID NO: 32, and the heavy chain variable region comprises the heavy chain CDR1, the heavy chain CDR2, and the heavy chain CDR3 of SEQ ID NO: 27.

2. The antibody or antigen-binding fragment of claim 1 , wherein (i) the light chain CDR1 comprises SEQ ID NO: 51, the light chain CDR2 comprises SEQ ID NO: 52, and the light chain CDR3 comprises SEQ ID NO: 53, and (ii) the heavy chain CDR1 comprises SEQ ID NO: 54, the heavy chain CDR2 comprises SEQ ID NO: 55, and the heavy chain CDR3 comprises SEQ ID NO: 56.

3. The antibody or antigen-binding fragment of claim 1 , wherein the light chain variable region comprises SEQ ID NO: 32, and the heavy chain variable region comprises SEQ ID NO: 27.

4. The antibody or antigen-binding fragment of claim 1 , comprising an unnatural amino acid, wherein the unnatural amino acid optionally comprises para-acetylphenylalanine (pAcF).

5. The antibody or antigen-binding fragment of claim 4 , comprising a first heavy chain constant region (CH1), wherein the unnatural amino acid is positioned in the CH1 at position 129 per Kabat numbering.

6. The antibody or antigen-binding fragment of claim 1 , comprising a first heavy chain constant region (CH1) comprising a sequence at least 95% identical to SEQ ID NO: 98, wherein the CH1 comprises the para-acetylphenylalanine of SEQ ID NO: 98.

7. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain at least 95% identical to SEQ ID NO: 44, and a light chain at least 95% identical to SEQ ID NO-39.

8. The antibody or antigen-binding fragment of claim 7 , wherein the heavy chain comprises SEQ ID NO: 44 and the light chain comprises SEQ ID NO: 39.

9. An antibody or antigen-binding fragment thereof that binds to cluster of differentiation 3 (CD3), comprising:

(a) a heavy chain variable domain comprising

a first heavy chain framework region comprising EVQLVESGGGLVQPGGSL(X1)LSCAAS (SEQ ID NO: 69), wherein X1 is selected from lysine (K) and arginine (R),

a heavy chain CDR1 comprising GFTFNTYAMN (SEQ ID NO: 54),

a second heavy chain framework region comprising WVRQAPGKGLEWV(X2) (SEQ ID NO: 71), wherein X2 is selected from glycine (G) and alanine (A),

a heavy chain CDR2 comprising RIRSKYNNYATYYADSVKD (SEQ ID NO: 55),

a third heavy chain framework region comprising RFTISRDDSKNTLYLQMNSL(X3)(X4)EDTAVYYCVR (SEQ ID NO: 79), wherein X3 is selected from lysine (K) and arginine (R), and X4 is selected from threonine (T) and alanine (A),

a heavy chain CDR3 comprising HGNFGNSYVSWFAY (SEQ ID NO: 56), and

a fourth heavy chain framework region comprising WGQGTLVTVSS (SEQ ID NO: 124); and

(b) a light chain variable domain comprising

a first light chain framework region comprising QAVVTQEPSLTVSPGGTVTLTC (SEQ ID NO: 97),

a light chain CDR1 comprising RSSTGAVTTSNYAN (SEQ ID NO: 51),

a second light chain framework region comprising DHLFR (SEQ ID NO: 62),

a light chain CDR2 comprising GTNKRAP (SEQ ID NO: 52),

a third light chain framework region comprising GTPARFSGSLLGDKAALTISGAQPEDEAEYYC (SEQ ID NO: 74),

a light chain CDR3 comprising ALWYSNLWV (SEQ ID NO: 53), and

a fourth light chain framework region comprising FGGGTKLTVL (SEQ ID NO: 110).

10. The antibody or antigen-binding fragment of claim 9 , wherein (i) X1 is arginine, (ii) X2 is alanine, (iii) X3 is arginine, (iv) X4 is alanine, or (v) any combination of one or more of (i) to (iv).

11. The antibody or antigen-binding fragment of claim 9 , wherein the second light chain framework region comprises (i) (X5)V(X6)(X7)(X8)(X9)DHLFRG(X10)(X11)G (SEQ ID NO: 66), wherein X5, X6, X7, X8, X9, X10, and X11 are selected from any amino acid, or

(ii) (X12)V(X13)Q (X14)(X15)DHLF(X16)G(X17)(X18)G (SEQ ID NO: 67), wherein X12, X13, X14, X15, X16, X17, and X18 are selected from any amino acid.

12. The antibody or antigen-binding fragment of claim 9 , wherein the second light chain framework region comprises WVQQKPDIILFRGLIG (SEQ ID NO: 59).

13. The antibody or antigen-binding fragment of claim 9 , comprising an unnatural amino acid, where the unnatural amino acid comprises para-acetylphenylalanine (pAcF).

14. The antibody or antigen-binding fragment of claim 13 , comprising a first heavy chain constant region (CH1), wherein the unnatural amino acid is positioned in the CH1 at position 129 using Kabat numbering.

15. The antibody or antigen-binding fragment of claim 9 , comprising a first heavy chain constant region (CH1) comprising a sequence at least 95% identical to SEQ ID NO: 98, wherein the CH1 comprises the para-acetylphenylalanine of SEQ ID NO: 98.

16. A composition comprising a sequence at least 95% identical to SEQ ID NO: 98, wherein the sequence comprises the para-acetylphenylalanine of SEQ ID NO: 98.

17. The composition of claim 16 , comprising a human or humanized antibody or antigen-binding fragment thereof.

18. The composition of claim 17 , wherein the antibody or antigen-binding fragment binds to cluster of differentiating 3 (CD3).

19. The composition of claim 17 , wherein the antibody or antigen-binding fragment comprises a light chain complementarity determining region 1 (CDR1) comprising SEQ ID NO: 51, a light chain CDR2 comprising SEQ ID NO: 52, and a light chain CDR3 comprising SEQ ID NO: 53, and (ii) a heavy chain CDR1 comprising SEQ ID NO: 54, a heavy chain CDR2 comprising SEQ ID NO: 55, and a heavy chain CDR3 comprising SEQ ID NO: 56.

20. The composition of claim 19 , comprising SEQ ID NO: 98.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 9, 2020
From: KIM, CHANHYUK; YOUNG, TRAVIS; KIM, MINSOO; MA, JENNIFER; PRESTA, LEONARD; SCHULTZ, PETER G.
To: THE CALIFORNIA INSTITUTE FOR BIOMEDICAL RESEARCH
Reel/Frame 053727/0347 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 30, 2019
From: KIM, CHANHYUK; KIM, MINSOO; PRESTA, LEONARD; YOUNG, TRAVIS; MA, JENNIFER; SCHULTZ, PETER G.
To: THE SCRIPPS RESEARCH INSTITUTE
Reel/Frame 050569/0312 →
Continuity (2)
Provisional Application 62291143 · Feb 4, 2016
Related Publication 20230192844A1 · Jun 22, 2023
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