IP Library › Granted Patent US 12,552,863
Granted Patent B2
US 12,552,863 · App. 17/617,046 · Granted Feb 17, 2026

High affinity anti-CD3 antibodies, and methods for their generation and use

Inventors: Robert Pejchal (Lebanon, NH); Caitlin Stein (Lebanon, NH); Julia McCreary (Lebanon, NH)
Assignee: ADIMAB, LLC
C07K16/2809C07K2317/31C07K2317/622C07K2317/92
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Quick Facts
Patent No.
US 12,552,863
App. No.
17/617,046
Granted
Feb 17, 2026
Kind
B2
Abstract

Antibodies and antigen-binding fragments thereof with high affinity for CD3 and desirable developability profiles are provided, as well as methods for their manufacture and use.

Claims (158)

1 . An anti-cluster of differentiation three (CD3) antibody or antigen-binding antibody fragment, which comprises:

a. a heavy chain variable region (VH) polypeptide comprising:

i. a VH CDR1 (CDRH1) comprising FNIKDYYMH (SEQ ID NO: 13);

ii. a VH CDR2 (CDRH2) comprising WIDLENANTVYDAKFQG (SEQ ID NO: 15); and

iii. a VH CDR3 (CDRH3) comprising ARDAYGRYFYDV (SEQ ID NO: 103); and

b. a light chain variable region (VL) polypeptide comprising:

i. a VL CDR1 (CDRL1) comprising KSSQSLLNARTGKNYLA (SEQ ID NO: 8);

ii. a VL CDR2 (CDRL2) comprising WASTRX 1 S (SEQ ID NO: 133); and

iii. a VL CDR3 (CDRL3) comprising X 2 QSYFRRT (SEQ ID NO: 134);

wherein:

(i) X 1 is S and X 2 is V;

(ii) X 1 is E and X 2 is V; or

(iii) X 1 is E and X 2 is A.

2 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 1 , which:

(i) binds to human CD3 with a dissociation constant (K D ) of about 200 pM or less; and/or

(ii) elicits T cell activation or T cell killing while displaying a decreased propensity to elicit cytokine production to levels capable of inducing cytokine release syndrome.

3 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 1 , which comprises one or more of the following features:

a. comprises an scFv, a Fv, a Fab, a Fab′, a Fab′-SH, a F(ab′)2, a diabody, a scFv2-Fc2, or a scFv-IgG;

b. comprises:

(A) a heavy chain comprising the VH polypeptide and a heavy chain constant region (CH) polypeptide; and

(B) a light chain comprising the VL polypeptide and a light chain constant region (CL) polypeptide;

c. comprises an IgG, IgA, IgD, IgE, or IgM antibody;

d. is comprised in a chimeric antigen receptor (CAR), which comprises at least one transmembrane domain, at least one intracellular domain from a T-cell receptor, and at least one co-stimulatory domain;

e. comprises an IgG constant domain.

4 . An isolated or recombinant nucleic acid encoding an anti-CD3 antibody or antigen-binding antibody fragment of claim 1 , or an expression vector containing said nucleic acid.

5 . A host cell transfected, transformed, or transduced with a nucleic acid according to claim 4 , or with a vector containing said nucleic acid sequence.

6 . A pharmaceutical composition comprising: an anti-CD3 antibody or antigen-binding antibody fragment of claim 1 ; and a pharmaceutically acceptable carrier and/or excipient.

7 . An anti-CD3 antibody or antigen-binding antibody fragment, which comprises:

(A) a heavy chain variable region (VH) polypeptide comprising a VH CDR1 (CDRH1), a VH CDR2 (CDRH2), and a VH CDR3 (CDRH3); and

(B) a light chain variable region (VL) polypeptide comprising a VL CDR1 (CDRL1), a VL CDR2 (CDRL2), and a VL CDR3 (CDRL3),

wherein:

(I) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 17, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 34; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 11, and 4, respectively;

(II) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 22, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 23; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 4, respectively;

(III) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 29, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 23; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 4, respectively;

(IV) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 49, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 23; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 4, respectively;

(V) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 58, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 23; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 4, respectively;

(VI) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 59, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 23; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 4, respectively;

(VII) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 70, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 23; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 4, respectively;

(VIII) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 24, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 25; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 2, respectively;

(IX) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 17, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 47; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 2, respectively;

(X) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 17, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 25; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 2, respectively; or

(XI) (i) (a) the amino acid sequences of the CDRH1, the CDRH2, and the CDRH3 comprise or consist of the heavy chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 55, and

(b) the amino acid sequences of the CDRL1, the CDRL2, and the CDRL3 comprise or consist of the light chain CDR 1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 25; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 10, and 2, respectively.

8 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 7 , wherein

in (I), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 34;

in (II), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 22, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 23;

in (III), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 29, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 23;

in (IV), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 49, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 23;

in (V), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 58, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 23;

in (VI), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 59, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 23;

in (VII), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 70, and

(B) the amino acid sequence of the V L polypeptide has at least 90% sequence identity to SEQ ID NO: 23;

in (VIII), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 24, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 25;

in (IX), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 47;

in (X), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 25; or

in (XI), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 55, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 25.

9 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 7 , wherein

in (I), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 34;

in (II), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 22, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 23;

in (IV), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 29, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 23;

in (IV), (A) the amino acid sequence of the VH polypeptide has at least 9500 sequence identity to SEQ ID NO: 49, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 23;

in (V), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 58, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 23;

in (VI), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 59, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 23;

in (VII), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 70, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 23;

in (VIII), (A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 24, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 25;

in (IX), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 47;

in (X), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 25; or

in (XI), (A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 55, and

(B) the amino acid sequence of the VL polypeptide has ng at least 95% sequence identity to SEQ ID NO: 25.

10 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 7 ,

wherein:

(i) (A) the amino acid sequence of the CDRH1, the CDRH2, and the CDRH3 comprise heavy chain CDR1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 17; and

(B) the amino acid sequence of the CDRL1, the CDRL2, and the CDRL3 comprise light chain CDR1, 2, and 3 sequences, respectively, contained in SEQ ID NO: 34; or

(ii) the amino acid sequences of the CDRH1, the CDRH2, the CDRH3, the CDRL1, the CDRL2, and the CDRL3 comprise or consist of SEQ ID NO: 13, 15, 103, 8, 11, and 4, respectively.

11 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 10 ,

(A) the amino acid sequence of the VH polypeptide has at least 90% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 90% sequence identity to SEQ ID NO: 34.

12 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 10 ,

(A) the amino acid sequence of the VH polypeptide has at least 95% sequence identity to SEQ ID NO: 17, and

(B) the amino acid sequence of the VL polypeptide has at least 95% sequence identity to SEQ ID NO: 34.

13 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 10 , wherein the amino acid sequences of the VH polypeptide and the VL polypeptide comprise or consist of SEQ ID NOS: 17 and 34, respectively.

14 . A pharmaceutical composition comprising: an anti-CD3 antibody or antigen-binding antibody fragment of claim 13 ; and a pharmaceutically acceptable carrier and/or excipient.

15 . The anti-CD3 antibody or antigen-binding antibody fragment of claim 10 , which comprises one or more of the following features:

a. comprises an scFv, a Fv, a Fab, a Fab′, a Fab′-SH, a F(ab′)2, a diabody, a scFv2-Fc2, or a scFv-IgG;

b. comprises:

(A) a heavy chain comprising the VH polypeptide and a heavy chain constant region (CH) polypeptide; and

(B) a light chain comprising the VL polypeptide and a light chain constant region (CL) polypeptide;

c. comprises an IgG, IgA, IgD, IgE, or IgM antibody;

d. is comprised in a chimeric antigen receptor (CAR), which comprises at least one transmembrane domain, and at least one intracellular domain from a T-cell receptor, and at least one co-stimulatory domain; and/or

e. comprises an IgG constant domain.

16 . An isolated or recombinant nucleic acid encoding an anti-CD3 antibody or antigen-binding antibody fragment of claim 10 , or an expression vector containing said nucleic acid.

17 . A host cell transfected, transformed, or transduced with a nucleic acid according to claim 16 or with a vector containing said nucleic acid sequence.

18 . A pharmaceutical composition comprising: an anti-CD3 antibody or antigen-binding antibody fragment of claim 10 ; and a pharmaceutically acceptable carrier and/or excipient.

19 . An anti-cluster of differentiation three (CD3) antibody or antigen-binding antibody fragment, which comprises:

(A) a heavy chain variable region (VH) polypeptide; and

(B) a light chain variable region (VL) polypeptide,

wherein the amino acid sequences of the VH polypeptide and the VH polypeptide comprise or consist of:

(I) SEQ ID NOS: 17 and 34, respectively;

(II) SEQ ID NOS: 22 and 23, respectively;

(III) SEQ ID NOS: 29 and 23, respectively;

(IV) SEQ ID NOS: 49 and 23, respectively;

(V) SEQ ID NOS: 58 and 23, respectively;

(VI) SEQ ID NOS: 59 and 23, respectively;

(VII) SEQ ID NOS: 70 and 23, respectively;

(VIII) SEQ ID NOS: 24 and 25, respectively;

(IX) SEQ ID NOS: 17 and 47, respectively;

(X) SEQ ID NOS: 17 and 25, respectively;

(XI) SEQ ID NOS: 55 and 25, respectively;

(XII) SEQ ID NOS: 20 and 21, respectively;

(XIII) SEQ ID NOS: 54 and 36, respectively;

(XIV) SEQ ID NOS: 31 and 36, respectively;

(XV) SEQ ID NOS: 67 and 68, respectively;

(XVI) SEQ ID NOS: 17 and 36, respectively;

(XVII) SEQ ID NOS: 59 and 36, respectively;

(XVIII) SEQ ID NOS: 30 and 18, respectively;

(XIX) SEQ ID NOS: 31 and 18, respectively; or

(XX) SEQ ID NOS: 50 and 18, respectively.

Assignments (2)
SECURITY INTEREST Recorded Mar 4, 2025
From: AFFINI-T THERAPEUTICS, INC.
To: CATALIO NEXUS FUND III, LP
Reel/Frame 070403/0862 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 3, 2022
From: PEJCHAL, ROBERT; STEIN, CAITLIN; MCCREARY, JULIA
To: ADIMAB, LLC
Reel/Frame 058870/0857 →
Continuity (2)
Provisional Application 62858949 · Jun 7, 2019
Related Publication 20230002487A1 · Jan 5, 2023
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