IP Library › Granted Patent US 12703759

Granted Patent B2

US 12703759 · App. 18/015,508 · Granted Aug 11, 2026

CD19 binding molecules and uses thereof

Inventors: Xiaohu Fan (Edmonton, CA); Zhe Zhou (Nanjing, CN); Qiuchuan Zhuang (Nanjing, CN); Xu Fang (Nanjing, CN); Yue Han (Nanjing, CN); Youguo Peng (Nanjing, CN); Manman Lu (Nanjing, CN)

Assignee: Legend Biotech USA Inc.

C07K16/2896 A61K40/11 A61K40/31 A61K40/4211 A61P35/00 C12N5/0636 C12N15/63 A61K2239/31 A61K2239/38 A61K2239/48 C07K2317/20 C07K2317/565 C07K2317/567 C07K2319/02 C07K2319/03

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 12703759
App. No.: 18/015,508
Granted: Aug 11, 2026
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present disclosure provides single domain antibodies that bind to CD19, and chimeric antigen receptors comprising same. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating a disease or disorder are also provided.

Claims (53)

1 . An anti-CD19 single domain antibody (sdAb) comprising:

(i) a CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

(ii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 22 or 108; a CDR2 comprising the amino acid sequence of SEQ ID NO: 29; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 36;

(iii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 2; a CDR2 comprising the amino acid sequence of SEQ ID NO: 9; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 16;

(iv) a CDR1 comprising the amino acid sequence of SEQ ID NO: 23 or 109; a CDR2 comprising the amino acid sequence of SEQ ID NO: 30; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 37;

(v) a CDR1 comprising the amino acid sequence of SEQ ID NO: 3; a CDR2 comprising the amino acid sequence of SEQ ID NO: 10; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 17;

(vi) a CDR1 comprising the amino acid sequence of SEQ ID NO: 24 or 110; a CDR2 comprising the amino acid sequence of SEQ ID NO: 31; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 38;

(vii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 18;

(viii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 25 or 111; a CDR2 comprising the amino acid sequence of SEQ ID NO: 32; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 39;

(ix) a CDR1 comprising the amino acid sequence of SEO ID NO: 5: a CDR2 comprising the amino acid sequence of SEQ ID NO: 12; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 19;

(x) a CDR1 comprising the amino acid sequence of SEQ ID NO: 26 or 112; a CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 40;

(xi) a CDR1 comprising the amino acid sequence of SEQ ID NO: 6; a CDR2 comprising the amino acid sequence of SEQ ID NO: 13; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 20;

(xii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 27 or 113; a CDR2 comprising the amino acid sequence of SEQ ID NO: 34; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 41;

(xiii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 7; a CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 21;

(xiv) a CDR1 comprising the amino acid sequence of SEQ ID NO: 28 or 114; a CDR2 comprising the amino acid sequence of SEQ ID NO: 35; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 42; or

(xv) a CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 50; or

(xvi) a CDR1 comprising the amino acid sequence of SEQ ID NO: 22 or 108; a CDR2 comprising the amino acid sequence of SEQ ID NO: 103; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 36.

2 . The anti-CD19 sdAb of claim 1 , further comprising one or more FR regions as set forth in SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and/or SEQ ID NO: 104.

3 . The anti-CD19 sdAb of claim 1 , wherein anti-CD19 sdAb comprises or consists of an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, sequence identity with the sequence of SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, or SEQ ID NO: 104.

4 . The anti-CD19 sdAb of claim 1 , wherein anti-CD19 sdAb is a camelid sdAb or a humanized sdAb.

5 . The anti-CD19 sdAb of claim 1 , wherein the anti-CD19 sdAb is genetically fused or chemically conjugated to an agent.

6 . A chimeric antigen receptor (CAR), comprising:

(a) an extracellular antigen binding domain comprising the anti-CD19 sdAb of claim 1 ;

(b) a transmembrane domain; and

7 . The CAR of claim 6 , further comprising a signal peptide located at the N-terminus of the polypeptide.

8 . The CAR of claim 6 , further comprising a hinge domain located between the C-terminus of the extracellular antigen binding domain and the N-terminus of the transmembrane domain.

9 . The CAR of claim 6 , wherein the extracellular antigen binding domain further comprises one or more additional antigen binding domain(s).

10 . The CAR of claim 9 , wherein the one or more additional antigen binding domain(s) bind to one or more antigen(s) selected from a group consisting of CD20, CD22, CD33, CD38, BCMA, CS1, ROR1, GPC3, CD123, IL-13R, CD138, c-Met, EGFRvIII, GD-2, NY-ESO-1, MAGE A3, and glycolipid F77.

11 . An isolated nucleic acid comprising a nucleic acid sequence encoding the CAR of claim 6 .

12 . A vector comprising the isolated nucleic acid of claim 11 .

13 . An engineered immune effector cell, comprising the CAR of claim 6 .

14 . The engineered immune effector cell of claim 13 , wherein the immune effector cell is a T cell or B cell.

15 . A pharmaceutical composition, comprising the engineered immune effector cell of claim 13 , and a pharmaceutically acceptable excipient.

16 . A method of treating a disease or disorder in a subject, comprising administering to the subject an effective amount of the engineered immune effector cell of claim 13 , wherein the disease or disorder is a B cell associated disease or disorder and/or CD19 associated disease or disorder.

17 . The method of claim 16 , wherein the disease or disorder is selected from a group consisting of marginal zone lymphoma, diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), primary central nervous system (CNS) lymphoma, primary mediastinal B cell lymphoma (PMBL), small lymphocytic lymphoma (SLL), B cell prolymphocytic leukemia (B-PLL), follicular lymphoma (FL), burkitt lymphoma, primary intraocular lymphoma, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia (HCL), precursor B lymphoblastic leukemia, non-hodgkin lymphoma (NHL), high-grade B-cell lymphoma (HGBL), and multiple myelomia (MM).

18 . An anti-CD19 single domain antibody (sdAb) comprising:

(i) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 43;

(ii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 44;

(iii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 45;

(iv) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 46;

(v) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 47;

(vi) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 48;

(vii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 49;

(viii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 51;

(ix) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 52;

(x) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 53;

(xi) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 54;

(xii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 55;

(xiii) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 56; or

(xiv) a CDR1, a CDR2, and a CDR3 having the amino acid sequences of the CDR1, CDR2, and CDR3, respectively, as set forth in SEQ ID NO: 104.

19 . The anti-CD19 sdAb of claim 18 , wherein the CDR1, CDR2 or CDR3 are determined according to the Kabat numbering scheme, the IMGT numbering scheme, the AbM numbering scheme, the Chothia numbering scheme, the Contact numbering scheme, or a combination thereof.

20 . A chimeric antigen receptor (CAR), comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 105.