Anti-CD19 antibodies and their uses

By developing human anti-CD19 antibodies and their fragments, the lack of effective methods for treating B-cell lymphoma and leukemia in the existing technology has been solved, and specific targeted treatment of B-cell lymphoma and leukemia has been achieved, with therapeutic effects of ADCC activity and cell apoptosis induction.

CN115605229BActive Publication Date: 2025-09-16MILLENNIUM PHARMACEUTICALS INC
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Patent Information

Application Number
CN202180030649.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2020-04-24
Filing Date
2021-04-23
Publication Date
2025-09-16
Estimated Expiration
2041-04-23

AI Technical Summary

Technical Problem

The existing technology lacks effective anti-CD19 antibodies for the treatment of B cell lymphoma and leukemia, and existing treatment methods have difficulty in achieving specific targeting and effective killing of B cells.

Method used

A human anti-CD19 antibody and its fragments have been developed, which contain specific heavy chain and light chain variable region complementary determining region sequences, can bind to CD19 with high affinity, exhibit ADCC activity, apoptosis induction and B cell proliferation inhibition, and are used alone or conjugated with diagnostic and therapeutic agents for cancer treatment.

Benefits of technology

It has achieved specific targeted treatment for B-cell lymphoma and leukemia, effectively killing tumor cells through ADCC activity and cell apoptosis induction, providing a new treatment method.

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Abstract

Antibodies, fragments thereof, and fusion proteins that specifically bind to CD19, as well as methods of making and using such antibodies, are described. Such antibodies, fusion proteins, and fragments thereof can be used to treat and diagnose various B cell disorders, including B cell malignancies and autoimmune diseases.
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Claims

1. A CD19 antibody or an antigen-binding fragment thereof, comprising: (a) the heavy chain variable complementarity determining region (CDR) sequences of SYGMH (SEQ ID NO: 1) (HCDR1), LIWYDGSNKYYADSVKG (SEQ ID NO: 2) (HCDR2), and PVEGLLRGFDY (SEQ ID NO: 3) (HCDR3); and (b) a light chain variable region having the following complementarity determining region (CDR) sequence: i. RASQSVSSSYLA (SEQ ID NO: 7) (LCDR1), GASSRAT (SEQ ID NO: 9) (LCDR2), and QQAGAVPIT (SEQ ID NO: 12) (LCDR3); or ii. RASQSVSSSYLA (SEQ ID NO: 7) (LCDR1), GASSRAT (SEQ ID NO: 9) (LCDR2) and QQVDSLHPFT (SEQ ID NO: 13) (LCDR3); or iii. RASQSVSSSYLA (SEQ ID NO: 7) (LCDR1), GASSRAT (SEQ ID NO: 9) (LCDR2) and QQAGGVPPLT (SEQ ID NO: 14) (LCDR3); or iv. RASQSVRSSYLA (SEQ ID NO: 8) (LCDR1), GASSRAT (SEQ ID NO: 9) (LCDR2), and QQLFDSPYT (SEQ ID NO: 15) (LCDR3); or v. RASQSVRSSYLA (SEQ ID NO: 8) (LCDR1), GASSRAT (SEQ ID NO: 9) (LCDR2), and QQAGVPPLT (SEQ ID NO: 16) (LCDR3); or vi. RASQSVSSSYLA (SEQ ID NO: 7) (LCDR1), GASSRAT (SEQ ID NO: 9) (LCDR2), and QQAGGVPPFT (SEQ ID NO: 17) (LCDR3); or vii.RASQSVSSSYLA(SEQ ID NO:7)(LCDR1), GASNRAT(SEQ ID NO:10)(LCDR2) and QQAGVFPFT(SEQ ID NO:18)(LCDR3); or viii. RASQSVSSSYLA (SEQ ID NO:7) (LCDR1), GASRRAT (SEQ ID NO:11) (LCDR2) and QQAGIPPYT (SEQ ID NO:19) (LCDR3).

2. The CD19 antibody or antigen-binding fragment thereof according to claim 1, wherein the V L The region comprises an amino acid sequence identical to SEQ ID NOs: 20-27.

3. The CD19 antibody or antigen-binding fragment thereof according to claim 1, wherein the V H The region comprises an amino acid sequence identical to SEQ ID NO:

5.

4. The CD19 antibody or antigen-binding fragment thereof according to claim 1, wherein the V L The region comprises an amino acid sequence identical to one of SEQ ID NOs: 20-27, and the V H The amino acid sequence of the region is identical to SEQ ID NO:

5.

5. The CD19 antibody or antigen-binding fragment thereof of claim 1, wherein the CD19 antibody or fragment thereof is selected from the group consisting of: an IgA antibody, an IgG antibody, an IgE antibody, an IgM antibody, a bispecific or multispecific antibody, a Fab fragment, a Fab' fragment, a F(ab')2 fragment, a single-chain variable fragment (scFv), a masked antibody, and a tandem diabody.

6. The CD19 antibody or antigen-binding fragment thereof according to claim 1, wherein the CD19 antibody or fragment thereof is (i) monoclonal antibodies; or (ii) Antibodies comprising an IgG constant region.

7. The CD19 antibody or antigen-binding fragment thereof of claim 5, wherein the CD19 antibody or fragment thereof is a single-chain variable fragment (scFv).

8. The CD19 antibody or antigen-binding fragment thereof of claim 7, wherein the scFv comprises a linker sequence comprising SEQ ID Nos: 36-39.

9. The CD19 antibody or antigen-binding fragment thereof of claim 7, wherein the scFv comprises a signal peptide selected from SEQ ID NO: 40 or 41.

10. The CD19 antibody or antigen-binding fragment thereof according to claim 7, wherein the scFv comprises the amino acid sequence shown in SEQ ID NO: 42, 43 or 44.

11. The CD19 antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody or fragment thereof (i) with a K between 8 nanomolar (nM) and 242 nM D binds to CD19; and / or (ii) with an EC between 0.1 nM and 2.7 nM 50 Binds to CD19 on target cells.

12. A pharmaceutical composition comprising the CD19 antibody or antigen-binding fragment thereof according to any one of claims 1 to 11 and a pharmaceutically acceptable carrier.

13. A nucleic acid encoding The heavy chain variable region of the CD19 antibody or antigen-binding fragment thereof according to claim 1.

14. A nucleic acid encoding the light chain variable region of the CD19 antibody or antigen-binding fragment thereof according to claim 1.

15. A nucleic acid encoding (i) the heavy chain variable region of the CD19 antibody or antigen-binding fragment thereof according to claim 1; and (ii) the light chain variable region of the CD19 antibody or antigen-binding fragment thereof according to claim 1.

16. A vector comprising the nucleic acid of any one of claims 13-15.

17. An isolated cell comprising the vector of claim 16.

Citation Information

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