IP Library › Granted Patent US 12,252,538
Granted Patent B2
US 12,252,538 · App. 17/294,560 · Granted Mar 18, 2025

Monoclonal antibodies against IgV domain of B7-H3 and uses thereof

Inventor: Xingxing Zang (New York, NY)
Assignee: ALBERT EINSTEIN COLLEGE OF MEDICINE
C07K16/2827C07K16/2809C07K2317/24C07K2317/31C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,252,538
App. No.
17/294,560
Granted
Mar 18, 2025
Kind
B2
Abstract

The present disclosure provides monoclonal antibodies that bind to an IgV domain of human B7-H3. Also provided are methods of using these antibodies in treating cancer and infection and in imaging B7-H3 positive cells.

Claims (31)

1. An antibody or an antigen-binding fragment thereof that specifically binds to an IgV domain of a B7-H3 protein;

wherein the antibody is monoclonal 8B12 or the antigen-binding fragment thereof is an antigen binding fragment of the monoclonal 8B12 antibody comprising:

(a) a VH region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 1, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 3; and

(b) a VL region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 4, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 5, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 6; or

wherein the antibody is monoclonal 12B4 or the antigen-binding fragment thereof is an antigen binding fragment of the monoclonal 12B4 antibody comprising:

(a) a VH region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 7, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 8, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 9; and

(b) a VL region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 10, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 11, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 12; or

wherein the antibody is monoclonal 24D12 or the antigen-binding fragment thereof is an antigen binding fragment of the monoclonal 24D12 antibody comprising:

(a) a VH region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 7, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 8, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 15; and

(b) a VL region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 13, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 14, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 16.

2. The antibody or the antigen-binding fragment thereof of claim 1 , further comprising an antigen-binding fragment of a monoclonal antibody that binds to a CD3 component of a T-cell receptor (TCR) complex on T cells.

3. The antibody or the antigen-binding fragment thereof of claim 1 , further comprising a detectable marker.

4. The antibody or the antigen-binding fragment thereof of claim 1 , further comprising a cytotoxic agent conjugated thereto.

5. The antigen or the antigen-binding fragment thereof of claim 1 , for use in the manufacture of a medicament.

6. A composition comprising an isolated nucleic acid comprising a nucleotide sequence that encodes a CDR of the antibody or the antigen-binding fragment thereof of claim 1 .

7. The composition of claim 6 , further comprising a host cell or a vector comprising the isolated nucleic acid of claim 6 .

8. An antibody or an antigen-binding fragment thereof that specifically binds to an IgV domain of a B7-H3 protein;

wherein the antibody is humanized 8B12 or the antigen-binding fragment thereof is an antigen binding fragment of the humanized 8B12 antibody comprising:

(a) a VH region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 1, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 2, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 3; and

(b) a VL region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 4, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 5, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 6; or

wherein the antibody is humanized 12B4 or the antigen-binding fragment thereof is an antigen binding fragment of the humanized 12B4 antibody comprising:

(a) a VH region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 7, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 8, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 9; and

(b) a VL region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 10, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 11, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 12; or

wherein the antibody is humanized 24D12 or the antigen-binding fragment thereof is an antigen binding fragment of the humanized 24D12 antibody comprising:

(a) a VH region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 7, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 8, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 15; and

(b) a VL region comprising: CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 13, CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 14, and CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 16.

9. The antibody or the antigen-binding fragment thereof of claim 8 , further comprising a detectable marker.

10. The antibody or the antigen-binding fragment thereof of claim 8 , further comprising a cytotoxic agent conjugated thereto.

11. The antigen or the antigen-binding fragment thereof of claim 8 for use in the manufacture of a medicament.

12. A composition comprising an isolated nucleic acid comprising a nucleotide sequence that encodes a CDR of the antibody or the antigen-binding fragment thereof of claim 8 .

13. The composition of claim 12 , further comprising a host cell or a vector comprising the isolated nucleic acid of claim 12 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2022
From: ZANG, XINGXING
To: ALBERT EINSTEIN COLLEGE OF MEDICINE
Reel/Frame 059324/0462 →
Continuity (2)
Provisional Application 62768128 · Nov 16, 2018
Related Publication 20220010018A1 · Jan 13, 2022
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