Tissue factor binding antibodies and uses thereof

By providing antibodies that specifically bind to TF for IHC detection, the problem of accuracy in detecting TF expression and distribution has been solved, enabling accurate diagnosis and treatment decision support for TF-related cancers.

CN121895455BActive Publication Date: 2026-06-09EVOPOINT BIOSCIENCES CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
EVOPOINT BIOSCIENCES CO LTD
Filing Date
2026-03-25
Publication Date
2026-06-09

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Abstract

The present application relates to tissue factor binding antibodies and uses thereof, in particular to an antibody or antigen binding fragment thereof specifically binding to TF, and a kit containing the antibody or antigen binding fragment, the antibody or antigen binding fragment comprising: (i) LCDR1, LCDR2 and LCDR3 sequences of a light chain variable region as shown in SEQ ID NO: 1, and (ii) HCDR1, HCDR2 and HCDR3 sequences of a heavy chain variable region as shown in SEQ ID NO: 2, wherein the CDR is defined according to IMGT, Kabat, Chothia or Contact or any combination thereof. The tissue factor binding antibody provided by the present application has high sensitivity, high accuracy and high precision, and can meet the demand for accurate detection of tissue factor.
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Claims

1. An antibody or antigen-binding fragment thereof that binds to tissue factor TF, comprising a light chain variable region and a heavy chain variable region, wherein the three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the light chain variable region and the three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the heavy chain variable region are: (i) According to the CDR defined by IMGT, LCDR1 is the amino acid sequence shown in SEQ ID NO: 3, LCDR2 is the amino acid sequence shown in SEQ ID NO: 4, LCDR3 is the amino acid sequence shown in SEQ ID NO: 5, and HCDR1 is the amino acid sequence shown in SEQ ID NO: 6, HCDR2 is the amino acid sequence shown in SEQ ID NO: 7, and HCDR3 is the amino acid sequence shown in SEQ ID NO: 8; or (ii) According to the CDR defined by Kabat, LCDR1 is the amino acid sequence shown in SEQ ID NO: 9, LCDR2 is the amino acid sequence shown in SEQ ID NO: 10, LCDR3 is the amino acid sequence shown in SEQ ID NO: 11, and HCDR1 is the amino acid sequence shown in SEQ ID NO: 12, HCDR2 is the amino acid sequence shown in SEQ ID NO: 13, and HCDR3 is the amino acid sequence shown in SEQ ID NO: 14; or (iii) According to the CDR defined by Chothia, LCDR1 is the amino acid sequence shown in SEQ ID NO: 15, LCDR2 is the amino acid sequence shown in SEQ ID NO: 16, LCDR3 is the amino acid sequence shown in SEQ ID NO: 17, and HCDR1 is the amino acid sequence shown in SEQ ID NO: 18, HCDR2 is the amino acid sequence shown in SEQ ID NO: 19, and HCDR3 is the amino acid sequence shown in SEQ ID NO: 20; or (iv) According to the CDR defined by Contact, LCDR1 is the amino acid sequence shown in SEQ ID NO: 21, LCDR2 is the amino acid sequence shown in SEQ ID NO: 22, LCDR3 is the amino acid sequence shown in SEQ ID NO: 23, and HCDR1 is the amino acid sequence shown in SEQ ID NO: 24, HCDR2 is the amino acid sequence shown in SEQ ID NO: 25 and HCDR3 is the amino acid sequence shown in SEQ ID NO:

26.

2. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein: The heavy chain variable region contains the amino acid sequence shown in SEQ ID NO:

2.

3. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein: The heavy chain variable region contains an amino acid sequence that is at least 80% identical to the sequence of SEQ ID NO:

2.

4. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein: The light chain variable region contains the amino acid sequence shown in SEQ ID NO:

1.

5. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein: The light chain variable region contains an amino acid sequence that has at least 80% sequence identity with SEQ ID NO:

1.

6. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:2, and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:

1.

7. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein, The antibody is a full-length antibody composed of two heavy chains and two light chains. The antigen-binding fragment is selected from the following antibody fragments: Fab, Fab', Fab'-SH, Fv, scFv, scFab, or (Fab')2.

8. The antibody or antigen-binding fragment thereof that binds to tissue factor TF according to claim 1, wherein the antibody is a murine antibody.

9. An isolated nucleic acid encoding an antibody or antigen-binding fragment thereof that binds to tissue factor TF as described in any one of claims 1-8.

10. A vector comprising the nucleic acid of claim 9.

11. A host cell comprising the nucleic acid of claim 9 or the vector of claim 10.

12. A method for preparing an antibody or antigen-binding fragment thereof that binds to tissue factor TF, the method comprising culturing a host cell containing the nucleic acid under conditions suitable for expressing a nucleic acid encoding an antibody or antigen-binding fragment thereof that binds to tissue factor TF as described in any one of claims 1-8, and isolating the antibody or antigen-binding fragment thereof.

13. A method for detecting TF in a biological sample for non-diagnostic and non-therapeutic purposes, the method comprising: (a) Contacting a biological sample with an antibody or antigen-binding fragment thereof that binds tissue factor TF as described in any one of claims 1-8; and (b) Detect the complex formed by the antibody or its antigen-binding fragment and TF to determine whether the biological sample contains TF.

14. The method of claim 13, wherein the biological sample is selected from one or more of cell samples, tissue samples, and body fluid samples.

15. The method according to any one of claims 13-14, wherein the complex is detected by immunohistochemical staining.

16. The method of claim 15, wherein the method comprises: (i) Obtain paraffin sections; (ii) Dewaxing and hydration; (iii) Antigen retrieval; (iv) Contact the slide with the antibody that binds tissue factor TF; as well as (v) Detect TF antigens that bind to the antibody or its antigen-binding fragment.

17. The method of claim 16, wherein the antigen retrieval step comprises treating the slide at 95-100°C for 5-30 minutes using an antigen retrieval buffer; And / or, the antigen retrieval is performed using an antigen retrieval buffer containing citrate buffer or EDTA buffer.

18. The method according to claim 16 or 17, wherein step (iv) comprises incubating the antibody at a concentration of 1-10 μg / ml at 15-30°C for 30-90 minutes.

19. The method of claim 16 or 17, wherein step (v) comprises detection using a secondary antibody detection system, wherein the secondary antibody detection system comprises the following components: (i) Peroxidase blocking agent; (ii) Reagents after primary antibody used to amplify the detection signal; (iii) Enzyme-labeled secondary antibodies; (iv) The chromogenic substrate of the enzyme; and (v) Nuclear counterstaining reagent.

20. The method according to claim 19, wherein the enzyme-labeled secondary antibody is a polyhortradiction peroxidase or alkaline phosphatase-labeled secondary antibody.

21. A kit comprising an antibody or antigen-binding fragment thereof that binds to tissue factor TF as described in any one of claims 1-8.

22. The kit according to claim 21, further comprising antigen retrieval buffer.

23. The kit according to any one of claims 21-22, further comprising a secondary antibody detection system, the secondary antibody detection system comprising the following components: (i) Peroxidase blocking agent; (ii) Reagents after primary antibody used to amplify the detection signal; (iii) Enzyme-labeled secondary antibodies; (iv) The chromogenic substrate of the enzyme; and (v) Nuclear counterstaining reagent.

24. Use of the antibody or antigen-binding fragment thereof for binding tissue factor TF according to any one of claims 1-8, or the kit according to any one of claims 21-23, in the preparation of a medicament for the adjunctive diagnosis of TF-related diseases, or in the preparation of a product for determining whether a subject is suitable for anti-TF drug treatment, or in the preparation of a product for predicting a subject's responsiveness to anti-TF drug treatment, wherein, TF-related diseases are tumors associated with abnormal TF expression, and the anti-TF drugs are ADC drugs based on anti-TF antibodies; the tumors associated with abnormal TF expression include cervical cancer, pancreatic cancer, skin cancer, ovarian cancer, breast cancer, colorectal cancer, esophageal cancer, glioma, head and neck squamous cell carcinoma, prostate cancer, gastric cancer, non-small cell lung cancer, melanoma, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, or acute myeloid leukemia.