Granted Patent B2

US 12,552,874 · App. 17/779,720 · Granted Feb 17, 2026

Inventors: Vered Padler-Karavani (Tel Aviv, IL); Ron Amon (Tel Aviv, IL); Ronit Rosenfeld (Tel Aviv, IL)

Assignee: RAMOT AT TEL-AVIV UNIVERSITY LTD.

C07K16/2896A61K47/6849A61P35/00G01N33/57492C07K16/00C07K16/46C07K2317/565C07K2317/567C07K2317/622C07K2317/734C07K2317/92G01N2400/02

Abstract

Claims (26)

1 . A monoclonal antibody (mAb) or a fragment thereof that specifically binds to Sialyl Lewis A glycan (SLeA), wherein the mAb or the fragment comprises an antigen binding domain comprising a heavy-chain variable domain (VH) and a light-chain variable domain (VL) each comprising three complementarity determining regions (CDRs), wherein the VH-CDR 1, 2 and 3 comprise amino acid sequences SEQ ID NOs: 15, 12, and 8, respectively, and the VL-CDRs 1, 2 and 3 comprise amino acid sequences SEQ ID NO: 9, 10, and 11, respectively.

2 . The mAb or fragment according to claim 1 , wherein VH-CDR1 comprises amino acid sequence selected from SEQ ID NO: 6 and 15, and the VH-CDR2 comprises amino acid sequence selected from SEQ ID NO: 12 and 21.

3 . The mAb or fragment according to claim 1 , wherein the CDRs 1, 2, and 3 of the VH domain comprises amino acid sequences SEQ ID NOs: 15, 21 and 8, respectively, the CDRs 1, 2, and 3 of the VL domain comprise amino acid sequences SEQ ID NOs: 9, 10 and 11, respectively, VH-framework domains (FRs) 1, 2 and 4 comprising amino acid sequences SEQ ID NOs: 24, 26 and 27, respectively, and a VL-FR1 comprising the amino acid sequence SEQ ID NO: 28.

4 . The mAb or fragment according to claim 1 , comprising:

i. a set of six CDR sequences comprising SEQ ID NOs: 15, 21, 8, 9, 10 and 11;

ii. a set of four VH framework sequences comprising SEQ ID NOs: 24, 26, 29 and 27;

and

iii. a set of four VL framework sequences comprising SEQ ID NOs: 28, 30, 31 and 32.

5 . The mAb or the fragment according claim 1 , wherein the VH domain comprises amino acid sequence set forth in SEQ ID NO: 3 and the VL domain comprises amino acid sequence set forth in SEQ ID NO: 5.

6 . The mAb or the fragment according to claim 1 , wherein the fragment is a single chain variable fragment (scFv).

7 . The mAb or the fragment according to claim 6 , wherein the scFv comprises amino acid sequences SEQ ID NO: 3 and SEQ ID NO: 5.

8 . The mAb or the fragment according to claim 7 , wherein the scFv comprises amino acid sequence SEQ ID NO: 22 or an analog thereof having at least 90% sequence identity to said sequence.

9 . The mAb or the fragment according to claim 1 , characterized by at least one of:

(i) the mAb or the fragment binds SLeA glycan with an equilibrium dissociation constant (K D ) of from about 0.1 to about 30 nM;

(ii) the selectivity of said mAb or the fragment to SLeA glycan is at least 90%;

(iii) the mAb or the fragment is a chimeric antibody or fragment:

(iv) the mAb or the fragment has an IgG structure; and

(v) the light chain constant region is selected from kappa and lambda.

10 . A conjugate comprising the mAb or the fragment according to claim 1 .

11 . A pharmaceutical composition comprising the mAb or the fragment according to claim 1 or a conjugate thereof, and a pharmaceutically acceptable carrier.

12 . A kit for diagnosing a cancer in a subject, wherein the kit comprises the mAb or the fragment according to claim 1 or a conjugate thereof and means for detecting the amount of the mAb or the fragment bound to cells of the biological sample.

13 . A monoclonal antibody (mAb) or a fragment thereof that specifically binds to Sialyl Lewis A glycan (SLeA), wherein the mAb or the fragment comprises an antigen binding domain comprising a heavy-chain variable domain (VH) and a light-chain variable domain (VL) each comprising three complementarity determining regions (CDRs) and four framework (FR) domains, wherein the VH-CDR 1, 2 and 3 comprise amino acid sequences SEQ ID NOs: 15, 12, and 8, respectively, the VL-CDRs 1, 2 and 3 comprise amino acid sequences SEQ ID NOs: 9, 10 and 11, respectively, the VH-FRs 1, 2 and 4 comprises acid sequences SEQ ID NOs: 23, 26 and 27, respectively, and the VL-FR 1 comprises acid sequence SEQ ID NO: 28.

14 . The mAb or fragment according to claim 13 , wherein the CDRs 1, 2, and 3 of the VH domain comprises amino acid sequences SEQ ID NOs: 15, 21 and 8, respectively, the CDRs 1, 2, and 3 of the VL domain comprise amino acid sequences SEQ ID NOs: 9, 10 and 11, respectively, the VH-(FRs) 1, 2 and 4 comprise amino acid sequences SEQ ID NOs: 24, 26 and 27, respectively, and the VL-FR1 comprising the amino acid sequence SEQ ID NO: 28.

15 . The mAb or the fragment according to claim 13 , wherein the fragment is a single chain variable fragment (scFv).

16 . A conjugate comprising the mAb or the fragment according to claim 13 .

17 . A kit for diagnosing, cancer in a subject, wherein the kit comprises the mAb or fragment thereof according to claim 15 or a conjugate thereof and means for detecting the amount of the antibodies or antibody fragments bound to cells of the biological sample.

Assignments (1)

Continuity (3)

References Cited (77)