CD22 targeting-moiety for the treatment of B-cell acute lymphoblastic leukemia (B-ALL)

Patent metadata

Field	Value
Publication number	US-12522666-B2
Application number	US-202117910564-A
Country	US
Kind code	B2
Filing date	Mar 11, 2021
Priority date	Mar 11, 2020
Publication date	Jan 13, 2026
Grant date	Jan 13, 2026

Abstract

The present invention provides therapeutics for the treatment of CD22-positive cancers such as B-cell acute lymphoblastic leukemia (B-ALL). In particular, the present invention provides an anti-CD22 monoclonal antibody whose scFv as a part of chimeric antigen receptors (CAR) T-cells can target the fcst Ig extracellular domain of the CD22 antigen, the farthest domain from the membrane, for use in the treatment of CD22-positive cancers.

First claim

The invention claimed is:

1 . A CD22 targeting-moiety, wherein the CD22 targeting-moiety has binding affinity for the region of the first Ig extracellular domain of the CD22 antigen defined as SEQ ID NO 15, and wherein the CD22 targeting-moiety comprises a VL domain and VH domain, wherein the VL domain comprises LCDR1, LCDR2 and LCDR3 polypeptides and the VH domain comprises HCDR1, HCDR2 and HCDR3 polypeptides, and wherein LCDR1 consists of [QSLLDSDGKTY] (SEQ ID NO: 1), LCDR2 consists of [LVS] (SEQ ID NO: 2), LCDR3 consists of [WQGTHFPWT] (SEQ ID NO: 3), HCDR1 consists of [GDSITSGY] (SEQ ID NO: 4, HCDR2 consists of [ISYSGST] (SEQ ID NO: 5), and HCDR3 consists of [ARYPSPDAMNY] (SEQ ID NO: 6).

2 . A CD22 targeting-moiety according to claim 1 , wherein the CD22 targeting-moiety is an antibody, F(ab′) 2 , Fab, scFab or scFv, and wherein the VL domain consists of SEQ ID NO: 21 and the VH domain consists of SEQ ID NO: 20.

3 . The CD22 targeting-moiety of claim 1 , wherein the CD22 targeting-moiety is an antibody, F(ab′) 2 , Fab, scFab or scFv, comprising a VL domain and VH domain, wherein the VL domain consists of SEQ ID NO: 7 and the VH domain consists of SEQ ID NO: 8.

4 . The CD22 targeting-moiety of claim 3 , wherein the CD22 targeting-moiety is a scFv comprising a VL domain and VH domain, wherein the VL domain consists of SEQ ID NO: 7 and the VH domain consists of SEQ ID NO: 8.

5 . The CD22 targeting-moiety of claim 1 , wherein the CD22 targeting-moiety is a scFv consisting of SEQ ID NO: 9.

6 . A chimeric antigen receptor (CAR) comprising:
a. an extracellular domain comprising a CD22 targeting-moiety, wherein the CD22 targeting-moiety is as defined in claim 1 ; b. a transmembrane domain; and c. an intracellular signaling domain.

7 . The CAR according to claim 6 , wherein the transmembrane domain comprises the transmembrane domain of CD28, CD3, CD45, CD4, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, or CD154.

8 . The CAR according to claim 7 , wherein the transmembrane domain comprises the transmembrane domain of CD8.

9 . The CAR according to claim 6 , wherein the intracellular signaling domain comprises the intracellular domain of CD3ζ, FcRγ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b or CD66b.

10 . The CAR according to claim 9 , wherein the intracellular signaling domain comprises the intracellular domain of CD3ζ.

11 . The CAR according to claim 6 , wherein the CAR further comprises a costimulatory signaling domain, preferably the costimulatory signaling domain comprises the intracellular domain of CD27, CD28, CD137, CD134, CD30, CD40, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, or CD276.

12 . The CAR according to claim 11 , wherein the costimulatory signaling domain comprises the intracellular domain of CD137.

13 . The CAR according to claim 6 , wherein the CD22 targeting moiety is a scFV, preferably, the scFV comprises a VL domain consisting of SEQ ID NO: 7 and a VH domain consisting of SEQ ID NO: 8.

14 . A nucleic acid encoding the CAR according to claim 6 .

15 . A T-cell comprising the nucleic acid according to claim 14 .

16 . A method of treating a CD22-positive cancer, wherein the method comprises administering the CD22 targeting moiety of claim 1 to a patient in need thereof, and wherein the CD22-positive cancer is B-cell acute lymphoblastic leukemia (B-ALL).

17 . A method of treating a CD22-positive cancer, wherein the method comprises administering the T-cell of claim 15 to a patient in need thereof, and wherein the CD22-positive cancer is B-cell acute lymphoblastic leukemia (B-ALL).

18 . The method of claim 16 , wherein the CD22-positive cancer, wherein the CD22-positive cancer is B-cell acute lymphoblastic leukemia (B-ALL), which is a CD19 − B-ALL relapse.

19 . The method of claim 17 , wherein the CD22-positive cancer, wherein the CD22-positive cancer is B-cell acute lymphoblastic leukemia (B-ALL), which is a CD19 − B-ALL relapse.

Assignees

• Fundacio Inst De Recerca Contra La Leucemia Josep Carreras
• Inst Catalana De Recerca I Estudis Avancats Icrea
• Univ Barcelona
• Fundacio Inst Dinvestigacio En Ciencies De La Salut Germans Trias I Pujol Igtp
• Onechain Immunotherapeutics S L

Inventors

• Menéndez Buján Pablo
• Velasco Hernández Talía
• Zanetti Samanta Romina
• Engel Rocamora Pablo
• Sánchez Martínez Diego
• Gutierrez Agüera Francisco
• Fernández Martín Adrián
• Díaz Cortés Victor Manuel

Classifications

• A61K40/4212

  CD22, BL-CAM, siglec-2 or sialic acid binding Ig-related lectin 2 · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/48

  Blood cells, e.g. leukemia or lymphoma · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title