Granted Patent
B2
US 12,195,513 · App. 17/589,093 · Granted Jan 14, 2025
LILRB1-based chimeric antigen receptor
Inventors:
Carl Alexander Kamb (Westlake Village, CA); Agnes E. Hamburger (Newbury Park, CA); Breanna Diandreth (Agoura Hills, CA); Mark E. Daris (Newbury Park, CA); Kiran Deshmukh (Culver City, CA)
Assignee:
A2 Biotherapeutics, Inc.
C07K14/70503A61K35/17A61P35/00C07K14/7051C07K14/70521C07K14/70578C07K16/2803C07K16/2833C07K16/3069A61K2039/505C07K2317/622C07K2317/76C07K2317/92C07K2319/03
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Abstract
Provided are chimeric antigen receptors having the hinge, transmembrane region, and/or intracellular domain of LILRB1, or functional fragments or variants thereof. Also provided herein are cells comprising the LILRB1 based receptors, and methods of making and using same.
Claims (23)
1. A method of treating a subject with a disease or a disorder, comprising administering to the subject an immune cell comprising an inhibitory receptor comprising:
a) an antigen binding domain comprising a single chain variable fragment (scFv);
b) an LILRB1 hinge domain;
c) a transmembrane domain; and
d) an LILRB1 intracellular domain comprising at least one immunoreceptor tyrosine-based inhibitory motif (ITIM) selected from the group consisting of NLYAAV (SEQ ID NO: 8), VTYAEV (SEQ ID NO: 9), VTYAQL (SEQ ID NO: 10), and SIYATL (SEQ ID NO: 11),
wherein the LILRB1 hinge domain, transmembrane domain, and LILRB1 intracellular domain comprises a sequence at least 95% identical to SEQ ID NO: 2 or 3.
2. The method of claim 1 , wherein the immune cell comprises an activator receptor.
3. The method of claim 2 , wherein the activator receptor is a chimeric antigen receptor or a T cell receptor.
4. The method of claim 3 , wherein the chimeric antigen receptor or T cell receptor specifically binds to a target antigen expressed on cancer cells.
5. The method of claim 1 , wherein the intracellular domain comprises a sequence at least 95% identical to SEQ ID NO: 7.
6. The method of claim 1 , wherein the transmembrane domain comprises a LILRB1 transmembrane domain.
7. The method of claim 6 , wherein the LILRB1 transmembrane domain comprises a sequence at least 95% identical to SEQ ID NO: 5.
8. The method of claim 1 , wherein the LILRB1 hinge domain comprises a sequence at least 95% identical to any one of SEQ ID NO 4, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 80 or SEQ ID NO: 81.
9. The method of claim 1 , wherein the LILRB1 hinge and transmembrane domains comprises a sequence at least 95% identical to SEQ ID NO: 20.
10. The method of claim 1 , wherein the transmembrane and LILRB1 intracellular domain comprises a sequence at least 95% identical to SEQ ID NO: 21.
11. The method of claim 1 , wherein the LILRB1 hinge, transmembrane and LILRB1 intracellular domains comprises SEQ ID NO: 2.
12. The method of claim 1 , wherein the antigen binding domain is specific to a major histocompatibility class I allele.
13. The method of claim 12 , wherein the major histocompatibility class I allele comprises HLA-A allele, HLA-B allele, HLA-C allele or HLA-E allele.
14. The method of claim 13 , wherein the HLA-A allele is HLA-A*02.
15. The method of claim 1 , wherein the scFv comprises complementarity determined regions (CDRs) comprising SEQ ID NOS: 22-27 or SEQ ID NOS: 28-33.
16. The method of claim 15 , wherein the scFv comprises a sequence at least 95% identical to any one of SEQ ID NOS: 35, 37, 45 or 125.
17. The method of claim 1 , wherein the inhibitory receptor comprises an amino acid sequence of any one of SEQ ID NOS: 50, 64, 89, 120, or 122.
18. The method of claim 1 , wherein the immune cell is a T cell.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 18, 2022
From: KAMB, CARL ALEXANDER; HAMBURGER, AGNES E.; DIANDRETH, BREANNA; DARIS, MARK E.; DESHMUKH, KIRAN
To: A2 BIOTHERAPEUTICS, INC.
Reel/Frame 060534/0834 →
Continuity (5)
Continuation
PCTUS2020064607
· Dec 11, 2020
Provisional Application
63085969
· Sep 30, 2020
Provisional Application
62946888
· Dec 11, 2019
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