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Humanized Anti-folate receptor 1 chimeric antigen receptors and uses thereof

A chimeric antigen receptor and antigen technology, applied in the direction of anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, receptor/cell surface antigen/cell surface determinant, antibody, etc., can solve the problem of efficacy , poor response, etc.

Pending Publication Date: 2021-11-30
PHANES BIOPHARMACEUTICALS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, poor response, insufficient efficacy and / or safety issues still need to be addressed

Method used

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  • Humanized Anti-folate receptor 1 chimeric antigen receptors and uses thereof
  • Humanized Anti-folate receptor 1 chimeric antigen receptors and uses thereof
  • Humanized Anti-folate receptor 1 chimeric antigen receptors and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0471] Embodiment 1 is an isolated polynucleotide comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises: (a) an extracellular domain, the cellular The ectodomain comprises at least one antigen binding domain that specifically binds folate receptor 1 (FOLR1); (b) a hinge region; (c) a transmembrane region; and (d) an intracellular signaling domain.

Embodiment approach 2

[0472] Embodiment 2 is the isolated polynucleotide of embodiment 1, wherein the antigen binding domain comprises heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining region, each having the following polypeptide sequences 1 (LCDR1), LCDR2, and LCDR3:

[0473] (1) SEQ ID NO: 17, 18, 19, 41, 42 and 43;

[0474] (2) SEQ ID NO: 20, 21, 22, 44, 45 and 46;

[0475] (3) SEQ ID NO: 23, 24, 25, 47, 48 and 49;

[0476] (4) SEQ ID NO: 26, 27, 28, 50, 51 and 52;

[0477] (5) SEQ ID NO:29, 30, 31, 53, 54 and 55;

[0478] (6) SEQ ID NO: 32, 33, 34, 56, 57 and 58;

[0479] (7) SEQ ID NO: 35, 36, 37, 59, 60 and 61; or

[0480] (8) SEQ ID NO: 38, 39, 40, 62, 63 and 64;

[0481] Wherein the antigen binding domain specifically binds to FOLR1, preferably human FOLR1.

Embodiment approach 3

[0482] Embodiment 3 is the isolated polynucleotide of embodiment 1, wherein the antigen binding domain comprises heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, light chain complementarity determining region, each having the following polypeptide sequences 1 (LCDR1), LCDR2, and LCDR3:

[0483] (1) SEQ ID NO:65, 66, 67, 89, 90 and 91;

[0484] (2) SEQ ID NO:68, 69, 70, 92, 93 and 94;

[0485] (3) SEQ ID NO:71, 72, 73, 95, 96 and 97;

[0486] (4) SEQ ID NO: 74, 75, 76, 98, 99 and 100;

[0487] (5) SEQ ID NO:77, 78, 79, 101, 102 and 103;

[0488] (6) SEQ ID NO:80, 81, 82, 104, 105 and 106;

[0489] (7) SEQ ID NO: 83, 84, 85, 107, 108 and 109; or

[0490] (8) SEQ ID NO:86, 87, 88, 110, 111 and 112;

[0491] Wherein the antigen binding domain specifically binds to FOLR1, preferably human FOLR1.

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PUM

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Abstract

Chimeric antigen receptors (CARs) specific to F0LR1, vectors encoding the FOLR1 CAR, recombinant host cells comprising the FOLR1 CAR (CAR-Ts or CAR-NKs), and methods of using the CAR-Ts or CAR-NKs to treat a disease associated with the expression of FOLR1 thereof are described. Humanized anti-FOLRl monoclonal antibodies and antigen-binding fragments thereof are also described.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application 62 / 832,975, filed April 12, 2019, U.S. Provisional Application 62 / 863,330, filed June 19, 2019, and U.S. Provisional Application 62 / 931,988, filed November 7, 2019 . Each disclosure is incorporated herein by reference in its entirety. technical field [0003] The present invention relates to anti-folate receptor 1 (FOLR1) chimeric antigen receptor (CAR), nucleic acid encoding CAR and expression vector, T cells engineered to express CAR (CAR-T) and NK cells engineered to express CAR (CAR-NK). Also provided are methods for preparing CAR, methods for preparing CAR-T / CAR-NK, and methods for using CAR-T / CAR-NK to treat diseases related to FOLR1 expression, including cancer. [0004] Sequence Listing References Submitted Electronically [0005] This application contains a Sequence Listing submitted electronically via EFS-Web as a Sequence Listing in ASCII for...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K16/30A61K39/395
CPCC07K16/28C07K2317/24C07K2317/622C07K2319/03C07K14/7051A61K39/4611A61K39/4613A61K39/4631A61K39/464402C12N5/0636C07K14/705A61P35/00C07K2319/02C12N2510/00C07K16/2809A61K35/17A61K38/1774A61K39/3955A61K45/06C07K14/70517C07K14/70521C07K2317/565C07K2319/30C07K2319/33
Inventor 王明晗邹晖贾海群
Owner PHANES BIOPHARMACEUTICALS LTD