Guided combinational therapeutic antibody
AssigneeAntibody Biopharm Inc.
InventorGuan Yongjun
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Abstract
The present invention relates to novel multi-specific antibodies comprising fine tuned combination of low affinity single binding domain fragments to selectively target double targets on cancer cell, and use thereof for therapy, such as for guided immunotherapy.
Claims14
An engineered bi-specific antibody, comprising:
- (i) a first chain comprising a first antigen binding domain which binds a first target, and having a first affinity about 10−5˜10−8M;
- and
- (ii) a second chain comprising a second antigen binding domain which binds a second target, and having a second affinity about 10−5˜10−8M;
- wherein said first antigen binding domain is linked to the N-terminal of the first constant heavy chain of said bi-specific antibody, wherein said second antigen binding domain is linked to the N-terminal of a light chain of said bi-specific antibody, wherein said first target and second target are both co-localized on a target cell;
- and
- wherein said bi-specific antibody preferably bind to said target cell than to cells only expressing either said first target or said second target, with an avidity about 10−9˜10−12M. (Currently amended) The antibody of claim 1, wherein said first target and second target is selected from a list comprising a tumor target, a disease-specific receptor, and an immune regulatory function target.
The antibody of claim 2, wherein said tumor target is selected from a list comprising Her2, CEA, ROR2, TROP2, mGluR1 and EGFR.
The antibody of claim 2, wherein said checkpoint receptor is selected from a list comprising PD-L1, CD47, LAG3, CD59 and Tim 3.
An engineered tri-specific antibody, comprising:
- (i) a first chain comprising a first antigen binding domain that binds a first target, having a first affinity about 10−5˜10−8M;
- (ii) a second chain comprising a second antigen binding domain which binds a second target, having a second affinity about 10−5˜10−8M;
- and a third antigen binding domain which binds a third target, having a third affinity about 10−5˜10−8M;
- wherein said first antigen binding domain is linked to the N-terminal of the first constant heavy chain of said tri-specific antibody, wherein said second antigen binding domain is linked to the N-terminal of a light chain of said tri-specific antibody, wherein said first target and second target are both co-localized on a same target cell;
- and
- wherein said tri-specific antibody preferably bind to said target cell than to cells only expressing either said first target or said second target, with an avidity about 10−9˜10−12M, wherein said third antigen binding domain is linked to the c-terminal of the light chain of said tri-specific antibody;
- and wherein said third target is an effector function target or a regulatory factor;
- and wherein said third antigen binding domain preferably mediates effector cells or a regulatory factor to the target cell.
The antibody of claim 2, wherein the heavy chain comprises any one of the sequences of Seq ID No. 1, Seq ID No. 2, Seq ID No. 3, Seq ID No. 4, Seq ID No. 5, Seq ID No. 6, Seq ID No. 7. Seq ID No. 8, Seq ID No. 9, Seq ID No. 10, Seq ID No. 11, Seq ID No. 2, Seq ID No. 28, Seq ID No. 29, Seq ID No. 32, Seq ID No. 33, Seq ID No. 36, Seq ID No. 37, Seq ID No. 40, Seq ID No. 41, Seq ID No. 60, Seq ID No. 61, Seq ID No. 66, Seq ID No. 67, Seq ID No. 68, and Seq ID No. 69.
An antibody of claim 2, therein the light chain comprises any one of the sequences of Seq ID No. 1, Seq ID No. 2, Seq ID No. 3, Seq ID No. 4, Seq ID No. 5, Seq ID No. 6, Seq ID No. 7, Seq ID No. 8, Seq ID No. 9, Seq ID No. 10, Seq ID No. 11, Seq ID No. 12, Seq ID No. 30, Seq ID No. 31, Seq ID No. 34, Seq ID No. 35, Seq ID No. 38, Seq ID No. 39, Seq ID No. 42, and Seq ID No. 43.
The antibody of claim 2, wherein
- (i) the heavy chain comprises any one of the sequences of SEQ ID No. 1, No. 2, No. 3, No. 4, No. 36, No. 37, No. 40, No. 41;
- and
- (ii) the light chain comprises any one of the sequences of SEQ ID No. 5, No. 6, No. 7, No. 8, No. 38, No. 39, No. 42, No. 43, wherein said antibody binds to Her2 and CD47 double positive target cell.
The antibody of claim 2, wherein
- (i) the heavy chain comprises any one of the sequences of SEQ ID No. 5, No. 6, No. 7, No. 8, No. 28, No. 29, No. 32, No. 33;
- and
- (ii) the light chain comprises any one of the sequences of SEQ ID No. 9, No. 10, No. 11, No. 12, No. 30, No. 31, No. 34, No. 35, wherein said antibody binds to PD-L1 and CD47 double positive target cell.
Dependencies are inferred from the claim text.