IP Library Granted Patent US 11,286,312
Granted Patent B2
US 11,286,312 · App. 15/779,417 · Granted Mar 29, 2022

Multispecific antibodies

Inventors: Pallavi Bhatta (Slough, GB); Laura Starkie (Slough, GB); Michael John Wright (Slough, GB)
Assignee: UCB BIOPHARMA SRL
C07K16/468C07K14/395C07K16/00C07K16/14C12N15/1037C07K2317/31C07K2317/55C07K2317/569C07K2317/622C07K2317/92C07K2319/00C07K2319/21C07K2319/23C07K2319/30
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Quick Facts
Patent No.
US 11,286,312
App. No.
15/779,417
Granted
Mar 29, 2022
Kind
B2
Abstract

The present invention relates to heterodimerically-tethered bispecific protein complexes (according to the general formula of A-X:Y-B) and libraries/multiplexes thereof for use in research and therapy and in particular an in vitro/ex vivo method of detecting synergistic biological function of otherwise unknown pairs of targets.

Claims (29)

1. A bispecific protein complex comprising A-X and Y-B wherein:

A-X is a first fusion protein;

Y-B is a second fusion protein;

X and Y are first and second binding partners of a binding pair;

A is a first protein component of the bispecific protein complex that is specific for a first target, wherein A is independently selected from the group consisting of a Fab fragment, a Fab′ fragment, and a single chain Fv (scFv);

B is a second protein component of the bispecific protein complex that is specific for a second target, wherein B is a single chain Fv;

X is the first binding partner of the binding pair independently selected from an antigen and a single chain Fv; and

Y is the second binding partner of the binding pair independently selected from an antigen and a single chain Fv;

with the proviso that when X is an antigen, Y is a single chain Fv specific to the antigen represented by X; and when Y is an antigen, X is a single chain Fv specific to the antigen represented by Y;

wherein the first target and the second target are different; and

wherein the antigen is a GCN4 peptide having SEQ ID NO: 1 or amino acids 1 to 38 of SEQ ID NO: 1, and the scFv is 52SR4 having SEQ ID NO: 3 or amino acids 1 to 243 of SEQ ID NO: 3.

2. The bispecific protein complex according to claim 1 , wherein X is fused to the C-terminal of A, or to the C-terminus of the scFv.

3. The bispecific protein complex according to claim 1 , wherein Y is fused to the C-terminal of B.

4. The bispecific protein complex according to claim 1 , wherein A is a Fab fragment.

5. The bispecific protein complex according to claim 1 , wherein X is the scFv 52SR4 having SEQ ID NO: 3 or amino acids 1 to 243 of SEQ ID NO: 3, and Y is the GCN4 peptide having SEQ ID NO: 1 or amino acids 1 to 38 of SEQ ID NO: 1.

6. The bispecific protein complex according to claim 1 , wherein X is the GCN4 peptide having SEQ ID NO: 1 or amino acids 1 to 38 of SEQ ID NO: 1 and Y is the scFv 52SR4 having SEQ ID NO: 3 or amino acids 1 to 243 of SEQ ID NO: 3.

7. The bispecific protein complex according to claim 6 , wherein A is a scFV.

8. The bispecific protein complex according to claim 1 , which comprises no more than two scFvs.

9. The bispecific protein complex according to claim 1 , wherein A and/or B is specific for an antigen selected from the group consisting of: cell surface receptors, co-stimulatory molecules, checkpoint inhibitors, natural killer cell receptors, Immunoglobulin receptors, TNFR family receptors, B7 family receptors, adhesion molecules, integrins, cytokine/chemokine receptors, GPCRs, growth factor receptors, kinase receptors, tissue-specific antigens, cancer antigens, pathogen recognition receptors, complement receptors, hormone receptors and soluble molecules.

10. A composition comprising one or more bispecific protein complexes defined in claim 1 .

11. A method for detecting synergistic biological function in the bispecific protein complex of claim 1 ,

said method comprising:

(i) testing for activity in a functional assay for part or all of a multiplex comprising at least one bispecific protein complex; and

(ii) analysing the readout(s) from the functional assay to detect synergistic biological function in the bispecific protein complex.

12. The method according to claim 11 , wherein:

a. the multiplex comprises at least two bispecific protein complexes or

b. the bispecific protein complex(es) do not contain an Fc region or

c. the bispecific protein complexes are not purified prior to testing or

d. the A-X and Y-B fusion proteins are expressed transiently and not purified before being mixed in a 1:1 molar ratio to generate each bispecific protein complex.

Assignments (2)
CHANGE OF NAME Recorded Sep 27, 2021
From: UCB BIOPHARMA SPRL
To: UCB BIOPHARMA SRL
Reel/Frame 057603/0291 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 7, 2018
From: BHATTA, PALLAVI; STARKIE, LAURA ELLEN; WRIGHT, MICHAEL JOHN
To: UCB BIOPHARMA SPRL
Reel/Frame 046313/0533 →
Priority Claims (1)
GB 1521382 · Dec 3, 2015 · national
Continuity (1)
Related Publication 20180346603A1 · Dec 6, 2018