IP Library Granted Patent US 11,542,342
Granted Patent B2
US 11,542,342 · App. 16/745,059 · Granted Jan 3, 2023

Binding molecules with modified J-chain

Inventors: Bruce A. Keyt (Hillsborough, CA); Leonard G. Presta (San Francisco, CA); Ramesh Baliga (Redwood City, CA)
Assignee: IGM Biosciences, Inc.
C07K16/468A61K39/39541A61K39/39558C07K16/28C07K16/2809C07K16/2881C07K16/2887A61K2039/505A61P27/00A61P35/02C07K2317/24C07K2317/31C07K2317/35C07K2317/52C07K2317/569C07K2317/622C07K2317/734C07K2317/90C07K2319/31C07K2319/735C07K2319/91
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Quick Facts
Patent No.
US 11,542,342
App. No.
16/745,059
Granted
Jan 3, 2023
Kind
B2
Abstract

The present invention concerns binding molecules that comprise an IgM, IgA, IgG/IgM or IgG/IgA antibody with a J-chain modified to include an ADME-modulating moiety, and their uses.

Claims (27)

1. A polymeric antibody comprising two or five immunoglobulin monomers and a modified J-chain, wherein the modified J-chain comprises a moiety introduced into a J-chain, wherein each immunoglobulin monomer comprises two heavy chains, and wherein each heavy chain comprises a tail-piece domain and a heavy chain constant domain, wherein the moiety comprises an albumin protein.

2. The polymeric antibody of claim 1 , wherein the J-chain is a native human J-chain.

3. The polymeric antibody of claim 2 , wherein the native human J-chain comprises SEQ ID NO: 1.

4. The polymeric antibody of claim 3 , wherein the moiety is introduced into the J-chain by indirect fusion through a peptide linker.

5. The polymeric antibody of claim 4 , wherein the peptide linker is located at or around the C- or N-terminus of the moiety.

6. The polymeric antibody of claim 4 , wherein the moiety is introduced at the C-terminus of the J-chain.

7. The polymeric antibody of claim 4 , wherein the moiety is introduced at the N-terminus of the J-chain.

8. The polymeric antibody of claim 4 , wherein the peptide linker is about 10 to 20 amino acids long.

9. The polymeric antibody of claim 4 , wherein the peptide linker is 15 amino acids long.

10. The polymeric antibody of claim 4 , wherein the modified J chain further comprising a binding moiety.

11. The polymeric antibody of claim 10 , wherein the binding moiety is a polypeptide introduced into the J-chain by direct or indirect fusion.

12. The polymeric antibody of claim 10 , wherein the moiety is located at an N-terminus of the modified J-chain, and the binding moiety is located at a C-terminus of the modified J-chain.

13. The polymeric antibody of claim 10 , wherein the moiety is located at a C-terminus of the modified J-chain, and the binding moiety is located at an N-terminus of the modified J-chain.

14. The polymeric antibody of claim 10 , wherein the binding moiety binds human CD3.

15. The polymeric antibody of claim 14 , wherein the binding moiety comprises a human CD3-binding scFv.

16. The polymeric antibody of claim 1 , which comprises five immunoglobulin monomers to form a pentamer, wherein the two heavy chains of each immunoglobulin monomer comprise an IgM tail-piece (μtp) and a Cμ4 domain.

17. The polymeric antibody of claim 16 , wherein the two heavy chains of each immunoglobulin monomer each further comprise a Cμ1 domain, a Cμ2 domain, and a Cμ3 domain.

18. The polymeric antibody of claim 1 , wherein each immunoglobulin monomer further comprises two light chains associated with the two heavy chains.

19. The polymeric antibody of claim 16 , wherein the two heavy chains of immunoglobulin monomer are hybrid heavy chains further comprising one or more heavy chain constant region domains of a non-IgM isotype.

20. The polymeric antibody of claim 19 , wherein the non-IgM isotype is IgG.

21. The polymeric antibody of claim 1 , which comprises two immunoglobulin monomers to form a dimer, wherein each immunoglobulin monomer comprise an IgA tail-piece (αtp) and a Cα3 domain.

22. The polymeric antibody of claim 21 , wherein the two heavy chains of each immunoglobulin monomer each further comprise a Cα1 domain, and a Cα2 domain.

23. The polymeric antibody of claim 22 , wherein the two heavy chains of each immunoglobulin monomer comprise a heavy chain variable domain (VH), and wherein each heavy chain comprises, starting at the N-terminus, the VH, the Cα1 domain, the Cα2 domain, the Cα3 domain, and the αtp.

24. The polymeric antibody of claim 23 , wherein each immunoglobulin monomer further comprises two light chains associated with the two heavy chains.

25. The polymeric antibody of claim 21 , wherein the two heavy chains of immunoglobulin monomer are hybrid heavy chains further comprising one or more heavy chain constant region domains of a non-IgA isotype.

26. The polymeric antibody of claim 25 , wherein the non-IgA isotype is IgG.

27. The polymeric antibody of claim 1 , wherein the albumin protein is human serum albumin.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 16, 2020
From: KEYT, BRUCE ALAN; PRESTA, LEONARD GEORGE; BALIGA, RAMESH
To: IGM BIOSCIENCES A/S
Reel/Frame 051540/0054 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 16, 2020
From: IGM BIOSCIENCES A/S
To: IGM BIOSCIENCES, INC.
Reel/Frame 051625/0694 →
Continuity (3)
Continuation 15764859
Provisional Application 62235518 · Sep 30, 2015
Related Publication 20200255546A1 · Aug 13, 2020
Cited By (2)
US 12,486,336 US 12,649,791