IP Library › Granted Patent US 12,378,325
Granted Patent B2
US 12,378,325 · App. 16/996,534 · Granted Aug 5, 2025

Multispecific antigens binding fragments and multspecific antibodies

Inventors: Jean Kadouche (Paris, FR); Jean-Pierre Mach (Bellevue, CH); Olivier Michielin (Lausanne, CH); Vincent Zoete (Morges, CH); Justyna Iwaszkiewicz (Geneva, CH); Martine Cerutti (Saint-Christol-lez-Ales, FR); Sylvie Choblet (Ales, FR); Josee Golay (Bergamo, IT)
Assignees: Centre National de la Recherche Scientifique; Universite de Lausanne; Jean Kadouche
C07K16/468C07K16/2833C07K16/2896C07K2317/31C07K2317/522C07K2317/55C07K2317/732
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Quick Facts
Patent No.
US 12,378,325
App. No.
16/996,534
Granted
Aug 5, 2025
Kind
B2
Abstract

The invention relates to multispecific antibody constructs comprising Fab fragments having mutations at the interface of the CHI and CL domains, said mutations preventing heavy chain/light chain mispairing.

Claims (6)

1. A multispecific antibody construct comprising at least two Fab fragments with different CH1 and CL domains, wherein each Fab fragment recognizes a different epitope of interest, and wherein at least one Fab fragment is a mutated Fab fragment that comprises:

(i) the VH and VL domains of an antibody recognizing an epitope of interest;

(ii) a CH1 domain of a human immunoglobulin comprising substitution of the threonine residue at position 192 of said CHI domain with a glutamic acid residue; and

(iii) a CL-kappa domain of a human immunoglobulin comprising substitution of the asparagine residue at position 137 of said CL-kappa domain with a lysine residue and substitution of the serine residue at position 114 of said CL-kappa domain with an alanine residue,

wherein the position numbers used for the CH1 and CL-kappa domains refer to Kabat numbering.

2. A therapeutic composition comprising a multispecific antibody construct of claim 1 and a pharmaceutically acceptable vehicle.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 8, 2023
From: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; AZIENDA OSPEDALIERA PAPA GIOVANNI XXIII; UNIVERSITY OF LAUSANNE
To: KADOUCHE, JEAN
Reel/Frame 065814/0180 →
MERGER AND CHANGE OF NAME Recorded Apr 6, 2021
From: AZIENDA OSPEDALIERA PAPA GIOVANNI XXIII; AZIENDA SOCIO SANITARIA TERRITORIALE PAPA GIOVANNI XXIII
To: AZIENDA SOCIO SANITARIA TERRITORIALE PAPA GIOVANNI XXIII
Reel/Frame 055839/0419 →
Priority Claims (1)
EP 11305872 · Jul 7, 2011 · regional
Continuity (3)
Continuation 15463498 · Mar 20, 2017
Division 14130773
Related Publication 20210040235A1 · Feb 11, 2021
References Cited (21)
US 5959083A · Bosslet et al. · 1999 [cited by applicant]
US 20100081796A1 · Brinkmann et al. · 2010 [cited by applicant]
CN 101952312 · 2011 [cited by applicant]
DE 4419399C1 · 1995 [cited by applicant]
EP 0826696A1 · 1998 [cited by applicant]
WO 0177342A1 · 2001 [cited by applicant]
WO 2007147901A1 · 2007 [cited by applicant]
WO 2009018386A1 · 2009 [cited by applicant]
WO 2009089004A1 · 2009 [cited by applicant]
WO 2009155513A2 · 2009 [cited by applicant]
WO 2009155518A1 · 2009 [cited by applicant]
WO 2010145793A1 · 2010 [cited by applicant]
WO 2010145895A1 · 2010 [cited by applicant]
Paul, ed., Fundamental Immunology, 3rd Edition, 292-295 (1993). [cited by applicant]
Bendig, “Humanization of Rodent Monoclonal Antibodies by CDR Grafting,” Methods: A Companion to Methods in Enzymology, 8: 83-93 (1995). [cited by applicant]
Müller et al., “The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific miniantibodies,” FEBS Letters, 422: 259-264 (1998). [cited by applicant]
Plückthun et al., “New protein engineering approaches to multivalent and bispecific antibody fragments,” Immunotechnology, 3, 83-105 (1997). [cited by applicant]
Marvin et al., “Recombinant approaches to lgG-like bispecific antibodies,” Acta Pharmacologica Sinica, 26: 649-658 (2005). [cited by applicant]
Teerinen et al., “Structure-based Stability Engineering of the Mouse lgG1 Fab Fragment by Modifying Constant Domains,”Journal of Molecular Biology, 361: 687-697 (2006). [cited by applicant]
Houdebine et al., “Production of pharmaceutical proteins from transgenic animals,” Journal of Biotechnology, 34: 269-287 (1994). [cited by applicant]
Kappell et al., “Regulating gene expression in transgenic animals,” Current Biology, (3): 548-553 (1992). [cited by applicant]