PDBsum entry 4bsw

Immune system

PDB id: 4bsw

Contents

Protein chains

216 a.a.

216 a.a.

Ligands

NAG-NAG-BMA-MAN-NAG-GAL-MAN-NAG-FUC

NAG-NAG-BMA-MAN-NAG-GAL

MAN-NAG

FUC

EDO ×5

Metals

IOD ×3

Waters ×371

PDB id:

4bsw

Name:

Immune system

Title:

Heterodimeric fc antibody azymetric variant 2

Structure:

Heterodimeric fc antibody azymetric variant 2. Chain: a. Fragment: ig gamma 1 fc domain, residues 106-330. Engineered: yes. Mutation: yes. Heterodimeric fc antibody azymetric variant 2. Chain: b. Fragment: ig gamma 1 fc domain, residues 106-330. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho. Expression_system_cell_line: cho

Resolution:

2.15Å R-factor: 0.203 R-free: 0.259

Authors:

M.D.L.Suits,T.Spreter,E.E.Cabrera,S.B.Dixit,P.I.Lario,D.K.Y.Poon, I.E.P.D'Angelo,M.J.Boulanger

Key ref:

T.S.Von Kreudenstein et al. (2013). Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design. Mabs, 5, 646-654. PubMed id: 23924797 DOI: 10.4161/mabs.25632

Date:

11-Jun-13 Release date: 21-Aug-13

Protein chain

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 216 a.a.*

Protein chain

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 216 a.a.*

* PDB and UniProt seqs differ at 15 residue positions (black crosses)

DOI no: 10.4161/mabs.25632

Mabs 5:646-654 (2013)

PubMed id: 23924797

Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design.

T.S.Von Kreudenstein, E.Escobar-Carbrera, P.I.Lario, I.D'Angelo, K.Brault, J.Kelly, Y.Durocher, J.Baardsnes, R.J.Woods, M.H.Xie, P.A.Girod, M.D.Suits, M.J.Boulanger, D.K.Poon, G.Y.Ng, S.B.Dixit.

ABSTRACT

While the concept of Quality-by-Design is addressed at the upstream and downstream process development stages, we questioned whether there are advantages to addressing the issues of biologics quality early in the design of the molecule based on fundamental biophysical characterization, and thereby reduce complexities in the product development stages. Although limited number of bispecific therapeutics are in clinic, these developments have been plagued with difficulty in producing materials of sufficient quality and quantity for both preclinical and clinical studies. The engineered heterodimeric Fc is an industry-wide favorite scaffold for the design of bispecific protein therapeutics because of its structural, and potentially pharmacokinetic, similarity to the natural antibody. Development of molecules based on this concept, however, is challenged by the presence of potential homodimer contamination and stability loss relative to the natural Fc. We engineered a heterodimeric Fc with high heterodimeric specificity that also retains natural Fc-like biophysical properties, and demonstrate here that use of engineered Fc domains that mirror the natural system translates into an efficient and robust upstream stable cell line selection process as a first step toward a more developable therapeutic.