Zymeworks Inc.

National Research Council of Canada

Zymeworks Bc Inc.

Yang-Chieh Chou

Dunja Urosev

Adam Louis Corper

Surjit Bhimarao Dixit

Thomas Spreter Von Kreudenstein

Mario Sanches

Gordon Yiu Kon Ng

Maureen D O'Connor-McCourt

Igor Edmondo Paolo D'Angelo

Jason Baardsnes

Stacey A L Tom-Yew

Anders Ohrn

Antonios Samiotakis

Stacey A Tom-Yew

Maureen O'CONNOR-Mccourt

Igor Edmondo D'angelo

Provided herein are stabilized chimeric Fabs derived from a parent chimeric Fab having a lambda light chain. The stabilized chimeric Fabs comprise an immunoglobulin heavy chain polypeptide construct from the parent chimeric Fab, having a CH1 sequence and a VH sequence, as well as a Vlambda-Ckappa chimeric light chain construct. The Vlambda sequence of the chimeric light chain construct corresponds to that of the parent chimeric Fab, and comprises one or more stabilizing amino acid modifications that increase the thermal stability of the stabilized chimeric Fab compared to the parent chimeric Fab. The stabilized Fabs are useful as therapeutic polypeptides, or can be used to prepare antibody constructs in other formats. The stabilized chimeric Fabs may also be useful generally to increase the stability of antibodies having lambda light chains.

Stabilized chimeric Fabs

The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the CH1 and/or CL domains, one or more amino acid modifications in the VH and/or VL domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer typically preferentially pairs with the second light chain rather than first.

Modified antigen binding polypeptide constructs and uses thereof

Provided is a method of quantitatively determining the ability of individual IgG heavy chains to selectively pair with a particular IgG light chain when the heavy chains and two unique light chains are co-expressed. The method provides results with reasonable throughput and is robust and accurate. The co-expressed heavy and light chains do not need to be isolated and purified which enables more efficient screening.

Methods of quantitating heavy and light chain polypeptide pairs

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San Francisco, CA, United States of America

Yang-Chieh Chou