Evidence map›Paper›PMID 34877503›Full record

ArticleiScience2021

Next generation Fc scaffold for multispecific antibodies.

Bram Estes, Athena Sudom, Danyang Gong, Douglas A Whittington, Vivian Li, Christopher Mohr, Danqing Li, Timothy P Riley, Stone D-H Shi, Jun Zhang and 2 more

Abstract read
In one paragraph

Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Bram EstesDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Athena SudomDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., San Francisco, CA 94080, USA.
Danyang GongDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Douglas A WhittingtonDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Cambridge, MA 02141, USA.
Vivian LiDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Christopher MohrDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Danqing LiDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Timothy P RileyDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Stone D-H ShiDepartment of Process Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
Jun ZhangDepartment of Process Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
Fernando GarcesDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320, USA.
Zhulun WangDepartment of Therapeutics Discovery, Amgen Research, Amgen Inc., San Francisco, CA 94080, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific antibodies (Bispecifics) demonstrate exceptional clinical potential to address some of the most complex diseases. However, Bispecific production in a single cell often requires the correct pairing of multiple polypeptide chains for desired assembly. This is a considerable hurdle that hinders the development of many immunoglobulin G (IgG)-like bispecific formats. Our approach focuses on the rational engineering of charged residues to facilitate the chain pairing of distinct heavy chains (HC). Here, we deploy structure-guided protein design to engineer charge pair mutations (CPMs) placed in the CH3-CH3' interface of the fragment crystallizable (Fc) region of an antibody (Ab) to correctly steer heavy chain pairing. When used in combination with our stable effector functionless 2 (SEFL2.2) technology, we observed high pairing efficiency without significant losses in expression yields. Furthermore, we investigate the relationship between CPMs and the sequence diversity in the parental antibodies, proposing a rational strategy to deploy these engineering technologies.

Indexed as

BiochemistryBioengineeringBiomolecular engineeringStructural biology

Identifiers

PMID34877503
PMCPMC8633962

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.