The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Jul. 13, 2021

Filed:

Mar. 24, 2015
Applicant:

University of Southampton, Southampton, GB;

Inventors:

Martin J. Glennie, Southampton, GB;

Ann White, Southampton, GB;

Assignee:
Attorneys:
Primary Examiner:
Int. Cl.
CPC ...
C07K 16/28 (2006.01); C07K 16/24 (2006.01); C07K 16/30 (2006.01); A61K 39/00 (2006.01);
U.S. Cl.
CPC ...
C07K 16/2878 (2013.01); C07K 16/2818 (2013.01); C07K 16/30 (2013.01); A61K 2039/505 (2013.01); C07K 16/242 (2013.01); C07K 16/2896 (2013.01); C07K 2317/24 (2013.01); C07K 2317/522 (2013.01); C07K 2317/53 (2013.01); C07K 2317/70 (2013.01); C07K 2317/75 (2013.01); C07K 2317/76 (2013.01);
Abstract

Through a combination of in vitro and in vivo approaches, the inventors show that human IgG2 (h2) delivers unique FcγR-independent agonistic activity to anti-CD40 antibodies and to antibodies specific to other immunostimulatory receptors, including 4-1BB and CD28. Investigation of an anti-human CD40 mAb, LOB7.4, revealed that the unique activity of h2 was dependent upon the precise arrangement of hinge and CH1 disulfide bonds. Chemical 'shuffling' or mutagenesis to 'lock' LOB7.4 into either a more flexible ‘h2A’ or more compact ‘h2B’ conformation endowed antagonistic and agonistic properties, respectively. Engineering of h2 in this way allows development of reagents with either immunostimulatory or immunosuppressive characteristics, with direct implication for the design of therapeutic mAb agents and fusion proteins.


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