Manipulation of Immunoglobulin Gene Diversity and Multi-Antibody Therapeutics

59 Pages·2014·5.77 MB·English

US 20140212416Al
(19) United States
(12) Patent Application Publication (10) Pub. N0.2 US 2014/0212416 A1
Friedrich et a]. (43) Pub. Date: Jul. 31, 2014
(54) MANIPULATION 0F IMMUNOGLOBULIN Publication Classi?cation
GENE DIVERSITY AND MULTI-ANTIBODY
THERAPEUTICS (51) Int. Cl.
C07K16/12 (2006.01)
(71) Applicant: Kymab Limited, Cambridge (GB) C07K 16/10 (2006.01)
C07K16/08 (2006.01)
(72) Inventors: Glenn Friedrich, Cambridge (GB); (52) us CL
E-Chiang Lee, Cambridge (GB); Jasper CPC ....... .. C07K16/1242 (2013.01); C07K16/1232
Clube, Cambridge (GB); Nicholas (2013.01); C07K16/085 (2013.01); C07K
England, Cambridge (GB)
16/088 (2013.01); C07K16/1045 (2013.01);
C07K16/1018 (2013.01); C07K16/1217
(73) Assignee: Kymab Limited, Cambridge (GB) (2013.01)
USPC ..... .. 424/1331; 800/13; 435/328; 530/3873;
435/69.6; 536/23.53; 435/455
(21) Appl. No.: 14/220,074
(57) ABSTRACT
(22) Filed: Mar. 19, 2014 The invention provides improved non-human vertebrates and
non-vertebrate cells capable of expressing antibodies com
Related US. Application Data prising human variable region sequences. The present inven
tion is directed to the provision of long HCDR3s from non
(63) Continuation of application No. PCT/GB2012/
human vertebrates and cells. The present invention is also
052298, ?led on Sep. 18,2012.
directed to the provision of novel V, D and J pairings in
immunoglobulin heavy and light chain loci. Novel, biased
(30) Foreign Application Priority Data
antibody diversities and potentially expanded diversities are
provided. The invention also provides for novel and poten
Sep. 19, 2011 (GB) ................................. .. 1116120.5
tially expanded diversity or diversity that is biased towards
Sep. 19,2011 1116122.1
variable gene usage common to antibodies useful for treating
Feb. 24, 2012 . 1203257.9
and/or preventing certain diseases or conditions, such as
Mar. 15,2012 12045928
infectious diseases. The invention also provides methods of
Mar. 29, 2012 12057022
generating antibodies using such vertebrates, as well as the
May 18, 2012 . 1208749.0
antibodies per se, therapeutic compositions thereof and uses.
Jul. 2, 2012 12116927
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