Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.
Type:
Grant
Filed:
February 19, 2021
Date of Patent:
August 2, 2022
Assignee:
Kymab Limited
Inventors:
E-Chiang Lee, Jasper Clube, Allan Bradley
Abstract: The present invention relates inter alia to expression vector production as well as application to the production of host cells for protein repertoire expression and high-throughput screening. The invention also relates to primers useful for PCR amplification of nucleotide sequences encoding human antibody variable domains.
Type:
Grant
Filed:
May 9, 2019
Date of Patent:
June 28, 2022
Assignee:
Kymab Limited
Inventors:
Allan Bradley, E-Chiang Lee, Qi Liang, Hui Liu, Andrew Wood, Vivian Wong
Abstract: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.
Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising the antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in the methods.
Type:
Grant
Filed:
March 7, 2019
Date of Patent:
April 12, 2022
Assignee:
Kymab Limited
Inventors:
Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Dominik Spensberger, Hui Liu, Jasper Clube
Abstract: Antibodies that bind to the circumsporozoite protein (CSP) of Plasmodium falciparum. Use of such antibodies as anti-malarial agents, to confer protection against infection by malarial parasites such as P. falciparum by insect vector transmission. Diagnosis of malaria using anti-CSP antibodies. Methods of determining efficacy of candidate vaccine compositions in development and testing of anti-malarial vaccines.
Type:
Grant
Filed:
May 11, 2018
Date of Patent:
July 20, 2021
Assignees:
KYMAB LIMITED, ATRECA, INC.
Inventors:
Qi Liang, Sean Matthew Carroll, Daniel Eric Emerling, Allan Bradley, Paul Kellam, {hacek over (S)}pela Binter, Simon James Watson
Abstract: The invention provides improved non-human vertebrates and non-vertebrate cells capable of expressing antibodies comprising human variable region sequences. The present invention is directed to the provision of long HCDR3s from non-human vertebrates and cells. The present invention is also directed to the provision of novel V, D and J pairings in immunoglobulin heavy and light chain loci. Novel, biased antibody diversities and potentially expanded diversities are provided. The invention also provides for novel and potentially expanded diversity or diversity that is biased towards variable gene usage common to antibodies useful for treating and/or preventing certain diseases or conditions, such as infectious diseases. The invention also provides methods of generating antibodies using such vertebrates, as well as the antibodies per se, therapeutic compositions thereof and uses.
Type:
Grant
Filed:
March 19, 2014
Date of Patent:
July 6, 2021
Assignee:
Kymab Limited
Inventors:
Glenn Friedrich, E-Chiang Lee, Jasper Clube, Nicholas England
Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.
Type:
Grant
Filed:
December 11, 2018
Date of Patent:
April 6, 2021
Assignee:
Kymab Limited
Inventors:
E-Chiang Lee, Jasper Clube, Allan Bradley
Abstract: Bispecific antigen binding molecules (e.g., antibodies) that bind blood clotting factors, factor IXa (FIXa) and factor X (FX), and enhance the FIXa-catalysed activation of FX to FXa. Use of the bispecific antigen binding molecules to control bleeding, by replacing natural cofactor FVIIIa which is deficient in patients with haemophilia A.
Type:
Grant
Filed:
December 20, 2019
Date of Patent:
October 27, 2020
Assignee:
KYMAB LIMITED
Inventors:
Wei Wang, E-Chiang Lee, John Kenneth Blackwood, Roberto Magliozzi
Abstract: The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.
Abstract: The invention relates to the provision of antibody therapeutics and prophylactics that are tailored specifically for human use. The present invention provides libraries, vertebrates and cells, such as transgenic mice or rats or transgenic mouse or rat cells. Furthermore, the invention relates to methods of using the vertebrates to isolate antibodies or nucleotide sequences encoding antibodies. Antibodies, heavy chains, polypeptides, nucleotide sequences, pharmaceutical compositions and uses are also provided by the invention.
Type:
Grant
Filed:
July 21, 2017
Date of Patent:
August 4, 2020
Assignee:
Kymab Limited
Inventors:
Allan Bradley, Glenn Friedrich, E-Chiang Lee, Mark Strivens, Nicholas England
Abstract: The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.
Type:
Grant
Filed:
November 17, 2014
Date of Patent:
June 2, 2020
Assignee:
Kymab Limited
Inventors:
Volker Germaschewski, E-Chiang Lee, Hanif Ali, Jasper Clube