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US 11,534,502 B2Granted
Genetically modified non-human animal with human or chimeric TIGIT
AssigneeBiocytogen Pharmaceuticals (Beijing) Co., Ltd.
InventorsYuelei Shen, Yang Bai, Rui Huang, Yanan Guo, Xiaofei Zhou, Meiling Zhang
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.
Claims6
A method of determining effectiveness of an anti-human TIGIT (T cell immunoreceptor with Ig and ITIM domains) antibody for treating cancer, comprising:
- administering the anti-human TIGIT antibody to a genetically-modified mouse, wherein the mouse has a tumor;
- determining inhibitory effects of the anti-human TIGIT antibody on the tumor by measuring the size of the tumor in the mouse;
- and
- comparing the size of the tumor in the mouse with the size of a tumor in a control mouse that is not treated with the anti-human TIGIT antibody,
- wherein the genome of the mouse comprises a nucleic acid sequence encoding a chimeric TIGIT at an endogenous TIGIT gene locus, wherein the chimeric TIGIT comprises the amino acid sequence of SEQ ID NO:
- 34, and the nucleic acid sequence encoding the chimeric TIGIT is operably linked to an endogenous regulatory element at the endogenous TIGIT locus, wherein the mouse expresses the chimeric TIGIT and does not express endogenous TIGIT,
- wherein the anti-human TIGIT antibody can bind to the expressed chimeric TIGIT protein and block the interaction of the chimeric TIGIT protein with a TIGIT ligand, thereby increasing immune response.
4 more elements
A method of determining effectiveness of an anti-human TIGIT antibody for treating cancer, comprising:
- administering the anti-human TIGIT antibody to a genetically-modified mouse, wherein the mouse has a tumor;
- determining inhibitory effects of the anti-human TIGIT antibody to the tumor by measuring the size of the tumor;
- and
- comparing the size of the tumor in the mouse with the size of a tumor in a control mouse that is not treated with the anti-human TIGIT antibody,
- wherein the genome of the mouse comprises a replacement of a portion of endogenous TIGIT exon 2 with a corresponding portion of human TIGIT exon 2, forming a chimeric TIGIT gene sequence at an endogenous TIGIT gene locus encoding a chimeric TIGIT, wherein a sequence within endogenous TIGIT exon 2 encoding at least 50 amino acid residues of the extracellular region of endogenous TIGIT protein is replaced with a sequence within human TIGIT exon 2 encoding at least 50 amino acid residues of the extracellular region of human TIGIT protein, wherein the chimeric TIGIT gene sequence is operably linked to an endogenous regulatory element, wherein the mouse expresses the chimeric TIGIT and does not express endogenous TIGIT, wherein the anti-human TIGIT antibody can bind to the expressed chimeric TIGIT protein and block the interaction of the chimeric TIGIT protein with a TIGIT ligand, thereby increasing immune response, wherein the chimeric TIGIT comprises the amino acid sequence of SEQ ID NO:
- 34.
3 more elements
Dependencies are inferred from the claim text.