Granted Patent
B2
US 12,188,938 · App. 17/205,193 · Granted Jan 7, 2025
Anti-VISTA antibodies and fragments
Inventors:
Linda A. Snyder (Pottstown, PA); Gordon Powers (Malvern, PA); Manuel Alejandro Sepulveda (Spring House, PA); John D. Alvarez (Spring House, PA)
Assignee:
JANSSEN PHARMACEUTICA NV
G01N33/57492C07K16/2827A61K2039/505C07K2317/24C07K2317/34C07K2317/55C07K2317/56C07K2317/732C07K2317/74C07K2317/76C07K2317/92G01N2333/70532
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Abstract
The present invention relates to novel antibodies and fragments that bind to a V-domain Ig Suppressor of T cell Activation (VISTA), and methods of detecting VISTA.
Claims (42)
1. A nucleic acid which encodes an antibody that binds to human V-domain Ig Suppressor of T cell Activation (VISTA) protein, wherein the antibody comprises:
a) an antibody VH domain comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 31, a VH CDR2 having the amino acid sequence of SEQ ID NO:32 and a VH CDR3 having the amino acid sequence of SEQ ID NO:33;
b) an antibody VL domain comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 34, a VL CDR2 having the amino acid sequence of SEQ ID NO:35 and a VL CDR3 having the amino acid sequence of SEQ ID NO:36;
c) a murine antibody heavy chain constant region; and
d) a murine antibody light chain constant region.
2. The nucleic acid of claim 1 , wherein the antibody VH domain comprises SEQ ID NO:64 and/or the antibody VL domain comprises SEQ ID NO:45.
3. The nucleic acid of claim 1 , wherein the murine antibody heavy chain constant region is a murine IgG1 heavy chain constant region.
4. The nucleic acid of claim 3 , wherein the murine IgG1 antibody heavy chain constant region comprises the murine heavy chain constant region in SEQ ID NO:76.
5. The nucleic acid of claim 1 , wherein the murine antibody light chain constant region is a murine IgG1 or murine IgG2a light chain constant region.
6. The nucleic acid of claim 5 , wherein the murine IgG1 antibody light chain constant region comprises the light chain constant region in SEQ ID NO:77.
7. The nucleic acid of claim 5 , wherein the murine antibody light chain constant region is a murine IgG2a light chain constant region.
8. A nucleic acid encoding an antibody, comprising an antigen-binding region that binds to human V-domain Ig Suppressor of T cell Activation (VISTA) protein and murine heavy and light chain constant regions, wherein the antibody comprises an antibody heavy chain comprising SEQ ID NO:76 and an antibody light chain comprising SEQ ID NO:77.
9. A vector comprising the nucleic acid of claim 1 .
10. A method for detecting a human VISTA protein in a sample, comprising contacting the sample with the antibody encoded by the nucleic acid of claim 1 under conditions in which the antibody binds to human VISTA protein in the sample, and detecting the antibody that is bound to VISTA protein in the sample.
11. The method of claim 10 , wherein
(i) the sample comprises human cells;
(ii) the sample comprises a human tissue;
(iii) the sample comprises human immune cells or human stromal cells, or a combination thereof;
(iv) the sample comprises human immune cells including one or more of human myeloid cells, human monocytes or human T cells;
(v) the sample comprises human cancer cells;
(vi) the sample comprises human cancer cells selected from the group consisting of human lung cancer cells, human prostate cancer cells, human acute myeloid leukemia (AML) cells, human melanoma cells, human ovarian cancer cells and human colon cancer cells;
(vii) the antibody comprises a detectable label;
(viii) the method includes an immunohistochemical (IHC) staining assay;
(ix) the method includes a flow cytometry assay; or
(x) a combination of any of the foregoing.
12. A vector comprising the nucleic acid of claim 8 .
13. A method for detecting human VISTA protein in a sample, comprising contacting the sample with the antibody encoded by the nucleic acid of claim 8 under conditions in which the antibody binds to human VISTA protein in the sample, and detecting the antibody that is bound to the human VISTA protein in the sample.
14. The method of claim 13 , wherein
(i) the sample comprises human cells;
(ii) the sample comprises a human tissue;
(iii) the sample comprises human immune cells or human stromal cells, or a combination thereof;
(iv) the sample comprises human immune cells including one or more of human myeloid cells, human monocytes or human T cells;
(v) the sample comprises human cancer cells;
(vi) the sample comprises human cancer cells selected from the group consisting of human lung cancer cells, human prostate cancer cells, human acute myeloid leukemia (AML) cells, human melanoma cells, human ovarian cancer cells and human colon cancer cells;
(vii) the antibody comprises a detectable label;
(viii) the method includes an immunohistochemical (IHC) staining assay;
(ix) the method includes a flow cytometry assay; or
(x) a combination of any of the foregoing.
15. An isolated or recombinant cell comprising the nucleic acid of claim 1 or a vector containing said nucleic acid.
16. An isolated or recombinant cell comprising the nucleic acid of claim 8 or a vector containing said nucleic acid.
17. A method of producing an antibody encoded by the nucleic acid of claim 1 , comprising culturing a cell which comprises said nucleic acid or a vector containing said nucleic under conditions that permit the expression of the antibody.
18. A method of producing an antibody encoded by the nucleic acid of claim 8 , comprising culturing a cell which comprises said nucleic acid or a vector containing said nucleic acid under conditions that permit the expression of the antibody.
Continuity (4)
Division
15738013
Provisional Application
62187659
· Jul 1, 2015
Provisional Application
62184108
· Jun 24, 2015
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