Fully canine anti-canine pd-1 antibodies and uses thereof
AssigneeThe Trustees of the University of Pennsylvania
InventorsDonald L. Siegel, Nicola J. Mason, Nicholas Chester, Keren Paz
Life of this patent
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Abstract
The present disclosure relates to canine antibodies, binding polypeptides, scFvs specific for canine programmed death protein 1 (PD-1), nucleic acids encoding the same, and the methods to prepare the same and to use the same to treat a disease or a condition.
Claims97
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain complementarity determining region 1 (HCDR1), comprising the amino acid sequence set forth in SEQ ID NOs:
- 1, 27, or 43,
- (b) a heavy chain complementarity determining region 2 (HCDR2), comprising the amino acid sequence set forth in SEQ ID NOs:
- 2, 28, or 44,
- (c) a heavy chain complementarity determining region 3 (HCDR3), comprising the amino acid sequence set forth in SEQ ID NOs:
- 3, 29, or 45,
- (d) a light chain complementarity determining region 1 (LCDR1), comprising the amino acid sequence set forth in SEQ ID NOs:
- 4, 30, or 46,
- (e) a light chain complementarity determining region 2 (LCDR2), comprising the amino acid sequence set forth in SEQ ID NOs:
- 5, 31, or 47, and
- (f) a light chain complementarity determining region 3 (LCDR3), comprising the amino acid sequence set forth in SEQ ID NOs:
- 6, 32, or 48.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NOs:
- 7, 9, 33, or 49;
- and
- (b) a light chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NOs:
- 11, 35, or 51.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NOs:
- 7, 9, 33, or 49;
- and
- (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NOs:
- 11, 35, or 51.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NOs:
- 19, 21, 23, 39, or 55, and
- (b) an immunoglobulin light chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NOs:
- 25, 41, or 57.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising the amino acid sequence set forth in SEQ ID NOs:
- 19, 21, 23, 39, or 55, and
- (b) an immunoglobulin light chain, comprising the amino acid sequence set forth in SEQ ID NOs:
- 25, 41, or 57.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain complementarity determining region 1 (HCDR1), comprising the amino acid sequence set forth in SEQ ID NO:
- 1,
- (b) a heavy chain complementarity determining region 2 (HCDR2), comprising the amino acid sequence set forth in SEQ ID NO:
- 2,
- (c) a heavy chain complementarity determining region 3 (HCDR3), comprising the amino acid sequence set forth in SEQ ID NO:
- 3,
- (d) a light chain complementarity determining region 1 (LCDR1), comprising the amino acid sequence set forth in SEQ ID NO:
- 4,
- (e) a light chain complementarity determining region 2 (LCDR2), comprising the amino acid sequence set forth in SEQ ID NO:
- 5, and
- (f) a light chain complementarity determining region 3 (LCDR3), comprising the amino acid sequence set forth in SEQ ID NO:
- 6.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NOs:
- 7 or 9;
- and
- (b) a light chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 11.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 7;
- and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 11;
- or
- (b) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 9 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 11;
(canceled)
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NOs:
- 19, 21, or 23, and
- (b) an immunoglobulin light chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 25.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising the amino acid sequence set forth in SEQ ID NOs:
- 19, and an immunoglobulin light chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 25;
- (b) an immunoglobulin heavy chain, comprising the amino acid sequence set forth in SEQ ID NOs:
- 21, and an immunoglobulin light chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 25;
- or
- (c) an immunoglobulin heavy chain, comprising the amino acid sequence set forth in SEQ ID NOs:
- 23, and an immunoglobulin light chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 25.
-17. (canceled)
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain complementarity determining region 1 (HCDR1), comprising the amino acid sequence set forth in SEQ ID NO:
- 27,
- (b) a heavy chain complementarity determining region 2 (HCDR2), comprising the amino acid sequence set forth in SEQ ID NO:
- 28,
- (c) a heavy chain complementarity determining region 3 (HCDR3), comprising the amino acid sequence set forth in SEQ ID NO:
- 29,
- (d) a light chain complementarity determining region 1 (LCDR1), comprising the amino acid sequence set forth in SEQ ID NO:
- 30,
- (e) a light chain complementarity determining region 2 (LCDR2), comprising the amino acid sequence set forth in SEQ ID NO:
- 31, and
- (f) a light chain complementarity determining region 3 (LCDR3), comprising the amino acid sequence set forth in SEQ ID NO:
- 32.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 33;
- and
- (b) a light chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 35.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 33;
- and
- (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 35.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 39, and
- (b) an immunoglobulin light chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 41.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 39, and
- (b) an immunoglobulin light chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 41.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain complementarity determining region 1 (HCDR1), comprising the amino acid sequence set forth in SEQ ID NO:
- 43,
- (b) a heavy chain complementarity determining region 2 (HCDR2), comprising the amino acid sequence set forth in SEQ ID NO:
- 44,
- (c) a heavy chain complementarity determining region 3 (HCDR3), comprising the amino acid sequence set forth in SEQ ID NO:
- 45,
- (d) a light chain complementarity determining region 1 (LCDR1), comprising the amino acid sequence set forth in SEQ ID NO:
- 46,
- (e) a light chain complementarity determining region 2 (LCDR2), comprising the amino acid sequence set forth in SEQ ID NO:
- 47, and
- (f) a light chain complementarity determining region 3 (LCDR3), comprising the amino acid sequence set forth in SEQ ID NO:
- 48.
(canceled)
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 49;
- and
- (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
- 51.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 55, and
- (b) an immunoglobulin light chain, comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity to the amino acid sequence set forth in SEQ ID NO:
- 57.
An antibody or antigen-binding fragment thereof that specifically binds to canine programmed death protein 1 (cPD-1), wherein the antibody or antigen-binding fragment thereof comprises:
- (a) an immunoglobulin heavy chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 55, and
- (b) an immunoglobulin light chain, comprising the amino acid sequence set forth in SEQ ID NO:
- 57.
(canceled)
A single-chain variable fragment (scFv) specifically binds canine programmed death protein 1 (cPD-1), comprising:
- (a) a heavy chain variable region that comprises heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3, wherein HCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 1, 27, and 43, HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 28, and 44, and HCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 3, 29, and 45;
- and
- (b) a light chain variable region that comprises light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, wherein LCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 4, 30, and 46, LCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 5, 31 and 47, and LCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 6, 32, and 48,
- wherein the heavy chain variable region and the light chain variable region are connected by a linker.
A single-chain variable fragment (scFv) specifically binds to canine programmed death protein 1 (cPD-1), comprising:
- (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NOs:
- 7, 9, 33, or 49;
- and
- (b) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NOs:
- 11, 35, or 51,
- wherein the heavy chain variable region and the light chain variable region are connected by a linker.
A single chain variable fragment (scFv) specifically binds to canine programmed death protein 1 (cPD-1), comprising the amino acid sequence set forth in SEQ ID NOs:
- 13, 15, 17, 37, or 53.
An isolated nucleic acid encoding an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
- (a) a heavy chain variable region encoded by a nucleic acid comprising a polynucleotide sequence having at least 80%, 85%, 90%, 95%, 96%, 96%, 97%, 98%, 99% identity to the polynucleotide sequence set forth in SEQ ID NOs:
- 8, 10, 34, or 50;
- and
- (b) a light chain variable region encoded by a nucleic acid comprising a polynucleotide sequence having at least 80%, 85%, 90%, 95%, 96%, 96%, 97%, 98%, 99% identity to the polynucleotide sequence set forth in SEQ ID NOs:
- 12, 36, or 52;
An isolated nucleic acid encoding an antibody or antigen binding fragment thereof comprising:
- (a) a heavy chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 8;
- and a light chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 12;
- (b) a heavy chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 10;
- and a light chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 12;
- (c) a heavy chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 34 and a light chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 36;
- or
- (d) a heavy chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 50 and a light chain variable region encoded by a nucleic acid sequence comprising the polynucleotide sequence set forth in SEQ ID NO:
- 52.
-55. (canceled)
An isolated nucleic acid encoding a single-chain variable fragment (scFv) comprising:
- (a) a heavy chain variable region comprising the nucleotide sequence set forth in SEQ ID NOs:
- 8, 10, 34, or 50;
- and
- (b) a light chain variable region comprising the nucleotide sequence set forth in SEQ ID NOs:
- 12, 36, or 52,
- wherein the heavy chain variable region and the light chain variable region are connected by a linker.
An isolated nucleic acid encoding a single-chain variable fragment (scFv) comprising the polynucleotide sequence set forth in SEQ ID NOs:
- 14, 16, 18, 38, or 54.
-101. (canceled)
Dependencies are inferred from the claim text.