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US 2025/0026850 A1Published application
Anti-cd39 antibodies, compositions comprising anti-cd39 antibodies and methods of using anti-cd39 antibodies
AssigneeTrishula Therapeutics, Inc.
InventorsVanessa Soros, Maria Kovalenko, John Corbin, Courtney Beers, Paul Fredrick Widboom, Joseph Robert Warfield
Life of this patent
Estimating the term…
Abstract
Provided herein are antibodies with binding specificity for CD39 and compositions comprising the antibodies, including pharmaceutical compositions, diagnostic compositions and kits. Also provided are methods of using anti-CD39 antibodies for therapeutic and diagnostic purposes.
Claims53
An antigen binding protein that binds specifically to a human CD39 (hCD39) and is capable of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 of the following:
- a) inhibiting binding of CD39 to ATP;
- b) inhibiting conversion by CD39 of ATP to ADP and/or ADP to AMP;
- c) decreasing affinity of CD39 for ATP or ADP;
- d) inhibiting or impeding release of ADP or AMP from CD39;
- e) impeding or inhibiting CD39 processivity;
- f) inhibiting platelet aggregation;
- g) decreasing levels of phosphate, ADP, AMP, and/or adenosine and/or increasing levels of ATP;
- h) increasing T effector cell function;
- i) decreasing the number of regulatory T cells in tissues or in circulation;
- j) suppressing regulatory T cells or regulatory T cell activity;
- k) increasing B cell function;
- l) increasing antigen presenting cell function;
- m) inhibiting CD39 function on tumor cells;
- n) inhibiting processing of at least one of phospho-antigen from phosphorylated isoprenoid, phosphorylated vitamin B metabolite, and/or phosphorylated riboflavin;
- o) decreasing or preventing activation of phospho antigen specific T cells selected from MAIT cells and γδ T cells;
- p) inhibiting angiogenesis;
- q) increasing proliferation of stimulated CD4+ and CD8+ T cells;
- r) increasing stimulated PBMC Secretion of INF-γ, TNF-α, IL-2 and/or IL-1β.
15 more elements
A pharmaceutical composition comprising an effective amount of an antibody which binds to hCD39 and has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 of the following of characteristics:
- a) blocks or decreases hydrolysis of ATP to ADP and/or ADP to AMP as determined by at least one of:
- (i) a decreased phosphate release (Pi), (ii) an increase in ATP levels, and (iii) a decrease of ADP, AMP, and/or adenosine levels,
- b) increases T effector cell activity;
- c) suppresses regulatory T cell or decreases a regulatory T cell activity;
- d) decreases number of regulatory T cells in tissues or in circulation;
- e) increases B cell function;
- f) increases antigen presenting cell function;
- g) inhibits CD39 function on tumor cells;
- h) blocks or inhibits processing of at least one of phospho-antigen from a phosphorylated isoprenoid, phosphorylated vitamin B metabolite, and phosphorylated riboflavin;
- i) decreases or prevents activation of phospho antigen specific T cells selected from MAIT cells and γδ T cells;
- k) inhibits angiogenesis;
- l) decreases affinity for ATP and/or ADP;
- m) inhibits release of ADP or AMP from CD39;
- n) impedes or inhibits CD39 processivity;
- o) inhibits platelet aggregation;
- p) increases proliferation of stimulated CD4+ and CD8+ T cells;
- r) increases stimulated PBMC Secretion of INF-γ, TNF-α, IL-2, and/or IL-1β.
14 more elements
An antigen binding protein that binds to or is capable of competing for binding to human CD39 with a reference antigen binding protein, wherein the reference antigen binding protein binds to an epitope at positions 143-158 or 274-277 of SEQ ID NO:
- 249 on a human CD39 polypeptide, including, but not limited to, D150, E153, R154 or N99 alone or in combination with D150, E153, R154 or any combination thereof.
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH and/or VL comprising 1, 2, 3, 4, 5, or 6 of:
- a) a VHCDR1 having the sequence set forth in SEQ ID NOs:
- 1-45,
- b) a VHCDR2 having the sequence set forth in SEQ ID NOs:
- 46-81,
- c) a VHCDR3 having the sequence set forth in SEQ ID NOs:
- 82-109,
- d) a VLCDR1 having the sequence set forth in SEQ ID NOs:
- 110-124,
- e) a VLCDR2 having the sequence set forth in SEQ ID NOs:
- 125-140, and
- f) a VLCDR3 having the sequence set forth in SEQ ID NOs:
- 141-166.
9 more elements
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising,
- a) a VHCDR1 having a sequence set forth in SEQ ID NOs:
- 1-45,
- b) a VHCDR2 having a sequence set forth in SEQ ID NOs:
- 46-81, and
- c) a VHCDR3 having a sequence set forth in SEQ ID NOs:
- 82-109;
- and the VL comprising,
- a) a VLCDR1 having a sequence set forth in SEQ ID NO:
- 110-124,
- b) a VLCDR2 having a sequence set forth in SEQ ID NO:
- 125-140, and
- c) a VLCDR3 having a sequence set forth in SEQ ID NO:
- 141-166.
10 more elements
A method for inducing or enhancing an immune response in a subject in need thereof, comprising the step of administering to the subject a pharmaceutical composition comprising an antigen binding protein, wherein the immune response is generated against a tumor antigen.
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH comprising at least one of:
- a) a VHCDR1 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs:
- 1-45,
- b) a VHCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs:
- 46-81, and
- c) a VHCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs:
- 82-109;
- and
- VL comprising at least one of:
- a) a VLCDR1 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs:
- 110-124,
- b) a VLCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs:
- 125-140, and
- c) a VLCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs 141-166.
10 more elements
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL),
- VH comprising at least one of:
- a) a VHCDR1 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs:
- 1-45,
- b) a VHCDR2 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs:
- 46-81, and
- c) a VHCDR3 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs:
- 82-109;
- and
- VL comprising at least one of:
- a) a VLCDR1 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs:
- 110-124,
- b) a VLCDR2 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs:
- 125-140, and
- c) a VLCDR3 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs:
- 141-166.
12 more elements
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain and a light chain, the heavy chain comprising one or more molecules having a sequence consisting of one of SEQ ID NO:
- 255, SEQ ID NO:
- 257, SEQ ID NO:
- 259, SEQ ID NO:
- 261, SEQ ID NO:
- 263, SEQ ID NO:
- 265, SEQ ID NO:
- 267, SEQ ID NO:
- 269, SEQ ID NO:
- 271, SEQ ID NO:
- 273, SEQ ID NO:
- 275, SEQ ID NO:
- 277, SEQ ID NO:
- 279, SEQ ID NO:
- 281, SEQ ID NO:
- 283, SEQ ID NO:
- 285, SEQ ID NO:
- 287, SEQ ID NO:
- 289, SEQ ID NO:
- 291, SEQ ID NO:
- 293, or SEQ ID NO:
- 295 and the light chain comprising one or more molecules having a sequence consisting of one of SEQ ID NO:
- 256, SEQ ID NO:
- 258, SEQ ID NO:
- 260, SEQ ID NO:
- 262, SEQ ID NO:
- 264, SEQ ID NO:
- 266, SEQ ID NO:
- 268, SEQ ID NO:
- 270, SEQ ID NO:
- 272, SEQ ID NO:
- 274, SEQ ID NO:
- 276, SEQ ID NO:
- 278, SEQ ID NO:
- 280, SEQ ID NO:
- 282, SEQ ID NO:
- 284, SEQ ID NO:
- 286, SEQ ID NO:
- 288, SEQ ID NO:
- 290, SEQ ID NO:
- 292, SEQ ID NO:
- 294, or SEQ ID NO:
- 296.
39 more elements
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain and a light chain,
- a) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 255 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO:
- 256;
- b) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 257 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 258;
- c) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 259 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 260;
- d) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 261 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 262;
- c) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 263 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 264;
- f) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 265 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 266;
- g) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 267 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 268;
- h) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 269 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 270;
- i) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 271 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 272;
- j) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 273 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 274;
- k) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 275 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 276;
- l) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 277 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 278
- m) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 279 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 280;
- n) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 281 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 282;
- o) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 283 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 284;
- p) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 285 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 286;
- q) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 287 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 288;
- r) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 289 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 290;
- s) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 291 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 292;
- t) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 293 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 294;
- or
- u) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 295 and the light chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO:
- 296.
61 more elements
An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH and/or VL comprising 1, 2, 3, 4, 5, or 6 of:
- a) a VHCDR1 sequence comprising:
- (i) a Kabat CDRH1 sequence defined by the consensus sequence S-Y-Δ3-M-Δ5 (SEQ ID NOS:
- 25-29 and 44-45), where Δ3 is E, F, Q, or Y and Δ5 is H or Y;
- (ii) a Kabat CDR-H1 sequence defined by the consensus sequence θ1-θ2-θ3-I-S (SEQ ID NOS:
- 30-37), where θ1 is A, H, K, L, S, or W;
- θ2 is L, M, N, or T;
- and θ3 is A or P;
- (iii) a Kabat CDR-H1 sequence defined by the consensus sequence η1-Y-η3-I-S SEQ ID NOS:
- 38-41), where η1 is S, K, N, or R and η3 is A or G;
- (iv) a Chothia CDR-H1 sequence defined by the consensus sequence G-Y-T-F-Ω5-S-Y (SEQ ID NOS:
- 1-2 and 4-6), where Ω5 is T, K, Q, F, or V;
- (v) a Chothia CDR-H1 sequence defined by the consensus sequence G-G-T-F-ν5-ν6-Y (SEQ ID NOS:
- 17-22 and 24), where ν5 is S, G, or E and ν6 is S, K, R, or S;
- or
- (vi) a Chothia CDR-H1 consensus sequence defined by the consensus sequence G-G-T-F-κ5-κ6-κ7 (SEQ ID NOS:
- 7-16), where κ5 is S, Q, P, or A;
- κ6 is S, K, H, L, A, or W;
- and κ7 is Y, L, T, N, or M,
- b) a VHCDR2 sequence comprising:
- (i) a Kabat CDR-H2 sequence defined by the consensus sequence ε1-I-N-P-ε5-ε6-G-S-T-ε10-Y-A-Q-K-F-Q-G (SEQ ID NOS:
- 63-66 and 68), where ε1 is K, S, R, or V;
- ε5 is L, R, or S;
- ε6 is G or V;
- and ε10 is S or W;
- (ii) a Kabat CDR-H2 sequence defined by the consensus sequence G-I-α3-α4-α5-α6-G-T-A-N-Y-A-Q-K-F-Q-G (SEQ ID NOS:
- 69-72), where α3 is I or L or is absent;
- α4 is P or is absent;
- and α5 is I, G, or R;
- and α6 is A, F, or G;
- (iii) a Kabat CDR-H2 sequence defined by the consensus sequence β1-I-I-P-β5-β6-G-β8-A-N-Y-A-Q-K-F-G-Q (SEQ ID NOS:
- 74 and 76-79), where β1 is S or G;
- β5 is I, E, S, or T;
- β6 is F, I, or S;
- and β8 is I or T;
- (iv) a Chothia CDR-H2 sequence defined by the consensus sequence N-P-ε5-ε6-G-S-T (SEQ ID NOS:
- 46-48), where ε5 is L, R, or S and ε6 is G or V;
- (v) a Chothia CDR-H2 sequence defined by the consensus sequence α3-α4-α5-α6-G-T-A (SEQ ID NOS:
- 51-54), where α3 is I or L or is absent;
- α4 is P or is absent;
- and α5 is I, G, or R;
- and α6 is A, F, or G;
- or
- (vi) a Chothia CDR-H2 sequence defined by the consensus sequence I-P-β5-β6-G-β8-A (SEQ ID NOS:
- 56-60), where β5 is I, E, S, or T;
- β6 is F, I, or S;
- and β8 is I or T,
- c) a VHCDR3 sequence comprising:
- (i) a CDR-H3 sequence defined by the consensus sequence G-K-R-E-G-G-T-E-Y-L-R-γ12 (SEQ ID NOS:
- 82-86), where γ12 is H, K, S, N, or V;
- (ii) a CDR-H3 sequence defined by the consensus sequence E-S-G-Φ4-Y-R-D-H-R-L-Φ11-V (SEQ ID NOS:
- 94-96), where Φ4 is G or T and Φ11 is D or G;
- or
- (iii) a CDR-H3 sequence defined by the consensus sequence G-G-A-K-Y-A-∃7-∃8-∃9-G-M-D-V (SEQ ID NOS:
- 87-93), where is, V, G or R;
- ∃8 T, Q, K, G, or R;
- and ∃9 is Y, H, L, or W,
- d) a VLCDR1 sequence comprising:
- (i) a CDR-L1 sequence defined by the consensus sequence ϕ1-A-S-ϕ4-ϕ5-V-ϕ7-ϕ8-ϕ9-Y-L-A (SEQ ID NOS:
- 1101-114), where ϕ1 is E, K, or R;
- ϕ4 is Q or E;
- ϕ5 is S or Y;
- ϕ7 is S or A;
- ϕ8 is S or Y;
- and ϕ9 is D or S;
- (ii) a CDR-L1 sequence defined by the consensus sequence σ1-A-S-Q-σ5-σ6-σ7-σ8-σ9-L-σ11 (SEQ ID NOS:
- 118 and 120-123), where σ1 is Q or R1;
- σ5 is D or S;
- σ6 is I or V;
- σ7 is G or S;
- σ8 is N, R, or S;
- σ9 is N, Y, or W;
- and σ11 is A or N;
- or
- (iii) a CDR-L1 sequence defined by the consensus sequence K-S-S-Γ4-S-V-L-Γ8-S-Γ10-N-N-K-N-Y-L-A (SEQ ID NOS:
- 115-117), where Γ4 is Q, R or K;
- Γ8 is F or Y;
- and Γ10 is S or N,
- e) a VLCDR2 sequence comprising:
- (i) a CDR-L2 sequence defined by the consensus sequence ψ1-A-S-ψ4-R-ψ6-ψ7 (SEQ ID NOS:
- 125-136), where ψ1 is G or Y, ψ4 is S or N;
- ψ6 is A or H;
- and ψ7 is T, Y, or N;
- (ii) a CDR-L2 sequence defined by the consensus sequence D-A-S-χ4-R-A-T (SEQ ID NOS:
- 138 and 139), where £4 is N or K;
- or
- (iii) a CDR-L2 sequence defined by the consensus sequence W-A-S-T-R-σ6-S (SEQ ID NOS:
- 131 and 133-134), where σ6 is A, E, or Q, and
- f) a VLCDR3 sequence comprising:
- (i) a CDR-L3 sequence defined by the consensus sequence Q-Q-Y-π4-π5-π6-π7-T (SEQ ID NOS:
- 141-147), where π4 is G, H, or Y;
- π5 is S, N, F, G, or R;
- π6 is S, Y, A, G, or R;
- and π7 is P, I, or L;
- (ii) a CDR-L3 sequence defined by consensus sequence Q-Q-λ3-λ4-λ5-λ6-P-T (SEQ ID NOS:
- 148-150), where λ3 is R, F, H, S, L, D, Y, or V;
- λ4 is S, V, T, G, L, Y, or N;
- λ5 is N, L, F, K, or V;
- and λ6 is W, F, Y, or L;
- (iii) a CDR-L3 sequence defined by the consensus sequence Q-Q-Y-ρ3-ρ4-W-P-L-T (SEQ ID NOS:
- 151 and 152), where ρ3 is N or L and ρ4 is N or L;
- or
- (iv) a CDR-L3 sequence defined by the consensus sequence Q-Q-ω3-ω4-ω5-ω6-P-ω8-T (SEQ ID NOS:
- 153-156), where ω3 is Y or F;
- ω4 is Y or W;
- ω5 is S, L, T, or F;
- ω6 is T, Y, or F;
- and ω8 is L or P.
104 more elements
Dependencies are inferred from the claim text.