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US 2026/0232829 A1Published application
Novel immunoconjugates
AssigneeCytospire Therapeutics Limited
InventorsNatalie Marianne Mount, Mark Uden
Life of this patent
Estimating the term…
Abstract
The invention provides immunoconjugates comprising at least two IL-15 polypeptides, each comprising an IL-15 cytokine and IL-15 receptor alpha (CD215) or a functional fragment thereof; and a multivalent antibody or antigen-binding fragment thereof that specifically binds to an antigen selected from the group consisting of NKG2D, NKp30, NKp46, NKp44 and DNAM-1. Also provided are uses of said immunoconjugates and methods of using said immunoconjugates.
Claims38
An immunoconjugate, comprising:
- a) at least two IL-15 polypeptides, each comprising
- i. an IL-15 cytokine;
- and
- ii. IL-15 receptor alpha (CD215) or a functional fragment thereof;
- and
- b) a multivalent antibody or antigen-binding fragment thereof, comprising at least two antibody binding domains that each specifically bind to an antigen selected from the group consisting of NKG2D, NKp30, NKp46, NKp44 and DNAM-1.
3 more elements
The immunoconjugate of any preceding claim, wherein the multivalent antibody or antigen-binding fragment thereof comprises at least two heavy chains and at least two light chains, and the IL-15 pol-ypeptides conjugated to the C-termini or the N-termini of the heavy chains, or the C-termini or the N-termini of the light chains, optionally via a linker.
The immunoconjugate of any preceding claim, wherein the multivalent antibody or antigen binding fragment thereof comprises:
- a) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 1, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 14, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 27, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 40, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 53, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 66, optionally having up to 2 amino acid substitutions therefrom;
- b) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 2, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 15, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 28, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 41, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 54, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 67, optionally having up to 2 amino acid substitutions therefrom;
- c) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 3, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 16, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 29, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 42, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 55, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 68, optionally having up to 2 amino acid substitutions therefrom;
- d) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 4, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 17, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 30, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 43, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 56, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 69, optionally having up to 2 amino acid substitutions therefrom;
- e) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 5, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 18, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 31, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 44, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 57, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 70, optionally having up to 2 amino acid substitutions therefrom;
- f) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 6, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 19, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 32, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 45, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 58, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 71, optionally having up to 2 amino acid substitutions therefrom;
- g) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 7, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 20, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 33, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 46, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 59, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 72, optionally having up to 2 amino acid substitutions therefrom;
- h) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 8, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 21, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 34, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 47, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 60, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 73, optionally having up to 2 amino acid substitutions therefrom;
- i) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 9, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 22, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 35, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 48, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 61, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 74, optionally having up to 2 amino acid substitutions therefrom;
- j) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 10, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 23, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 36, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 49, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 62, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 75, optionally having up to 2 amino acid substitutions therefrom;
- k) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 11, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 24, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 37, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 50, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 63, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 76, optionally having up to 2 amino acid substitutions therefrom;
- l) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 12, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 25, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 38, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 51, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 64, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 77, optionally having up to 2 amino acid substitutions therefrom;
- or
- m) a heavy chain variable region (VH) comprising:
- a HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 13, optionally having up to 2 amino acid substitutions therefrom;
- a HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 26, optionally having up to 2 amino acid substitutions therefrom;
- and
- a HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 39, optionally having up to 2 amino acid substitutions therefrom;
- and a light chain variable region (VL) comprising:
- a LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 52, optionally having up to 2 amino acid substitutions therefrom;
- a LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 65, optionally having up to 2 amino acid substitutions therefrom;
- and
- a LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 78, optionally having up to 2 amino acid substitutions therefrom, optionally wherein the op-tional amino acid substitutions are conservative substitutions.
206 more elements
The immunoconjugate of any preceding claim, wherein the multivalent antibody or antigen binding fragment thereof comprises:
- a) a VH comprising or consisting of the sequence of SEQ ID NO:
- 79 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 92;
- b) a VH comprising or consisting of the sequence of SEQ ID NO:
- 202 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 92;
- c) a VH comprising or consisting of the sequence of SEQ ID NO:
- 80 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 93;
- d) a VH comprising or consisting of the sequence of SEQ ID NO:
- 81 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 94;
- e) a VH comprising or consisting of the sequence of SEQ ID NO:
- 82 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 95;
- f) a VH comprising or consisting of the sequence of SEQ ID NO:
- 83 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 96;
- g) a VH comprising or consisting of the sequence of SEQ ID NO:
- 84 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 97;
- h) a VH comprising or consisting of the sequence of SEQ ID NO:
- 85 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 98;
- i) a VH comprising or consisting of the sequence of SEQ ID NO:
- 86 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 99;
- j) a VH comprising or consisting of the sequence of SEQ ID NO:
- 87 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 100;
- k) a VH comprising or consisting of the sequence of SEQ ID NO:
- 88 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 101;
- l) a VH comprising or consisting of the sequence of SEQ ID NO:
- 89 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 102;
- m) a VH comprising or consisting of the sequence of SEQ ID NO:
- 90 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 103;
- or
- n) a VH comprising or consisting of the sequence of SEQ ID NO:
- 91 and a VL comprising or consisting of the sequence of SEQ ID NO:
- 104.
40 more elements
The immunoconjugate of any preceding claim, wherein the multivalent antibody or antigen binding fragment thereof comprises:
- a) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 109 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 135;
- b) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 110 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 136;
- c) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 111 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 137;
- d) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 112 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 138;
- e) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 113 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 139;
- f) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 114 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 140;
- g) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 115 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 141;
- h) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 116 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 142;
- i) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 117 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 143;
- j) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 118 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 144;
- k) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 119 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 145;
- l) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 120 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 146;
- m) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 121 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 147;
- n) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 122 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 135;
- o) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 123 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 136;
- p) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 124 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 137;
- q) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 125 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 138;
- r) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 126 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 139;
- s) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 127 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 140;
- t) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 128 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 141;
- u) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 129 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 142;
- v) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 130 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 143;
- w) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 131 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 144;
- x) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 132 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 145;
- y) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 133 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 146;
- or
- z) a heavy chain comprising or consisting of the sequence of SEQ ID NO:
- 134 and a light chain comprising or consisting of the sequence SEQ ID NO:
- 147.
76 more elements
The immunoconjugate of any preceding claim, wherein the multivalent antibody or antigen binding fragment thereof comprises an Fc domain, optionally wherein the Fc domain is a human Fc domain, optionally wherein the Fc domain is a human IgG Fc domain, optionally wherein the human IgG Fc domain is a human IgG1 domain, optionally wherein the Fc domain is Fc disabled.
The immunoconjugate of any preceding claim, wherein the IL-15 polypeptide is an IL-15 superagonist.
The immunoconjugate of any preceding claim, wherein the IL-15 receptor alpha (CD215) fragment comprises up to 100 consecutive amino acids of the IL-15 receptor alpha (CD215) sequence and com-prises the IL-15 receptor alpha (CD215) sushi domain or wherein the IL-15 polypeptide comprises the IL-15 receptor alpha (CD215) sushi domain, optionally wherein the IL-15 receptor alpha (CD215) sushi domain is a human IL-15 receptor alpha (CD215) sushi domain.
The immunoconjugate of any preceding claim, wherein the IL-15 polypeptide comprises, in an N- to C-terminal direction, a human IL-15 cytokine and IL-15 receptor alpha (CD215) or functional fragment thereof, optionally joined by a linker, or wherein the IL-15 polypeptide comprises, in an N- to C-terminal direction, an IL-15 receptor alpha (CD215) or functional fragment thereof and a human IL-15 cytokine, optionally joined by a linker.
The immunoconjugate of any preceding claim, wherein the IL-15 cytokine is an IL-15 mutein, optionally wherein the IL-15 mutein comprises a N72D mutation.
The immunoconjugate of any preceding claim, wherein the IL-15 cytokine comprises or consists of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 151 to 153.
The immunoconjugate of any preceding claim, wherein the IL-15 polypeptide comprises or consists of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 154 to 155, 206 and 207.
The immunoconjugate of any previous claim, wherein the IL-15 cytokine and the IL-15 receptor alpha (CD215) or functional fragment thereof are directly fused to each other or are joined by a linker.
The immunoconjugate of any previous claim, wherein one or more of the linkers is a peptide linker, optionally a peptide of from about 1 to about 60 amino acid residues in length, optionally wherein the linker comprises or consists of the sequence [[G]mS]nX, wherein m is from 2 to 4, n is from 1 to 6 and X is G or is absent.
The immunoconjugate of any previous claim, wherein the linker comprises or consists of a sequence selected from the group consisting of SEQ ID NOs:
- 182 to 187 and 204 to 205.
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- b) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain of an anti-NKG2D antibody, an anti-NKp30 antibody, an anti-NKp46 antibody, an anti-NKp44 antibody or an anti-DNAM-1 antibody;
- ii. optionally a linker;
- and
- iii. the IL-15 polypeptide;
- and
- b) a second polypeptide chain comprising a light chain of an anti-NKG2D antibody, an anti-NKp30 antibody, an anti-NKp46 antibody, an anti-NKp44 antibody or an anti-DNAM-1 antibody;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
5 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- v. a heavy chain variable region (VH) of an anti-NKG2D antibody, an anti-NKp30 antibody, an anti-NKp46 antibody, an anti-NKp44 antibody or an anti-DNAM-1 antibody, the VH comprising an HCDR1, an HCDR2 and an HCDR3;
- vi. a heavy chain constant region comprising an CH1, a hinge, a CH2 and a CH3 re-gion;
- vii. optionally a linker, and
- viii. the IL-15 polypeptide;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- iii. a light chain variable region (VL) of an anti-NKG2D antibody, an anti-NKp30 antibody, an anti-NKp46 antibody, an anti-NKp44 antibody or an anti-DNAM-1 antibody, the VL comprising an LCDR1, an LCDR2 and an LCDR3;
- and
- iv. a light chain constant (CL) region;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
8 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 6, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 19 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 32, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:84;
- ii. a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105, 106 and 203;
- iii. optionally a linker;
- and
- iv. an IL-15 polypeptide comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 148 to 155, 206 and 207;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- iii. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 45, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 58 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 71, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 97;
- and
- iv. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 107;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
19 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 6, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 19 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 32, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:84;
- ii. a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105;
- iii. optionally a linker;
- and
- iv. an IL-15 polypeptide comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 154, 206 and 207;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- v. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 45, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 58 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 71, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 97;
- and
- vi. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 107;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
19 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 6, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 19 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 32, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:84;
- ii. a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105;
- iii. optionally a linker comprising or consisting of the sequence of SEQ ID NO:
- 182;
- and
- iv. an IL-15 polypeptide comprising or consisting of the sequence of SEQ ID NOs:
- 154;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- vii. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 45, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 58 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 71, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 97;
- and
- viii. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 107;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
20 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 6, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 19 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 32, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:84;
- ii. a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105;
- iii. optionally a linker comprising or consisting of the sequence of SEQ ID NO:
- 184;
- and
- iv. an IL-15 polypeptide comprising or consisting of the sequence of SEQ ID NOs:
- 154;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- ix. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 45, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 58 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 71, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 97;
- and
- x. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 107;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
20 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 6, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 19 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 32, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:84;
- ii. a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105;
- iii. optionally a linker comprising or consisting of the sequence of SEQ ID NO:
- 182;
- and
- iv. an IL-15 polypeptide comprising or consisting of the sequence of SEQ ID NOs:
- 207;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- xi. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 45, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 58 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 71, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 97;
- and
- xii. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 107;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
20 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 1, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 14 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 27, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:79 or 202;
- ii. a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105, 106 and 203;
- iii. optionally a linker;
- and
- iv. an IL-15 polypeptide comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 148 to 155, 206 and 207;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- xiii. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 40, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 53 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 66, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 92;
- and
- xiv. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 108;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
19 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- i) a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 1, an HCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 14 and an HCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 27, optionally wherein the VH region comprises or consists of the sequence of SEQ ID NO:79 or 202;
- ii) a heavy chain constant region comprising or consisting of a sequence of SEQ ID NO:
- 105;
- iii) optionally a linker;
- and
- iv) an IL-15 polypeptide comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 154, 206 and 207;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- a. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of the sequence of SEQ ID NO:
- 40, an LCDR2 comprising or consisting of the sequence of SEQ ID NO:
- 53 and an LCDR3 comprising or consisting of the sequence of SEQ ID NO:
- 66, optionally wherein the VL region comprises or consists of the sequence of SEQ ID NO:
- 92;
- and
- b. a light chain constant region comprising or consisting of the sequence of SEQ ID NO:
- 108;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
19 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- c) a first polypeptide chain comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 156 to 168;
- and
- d) a second polypeptide chain comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 135 to 147;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
3 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- iii. a heavy chain variable region (VH) of an anti-NKG2D antibody, an anti-NKp30 antibody, an anti-NKp46 antibody, an anti-NKp44 antibody or an anti-DNAM-1 antibody, the VH comprising an HCDR1, an HCDR2 and an HCDR3;
- iv. a heavy chain constant region comprising an CH1, a hinge, a CH2 and a CH3 region;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- v. a light chain variable region (VL) of an anti-NKG2D antibody, an anti-NKp30 antibody, an anti-NKp46 antibody, an anti-NKp44 antibody or an anti-DNAM-1 antibody, the VL comprising an LCDR1, an LCDR2 and an LCDR3;
- and
- vi. a light chain constant (CL) region;
- vii. optionally a linker, and
- viii. the IL-15 polypeptide;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
8 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising, in an N- to C-terminal direction:
- iii. a heavy chain variable region (VH) of an anti-NKG2D antibody comprising an HCDR1 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 1 to 10 and optionally having up to 2 amino acid substitutions thereto, an HCDR2 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 14 to 23 and optionally having up to 2 amino acid substitutions thereto, and an HCDR3 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 27 to 36 and optionally having up to 2 amino acid substitutions thereto;
- iv. a heavy chain constant region comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 105, 106 and 203;
- and
- b) a second polypeptide chain comprising, in an N- to C-terminal direction:
- v. a light chain variable region (VL) of an anti-NKG2D antibody comprising an LCDR1 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 40 to 49 and optionally having up to 2 amino acid substitutions thereto, an LCDR2 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 53 to 62 and optionally having up to 2 amino acid substitutions thereto, and an LCDR3 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 66 to 75 and optionally having up to 2 amino acid substitutions thereto;
- and
- vi. a light chain constant region comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 107 to 108;
- vii. optionally a linker;
- and
- viii. an IL-15 polypeptide comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 148 to 155, 206 and 207;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides;
- or
- c) a first polypeptide chain comprising, in an N- to C-terminal direction:
- iii. a heavy chain variable region (VH) of an anti-NKp30 antibody comprising an HCDR1 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 11 to 12 and optionally having up to 2 amino acid substitutions thereto, an HCDR2 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 24 to 25 and optionally having up to 2 amino acid substitutions thereto, and an HCDR3 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 37 to 38 and optionally having up to 2 amino acid substitutions thereto;
- iv. a heavy chain constant region comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 105, 106 and 203;
- and
- d) a second polypeptide chain comprising, in an N- to C-terminal direction:
- v. a light chain variable region (VL) of an anti-NKp30 antibody comprising an LCDR1 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 50 to 51 and optionally having up to 2 amino acid substitutions thereto, an LCDR2 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 63 to 64 and optionally having up to 2 amino acid substitutions thereto, and an LCDR3 comprising or consisting of a sequence selected from the group consisting of SEQ ID NOs:
- 76 to 77 and optionally having up to 2 amino acid substitutions thereto;
- and
- vi. a light chain constant region comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 107 to 108;
- vii. optionally a linker;
- and
- viii. an IL-15 polypeptide comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 148 to 155;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides;
- or
- e) a first polypeptide chain comprising, in an N- to C-terminal direction:
- iii. a heavy chain variable region (VH) of an anti-NKp46 antibody comprising an HCDR1 comprising or consisting of SEQ ID NO:
- 13 and optionally having up to 2 amino acid substitutions thereto, an HCDR2 comprising or consisting of SEQ ID NO:
- 26 and optionally having up to 2 amino acid substitutions thereto, and an HCDR3 comprising or consisting of SEQ ID NO:
- 39 and optionally having up to 2 amino acid substitutions thereto;
- iv. a heavy chain constant region comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NO:
- 105 to 106;
- and
- f) a second polypeptide chain comprising, in an N- to C-terminal direction:
- v. a light chain variable region (VL) of an anti-NKp46 antibody comprising an LCDR1 comprising or consisting of SEQ ID NO:
- 52 and optionally having up to 2 amino acid substitutions thereto, an LCDR2 comprising or consisting of SEQ ID NO:
- 65 and optionally having up to 2 amino acid substitutions thereto, and an LCDR3 comprising or consisting of SEQ ID NO:
- 78 and optionally having up to 2 amino acid substitutions thereto;
- and
- vi. a light chain constant region comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:
- 107;
- vii. optionally a linker;
- and
- viii. an IL-15 polypeptide comprising or consisting of a sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 95%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs:
- 148 to 155, 206 and 207;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides.
62 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugate comprises:
- a) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 156;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 135;
- b) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 157;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 136;
- c) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 158;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 137;
- d) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 159;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 138;
- e) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 160;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 139;
- f) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 161;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- g) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 162;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 141;
- h) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 163;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 142;
- i) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 164;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 143;
- j) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 165;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 144;
- k) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 166;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 145;
- l) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 167;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 146
- m) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 168;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 147;
- n) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 109;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 169;
- o) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 110;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 170;
- p) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 111;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 171
- q) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 112;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 172;
- r) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 113;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 173;
- s) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 114;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 174;
- t) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 115;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 175;
- u) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 116;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 176;
- v) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 117;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 177;
- w) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 118;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 178;
- x) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 119;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 179;
- y) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 120;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 180;
- z) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 121;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 181;
- aa) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 122;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 169;
- bb) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 123;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 170;
- cc) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 124;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 171;
- dd) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 125;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 172;
- ee) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 126;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 173;
- ff) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 127;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 174;
- gg) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 128;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 175;
- hh) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 129;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 176;
- ii) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 130;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 177;
- jj) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 131;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 178;
- kk) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 132;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 179;
- ll) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 133;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 180;
- mm) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 134;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 181;
- nn) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 188;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 135;
- oo) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 189;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- pp) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 191;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- qq) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 192;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- rr) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 195;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- ss) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 200;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- tt) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 190;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 140;
- or
- uu) a first polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 114;
- and a second polypeptide chain comprising or consisting of the sequence of SEQ ID NO:
- 199;
- and the immunoconjugate comprises or consists of first and second copies of said first and second polypeptides
187 more elements
The immunoconjugate of any preceding claim, wherein the immunoconjugates are homodimeric.
An immunoconjugate, comprising:
- a) at least two IL-15 polypeptides, each comprising
- i. an IL-15 cytokine;
- and
- ii. IL-15 receptor alpha (CD215) or a functional fragment thereof;
- and
- b) a multivalent antibody or antigen-binding fragment thereof, comprising at least two antibody binding domains, wherein the multivalent antibody or antigen-binding fragment thereof specifically binds to NKG2D.
3 more elements
Dependencies are inferred from the claim text.