CD27L antigen binding proteins
The present invention relates to CD27L antigen binding proteins, such an antibodies, polynucleotides encoding said CD27l antigen binding proteins, antibody drug conjugate compositions, and methods for diagnosing and treating diseases associated with CD27L expression.
1. A method of treating a CD27L-expressing cancer, said method comprising administering a therapeutically effective amount of an anti-CD27L antibody or antigen-binding fragment thereof to a patient in need thereof, wherein the antibody or antigen-binding fragment thereof comprises:
a) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 71; an LCDR2 sequence as set forth in SEQ ID NO: 79; and an LCDR3 sequence as set forth in SEQ ID NO: 87; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 25; an HCDR2 sequence as set forth in SEQ ID NO: 33; and an HCDR3 sequence as set forth in SEQ ID NO: 41;
b) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 72; an LCDR2 sequence as set forth in SEQ ID NO: 80; and an LCDR3 sequence as set forth in SEQ ID NO: 88; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 26; an HCDR2 sequence as set forth in SEQ ID NO: 34; and an HCDR3 sequence as set forth in SEQ ID NO: 42;
c) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 73; an LCDR2 sequence as set forth in SEQ ID NO: 81; and an LCDR3 sequence as set forth in SEQ ID NO: 89; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 27; an HCDR2 sequence as set forth in SEQ ID NO: 35; and an HCDR3 sequence as set forth in SEQ ID NO: 43;
d) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 74; an LCDR2 sequence as set forth in SEQ ID NO: 82; and an LCDR3 sequence as set forth in SEQ ID NO: 90; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 28; an HCDR2 sequence as set forth in SEQ ID NO: 36; and an HCDR3 sequence as set forth in SEQ ID NO: 44;
e) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 75; an LCDR2 sequence as set forth in SEQ ID NO: 83; and an LCDR3 sequence as set forth in SEQ ID NO: 91; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 29; an HCDR2 sequence as set forth in SEQ ID NO: 37; and an HCDR3 sequence as set forth in SEQ ID NO: 45;
f) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 76; an LCDR2 sequence as set forth in SEQ ID NO: 84; and an LCDR3 sequence as set forth in SEQ ID NO: 92; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 30; an HCDR2 sequence as set forth in SEQ ID NO: 38; and an HCDR3 sequence as set forth in SEQ ID NO: 46;
g) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 77; an LCDR2 sequence as set forth in SEQ ID NO: 85; and an LCDR3 sequence as set forth in SEQ ID NO: 93; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 31; an HCDR2 sequence as set forth in SEQ ID NO: 39; and an HCDR3 sequence as set forth in SEQ ID NO: 47; or
h) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO: 78; an LCDR2 sequence as set forth in SEQ ID NO: 86; and an LCDR3 sequence as set forth in SEQ ID NO: 94; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO: 32; an HCDR2 sequence as set forth in SEQ ID NO: 40; and an HCDR3 sequence as set forth in SEQ ID NO: 48;
i) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with an R24K-S26G mutation; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3 sequence as set forth in SEQ ID NO:44, but with an N31S-134M mutation;
j) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with an R24K-S26G mutation; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3 sequence as set forth in SEQ ID NO:44;
k) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with an L551-Y58F mutation; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3 sequence as set forth in SEQ ID NO:44;
l) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with a Q95N-T96S mutation; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3 sequence as set forth in SEQ ID NO:44, but with an N31S-134M mutation; or
m) a light chain variable domain comprising an LCDR1 sequence as set forth in SEQ ID NO:74; an LCDR2 sequence as set forth in SEQ ID NO:82; and an LCDR3 sequence as set forth in SEQ ID NO:90, but with a Q95N-T96S mutation; and a heavy chain variable domain comprising an HCDR1 sequence as set forth in SEQ ID NO:28; an HCDR2 sequence as set forth in SEQ ID NO:36; and an HCDR3 sequence as set forth in SEQ ID NO:44.
2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
a) a light chain variable domain having at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70;
b) a heavy chain variable domain having at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24;
c) the light chain variable domain of a) and the heavy chain variable domain of b);
d) a light chain variable domain having no more than ten amino acid additions, deletions or substitutions from the amino acid sequence set forth in SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70;
e) a heavy chain variable domain having no more than ten amino acid additions, deletions or substitutions from the amino acid sequence set forth in SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24; or
f) the light chain variable domain of d) and the heavy chain variable domain of e).
3. The method of claim 1 or 2 , wherein the anti-CD27L antibody or antigen-binding fragment thereof is an antibody.
4. The method of claim 3 , wherein the antibody comprises:
a) a light chain variable domain amino acid sequence as set forth in SEQ ID NO: 63 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO: 17,
b) a light chain variable domain amino acid sequence as set forth in SEQ ID NO: 64 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO: 18,
c) a light chain variable domain amino acid sequence as set forth in SEQ ID NO:65 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO:19,
d) a light chain variable domain amino acid sequence as set forth in SEQ ID NO:66 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO:20,
e) a light chain variable domain amino acid sequence as set forth in SEQ ID NO:67 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO:21,
f) a light chain variable domain amino acid sequence as set forth in SEQ ID NO:68 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO:22,
g) a light chain variable domain amino acid sequence as set forth in SEQ ID NO:69 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO:23, or
h) a light chain variable domain amino acid sequence as set forth in SEQ ID NO:70 and a heavy chain variable domain amino acid sequence as set forth in SEQ ID NO:24.
5. The method of claim 4 , wherein the antibody comprises
a) a light chain amino acid sequence as set forth in SEQ ID NO: 56 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 10,
b) a light chain amino acid sequence as set forth in SEQ ID NO: 57 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 11,
c) a light chain amino acid sequence as set forth in SEQ ID NO: 58 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 12,
d) a light chain amino acid sequence as set forth in SEQ ID NO: 59 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 13,
e) a light chain amino acid sequence as set forth in SEQ ID NO: 60 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 14,
f) a light chain amino acid sequence as set forth in SEQ ID NO: 61 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 15, or
g) a light chain amino acid sequence as set forth in SEQ ID NO: 62 and a heavy chain amino acid sequence as set forth in SEQ ID NO: 16.
6. The method of claim 3 , wherein a pharmaceutical composition comprises the antibody.
7. The method of claim 6 , wherein the pharmaceutical composition comprises a population of antibody drug conjugates.
8. The method of claim 7 , wherein the antibody drug conjugate comprises a non-cleavable linker.
9. The method of claim 8 , wherein the linker comprises an N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate (MCC) linker.
10. The method of claim 7 , wherein the drug is conjugated to one or more lysines contained within a polypeptide of the anti-CD27L antibody or an antigen-binding fragment thereof.
11. The method of claim 7 , wherein the antibody drug conjugate comprises N 2′ -deacetyl-N 2′ (3-mercapto-1-oxopropyl)-maytansine (DM1).
12. The method of claim 11 , wherein the average number of DM1 molecules per antibody is between 1 and 10.
13. The method of claim 12 , wherein the average number of DM1 molecules per antibody is between 3 and 7.
14. The method of claim 13 , wherein the average number of DM1 molecules per antibody is between 4 and 6.
15. The method of claim 14 , wherein the average number of DM1 molecules per antibody is about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, or about 6.0.
16. The method of claim 3 , wherein a sample from the patient is tested for CD27L expression.
17. The method of claim 16 , wherein the sample is tested for CD27L mRNA expression or for CD27L protein expression.
18. The method of claim 16 , wherein the sample is a blood sample or a biopsy.
19. The method of claim 3 , wherein the cancer is renal cell carcinomas (RCC), clear cell RCC, head and neck cancer, glioblastoma, breast cancer, brain tumor, nasopharangeal carcinoma, non-Hodgkin's lymphoma (NHL), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), Burkitt's lymphoma, anaplastic large-cell lymphomas (ALCL), multiple myeloma, cutaneous T-cell lymphomas, nodular small cleaved-cell lymphomas, lymphocytic lymphomas, peripheral T-cell lymphomas, Lennert's lymphomas, immunoblastic lymphoma, T-cell leukemia/lymphomas (ATLL), adult T-cell leukemia (T-ALL), entroblastic/centrocytic (cb/cc) follicular lymphoma cancer, diffuse large cell lymphoma of B lineage, angioimmunoblastic lymphadenopathy (AILD)-like T cell lymphoma, HIV associated body cavity based lymphoma, embryonal carcinoma, undifferentiated carcinoma of the rhino-pharynx, Castleman's disease, Kaposi's Sarcoma, multiple myeloma, Waldenstrom's macroglobulinemia or other B-cell lymphoma.
20. The method of claim 3 , wherein the antibody is a bispecific antibody.
21. The method of claim 20 , wherein the bispecific antibody binds CD27L and a human effector cell antigen which is CD3.
22. The method of claim 1 or 2 , wherein the antibody or antigen-binding fragment thereof is an antibody fragment.
23. The method of claim 22 , wherein the antibody fragment is selected from the group consisting of an F(ab), Fab fragments consisting of VL, VH, CL and CH1 domains, F(ab′), F(ab′)2, bivalent fragments comprising two linked Fab fragments, Fd fragments consisting of the VH and CH1 domains, Fv, Fv fragments consisting of the VL and VH domains of a single antibody, dAb fragments, single chain Fv molecules (scFv), bispecific single chain Fv dimers, diabodies and triabodies.