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 CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
2. A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
3. A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
4. A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
5. The A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
6. A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
7. A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
8. A CD27L antigen binding protein having a light chain variable domain comprising an LCDR1 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 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.
9. The CD27L antigen binding protein of claim 1 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:56 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:10.
10. The CD27L antigen binding protein of claim 2 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:57 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:11.
11. The CD27L antigen binding protein of claim 4 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:58 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:12.
12. The CD27L antigen binding protein of claim 5 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:59 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:13.
13. The CD27L antigen binding protein of claim 6 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:60 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:14.
14. The CD27L antigen binding protein of claim 7 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:61 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:15.
15. The CD27L antigen binding protein of claim 8 , wherein the light chain comprises the amino acid sequence set forth in SEQ ID:62 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:16.
16. A variant of the CD27L antigen binding protein of claim 11 , wherein the variant is selected from the group consisting of:
an R24K-S26G light chain modification in SEQ ID NO:58 in combination with an N31S-I34M heavy chain modification in SEQ ID NO:12;
an R24K-S26G light chain modification in SEQ ID NO:58;
an L55I-Y58F light chain modification in SEQ ID NO:58;
an Q95N-T96S light chain modification in SEQ ID NO:58 in combination with an N31S-I34M heavy chain modification in SEQ ID NO:12; and
an Q95N-T96S light chain modification in SEQ ID NO:58.
17. A variant of the CD27L antigen binding protein of claim 11 , wherein the variant is selected from the group consisting of:
an N31H-Y58N light chain modification in SEQ ID NO:58 in combination with an N31S-I34M heavy chain modification in SEQ ID NO:12;
an N31H-Y58N light chain modification in SEQ ID NO:58;
an R24K-S26G light chain modification in SEQ ID NO:58 in combination with an D54E-G55S heavy chain modification in SEQ ID NO:12;
an R24K-S26G light chain modification in SEQ ID NO:58 in combination with an S103G-G104S heavy chain modification in SEQ ID NO:12;
an L55I-Y58F light chain modification in SEQ ID NO:58 in combination with an N31S-I34M heavy chain modification in SEQ ID NO:12;
an L55I-Y58F light chain modification in SEQ ID NO:58 in combination with an D54E-G55S heavy chain modification in SEQ ID NO:12;
an L55I-Y58F light chain modification in SEQ ID NO:58 in combination with an S103G-G104S heavy chain modification in SEQ ID NO:12;
an Q95N-T96S light chain modification in SEQ ID NO:58 in combination with an D54E-G55S heavy chain modification in SEQ ID NO:12;
an N31S-I34M heavy chain modification in SEQ ID NO:12; and
an D54E-G55S heavy chain modification in SEQ ID NO:12.
18. The CD27L antigen binding protein of any one of claims 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , or 17 , wherein the CD27L antigen binding protein is conjugated to a chemotherapeutic agent.
19. The CD27L antigen binding protein of claim 18 , wherein a linker conjugates the chemotherapeutic agent to the CD27L antigen binding protein.
20. The CD27L antigen binding protein of claim 19 , wherein the linker is a non-cleavable linker.
21. The CD27L antigen binding protein of claim 20 , wherein the linker comprises N-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1 carboxylate (MCC).
22. The CD27L antigen binding protein of claim 21 , wherein the chemotherapeutic agent is conjugated to one or more lysines contained within a polypeptide of the CD27L antigen binding protein.
23. The CD27L antigen binding protein of claim 22 , wherein the chemotherapeutic agent is N 2′ -deacetyl-N 2′ (3-mercapto-1-oxopropyl)-maytansine (DM1).
24. A composition of CD27L antigen binding proteins of claim 23 , wherein the average number of DM1 molecules per CD27L antigen binding protein is between 1 and 10.
25. The composition of CD27L antigen binding proteins of claim 24 , wherein the average number of DM1 molecules per CD27L antigen binding protein is between 3 and 7.
26. The composition of CD27L antigen binding proteins of claim 25 , wherein the average number of DM1 molecules per CD27L antigen binding protein is between 4 and 6.
27. The composition of CD27L antigen binding proteins of claim 25 , wherein the average number of DM1 molecules per CD27L antigen binding protein 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.
28. The composition of CD27L antigen binding proteins of claim 24 , wherein the composition is a pharmaceutical composition comprising a therapeutically effective amount of the CD27L antigen binding protein.
29. The composition of CD27L antigen binding proteins of claim 28 , wherein the pharmaceutical composition is lyophilized.