阅读说明：本技术 抗cd38抗体 (anti-CD 38 antibodies ) 是由 K·A·伊莱亚斯 G·兰德斯 S·辛格 W·科尔韦尔 A·W·德雷克 M·哈克-弗伦德斯邵 于 2020-01-23 设计创作，主要内容包括：本公开涉及抗CD38结合结构域,特征在于其CDR序列。利用具有权利要求1至9中要求的序列的抗体提供了一些实验数据。参见表4中的亲和力值。CD38-TM1、CD38-TM2和CD38-TM5结合人CD38上与达雷木单抗相比非重叠的表位残基。CD38-TM3和CD38-TM4结合人CD38上部分重叠于达雷木单抗的表位。(The present disclosure relates to anti-CD 38 binding domains characterized by their CDR sequences. The use of antibodies having the sequences as claimed in claims 1 to 9 provides some experimental data. See table 4 for affinity values. CD38-TM1, CD38-TM2 and CD38-TM5 bind to non-overlapping epitope residues on human CD38 compared to Daraquine. CD38-TM3 and CD38-TM4 bind to an epitope on human CD38 that partially overlaps with daratumab.)

1. A composition comprising an anti-CD 38 antigen binding domain comprising:

a) a heavy chain variable domain (VH) comprising:

i) a VHCDR1 comprising the sequence of SEQ ID NO. 2;

ii) a VHCDR2 comprising the sequence of SEQ ID NO. 3; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO. 4; and

b) a light chain variable domain (VL) comprising:

i) a VLCDR1 comprising the sequence of SEQ ID NO 6;

ii) a VLCDR2 comprising the sequence of SEQ ID NO. 7; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO 8.

2. The composition of claim 1, wherein said VH comprises the sequence of SEQ ID No. 1 and said VL comprises the sequence of SEQ ID No. 25.

3. The composition of claim 1, wherein said VH comprises the sequence of SEQ ID No. 1 and said VL comprises the sequence of SEQ ID No. 5.

4. A composition comprising an anti-CD 38 antigen binding domain, the anti-CD 38 antigen binding domain comprising:

a) a heavy chain variable domain (VH) comprising:

i) VHCDR1 comprising the sequence of SEQ ID NO. 10;

ii) a VHCDR2 comprising the sequence of SEQ ID NO. 11; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO. 12; and

b) a light chain variable domain (VL) comprising:

i) a VLCDR1 comprising the sequence of SEQ ID NO. 14;

ii) a VLCDR2 comprising the sequence of SEQ ID NO. 15; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO 16.

5. The composition of claim 4, wherein said VH comprises the sequence of SEQ ID NO 9 and said VL comprises the sequence of SEQ ID NO 13.

6. A composition comprising an anti-CD 38 antigen binding domain, the anti-CD 38 antigen binding domain comprising:

a) a heavy chain variable domain (VH) comprising:

i) VHCDR1 comprising the sequence of SEQ ID NO. 18;

ii) a VHCDR2 comprising the sequence of SEQ ID NO 19; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO 20; and

b) a light chain variable domain (VL) comprising:

i) a VLCDR1 comprising the sequence of SEQ ID NO. 22;

ii) a VLCDR2 comprising the sequence of SEQ ID NO. 23; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO. 24.

7. The composition of claim 6, wherein said VH comprises the sequence of SEQ ID NO 17 and said VL comprises the sequence of SEQ ID NO 21.

8. A composition comprising an anti-CD 38 antigen binding domain, the anti-CD 38 antigen binding domain comprising:

a) a heavy chain variable domain (VH) comprising:

i) 54 comprising the sequence of SEQ ID No.: VHCDR 1;

ii) a VHCDR2 comprising the sequence of SEQ ID NO. 55; and

iii) a VHCDR3 comprising the sequence of SEQ ID NO 56; and

b) a light chain variable domain (VL) comprising:

i) a VLCDR1 comprising the sequence of SEQ ID NO. 58;

ii) a VLCDR2 comprising the sequence of SEQ ID NO 59; and

iii) a VLCDR3 comprising the sequence of SEQ ID NO 60.

9. The composition of claim 8, wherein said VH comprises the sequence of SEQ ID No. 53 and said VL comprises the sequence of SEQ ID No. 57.

10. The composition of any one of the preceding claims, wherein the VH and the VL are in a single polypeptide.

11. The composition of claim 10, wherein the polypeptide comprises an scFv linker and the polypeptide has an N-to-C orientation of VH-scFv linker-VL.

12. The composition of claim 10, wherein the polypeptide comprises an scFv linker and the polypeptide has an N-to-C orientation of VL-scFv linker-VH.

13. The composition of any one of claims 1 to 9, wherein said composition comprises a first polypeptide comprising said VH and a second polypeptide comprising said VL.

14. The composition of any one of claims 1 to 9, wherein the composition is an antibody comprising:

a) a heavy chain comprising said VH; and

b) a light chain comprising said VL.

15. The composition of claim 14, wherein the heavy chain comprises the heavy chain variable domain and a heavy chain constant domain selected from the group consisting of the heavy chain constant domains of human IgG1, IgG2, and IgG4, or variants thereof.

16. The composition of claim 15, wherein the heavy chain constant domain is a heavy chain constant domain of human IgG 1.

17. The composition of claim 16, wherein the heavy chain constant domain is a variant heavy chain constant domain of the human IgG 1.

18. The composition of claim 17, wherein the variant heavy chain constant domain of human IgG1 has abolished fcyr binding.

19. The composition of claim 15, wherein the heavy chain constant domain is a variant of a human IgG4 heavy chain constant domain comprising an S228P amino acid substitution compared to a wild-type heavy chain constant domain of human IgG 4.

20. A nucleic acid composition encoding the composition of claim 15, wherein the nucleic acid composition comprises:

a) a first nucleic acid encoding the first polypeptide; and

b) a second nucleic acid encoding the second polypeptide.

21. A nucleic acid composition comprising a nucleic acid encoding the composition of claim 10.

22. An expression vector composition comprising the nucleic acid of claim 21.

23. An expression vector composition comprising the first nucleic acid of claim 20 and a second nucleic acid.

24. An expression vector composition comprising:

a) a first expression vector comprising the first nucleic acid of claim 20; and

b) a second expression vector comprising the second nucleic acid of claim 20.

25. A host cell comprising the expression vector composition of any one of claims 22 to 24.

26. A method of making a composition comprising an anti-CD 38 antigen-binding domain, comprising culturing the host cell of claim 25 under conditions in which the composition comprising an anti-CD 38 binding domain is expressed, and recovering the composition.

27. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of a composition according to any one of claims 1 to 19.