Human cd6 binding molecules

HK40137835APending Publication Date: 2026-09-18THE CLEVELAND CLINIC FOUND
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Patent Information

Application Number
HK62026126481
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-03-23
Filing Date
2026-07-22
Publication Date
2026-09-18
Estimated Expiration
2044-03-21

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Abstract

Provided herein are human Cluster of Differentiation 6 (CD6) binding molecules and nucleic acid sequences encoding such molecules. In particular embodiments, provided herein are human CD6 binding molecules (e.g., nanobodies) having a first, and optionally a second, single monomeric variable antibody domain (SMVAD) that comprises certain CDRs, and methods for using such molecules to treat T-cell related diseases (e.g., cancer, such as T-cell lymphoma). In certain embodiments, the SMVAD comprises camelid, human, or humanized framework regions.
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Description

Abstract This article provides human differentiation cluster 6 (CD6) binding molecules and nucleic acid sequences encoding such molecules. In specific embodiments, this article provides human CD6 binding molecules (e.g., nanobodies) having a first and optionally a second single monomeric variable antibody domain (SMVAD) comprising certain CDRs, and methods for treating T-cell-related diseases (e.g., cancers such as T-cell lymphoma). In some embodiments, the SMVAD comprises a camel, human, or humanized framework region.

Claims

CLAIMS:We claim:

1. A composition comprising a human Cluster of Differentiation 6 (CD6) binding molecule, or one or more nucleic acid molecules encoding said human CD6 binding molecule, wherein said human CD6 binding molecule comprises a first single monomeric variable antibody domain (SMVAD) that comprises:A) a CDR1 amino acid sequence comprising SEQ ID NO:2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; or SEQ ID NO:2, 6, 10, 14, 18, 22, 26,30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; with one with one or two conservative amino acid changes,B) a CDR2 amino acid sequence comprising SEQ ID NO:3, 7, 11, 15, 19, 23, 27,31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79; or SEQ ID NO:3, 7, 11, 15, 19, 23, 27,31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79 with one or two conservative amino acid changes, andC) a CDR3 amino acid sequence comprising SEQ ID NO:4, 8, 12, 16, 20, 24, 28,32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80; or SEQ ID NO:4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80 with one with one or two conservative amino acid changes.

2. The composition of claim 1 , wherein said first SMVAD further comprises four Framework regions, wherein said four Framework regions are camelid, humanized, or human Framework regions.

3. The composition of claim 1, wherein said human CD6 binding molecule further comprises a second SMVAD that comprises:D) a CDR1 amino acid sequence comprising SEQ ID NO:2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; or SEQ ID NO:2, 6, 10, 14, 18, 22, 26,30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; with one with one or two conservative amino acid changes,E) a CDR2 amino acid sequence comprising SEQ ID NO:3, 7, 11, 15, 19, 23, 27,31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79; or SEQ ID NO:3, 7, 11, 15, 19, 23, 27,31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79 with one or two conservative amino acid changes, andF) a CDR3 amino acid sequence comprising SEQ ID NO:4, 8, 12, 16, 20, 24, 28,32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80; or SEQ ID NO:4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80 with one with one or two conservative amino acid changes.

4. The composition of claim 3, wherein said human CD6 binding molecule further comprises a linker which is attached to both said first SMVAD and said second SMVAD.

5. The composition of claim 3, wherein said one or more nucleic acid molecules comprise: i) a first nucleic acid sequence encoding said first SMVAD, and optionally further encoding a CH2 heavy chain constant region and / or a CH3 heavy chain constant region and ii) a second nucleic acid sequence encoding said second SMVAD, and optionally further encoding a CH2 heavy chain constant region and / or a CH3 heavy chain constant region.

6. The composition of claim 1, wherein said first SMVAD comprises the amino acid sequence shown in SEQ ID NO:1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, or 77; or SEQ ID NO:1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, or 77 with one, two, three, or four deletions and / or conservative amino acid changes.

7. The composition of claim 1, wherein said human CD6 binding molecule further comprises a CH2 heavy chain constant region and / or a CH3 heavy chain constant region.

8. The composition of claim 1, wherein said CH2 and / or CH3 heavy chain constant regions are camelid, humanized, or human.

9. The composition of claim 1, wherein said human CD6 binding molecule is conjugated to a cytotoxic agent, and optionally wherein said cytotoxic agent comprises Monomethyl auristatin (MMAE).

10. The composition of claim 1, further comprising a physiologically tolerable buffer.

11. The composition of claim 1 , wherein said composition comprises said one or more nucleic acid molecules, and optionally the composition further comprises an expression vector, and wherein said one or more nucleic acid sequences are present in said expression vector.

12. The composition of claim 1, wherein said composition comprises said human CD6 binding molecule.

13. The composition of claim 1, wherein: said CDR1 amino acid sequence comprises SEQ ID NO:2, 6, 10, 14, 18, 22, 26, 30,34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; said CDR2 amino acid sequence comprises SEQ ID NO:3, 7, 11, 15, 19, 23, 27, 31,35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79, and said CDR3 amino acid sequence comprises SEQ ID NO:4, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80.

14. A method of treating or preventing a T-cell related disease or condition comprising: treating a subject with a composition comprising a human Cluster of Differentiation 6(CD6) binding molecule, or an expression vector comprising said one or more nucleic acid molecules encoding said CD6 binding molecule, as recited in any of Claims 1-13, and wherein said subject has, or is suspected to develop, a T-cell related disease or condition.

15. The method of claim 14, wherein said T-cell related disease comprises cancer, and optionally wherein said cancer comprises T-cell lymphoma.

16. The method of claim 14, wherein said T-cell related disease comprises acute respiratory distress syndrome (ARDS), cytokine-release syndrome in a Covid- 19 subject, or acute graft vs host disease (aCGDH).

17. The method of claim 14, wherein said T-cell related disease comprises lupus nephritis, uncontrolled asthma, psoriasis, or multiple schlerosis.

18. The method of claim 14, wherein said first SMVAD further comprises four Framework regions, wherein said four Framework regions are camelid, humanized, or human Framework regions.

19. The method of claim 14, wherein said human CD6 binding molecule further comprises a second SMVAD that comprises:D) a CDR1 amino acid sequence comprising SEQ ID NO:2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; or SEQ ID NO:2, 6, 10, 14, 18, 22, 26,30, 34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; with one with one or two conservative amino acid changes,E) a CDR2 amino acid sequence comprising SEQ ID NO:3, 7, 11, 15, 19, 23, 27,31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71 , 75, or 79; or SEQ ID NO:3, 7, 11, 15, 19, 23, 27,31, 35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79 with one or two conservative amino acid changes, andF) a CDR3 amino acid sequence comprising SEQ ID NO:4, 8, 12, 16, 20, 24, 28,32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80; or SEQ ID NO:4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80 with one with one or two conservative amino acid changes.

20. The method of claim 19, wherein said human CD6 binding molecule further comprises a linker which is attached to both said first SMVAD and said second SMVAD.

21. The method of claim 19, wherein said one or more nucleic acid molecules comprise: i) a first nucleic acid sequence encoding said first SMVAD, and optionally further encoding a CH2 heavy chain constant region and / or a CH3 heavy chain constant region and ii) a second nucleic acid sequence encoding said second SMVAD, and optionally further encoding a CH2 heavy chain constant region and / or a CH3 heavy chain constant region.

22. The method of claim 14, wherein said first SMVAD comprises the amino acid sequence shown in SEQ ID NO: 1 , or SEQ ID NO: 1 with one, two, three, or four deletions and / or conservative amino acid changes.

23. The method of claim 14, wherein said human CD6 binding molecule further comprises a CH2 heavy chain constant region and / or a CH3 heavy chain constant region.

124. The method of claim 14, wherein said CH2 and / or CH3 heavy chain constant regions are camelid, humanized, or human.

25. The method of claim 14, wherein said human CD6 binding molecule comprises at least an antigen binding portion of Clone 2G1 CD6 nanobody.

26. The method of claim 14, wherein said composition further comprises a physiologically tolerable buffer.

27. The method of claim 14, wherein said composition comprises said expression vector, and wherein said one or more nucleic acid sequences are present in said expression vector.

28. The method of claim 14, wherein said composition comprises said human CD6 binding molecule.

29. The method of claim 14, wherein: said CDR1 amino acid sequence comprises SEQ ID NO:2, 6, 10, 14, 18, 22, 26, 30,34, 38, 42, 46, 50, 54, 58, 62, 66, 70, 74, or 78; said CDR2 amino acid sequence comprises SEQ ID NO:3, 7, 11, 15, 19, 23, 27, 31,35, 39, 43, 47, 51, 55, 59, 63, 67, 71, 75, or 79, and said CDR3 amino acid sequence comprises SEQ ID NO:4, 8, 12, 16, 20, 24, 28, 32,36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, or 80.

30. A method of detecting human Cluster of Differentiation 6 (CD6) in a sample comprising: a) contacting a sample with the human CD6 binding molecule of any of Claims 1-13, wherein said sample is suspected of containing human CD6, and wherein said human CD6 binding molecule forms a complex with said human CD6 if present in said sample; and b) detecting the presence or absence of said complex in said sample.

31. The method of Claim 30, wherein said sample is from a subject that has, or is suspected to develop, a T-cell related disease or condition.

32. The method of Claim 30, wherein said human CD6 binding molecule comprises a detectable label.

33. The method of Claim 30, further comprising contacting said sample with a conjugate molecule capable of binding to said human CD6 binding molecule, wherein said conjugate molecule comprises a detectable label.