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1. (WO2017066714) ANTI-VSIG1 ANTIBODIES AND DRUG CONJUGATES
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

WHAT IS CLAIMED;

1. An antibody that binds V-set and immunoglobulin domain-containing protein 1 (VSIGl), wherein said antibody is selected from the group consisting of: CPA.4.028, CPA.4.013, CPA.4.016, CPA.4.017, CPA.4.019, CPA.4.020, CPA.4.023, CPA.4.005, CPA.4.009, CPA.4.027, CPA.4.031, CPA.4.033, CPA.4.012, CPA.4.008, and CPA.4.011.

2. The anti-VSIGl antibody of claim 1 where said antibody is an antibody drug conjugate compound that binds V-set and immunoglobulin domain-containing protein 1 (VSIGl), comprising at least one drug moiety and an anti-VSIGl antibody according to claim 1.

3. The anti-VSIGl antibody according to claim 2 wherein said drug moiety is attached to said antibody by an ADC linker.

4. The anti-VSIGl antibody according to claim 2 wherein said ADC linker is cleavable.

5. The anti-VSIGl antibody according to claims 3 or 4 wherein said ADC linker is self-immolative.

6. The anti-VSIGl antibody according to any of claims 2 to 5 wherein said drug moiety is selected from the group consisting of: taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine, mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU), lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) ((DDP) cisplatin), daunorubicin, doxorubicin), dactinomycin, bleomycin, mithramycin, anthramycin (AMC)), vincristine, vinblastine, a duocarmycin, a calicheamicin, a dolastatin, a maytansine, an auristatin, iodine 131, indium 111, yttrium 90, and lutetium 177.

7. The anti-VSIGl antibody according to any of claims 2 to 6 wherein said drug moiety is selected from the group consisting of: the maytansinoid (N2'-deacetyl-N2'-(3-mercapto-l-oxopropyl)maytansine) (DM1), monomethyl auristatin (MMAE), monomethyl auristatin phenylalanine (MMAF), and duocarmycin.

8. The anti-VSIGl antibody of any of claims 2 to 7, wherein the antibody-drug conjugate compound is cytostatic to cancer cells.

9. The anti-VSIGl antibody of any of claims 1 to 8, wherein said anti-VSIGl antibody binds to an epitope located within the extracellular domain of VSIGl .

10. The anti -VSIGl antibody of any of claims

competes for binding at an epitope located within the extracellular domain of VSIGl.

11. The anti -VSIGl antibody of any of claims 1 to 10, wherein the anti -VSIGl antibody is a human monoclonal anti-VSIGl antibody.

12. The anti-VSIGl antibody of claim 11, wherein the human monoclonal anti-VSIGl antibody is CPA.4.028.

13. The anti-VSIGl antibody of claim 11, wherein the human monoclonal anti-VSIGl antibody comprises a variable heavy and variable light chain pair selected from the group consisting of: the variable heavy and variable light chain pair from CPA.4.028, the variable heavy and variable light chain pair from CPA.4.013, the variable heavy and variable light chain pair from CPA.4.016, the variable heavy and variable light chain pair from CPA.4.017, the variable heavy and variable light chain pair from CPA.4.019, the variable heavy and variable light chain pair from CPA.4.020, the variable heavy and variable light chain pair from CPA.4.023, the variable heavy and variable light chain pair from CPA.4.005, the variable heavy and variable light chain pair from CPA.4.009, the variable heavy and variable light chain pair from CPA.4.027, the variable heavy and variable light chain pair from CPA.4.031, the variable heavy and variable light chain pair from CPA.4.033, the variable heavy and variable light chain pair from CPA.4.012, the variable heavy and variable light chain pair from CPA.4.008, and the variable heavy and variable light chain pair from

CPA.4.011.

14. An antibody that binds V-set and immunoglobulin domain-containing protein 1 (VSIGl), wherein said antibody comprises a variable heavy chain sequence and a variable light chain sequence selected from the group consisting of:

i) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.028, wherein

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFTFSSYG (SEQ ID NO:X), a vHCDR2 having the sequence IWYDGSNK (SEQ ID NO:X), and a vHCDR3 having the sequence

ARGGPWGIVVVNQFDY (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence SDINVSSYN (SEQ ID NO:X), a vLCDR2 having the sequence YYSDSDK (SEQ ID NO:X), and a vLCDR3 having the sequence MIWPSTGRWV (SEQ ID NO:X); and

ii) a variable heavy chain sequence and

4.013, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFTFSSYS (SEQ ID NO:X), a vHCDR2 having the sequence ISSSSSYI (SEQ ID NO:X), and a vHCDR3 having the sequence

ARNVLRGAAQYYFDY (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence QSLLHGTGYNY (SEQ ID NO:X), a vLCDR2 having the sequence LGS (SEQ ID NO:X), and a vLCDR3 having the sequence MQALQTPLT (SEQ ID NO:X); and

iii) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.016, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFTFSSYG (SEQ ID NO:X), a vHCDR2 having the sequence ISYDGSNK (SEQ ID NO:X), and a vHCDR3 having the sequence

VRGINVNFHYYGMDV (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence NTNIGADYH (SEQ ID NO:X), a vLCDR2 having the sequence SNN (SEQ ID NO:X), and a vLCDR3 having the sequence QSFDSSLSAWV (SEQ ID NO:X); and

iv) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.017, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFTFSSYA (SEQ ID NO:X), a vHCDR2 having the sequence ISGSGGST (SEQ ID NO:X), and a vHCDR3 having the sequence

AKDSYFDWQIGSNDAFDI (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence SNNVGYQG (SEQ ID NO:X), a vLCDR2 having the sequence RNN (SEQ ID NO:X), and a vLCDR3 having the sequence

SAWDSSLTAWV (SEQ ID NO:X); and

v) a variable heavy chain sequence and a variable light chain sequence from

CP A.4.019, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFTFSSYA (SEQ ID NO:X), a vHCDR2 having the sequence

ISGSGGST (SEQ ID NO:X), an

AKAYGSGSYFHYWYFDL (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence QSLLQSNGYNY (SEQ ID NO:X), a vLCDR2 having the sequence LGS (SEQ ID NO:X), and a vLCDR3 having the sequence MQALQTPPT (SEQ ID NO:X); and

vi) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.020, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GGTFSSYA (SEQ ID NO:X), a vHCDR2 having the sequence IIPIFGTA (SEQ ID NO:X), and a vHCDR3 having the sequence

ATQYSSGWYIWGAFDI (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence QSLLHSSGDNF (SEQ ID NO:X), a vLCDR2 having the sequence LAS (SEQ ID NO:X), and a vLCDR3 having the sequence MQTLQTPLT (SEQ ID NO:X); and

vii) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.023, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GYSFTSYW (SEQ ID NO:X), a vHCDR2 having the sequence IYPGDSDT (SEQ ID NO:X), and a vHCDR3 having the sequence

ARLGIVDTSWSAFDI (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence SSNIGSNA (SEQ ID NO:X), a vLCDR2 having the sequence YDD (SEQ ID NO:X), and a vLCDR3 having the sequence AAWDDSLNGVV (SEQ ID NO:X); and

viii) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.005, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GDTFSSYT (SEQ ID NO:X), a vHCDR2 having the sequence FIPPLDIA (SEQ ID NO:X), and a vHCDR3 having the sequence

ATGGATIFFYYFGMDV (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence RSNIGSGS (SEQ ID NO:X), a vLCDR2 having the sequence TNS

(SEQ ID NO:X), and a vLCDR3

(SEQ ID NO:X); and

) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.009, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GYTFTSYA (SEQ ID NO:X), a vHCDR2 having the sequence INAGNGNT (SEQ ID NO:X), and a vHCDR3 having the sequence

ASS FHGS GS YYNKV VGMWY (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence QSLKHNNGYSY (SEQ ID NO:X), a vLCDR2 having the sequence LDS (SEQ ID NO:X), and a vLCDR3 having the sequence MQGLQIPVT (SEQ ID NO:X); and

a variable heavy chain sequence and a variable light chain sequence from

CPA.4.027, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFSISDYW (SEQ ID NO:X), a vHCDR2 having the sequence VSPGGGHLT (SEQ ID NO:X), and a vHCDR3 having the sequence VRGTHLWRGVDY (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence QSVSSY (SEQ ID NO:X), a vLCDR2 having the sequence DAS (SEQ ID NO:X), and a vLCDR3 having the sequence QQRSNWPVT (SEQ ID NO:X); and

) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.031, wherein

a) the variable heavy chain sequence comprises a vHCDRl having the sequence SGSIRSSNW (SEQ ID NO:X), a vHCDR2 having the sequence IYHSGST (SEQ ID NO:X), and a vHCDR3 having the sequence

AGRNIAGGSFDY (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence SGIDVGPYR (SEQ ID NO:X), a vLCDR2 having the sequence YNSDSDK (SEQ ID NO:X), and a vLCDR3 having the sequence

MIWHNKSRV (SEQ ID NO:X); and

') a variable heavy chain sequence and a variable light chain sequence from

CPA.4.033, wherein:

a) the variable heavy chain s

sequence GGSISTYY (SEQ ID NO:X), a vHCDR2 having the sequence IYFNDIT (SEQ ID NO:X), and a vHCDR3 having the sequence

VRGRGGSPALDY (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence QSLLHSNGYNY (SEQ ID NO:X), a vLCDR2 having the sequence LGS (SEQ ID NO:X), and a vLCDR3 having the sequence KQALQTIT (SEQ ID NO:X); and

xiii) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.012, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFSFSNYV (SEQ ID NO:X), a vHCDR2 having the sequence ISYDGSDK (SEQ ID NO:X), and a vHCDR3 having the sequence

ARSLRPAYYDASGV (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence RSNIGAGFD (SEQ ID NO:X), a vLCDR2 having the sequence GDT (SEQ ID NO:X), and a vLCDR3 having the sequence

QSYDSSLSVFYV (SEQ ID NO:X); and

xiv) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.008, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GGTFSSYS (SEQ ID NO:X), a vHCDR2 having the sequence IIPLFGTT (SEQ ID NO:X), and a vHCDR3 having the sequence

ARSKDYYGSGMEALLMDV (SEQ ID NO:X); and

b) the variable light chain sequence comprises a vLCDRl having the sequence SGSVSTRNY (SEQ ID NO:X), a vLCDR2 having the sequence NTN (SEQ ID NO:X), and a vLCDR3 having the sequence VFYMGSGRWV (SEQ ID NO:X); and

xv) a variable heavy chain sequence and a variable light chain sequence from

CPA.4.011, wherein:

a) the variable heavy chain sequence comprises a vHCDRl having the sequence GFTFSSYA (SEQ ID NO:X), a vHCDR2 having the sequence ISGSGGST (SEQ ID NO:X), and a vHCDR3 having the sequence

AKELRGGSYYFTGTDAFDI (SEQ ID NO:X); and

b) the variable light chain sei

sequence QSLLKSNGYNY (SEQ ID NO:X), a vLCDR2 having the sequence LGS (SEQ ID NO:X), and a vLCDR3 having the sequence MQALQTPPT (SEQ ID NO:X).

15. The anti-VSIGl antibody according to claim 14 wherein said variable heavy chain is CPA.4.028.VH.

16. The anti-VSIGl antibody according to claim 14 wherein said variable light chain is CPA.4.028.VL.

17. The anti-VSIGl antibody according to any of the preceding claims further comprising at least one covalently attached drug moiety.

18. A nucleic acid composition comprising:

a) a first nucleic acid encoding a variable heavy chain, said variable heavy chain comprising a vHCDRl , a vHCDR2, and a vHCDR3 according to any of the preceding claims; and

b) a second nucleic acid encoding a variable light chain, said variable light chain comprising a vLCDRl, a vLCDR2, and a vLCDR3 according to any of the preceding claims.

19. An expression vector composition comprising:

a) a first expression vector comprising the first nucleic acid of claim 18; and b) a second expression vector comprising the second nucleic acid of claim 18.

20. An expression vector comprising the first nucleic acid of claim 18 and the second nucleic acid of claim 18.

21. A host cell comprising a nucleic acid composition consisting of said nucleic acids of claim 18.

22. A host cell comprising an expression vector composition selected from the group consisting of the expression vector compositions of claims 19 and 20.

23. A method of making a composition comprising an anti-VSIGl antibody according to any of claims 1 to 17 comprising culturing a host cell according to either claim 21 or 22 under conditions whereby said antibody is expressed, and recovering said antibody.

24. A method of making a composition according to any of claims 1 to 17 comprising: a) culturing a host cell according to either claim 21 or 22 under conditions whereby said antibody is expressed;

b) recovering said antibody; and

c) contacting said antibody with an actn

wherein at least one drug is covalently attached to said antibody.

25. An isolated anti-VSIGl ADC antibody comprising:

a) a variable heavy chain comprising a vHCDRl having the sequence GFTFSSYG (SEQ ID NO:X), a vHCDR2 having the sequence IWYDGSNK (SEQ ID NO:X), and a vHCDR.3 having the sequence ARGGPWGIVVVNQFDY (SEQ ID NO:X); and b) a variable light chain comprising a vLCDRl having the sequence SDINVSSYN (SEQ ID NO:X), a vLCDR2 having the sequence YYSDSDK (SEQ ID NO:X), and a vLCDR3 having the sequence MIWPSTGRWV (SEQ ID NO:X).

wherein said antibody further comprises a chemotherapeutic drug covalently attached via an ADC linker.

26. The anti-VSIGl antibody according to claim 25 wherein said drug is selected from the group consisting of duocarmycin, maytansinoid, auristatin, dolastatin, and calicheamicin.

27. The anti-VSIGl antibody according to claim 26 wherein said duocarmycin is a duocarmycin analog.

28. The anti-VSIGl antibody according to claim 26 wherein said maytansinoid is a maytansinoid analog.

29. The anti-VSIGl antibody according to claim 26 wherein said auristatin is an auristatin analog.

30. The anti-VSIGl antibody according to claim 29 wherein said auristatin analog is selected from the group consisting of monomethyl auristatin (MMAE) and monomethyl auristatin phenylalanine (MMAF).

31. The anti-VSIGl antibody according to claim 26 wherein said dolastatin is a dolastatin analog.

32. The anti-VSIGl antibody according to claim 26 wherein said calicheamicin is a calicheamicin analog.

33. The anti-VSIGl antibody according to any of claims 25 to 32 wherein said ADC linker is susceptible to cleavage by an enzyme.

34. The anti-VSIGl antibody according to claim 33 wherein said enzyme is a protease.

35. The anti-VSIGl antibody according to any of claims 25 to 34 wherein said ADC linker is self-immolative.

36. The anti-VSIGl antibody according to any of claims 25 to 35 wherein said ADC linker is stable under physiological conditions.

37. The anti-VSIGl antibody according to any

heavy chain is CPA.4.028.VH and said variable light chain is CPA.4.028.VL.

38. A method of treating liver cancer comprising administering an anti-VSIGl ADC antibody according to any of claims 25 to 37 to a patient with liver cancer.

39. A method of treating stomach cancer comprising administering an anti-VSIGl ADC antibody according to any of claims 25 to 37 to a patient with stomach cancer.

40. A method of treating ovarian cancer comprising administering an anti-VSIGl ADC antibody according to any of claims 25 to 37 to a patient with ovarian cancer.

41. A method of treating pancreatic cancer comprising administering an anti-VSIGl ADC antibody according to any of claims 25 to 37 to a patient with pancreatic cancer.

42. A nucleic acid composition comprising:

a) a first nucleic acid encoding a variable heavy chain from CPA.4.028; and b) a second nucleic acid encoding a variable light chain from CPA.4.028.

43. An expression vector composition comprising:

a) a first expression vector comprising the first nucleic acid of claim 42; and b) a second expression vector comprising the second nucleic acid of claim 42.

44. An expression vector comprising the first nucleic acid of claim 42 and the second nucleic acid of claim 42.

45. A host cell comprising a nucleic acid composition consisting of said nucleic acids of claim 42.

46. A host cell comprising an expression vector composition selected from the group consisting of the expression vector compositions of claims 43 and 44.

47. A method of making a composition according to any of claims 25 to 37 comprising culturing a host cell according to either claim 45 or 46 under conditions whereby said antibody is expressed, and recovering said antibody.

48. A method of making a composition according to any of claims 25 to 37 comprising: a) culturing a host cell according to either claim 45 or 46 under conditions whereby said antibody is expressed;

b) recovering said antibody; and

c) contacting said antibody with an activated chemotherapeutic agent under conditions wherein at least one drug is covalently attached to said antibody.