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1. (WO2019064073) USE OF CA125 TO PREDICT ANTI-MESOTHELIN TREATMENT OF MESOTHELIOMAS
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What is claimed:

1. A method for predicting response of a subject having mesothelin-expressing mesothelioma to treatment with an anti-mesothelin therapeutic agent comprising determining a baseline level of steady state soluble cancer antigen 125 (sCA125) expression of the subject, wherein a baseline steady state CA125 level greater than 6.5 U/mL and less than about 80 U/mL or a baseline steady state CA125 level greater than the upper limit of normal (ULN) and less than about four times the ULN is predictive of response to the treatment.

2. The method according to claim 1 wherein the anti-mesothelin therapeutic agent comprises:

(a) an antibody comprising SEQ ID NO: 1 (GYSFTGYTMN) as CDRH1, SEQ ID NO:2 (LITP YNGAS S YNQ) as CDRH2, SEQ ID NO:3 (GGYDGRGFDY) as CDRH3, SEQ ID NO:4 (SASSSVSYMH) as CDRL1, SEQ ID NO:5 (DTSKLAS) as CDRL2 and SEQ ID NO: 6 (QQWSKHPLT) as CDRL3, numbered according to Kabat;

(b) an antibody comprising SEQ ID NO:7 (GYSFTGYT) as CDRH1, SEQ ID NO:8 (ITP YNGAS) as CDRH2, SEQ ID NO: 9 (GGYDGRGFDY) as CDRH3, SEQ ID NO: 10 (SSVSY) as CDRL1, SEQ ID NO: 11 (DTS) as CDRL2 and SEQ ID NO: 12 (QQWSKHPLT) as CDRL3, numbered according to EVIGT;

(c) an antibody produced by cells assigned ATCC Accession No. PTA-7553; or

(d) an antibody that binds the same epitope as amatuximab.

3. The method according to claim 2 wherein the antibody comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 13 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 14.

4. The method according to claim 2 wherein the anti-mesothelin therapeutic agent comprises amatuximab.

5. The method according to claim 1 wherein the treatment further comprises at least a folate antimetabolite and a platinum-based chemotherapy.

6. The method according to claim 5 wherein the folate antimetabolite comprises pemetrexed and the platinum-based chemotherapy comprises cisplatin.

7. A method of treating a subject having mesothelin-expressing mesothelioma, the method comprising administering to a subject having mesothelin-expressing mesothelioma and a baseline steady state soluble cancer antigen 125 (sCA125) level that is greater than 6.5 U/mL and less than about 80 U/mL or that is greater than the upper limit of normal (ULN) for sCA125 and less than about four times the ULN for sCA125 an anti-mesothelin therapeutic agent.

8. A method of treating a subject having mesothelin-expressing mesothelioma, the method comprising:

detecting a baseline steady state soluble cancer antigen 125 (sCA125) level in a biological sample obtained from the subject, and

administering an anti-mesothelin therapeutic agent to the subject when the subject's baseline sCA125 level is determined to be greater than 6.5 U/mL and less than about 80 U/mL or greater than the upper limit of normal (ULN) for sCA125 and less than about four times the ULN for sCA125.

9. The method according to claim 7 or 8 wherein the anti-mesothelin therapeutic agent comprises:

(e) an antibody comprising SEQ ID NO: l (GYSFTGYTMN) as CDRH1, SEQ ID NO:2 (LITPYNGASSYNQ) as CDRH2, SEQ ID NO:3 (GGYDGRGFDY) as CDRH3, SEQ ID NO:4 (SASSSVSYMH) as CDRL1, SEQ ID NO:5 (DTSKLAS) as CDRL2 and SEQ ID NO:6 (QQWSKHPLT) as CDRL3, numbered according to Kabat;

(f) an antibody comprising SEQ ID NO:7 (GYSFTGYT) as CDRH1, SEQ ID NO:8

(ITPYNGAS) as CDRH2, SEQ ID NO: 9 (GGYDGRGFDY) as CDRH3, SEQ ID NO: 10

(SSVSY) as CDRL1, SEQ ID NO: 11 (DTS) as CDRL2 and SEQ ID NO: 12 (QQWSKHPLT) as CDRL3, numbered according to IMGT;

(g) an antibody produced by cells assigned ATCC Accession No. PTA-7553; or

(h) an antibody that binds the same epitope as amatuximab.

10. The method according to claim 9 wherein the antibody comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 13 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 14.

11. The method according to claim 7, 8 or 9 wherein the anti-mesothelin therapeutic agent comprises amatuximab.

12. The method according to claim 7, 8, or 9, further comprising administering at least a folate antimetabolite and a platinum -based chemotherapy to the subject.

13. The method according to claim 12 wherein the folate antimetabolite comprises pemetrexed and the platinum-based chemotherapy comprises cisplatin.

14. The method according to any one of claims 9 to 13 wherein the anti-mesothelin antibody is an antibody that is bound by CA125.

15. The method according to any preceding claim wherein the mesothelin-expressing mesothelioma is malignant pleural mesothelioma.

16. The method according to any preceding claim wherein the sCA125 level is a sCA125 serum level.

17. The method according to any preceding claim wherein the ULN for sCA125 is 21 U/mL.

18. Use of a baseline steady state soluble cancer antigen 125 (sCA125) level greater than 6.5 U/mL and less than about 80 U/mL or greater than the upper limit of normal (ULN) for sCA125 and less than about four times the ULN for sCA125 in predicting response to treatment with an anti-mesothelin therapeutic agent by a subject having mesothelin-expressing mesothelioma.

19. The use according to claim 18 wherein the treatment further comprises at least a folate antimetabolite and a platinum-based chemotherapy.

20. The use according to claim 19 wherein the folate antimetabolite comprises pemetrexed and the platinum-based chemotherapy comprises cisplatin.

21. The use according to any one of claims 18 to 20 wherein the mesothelin-expressing mesothelioma is malignant pleural mesothelioma.

22. The use according to any one of claims 18 to 21 wherein the anti-mesothelin therapeutic agent comprises:

(a) an antibody comprising SEQ ID NO: 1 (GYSFTGYTMN) as CDRH1, SEQ ID NO:2 (LITPYNGASSYNQ) as CDRH2, SEQ ID NO:3 (GGYDGRGFDY) as CDRH3, SEQ ID NO:4 (SASSSVSYMH) as CDRL1, SEQ ID NO:5 (DTSKLAS) as CDRL2 and SEQ ID NO:6 (QQWSKHPLT) as CDRL3, numbered according to Kabat;

(b) an antibody comprising SEQ ID NO:7 (GYSFTGYT) as CDRH1, SEQ ID NO:8 (ITPYNGAS) as CDRH2, SEQ ID NO: 9 (GGYDGRGFDY) as CDRH3, SEQ ID NO: 10 (SSVSY) as CDRLl, SEQ ID NO: 11 (DTS) as CDRL2 and SEQ ID NO: 12 (QQWSKHPLT) as CDRL3, numbered according to EVIGT;

(c) an antibody produced by cells assigned ATCC Accession No. PTA-7553; or

(d) an antibody that binds the same epitope as amatuximab.

23. The use according to claim 22 wherein the antibody comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 13 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 14.

24. The use according to any one of claims 18 to 23 wherein the anti-mesothelin therapeutic agent comprises amatuximab.

25. The use according to any one of claims 22 to 24 wherein the anti-mesothelin therapeutic antibody is an antibody that is bound by CA125.

26. The use according to any one of claims 18 to 25 wherein the sCA125 level is a sCA125 serum level.

27. The use according to any one of claims 18 to 26 wherein the ULN for sCA125 is 21 U/mL.