Claims
- 1. A method for inhibiting metastasis of a cancer in a patient, comprising administering to a patient an antimetastatic agent that comprises an OB-cadherin CAR sequence, or an analogue thereof that is at least 50% identical to an OB-cadherin CAR sequence such that the ability to inhibit OB-cadherin mediated cell adhesion is not substantially diminished relative to an OB-cadherin CAR sequence.
- 2. A method according to claim 1, wherein the agent is a peptide consisting of 3-50 amino acid residues linked by peptide bonds.
- 3. A method according to claim 1, wherein the agent is a peptide consisting of 4-16 amino acid residues linked by peptide bonds.
- 4. A method according to claim 2, wherein the agent comprises one or more OB-cadherin CAR sequences selected from the group consisting DDK, IDDK (SEQ ID NO:37) DDKS (SEQ ID NO:38), VIDDK (SEQ ID NO:39), IDDKS (SEQ ID NO:40), VIDDKS (SEQ ID NO:41), DDKSG (SEQ ID NO:42), IDDKSG (SEQ ID NO:43), VIDDKSG (SEQ ID NO:44), FVIDDK (SEQ ID NO:45), FVIDDKS (SEQ ID NO:46), FVIDDKSG (SEQ ID NO:47), IFVIDDK (SEQ ID NO:48), IFVIDDKS (SEQ ID NO:49), IFVIDDKSG (SEQ ID NO:50), EEY, IEEY (SEQ ID NO:51), EEYT (SEQ ID NO:52), VIEEY (SEQ ID NO:53), IEEYT (SEQ ID NO:54), VIEEYT (SEQ ID NO:55), EEYTG (SEQ ID NO:56), IEEYTG (SEQ ID NO:56), VIEEYTG (SEQ ID NO:58), FVIEEY (SEQ ID NO:59), FVIEEYT (SEQ ID NO:60), FVIEEYTG (SEQ ID NO:61), FFVIEEY (SEQ ID NO:62), FFVIEEYT (SEQ ID NO:63), FFVIEEYTG (SEQ ID NO:64), EAQ, VEAQ (SEQ ID NO:65), EAQT (SEQ ID NO:66), SVEAQ (SEQ ID NO:67), VEAQT (SEQ ID NO:68), SVEAQT (SEQ ID NO:69), EAQTG (SEQ ID NO:70), VEAQTG (SEQ ID NO:71), SVEAQTG (SEQ ID NO:72), FSVEAQ (SEQ ID NO:73), FSVEAQT (SEQ ID NO:74), FSVEAQTG (SEQ ID NO:75), YFSVEAQ (SEQ ID NO:76), YFSVEAQT (SEQ ID NO:77) and YFSVEAQTG (SEQ ID NO:78).
- 5. A method according to claim 4, wherein the agent comprises a linear peptide having the sequence N-Ac-IFVIDDKSG-NH2 (SEQ ID NO:50), N-Ac-FFVIEEYTG-NH2 (SEQ ID NO:64) or N-Ac-YFSVEAQTG-NH2 (SEQ ID NO:78).
- 6. A method according to claim 1, wherein the CAR sequence is present within a cyclic peptide.
- 7. A method according to claim 6, wherein the cyclic peptide has the formula:
- 8. A method according to claim 7, wherein the agent has a sequence selected from the group consisting of CDDKC (SEQ ID NO:79), CIDDKC (SEQ ID NO:80), CDDKSC (SEQ ID NO:81), CVIDDKC (SEQ ID NO:82), CIDDKSC (SEQ ID NO:83), CVIDDKSC (SEQ ID NO:84), CDDKSGC (SEQ ID NO:85), CIDDKSGC (SEQ ID NO:86), CVIDDKSGC (SEQ ID NO:87), CFVIDDKC (SEQ ID NO:88), CFVIDDKSC (SEQ ID NO:89), CFVIDDKSGC (SEQ ID NO:90), CIFVIDDKC (SEQ ID NO:91), CIFVIDDKSC (SEQ ID NO:92), CIFVIDDKSGC (SEQ ID NO:93), DDDKK (SEQ ID NO:94), DIDDKK (SEQ ID NO:95), DVIDDKK (SEQ ID NO:96), DFVIDDKK (SEQ ID NO:97), DIFVIDDKK (SEQ ID NO:98), EDDKK (SEQ ID NO:99), EIDDKK (SEQ ID NO:100), EVIDDKK (SEQ ID NO:101), EFVIDDKK (SEQ ID NO:102), EIFVIDDKK (SEQ ID NO:103), FVIDDK (SEQ ID NO:104), FVIDDKS (SEQ ID NO:105), FVIDDKSG (SEQ ID NO:106), KDDKD (SEQ ID NO:107), KIDDKD (SEQ ID NO:108), KDDKSD (SEQ ID NO:109), KVIDDKD (SEQ ID NO:110), KIDDKSD (SEQ ID NO:111), KVIDDKSD (SEQ ID NO:112), KDDKSGD (SEQ ID NO:113), KIDDKSGD (SEQ ID NO:114), KVIDDKSGD (SEQ ID NO:115), KFVIDDKD (SEQ ID NO:116), KFVIDDKSD (SEQ ID NO:117), KFVIDDKSGD (SEQ ID NO:118), KIFVIDDKD (SEQ ID NO:119), KIFVIDDKSD (SEQ ID NO:120), KIFVIDDKSGD (SEQ ID NO:121), VIDDK (SEQ ID NO: 122), IDDKS (SEQ ID NO:123), VIDDKS (SEQ ID NO:124), VIDDKSG (SEQ ID NO:125), DDKSG (SEQ ID NO:126), IDDKSG (SEQ ID NO:127), IFVIDDK (SEQ ID NO:128), IFVIDDKS (SEQ ID NO:129), IFVIDDKSG (SEQ ID NO:130), KDDKE (SEQ ID NO:131), KIDDKE (SEQ ID NO:132), KDDKSE (SEQ ID NO:133), KVIDDKE (SEQ ID NO:134), KIDDKSE (SEQ ID NO:135), KVIDDKSE (SEQ ID NO:136), KDDKSGE (SEQ ID NO:137), KIDDKSGE (SEQ ID NO:138), KVIDDKSGE (SEQ ID NO:139), KFVIDDKE (SEQ ID NO:140), KFVIDDKSE (SEQ ID NO:141), KFVIDDKSGE (SEQ ID NO:142), KIFVIDDKE (SEQ ID NO:143), KIFVIDDKSE (SEQ ID NO:144), KIFVIDDKSGE (SEQ ID NO:145), CEEYC (SEQ ID NO:146), CIEEYC (SEQ ID NO:147), CEEYTC (SEQ ID NO:148), CVIEEYC (SEQ ID NO: 149), CIEEYTC (SEQ ID NO:150), CVIEEYTC (SEQ ID NO:151), CEEYTGC (SEQ ID NO:152), CIEEYTGC (SEQ ID NO: 153), CVIEEYTGC (SEQ ID NO:154), CFVIEEYC (SEQ ID NO:155), CFVIEEYTC (SEQ ID NO:156), CFVIEEYTGC (SEQ ID NO:157), CFFVIEEYC (SEQ ID NO:158), CFFVIEEYTC (SEQ ID NO:159), CFFVIEEYTGC (SEQ ID NO:160), KEEYD (SEQ ID NO:161), KIEEYD (SEQ ID NO:162), KEEYTD (SEQ ID NO:163), KVIEEYD (SEQ ID NO:164), KIEEYTD (SEQ ID NO:165), KVIEEYTD (SEQ ID NO:166), KEEYTGCD (SEQ ID NO:167), KIEEYTGD (SEQ ID NO:168), KVIEEYTGD (SEQ ID NO:169), KFVIEEYD (SEQ ID NO:170), KFVIEEYTD (SEQ ID NO:171), KFVIEEYTGD (SEQ ID NO:172), KFFVIEEYD (SEQ ID NO:173), KFFVIEEYTD (SEQ ID NO:174), KFFVIEEYTGD (SEQ ID NO:175), EEEYK (SEQ ID NO:176), EIEEYK (SEQ ID NO:177), EEEYTK (SEQ ID NO:178), EVIEEYK (SEQ ID NO:179), EIEEYTK (SEQ ID NO:180), EVIEEYTK (SEQ ID NO:181), EEEYTGK (SEQ ID NO:182), EIEEYTGK (SEQ ID NO:183), EVIEEYTGK (SEQ ID NO:184), EFVIEEYK (SEQ ID NO:185), EFVIEEYTK (SEQ ID NO:186), EFVIEEYTGK (SEQ ID NO:187), EFFVIEEYK (SEQ ID NO:188), EFFVIEEYTK (SEQ ID NO:189), EFFVIEEYTGK (SEQ ID NO:190), DCEEYK (SEQ ID NO:191), DIEEYCK (SEQ ID NO:192), DEEYTK (SEQ ID NO:193), DVIEEYK (SEQ ID NO:194), DIEEYTK (SEQ ID NO:195), DVIEEYTK (SEQ ID NO:196), DEEYTGK (SEQ ID NO:197), DIEEYTGK (SEQ ID NO:198), DVIEEYTGK (SEQ ID NO:199), DFVIEEYK (SEQ ID NO:200), DFVIEEYTK (SEQ ID NO:201), DFVIEEYTGK (SEQ ID NO:202), DFFVIEEYK (SEQ ID NO:203), DFFVIEEYTK (SEQ ID NO:204), DFFVIEEYTGK (SEQ ID NO:205), KEEYE (SEQ ID NO:206), KIEEYE (SEQ ID NO:207), KEEYTE (SEQ ID NO:208), KVIEEYE (SEQ ID NO:209), KIEEYTE (SEQ ID NO:210), KVIEEYTE (SEQ ID NO:211), KEEYTGE (SEQ ID NO:212), KIEEYTGE (SEQ ID NO:213), KVIEEYTGE (SEQ ID NO:214), KFVIEEYE (SEQ ID NO:215), KFVIEEYTE (SEQ ID NO:216), KFVIEEYTGE (SEQ ID NO:217), KFFVIEEYE (SEQ ID NO:218), KFFVIEEYTE (SEQ ID NO:219), KFFVIEEYTGE (SEQ ID NO:220), VIEEY (SEQ ID NO:221), IEEYT (SEQ ID NO:222), VIEEYT (SEQ ID NO:223), EEYTG (SEQ ID NO:224), IEEYTG (SEQ ID NO:225), VIEEYTG (SEQ ID NO:226), FVIEEY (SEQ ID NO:227), FVIEEYT (SEQ ID NO:228), FVIEEYTG (SEQ ID NO:229), FFVIEEY (SEQ ID NO:230), FFVEEYT (SEQ ID NO:231), FFVIEEYTG (SEQ ID NO:232), CEAC (SEQ ID NO:233), CVEAC (SEQ ID NO:234), CEAQTC (SEQ ID NO:235), CSVEAQC (SEQ ID NO:236), CVEAQTC (SEQ ID NO:237), CSVEAQTC (SEQ ID NO:238), CEAQTGC (SEQ ID NO:239), CVEAQTGC (SEQ ID NO:240), CSVEAOTGC (SEQ ID NO:241), CFSVEAQC (SEQ ID NO:242), CFSVEAQTC (SEQ ID NO:243), CFSVEAQTGC (SEQ ID NO:244), CYFSVEAQC (SEQ ID NO:245), CYFSVEAQTC (SEQ ID NO:246), CYFSVEAQTGC (SEQ ID NO:247), KEAQD (SEQ ID NO:248), KVEAQD (SEQ ID NO:249), KEAOTD (SEQ ID NO:250), KSVEAQD (SEQ ID NO:251), KVEAQTD (SEQ ID NO:252), KSVEAQTD (SEQ ID NO:253), KEAQTGD (SEQ ID NO:254), KVEAQTGD (SEQ ID NO:255), KSVEAQTGD (SEQ ID NO:256), KFSVEAQD (SEQ ID NO:257), KFSVEAQTD (SEQ ID NO:258), KFSVEAQTGD (SEQ ID NO:259), KYFSVEAQD (SEQ ID NO:260), KYFSVEAQTD (SEQ ID NO:261), KYFSVEAQTGD (SEQ ID NO:262), EEAQK (SEQ ID NO:263), EVEAQK (SEQ ID NO:264), EEAQTK (SEQ ID NO:265), ESVEAQK (SEQ ID NO:266), EVEAQTK (SEQ ID NO:267), ESVEAQTK (SEQ ID NO:268), EEAQTGK (SEQ ID NO:269), EVEAQTGK (SEQ ID NO:270), ESVEAQTGK (SEQ ID NO:271), EFSVEAQK (SEQ ID NO:272), EFSVEAQTK (SEQ ID NO:273), EFSVEAQTGK (SEQ ID NO:274), EYFSVEAQK (SEQ ID NO:275), EYFSVEAQTK (SEQ ID NO:276), EYFSVEAQTGK (SEQ ID NO:277), DEAQK (SEQ ID NO:278), DVEAQK (SEQ ID NO:279), DEAQTK (SEQ ID NO:280), DSVEAQK (SEQ ID NO:281), DVEAQTK (SEQ ID NO:282), DSVEAQTK (SEQ ID NO:283), DEAQTGK (SEQ ID NO:284), DVEAQTGK (SEQ ID NO:285), DSVEAQTGK (SEQ ID NO:286), DFSVEAQK (SEQ ID NO:287), DFSVEAQTK (SEQ ID NO:288), DFSVEAQTGK (SEQ ID NO:289), DYFSVEAQK (SEQ ID NO:290), DYFSVEAQTK (SEQ ID NO:291), DYFSVEAQTGK (SEQ ID NO:292), KEAQE (SEQ ID NO:293), KVEAQE (SEQ ID NO:294), KEAQTE (SEQ ID NO:295), KSVEAQE (SEQ ID NO:296), KVEAQTE (SEQ ID NO:297), KSVEAQTE (SEQ ID NO:298), KEAQTGE (SEQ ID NO:299), KVEAQOTGE (SEQ ID NO:300), KSVEAQTGE (SEQ ID NO:301), KFSVEAQE (SEQ ID NO:302), KFSVEAQTE (SEQ ID NO:303), KFSVEAQTGE (SEQ ID NO:304), KYFSVEAQE (SEQ ID NO:305), KYFSVEAQTE (SEQ ID NO:306), KYFSVEAQTGE (SEQ ID NO:307), SVEAQ (SEQ ID NO:308), VEAQT (SEQ ID NO:309), SVEAQT (SEQ ID NO:310), EAQTG (SEQ ID NO:311), VEAQTG (SEQ ID NO:312), SVEAQTG (SEQ ID NO:313), FSVEAQ (SEQ ID NO:314), FSVEAQT (SEQ ID NO:315), FSVEAQTG (SEQ ID NO:316), YFSVEAQ (SEQ ID NO:317), YFSVEAQT (SEQ ID NO:318) and YFSVEAQTG (SEQ ID NO:319).
- 9. A method according to claim 1, wherein the agent is linked to a drug.
- 10. A method according to claim 1, wherein the agent is linked to a targeting moiety.
- 11. A method according to claim 1, wherein the agent is linked to:
(a) a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin.
- 12. A method according to claim 10, wherein the adhesion molecule is selected from the group consisting of cadherins, integrins, occludin, claudins and members of the immunoglobulin superfamily.
- 13. A method according to claim 1, wherein the agent is present within a pharmaceutical composition comprising a physiologically acceptable carrier.
- 14. A method according to claim 12, wherein the composition further comprises a drug.
- 15. A method according to claim 12, wherein the composition further comprises a modulator of cell adhesion comprising:
(a) a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin.
- 16. A method according to claim 14, wherein the adhesion molecule is selected from the group consisting of cadherins, integrins, occludin, claudins and members of the immunoglobulin superfamily.
- 17. A method for inhibiting metastasis of a cancer in a patient, comprising administering to a patient a polynucleotide encoding an antimetastatic agent that comprises an OB-cadherin CAR sequence, or an analogue thereof that is at least 50% identical to an OB-cadherin CAR sequence such that the ability to inhibit OB-cadherin mediated cell adhesion is not substantially diminished relative to an OB-cadherin CAR sequence.
- 18. A method according to claim 16, wherein the agent is a peptide consisting of 3-50 amino acid residues linked by peptide bonds.
- 19. A method for inhibiting metastasis of a cancer in a patient, comprising administering to a patient an antimetastatic agent comprising an antibody or antigen-binding fragment thereof that specifically binds to an OB-cadherin CAR sequence.
- 20. A method according to claim 18, wherein the OB-cadherin CAR sequence is selected from the group consisting of IFVIDDKSG (SEQ ID NO:50), FFVIEEYTG (SEQ ID NO:64) and YFSVEAQTG (SEQ ID NO:78).
- 21. A method according to claim 18, wherein the agent is linked to a drug.
- 22. A method according to claim 18, wherein the agent is linked to a targeting moiety.
- 23. A method according to claim 18, wherein the agent is linked to:
(a) a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin.
- 24. A method according to claim 22, wherein the adhesion molecule is selected from the group consisting of cadherins, integrins, occludin, claudins and members of the immunoglobulin superfamily.
- 25. A method according to claim 18, wherein the agent is present within a pharmaceutical composition comprising a physiologically acceptable carrier.
- 26. A method according to claim 24, wherein the composition further comprises a drug.
- 27. A method according to claim 24, wherein the composition further comprises a modulator of cell adhesion comprising:
(a) a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin.
- 28. A method according to claim 26, wherein the adhesion molecule is selected from the group consisting of cadherins, integrins, occludin, claudins and members of the immunoglobulin superfamily.
- 29. A method for removing metastatic cells from a biological sample, comprising the steps of:
(a) contacting a biological sample with an antimetastatic agent that comprises:
(i) an OB-cadherin CAR sequence or an analogue thereof that is at least 50% identical to an OB-cadherin CAR sequence such that the ability to inhibit OB-cadherin mediated cell adhesion is not substantially diminished relative to an OB-cadherin CAR sequence; or (ii) an antibody or antigen-binding fragment thereof that specifically binds to an OB-cadherin CAR sequence; wherein the contact takes place under conditions and for a time sufficient to allow OB-cadherin-expressing cells within the biological sample to bind to the antimetastatic agent; and (b) separating OB-cadherin expressing cells bound to the antimetastatic agent from the biological sample.
- 30. A method according to claim 28, wherein the antimetastatic agent is linked to a support material.
- 31. A method according to claim 28, wherein the biological sample is further contacted with a modulator of cell adhesion comprising:
(a) a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin.
- 32. A method according to claim 30, wherein the adhesion molecule is selected from the group consisting of cadherins, integrins, occludin, claudins and members of the immunoglobulin superfamily.
- 33. A method according to claim 28, wherein the biological sample is blood or bone marrow obtained from a patient.
- 34. A method for removing metastatic cells from a patient, comprising the steps of:
(a) obtaining a biological sample from a patient; (b) contacting the biological sample with an antimetastatic agent that comprises:
(i) an OB-cadherin CAR sequence or an analogue thereof that is at least 50% identical to an OB-cadherin CAR sequence such that the ability to inhibit OB-cadherin mediated cell adhesion is not substantially diminished relative to an OB-cadherin CAR sequence; or (ii) an antibody or antigen-binding fragment thereof that specifically binds to an OB-cadherin CAR sequence; wherein the contact takes place under conditions and for a time sufficient to allow OB-cadherin-expressing cells within the biological sample to bind to the antimetastatic agent; and (c) separating OB-cadherin expressing cells bound to the antimetastatic agent from the remainder of the biological sample; and (d) returning the remainder of the biological sample to the patient.
- 35. A method according to claim 33, wherein the antimetastatic agent is linked to a support material.
- 36. A method according to claim 33, wherein the biological sample is further contacted with a modulator of cell adhesion comprising:
(a) a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin; and/or (b) an antibody or antigen-binding fragment thereof that specifically binds to a CAR sequence that is specifically recognized by an adhesion molecule other than OB-cadherin.
- 37. A method according to claim 35, wherein the adhesion molecule is selected from the group consisting of cadherins, integrins, occludin, claudins and members of the immunoglobulin superfamily.
- 38. A method according to claim 33, wherein the biological sample is blood or bone marrow.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 09/234,395, filed Jan. 20, 1999; which is a continuation-in-part of U.S. Ser. No. 09/187,859, filed Nov. 6, 1998; which is a continuation-in-part of U.S. Ser. No. 09/073,040, filed May 5, 1998.
Continuation in Parts (3)
|
Number |
Date |
Country |
Parent |
09234395 |
Jan 1999 |
US |
Child |
09264516 |
Mar 1999 |
US |
Parent |
09187859 |
Nov 1998 |
US |
Child |
09234395 |
Jan 1999 |
US |
Parent |
09073040 |
May 1998 |
US |
Child |
09187859 |
Nov 1998 |
US |