KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-049/00
A61B-008/00
출원번호
US-0480578
(2009-06-08)
등록번호
US-8642010
(2014-02-04)
발명자
/ 주소
Sato, Aaron K.
Sexton, Daniel J.
Dransfield, Daniel T.
Ladner, Robert C.
Arbogast, Christophe
Bussat, Philippe
Fan, Hong
Khurana, Sudha
Linder, Karen E.
Marinelli, Edmund R.
Nanjappan, Palaniappa
Nunn, Adrian D.
Pillai, Radhakrishna K.
Pochon, Sibylle
Yan, Feng
Ramalingam, Kondareddiar
Shrivastava, Ajay
Song, Bo
Swenson, Rolf E.
Von Wronski, Mathew A.
출원인 / 주소
Dyax Corp.
대리인 / 주소
Pearl Cohen Zedek Latzer Baratz LLP
인용정보
피인용 횟수 :
7인용 특허 :
161
초록▼
The present invention provides polypeptides, peptide dimer, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthet
The present invention provides polypeptides, peptide dimer, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD1 μM), and dimer and multimeric constructs comprising these polypeptides.
대표청구항▼
1. An ultrasound contrast agent comprising a microvesicle conjugated to at least one polypeptide having the ability to bind to KDR or VEGF/KDR complex, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of AGDSWCSTEYTYCEMIGTGGGK;(SEQ ID NO: 263)AGPKWCEEDWYYCM
1. An ultrasound contrast agent comprising a microvesicle conjugated to at least one polypeptide having the ability to bind to KDR or VEGF/KDR complex, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of AGDSWCSTEYTYCEMIGTGGGK;(SEQ ID NO: 263)AGPKWCEEDWYYCMITGTGGGK;(SEQ ID NO: 264)AGVWECAKTFPFCHWFGTGGGK;(SEQ ID NO: 265)AGWVECWWKSGQCYEFGTGGGK;(SEQ ID NO: 266)AGWIQCNSITGHCTSGGTGGGK;(SEQ ID NO: 268)AGWIECYHPDGICYHFGTGGGK;(SEQ ID NO: 269)AGSDWCRVDWYYCWLMGTGGGK;(SEQ ID NO: 270)AGANWCEEDWYYCFITGTGGGK;(SEQ ID NO: 271)AGANWCEEDWYYCWITGTGGGK;(SEQ ID NO: 272)AGPDWCEEDWYYCWITGTGGGK;(SEQ ID NO: 273)AGSNWCEEDWYYCYITGTGGGK;(SEQ ID NO: 274)AGPDWCAADWYYCYITGTGGGK;(SEQ ID NO: 275)AGPEWCEVDWYYCWLLGTGGGK;(SEQ ID NO: 276)AGPTWCEDDWYYCWLFGTGGGK;(SEQ ID NO: 277)AGSKWCEQDWYYCWLLGTGGGK;(SEQ ID NO: 278)AGRNWCEEDWYYCFITGTGGGK;(SEQ ID NO: 279)AGVNWCEEDWYYCWITGTGGGK;(SEQ ID NO: 280)AGANWCEEDWYYCYITGTGGGK;(SEQ ID NO: 281)AGQAWVECYAETGYCWPRSWGTGGGK;(SEQ ID NO: 282)AGQAWIECYAEDGYCWPRSWGTGGGK;(SEQ ID NO: 283)AGVGWVECYQSTGFCYHSRDGTGGGK;(SEQ ID NO: 284)AGFTWVECHQATGRVCVEWTTGTGGGK;(SEQ ID NO: 285)AGDWWVECRVGTGLCYRYDTGTGGGK;(SEQ ID NO: 286)AGDSWVECDAQTGFCYSFLYGTGGGK;(SEQ ID NO: 287)AGERWVECRAETGFCYTWVSGTGGGK;(SEQ ID NO: 289)AGGGWVECRAETGHCQEYRLGTGGGK;(SEQ ID NO: 290)AGVAWVECYQTTGKCYTFRGGTGGGK;(SEQ ID NO: 291)AGEGWVECFANTGACFTYPRGTGGGK;(SEQ ID NO: 292)GDYPWCHELSDSVTRFCVPWDPGGGK;(SEQ ID NO: 293)GDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 294)GDDHMCRSPDYQDHVCMYWDPGGGK;(SEQ ID NO: 295)GDPPLCYFVGTQEWHHCNPFDPGGGK;(SEQ ID NO: 296)GDDSYCMMNEKGWWNCYLYDPGGGK;(SEQ ID NO: 297)GDPAQCWESNYQGIFFCDNPDPGGGK;(SEQ ID NO: 298)GDGSWCEMRQDVGKWNCFSDDPGGGK;(SEQ ID NO: 299)GDGWACAKWPWGGEICQPSDPGGGK;(SEQ ID NO: 300)GDPDTCTMWGDSGRWYCFPADPGGGK;(SEQ ID NO: 301)GDNWKCEYTQGYDYTECVYLDPGGGK;(SEQ ID NO: 302)GDNWECGWSNMFQKEFCARPDPGGGK;(SEQ ID NO: 303)GDWWECKREEYRNTTWCAWADPGGGK;(SEQ ID NO: 486)GDSSVCFEYSWGGEVCFRYDPGGGK;(SEQ ID NO: 487)GDSRVCWEYSWGGQICLGYDPGGGK;(SEQ ID NO: 488)AQQVQYQFFLGTPRYEQWDLDKGGK;(SEQ ID NO: 304)AQEPEGYAYWEVITLYHEEDGDGGK;(SEQ ID NO: 305)AQAFPRFGGDDYWIQQYLRYTDGGK;(SEQ ID NO: 306)AQGDYVYWEIIELTGATDHTPPGGK;(SEQ ID NO: 307)AQRGDYQEQYWHQQLVEQLKLLGGK;(SEQ ID NO: 308)AQRSWYLGPPYYEEWDPIPNGGK;(SEQ ID NO: 309)AQDWYYDEILSMADQLRHAFLSGGGK;(SEQ ID NO: 310)AGIDFCKGMAPWLCADMGTGGGK;(SEQ ID NO: 311)AGPWTCWLEDHLACAMLGTGGGK;(SEQ ID NO: 312)AGDWGCSLGNWYWCSTEGTGGGK;(SEQ ID NO: 313)GSDHHCYLHNGQWICYPFAPGGGK;(SEQ ID NO: 314)GSNSHCYIWDGMWLCFPDAPGGGK;(SEQ ID NO: 315)SGRLDCDKVFSGPYGKVCVSYGSGGGK;(SEQ ID NO: 316)SGRLDCDKVFSGPHGKICVNYGSGGGK;(SEQ ID NO: 317)SGRTTCHHQISGPHGKICVNYGSGGGK;(SEQ ID NO: 318)SGAHQCHHWTSGPYGEVCFNYGSGGGK;(SEQ ID NO: 319)AGMPWCVEKDHWDCWWWGTGGGK;(SEQ ID NO: 320)AGPGPCKGYMPHQCWYMGTGGGK;(SEQ ID NO: 321)AGYGPCAEMSPWLCWYPGTGGGK;(SEQ ID NO: 322)AGYGPCKNMPPWMCWHEGTGGGK;(SEQ ID NO: 323)AGGHPCKGMLPHTCWYEGTGGGK;(SEQ ID NO: 324)AQAPAWTFGTNWRSIQRVDSLTGGGGGK;(SEQ ID NO: 325)AQEGWFRNPQEIMGFGDSWDKPGGGGGK;(SEQ ID NO: 326)AQEGWFRNPQEIMGFGDSWDKPGGGK;(SEQ ID NO: 330)AQRGDYQEQYWHQQLVEQLKLLGGGK;(SEQ ID NO: 331)AGWYWCDYYGIGCKWTGGGK;(SEQ ID NO: 332)AGWYWCDYYGIGCKWTGTGGGK;(SEQ ID NO: 333)AQWYYDWFHNQRKPPSDWIDNLGGGK;(SEQ ID NO: 334)WQPCPWESWTFCWDPGGGK;(SEQ ID NO: 336)VCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 337)AGPTWCEDDWYYCWLFGTJK;(SEQ ID NO: 338)AQAHMPPWRPVAVDALFDWVEGGGGGK;(SEQ ID NO: 340)AQAHMPPWWPLAVDAQEDWFEGGGGGK;(SEQ ID NO: 341)AQAQMPPWWPLAVDALFDWFEGGGGGK;(SEQ ID NO: 342)AQDWYWREWMPMHAQFLADDWGGGGGK;(SEQ ID NO: 343)AQKKEDAQQWYWTDYVPSYLYRGGGGGK;(SEQ ID NO: 344)AQPVTDWTPHHPKAPDVWLFYTGGGGGK;(SEQ ID NO: 345)AQDALEAPKRDWYYDWFLNHSPGGGGGK;(SEQ ID NO: 346)KWCEEDWYYCMITGTGGGK;(SEQ ID NO: 347)AGPKWCEEDWYYCMIGGGK;(SEQ ID NO: 348)KWCEEDWYYCMIGGGK;(SEQ ID NO: 349)AQPDNWKEFYESGWKYPSLYKPLGGGGGK;(SEQ ID NO: 350)AQMPPGFSYWEQVVLHDDAQVLGGGGGK;(SEQ ID NO: 351)AQARMGDDWEEAPPHEWGWADGGGGGK;(SEQ ID NO: 352)AQPEDSEAWYWLNYRPTMFHQLGGGGGK;(SEQ ID NO: 353)AQSTNGDSFVYWEEVELVDHPGGGGGK;(SEQ ID NO: 354)AQWESDYWDQMRQQLKTAYMKVGGGGGK;(SEQ ID NO: 355)AQDWYYDEILSMADQLRHAFLSGGGGGK;(SEQ ID NO: 356)VCWEDSWGGEVCFGGGK;(SEQ ID NO: 368)GDSRVCWEDSWGGEVCFGGGK;(SEQ ID NO: 369)SRVCWEDSWGGEVCFRYGGGGK;(SEQ ID NO: 371)GDSRVCWEDSWGGEVCFRYGGGK;(SEQ ID NO: 372)GDSRVCWEDSWGGEVCFRYDP;(SEQ ID NO: 374)ERVTTCWPGEYGGVECYSVAY;(SEQ ID NO: 504)DWYYGGGK;(SEQ ID NO: 462)AEDWYYDEILGRGRGGRGG;(SEQ ID NO: 465)AGPTWEEDDWYYKWLFGTGGGK;(SEQ ID NO: 453)AGPTWKEDDWYYEWLFGTGGGK;(SEQ ID NO: 454)AGPTWDprEDDWYYDWLFGTGGGK;(SEQ ID NO: 455)AGPTWDEDDWYYDprWLFGTGGGK;(SEQ ID NO: 456)AGPTWDEDDWYYKWLFGTGGGK;(SEQ ID NO: 457)andAGPTWCEDDWYYCWLFGTGGGGK.(SEQ ID NO: 480). wherein J is the spacer or linker group 8-amino- 3,6-dioxaoctanoyl. 2. The agent of claim 1, wherein the microvesicle is conjugated to a dimeric or multimeric compound comprising two or more polypeptides having the ability to bind KDR or VEGF/KDR complex. 3. The agent of claim 1, wherein the agent comprises two or more polypeptides and wherein the polypeptides have specificity for different epitopes on KDR. 4. The agent of claim 3, wherein the polypeptides comprise amino acid sequences that are independently selected from the group consisting of: AGPKWCEEDWYYCMITGTGGGK;(SEQ ID NO: 264)GDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 294)AQDWYYDEILSMADQLRHAFLSGGGK;(SEQ ID NO: 310)AGPTWCEDDWYYCWLFGTGGGK;(SEQ ID NO: 277)AGDWWVECRVGTGLCYRYDTGTGGGK;(SEQ ID NO: 286)andVCWEDSWGGEVCFRYDPGGGK.(SEQ ID NO: 337) 5. The agent of claim 1, wherein at least one of the polypeptides comprises an amino acid substitution, an amide bond substitution, a D-amino acid substitution, a glycosylated amino acid, a disulfide mimetic substitution, an amino acid translocation, a retro-inverso peptide, a peptoid, a retro-inverso peptoid, or a synthetic peptide and wherein the polypeptide maintains its ability to bind the receptor. 6. The agent of claim 1, wherein at least one of the polypeptides does not include the C terminal GGGK extension in its amino acid sequence. 7. The agent of claim 4, wherein the polypeptides comprise any of the following combinations of amino acid sequences: AGPTWCEDDWYYCWLFGTGGGK(SEQ ID NO: 277)andVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 337)AGPTWCEDDWYYCWLFGTGGGK(SEQ ID NO: 277)andGDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 294)AGPKWCEEDWYYCMITGTGGGK(SEQ ID NO: 264)andGDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 294)orAQDWYYDEILSMADQLRHAFLSGGGK(SEQ ID NO: 310)andVCWEDSWGGEVCFRYDPGGGK.(SEQ ID NO: 337) 8. The agent of claim 1, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: AGPKWCEEDWYYCMITGTGGGK;(SEQ ID NO: 264)AGPTWCEDDWYYCWLFGTGGGK;(SEQ ID NO: 277)GDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 294)AQDWYYDEILSMADQLRHAFLSGGGK;(SEQ ID NO: 310)andVCWEDSWGGEVCFRYDPGGGK.(SEQ ID NO: 337) 9. An ultrasound contrast agent comprising a microvesicle conjugated to at least two polypeptides having the ability to bind to KDR or VEGF/KDR complex, wherein the microvesicle is conjugated to a dimer selected from the group consisting of D1, D2, D3, D5, D6, D7, D8, D9, D17, D19, D20, D22, D23, D24, D25, D26, D27, D28, and D31, wherein J is the spacer or linker group 8-amino- 3,6-dioxaoctanoyl. 10. The agent of claim 9, wherein the dimer is selected from the group consisting of D5and D6. 11. The agent of claim 10, wherein the dimer is D5. 12. The agent of claim 1, wherein the polypeptide is linked to the microvesicle via a linker or spacer. 13. The agent of claim 12, wherein said linker or spacer is selected from the group consisting of a substituted alkyl chain, an unsubstituted alkyl chain, a polyethylene glycol derivative, an amino acid spacer, a sugar, an aliphatic spacer, an aromatic spacer, a lipid molecule, and combinations thereof. 14. The agent of claim 1, wherein the microvesicle comprises a microvesicle-forming material selected from the group consisting of surfactants, lipids, sphingolipids, oligolipids, phospholipids, proteins, polypeptides, carbohydrates and synthetic or natural polymeric materials. 15. The agent of claim 1, wherein the microvesicle is selected from the group consisting of a microbubble, a microballoon, a microparticle and a microsphere. 16. The agent of claim 15, wherein the microbubble comprises a phospholipid. 17. The agent of claim 1, wherein the microvesicle comprises a biocompatible gas, a mixture of biocompatible gases or a gas precursor. 18. The agent of claim 17, wherein the gas or gas mixture comprises a fluorinated gas. 19. The agent of claim 17, wherein the gas or gas mixture comprises at least one gas selected from the group consisting of air; nitrogen; oxygen; carbon dioxide; argon, xenon; krypton; a low molecular weight alkane, cycloalkane, alkene or alkyne; a hyperpolarized gas, SF6, a freon and a perfluorocarbon. 20. The agent of claim 17, wherein the gas or gas mixture comprises a gas selected from the group consisting of SF6, C3F8, C4F8, C4F10, and C5F12. 21. The agent of claim 1, further comprising a therapeutic agent. 22. A lyophilized residue for preparing an ultrasound contrast agent wherein said residue comprises a phospholipid and at least one polypeptide comprising an amino acid sequence selected from the group consisting of (SEQ ID NO: 263)AGDSWCSTEYTYCEMIGTGGGK;(SEQ ID NO: 264)AGPKWCEEDWYYCMITGTGGGK;(SEQ ID NO: 265)AGVWECAKTFPFCHWFGTGGGK;(SEQ ID NO: 266)AGWVECWWKSGQCYEFGTGGGK;(SEQ ID NO: 268)AGWIQCNSITGHCTSGGTGGGK;(SEQ ID NO: 269)AGWIECYHPDGICYHFGTGGGK;(SEQ ID NO: 270)AGSDWCRVDWYYCWLMGTGGGK;(SEQ ID NO: 271)AGANWCEEDWYYCFITGTGGGK;(SEQ ID NO: 272)AGANWCEEDWYYCWITGTGGGK;(SEQ ID NO: 273)AGPDWCEEDWYYCWITGTGGGK;(SEQ ID NO: 274)AGSNWCEEDWYYCYITGTGGGK;(SEQ ID NO: 275)AGPDWCAADWYYCYITGTGGGK;(SEQ ID NO: 276)AGPEWCEVDWYYCWLLGTGGGK;(SEQ ID NO: 277)AGPTWCEDDWYYCWLFGTGGGK;(SEQ ID NO: 278)AGSKWCEQDWYYCWLLGTGGGK;(SEQ ID NO: 279)AGRNWCEEDWYYCFITGTGGGK;(SEQ ID NO: 280)AGVNWCEEDWYYCWITGTGGGK;(SEQ ID NO: 281)AGANWCEEDWYYCYITGTGGGK;(SEQ ID NO: 282)AGQAWVECYAETGYCWPRSWGTGGGK;(SEQ ID NO: 283)AGQAWIECYAEDGYCWPRSWGTGGGK;(SEQ ID NO: 284)AGVGWVECYQSTGFCYHSRDGTGGGK;(SEQ ID NO: 285)AGFTWVECHQATGRCVEWTTGTGGGK;(SEQ ID NO: 286)AGDWWVECRVGTGLCYRYDTGTGGGK;(SEQ ID NO: 287)AGDSWVECDAQTGFCYSFLYGTGGGK;(SEQ ID NO: 289)AGERWVECRAETGFCYTWVSGTGGGK;(SEQ ID NO: 290)AGGGWVECRAETGHCQEYRLGTGGGK;(SEQ ID NO: 291)AGVAWVECYQTTGKCYTFRGGTGGGK;(SEQ ID NO: 292)AGEGWVECFANTGACFTYPRGTGGGK;(SEQ ID NO: 293)GDYPWCHELSDSVTRFCVPWDPGGGK;(SEQ ID NO: 294)GDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 295)GDDHMCRSPDYQDHVCMYWDPGGGK;(SEQ ID NO: 296)GDPPLCYFVGTQEWHHCNPFDPGGGK;(SEQ ID NO: 297)GDDSYCMMNEKGWWNCYLYDPGGGK;(SEQ ID NO: 298)GDPAQCWESNYQGIFFCDNPDPGGGK;(SEQ ID NO: 299)GDGSWCEMRQDVGKWNCFSDDPGGGK;(SEQ ID NO: 300)GDGWACAKWPWGGEICQPSDPGGGK;(SEQ ID NO: 301)GDPDTCTMWGDSGRWYCFPADPGGGK;(SEQ ID NO: 302)GDNWKCEYTQGYDYTECVYLDPGGGK;(SEQ ID NO: 303)GDNWECGWSNMFQKEFCARPDPGGGK;(SEQ ID NO: 486)GDWWECKREEYRNTTWCAWADPGGGK;(SEQ ID NO: 487)GDSSVCFEYSWGGEVCFRYDPGGGK;(SEQ ID NO: 488)GDSRVCWEYSWGGQICLGYDPGGGK;(SEQ ID NO: 304)AQQVQYQFFLGTPRYEQWDLDKGGK;(SEQ ID NO: 305)AQEPEGYAYWEVITLYHEEDGDGGK;(SEQ ID NO: 306)AQAFPRFGGDDYWIQQYLRYTDGGK;(SEQ ID NO: 307)AQGDYVYWEIIELTGATDHTPPGGK;(SEQ ID NO: 308)AQRGDYQEQYWHQQLVEQLKLLGGK;(SEQ ID NO: 309)AQRSWYLGPPYYEEWDPIPNGGK;(SEQ ID NO: 310)AQDWYYDEILSMADQLRHAFLSGGGK;(SEQ ID NO: 311)AGIDFCKGMAPWLCADMGTGGGK;(SEQ ID NO: 312)AGPWTCWLEDHLACAMLGTGGGK;(SEQ ID NO: 313)AGDWGCSLGNWYWCSTEGTGGGK;(SEQ ID NO: 314)GSDHHCYLHNGQWICYPFAPGGGK;(SEQ ID NO: 315)GSNSHCYIWDGMWLCFPDAPGGGK;(SEQ ID NO: 316)SGRLDCDKVFSGPYGKVCVSYGSGGGK;(SEQ ID NO: 317)SGRLDCDKVFSGPHGKICVNYGSGGGK;(SEQ ID NO: 318)SGRTTCHHQISGPHGKICVNYGSGGGK;(SEQ ID NO: 319)SGAHQCHHWTSGPYGEVCFNYGSGGGK;(SEQ ID NO: 320)AGMPWCVEKDHWDCWWWGTGGGK;(SEQ ID NO: 321)AGPGPCKGYMPHQCWYMGTGGGK;(SEQ ID NO: 322)AGYGPCAEMSPWLCWYPGTGGGK;(SEQ ID NO: 323)AGYGPCKNMPPWMCWHEGTGGGK;(SEQ ID NO: 324)AGGHPCKGMLPHTCWYEGTGGGK;(SEQ ID NO: 325)AQAPAWTFGTNWRSIQRVDSLTGGGGGK;(SEQ ID NO: 326)AQEGWFRNPQEIMGFGDSWDKPGGGGGK;(SEQ ID NO: 330)AQEGWFRNPQEIMGFGDSWDKPGGGK;(SEQ ID NO: 331)AQRGDYQEQYWHQQLVEQLKLLGGGK;(SEQ ID NO: 332)AGWYWCDYYGIGCKWTGGGK;(SEQ ID NO: 333)AGWYWCDYYGIGCKWTGTGGGK;(SEQ ID NO: 334)AQWYYDWFHNQRKPPSDWIDNLGGGK;(SEQ ID NO: 336)WQPCPWESWTFCWDPGGGK;(SEQ ID NO: 337)VCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 338)AGPTWCEDDWYYCWLFGTJK;(SEQ ID NO: 340)AQAHMPPWRPVAVDALFDWVEGGGGGK;(SEQ ID NO: 341)AQAHMPPWWPLAVDAQEDWFEGGGGGK;(SEQ ID NO: 342)AQAQMPPWWPLAVDALFDWFEGGGGGK;(SEQ ID NO: 343)AQDWYWREWMPMHAQFLADDWGGGGGK;(SEQ ID NO: 344)AQKKEDAQQWYWTDYVPSYLYRGGGGGK;(SEQ ID NO: 345)AQPVTDWTPHHPKAPDVWLFYTGGGGGK;(SEQ ID NO: 346)AQDALEAPKRDWYYDWFLNHSPGGGGGK;(SEQ ID NO: 347)KWCEEDWYYCMITGTGGGK;(SEQ ID NO: 348)AGPKWCEEDWYYCMIGGGK;(SEQ ID NO: 349)KWCEEDWYYCMIGGGK;(SEQ ID NO: 350)AQPDNWKEFYESGWKYPSLYKPLGGGGGK;(SEQ ID NO: 351)AQMPPGFSYWEQVVLHDDAQVLGGGGGK;(SEQ ID NO: 352)AQARMGDDWEEAPPHEWGWADGGGGGK;(SEQ ID NO: 353)AQPEDSEAWYWLNYRPTMFHQLGGGGGK;(SEQ ID NO: 354)AQSTNGDSFVYWEEVELVDHPGGGGGK;(SEQ ID NO: 355)AQWESDYWDQMRQQLKTAYMKVGGGGGK;(SEQ ID NO: 356)AQDWYYDEILSMADQLRHAFLSGGGGGK;(SEQ ID NO: 368)VCWEDSWGGEVCFGGGK;(SEQ ID NO: 369)GDSRVCWEDSWGGEVCFGGGK;(SEQ ID NO: 371)SRVCWEDSWGGEVCFRYGGGGK;(SEQ ID NO: 372)GDSRVCWEDSWGGEVCFRYGGGK;(SEQ ID NO: 374)GDSRVCWEDSWGGEVCFRYDP;(SEQ ID NO: 504)ERVTTCWPGEYGGVECYSVAY;(SEQ ID NO: 462)DWYYGGGK;(SEQ ID NO: 465)AEDWYYDEILGRGRGGRGG;(SEQ ID NO: 453)AGPTWEEDDWYYKWLFGTGGGK;(SEQ ID NO: 454)AGPTWKEDDWYYEWLFGTGGGK;(SEQ ID NO: 455)AGPTWDprEDDWYYDWLFGTGGGK;(SEQ ID NO: 456)AGPTWDEDDWYYDprWLFGTGGGK;(SEQ ID NO: 457)AGPTWDEDDWYYKWLFGTGGGK;and(SEQ ID NO: 480)AGPTWCEDDWYYCWLFGTGGGGK, wherein J is the spacer or linker group 8-amino- 3,6dioxaoctanoyl. 23. A method of imaging at least a portion of a patient comprising administering the ultrasound contrast agent of claim 1, and imaging at least a portion of the patient using ultrasound energy. 24. A method of treating a patient comprising administering the ultrasound contrast agent of claim 21 and applying ultrasound energy to the patient. 25. A method of detecting KDR or VEGF/KDR complex in a subject comprising the steps of: (a) administering the ultrasound contrast agent of claim 1;(b) detecting the ultrasound contrast agent in the subject. 26. The method of claim 25, further comprising constructing an image. 27. The agent of claim 4, wherein at least one of the polypeptides comprises an amino acid substitution, an amide bond substitution, a D-amino acid substitution, a glycosylated amino acid, a disulfide mimetic substitution, an amino acid translocation, a retro-inverso peptide, a peptoid, a retro-inverso peptoid, or a synthetic peptide and wherein the polypeptide maintains its ability to bind the receptor. 28. The agent of claim 4, wherein at least one of the polypeptides does not include the C terminal GGGK extension in its amino acid sequence. 29. The agent of claim 4, wherein the polypeptide is linked to the microvesicle via a linker or spacer. 30. The agent of claim 29, wherein said linker or spacer is selected from the group consisting of a substituted alkyl chain, an unsubstituted alkyl chain, a polyethylene glycol derivative, an amino acid spacer, a sugar, an aliphatic spacer, an aromatic spacer, a lipid molecule, and combinations thereof. 31. The agent of claim 4, wherein the microvesicle comprises a microvesicle-forming material selected from the group consisting of surfactants, lipids, sphingolipids, oligolipids, phospholipids, proteins, polypeptides, carbohydrates and synthetic or natural polymeric materials. 32. The agent of claim 4, wherein the microvesicle is selected from the group consisting of a microbubble, a microballoon, a microparticle and a microsphere. 33. The agent of claim 10, wherein the microvesicle comprises a microvesicle-forming material selected from the group consisting of surfactants, lipids, sphingolipids, oligolipids, phospholipids, proteins, polypeptides, carbohydrates and synthetic or natural polymeric materials. 34. The agent of claim 10, wherein the microvesicle is selected from the group consisting of a microbubble, a microballoon, a microparticle and a microsphere. 35. The agent of claim 32, wherein the microbubble comprises a phospholipid. 36. The agent of claim 34, wherein the microbubble comprises a phospholipid. 37. A method of imaging at least a portion of a patient comprising administering the ultrasound contrast agent of claim 4 and imaging at least a portion of the patient using ultrasound energy. 38. A method of imaging at least a portion of a patient comprising administering the ultrasound contrast agent of claim 10 and imaging at least a portion of the patient using ultrasound energy. 39. A method of detecting KDR or VEGF/KDR complex in a subject comprising the steps of: (a) administering the ultrasound contrast agent of claim 4;(b) detecting the ultrasound contrast agent in the subject. 40. The method of claim 39, further comprising constructing an image. 41. A method of detecting KDR or VEGF/KDR complex in a subject comprising the steps of: (a) administering the ultrasound contrast agent of claim 9;(b) detecting the ultrasound contrast agent in the subject. 42. The method of claim 41, further comprising constructing an image.
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Yan Feng,CHX ; Schneider Michel,CHX ; Brochot Jean,CHX, Gas mixtures useful as ultrasound contrast media contrast agents containing the media and method.
Yan Feng (Carouge CHX) Schneider Michel (Troinex CHX) Brochot Jean (Feigeres FRX), Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method.
Schneider Michel (Troinex CHX) Yan Feng (Geneva CHX) Grenier ; deceased Pascal (late of Ambilly FRX by Nadine Garcel ; legal heir ) Puginier Jerome (Le Chable-Beaumont FRX) Barrau Marie-Bernadette (G, Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the prepa.
Schneider Michel (Troinex CHX) Yan Feng (Genve CHX) Grenier ; deceased Pascal (late of Ambilly FRX by Nadine Garcel ; legal heir) Puginier Jrme (Le Chble-Beaumont FRX) Barrau Marie-Bernadette (Geneva, Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the prepa.
Wedeking Paul W. ; Wager Ruth E. ; Arunachalam Thangavel ; Ramalingam Kondareddiar ; Linder Karen E. ; Ranganathan Ramachandran S. ; Nunn Adrian D. ; Raju Natarajan ; Tweedle Michael F., Metal complexes derivatized with folate for use in diagnostic and therapeutic applications.
Srinivasan Ananthachari (Kirkland WA) Fritzberg Alan R. (Edmonds WA) Jones David S. (Seattle WA), Metal radionuclide chelating compounds for improved chelation kinetics.
Tweedle Michael F. ; Gaughan Glen T.,GBX ; Hagan James J., Method for imaging and radiopharmaceutical therapy using 1-substituted-4,7,10-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs.
Tweedle Michael F. ; Gaughan Glen T.,GB2 ; Hagan James J., Method for imaging mammalian tissue using 1-substituted-1,4,7-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analo.
Tweedle Michael F. (Hightstown NJ) Gaughan Glen T. (Oxford NJ GB2) Hagan James J. (Holmdel NJ), Method for imaging mammalian tissue using 1-substituted-1,4,7-tricarboxymethyl-1,4,7,10-tetraazacyclododecane and analog.
Unger Evan C. (Tucson AZ) Fritz Thomas A. (Tucson AZ) Matsunaga Terry (Tucson AZ) Ramaswami VaradaRajan (Tucson AZ) Yellowhair David (Tucson AZ) Wu Guanli (Tucson AZ), Method of preparing gas and gaseous precursor-filled microspheres.
Rong Sing ; Woude George Vande ; Faletto Donna L. ; Tsarfaty Ilan,ILX ; Oskarsson Marianne, Method of producing hepatocycte growth factor/scatter factor and related cell lines.
Unger Evan C. ; Matsunaga Terry ; Fritz Thomas A. ; Ramaswami Varadarajan, Methods for diagnostic imaging by regulating the administration rate of a contrast agent.
Fan, Hong; Marinelli, Edmund R.; Nanjappan, Palaniappa; Pillai, Radhakrishna; Swenson, Rolf E., Methods for preparing multivalent constructs for therapeutic and diagnostic applications and methods of preparing the same.
Unger Evan C. ; Fritz Thomas A. ; Gertz Edward W., Methods for ultrasound imaging involving the use of a contrast agent and multiple images and processing of same.
Unger Evan C. (Tucson AZ) Fritz Thomas A. (Tucson AZ) Matsunaga Terry (Tucson AZ) Ramaswami VaradaRajan (Tucson AZ) Yellowhair David (Tucson AZ) Wu Guanli (Tucson AZ), Methods of preparing gas-filled liposomes.
Klaveness Jo (Oslo NLX) Rongved Pal (Hellvik NLX) Stubberud Lars (Sodertalje NLX), Microbubble-generating contrast agents for ultrasound and magnetic resonance imaging.
Tam James P. (607 S. Wilson Blvd. Nashville TN 37215), Multiple antigen peptide system having adjuvant properties, vaccines prepared therefrom and methods of use thereof.
Moses Marsha A. ; Langer Robert S. ; Wiederschain Dimitri G. ; Wu Inmin ; Sytkowski Arthur, Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis.
Rajopadhye, Milind; Edwards, D. Scott; Barrett, John A.; Carpenter, Jr., Alan P.; Harris, Thomas D.; Heminway, Stuart J.; Liu, Shuang; Singh, Prahlad R., Pharmaceuticals for the imaging of angiogenic disorders.
Rajopadhye, Milind; Edwards, D. Scott; Barrett, John A.; Carpenter, Jr., Alan P.; Harris, Thomas D.; Heminway, Stuart J.; Liu, Shuang; Singh, Prahlad R., Pharmaceuticals for the imaging of angiogenic disorders.
Ramalingam Kondareddiar (Dayton NJ) Raju Natarajan (Kendall Park NJ), Polyaza heteroatom-bearing ligands and metal complexes thereof for imaging or radiotherapy.
Sieving Paul F. (3166 Impala Dr. #5 San Jose CA 95117) Watson Alan D. (262A Rincon Ave. Campbell CA 95008) Quay Steven C. (428 Oakmead Pkwy. Sunnyvale CA 94086) Rocklage Scott M. (255 Cresci Rd. Los , Polychelants containing macrocyclic chelant moieties.
Kleinsorgen Klaus,DEX ; Kohler Uwe,DEX ; Bouvier Alexander,ATX ; Folzer Andreas,ATX, Process for the recovery of metals from used nickel/metal/rare earth hydride storage batteries.
Trevino Leo A. ; Schutt Ernest George ; Klein David H. ; Tarara Thomas E. ; Weers Jeffry G. ; Kabalnov Alexey, Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonge S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonges S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonges S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonges S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonges S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Schneider Michel (Troinex CHX) Bichon Daniel (Montpellier FRX) Bussat Philippe (Collonqes S/Saleve FRX) Puginier Jerome (Le Chable-Beaumont FRX) Hybl-Sutherland Eva (Wiesbaden DEX), Stable microbubbles suspensions injectable into living organisms.
Flanagan Richard J. (St. Lazare CAX) Dufour Jean-Marc (Pierrefonds CAX) Hogan Keith T. (Dorval CAX), TC or RE radionuclide labelled chelate, hexapeptide complexes useful for diagnostic or therapeutic applications.
Unger Evan C. ; Fritz Thomas A. ; Matsunaga Terry ; Ramaswami VaradaRajan ; Yellowhair David ; Wu Guanli, Targeted gas and gaseous precursor-filled liposomes.
Erbel Raimund (Mainz DEX) Zotz Rainer (Mainz DEX) Krone Volker (Flrsheim DEX) Magerstdt Michael (Hofheim am Taunus DEX) Walch Axel (Frankfurt am Main DEX), Ultrasonic contrast agents, processes for their preparation and the use thereof as diagnostic and therapeutic agents.
Keyt Bruce A. ; Nguyen Francis Hung ; Ferrara Napoleone ; Cunningham Brian C. ; Wells James A. ; Li Bing, Variants of vascular endothelial cell growth factor.
Sato, Aaron K.; Sexton, Daniel J.; Dransfield, Daniel T.; Ladner, Robert Charles, KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy.
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