[미국특허]
KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-014/00
A61K-049/22
A61K-051/08
C07K-007/08
C07K-014/52
C07K-014/71
A61K-038/00
출원번호
US-0085645
(2013-11-20)
등록번호
US-9408926
(2016-08-09)
발명자
/ 주소
Arbogast, Christophe
Bussat, Philippe
Fan, Hong (Helen)
Khurana, Sudha
Linder, Karen E.
Marinelli, Edmund R.
Nanjappan, Palaniappa
Nunn, Adrian D.
Pillai, Radhakrishna K.
Pochon, Sibylle
Ramalingam, Kondareddiar
Shrivastava, Ajay
Song, Bo
Swenson, Rolf E.
Von Wronski, Mathew A.
Yan, Feng
출원인 / 주소
Bracco Suisse S.A.
대리인 / 주소
Pearl Cohen Zedek Latzer Baratz LLP
인용정보
피인용 횟수 :
0인용 특허 :
167
초록▼
The present invention provides polypeptides, peptide dimers, 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 synthe
The present invention provides polypeptides, peptide dimers, 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, particularly contrast agents. Also provided are methods for monitoring and evaluating the therapeutic effectiveness of treatment protocols for diseases associated with angiogenesis or endothelial cell hyperproliferation, such as cancer, using contrast agents of the invention.
대표청구항▼
1. A method for adjusting a treatment protocol comprising: (a) administering an ultrasound contrast agent comprising a KDR binding polypeptide having a sequence selected from the group consisting of: AGPKWCEEDWYYCMITGTGGGK;(SEQ ID NO: 264)GDSRVCWEDSWGGEVCFRYDPGGGK;(SEQ ID NO: 294)AQDWYYDEILSMADQLRHA
1. A method for adjusting a treatment protocol comprising: (a) administering an ultrasound contrast agent comprising a KDR binding polypeptide having a sequence 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)AGPTWCADDWYYCWLFGTGGGK;(SEQ ID NO: 390)andVCWEDSWGGEVCFRYDPGGGK.(SEQ ID NO: 337) to a subject with a disorder associated with cell hyperproliferation or angiogenesis; (b) obtaining an initial image of the subject;(c) administering a therapeutic agent appropriate for the treatment of the disorder;(d) obtaining a subsequent image of the subject;(e) comparing the initial and the subsequent images to evaluate the effectiveness of the therapy;(f) determining whether the effectiveness of the therapy is adequate; and(g) if the effectiveness of the therapy is determined not to be adequate, adjusting said treatment protocol, terminating said treatment protocol or administering a different treatment protocol. 2. The method of claim 1, wherein the disorder is cancer. 3. The method of claim 1, wherein the ultrasound contrast agent comprises one or more KDR binding dimers selected from the group consisting of: Ac-VCWEDSWGGEVCFRYDPGGGK (SEQ ID NO:337) (JJ-C(═O)(CH2)3C(═O)—K—NH(CH2)4—(S)—CH((Ac-AGPTWCEDDWYYCWLFGTGGGK (SEQ ID NO:277))-NH)CONH2)—NH2), a dimer comprising Ac-GDSRVCWEDSWGGEVCFRYDPGGGK (SEQ ID NO:294) and Ac-AGPTWCEDDWYYCWLFGTGGGK (SEQ ID NO:277), and Ac-AGPTWCEDDWYYCWLFGTGGGK (SEQ ID NO:277){Ac-VCWEDSWGGEVCFRYDPGGGK (SEQ ID NO:337) [JJ-Glut-K(SATA)]-NH2}—NH2. 4. The method of claim 1, wherein the ultrasound contrast agent comprises a dimer. 5. The method of claim 3, wherein the dimer is Ac-VCWEDSWGGEVCFRYDPGGGK (SEQ ID NO:337) (JJ-C(═O)(CH2)3C(═O)—K—NH(CH2)4—(S)-CH((Ac-AGPTWCEDDWYYCWLFGTGGGK (SEQ ID NO:277))-NH)CONH2)—NH2). 6. The method of claim 1, wherein the initial and subsequent images are obtained via diagnostic ultrasound. 7. The method of claim 1, wherein the therapeutic agent is an anti-cancer agent. 8. The method of claim 7, wherein the cancer is selected from the group consisting of prostate cancer, mammary cancer, ovarian cancer, liver cancer, colon cancer, renal cancer, bone cancer, bladder cancer, pancreatic cancer, lung cancer, uterine cancer and testicular cancer. 9. The method of claim 2, wherein comparing the initial and subsequent images to evaluate the effectiveness of therapy comprises comparing the size or vascularity of a tumor shown in the images of the subject. 10. The method of claim 2, wherein comparing the initial and subsequent images to evaluate the effectiveness of therapy comprises comparing a parameter selected from the group consisting of Imax (maximal peak enhancement values), AUC (area under the curve), WIR (Wash-in-rate), and TTP (Time-to Peak). 11. The method of claim 2, wherein comparing the initial and subsequent images to evaluate the effectiveness of therapy comprises comparing LPO (late phase opacification). 12. The method of claim 7, wherein the anti-cancer agent is selected from the group consisting of sunitinib, imatinib, sorafenib and bevacizumab. 13. The method of claim 1, wherein the ultrasound contrast agent comprises a microvesicle filled with a gas or gas mixture. 14. The method of claim 13, wherein the ultrasound contrast agent comprises a microbubble filled with a gas or gas mixture. 15. The method of claim 13, wherein the gas or gas mixture comprises fluorinated gas. 16. The method of claim 14 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 hyperpolarized gas, SF6, a freon and a perfluorocarbon. 17. The method of claim 15 wherein the gas comprises SF6 or C4F10. 18. The method of claim 14 wherein the gas-filed microbubble comprises at least one phospholipid. 19. The method of claim 18 wherein the phospholipid is selected from DPPE, DSPE and DMPE. 20. The method of claim 18 wherein the phospholipid is a saturated phospholipid. 21. The method of claim 14, wherein the gas or gas mixture comprises fluorinated gas. 22. The method of claim 5, wherein comparing the initial and subsequent images to evaluate the effectiveness of therapy comprises comparing a parameter selected from the group consisting of Imax (maximal peak enhancement values), AUC (area under the curve), WIR (Wash-in-rate), and TTP (Time-to Peak). 23. The method of claim 5, wherein comparing the initial and subsequent images to evaluate the effectiveness of therapy comprises comparing LPO (late phase opacification).
Berg Arne (Sandvika NOX) Klaveness Jo (Oslo NOX) Strande Per (Oslo NOX) Stubberud Lars (Sodertalje SEX), Aggregates of x-ray microparticles for ultrasound imaging.
Linder Karen E. (Highland Park NJ) Nunn Adrian D. (Ringoes NJ) Ramalingam Kondareddiar (North Brunswick NJ), Boronic acid adducts of metal dioxime complexes useful in labelling proteins and other amine-containing compounds.
Nunn Adrian D. (Ringoes NJ) Linder Karen E. (Kingston NJ) Jurisson Silvia (Columbia MO) Eckelman William C. (Bethesda MD), Boronic acid adducts of rhenium dioxime and technetium-99m dioxime complexes containing a biochemically active group.
Toner John L. (Downingtown PA) Hilborn David A. (Henrietta NY) Murray Bruce J. (Walworth NY) Hossain Timothy Z. (Dallas TX), Complexing agents and targeting radioactive immunoreagents useful in therapeutic and diagnostic imaging compositions and.
Linder Karen (Kingston NJ) Nunn Adrian D. (Ringoes NJ) Nowotnik David P. (Flemington NJ) Ramalingam Kondareddiar (Dayton NJ) DiRocco Richard J. (Allentown NJ) Rumsey William L. (Wyndmoor PA) Pirro Jo, Diagnostic imaging methods using rhenium and technetium complexes containing a hypoxia-localizing moiety.
Ladner Robert C. (Ijamsville MD) Guterman Sonia K. (Belmont MA) Roberts Bruce L. (Milford MA) Markland William (Milford MA) Ley Arthur C. (Newton MA) Kent Rachel B. (Boxborough MA), Directed evolution of novel binding proteins.
Alitalo,Kari; Aprelikova,Olga; Pajusola,Katri; Armstrong,Elina; Korhonen,Jaana; Kaipainen,Arja, FLT4 (VEGFR-3) as a target for tumor imaging and anti-tumor therapy.
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.
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., KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy.
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.
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