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In connection columnar packing materials ^ SKZt effector platform may be employed with with the foregoing, the mventtoo ? et ^By-passing selection: direct screening for antibody-antigen interactions using protein arrays.. 2000Au^";28(15): E72 and the references cited therein. used her«n for^ greater ^ertamty tadudes decoy receptors. receptors Indude TRAIL decoy receptors (APO-2U, CD44 decoy like ^ m SS receptor lik. Vascular endothelial growth factor receptor- 3 in lymphangiogenesis in wouridhealmg. 2000 May;1 66(5): 1499-504.31: Frelin C, Ladoux A, D'angeto G. Monoclonal antibodies to vascular endothelial growth faotor-D block itslnteractions with both VEGF receptor-2 and VEGF receptor-3 . VEGFc and VEGFR3 expression in human thyroid J Cancer, 2000 Apr 1 ;86(1):47-52.36: Jacquernler J, Matboulln-Portier MP, Valtola R, Charafe-Jauffret E,. S^S^S^7m^Sm P"* 0 ™ « Imrnunooytokine approach should varying affect on the non-d,seased JSght well have some effect on normal cells, have a minimal effect on normal cells, ^J^^Xc Si SMt radionuclide; in each case the effects and radionuclide effect win have ^ ade ^ te d ^ ^the ^ti«*e Sfic ligand for non-dfeeased cells. Anbtody arrays far Shi* o^ghput screening of antibody-antigen Interacticni Nat Blotechncl. protein (1L-17) ( see J Bid Chem 2001 Nov 12), cp95-Fo decoy receptor, TRAMP, l Ul Ril receptor, osteoprotogerln (OPS), IL13Rdpha2. Vasoular endothelial growth factors and angiogenesls. Geneix J, Houvenae'ghel G, Pulg B, Bardou VJ, Hassoun J, vlens P, Birnbaum D. factions and optionally also *^^^^^C^Z» the greatest potential for hydrogen bondmg The invention also «*«»*"^^ target ligand to diminish »e on-rate will Introduce an- aqueous -cushion Into the interlace ream » „ composition of an existing binder co Stio Tto affinity. nfl ^f""'"" 68 routinely measured using various technologies ^"^^^^e method the antibodies have peptide tags m«asurina these rates In real-time ment o t me nmn anybodies are evaluated *a? Histoohem Cell Biol, 200O Nov;1 14(3-85.17: Mimura T, Amano S, Usui T, Kaji Y, Oshika T, Ishii Yi. Molecular biology of the VEQF and the VEGF receptor famlly. VEGF-C signanng pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis andhematopolesis. .2000 Deo 1;96(12):3793-800,21: Lymboussaki A, Achen MG, Stacker SA, Alitalo K. Neuhauser T5, Derringer GA) Thompson LD, Fanburg-Smith JC, Miettihen M, Saaristo A, Abbondanzo SL. Mo abstract ayallable,81: Kalpatoen kinases involved in angiogenesw J 1 Cell Bloh 1995 ' M^* 8 ^ Dfilt Xlmm M . Kem to their D N A eg a phage ^^^^^^n S^curate measure of titeir true Independently of the phage or dther be lengthened in a relatively high affinity on rates and off ext9rt . Expression of vascular endothelial growth factor C and vascular endothelialgrowth factor receptor 3 in corneal lymphangiogenesis. Growth factors regulating lymphatic vessel&Curr Top Microbiol Immunol. Splenic angiosarcoma: a ctinicopathologlo and Immunophenotyplc study of 28cases. 2000 Sep;13(9):978-87.23: Leu AJ, Berk DA, Lymboussaki A, Alitalo K; Jain RK. In another P referred heterofunotional ligand Is a btepecifio antibody. «(■" _ h other aspects the Invention le Erected to a f ^«Ttina strategies by administering a heterofunctiona. Hhamow , Av I Ashkenazl ^^Ot W 3-5*bw.» 1 naan d exerta rea function endothelial cells. Itiscontemplatedth^^ the manner described above, could be •*«22ESK«d conjugates/fusions therewith used or currently foe example oytoxic drugs, other ^mor^ ™ ^ c 9 (re ovogenesis sea for example ^g^^^^ 407(6809-571. to delay a cancer cell for targeted killing cr Stated / inmtihnl 2001 Mar 1 • 166(66-3265; Nippon Rinsho. n Wractionrby^dministering tea test subject two different multifunctional Uganda of the invention with cooperating second portions. 2001 Z^fi SS* Sewley JP f Recombinant protein arraya. 1 999 Sep 24;274t39):2761 7-22.46: Ohta Y, Shrtdhar V, Bright RK; Kalemkerian GPi Du W, 45 CA 02368708 2002-01-14 motastasis. at ^™™ y ^ Mnds to at least one ligand located on the embodiment the heterofunetional Ogand J Mh« ^*5^o^«S associated ligand, as hereinafter defined. ' J™*^ adaptations thereof r^^r S^o drug ^^^^Satv^c^o^od to a S* Hgahd in the form fo, such purposes as her am* « *^^/and impositions thereof. In other aspects the Invention is ■ targeting strategic by admlntstei a method of inira4ymphatic drug =-! ^'^.^C^ugft (to /y/nphetfo '^^ppression (for example, ce/te and/or ™'° c, ^S™St w Tvt Tw an undated deflree of imm^o^PP^a ^ SU ch effect, CA 02363708 2002-01-14 7. •« «f the invention could be used to bind to antigens/ligands on lymphocytes which are Stt STK? Optiona Jly.'the tumor ahtigen or one or both of the antigens are a pan- carcinomio antig« like TAG-72, CEA. The invention also contemplates usmg one or more Sage display libraries to optimize the development of MHC/B7 costimutetory Wspeclfic anhbodles. SKp Sm* complexes In eomblnetion with adoptive ^"^^^"X^TSe^ Ss and patent applications referenced in these patenta; wrth respect to MHC peptide c.omplexesl see for example WO 99/64597, WO 98/03652, WO 98/0674? As described above, the invention also contemplates that the lower affinity ligand binding arm of the Tmu^notional ligand (ie. Hnd«oftaanfibodv(10 the antibody binds to a portion of the effector which la not cnbcally S£the^ ti^reo Thas, when combined with the effector, a suitably lower affinity for the reoepto. Br J c ^ c f^ 9 w A ^ r Lion of novel surface antigens ? According to will be exerted to a degree depending on tt modifie r "™! With respect to affinity maturation see for example Cola G, Hudson PJ, Irving RA. Prognosis of breast-carcinoma lymphagenesis evaluated by immunohistochemlcalinvestigation of vascular-endothetial-growth- factor receptor 3Jnt J Cancer. n , Aaato fte Ss of the Fab-ttoresponse modifier for the target receptor could be the bioresponse modffler onto ,an X^S^SXI. Protein arrays for gene expression and molecular Interaction Protein affinity nwtoraticn in vivo ulna E coli mutator cells. 2000 Jan ;2Q;89|1 ):69-73.37: Folpe AL, Veikkola T, Valtola R, Weiss! Vasoular endothelial growth factor receptor-3 (VEGFR-3): a marker of Vasciilartumors with presumed lymphatic Differentiation, including Kaposi's sarcoma,kaposifbrm and Dabska-type hemangioendotheliomas, and a. Review.39: Skobe M, Brown LF, Tognazzi K, Ganju RK, Dezube BJ, Afitalo K, Dotmar M.
rector but hinders the binding to at least one seoond r£c? athibutoble to the proximity of the the BRM to the BRM'e receptor binding site and optionally also the amino acid composlbon of the antibody at that interface. Laok of lymphatic vascular specificity of vasoular endothelial growth factorreceptor 3 in 185 vascular tumors. 1999 Ded 1;86(1 1 06-1 2.41 : Petrova TV, Makinen T, Alitalo K. Review.42: Lymboussaki A, Olofsson B, Eriksson U, Alitalo K.
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